The effect of N-acetylcysteine on mechanical fatigue resistance of antibiotic-loaded bone cement.

PubMed

Sukur, Erhan; Akar, Abdulhalim; Topcu, Huseyin Nevzat; Cicekli, Ozgur; Kochai, Alauddin; Turker, Mehmet

2018-05-31

This biomechanical study evaluates the effect of N-acetylcysteine alone and in combination with the most commonly used antibiotic-loaded bone cement mixtures. We mixed eight bone cement mixture groups including combinations of N-acetylcysteine, gentamicin, teicoplanin, and vancomycin and applied a four-point bending test individually to each sample on days 1 and 15 using an MTS Acumen test device. The result was less than 50 MPa-the limit declared by the ISO (International Standards Organization)-in only the "gentamicin + bone cement + N-acetylcysteine" group. Mechanical fatigue resistance of the bone cement decreased significantly with the addition of N-acetylcysteine both on day 1 and day 15 (p <  0.001). With the addition of N-acetylcysteine into the "gentamicin + bone cement" and "vancomycin + bone cement" mixtures, a significant decrease in mechanical fatigue resistance was observed both on day 1 and day 15 (p <  0.001). In contrast, with the addition of N-acetylcysteine into the "teicoplanin + bone cement" mixture, no significant difference in mechanical fatigue resistance was observed on days 1 and 15 (p = 0.093, p = 0.356). Preliminary results indicate that adding N-acetylcysteine to teicoplanin-loaded bone cement does not significantly affect the cement's mechanical resistance, potentially leading to a new avenue for preventing and treating peri-prosthetic joint infection. N-acetylcysteine may, therefore, be considered as an alternative agent to be added to antibiotic-loaded bone cement mixtures used in the prevention of peri-prosthetic joint infection.

Skeletal muscle contractions uncoupled from gravitational loading directly increase cortical bone blood flow rates in vivo.

PubMed

Caulkins, Carrie; Ebramzadeh, Edward; Winet, Howard

2009-05-01

The direct and indirect effects of muscle contraction on bone microcirculation and fluid flow are neither well documented nor explained. However, skeletal muscle contractions may affect the acquisition and maintenance of bone via stimulation of bone circulatory and interstitial fluid flow parameters. The purposes of this study were to assess the effects of transcutaneous electrical neuromuscular stimulation (TENS)-induced muscle contractions on cortical bone blood flow and bone mineral content, and to demonstrate that alterations in blood flow could occur independently of mechanical loading and systemic circulatory mechanisms. Bone chamber implants were used in a rabbit model to observe real-time blood flow rates and TENS-induced muscle contractions. Video recording of fluorescent microspheres injected into the blood circulation was used to calculate changes in cortical blood flow rates. TENS-induced repetitive muscle contractions uncoupled from mechanical loading instantaneously increased cortical microcirculatory flow, directly increased bone blood flow rates by 130%, and significantly increased bone mineral content over 7 weeks. Heart rates and blood pressure did not significantly increase due to TENS treatment. Our findings suggest that muscle contraction therapies have potential clinical applications for improving blood flow to cortical bone in the appendicular skeleton. Copyright 2008 Orthopaedic Research Society

Gene delivery nanocarriers of bioactive glass with unique potential to load BMP2 plasmid DNA and to internalize into mesenchymal stem cells for osteogenesis and bone regeneration

NASA Astrophysics Data System (ADS)

Kim, Tae-Hyun; Singh, Rajendra K.; Kang, Min Sil; Kim, Joong-Hyun; Kim, Hae-Won

2016-04-01

The recent development of bioactive glasses with nanoscale morphologies has spurred their specific applications in bone regeneration, for example as drug and gene delivery carriers. Bone engineering with stem cells genetically modified with this unique class of nanocarriers thus holds great promise in this avenue. Here we report the potential of the bioactive glass nanoparticle (BGN) system for the gene delivery of mesenchymal stem cells (MSCs) targeting bone. The composition of 15% Ca-added silica, proven to be bone-bioactive, was formulated into surface aminated mesoporous nanospheres with enlarged pore sizes, to effectively load and deliver bone morphogenetic protein-2 (BMP2) plasmid DNA. The enlarged mesopores were highly effective in loading BMP2-pDNA with an efficiency as high as 3.5 wt% (pDNA w.r.t. BGN), a level more than twice than for small-sized mesopores. The BGN nanocarriers released the genetic molecules in a highly sustained manner (for as long as 2 weeks). The BMP2-pDNA/BGN complexes were effectively internalized to rat MSCs with a cell uptake level of ~73%, and the majority of cells were transfected to express the BMP2 protein. Subsequent osteogenesis of the transfected MSCs was demonstrated by the expression of bone-related genes, including bone sialoprotein, osteopontin, and osteocalcin. The MSCs transfected with BMP2-pDNA/BGN were locally delivered inside a collagen gel to the target calvarium defects. The results showed significantly improved bone regeneration, as evidenced by the micro-computed tomographic, histomorphometric and immunohistochemical analyses. This study supports the excellent capacity of the BGN system as a pDNA-delivery nanocarrier in MSCs, and the engineered system, BMP2-pDNA/BGN with MSCs, may be considered a new promising candidate to advance the therapeutic potential of stem cells through genetic modification, targeting bone defects and diseases.The recent development of bioactive glasses with nanoscale morphologies has spurred their specific applications in bone regeneration, for example as drug and gene delivery carriers. Bone engineering with stem cells genetically modified with this unique class of nanocarriers thus holds great promise in this avenue. Here we report the potential of the bioactive glass nanoparticle (BGN) system for the gene delivery of mesenchymal stem cells (MSCs) targeting bone. The composition of 15% Ca-added silica, proven to be bone-bioactive, was formulated into surface aminated mesoporous nanospheres with enlarged pore sizes, to effectively load and deliver bone morphogenetic protein-2 (BMP2) plasmid DNA. The enlarged mesopores were highly effective in loading BMP2-pDNA with an efficiency as high as 3.5 wt% (pDNA w.r.t. BGN), a level more than twice than for small-sized mesopores. The BGN nanocarriers released the genetic molecules in a highly sustained manner (for as long as 2 weeks). The BMP2-pDNA/BGN complexes were effectively internalized to rat MSCs with a cell uptake level of ~73%, and the majority of cells were transfected to express the BMP2 protein. Subsequent osteogenesis of the transfected MSCs was demonstrated by the expression of bone-related genes, including bone sialoprotein, osteopontin, and osteocalcin. The MSCs transfected with BMP2-pDNA/BGN were locally delivered inside a collagen gel to the target calvarium defects. The results showed significantly improved bone regeneration, as evidenced by the micro-computed tomographic, histomorphometric and immunohistochemical analyses. This study supports the excellent capacity of the BGN system as a pDNA-delivery nanocarrier in MSCs, and the engineered system, BMP2-pDNA/BGN with MSCs, may be considered a new promising candidate to advance the therapeutic potential of stem cells through genetic modification, targeting bone defects and diseases. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07933k

Comparative study of (Asp)7-CHOL-modified liposome prepared using pre-insertion and post-insertion methods for bone targeting in vivo.

PubMed

Zhang, Lijing; Cao, Hua; Zhang, Jiaxin; Yang, Chengli; Hu, Tingting; Li, Huili; Yang, Wu; He, Gu; Song, Xiangrong; Tong, Aiping; Guo, Gang; Li, Rui; Jiang, Yu; Liu, Jiyan; Cai, Lulu; Zheng, Yu

2017-02-01

Specific delivery of drugs to bone tissue is very challenging due to the architecture and structure of bone tissue. A seven-repeat sequence of aspartate, a representative bone-targeting oligopeptide, is preferentially used for targeted therapy for bone diseases. In this study, Asp7-cholesterol((Asp)7-CHOL) was synthesized and (Asp)7-CHOL-modified liposome loaded with doxorubicin (DOX) was successfully prepared using both pre-insertion (pre-L) and post-insertion (post-L) methods. The formulation was optimized according to particle size, zeta potential and the drug-loading efficiency of the liposome. In addition, the bone affinity of the (Asp)7-CHOL-modified liposome was evaluated using a hydroxyapatite (HA) absorption method. The results suggested that (Asp)7-CHOL-modified liposome show excellent HA absorption; pre-L showed slightly higher HA binding than post-L. However, post-L had a higher DOX entrapment efficiency than pre-L. In vivo imaging further demonstrated that pre-L showed a higher bone-targeting efficiency than post-L, which was consistent with in vitro results. In all, (Asp)7-CHOL-modified liposome showed excellent bone-targeting activity, suggesting their potential for use as a drug delivery system for bone disease-targeted therapies.

Skeletal Adaptation to Intramedullary Pressure-Induced Interstitial Fluid Flow Is Enhanced in Mice Subjected to Targeted Osteocyte Ablation

PubMed Central

Kwon, Ronald Y.; Meays, Diana R.; Meilan, Alexander S.; Jones, Jeremiah; Miramontes, Rosa; Kardos, Natalie; Yeh, Jiunn-Chern; Frangos, John A.

2012-01-01

Interstitial fluid flow (IFF) is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP) to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∼50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of pressure loading. Collectively, these studies indicate that structural adaptation to ImP-driven IFF can proceed unimpeded following a significant depletion in osteocytes, consistent with the potential existence of a non-osteocytic bone cell population that senses ImP-driven IFF independently and potentially parallel to osteocytic sensation of poroelasticity-derived IFF. PMID:22413015

Electrically active bioceramics: a review of interfacial responses.

PubMed

Baxter, F R; Bowen, C R; Turner, I G; Dent, A C E

2010-06-01

Electrical potentials in mechanically loaded bone have been implicated as signals in the bone remodeling cycle. Recently, interest has grown in exploiting this phenomenon to develop electrically active ceramics for implantation in hard tissue which may induce improved biological responses. Both polarized hydroxyapatite (HA), whose surface charge is not dependent on loading, and piezoelectric ceramics, which produce electrical potentials under stress, have been studied in order to determine the possible benefits of using electrically active bioceramics as implant materials. The polarization of HA has a positive influence on interfacial responses to the ceramic. In vivo studies of polarized HA have shown polarized samples to induce improvements in bone ingrowth. The majority of piezoelectric ceramics proposed for implant use contain barium titanate (BaTiO(3)). In vivo and in vitro investigations have indicated that such ceramics are biocompatible and, under appropriate mechanical loading, induce improved bone formation around implants. The mechanism by which electrical activity influences biological responses is yet to be clearly defined, but is likely to result from preferential adsorption of proteins and ions onto the polarized surface. Further investigation is warranted into the use of electrically active ceramics as the indications are that they have benefits over existing implant materials.

Current Approaches to Bone Tissue Engineering: The Interface between Biology and Engineering.

PubMed

Li, Jiao Jiao; Ebied, Mohamed; Xu, Jen; Zreiqat, Hala

2018-03-01

The successful regeneration of bone tissue to replace areas of bone loss in large defects or at load-bearing sites remains a significant clinical challenge. Over the past few decades, major progress is achieved in the field of bone tissue engineering to provide alternative therapies, particularly through approaches that are at the interface of biology and engineering. To satisfy the diverse regenerative requirements of bone tissue, the field moves toward highly integrated approaches incorporating the knowledge and techniques from multiple disciplines, and typically involves the use of biomaterials as an essential element for supporting or inducing bone regeneration. This review summarizes the types of approaches currently used in bone tissue engineering, beginning with those primarily based on biology or engineering, and moving into integrated approaches in the areas of biomaterial developments, biomimetic design, and scalable methods for treating large or load-bearing bone defects, while highlighting potential areas for collaboration and providing an outlook on future developments. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vivo evaluation of a simvastatin-loaded nanostructured lipid carrier for bone tissue regeneration

NASA Astrophysics Data System (ADS)

Yue, Xinxin; Niu, Mao; Zhang, Te; Wang, Cheng; Wang, Zhonglei; Wu, Wangxi; Zhang, Qi; Lai, Chunhua; Zhou, Lei

2016-03-01

Alveolar bone loss has long been a challenge in clinical dental implant therapy. Simvastatin (SV) has been demonstrated to exert excellent anabolic effects on bone. However, the successful use of SV to increase bone formation in vivo largely depends on the local concentration of SV at the site of action, and there have been continuing efforts to develop an appropriate delivery system. Specifically, nanostructured lipid carrier (NLC) systems have become a popular type of encapsulation carrier system. Therefore, SV-loaded NLCs (SNs) (179.4 nm in diameter) were fabricated in this study, and the osteogenic effect of the SNs was evaluated in a critical-sized rabbit calvarial defect. Our results revealed that the SNs significantly enhanced bone formation in vivo, as evaluated by hematoxylin and eosin (HE) staining, immunohistochemistry, and a fluorescence analysis. Thus, this novel nanostructured carrier system could be a potential encapsulation carrier system for SV in bone regeneration applications.

Effect of a novel load-bearing trabecular Nitinol scaffold on rabbit radius bone regeneration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gotman, Irena, E-mail: gotman@technion.ac.il; Gutmanas, Elazar Y., E-mail: gutmanas@technion.ac.il; National Research Tomsk Polytechnic University, Tomsk, 634050

The research aim was to evaluate the bone regeneration capability of novel load-bearing NiTi alloy (Nitinol) scaffolds in a critical-size defect (CSD) model. High strength “trabecular Nitinol” scaffolds were prepared by PIRAC (Powder Immersion Reaction Assisted Coating) annealing of the highly porous Ni foam in Ti powder at 900°C. This was followed by PIRAC nitriding to mitigate the release of potentially toxic Ni ions. Scaffolds phase composition and microstructure were characterized by X-ray diffraction and scanning electron microscopy (SEM/EDS), and their mechanical properties were tested in compression. New Zealand white rabbits received bone defect in right radius and were dividedmore » in four groups randomly. In the control group, nothing was placed in the defect. In other groups, NiTi scaffolds were implanted in the defect: (i) as produced, (ii) loaded with bone marrow aspirate (BMA), and (iii) biomimetically CaP-coated. The animals were sacrificed after 12 weeks. The forelimbs with scaffolds were resected, fixed, sectioned and examined in SEM. New bone formation inside the scaffold was studied by EDS analysis and by the processing of backscattered electron images. Bone ingrowth into the scaffold was observed in all implant groups, mostly next to the ulna. New bone formation was strongly enhanced by BMA loading and biomimeatic CaP coating, the bone penetrating as much as 1–1.5 mm into the scaffold. The results of this preliminary study demonstrate that the newly developed high strength trabecular Nitinol scaffolds can be successfully used for bone regeneration in critical size defects.« less

Local administration of calcitriol positively influences bone remodeling and maturation during restoration of mandibular bone defects in rats.

PubMed

Liu, Hongrui; Cui, Jian; Feng, Wei; Lv, Shengyu; Du, Juan; Sun, Jing; Han, Xiuchun; Wang, Zhenming; Lu, Xiong; Yimin; Oda, Kimimitsu; Amizuka, Norio; Li, Minqi

2015-04-01

The aim of this study was to investigate the influence of calcitriol on osteoinduction following local administration into mandibular bone defects. Calcitriol-loaded absorbable collagen membrane scaffolds were prepared using the polydopamine coating method and characterized by scanning electron microscopy. Composite scaffolds were implanted into rat mandibular bone defects in the following groups: no graft material (control), bare collagen membrane (CM group), collagen membrane bearing polydopamine coating (DOP/CM group), and collagen membrane bearing polydopamine coating absorbed with calcitriol (CAL/DOP/CM group). At 1, 2, 4 and 8weeks post-surgery, the osteogenic potential of calcitriol was examined by histological and immunohistochemical methods. Following in vivo implantation, calcitriol-loaded composite scaffolds underwent rapid degradation with pronounced replacement by new bone and induced reunion of the bone marrow cavity. Calcitriol showed strong potential in inhibiting osteoclastogenesis and promotion of osteogenic differentiation at weeks 1, and 2. Furthermore, statistical analysis revealed that the newly formed bone volume in the CAL/DOP/CM group was significantly higher than other groups at weeks 1, and 2. At weeks 4, and 8, the CAL/DOP/CM group showed more mineralized bone and uniform collagen structure. These data suggest that local administration of calcitriol is promising in promoting osteogenesis and mineralization for restoration of mandibular bone defects. Copyright © 2014 Elsevier B.V. All rights reserved.

Engineered Fibrin Gels for Parallel Stimulation of Mesenchymal Stem Cell Proangiogenic and Osteogenic Potential

PubMed Central

Murphy, Kaitlin C.; Hughbanks, Marissa L.; Binder, Bernard Y.K.; Vissers, Caroline B.; Leach, J. Kent

2014-01-01

Mesenchymal stem/stromal cells (MSCs) are under examination for use in cell therapies to repair bone defects resulting from trauma or disease. MSCs secrete proangiogenic cues and can be induced to differentiate into bone-forming osteoblasts, yet there is limited evidence that these events can be achieved in parallel. Manipulation of the cell delivery vehicle properties represents a candidate approach for directing MSC function in bone healing. We hypothesized that the biophysical properties of a fibrin gel could simultaneously regulate the proangiogenic and osteogenic potential of entrapped MSCs. Fibrin gels were formed by supplementation with NaCl (1.2, 2.3, and 3.9% w/v) to modulate gel biophysical properties without altering protein concentrations. MSCs entrapped in 1.2% w/v NaCl gels were the most proangiogenic in vitro, yet cells in 3.9% w/v gels exhibited the greatest osteogenic response. Compared to the other groups, MSCs entrapped in 2.3% w/v gels provided the best balance between proangiogenic potential, osteogenic potential, and gel contractility. The contribution of MSCs to bone repair was then examined when deployed in 2.3% w/v NaCl gels and implanted into an irradiated orthotopic bone defect. Compared to acellular gels after 3 weeks of implantation, defects treated with MSC-loaded fibrin gels exhibited significant increases in vessel density, early osteogenesis, superior morphology, and increased cellularity of repair tissue. Defects treated with MSC-loaded gels exhibited increased bone formation after 12 weeks compared to blank gels. These results confirm that fibrin gel properties can be modulated to simultaneously promote both the proangiogenic and osteogenic potential of MSCs, and fibrin gels modified by supplementation with NaCl are promising carriers for MSCs to stimulate bone repair in vivo. PMID:25527322

Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice.

PubMed

Govey, Peter M; Zhang, Yue; Donahue, Henry J

2016-01-01

Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone's capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure.

Polyglutamate directed coupling of bioactive peptides for the delivery of osteoinductive signals on allograft bone

PubMed Central

Culpepper, Bonnie K.; Bonvallet, Paul P.; Reddy, Michael S.; Ponnazhagan, Selvarangan; Bellis, Susan L.

2012-01-01

Allograft bone is commonly used as an alternative to autograft, however allograft lacks many osteoinductive factors present in autologous bone due to processing. In this study, we investigated a method to reconstitute allograft with osteoregenerative factors. Specifically, an osteoinductive peptide from collagen I, DGEA, was engineered to express a heptaglutamate (E7) domain, which binds the hydroxyapatite within bone mineral. Addition of E7 to DGEA resulted in 9× greater peptide loading on allograft, and significantly greater retention after a 5-day interval with extensive washing. When factoring together greater initial loading and retention, the E7 domain directed a 45-fold enhancement of peptide density on the allograft surface. Peptide-coated allograft was also implanted subcutaneously into rats and it was found that E7DGEA was retained in vivo for at least 3 months. Interestingly, E7DGEA peptides injected intravenously accumulated within bone tissue, implicating a potential role for E7 domains in drug delivery to bone. Finally, we determined that, as with DGEA, the E7 modification enhanced coupling of a bioactive BMP2-derived peptide on allograft. These results suggest that E7 domains are useful for coupling many types of bone-regenerative molecules to the surface of allograft to reintroduce osteoinductive signals and potentially advance allograft treatments. PMID:23182349

Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice

PubMed Central

Govey, Peter M.; Zhang, Yue; Donahue, Henry J.

2016-01-01

Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone’s capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure. PMID:27936104

Bone regeneration capacity of magnesium phosphate cements in a large animal model.

PubMed

Kanter, Britta; Vikman, Anna; Brückner, Theresa; Schamel, Martha; Gbureck, Uwe; Ignatius, Anita

2018-03-15

Magnesium phosphate minerals have captured increasing attention during the past years as suitable alternatives for calcium phosphate bone replacement materials. Here, we investigated the degradation and bone regeneration capacity of experimental struvite (MgNH 4 PO 4 ·6H 2 O) forming magnesium phosphate cements in two different orthotopic ovine implantation models. Cements formed at powder to liquid ratios (PLR) of 2.0 and 3.0 g ml -1 were implanted into trabecular bone using a non-load-bearing femoral drill-hole model and a load-bearing tibial defect model. After 4, 7 and 10 months the implants were retrieved and cement degradation and new bone formation was analyzed by micro-computed tomography (µCT) and histomorphometry. The results showed cement degradation in concert with new bone formation at both defect locations. Both cements were almost completely degraded after 10 months. The struvite cement formed with a PLR of 2.0 g ml -1 exhibited a slightly accelerated degradation kinetics compared to the cement with a PLR of 3.0 g ml -1 . Tartrat-resistant acid phosphatase (TRAP) staining indicated osteoclastic resorption at the cement surface. Energy dispersive X-ray analysis (EDX) revealed that small residual cement particles were mostly accumulated in the bone marrow in between newly formed bone trabeculae. Mechanical loading did not significantly increase bone formation associated with cement degradation. Concluding, struvite-forming cements might be promising bone replacement materials due to their good degradation which is coupled with new bone formation. Recently, the interest in magnesium phosphate cements (MPC) for bone substitution increased, as they exhibit high initial strength, comparably elevated degradation potential and the release of valuable magnesium ions. However, only few in vivo studies, mostly including non-load-bearing defects in small animals, have been performed to analyze the degradation and regeneration capability of MPC derived compounds. The present study examined the in vivo behavior of magnesiumammoniumphosphate hexahydrate (struvite) implants with different porosity in both mechanically loaded and non-loaded defects of merino sheep. For the first time, the effect of mechanical stimuli on the biological outcome of this clinically relevant replacement material is shown and directly compared to the conventional unloaded defect situation in a large animal model. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Phelligridin D-loaded oral nanotube titanium implant enhances osseointegration and prevents osteolysis in rat mandible.

PubMed

Kim, Ji-Eun; Takanche, Jyoti Shrestha; Kim, Jeong-Seok; Lee, Min-Ho; Jeon, Jae-Gyu; Park, Il-Song; Yi, Ho-Keun

2018-04-12

Poor bone quality and osteolysis are the major causes of implant failure in dentistry. Here, this study tested the effect of phelligridin D-loaded nanotubes titanium (Ti) for bone formation around the dental implants. The purpose of this study was to enhance osseointegration of phelligridin D-loaded implant into the bone for bone formation and prevention of osteolysis. Cell viability, crystal violet staining, Western blot, alizarin red S staining, alkaline phosphatase activity, tartrate-resistant acid phosphatase staining, micro-computed tromography (μ-CT), hematoxylin and eosin (H&E) and immunohistochemical staining were used in vitro and in vivo to test the biocompatibility of phelligridin D. Phelligridin D enhanced osteoblast differentiation and mineralization by increasing bone morphogenic protein-2/7 (BMP-2/7), Osterix, Runx-2, osteoprotegerin (OPG), alkaline phosphatase and inhibited osteoclast differentiation by decreasing receptor activator of nuclear factor kappa-B ligand (RANKL) in MC-3T3 E1 cells. Further, phelligridin D promoted bone regeneration around nanotube Ti implant surface by increasing the levels of BMP-2/7 and OPG in a rat model. Phelligridin D also inhibited osteolysis by suppressing the expression of RANKL. These findings strongly suggest that phelligridin D is a new compound representing a potential therapeutic candidate for implant failure caused by osteolysis and poor bone quality of teeth.

IGF-1 signaling mediated cell-specific skeletal mechano-transduction.

PubMed

Tian, Faming; Wang, Yongmei; Bikle, Daniel D

2018-02-01

Mechanical loading preserves bone mass and stimulates bone formation, whereas skeletal unloading leads to bone loss. In addition to osteocytes, which are considered the primary sensor of mechanical load, osteoblasts, and bone specific mesenchymal stem cells also are involved. The skeletal response to mechanical signals is a complex process regulated by multiple signaling pathways including that of insulin-like growth factor-1 (IGF-1). Conditional osteocyte deletion of IGF-1 ablates the osteogenic response to mechanical loading. Similarly, osteocyte IGF-1 receptor (IGF-1R) expression is necessary for reloading-induced periosteal bone formation. Transgenic overexpression of IGF-1 in osteoblasts results in enhanced responsiveness to in vivo mechanical loading in mice, a response which is eliminated by osteoblastic conditional disruption of IGF-1 in vivo. Bone marrow derived stem cells (BMSC) from unloaded bone fail to respond to IGF-1 in vitro. IGF-1R is required for the transduction of a mechanical stimulus to downstream effectors, transduction which is lost when the IGF-1R is deleted. Although the molecular mechanisms are not yet fully elucidated, the IGF signaling pathway and its interactions with potentially interlinked signaling cascades involving integrins, the estrogen receptor, and wnt/β-catenin play an important role in regulating adaptive response of cancer bone cells to mechanical stimuli. In this review, we discuss recent advances investigating how IGF-1 and other interlinked molecules and signaling pathways regulate skeletal mechano-transduction involving different bone cells, providing an overview of the IGF-1 signaling mediated cell-specific response to mechanical stimuli. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:576-583, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Dietary protein, calcium metabolism and bone health in humans

USDA-ARS?s Scientific Manuscript database

Protein is the major structural constituent of bone (50% by volume). But it is also a major source of metabolic acid, especially protein from animal sources because it contains sulfur amino acids that generate sulfuric acid. Increased potential renal acid load has been closely associated with increa...

Guided bone regeneration with asymmetric collagen-chitosan membranes containing aspirin-loaded chitosan nanoparticles

PubMed Central

Zhang, Jiayu; Ma, Shiqing; Liu, Zihao; Geng, Hongjuan; Lu, Xin; Zhang, Xi; Li, Hongjie; Gao, Chenyuan; Zhang, Xu; Gao, Ping

2017-01-01

Introduction Membranes allowing the sustained release of drugs that can achieve cell adhesion are very promising for guided bone regeneration. Previous studies have suggested that aspirin has the potential to promote bone regeneration. The purpose of this study was to prepare a local drug delivery system with aspirin-loaded chitosan nanoparticles (ACS) contained in an asymmetric collagen-chitosan membrane (CCM). Methods In this study, the ACS were fabricated using different concentrations of aspirin (5 mg, 25 mg, 50 mg, and 75 mg). The drug release behavior of ACS was studied. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to examine the micromorphology of ACS and aspirin-loaded chitosan nanoparticles contained in chitosan-collagen membranes (ACS-CCM). In vitro bone mesenchymal stem cells (BMSCs) were cultured and critical-sized cranial defects on Sprague-Dawley rats were made to evaluate the effect of the ACS-CCM on bone regeneration. Results Drug release behavior results of ACS showed that the nanoparticles fabricated in this study could successfully sustain the release of the drug. TEM showed the morphology of the nanoparticles. SEM images indicated that the asymmetric membrane comprised a loose collagen layer and a dense chitosan layer. In vitro studies showed that ACS-CCM could promote the proliferation of BMSCs, and that the degree of differentiated BMSCs seeded on CCMs containing 50 mg of ACS was higher than that of other membranes. Micro-computed tomography showed that 50 mg of ACS-CCM resulted in enhanced bone regeneration compared with the control group. Conclusion This study shows that the ACS-CCM would allow the sustained release of aspirin and have further osteogenic potential. This membrane is a promising therapeutic approach to guiding bone regeneration. PMID:29276386

Guided bone regeneration with asymmetric collagen-chitosan membranes containing aspirin-loaded chitosan nanoparticles.

PubMed

Zhang, Jiayu; Ma, Shiqing; Liu, Zihao; Geng, Hongjuan; Lu, Xin; Zhang, Xi; Li, Hongjie; Gao, Chenyuan; Zhang, Xu; Gao, Ping

2017-01-01

Membranes allowing the sustained release of drugs that can achieve cell adhesion are very promising for guided bone regeneration. Previous studies have suggested that aspirin has the potential to promote bone regeneration. The purpose of this study was to prepare a local drug delivery system with aspirin-loaded chitosan nanoparticles (ACS) contained in an asymmetric collagen-chitosan membrane (CCM). In this study, the ACS were fabricated using different concentrations of aspirin (5 mg, 25 mg, 50 mg, and 75 mg). The drug release behavior of ACS was studied. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to examine the micromorphology of ACS and aspirin-loaded chitosan nanoparticles contained in chitosan-collagen membranes (ACS-CCM). In vitro bone mesenchymal stem cells (BMSCs) were cultured and critical-sized cranial defects on Sprague-Dawley rats were made to evaluate the effect of the ACS-CCM on bone regeneration. Drug release behavior results of ACS showed that the nanoparticles fabricated in this study could successfully sustain the release of the drug. TEM showed the morphology of the nanoparticles. SEM images indicated that the asymmetric membrane comprised a loose collagen layer and a dense chitosan layer. In vitro studies showed that ACS-CCM could promote the proliferation of BMSCs, and that the degree of differentiated BMSCs seeded on CCMs containing 50 mg of ACS was higher than that of other membranes. Micro-computed tomography showed that 50 mg of ACS-CCM resulted in enhanced bone regeneration compared with the control group. This study shows that the ACS-CCM would allow the sustained release of aspirin and have further osteogenic potential. This membrane is a promising therapeutic approach to guiding bone regeneration.

Zirconia toughened alumina ceramic foams for potential bone graft applications: fabrication, bioactivation, and cellular responses.

PubMed

He, X; Zhang, Y Z; Mansell, J P; Su, B

2008-07-01

Zirconia toughened alumina (ZTA) has been regarded as the next generation orthopedic graft material due to its excellent mechanical properties and biocompatibility. Porous ZTA ceramics with good interconnectivity can potentially be used as bone grafts for load-bearing applications. In this work, three-dimensional (3D) interconnected porous ZTA ceramics were fabricated using a direct foaming method with egg white protein as binder and foaming agent. The results showed that the porous ZTA ceramics possessed a bimodal pore size distribution. Their mechanical properties were comparable to those of cancellous bone. Due to the bio-inertness of alumina and zirconia ceramics, surface bioactivation of the ZTA foams was carried out in order to improve their bioactivity. A simple NaOH soaking method was employed to change the surface chemistry of ZTA through hydroxylation. Treated samples were tested by conducting osteoblast-like cell culture in vitro. Improvement on cells response was observed and the strength of porous ZTA has not been deteriorated after the NaOH treatment. The porous 'bioactivated' ZTA ceramics produced here could be potentially used as non-degradable bone grafts for load-bearing applications.

The Hopper: A Wearable Robotic Device Testbed for Micro-Gravity Bone-Loading Proof-of-Concept

NASA Technical Reports Server (NTRS)

Beck, C. E.; Rovekamp, R. N.; Neuhaus, P. D.

2015-01-01

Wearable robotic systems are showing increased potential for addressing crew countermeasures needs. Wearable robots offer a compactness, programmability, and eccentric loading capability not present in more conventional exercise equipment. Correspondingly, advancements in the man to machine interface has progressed, allowing for higher loads to be applied directly to the person in new and novel ways. Recently, the X1 exoskeleton, a lower extremity wearable robot originally designed for mobility assistance and rehabilitation, underwent human subject testing to assess its potential as a knee dynamometer. This was of interest to NASA physiologists because currently strength is not assessed in flight due to hardware limitations, and thus there is a poor understanding of the time course of in-flight changes to muscle strength. The study concluded that the X1 compared well with the Biodex, the "gold standard" in terrestrial dynamometry, with coefficients of variation less than 6.0%. In a following study, the X1 powered ankle was evaluated for its efficacy in exercising calf muscles. Current on-orbit countermeasures equipment does not adequately protect the calf from atrophy. The results of this study were also positive (targeted muscle activity demonstrated via comparing pre- and post-exercise magnetic resonance imaging T2 measurements), again showing the efficacy of wearable robotic devices for addressing the countermeasure needs of our astronauts. Based on these successes and lessons learned, the Grasshopper was co-developed between IHMC (Florida Institute for Human and Machine Cognition) and NASA. The Grasshopper, or the Hopper for short, is a wearable robotic device designed to address muscle and bone density loss for astronauts spending extended periods of time in micro-gravity. The Grasshopper connects to the user's torso like a hiking backpack, over the shoulders and around the waist. At the feet are footplates that strap to the user. There are two actuators, one at each "knee" joint, which are capable of high fidelity torque control. Because the Hopper uses motors instead of gravity to create the load on the user, the device is suited for use on space missions. Exercise in zero-gravity conditions is critical to maintain muscle strength and bone mass. In operation, the actuators try to fold up, or collapse, the device, putting a compressive load between the user's feet and torso. This force is similar to carrying a heavy backpack. The user then bends and extends his or her knees, replicating a weightlifting squat exercise. The applied load is precisely controlled by a computer, and can be programmed to simulate gravitation loads or any desired load prescription, such as free-weight squat exercise. It is even possible to perform eccentric exercises, or negatives, without the need for a spotter. Because the hip joints, as well as the spine and long leg bones, are in the applied load path, there is the potential to stimulate bone growth, countering the typical bone loss when astronauts return from extended duration space travel.

Bioactive calcium silicate ceramics and coatings.

PubMed

Liu, Xuanyong; Morra, Marco; Carpi, Angelo; Li, Baoe

2008-10-01

CaO-SiO2 based ceramics have been regarded as potential candidates for artificial bone due to their excellent bone bioactivity and biocompatibility. However, they cannot be used as implants under a heavy load because of their poor mechanical properties, in particular low fracture toughness. Plasma spraying CaO-SiO2 based ceramic coatings onto titanium alloys can expand their application to the hard tissue replacement under a heavy load. Plasma sprayed wollastonite, dicalcium silicate and diopside coatings have excellent bone bioactivity and high bonding strength to titanium alloys. It is possible that these plasma sprayed CaO-SiO2 based ceramic coatings will be applied in clinic after they are widely and systematically researched.

Effects of Loading Duration and Short Rest Insertion on Cancellous and Cortical Bone Adaptation in the Mouse Tibia

PubMed Central

Yang, Haisheng; Embry, Rachel E.; Main, Russell P.

2017-01-01

The skeleton’s osteogenic response to mechanical loading can be affected by loading duration and rest insertion during a series of loading events. Prior animal loading studies have shown that the cortical bone response saturates quickly and short rest insertions between load cycles can enhance cortical bone formation. However, it remains unknown how loading duration and short rest insertion affect load-induced osteogenesis in the mouse tibial compressive loading model, and particularly in cancellous bone. To address this issue, we applied cyclic loading (-9 N peak load; 4 Hz) to the tibiae of three groups of 16 week-old female C57BL/6 mice for two weeks, with a different number of continuous load cycles applied daily to each group (36, 216 and 1200). A fourth group was loaded under 216 daily load cycles with a 10 s rest insertion after every fourth cycle. We found that as few as 36 load cycles per day were able to induce osteogenic responses in both cancellous and cortical bone. Furthermore, while cortical bone area and thickness continued to increase through 1200 cycles, the incremental increase in the osteogenic response decreased as load number increased, indicating a reduced benefit of the increasing number of load cycles. In the proximal metaphyseal cancellous bone, trabecular thickness increased with load up to 216 cycles. We also found that insertion of a 10 s rest between load cycles did not improve the osteogenic response of the cortical or cancellous tissues compared to continuous loading in this model given the age and sex of the mice and the loading parameters used here. These results suggest that relatively few load cycles (e.g. 36) are sufficient to induce osteogenic responses in both cortical and cancellous bone in the mouse tibial loading model. Mechanistic studies using the mouse tibial loading model to examine bone formation and skeletal mechanobiology could be accomplished with relatively few load cycles. PMID:28076363

Adaptive scapula bone remodeling computational simulation: Relevance to regenerative medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sharma, Gulshan B., E-mail: gbsharma@ucalgary.ca; University of Pittsburgh, Swanson School of Engineering, Department of Bioengineering, Pittsburgh, Pennsylvania 15213; University of Calgary, Schulich School of Engineering, Department of Mechanical and Manufacturing Engineering, Calgary, Alberta T2N 1N4

Shoulder arthroplasty success has been attributed to many factors including, bone quality, soft tissue balancing, surgeon experience, and implant design. Improved long-term success is primarily limited by glenoid implant loosening. Prosthesis design examines materials and shape and determines whether the design should withstand a lifetime of use. Finite element (FE) analyses have been extensively used to study stresses and strains produced in implants and bone. However, these static analyses only measure a moment in time and not the adaptive response to the altered environment produced by the therapeutic intervention. Computational analyses that integrate remodeling rules predict how bone will respondmore » over time. Recent work has shown that subject-specific two- and three dimensional adaptive bone remodeling models are feasible and valid. Feasibility and validation were achieved computationally, simulating bone remodeling using an intact human scapula, initially resetting the scapular bone material properties to be uniform, numerically simulating sequential loading, and comparing the bone remodeling simulation results to the actual scapula’s material properties. Three-dimensional scapula FE bone model was created using volumetric computed tomography images. Muscle and joint load and boundary conditions were applied based on values reported in the literature. Internal bone remodeling was based on element strain-energy density. Initially, all bone elements were assigned a homogeneous density. All loads were applied for 10 iterations. After every iteration, each bone element’s remodeling stimulus was compared to its corresponding reference stimulus and its material properties modified. The simulation achieved convergence. At the end of the simulation the predicted and actual specimen bone apparent density were plotted and compared. Location of high and low predicted bone density was comparable to the actual specimen. High predicted bone density was greater than actual specimen. Low predicted bone density was lower than actual specimen. Differences were probably due to applied muscle and joint reaction loads, boundary conditions, and values of constants used. Work is underway to study this. Nonetheless, the results demonstrate three dimensional bone remodeling simulation validity and potential. Such adaptive predictions take physiological bone remodeling simulations one step closer to reality. Computational analyses are needed that integrate biological remodeling rules and predict how bone will respond over time. We expect the combination of computational static stress analyses together with adaptive bone remodeling simulations to become effective tools for regenerative medicine research.« less

Adaptive scapula bone remodeling computational simulation: Relevance to regenerative medicine

NASA Astrophysics Data System (ADS)

Sharma, Gulshan B.; Robertson, Douglas D.

2013-07-01

Shoulder arthroplasty success has been attributed to many factors including, bone quality, soft tissue balancing, surgeon experience, and implant design. Improved long-term success is primarily limited by glenoid implant loosening. Prosthesis design examines materials and shape and determines whether the design should withstand a lifetime of use. Finite element (FE) analyses have been extensively used to study stresses and strains produced in implants and bone. However, these static analyses only measure a moment in time and not the adaptive response to the altered environment produced by the therapeutic intervention. Computational analyses that integrate remodeling rules predict how bone will respond over time. Recent work has shown that subject-specific two- and three dimensional adaptive bone remodeling models are feasible and valid. Feasibility and validation were achieved computationally, simulating bone remodeling using an intact human scapula, initially resetting the scapular bone material properties to be uniform, numerically simulating sequential loading, and comparing the bone remodeling simulation results to the actual scapula's material properties. Three-dimensional scapula FE bone model was created using volumetric computed tomography images. Muscle and joint load and boundary conditions were applied based on values reported in the literature. Internal bone remodeling was based on element strain-energy density. Initially, all bone elements were assigned a homogeneous density. All loads were applied for 10 iterations. After every iteration, each bone element's remodeling stimulus was compared to its corresponding reference stimulus and its material properties modified. The simulation achieved convergence. At the end of the simulation the predicted and actual specimen bone apparent density were plotted and compared. Location of high and low predicted bone density was comparable to the actual specimen. High predicted bone density was greater than actual specimen. Low predicted bone density was lower than actual specimen. Differences were probably due to applied muscle and joint reaction loads, boundary conditions, and values of constants used. Work is underway to study this. Nonetheless, the results demonstrate three dimensional bone remodeling simulation validity and potential. Such adaptive predictions take physiological bone remodeling simulations one step closer to reality. Computational analyses are needed that integrate biological remodeling rules and predict how bone will respond over time. We expect the combination of computational static stress analyses together with adaptive bone remodeling simulations to become effective tools for regenerative medicine research.

Preparation and Evaluations of Mangiferin-Loaded PLGA Scaffolds for Alveolar Bone Repair Treatment Under the Diabetic Condition.

PubMed

Li, Hao; Liao, Hongbing; Bao, Chongyun; Xiao, Yu; Wang, Qi

2017-02-01

The aim of the present study was to prepare and evaluate a sustained-release mangiferin scaffold for improving alveolar bone defect repair in diabetes. Mangiferin-loaded poly(D,L-lactide-co-glycolide) (PLGA) scaffolds were prepared using a freeze-drying technique with ice particles as the porogen material. The produced scaffolds were examined using a scanning electron microscope (SEM). Drug content and drug release were detected using a spectrophotometer. Degradation behaviors were monitored as a measure of weight loss and examined using SEM. Then, the scaffolds were incubated with rat bone marrow stromal cells under the diabetic condition in vitro, and cell viability was assessed using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Afterward, the scaffolds were implanted into alveolar bone defects of diabetic rats, and bone repair was examined using hematoxylin and eosin staining. The fabricated scaffolds showed porous structures, with average pore size range from 111.35 to 169.45 μm. A higher PLGA concentration led to decreased average pore size. A lower PLGA concentration or a higher mangiferin concentration resulted in increased drug content. The prepared scaffolds released mangiferin in a sustained manner with relatively low initial burst during 10 weeks. Their degradation ratios gradually increased as degradation proceeded. The mangiferin-loaded scaffolds attenuated cell viability decrease under the diabetic condition in vitro. Moreover, they increased histological scorings of bone regeneration and improved delayed alveolar bone defect healing in diabetic rats. These results suggest that the produced mangiferin-loaded scaffolds may provide a potential approach in the treatment of impaired alveolar bone healing in diabetes.

Establishment of a bilateral femoral large segmental bone defect mouse model potentially applicable to basic research in bone tissue engineering.

PubMed

Xing, Junchao; Jin, Huiyong; Hou, Tianyong; Chang, Zhengqi; Luo, Fei; Wang, Pinpin; Li, Zhiqiang; Xie, Zhao; Xu, Jianzhong

2014-12-01

To understand the cellular mechanism underlying bone defect healing in the context of tissue engineering, a reliable, reproducible, and standardized load-bearing large segmental bone defect model in small animals is indispensable. The aim of this study was to establish and evaluate a bilateral femoral defect model in mice. Donor mouse bone marrow mesenchymal stem cells (mBMSCs) were obtained from six mice (FVB/N) and incorporated into partially demineralized bone matrix scaffolds to construct tissue-engineered bones. In total, 36 GFP(+) mice were used for modeling. Titanium fixation plates with locking steel wires were attached to the femurs for stabilization, and 2-mm-long segmental bone defects were created in the bilateral femoral midshafts. The defects in the left and right femurs were transplanted with tissue-engineered bones and control scaffolds, respectively. The healing process was monitored by x-ray radiography, microcomputed tomography, and histology. The capacity of the transplanted mBMSCs to recruit host CD31(+) cells was investigated by immunofluorescence and real-time polymerase chain reaction. Postoperatively, no complication was observed, except that two mice died of unknown causes. Stable fixation of femurs and implants with full load bearing was achieved in all animals. The process of bone defect repair was significantly accelerated due to the introduction of mBMSCs. Moreover, the transplanted mBMSCs attracted more host CD31(+) endothelial progenitors into the grafts. The present study established a feasible, reproducible, and clinically relevant bilateral femoral large segmental bone defect mouse model. This model is potentially suitable for basic research in the field of bone tissue engineering. Copyright © 2014 Elsevier Inc. All rights reserved.

Combination of Heel-strike like Mechanical Loading with Deproteinized Cancellous Bone Scaffold Implantation to Repair Segmental Bone Defects in Rabbits.

PubMed

Huang, Guofeng; Liu, Guojun; Zhang, Feng; Gao, Jianting; Wang, Jiangze; Chen, Qi; Wu, Benwen; Ding, Zhenqi; Cai, Taoyi

2017-01-01

Under physiological conditions bone defects often occur at mechanical load bearing sites and bone substitutes used for regeneration should be similarly subjected to mechanical loading stress. In this study, we investigated whether a novel heel-strike like mechanical loading method can be used as a complementary therapy to promote bone regeneration following bone substitute grafting. To test this, three groups of rabbits with segmental bone defects in the tibia were implanted with bovine deproteinized cancellous bone scaffold (DCBS), with one group also receiving heel-strike like mechanical loading generated by a rap stress stimulator. From weeks 4-12 post-operation X-ray and micro-CT scanning showed that rabbits receiving combination therapy had significantly more callus at the bone defect. Moreover, bone defects in the combination group were completely replaced with new bone at week 12, while the DCBS implantation alone group healed only partially and rabbits receiving neither DCBS nor mechanical loading developed only small calluses throughout the observation period. Analysis of micro-CT scanning results demonstrated that new bone density in the combination group was significantly higher than the DCBS only group at weeks 4 and 12 ( p <0.05). H&E staining results also indicated a significantly higher percentage of new bone in the bone defect area and a lower percentage of residual scaffold in the combination group compared to the DCBS only group ( p <0.05). Thus, this heel-strike like mechanical loading method appears to accelerate bone regeneration following substitute implantation by restoring a local mechanical loading environment in segmental bone defects.

Technetium-99m-labeled ceftizoxime loaded long-circulating and pH-sensitive liposomes used to identify osteomyelitis.

PubMed

Ferreira, Soraya Maria Zandim Maciel Dias; Domingos, Giselle Pires; Ferreira, Diego dos Santos; Rocha, Talita Guieiro Ribeiro; Serakides, Rogéria; de Faria Rezende, Cleuza Maria; Cardoso, Valbert Nascimento; Fernandes, Simone Odília Antunes; Oliveira, Mônica Cristina

2012-07-15

Osteomyelitis is an infectious disease located in the bone or bone marrow. Long-circulating and pH-sensitive liposomes containing a technetium-99m-labeled antibiotic, ceftizoxime, (SpHL-(99m)Tc-CF) were developed to identify osteomyelitis foci. Biodistribution studies and scintigraphic images of bone infection or non infection-bearing rats that had been treated with these liposomes were performed. A high accumulation in infectious foci and high values in the target-non target ratio could be observed. These results indicate the potential of SpHL-(99m)Tc-CF as a potential agent for the diagnosis of bone infections. Copyright © 2012 Elsevier Ltd. All rights reserved.

Amino acid supplementation alters bone metabolism during simulated weightlessness

NASA Technical Reports Server (NTRS)

Zwart, S. R.; Davis-Street, J. E.; Paddon-Jones, D.; Ferrando, A. A.; Wolfe, R. R.; Smith, S. M.

2005-01-01

High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

Load transfer in the proximal tibia following implantation with a unicompartmental knee replacement: a static snapshot.

PubMed

Simpson, D J; Kendrick, B J L; Dodd, C A F; Price, A J; Gill, H S; Murray, D W

2011-05-01

Unicompartmental knee replacement (UKR) is an appealing alternative to total knee replacement when the patient has isolated medial compartment osteoarthritis. A common observation post-operatively is radiolucency between the tibial tray wall and the bone. In addition, some patients complain of persistent pain over the proximal tibia antero-medially; this may be related to elevated bone strains in the tibia. Currently, there is no intentionally made mechanical bond between the vertical wall of an Oxford UKR and the adjacent bone; whether one exists or not will influence the load transmission in the proximal tibia and may affect the elevated tibia strain. The aim of this study was to investigate how introducing a mechanical tie between the tibial tray wall and the adjacent bone might alter the load carried into the tibia for both cemented and cementless UKRs. Strain energy density in the region of bone adjacent to the tray wall was considerably increased when a mechanical tie was introduced; this has the potential of reducing the likelihood of a radiolucency occurring in that region. Moreover, a mechanical tie had the effect of reducing proximal tibia strain, which may decrease the incidence of pain following implantation with a UKR.

3D printed hyperelastic "bone" scaffolds and regional gene therapy: A novel approach to bone healing.

PubMed

Alluri, Ram; Jakus, Adam; Bougioukli, Sofia; Pannell, William; Sugiyama, Osamu; Tang, Amy; Shah, Ramille; Lieberman, Jay R

2018-04-01

The purpose of this study was to evaluate the viability of human adipose-derived stem cells (ADSCs) transduced with a lentiviral (LV) vector to overexpress bone morphogenetic protein-2 (BMP-2) loaded onto a novel 3D printed scaffold. Human ADSCs were transduced with a LV vector carrying the cDNA for BMP-2. The transduced cells were loaded onto a 3D printed Hyperelastic "Bone" (HB) scaffold. In vitro BMP-2 production was assessed using enzyme-linked immunosorbent assay analysis. The ability of ADSCs loaded on the HB scaffold to induce in vivo bone formation in a hind limb muscle pouch model was assessed in the following groups: ADSCs transduced with LV-BMP-2, LV-green fluorescent protein, ADSCs alone, and empty HB scaffolds. Bone formation was assessed using radiographs, histology and histomorphometry. Transduced ADSCs BMP-2 production on the HB scaffold at 24 hours was similar on 3D printed HB scaffolds versus control wells with transduced cells alone, and continued to increase after 1 and 2 weeks of culture. Bone formation was noted in LV-BMP-2 animals on plain radiographs at 2 and 4 weeks after implantation; no bone formation was noted in the other groups. Histology demonstrated that the LV-BMP-2 group was the only group that formed woven bone and the mean bone area/tissue area was significantly greater when compared with the other groups. 3D printed HB scaffolds are effective carriers for transduced ADSCs to promote bone repair. The combination of gene therapy and tissue engineered scaffolds is a promising multidisciplinary approach to bone repair with significant clinical potential. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1104-1110, 2018. © 2018 Wiley Periodicals, Inc.

Mechanical loading, damping, and load-driven bone formation in mouse tibiae.

PubMed

Dodge, Todd; Wanis, Mina; Ayoub, Ramez; Zhao, Liming; Watts, Nelson B; Bhattacharya, Amit; Akkus, Ozan; Robling, Alexander; Yokota, Hiroki

2012-10-01

Mechanical loads play a pivotal role in the growth and maintenance of bone and joints. Although loading can activate anabolic genes and induce bone remodeling, damping is essential for preventing traumatic bone injury and fracture. In this study we investigated the damping capacity of bone, joint tissue, muscle, and skin using a mouse hindlimb model of enhanced loading in conjunction with finite element modeling to model bone curvature. Our hypothesis was that loads were primarily absorbed by the joints and muscle tissue, but that bone also contributed to damping through its compression and natural bending. To test this hypothesis, fresh mouse distal lower limb segments were cyclically loaded in axial compression in sequential bouts, with each subsequent bout having less surrounding tissue. A finite element model was generated to model effects of bone curvature in silico. Two damping-related parameters (phase shift angle and energy loss) were determined from the output of the loading experiments. Interestingly, the experimental results revealed that the knee joint contributed to the largest portion of the damping capacity of the limb, and bone itself accounted for approximately 38% of the total phase shift angle. Computational results showed that normal bone curvature enhanced the damping capacity of the bone by approximately 40%, and the damping effect grew at an accelerated pace as curvature was increased. Although structural curvature reduces critical loads for buckling in beam theory, evolution apparently favors maintaining curvature in the tibia. Histomorphometric analysis of the tibia revealed that in response to axial loading, bone formation was significantly enhanced in the regions that were predicted to receive a curvature-induced bending moment. These results suggest that in addition to bone's compressive damping capacity, surrounding tissues, as well as naturally-occurring bone curvature, also contribute to mechanical damping, which may ultimately affect bone remodeling and bone quality. Copyright © 2012 Elsevier Inc. All rights reserved.

A poly (lactide-co-glycolide) film loaded with abundant bone morphogenetic protein-2: A substrate promoting osteoblast attachment, proliferation and differentiation in bone tissue engineering.

PubMed

Qu, Xiangyang; Cao, Yujiang; Chen, Cong; Die, Xiaohong; Kang, Quan

2014-12-10

We explored a novel biodegradable poly (lactide-co-glycolide) (PLGA) film loaded with over 80 wt% bone morphogenetic protein (BMP-2), which was regarded as a substrate promoting osteoblast attachment, proliferation and differentiation for application of bone tissue engineering. Using phospholipid as a surfactant, BMP-2 was modified as a complex (PBC) for dispersing in PLGA/dichloromethane solution. The PLGA film loaded with BMP-2 and phospholipid complex (PBC-PF) showed rough and draped morphology with high entrapment efficiency exceeding 80% and good hydrophilicity respectively. The in-vitro release study of BMP-2 showed that about 50% BMP-2 was slowly and continuously released from PBC-PF within 5 weeks and had a short initial burst release only in the last 1.5 days, which was better than serious burst release of PLGA film loaded with pure BMP-2 without phospholipid (BMP-PF) controlling. By comparison with other PLGA films and tissue culture plates, it was confirmed that PBC-PF significantly promoted the attachment, proliferation and differentiation of osteoblasts with higher entrapment efficiency and better sustained release. These advantages illustrated that PBC-PF could be a potential substrate providing long-term requisite growth factors for osteoblasts, which might be applied in bone tissue engineering. This article is protected by copyright. All rights reserved. Copyright © 2014 Wiley Periodicals, Inc., A Wiley Company.

A poly(lactide-co-glycolide) film loaded with abundant bone morphogenetic protein-2: A substrate-promoting osteoblast attachment, proliferation, and differentiation in bone tissue engineering.

PubMed

Qu, Xiangyang; Cao, Yujiang; Chen, Cong; Die, Xiaohong; Kang, Quan

2015-08-01

We explored a novel biodegradable poly(lactide-co-glycolide) (PLGA) film loaded with over 80 wt % bone morphogenetic protein (BMP)-2, which was regarded as a substrate-promoting osteoblast attachment, proliferation, and differentiation for application of bone tissue engineering. Using phospholipid as a surfactant, BMP-2 was modified as a complex (PBC) for dispersing in PLGA/dichloromethane solution. The PLGA film loaded with BMP-2 and phospholipid complex (PBC-PF) showed rough and draped morphology with high entrapment efficiency exceeding 80% and good hydrophilicity, respectively. The in vitro release study of BMP-2 showed that about 50% BMP-2 was slowly and continuously released from PBC-PF within 5 weeks and had a short initial burst release only in the last 1.5 days, which was better than serious burst release of PLGA film loaded with pure BMP-2 without phospholipid (BMP-PF) as control. By comparison with other PLGA films and tissue culture plates, it was confirmed that PBC-PF significantly promoted the attachment, proliferation, and differentiation of osteoblasts with higher entrapment efficiency and better sustained release. These advantages illustrated that PBC-PF could be a potential substrate providing long-term requisite growth factors for osteoblasts, which might be applied in bone tissue engineering. © 2015 Wiley Periodicals, Inc.

A theoretical framework for strain-related trabecular bone maintenance and adaptation.

PubMed

Ruimerman, R; Hilbers, P; van Rietbergen, B; Huiskes, R

2005-04-01

It is assumed that density and morphology of trabecular bone is partially controlled by mechanical forces. How these effects are expressed in the local metabolic functions of osteoclast resorption and osteoblast formation is not known. In order to investigate possible mechano-biological pathways for these mechanisms we have proposed a mathematical theory (Nature 405 (2000) 704). This theory is based on hypothetical osteocyte stimulation of osteoblast bone formation, as an effect of elevated strain in the bone matrix, and a role for microcracks and disuse in promoting osteoclast resorption. Applied in a 2-D Finite Element Analysis model, the theory explained the formation of trabecular patterns. In this article we present a 3-D FEA model based on the same theory and investigated its potential morphological predictability of metabolic reactions to mechanical loads. The computations simulated the development of trabecular morphological details during growth, relative to measurements in growing pigs, reasonably realistic. They confirmed that the proposed mechanisms also inherently lead to optimal stress transfer. Alternative loading directions produced new trabecular orientations. Reduction of load reduced trabecular thickness, connectivity and mass in the simulation, as is seen in disuse osteoporosis. Simulating the effects of estrogen deficiency through increased osteoclast resorption frequencies produced osteoporotic morphologies as well, as seen in post-menopausal osteoporosis. We conclude that the theory provides a suitable computational framework to investigate hypothetical relationships between bone loading and metabolic expressions.

Impact of mechanical stretch on the cell behaviors of bone and surrounding tissues

PubMed Central

Yu, Hye-Sun; Kim, Jung-Ju; Kim, Hae-Won; Lewis, Mark P; Wall, Ivan

2016-01-01

Mechanical loading is recognized to play an important role in regulating the behaviors of cells in bone and surrounding tissues in vivo. Many in vitro studies have been conducted to determine the effects of mechanical loading on individual cell types of the tissues. In this review, we focus specifically on the use of the Flexercell system as a tool for studying cellular responses to mechanical stretch. We assess the literature describing the impact of mechanical stretch on different cell types from bone, muscle, tendon, ligament, and cartilage, describing individual cell phenotype responses. In addition, we review evidence regarding the mechanotransduction pathways that are activated to potentiate these phenotype responses in different cell populations. PMID:26977284

Uniaxial and Multiaxial Fatigue Life Prediction of the Trabecular Bone Based on Physiological Loading: A Comparative Study.

PubMed

Fatihhi, S J; Harun, M N; Abdul Kadir, Mohammed Rafiq; Abdullah, Jaafar; Kamarul, T; Öchsner, Andreas; Syahrom, Ardiyansyah

2015-10-01

Fatigue assessment of the trabecular bone has been developed to give a better understanding of bone properties. While most fatigue studies are relying on uniaxial compressive load as the method of assessment, in various cases details are missing, or the uniaxial results are not very realistic. In this paper, the effect of three different load histories from physiological loading applied on the trabecular bone were studied in order to predict the first failure surface and the fatigue lifetime. The fatigue behaviour of the trabecular bone under uniaxial load was compared to that of multiaxial load using a finite element simulation. The plastic strain was found localized at the trabecular structure under multiaxial load. On average, applying multiaxial loads reduced more than five times the fatigue life of the trabecular bone. The results provide evidence that multiaxial loading is dominated in the low cycle fatigue in contrast to the uniaxial one. Both bone volume fraction and structural model index were best predictors of failure (p < 0.05) in fatigue for both types of loading, whilst uniaxial loading has indicated better values in most cases.

Selecting boundary conditions in physiological strain analysis of the femur: Balanced loads, inertia relief method and follower load.

PubMed

Heyland, Mark; Trepczynski, Adam; Duda, Georg N; Zehn, Manfred; Schaser, Klaus-Dieter; Märdian, Sven

2015-12-01

Selection of boundary constraints may influence amount and distribution of loads. The purpose of this study is to analyze the potential of inertia relief and follower load to maintain the effects of musculoskeletal loads even under large deflections in patient specific finite element models of intact or fractured bone compared to empiric boundary constraints which have been shown to lead to physiological displacements and surface strains. The goal is to elucidate the use of boundary conditions in strain analyses of bones. Finite element models of the intact femur and a model of clinically relevant fracture stabilization by locking plate fixation were analyzed with normal walking loading conditions for different boundary conditions, specifically re-balanced loading, inertia relief and follower load. Peak principal cortex surface strains for different boundary conditions are consistent (maximum deviation 13.7%) except for inertia relief without force balancing (maximum deviation 108.4%). Influence of follower load on displacements increases with higher deflection in fracture model (from 3% to 7% for force balanced model). For load balanced models, follower load had only minor influence, though the effect increases strongly with higher deflection. Conventional constraints of fixed nodes in space should be carefully reconsidered because their type and position are challenging to justify and for their potential to introduce relevant non-physiological reaction forces. Inertia relief provides an alternative method which yields physiological strain results. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

Functional adaptation to mechanical loading in both cortical and cancellous bone is controlled locally and is confined to the loaded bones.

PubMed

Sugiyama, Toshihiro; Price, Joanna S; Lanyon, Lance E

2010-02-01

In order to validate whether bones' functional adaptation to mechanical loading is a local phenomenon, we randomly assigned 21 female C57BL/6 mice at 19 weeks of age to one of three equal numbered groups. All groups were treated with isoflurane anesthesia three times a week for 2 weeks (approximately 7 min/day). During each anaesthetic period, the right tibiae/fibulae in the DYNAMIC+STATIC group were subjected to a peak dynamic load of 11.5 N (40 cycles with 10-s intervals between cycles) superimposed upon a static "pre-load" of 2.0 N. This total load of 13.5 N engendered peak longitudinal strains of approximately 1400 microstrain on the medial surface of the tibia at a middle/proximal site. The right tibiae/fibulae in the STATIC group received the static "pre-load" alone while the NOLOAD group received no artificial loading. After 2 weeks, the animals were sacrificed and both tibiae, fibulae, femora, ulnae and radii analyzed by three-dimensional high-resolution (5 mum) micro-computed tomography (microCT). In the DYNAMIC+STATIC group, the proximal trabecular percent bone volume and cortical bone volume at the proximal and middle levels of the right tibiae as well as the cortical bone volume at the middle level of the right fibulae were markedly greater than the left. In contrast, the left bones in the DYNAMIC+STATIC group showed no differences compared to the left or right bones in the NOLOAD or STATIC group. These microCT data were confirmed by two-dimensional examination of fluorochrome labels in bone sections which showed the predominantly woven nature of the new bone formed in the loaded bones. We conclude that the adaptive response in both cortical and trabecular regions of bones subjected to short periods of dynamic loading, even when this response is sufficiently vigorous to stimulate woven bone formation, is confined to the loaded bones and does not involve changes in other bones that are adjacent, contra-lateral or remote to them. (c) 2009 Elsevier Inc. All rights reserved.

Design and biomechanical evaluation of a cementable endosteal blade implant.

PubMed

Pugh, J; Weiss, C; Weiss, F; Malkin, D

1976-07-01

A cementable endosteal blade implant has been developed and evaluated. Inherent in the design are the following factors: minimization of stress concentrators, ease of implantation, and high resistance to loosening. Other potential advantages of this design as compared with conventional endosteal blade implants include reduced hazards of postoperative infection and reduced likelihood of metallic corrosion. Six conventional endosteal implants and six cementable implants were installed in steer mandibles using standard dental surgical techniques and Simplex-brand methyl methacrylate bone cement. They were loaded in uniaxial compresstion at a loading rate of 0.0122 in./min. the stiffness (S), deformation at 900-lb load (D900), proportional limil (PL), and load at 0.04 in. deformation (L0.04) were calculated for each test. The cementable design showed a twofold increase in stiffness, only 17% of the deformation at 900lb, more than twice the proportional limit, and at least twice the load at 0.04 in. deformation when compared with similar values for the conventional endosteal implants. This study reveals that, in addition to being unstable in bone, conventional endosteal implants are also unstable when used with acrylic bone cement. The new design should eliminate most of the problems associated with endosteal blade implantation.

Hindlimb unloading of growing rats: a model for predicting skeletal changes during space flight.

PubMed

Morey-Holton, E R; Globus, R K

1998-05-01

A model that uses hindlimb unloading of rats was developed to study the consequences of skeletal unloading and reloading as occurs during and following space flight. Studies using the model were initiated two decades ago and further developed at National Aeronautics and Space Administration (NASA)-Ames Research Center. The model mimics some aspects of exposure to microgravity by removing weightbearing loads from the hindquarters and producing a cephalic fluid shift. Unlike space flight, the forelimbs remain loaded in the model, providing a useful internal control to distinguish between the local and systemic effects of hindlimb unloading. Rats that are hindlimb unloaded by tail traction gain weight at the same rate as pairfed controls, and glucocorticoid levels are not different from controls, suggesting that systemic stress is minimal. Unloaded bones display reductions in cancellous osteoblast number, cancellous mineral apposition rate, trabecular bone volume, cortical periosteal mineralization rate, total bone mass, calcium content, and maturation of bone mineral relative to controls. Subsequent studies reveal that these changes also occur in rats exposed to space flight. In hindlimb unloaded rats, bone formation rates and masses of unloaded bones decline relative to controls, while loaded bones do not change despite a transient reduction in serum 1,25-dihydroxyvitamin D (1,25D) concentrations. Studies using the model to evaluate potential countermeasures show that 1,25D, growth hormone, dietary calcium, alendronate, and muscle stimulation modify, but do not completely correct, the suppression of bone growth caused by unloading, whereas continuous infusion of transforming growth factor-beta2 or insulin-like growth factor-1 appears to protect against some of the bone changes caused by unloading. These results emphasize the importance of local as opposed to systemic factors in the skeletal response to unloading, and reveal the pivotal role that osteoblasts play in the response to gravitational loading. The hindlimb unloading model provides a unique opportunity to evaluate in detail the physiological and cellular mechanisms of the skeletal response to weightbearing loads, and has proven to be an effective model for space flight.

Hindlimb unloading of growing rats: a model for predicting skeletal changes during space flight

NASA Technical Reports Server (NTRS)

Morey-Holton, E. R.; Globus, R. K.

1998-01-01

A model that uses hindlimb unloading of rats was developed to study the consequences of skeletal unloading and reloading as occurs during and following space flight. Studies using the model were initiated two decades ago and further developed at National Aeronautics and Space Administration (NASA)-Ames Research Center. The model mimics some aspects of exposure to microgravity by removing weightbearing loads from the hindquarters and producing a cephalic fluid shift. Unlike space flight, the forelimbs remain loaded in the model, providing a useful internal control to distinguish between the local and systemic effects of hindlimb unloading. Rats that are hindlimb unloaded by tail traction gain weight at the same rate as pairfed controls, and glucocorticoid levels are not different from controls, suggesting that systemic stress is minimal. Unloaded bones display reductions in cancellous osteoblast number, cancellous mineral apposition rate, trabecular bone volume, cortical periosteal mineralization rate, total bone mass, calcium content, and maturation of bone mineral relative to controls. Subsequent studies reveal that these changes also occur in rats exposed to space flight. In hindlimb unloaded rats, bone formation rates and masses of unloaded bones decline relative to controls, while loaded bones do not change despite a transient reduction in serum 1,25-dihydroxyvitamin D (1,25D) concentrations. Studies using the model to evaluate potential countermeasures show that 1,25D, growth hormone, dietary calcium, alendronate, and muscle stimulation modify, but do not completely correct, the suppression of bone growth caused by unloading, whereas continuous infusion of transforming growth factor-beta2 or insulin-like growth factor-1 appears to protect against some of the bone changes caused by unloading. These results emphasize the importance of local as opposed to systemic factors in the skeletal response to unloading, and reveal the pivotal role that osteoblasts play in the response to gravitational loading. The hindlimb unloading model provides a unique opportunity to evaluate in detail the physiological and cellular mechanisms of the skeletal response to weightbearing loads, and has proven to be an effective model for space flight.

Biomechanical monitoring of healing bone based on acoustic emission technology.

PubMed

Hirasawa, Yasusuke; Takai, Shinro; Kim, Wook-Cheol; Takenaka, Nobuyuki; Yoshino, Nobuyuki; Watanabe, Yoshinobu

2002-09-01

Acoustic emission testing is a well-established method for assessment of the mechanical integrity of general construction projects. The purpose of the current study was to investigate the usefulness of acoustic emission technology in monitoring the yield strength of healing callus during external fixation. Thirty-five patients with 39 long bones treated with external fixation were evaluated for fracture healing by monitoring load for the initiation of acoustic emission signal (yield strength) under axial loading. The major criteria for functional bone union based on acoustic emission testing were (1) no acoustic emission signal on full weightbearing, and (2) a higher estimated strength than body weight. The yield strength monitored by acoustic emission testing increased with the time of healing. The external fixator could be removed safely and successfully in 97% of the patients. Thus, the acoustic emission method has good potential as a reliable method for monitoring the mechanical status of healing bone.

Asymmetric bone adaptations to soleus mechanical loading after spinal cord injury

PubMed Central

Dudley-Javoroski, S.; Shields, R.K.

2009-01-01

The purpose of this report is to examine longitudinal bone mineral density (BMD) changes in individuals with spinal cord injury (SCI) who began unilateral soleus electrical stimulation early after injury. Twelve men with SCI and seven without SCI underwent peripheral quantitative computed tomography assessment of distal tibia BMD. After 4.5 to 6 years of training, average trained limb BMD was 27.5% higher than untrained limb BMD. The training effect was more pronounced in the central core of the tibia cross-section (40.5% between-limb difference). No between-limb difference emerged in the anterior half of the tibia (19.2 mg/cm3 difference, p>0.05). A robust between-limb difference emerged in the posterior half of the tibia (76.1 mg/cm3 difference, p=0.0439). The posterior tibia BMD of one subject remained within the range of non-SCI values for 3.8 years post-SCI. The results support that the constrained orientation of soleus mechanical loads, administered over several years, elicited bone-sparing effects in the posterior tibia. This study provides a demonstration of the bone-protective potential of a carefully controlled dose of mechanical load. The specific orientation of applied mechanical loads may strongly influence the manifestation of BMD adaptations in humans with SCI. PMID:18799855

Evaluating the relationship between muscle and bone modeling response in older adults.

PubMed

Reider, Lisa; Beck, Thomas; Alley, Dawn; Miller, Ram; Shardell, Michelle; Schumacher, John; Magaziner, Jay; Cawthon, Peggy M; Barbour, Kamil E; Cauley, Jane A; Harris, Tamara

2016-09-01

Bone modeling, the process that continually adjusts bone strength in response to prevalent muscle-loading forces throughout an individual's lifespan, may play an important role in bone fragility with age. Femoral stress, an index of bone modeling response, can be estimated using measurements of DXA derived bone geometry and loading information incorporated into an engineering model. Assuming that individuals have adapted to habitual muscle loading forces, greater stresses indicate a diminished response and a weaker bone. The purpose of this paper was to evaluate the associations of lean mass and muscle strength with the femoral stress measure generated from the engineering model and to examine the extent to which lean mass and muscle strength account for variation in femoral stress among 2539 healthy older adults participating in the Health ABC study using linear regression. Mean femoral stress was higher in women (9.51, SD=1.85Mpa) than in men (8.02, SD=1.43Mpa). Percent lean mass explained more of the variation in femoral stress than did knee strength adjusted for body size (R(2)=0.187 vs. 0.055 in men; R(2)=0.237 vs. 0.095 in women). In models adjusted for potential confounders, for every percent increase in lean mass, mean femoral stress was 0.121Mpa lower (95% CI: -0.138, -0.104; p<0.001) in men and 0.139Mpa lower (95% CI: -0.158, -0.121; p<0.001) in women. The inverse association of femoral stress with lean mass and with knee strength did not differ by category of BMI. Results from this study provide insight into bone modeling differences as measured by femoral stress among older men and women and indicate that lean mass may capture elements of bone's response to load. Copyright © 2016 Elsevier Inc. All rights reserved.

Can physical activity improve peak bone mass?

PubMed

Specker, Bonny; Minett, Maggie

2013-09-01

The pediatric origin of osteoporosis has led many investigators to focus on determining factors that influence bone gain during growth and methods for optimizing this gain. Bone responds to bone loading activities by increasing mass or size. Overall, pediatric studies have found a positive effect of bone loading on bone size and accrual, but the types of loads necessary for a bone response have only recently been investigated in human studies. Findings indicate that responses vary by sex, maturational status, and are site-specific. Estrogen status, body composition, and nutritional status also may influence the bone response to loading. Despite the complex interrelationships among these various factors, it is prudent to conclude that increased physical activity throughout life is likely to optimize bone health.

Effects of mechanical repetitive load on bone quality around implants in rat maxillae

PubMed Central

Uto, Yusuke; Nakano, Takayoshi; Ishimoto, Takuya; Inaba, Nao; Uchida, Yusuke; Sawase, Takashi

2017-01-01

Greater understanding and acceptance of the new concept “bone quality”, which was proposed by the National Institutes of Health and is based on bone cells and collagen fibers, are required. The novel protein Semaphorin3A (Sema3A) is associated with osteoprotection by regulating bone cells. The aims of this study were to investigate the effects of mechanical loads on Sema3A production and bone quality based on bone cells and collagen fibers around implants in rat maxillae. Grade IV-titanium threaded implants were placed at 4 weeks post-extraction in maxillary first molars. Implants received mechanical loads (10 N, 3 Hz for 1800 cycles, 2 days/week) for 5 weeks from 3 weeks post-implant placement to minimize the effects of wound healing processes by implant placement. Bone structures, bone mineral density (BMD), Sema3A production and bone quality based on bone cells and collagen fibers were analyzed using microcomputed tomography, histomorphometry, immunohistomorphometry, polarized light microscopy and birefringence measurement system inside of the first and second thread (designated as thread A and B, respectively), as mechanical stresses are concentrated and differently distributed on the first two threads from the implant neck. Mechanical load significantly increased BMD, but not bone volume around implants. Inside thread B, but not thread A, mechanical load significantly accelerated Sema3A production with increased number of osteoblasts and osteocytes, and enhanced production of both type I and III collagen. Moreover, mechanical load also significantly induced preferential alignment of collagen fibers in the lower flank of thread B. These data demonstrate that mechanical load has different effects on Sema3A production and bone quality based on bone cells and collagen fibers between the inside threads of A and B. Mechanical load-induced Sema3A production may be differentially regulated by the type of bone structure or distinct stress distribution, resulting in control of bone quality around implants in jaw bones. PMID:29244883

Effects of mechanical repetitive load on bone quality around implants in rat maxillae.

PubMed

Uto, Yusuke; Kuroshima, Shinichiro; Nakano, Takayoshi; Ishimoto, Takuya; Inaba, Nao; Uchida, Yusuke; Sawase, Takashi

2017-01-01

Greater understanding and acceptance of the new concept "bone quality", which was proposed by the National Institutes of Health and is based on bone cells and collagen fibers, are required. The novel protein Semaphorin3A (Sema3A) is associated with osteoprotection by regulating bone cells. The aims of this study were to investigate the effects of mechanical loads on Sema3A production and bone quality based on bone cells and collagen fibers around implants in rat maxillae. Grade IV-titanium threaded implants were placed at 4 weeks post-extraction in maxillary first molars. Implants received mechanical loads (10 N, 3 Hz for 1800 cycles, 2 days/week) for 5 weeks from 3 weeks post-implant placement to minimize the effects of wound healing processes by implant placement. Bone structures, bone mineral density (BMD), Sema3A production and bone quality based on bone cells and collagen fibers were analyzed using microcomputed tomography, histomorphometry, immunohistomorphometry, polarized light microscopy and birefringence measurement system inside of the first and second thread (designated as thread A and B, respectively), as mechanical stresses are concentrated and differently distributed on the first two threads from the implant neck. Mechanical load significantly increased BMD, but not bone volume around implants. Inside thread B, but not thread A, mechanical load significantly accelerated Sema3A production with increased number of osteoblasts and osteocytes, and enhanced production of both type I and III collagen. Moreover, mechanical load also significantly induced preferential alignment of collagen fibers in the lower flank of thread B. These data demonstrate that mechanical load has different effects on Sema3A production and bone quality based on bone cells and collagen fibers between the inside threads of A and B. Mechanical load-induced Sema3A production may be differentially regulated by the type of bone structure or distinct stress distribution, resulting in control of bone quality around implants in jaw bones.

Bone healing response in cyclically loaded implants: Comparing zero, one, and two loading sessions per day.

PubMed

de Barros E Lima Bueno, Renan; Dias, Ana Paula; Ponce, Katia J; Wazen, Rima; Brunski, John B; Nanci, Antonio

2018-05-31

When bone implants are loaded, they are inevitably subjected to displacement relative to bone. Such micromotion generates stress/strain states at the interface that can cause beneficial or detrimental sequels. The objective of this study is to better understand the mechanobiology of bone healing at the tissue-implant interface during repeated loading. Machined screw shaped Ti implants were placed in rat tibiae in a hole slightly bigger than the implant diameter. Implants were held stable by a specially-designed bone plate that permits controlled loading. Three loading regimens were applied, (a) zero loading, (b) one daily loading session of 60 cycles with an axial force of 1.5 N/cycle for 7 days, and (c) two such daily sessions with the same axial force also for 7 days. Finite element analysis was used to characterize the mechanobiological conditions produced by the loading sessions. After 7 days, the implants with surrounding interfacial tissue were harvested and processed for histological, histomorphometric and DNA microarray analyses. Histomorphometric analyses revealed that the group subjected to repeated loading sessions exhibited a significant decrease in bone-implant contact and increase in bone-implant distance, as compared to unloaded implants and those subjected to only one loading session. Gene expression profiles differed during osseointegration between all groups mainly with respect to inflammatory and unidentified gene categories. The results indicate that increasing the daily cyclic loading of implants induces deleterious changes in the bone healing response, most likely due to the accumulation of tissue damage and associated inflammatory reaction at the bone-implant interface. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Abnormal distal renal tubular acidification in patients with low bone mass: prevalence and impact of alkali treatment.

PubMed

Sromicki, Jerzy Jan; Hess, Bernhard

2017-06-01

Chronic acid retention is known to promote bone dissolution. In this study, 23 % of patients with osteopenia/osteoporosis were diagnosed with abnormal distal renal tubular acidification (dRTA), a kidney dysfunction leading to chronic acid retention. Treating those patients with alkali-therapy shows improvement in bone density. To evaluate the prevalence of abnormal distal renal tubular acidification in patients with low bone mass (LBM) and the impact of additional alkali treatment on bone density in patients with concomitant LBM and dRTA,183 patients referred for metabolic evaluation of densitometrically proven low bone mass were screened for abnormal distal renal tubular acidification between 2006 and 2013. In all LBM urine pH (U-pH) was measured in the 2nd morning urines after 12 h of fasting. If U-pH was ≥5.80, LBM underwent a 1-day ammonium chloride loading, and U-pH was remeasured the next morning. If U-pH after acid loading did not drop below 5.45, patients were diagnosed with abnormal distal renal tubular acidification. Normal values were obtained from 21 healthy controls. All LBM with dRTA were recommended alkali citrate in addition to conventional therapy of LBM, and follow-up DXAs were obtained until 2014. 85 LBM underwent NH 4 Cl loading. 42 LBM patients were diagnosed with incomplete dRTA (idRTA; prevalence 23.0 %). During follow-up (1.6-8 years) of idRTA-LBM patients, subjects adhering to alkali treatment tended to improve BMD at all sites measured, whereas BMD of non-adherent idRTA patients worsened/remained unchanged. (1) About one out of four patients with osteopenia/osteoporosis has idRTA. (2) Upon NH 4 Cl loading, idRTA patients do not lower urine pH normally, but show signs of increased acid-buffering by bone dissolution. (3) In idRTA patients with low bone mass on conventional therapy, additional long-term alkali treatment improves bone mass at lumbar spine and potentially at other bone sites. (4) All patients with low bone mass undergoing metabolic evaluation should be screened for idRTA.

Engineering bone grafts with enhanced bone marrow and native scaffolds.

PubMed

Hung, Ben P; Salter, Erin K; Temple, Josh; Mundinger, Gerhard S; Brown, Emile N; Brazio, Philip; Rodriguez, Eduardo D; Grayson, Warren L

2013-01-01

The translation of tissue engineering approaches to the clinic has been hampered by the inability to find suitable multipotent cell sources requiring minimal in vitro expansion. Enhanced bone marrow (eBM), which is obtained by reaming long bone medullary canals and isolating the solid marrow putty, has large quantities of stem cells and demonstrates significant potential to regenerate bone tissues. eBM, however, cannot impart immediate load-bearing mechanical integrity or maintain the gross anatomical structure to guide bone healing. Yet, its putty-like consistency creates a challenge for obtaining the uniform seeding necessary to effectively combine it with porous scaffolds. In this study, we examined the potential for combining eBM with mechanically strong, osteoinductive trabecular bone scaffolds for bone regeneration by creating channels into scaffolds for seeding the eBM. eBM was extracted from the femurs of adult Yorkshire pigs using a Synthes reamer-irrigator-aspirator device, analyzed histologically, and digested to extract cells and characterize their differentiation potential. To evaluate bone tissue formation, eBM was seeded into the channels in collagen-coated or noncoated scaffolds, cultured in osteogenic conditions for 4 weeks, harvested and assessed for tissue distribution and bone formation. Our data demonstrates that eBM is a heterogenous tissue containing multipotent cell populations. Furthermore, coating scaffolds with a collagen hydrogel significantly enhanced cellular migration, promoted uniform tissue development and increased bone mineral deposition. These findings suggest the potential for generating customized autologous bone grafts for treating critical-sized bone defects by combining a readily available eBM cell source with decellularized trabecular bone scaffolds. © 2013 S. Karger AG, Basel

Specimen-specific modeling of hip fracture pattern and repair.

PubMed

Ali, Azhar A; Cristofolini, Luca; Schileo, Enrico; Hu, Haixiang; Taddei, Fulvia; Kim, Raymond H; Rullkoetter, Paul J; Laz, Peter J

2014-01-22

Hip fracture remains a major health problem for the elderly. Clinical studies have assessed fracture risk based on bone quality in the aging population and cadaveric testing has quantified bone strength and fracture loads. Prior modeling has primarily focused on quantifying the strain distribution in bone as an indicator of fracture risk. Recent advances in the extended finite element method (XFEM) enable prediction of the initiation and propagation of cracks without requiring a priori knowledge of the crack path. Accordingly, the objectives of this study were to predict femoral fracture in specimen-specific models using the XFEM approach, to perform one-to-one comparisons of predicted and in vitro fracture patterns, and to develop a framework to assess the mechanics and load transfer in the fractured femur when it is repaired with an osteosynthesis implant. Five specimen-specific femur models were developed from in vitro experiments under a simulated stance loading condition. Predicted fracture patterns closely matched the in vitro patterns; however, predictions of fracture load differed by approximately 50% due to sensitivity to local material properties. Specimen-specific intertrochanteric fractures were induced by subjecting the femur models to a sideways fall and repaired with a contemporary implant. Under a post-surgical stance loading, model-predicted load sharing between the implant and bone across the fracture surface varied from 59%:41% to 89%:11%, underscoring the importance of considering anatomic and fracture variability in the evaluation of implants. XFEM modeling shows potential as a macro-level analysis enabling fracture investigations of clinical cohorts, including at-risk groups, and the design of robust implants. © 2013 Published by Elsevier Ltd.

Bone's mechanostat: a 2003 update.

PubMed

Frost, Harold M

2003-12-01

The still-evolving mechanostat hypothesis for bones inserts tissue-level realities into the former knowledge gap between bone's organ-level and cell-level realities. It concerns load-bearing bones in postnatal free-living bony vertebrates, physiologic bone loading, and how bones adapt their strength to the mechanical loads on them. Voluntary mechanical usage determines most of the postnatal strength of healthy bones in ways that minimize nontraumatic fractures and create a bone-strength safety factor. The mechanostat hypothesis predicts 32 things that occur, including the gross anatomical bone abnormalities in osteogenesis imperfecta; it distinguishes postnatal situations from baseline conditions at birth; it distinguishes bones that carry typical voluntary loads from bones that have other chief functions; and it distinguishes traumatic from nontraumatic fractures. It provides functional definitions of mechanical bone competence, bone quality, osteopenias, and osteoporoses. It includes permissive hormonal and other effects on bones, a marrow mediator mechanism, some limitations of clinical densitometry, a cause of bone "mass" plateaus during treatment, an "adaptational lag" in some children, and some vibration effects on bones. The mechanostat hypothesis may have analogs in nonosseous skeletal organs as well. Copyright 2003 Wiley-Liss, Inc.

Micro-mechanical damage of trabecular bone-cement interface under selected loading conditions: a finite element study.

PubMed

Zhang, Qing-Hang; Tozzi, Gianluca; Tong, Jie

2014-01-01

In this study, two micro finite element models of trabecular bone-cement interface developed from high resolution computed tomography (CT) images were loaded under compression and validated using the in situ experimental data. The models were then used under tension and shear to examine the load transfer between the bone and cement and the micro damage development at the bone-cement interface. In addition, one models was further modified to investigate the effect of cement penetration on the bone-cement interfacial behaviour. The simulated results show that the load transfer at the bone-cement interface occurred mainly in the bone cement partially interdigitated region, while the fully interdigitated region seemed to contribute little to the mechanical response. Consequently, cement penetration beyond a certain value would seem to be ineffective in improving the mechanical strength of trabecular bone-cement interface. Under tension and shear loading conditions, more cement failures were found in denser bones, while the cement damage is generally low under compression.

Real-Time Measurement of Solute Transport Within the Lacunar-Canalicular System of Mechanically Loaded Bone: Direct Evidence for Load-Induced Fluid Flow

PubMed Central

Price, Christopher; Zhou, Xiaozhou; Li, Wen; Wang, Liyun

2011-01-01

Since proposed by Piekarski and Munro in 1977, load-induced fluid flow through the bone lacunar-canalicular system (LCS) has been accepted as critical for bone metabolism, mechanotransduction, and adaptation. However, direct unequivocal observation and quantification of load-induced fluid and solute convection through the LCS have been lacking due to technical difficulties. Using a novel experimental approach based on fluorescence recovery after photobleaching (FRAP) and synchronized mechanical loading and imaging, we successfully quantified the diffusive and convective transport of a small fluorescent tracer (sodium fluorescein, 376 Da) in the bone LCS of adult male C57BL/6J mice. We demonstrated that cyclic end-compression of the mouse tibia with a moderate loading magnitude (–3 N peak load or 400 µɛ surface strain at 0.5 Hz) and a 4-second rest/imaging window inserted between adjacent load cycles significantly enhanced (+31%) the transport of sodium fluorescein through the LCS compared with diffusion alone. Using an anatomically based three-compartment transport model, the peak canalicular fluid velocity in the loaded bone was predicted (60 µm/s), and the resulting peak shear stress at the osteocyte process membrane was estimated (∼5 Pa). This study convincingly demonstrated the presence of load-induced convection in mechanically loaded bone. The combined experimental and mathematical approach presented herein represents an important advance in quantifying the microfluidic environment experienced by osteocytes in situ and provides a foundation for further studying the mechanisms by which mechanical stimulation modulates osteocytic cellular responses, which will inform basic bone biology, clinical understanding of osteoporosis and bone loss, and the rational engineering of their treatments. © 2011 American Society for Bone and Mineral Research. PMID:20715178

Rest Intervals Reduce the Number of Loading Bouts Required to Enhance Bone Formation

PubMed Central

Srinivasan, Sundar; Ausk, Brandon J.; Bain, Steven D.; Gardiner, Edith M.; Kwon, Ronald Y.; Gross, Ted S.

2015-01-01

Purpose As our society becomes increasingly sedentary, compliance with exercise regimens that require numerous high-energy activities each week become less likely. Alternatively, given an osteogenic exercise intervention that required minimal effort, it is reasonable to presume that participation would be enhanced. Insertion of brief rest-intervals between each cycle of mechanical loading holds potential to achieve this result as substantial osteoblast function is activated by many fewer loading repetitions within each loading bout. Here, we examined the complementary hypothesis that the number of bouts/wk of rest-inserted loading could be reduced from 3/wk without loss of osteogenic efficacy. Methods We conducted a series of 3 wk in vivo experiments that non-invasively exposed the right tibiae of mice to either cyclic (1 Hz) or rest-inserted loading interventions and quantified osteoblast function via dynamic histomorphometry. Results While reducing loading bouts from 3/wk (i.e., 9 total bouts) to 1/wk (3 total bouts) effectively mitigated the osteogenic benefit of cyclic loading, the same reduction did not significantly reduce periosteal bone formation parameters induced by rest-inserted loading. The osteogenic response was robust to the timing of the rest-inserted loading bouts (3 bouts in the first week vs 1 bout/wk for three weeks). However, elimination of any single bout of the three 1/wk bouts mitigated the osteogenic response to rest-inserted loading. Finally, periosteal osteoblast function assessed after the 3 wk intervention was not sensitive to the timing or number of rest-inserted loading bouts. Conclusions We conclude that rest-inserted loading holds potential to retain the osteogenic benefits of mechanical loading with significantly reduced frequency of bouts of activity while also enabling greater flexibility in the timing of the activity. PMID:25207932

In vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae.

PubMed

Ko, Frank C; Dragomir, Cecilia; Plumb, Darren A; Goldring, Steven R; Wright, Timothy M; Goldring, Mary B; van der Meulen, Marjolein C H

2013-06-01

Alterations in the mechanical loading environment in joints may have both beneficial and detrimental effects on articular cartilage and subchondral bone, and may subsequently influence the development of osteoarthritis (OA). Using an in vivo tibial loading model, the aim of this study was to investigate the adaptive responses of cartilage and bone to mechanical loading and to assess the influence of load level and duration. Cyclic compression at peak loads of 4.5N and 9.0N was applied to the left tibial knee joint of adult (26-week-old) C57BL/6 male mice for 1, 2, and 6 weeks. Only 9.0N loading was utilized in young (10-week-old) mice. Changes in articular cartilage and subchondral bone were analyzed by histology and micro-computed tomography. Mechanical loading promoted cartilage damage in both age groups of mice, and the severity of joint damage increased with longer duration of loading. Metaphyseal bone mass increased with loading in young mice, but not in adult mice, whereas epiphyseal cancellous bone mass decreased with loading in both young and adult mice. In both age groups, articular cartilage thickness decreased, and subchondral cortical bone thickness increased in the posterior tibial plateau. Mice in both age groups developed periarticular osteophytes at the tibial plateau in response to the 9.0N load, but no osteophyte formation occurred in adult mice subjected to 4.5N peak loading. This noninvasive loading model permits dissection of temporal and topographic changes in cartilage and bone and will enable investigation of the efficacy of treatment interventions targeting joint biomechanics or biologic events that promote OA onset and progression. Copyright © 2013 by the American College of Rheumatology.

Vertical ridge augmentation with autogenous bone grafts 3 years after loading: resorbable barriers versus titanium-reinforced barriers. A randomized controlled clinical trial.

PubMed

Merli, Mauro; Lombardini, Francesco; Esposito, Marco

2010-01-01

To compare the efficacy of two different techniques for vertical bone regeneration at implant placement with particulated autogenous bone at 3 years after loading: resorbable collagen barriers supported by osteosynthesis plates and nonresorbable titanium-reinforced expanded polytetrafluoroethylene barriers. Twenty-two partially edentulous patients requiring vertical bone augmentation were randomly allocated to two treatment groups, each composed of 11 patients. Prosthetic and implant failures, complications, the amount of vertically regenerated bone, and peri-implant marginal bone levels were recorded by independent and blinded assessors. The implant site requiring the most vertical bone regeneration was selected in each patient for bone level assessment. The follow-up time ranged from provisional loading to 3 years after loading. Analysis of covariance and paired t tests were conducted to compare means at the .05 level of significance. No patient dropped out or was excluded at the 3-year follow-up. No prosthetic failures and no implant failures or complications occurred after loading. There was no statistically significant difference in bone loss between the two groups at either 1 year or 3 years. Both groups had gradually lost a statistically significant amount of peri-implant bone at 1 and 3 years (P < .05). After 3 years, patients treated with resorbable barriers had lost a mean of 0.55 mm of bone; patients who had received nonresorbable barriers showed a mean of 0.53 mm of bone loss. Up to 3 years after implant loading, no failures or complications occurred and peri-implant marginal bone loss was minimal. Vertically regenerated bone can be successfully maintained after functional loading.

Biomechanics of a Bone-Periodontal Ligament-Tooth Fibrous Joint

PubMed Central

Lin, Jeremy D.; Özcoban, Hüseyin; Greene, Janelle; Jang, Andrew T.; Djomehri, Sabra; Fahey, Kevin; Hunter, Luke; Schneider, Gerold A; Ho, Sunita P.

2013-01-01

This study investigates bone-tooth association under compression to identify strain amplified sites within the bone-periodontal ligament (PDL)-tooth fibrous joint. Our results indicate that the biomechanical response of the joint is due to a combinatorial response of constitutive properties of organic, inorganic, and fluid components. Second maxillary molars within intact maxillae (N=8) of 5-month-old rats were loaded with a μ-XCT-compatible in situ loading device at various permutations of displacement rates (0.2, 0.5, 1.0, 1.5, 2.0 mm/min) and peak reactionary load responses (5, 10, 15, 20 N). Results indicated a nonlinear biomechanical response of the joint, in which the observed reactionary load rates were directly proportional to displacement rates (velocities). No significant differences in peak reactionary load rates at a displacement rate of 0.2 mm/min were observed. However, for displacement rates greater than 0.2 mm/min, an increasing trend in reactionary rate was observed for every peak reactionary load with significant increases at 2.0 mm/min. Regardless of displacement rates, two distinct behaviors were identified with stiffness (S) and reactionary load rate (LR) values at a peak load of 5 N (S5 N=290–523 N/mm) being significantly lower than those at 10 N (LR5 N=1–10 N/s) and higher (S10N–20 N=380–684 N/mm; LR10N–20 N=1–19 N/s). Digital image correlation revealed the possibility of a screw-like motion of the tooth into the PDL-space, i.e., predominant vertical displacement of 35 μm at 5 N, followed by a slight increase to 40 μm at 10 N and 50 μm at 20 N of the tooth and potential tooth rotation at loads above 10 N. Narrowed and widened PDL spaces as a result of tooth displacement indicated areas of increased apparent strain within the complex. We propose that such highly strained regions are “hot spots” that can potentiate local tissue adaptation under physiological loading and adverse tissue adaptation under pathological loading conditions. PMID:23219279

Strontium (Sr) and silver (Ag) loaded nanotubular structures with combined osteoinductive and antimicrobial activities.

PubMed

Cheng, Hao; Xiong, Wei; Fang, Zhong; Guan, Hanfeng; Wu, Wei; Li, Yong; Zhang, Yong; Alvarez, Mario Moisés; Gao, Biao; Huo, Kaifu; Xu, Jiangwen; Xu, Na; Zhang, Chengcheng; Fu, Jijiang; Khademhosseini, Ali; Li, Feng

2016-02-01

Two frequent problems are associated with the titanium surfaces of bone/dental implants: lack of native tissue integration and associated infection. These problems have prompted a significant body of research regarding the modification of these surfaces. The present study describes a hydrothermal treatment for the fabrication of strontium (Sr) and silver (Ag) loaded nanotubular structures with different tube diameters on titanium surfaces. The Sr loading from a Sr(OH)2 solution was regulated by the size of the inner diameter of the titanium nanotubes (NT) (30nm or 80nm, formed at 10V or 40V, respectively). The quantity of Ag was adjusted by immersing the samples in 1.5 or 2.0M AgNO3 solutions. Sr and Ag were released in a controllable and prolonged matter from the NT-Ag.Sr samples, with negligible cytotoxicity. Prominent antibacterial activity was observed due to the release of Ag. Sr incorporation enhanced the initial cell adhesion, migration, and proliferation of preosteoblast MC3T3-E1 cells. Sr release also up-regulated the expression of osteogenic genes and induced mineralization, as suggested by the presence of more mineralized calcium nodules in cells cultured on NT-Ag.Sr surfaces. In vivo experiments showed that the Sr-loaded samples accelerated the formation of new bone in both osteoporosis and bone defect models, as confirmed by X-ray, Micro-CT evaluation, and histomorphometric analysis of rats implanted with NT-Ag.Sr samples. The antibacterial activity and outstanding osteogenic properties of NT-Ag.Sr samples highlight their excellent potential for use in clinical applications. Two frequent problems associated with Ti surfaces, widely used in orthopedic and dental arenas, are their lack of native tissue integration and risk of infection. We describe a novel approach for the fabrication of strontium (Sr) and silver (Ag) loaded nanotubular structures on titanium surfaces. A relevant aspect of this work is the demonstration of long-lasting and controllable Ag release, leading to excellent antibacterial and anti-adherent properties against methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative bacteria such as Escherichia coli. The extended release of Sr accelerates the filling of bone defects by improving the repair of damaged cortical bone and increasing trabecular bone microarchitecture. Our results highlight the potential of Sr and Ag loaded nanotubular structures for use in clinical applications. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Influence of Implant Positions and Occlusal Forces on Peri-Implant Bone Stress in Mandibular Two-Implant Overdentures: A 3-Dimensional Finite Element Analysis.

PubMed

Alvarez-Arenal, Angel; Gonzalez-Gonzalez, Ignacio; deLlanos-Lanchares, Hector; Brizuela-Velasco, Aritza; Dds, Elena Martin-Fernandez; Ellacuria-Echebarria, Joseba

2017-12-01

The aim of this study was to evaluate and compare the bone stress around implants in mandibular 2-implant overdentures depending on the implant location and different loading conditions. Four 3-dimensional finite element models simulating a mandibular 2-implant overdenture and a Locator attachment system were designed. The implants were located at the lateral incisor, canine, second premolar, and crossed-implant levels. A 150 N unilateral and bilateral vertical load of different location was applied, as was 40 N when combined with midline load. Data for von Mises stress were produced numerically, color coded, and compared between the models for peri-implant bone and loading conditions. With unilateral loading, in all 4 models much higher peri-implant bone stress values were recorded on the load side compared with the no-load side, while with bilateral occlusal loading, the stress distribution was similar on both sides. In all models, the posterior unilateral load showed the highest stress, which decreased as the load was applied more mesially. In general, the best biomechanical environment in the peri-implant bone was found in the model with implants at premolar level. In the crossed-implant model, the load side greatly altered the biomechanical environment. Overall, the overdenture with implants at second premolar level should be the chosen design, regardless of where the load is applied. The occlusal loading application site influences the bone stress around the implant. Bilateral occlusal loading distributes the peri-implant bone stress symmetrically, while unilateral loading increases it greatly on the load side, no matter where the implants are located.

A biodegradable antibiotic-eluting PLGA nanofiber-loaded deproteinized bone for treatment of infected rabbit bone defects.

PubMed

Gao, Jianting; Huang, Guofeng; Liu, Guojun; Liu, Yan; Chen, Qi; Ren, Lei; Chen, Changqing; Ding, Zhenqi

2016-08-01

We fabricated a biodegradable antibiotic-eluting poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (ANDB) scaffold that provided sustained delivery of vancomycin to repair methicillin-resistant Staphylococcus aureus bone defects. To fabricate the biodegradable ANDB, poly(d,l)-lactide-co-glycolide and vancomycin were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propano. The solution was then electrospun to produce biodegradable antibiotic-eluting membranes that were deposited on the surface of bovine deproteinized cancellous bone. We used scanning electron microscopy to determine the properties of the scaffold. Both elution and high-performance liquid chromatography assays were used to evaluate the in vitro vancomycin release rate from the ANDB scaffold. Three types of scaffolds were co-cultured with bacteria to confirm the in vitro antibacterial activity. The infected bone defect rabbit model was induced by injecting 10(7) colony forming units of a methicillin-resistant Staphylococcus aureus strain into the radial defect of rabbits. Animals were then separated into treatment groups and implanted according to the following scheme: ANDB scaffold in group A, poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (NDB) scaffold with intravenous (i.v.) vancomycin in group B, and NDB scaffold alone in group C. Treatment efficacy was evaluated after eight weeks using radiological, microbiological, and histological examinations. In vitro results revealed that biodegradable ANDB scaffolds released concentrations of vancomycin that were greater than the minimum inhibitory concentration for more than four weeks. Bacterial inhibition tests also confirmed antibacterial efficacy lasted for approximately four weeks. Radiological and histological scores obtained in vivo revealed significant differences between groups A, B and C. Importantly, group A had significantly lower bacterial load and better bone regeneration when compared to either group B or C. Collectively, these results show that our fabricated ANDB scaffolds possess: (1) effective bactericidal activity against methicillin-resistant Staphylococcus aureus, (2) the ability to promote site-specific bone regeneration, and (3) the potential for use in the treatment of infected bone defects. © The Author(s) 2016.

Assessment of function-graded materials as fracture fixation bone-plates under combined loading conditions using finite element modelling.

PubMed

Fouad, H

2011-05-01

In previous work by Fouad (Medical Engineering and Physics 2010 [23]), 3D finite element (FE) models for fractured bones with function-graded (FG) bone-plates and traditional bone-plates made of stainless steel (SS) and titanium (Ti) alloy were examined under compressive loading conditions using the ABAQUS Code. In this study, the effects of the presence of the torsional load in addition to the compressive load on the predicted stresses of the fracture fixation bone-plate system are examined at different healing stages. The effects on the stress on the fracture site when using contacted and non-contacted bone-plate systems are also studied. The FE modelling results indicate that the torsional load has significant effects on the resultant stress on the fracture fixation bone-plate system, which should be taken into consideration during the design and the analysis. The results also show that the stress shielding at the fracture site decreases significantly when using FG bone-plates compared to Ti alloy or SS bone-plates. The presence of a gap between the bone and the plate results in a remarkable reduction in bone stress shielding at the fracture site. Therefore, the significant effects of using an FG bone-plate with a gap and the presence of torsional load on the resultant stress on the fracture fixation bone-plate system should be taken into consideration. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

Optimally oriented grooves on dental implants improve bone quality around implants under repetitive mechanical loading.

PubMed

Kuroshima, Shinichiro; Nakano, Takayoshi; Ishimoto, Takuya; Sasaki, Muneteru; Inoue, Maaya; Yasutake, Munenori; Sawase, Takashi

2017-01-15

The aim was to investigate the effect of groove designs on bone quality under controlled-repetitive load conditions for optimizing dental implant design. Anodized Ti-6Al-4V alloy implants with -60° and +60° grooves around the neck were placed in the proximal tibial metaphysis of rabbits. The application of a repetitive mechanical load was initiated via the implants (50N, 3Hz, 1800 cycles, 2days/week) at 12weeks after surgery for 8weeks. Bone quality, defined as osteocyte density and degree of biological apatite (BAp) c-axis/collagen fibers, was then evaluated. Groove designs did not affect bone quality without mechanical loading; however, repetitive mechanical loading significantly increased bone-to-implant contact, bone mass, and bone mineral density (BMD). In +60° grooves, the BAp c-axis/collagen fibers preferentially aligned along the groove direction with mechanical loading. Moreover, osteocyte density was significantly higher both inside and in the adjacent region of the +60° grooves, but not -60° grooves. These results suggest that the +60° grooves successfully transmitted the load to the bone tissues surrounding implants through the grooves. An optimally oriented groove structure on the implant surface was shown to be a promising way for achieving bone tissue with appropriate bone quality. This is the first report to propose the optimal design of grooves on the necks of dental implants for improving bone quality parameters as well as BMD. The findings suggest that not only BMD, but also bone quality, could be a useful clinical parameter in implant dentistry. Although the paradigm of bone quality has shifted from density-based assessments to structural evaluations of bone, clarifying bone quality based on structural bone evaluations remains challenging in implant dentistry. In this study, we firstly demonstrated that the optimal design of dental implant necks improved bone quality defined as osteocytes and the preferential alignment degree of biological apatite c-axis/collagen fibers using light microscopy, polarized light microscopy, and a microbeam X-ray diffractometer system, after application of controlled mechanical load. Our new findings suggest that bone quality around dental implants could become a new clinical parameter as well as bone mineral density in order to completely account for bone strength in implant dentistry. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A Novel High Mechanical Property PLGA Composite Matrix Loaded with Nanodiamond-Phospholipid Compound for Bone Tissue Engineering.

PubMed

Zhang, Fan; Song, Qingxin; Huang, Xuan; Li, Fengning; Wang, Kun; Tang, Yixing; Hou, Canglong; Shen, Hongxing

2016-01-20

A potential bone tissue engineering material was produced from a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), loaded with nanodiamond phospholipid compound (NDPC) via physical mixing. On the basis of hydrophobic effects and physical absorption, we modified the original hydrophilic surface of the nanodiamond (NDs) with phospholipids to be amphipathic, forming a typical core-shell structure. The ND-phospholipid weight ratio was optimized to generate sample NDPC50 (i.e., ND-phospholipid weight ratio of 100:50), and NDPC50 was able to be dispersed in a PLGA matrix at up to 20 wt %. Compared to a pure PLGA matrix, the introduction of 10 wt % of NDPC (i.e., sample NDPC50-PF10) resulted in a significant improvement in the material's mechanical and surface properties, including a decrease in the water contact angle from 80 to 55°, an approximately 100% increase in the Young's modulus, and an approximate 550% increase in hardness, thus closely resembling that of human cortical bone. As a novel matrix supporting human osteoblast (hFOB1.19) growth, NDPC50-PFs with different amounts of NDPC50 demonstrated no negative effects on cell proliferation and osteogenic differentiation. Furthermore, we focused on the behaviors of NDPC-PFs implanted into mice for 8 weeks and found that NDPC-PFs induced acceptable immune response and can reduce the rapid biodegradation of PLGA matrix. Our results represent the first in vivo research on ND (or NDPC) as nanofillers in a polymer matrix for bone tissue engineering. The high mechanical properties, good in vitro and in vivo biocompatibility, and increased mineralization capability suggest that biodegradable PLGA composite matrices loaded with NDPC may potentially be useful for a variety of biomedical applications, especially bone tissue engineering.

A Radiographic Comparison of Progressive and Conventional Loading on Crestal Bone Loss and Density in Single Dental Implants: A Randomized Controlled Trial Study

PubMed Central

Ghoveizi, Rahab; Alikhasi, Marzieh; Siadat, Mohammad-Reza; Siadat, Hakimeh; Sorouri, Majid

2013-01-01

Objective: Crestal bone loss is a biological complication in implant dentistry. The aim of this study was to compare the effect of progressive and conventional loading on crestal bone height and bone density around single osseointegrated implants in the posterior maxilla by a longitudinal radiographic assessment technique. Materials and Methods: Twenty micro thread implants were placed in 10 patients (two implants per patient). One of the two implants in each patient was assigned to progressive and the other to conventional loading groups. Eight weeks after surgery, conventional implants were restored with a metal ceramic crown and the progressive group underwent a progressive loading protocol. The progressive loading group took different temporary acrylic crowns at 2, 4 and 6 months. After eight months, acrylic crowns were replaced with a metal ceramic crown. Computer radiography of both progressive and conventional implants was taken at 2, 4, 6, and 12 months. Image analysis was performed to measure the height of crestal bone loss and bone density. Results: The mean values of crestal bone loss at month 12 were 0.11 (0.19) mm for progressively and 0.36 (0.36) mm for conventionally loaded implants, with a statistically significant difference (P < 0.05) using Wilcoxon sign rank. Progressively loaded group showed a trend for higher bone density gain compared to the conventionally loaded group, but when tested with repeated measure ANOVA, the differences were not statistically significant (P > 0.05). Conclusion: The progressive group showed less crestal bone loss in single osseointegrated implant than the conventional group. Bone density around progressively loaded implants showed increase in crestal, middle and apical areas. PMID:23724215

In vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae

PubMed Central

Ko, Frank C.; Dragomir, Cecilia; Plumb, Darren A.; Goldring, Steven R.; Wright, Timothy M.; Goldring, Mary B.; van der Meulen, Marjolein C.H.

2013-01-01

Objectives Alterations in the mechanical loading environment in joints may have both beneficial and detrimental effects on articular cartilage and subchondral bone and subsequently influence the development of osteoarthritis (OA). We used an in vivo tibial loading model to investigate the adaptive responses of cartilage and bone to mechanical loading and to assess the influence of load level and duration. Methods We applied cyclic compression of 4.5 and 9.0N peak loads to the left tibia via the knee joint of adult (26-week-old) C57Bl/6 male mice for 1, 2, and 6 weeks. Only 9.0N loading was utilized in young (10-week-old) mice. The changes in articular cartilage and subchondral bone were analyzed by histology and microcomputed tomography. Results Loading promoted cartilage damage in both age groups, with increased damage severity dependent upon the duration of loading. Metaphyseal bone mass increased in the young mice, but not in the adult mice, whereas epiphyseal cancellous bone mass decreased with loading in both young and adult mice. Articular cartilage thickness decreased, and subchondral cortical bone thickness increased in the posterior tibial plateau in both age groups. Both age groups developed periarticular osteophytes at the tibial plateau in response to the 9.0N load, but no osteophyte formation occurred in adult mice subjected to 4.5N peak loading. Conclusion This non-invasive loading model permits dissection of temporal and topographical changes in cartilage and bone and will enable investigation of the efficacy of treatment interventions targeting joint biomechanics or biological events that promote OA onset and progression. PMID:23436303

Role of subchondral bone properties and changes in development of load-induced osteoarthritis in mice.

PubMed

Adebayo, O O; Ko, F C; Wan, P T; Goldring, S R; Goldring, M B; Wright, T M; van der Meulen, M C H

2017-12-01

Animal models recapitulating post-traumatic osteoarthritis (OA) suggest that subchondral bone (SCB) properties and remodeling may play major roles in disease initiation and progression. Thus, we investigated the role of SCB properties and its effects on load-induced OA progression by applying a tibial loading model on two distinct mouse strains treated with alendronate (ALN). Cyclic compression was applied to the left tibia of 26-week-old male C57Bl/6 (B6, low bone mass) and FVB (high bone mass) mice. Mice were treated with ALN (26 μg/kg/day) or vehicle (VEH) for loading durations of 1, 2, or 6 weeks. Changes in articular cartilage and subchondral and epiphyseal cancellous bone were analyzed using histology and microcomputed tomography. FVB mice exhibited thicker cartilage, a thicker SCB plate, and higher epiphyseal cancellous bone mass and tissue mineral density than B6 mice. Loading induced cartilage pathology, osteophyte formation, and SCB changes; however, lower initial SCB mass and stiffness in B6 mice did not attenuate load-induced OA severity compared to FVB mice. By contrast, FVB mice exhibited less cartilage damage, and slower-growing and less mature osteophytes. In B6 mice, inhibiting bone remodeling via ALN treatment exacerbated cartilage pathology after 6 weeks of loading, while in FVB mice, inhibiting bone remodeling protected limbs from load-induced cartilage loss. Intrinsically lower SCB properties were not associated with attenuated load-induced cartilage loss. However, inhibiting bone remodeling produced differential patterns of OA pathology in animals with low compared to high SCB properties, indicating that these factors do influence load-induced OA progression. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

A multiscale 3D finite element analysis of fluid/solute transport in mechanically loaded bone

PubMed Central

Fan, Lixia; Pei, Shaopeng; Lucas Lu, X; Wang, Liyun

2016-01-01

The transport of fluid, nutrients, and signaling molecules in the bone lacunar–canalicular system (LCS) is critical for osteocyte survival and function. We have applied the fluorescence recovery after photobleaching (FRAP) approach to quantify load-induced fluid and solute transport in the LCS in situ, but the measurements were limited to cortical regions 30–50 μm underneath the periosteum due to the constrains of laser penetration. With this work, we aimed to expand our understanding of load-induced fluid and solute transport in both trabecular and cortical bone using a multiscaled image-based finite element analysis (FEA) approach. An intact murine tibia was first re-constructed from microCT images into a three-dimensional (3D) linear elastic FEA model, and the matrix deformations at various locations were calculated under axial loading. A segment of the above 3D model was then imported to the biphasic poroelasticity analysis platform (FEBio) to predict load-induced fluid pressure fields, and interstitial solute/fluid flows through LCS in both cortical and trabecular regions. Further, secondary flow effects such as the shear stress and/or drag force acting on osteocytes, the presumed mechano-sensors in bone, were derived using the previously developed ultrastructural model of Brinkman flow in the canaliculi. The material properties assumed in the FEA models were validated against previously obtained strain and FRAP transport data measured on the cortical cortex. Our results demonstrated the feasibility of this computational approach in estimating the fluid flux in the LCS and the cellular stimulation forces (shear and drag forces) for osteocytes in any cortical and trabecular bone locations, allowing further studies of how the activation of osteocytes correlates with in vivo functional bone formation. The study provides a promising platform to reveal potential cellular mechanisms underlying the anabolic power of exercises and physical activities in treating patients with skeletal deficiencies. PMID:27722020

Static versus dynamic loads as an influence on bone remodelling

NASA Technical Reports Server (NTRS)

Lanyon, L. E.; Rubin, C. T.

1983-01-01

Bone remodelling activity in the avian ulna was assessed under conditions of disuse alone, disuse with a superimposed continuous compressive load, and disuse interrupted by a short daily period of intermittent loading. The ulna preparation is made by two submetaphyseal osteotomies, the cut ends of the bone being covered with stainless steel caps which, together with the bone they enclosed, are pierced by pins emerging transcutaneously on the dorsal and ventral surfaces of the wing. The 110 mm long undisturbed section of the bone shaft can be protected from functional loading, loaded continuously in compression by joining the pins with springs, or loaded intermittently in compression by engaging the pins in an Instron machine. Similar loads (525 n) were used in both static and dynamic cases engendering similar peak strains at the bone's midshaft (-2000 x 10-6). The intermitent load was applied at a frequency of 1 Hz during a single 100 second period per day as a ramped square wave, with a rate of change of strain during the ramp of 0.01 per second.

Protocol for a randomized controlled trial to compare bone-loading exercises with risedronate for preventing bone loss in osteopenic postmenopausal women.

PubMed

Bilek, Laura D; Waltman, Nancy L; Lappe, Joan M; Kupzyk, Kevin A; Mack, Lynn R; Cullen, Diane M; Berg, Kris; Langel, Meghan; Meisinger, Melissa; Portelli-Trinidad, Ashlee; Lang, Molly

2016-08-30

In the United States, over 34 million American post-menopausal women have low bone mass (osteopenia) which increases their risk of osteoporosis and fractures. Calcium, vitamin D and exercise are recommended for prevention of osteoporosis, and bisphosphonates (BPs) are prescribed in women with osteoporosis. BPs may also be prescribed for women with low bone mass, but are more controversial due to the potential for adverse effects with long-term use. A bone loading exercise program (high-impact weight bearing and resistance training) promotes bone strength by preserving bone mineral density (BMD), improving bone structure, and by promoting bone formation at sites of mechanical stress. The sample for this study will be 309 women with low bone mass who are within 5 years post-menopause. Subjects are stratified by exercise history (≥2 high intensity exercise sessions per week; < 2 sessions per week) and randomized to a control or one of two treatment groups: 1) calcium + vitamin D (CaD) alone (Control); 2) a BP plus CaD (Risedronate); or 3) a bone loading exercise program plus CaD (Exercise). After 12 months of treatment, changes in bone structure, BMD, and bone turnover will be compared in the 3 groups. Primary outcomes for the study are bone structure measures (Bone Strength Index [BSI] at the tibia and Hip Structural Analysis [HSA] scores). Secondary outcomes are BMD at the hip and spine and serum biomarkers of bone formation (alkaline phosphase, AlkphaseB) and resorption (Serum N-terminal telopeptide, NTx). Our central hypothesis is that improvements in bone strength will be greater in subjects randomized to the Exercise group compared to subjects in either Control or Risedronate groups. Our research aims to decrease the risk of osteoporotic fractures by improving bone strength in women with low bone mass (pre-osteoporotic) during their first 5 years' post-menopause, a time of rapid and significant bone loss. Results of this study could be used in developing a clinical management pathway for women with low bone mass at their peak period of bone loss that would involve lifestyle modifications such as exercises prior to medications such as BPs. Clinicaltrials.gov NCT02186600 . Initial registration: 7/7/2014.

Mechanical competence of ovariectomy-induced compromised bone after single or combined treatment with high-frequency loading and bisphosphonates

PubMed Central

Camargos G. V.; Bhattacharya P.; van Lenthe G. H.; Del Bel Cury A. A.; Naert I.; Duyck J.; Vandamme K.

2015-01-01

Osteoporosis leads to increased bone fragility, thus effective approaches enhancing bone strength are needed. Hence, this study investigated the effect of single or combined application of high-frequency (HF) loading through whole body vibration (WBV) and alendronate (ALN) on the mechanical competence of ovariectomy-induced osteoporotic bone. Thirty-four female Wistar rats were ovariectomized (OVX) or sham-operated (shOVX) and divided into five groups: shOVX, OVX-shWBV, OVX-WBV, ALN-shWBV and ALN-WBV. (Sham)WBV loading was applied for 10 min/day (130 to 150 Hz at 0.3g) for 14 days and ALN at 2 mg/kg/dose was administered 3x/week. Finite element analysis based on micro-CT was employed to assess bone biomechanical properties, relative to bone micro-structural parameters. HF loading application to OVX resulted in an enlarged cortex, but it was not able to improve the biomechanical properties. ALN prevented trabecular bone deterioration and increased bone stiffness and bone strength of OVX bone. Finally, the combination of ALN with HF resulted in an increased cortical thickness in OVX rats when compared to single treatments. Compared to HF loading, ALN treatment is preferred for improving the compromised mechanical competence of OVX bone. In addition, the association of ALN with HF loading results in an additive effect on the cortical thickness. PMID:26027958

Non-Invasive Investigation of Bone Adaptation in Humans to Mechanical Loading

NASA Technical Reports Server (NTRS)

Whalen, R.

1999-01-01

Experimental studies have identified peak cyclic forces, number of loading cycles, and loading rate as contributors to the regulation of bone metabolism. We have proposed a theoretical model that relates bone density to a mechanical stimulus derived from average daily cumulative peak cyclic 'effective' tissue stresses. In order to develop a non-invasive experimental model to test the theoretical model we need to: (1) monitor daily cumulative loading on a bone, (2) compute the internal stress state(s) resulting from the imposed loading, and (3) image volumetric bone density accurately, precisely, and reproducibly within small contiguous volumes throughout the bone. We have chosen the calcaneus (heel) as an experimental model bone site because it is loaded by ligament, tendon and joint contact forces in equilibrium with daily ground reaction forces that we can measure; it is a peripheral bone site and therefore more easily and accurately imaged with computed tomography; it is composed primarily of cancellous bone; and it is a relevant site for monitoring bone loss and adaptation in astronauts and the general population. This paper presents an overview of our recent advances in the areas of monitoring daily ground reaction forces, biomechanical modeling of the forces on the calcaneus during gait, mathematical modeling of calcaneal bone adaptation in response to cumulative daily activity, accurate and precise imaging of the calcaneus with quantitative computed tomography (QCT), and application to long duration space flight.

Lattice strains and load partitioning in bovine trabecular bone.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akhtar, R.; Daymond, M. R.; Almer, J. D.

2012-02-01

Microdamage and failure mechanisms have been well characterized in bovine trabecular bone. However, little is known about how elastic strains develop in the apatite crystals of the trabecular struts and their relationship with different deformation mechanisms. In this study, wide-angle high-energy synchrotron X-ray diffraction has been used to determine bulk elastic strains under in situ compression. Dehydrated bone is compared to hydrated bone in terms of their response to load. During compression, load is initially borne by trabeculae aligned parallel to loading direction with non-parallel trabeculae deforming by bending. Ineffective load partitioning is noted in dehydrated bone whereas hydrated bonemore » behaves like a plastically yielding foam« less

Dynamic Fluid Flow Mechanical Stimulation Modulates Bone Marrow Mesenchymal Stem Cells.

PubMed

Hu, Minyi; Yeh, Robbin; Lien, Michelle; Teeratananon, Morgan; Agarwal, Kunal; Qin, Yi-Xian

2013-03-01

Osteoblasts are derived from mesenchymal stem cells (MSCs), which initiate and regulate bone formation. New strategies for osteoporosis treatments have aimed to control the fate of MSCs. While functional disuse decreases MSC growth and osteogenic potentials, mechanical signals enhance MSC quantity and bias their differentiation toward osteoblastogenesis. Through a non-invasive dynamic hydraulic stimulation (DHS), we have found that DHS can mitigate trabecular bone loss in a functional disuse model via rat hindlimb suspension (HLS). To further elucidate the downstream cellular effect of DHS and its potential mechanism underlying the bone quality enhancement, a longitudinal in vivo study was designed to evaluate the MSC populations in response to DHS over 3, 7, 14, and 21 days. Five-month old female Sprague Dawley rats were divided into three groups for each time point: age-matched control, HLS, and HLS+DHS. DHS was delivered to the right mid-tibiae with a daily "10 min on-5 min off-10 min on" loading regime for five days/week. At each sacrifice time point, bone marrow MSCs of the stimulated and control tibiae were isolated through specific cell surface markers and quantified by flow cytometry analysis. A strong time-dependent manner of bone marrow MSC induction was observed in response to DHS, which peaked on day 14. After 21 days, this effect of DHS was diminished. This study indicates that the MSC pool is positively influenced by the mechanical signals driven by DHS. Coinciding with our previous findings of mitigation of disuse bone loss, DHS induced changes in MSC number may bias the differentiation of the MSC population towards osteoblastogenesis, thereby promoting bone formation under disuse conditions. This study provides insights into the mechanism of time-sensitive MSC induction in response to mechanical loading, and for the optimal design of osteoporosis treatments.

Fabrication and Characterization of Carbon Fiber-Reinforced Nano-Hydroxyapatite/Polyamide46 Biocomposite for Bone Substitute.

PubMed

Deng, Zhennan; Han, Hongjuan; Yang, Jingyuan; Li, Yuanyuan; Du, Shengnan; Ma, Jianfeng

2017-05-24

BACKGROUND Ideal bone repair material should be of good biocompatibility and high bioactivity. Besides, their mechanical properties should be equivalent to those of natural bone. The objective of this study was to fabricate a novel biocomposite suitable for load-bearing bone defect repair. MATERIAL AND METHODS A novel biocomposite composed of carbon fiber, hydroxyapatite and polyamide46 (CF/HA/PA46) was fabricated, and its mechanical performances and preliminary cell responses were evaluated to explore its feasibility for load-bearing bone defect repair. RESULTS The resultant CF/HA/PA46 biocomposite showed a bending strength of 159-223 MPa, a tensile strength of 127-199 MPa and a tensile modulus of 7.7-10.8 GPa, when the CF content was 5-20% (mass fraction) in biocomposite. The MG63 cells, showing an osteogenic phenotype, were well adhered and spread on the surface of the CF/HA/PA46 biocomposite. Moreover, the cells vitality and differentiation on the CF/HA/PA46 biocomposite surface were obviously increased during the culture time and there was no significant difference between the CF/HA/PA46 biocomposite and HA/PA (as control) at all the experimental time (P>0.05). CONCLUSIONS The addition of CF into HA/PA46 composite manifest improved the mechanical performances and showed favorable effects on biocompatibility of MG63 cells. The obtained biocomposite has high potential for bone repair in load-bearing sites.

Silk as a biocohesive sacrificial binder in the fabrication of hydroxyapatite load bearing scaffolds.

PubMed

McNamara, Stephanie L; Rnjak-Kovacina, Jelena; Schmidt, Daniel F; Lo, Tim J; Kaplan, David L

2014-08-01

Limitations of current clinical methods for bone repair continue to fuel the demand for a high strength, bioactive bone replacement material. Recent attempts to produce porous scaffolds for bone regeneration have been limited by the intrinsic weakness associated with high porosity materials. In this study, ceramic scaffold fabrication techniques for potential use in load-bearing bone repairs have been developed using naturally derived silk from Bombyx mori. Silk was first employed for ceramic grain consolidation during green body formation, and later as a sacrificial polymer to impart porosity during sintering. These techniques allowed preparation of hydroxyapatite (HA) scaffolds that exhibited a wide range of mechanical and porosity profiles, with some displaying unusually high compressive strength up to 152.4 ± 9.1 MPa. Results showed that the scaffolds exhibited a wide range of compressive strengths and moduli (8.7 ± 2.7 MPa to 152.4 ± 9.1 MPa and 0.3 ± 0.1 GPa to 8.6 ± 0.3 GPa) with total porosities of up to 62.9 ± 2.7% depending on the parameters used for fabrication. Moreover, HA-silk scaffolds could be molded into large, complex shapes, and further machined post-sinter to generate specific three-dimensional geometries. Scaffolds supported bone marrow-derived mesenchymal stem cell attachment and proliferation, with no signs of cytotoxicity. Therefore, silk-fabricated HA scaffolds show promise for load bearing bone repair and regeneration needs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Silk as a biocohesive sacrificial binder in the fabrication of hydroxyapatite load bearing scaffolds

PubMed Central

McNamara, Stephanie L.; Rnjak-Kovacina, Jelena; Schmidt, Daniel; Lo, Tim J.; Kaplan, David L.

2014-01-01

Limitations of current clinical methods for bone repair continue to fuel the demand for a high strength, bioactive bone replacement material. Recent attempts to produce porous scaffolds for bone regeneration have been limited by the intrinsic weakness associated with high porosity materials. In this study, ceramic scaffold fabrication techniques for potential use in load-bearing bone repairs have been developed using naturally derived silk from Bombyx mori. Silk was first employed for ceramic grain consolidation during green body formation, and later as a sacrificial polymer to impart porosity during sintering. These techniques allowed preparation of hydroxyapatite (HA) scaffolds that exhibited a wide range of mechanical and porosity profiles, with some displaying unusually high compressive strength up to 152.4 ± 9.1 MPa. Results showed that the scaffolds exhibited a wide range of compressive strengths and moduli (8.7 ± 2.7 MPa to 152.4 ± 9.1 MPa and 0.3 ± 0.1 GPa to 8.6 ± 0.3 GPa) with total porosities of up to 62.9 ± 2.7% depending on the parameters used for fabrication. Moreover, HA-silk scaffolds could be molded into large, complex shapes, and further machined post-sinter to generate specific three-dimensional geometries. Scaffolds supported bone marrow-derived mesenchymal stem cell attachment and proliferation, with no signs of cytotoxicity. Therefore, silk-fabricated HA scaffolds show promise for load bearing bone repair and regeneration needs. PMID:24881027

Fabrication and Characterization of Carbon Fiber-Reinforced Nano-Hydroxyapatite/Polyamide46 Biocomposite for Bone Substitute

PubMed Central

Deng, Zhennan; Han, Hongjuan; Yang, Jingyuan; Li, Yuanyuan; Du, Shengnan; Ma, Jianfeng

2017-01-01

Background Ideal bone repair material should be of good biocompatibility and high bioactivity. Besides, their mechanical properties should be equivalent to those of natural bone. The objective of this study was to fabricate a novel biocomposite suitable for load-bearing bone defect repair. Material/Methods A novel biocomposite composed of carbon fiber, hydroxyapatite and polyamide46 (CF/HA/PA46) was fabricated, and its mechanical performances and preliminary cell responses were evaluated to explore its feasibility for load-bearing bone defect repair. Results The resultant CF/HA/PA46 biocomposite showed a bending strength of 159–223 MPa, a tensile strength of 127–199 MPa and a tensile modulus of 7.7–10.8 GPa, when the CF content was 5–20% (mass fraction) in biocomposite. The MG63 cells, showing an osteogenic phenotype, were well adhered and spread on the surface of the CF/HA/PA46 biocomposite. Moreover, the cells vitality and differentiation on the CF/HA/PA46 biocomposite surface were obviously increased during the culture time and there was no significant difference between the CF/HA/PA46 biocomposite and HA/PA (as control) at all the experimental time (P>0.05). Conclusions The addition of CF into HA/PA46 composite manifest improved the mechanical performances and showed favorable effects on biocompatibility of MG63 cells. The obtained biocomposite has high potential for bone repair in load-bearing sites. PMID:28536416

POTASSIUM CITRATE DECREASES BONE RESORPTION IN POSTMENOPAUSAL WOMEN WITH OSTEOPENIA: A RANDOMIZED, DOUBLE-BLIND CLINICAL TRIAL.

PubMed

Gregory, Naina Sinha; Kumar, Rekha; Stein, Emily M; Alexander, Ellen; Christos, Paul; Bockman, Richard S; Rodman, John S

2015-12-01

Diets rich in animal protein, such as the typical American diet, are thought to create a high acid load. An association between acid load and bone loss has led to the idea that providing positive alkaline salt therapy could have beneficial effects on bone metabolism. The objective of this study was to investigate the effects of potassium citrate (K-citrate), 40 mEq daily, over 1 year on bone resorption and formation. A randomized, double-blind, placebo-controlled trial of 83 women with postmenopausal osteopenia. Levels of bone turnover markers, specifically urinary N-telopeptide of collagen type 1 (u-NTX), amino-terminal propeptide of type 1 procollagen (P1NP), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC) were compared. Changes in bone mineral density (BMD) were also examined. K-citrate decreased both u-NTX (P = .005) and serum P1NP (P<.001) starting at month 1 and continuing through month 12. No significant change was seen in BSAP or OC. No significant change was seen in lumbar or hip BMD between the 2 groups. In women with postmenopausal osteopenia, treatment with K-citrate for 1 year resulted in a significant decrease in markers of turnover. The effect on markers of bone formation was not consistent. K-citrate may serve as a potential treatment for bone loss that is well tolerated and without any significant known long-term consequences.

Localized tissue mineralization regulated by bone remodelling: A computational approach

PubMed Central

Decco, Oscar; Adams, George; Cook, Richard B.; García Aznar, José Manuel

2017-01-01

Bone is a living tissue whose main mechanical function is to provide stiffness, strength and protection to the body. Both stiffness and strength depend on the mineralization of the organic matrix, which is constantly being remodelled by the coordinated action of the bone multicellular units (BMUs). Due to the dynamics of both remodelling and mineralization, each sample of bone is composed of structural units (osteons in cortical and packets in cancellous bone) created at different times, therefore presenting different levels of mineral content. In this work, a computational model is used to understand the feedback between the remodelling and the mineralization processes under different load conditions and bone porosities. This model considers that osteoclasts primarily resorb those parts of bone closer to the surface, which are younger and less mineralized than older inner ones. Under equilibrium loads, results show that bone volumes with both the highest and the lowest levels of porosity (cancellous and cortical respectively) tend to develop higher levels of mineral content compared to volumes with intermediate porosity, thus presenting higher material densities. In good agreement with recent experimental measurements, a boomerang-like pattern emerges when plotting apparent density at the tissue level versus material density at the bone material level. Overload and disuse states are studied too, resulting in a translation of the apparent–material density curve. Numerical results are discussed pointing to potential clinical applications. PMID:28306746

Antibiotic-loaded bone void filler accelerates healing in a femoral condylar rat model.

PubMed

Shiels, S M; Cobb, R R; Bedigrew, K M; Ritter, G; Kirk, J F; Kimbler, A; Finger Baker, I; Wenke, J C

2016-08-01

Demineralised bone matrix (DBM) is rarely used for the local delivery of prophylactic antibiotics. Our aim, in this study, was to show that a graft with a bioactive glass and DBM combination, which is currently available for clinical use, can be loaded with tobramycin and release levels of antibiotic greater than the minimum inhibitory concentration for Staphylococcus aureus without interfering with the bone healing properties of the graft, thus protecting the graft and surrounding tissues from infection. Antibiotic was loaded into a graft and subsequently evaluated for drug elution kinetics and the inhibition of bacterial growth. A rat femoral condylar plug model was used to determine the effect of the graft, loaded with antibiotic, on bone healing. We found that tobramycin loaded into a graft composed of bioglass and DBM eluted antibiotic above the minimum inhibitory concentration for three days in vitro. It was also found that the antibiotic loaded into the graft produced no adverse effects on the bone healing properties of the DBM at a lower level of antibiotic. This antibiotic-loaded bone void filler may represent a promising option for the delivery of local antibiotics in orthopaedic surgery. Cite this article: Bone Joint J 2016;98-B:1126-31. ©2016 The British Editorial Society of Bone & Joint Surgery.

Biaxial Normal Strength Behavior in the Axial-Transverse Plane for Human Trabecular Bone—Effects of Bone Volume Fraction, Microarchitecture, and Anisotropy

PubMed Central

Sanyal, Arnav; Keaveny, Tony M.

2013-01-01

The biaxial failure behavior of the human trabecular bone, which has potential relevance both for fall and gait loading conditions, is not well understood, particularly for low-density bone, which can display considerable mechanical anisotropy. Addressing this issue, we investigated the biaxial normal strength behavior and the underlying failure mechanisms for human trabecular bone displaying a wide range of bone volume fraction (0.06–0.34) and elastic anisotropy. Micro-computer tomography (CT)-based nonlinear finite element analysis was used to simulate biaxial failure in 15 specimens (5 mm cubes), spanning the complete biaxial normal stress failure space in the axial-transverse plane. The specimens, treated as approximately transversely isotropic, were loaded in the principal material orientation. We found that the biaxial stress yield surface was well characterized by the superposition of two ellipses—one each for yield failure in the longitudinal and transverse loading directions—and the size, shape, and orientation of which depended on bone volume fraction and elastic anisotropy. However, when normalized by the uniaxial tensile and compressive strengths in the longitudinal and transverse directions, all of which depended on bone volume fraction, microarchitecture, and mechanical anisotropy, the resulting normalized biaxial strength behavior was well described by a single pair of (longitudinal and transverse) ellipses, with little interspecimen variation. Taken together, these results indicate that the role of bone volume fraction, microarchitecture, and mechanical anisotropy is mostly accounted for in determining the uniaxial strength behavior and the effect of these parameters on the axial-transverse biaxial normal strength behavior per se is minor. PMID:24121715

Evaluation of implants coated with rhBMP-2 using two different coating strategies: a critical-size supraalveolar peri-implant defect study in dogs.

PubMed

Lee, Jaebum; Decker, John F; Polimeni, Giuseppe; Cortella, Carlo Alberto; Rohrer, Michael D; Wozney, John M; Hall, Jan; Susin, Cristiano; Wikesjö, Ulf M E

2010-06-01

Implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce relevant bone formation but also resident bone remodelling. To compare the effect of implants fully or partially coated with rhBMP-2 on new bone formation and resident bone remodelling. Twelve, male, adult, Hound Labrador mongrel dogs were used. Critical-size, supraalveolar, peri-implant defects received titanium porous oxide surface implants coated in their most coronal aspect with rhBMP-2 (coronal-load/six animals) or by immersion of the entire implant in an rhBMP-2 solution (soak-load/six animals) for a total of 30 mug rhBMP-2/implant. All implants were air-dried. The animals were euthanized at 8 weeks for histometric evaluation. Clinical healing was uneventful. Supraalveolar bone formation was not significantly affected by the rhBMP-2 application protocol. New bone height and area averaged (+/- SE) 3.4 +/- 0.2 versus 3.5 +/- 0.4 mm and 2.6 +/- 0.4 versus 2.5 +/- 0.7 mm(2) for coronal-load and soak-load implants, respectively (p>0.05). The corresponding bone density and bone-implant contact (BIC) recordings averaged 38.0 +/- 3.8%versus 34.4 +/- 5.6% and 25.0 +/- 3.8%versus 31.2 +/- 3.3% (p>0.05). In contrast, resident bone remodelling was significantly influenced by the rhBMP-2 application protocol. Bone density outside the implants threads averaged 74.7 +/- 3.8% and 50.8 +/- 4.1% for coronal-load and soak-load implants, respectively (p<0.05); bone density within the thread area averaged 51.8 +/- 1.2% and 37.8 +/- 2.9%, and BIC 70.1 +/- 6.7% and 43.3 +/- 3.9% (p<0.05). Local application of rhBMP-2 appears to be a viable technology to support local bone formation and osseointegration. Coronal-load implants obviate resident bone remodelling without compromising new bone formation.

Alginate/Gelatin scaffolds incorporated with Silibinin-loaded Chitosan nanoparticles for bone formation in vitro.

PubMed

Leena, R S; Vairamani, M; Selvamurugan, N

2017-10-01

Silibinin is a plant derived flavonolignan known for its multiple biological properties, but its role in the promotion of bone formation has not yet been well studied. Moreover, the delivery of Silibinin is hindered by its complex hydrophobic nature, which limits its bioavailability. Hence, in this study, we fabricated a drug delivery system using chitosan nanoparticles loaded with Silibinin at different concentrations (20μM, 50μM, and 100μM). They were then incorporated into scaffolds containing Alginate and Gelatin (Alg/Gel) for the sustained and prolonged release of Silibinin. The Silibinin-loaded chitosan nanoparticles (SCN) were prepared using the ionic gelation technique, and the scaffolds (Alg/Gel-SCN) were synthesized by the conventional method of freeze drying. The scaffolds were subjected to physicochemical and material characterization studies. The addition of SCN did not affect the porosity of the scaffolds, yet increased the protein adsorption, degradation rates, and bio-mineralization. These scaffolds were biocompatible with mouse mesenchymal stem cells. The scaffolds loaded with 50μM Silibinin promoted osteoblast differentiation, which was determined at cellular and molecular levels. Recent studies indicated the role of microRNAs (miRNAs) in osteogenesis and we found that the Silibinin released from scaffolds regulated miRNAs that control the bone morphogenetic protein pathway. Hence, our results suggest the potential for sustained and prolonged release of Silibinin to promote bone formation and, thus, these Alg/Gel-SCN scaffolds may be candidates for bone tissue engineering applications. Copyright © 2017 Elsevier B.V. All rights reserved.

3D artificial bones for bone repair prepared by computed tomography-guided fused deposition modeling for bone repair.

PubMed

Xu, Ning; Ye, Xiaojian; Wei, Daixu; Zhong, Jian; Chen, Yuyun; Xu, Guohua; He, Dannong

2014-09-10

The medical community has expressed significant interest in the development of new types of artificial bones that mimic natural bones. In this study, computed tomography (CT)-guided fused deposition modeling (FDM) was employed to fabricate polycaprolactone (PCL)/hydroxyapatite (HA) and PCL 3D artificial bones to mimic natural goat femurs. The in vitro mechanical properties, in vitro cell biocompatibility, and in vivo performance of the artificial bones in a long load-bearing goat femur bone segmental defect model were studied. All of the results indicate that CT-guided FDM is a simple, convenient, relatively low-cost method that is suitable for fabricating natural bonelike artificial bones. Moreover, PCL/HA 3D artificial bones prepared by CT-guided FDM have more close mechanics to natural bone, good in vitro cell biocompatibility, biodegradation ability, and appropriate in vivo new bone formation ability. Therefore, PCL/HA 3D artificial bones could be potentially be of use in the treatment of patients with clinical bone defects.

Thermoelastic stress analysis to validate tibial fixation technique in total ankle prostheses - a pilot study.

PubMed

Ficklscherer, Andreas; Wegener, Bernd; Niethammer, Thomas; Pietschmann, Matthias F; Müller, Peter E; Jansson, Volkmar; Trouillier, Hans-Heinrich

2013-03-01

Recent literature has shown a persistently high rate of aseptic loosening of the tibial component in total ankle prostheses. We analyzed the interface between the tibial bone and tibial component with a thermoelastic stress analysis to demonstrate load transmission onto the distal tibia. In this regard, we used two established ankle prostheses, which were implanted in two human cadaveric and in two third-generation composite tibia bones (Sawbones®, Sweden). Subsequently, the bones were attached to a hydropulser and a sinusoidal load of 700 N was applied. Both prostheses had an inhomogeneous load transmission onto the distal tibia. Instead of distributing load equally to the subarticular bone, forces were focused around the bolting stem, accumulating as stress maxima with forces up to 90 MPa. Furthermore, we were able to demonstrate load transmission into the metaphysis of the bone. As demonstrated in this study, anchoring systems with stems used in all established total ankle prostheses lead to an inhomogeneous load transmission onto the distal tibia, and furthermore, to a distribution of load into the weaker metaphyseal bone. For these reasons, we favor a prosthetic design with minimal bone resection and without any stem or stem-like anchoring system, which facilitates a homogeneous load transmission onto the distal tibia. Thermoelastic stress analysis proved to be a fast and easy-to-perform method to visualize load transmission.

Effects of different loading patterns on the trabecular bone morphology of the proximal femur using adaptive bone remodeling.

PubMed

Banijamali, S Mohammad Ali; Oftadeh, Ramin; Nazarian, Ara; Goebel, Ruben; Vaziri, Ashkan; Nayeb-Hashemi, Hamid

2015-01-01

In this study, the changes in the bone density of human femur model as a result of different loadings were investigated. The model initially consisted of a solid shell representing cortical bone encompassing a cubical network of interconnected rods representing trabecular bone. A computationally efficient program was developed that iteratively changed the structure of trabecular bone by keeping the local stress in the structure within a defined stress range. The stress was controlled by either enhancing existing beam elements or removing beams from the initial trabecular frame structure. Analyses were performed for two cases of homogenous isotropic and transversely isotropic beams.Trabecular bone structure was obtained for three load cases: walking, stair climbing and stumbling without falling. The results indicate that trabecular bone tissue material properties do not have a significant effect on the converged structure of trabecular bone. In addition, as the magnitude of the loads increase, the internal structure becomes denser in critical zones. Loading associated with the stumbling results in the highest density;whereas walking, considered as a routine daily activity, results in the least internal density in different regions. Furthermore, bone volume fraction at the critical regions of the converged structure is in good agreement with previously measured data obtained from combinations of dual X-ray absorptiometry (DXA) and computed tomography (CT). The results indicate that the converged bone architecture consisting of rods and plates are consistent with the natural bone morphology of the femur. The proposed model shows a promising means to understand the effects of different individual loading patterns on the bone density.

Moderate tibia axial loading promotes discordant response of bone composition parameters and mechanical properties in a hindlimb unloading rat model.

PubMed

Yang, Peng-Fei; Huang, Ling-Wei; Nie, Xiao-Tong; Yang, Yue; Wang, Zhe; Ren, Li; Xu, Hui-Yun; Shang, Peng

2018-06-01

The purpose of the present study was to characterize the dynamic alterations of bone composition parameters and mechanical properties to disuse and mechanical intervention. A tail suspension hindlimb unloading model and an in vivo axial tibia loading model in rats were used. A moderate mechanical loading that was capable of engendering 800 µε tibia strain was applied to the right tibia of rats in both control and hindlimb unloading group across 28 days of the experimental period. The contralateral tibia served as control. Hindlimb unloading led to bone loss in tibia from day 14. Bone mineral density, mineral content and mechanical properties responded differently with microstructure to disuse in timing course. Mechanical loading of 800 µε tibia strain failed to alter the bone of the control group, but minimized the detrimental effects of unloading by completely prohibiting the decrease of bone mineral content and main mechanical properties after 28 days. Less obvious influence of mechanical loading on bone microstructure was found. The moderate mechanical loading is not able to stimulate the mechanical response of healthy tibia, but indeed lead to discordant recovery of bone composition parameters and mechanical properties.

Electrical signal transmission and gap junction regulation in a bone cell network: a cable model for an osteon

NASA Technical Reports Server (NTRS)

Zhang, D.; Cowin, S. C.; Weinbaum, S.

1997-01-01

A cable model is formulated to estimate the spatial distribution of intracellular electric potential and current, from the cement line to the lumen of an osteon, as the frequency of the loading and the conductance of the gap junction are altered. The model predicts that the characteristic diffusion time for the spread of current along the membrane of the osteocytic processes, 0.03 sec, is nearly the same as the predicted pore pressure relaxation time in Zeng et al. (Annals of Biomedical Engineering. 1994) for the draining of the bone fluid into the osteonal canal. This approximate equality of characteristic times causes the cable to behave as a high-pass, low-pass filter cascade with a maximum in the spectral response for the intracellular potential at approximately 30 Hz. This behavior could be related to the experiments of Rubin and McLeod (Osteoporosis, Academic Press, 1996) which show that live bone appears to be selectively responsive to mechanical loading in a specific frequency range (15-30 Hz) for several species.

Reduced functional loads alter the physical characteristics of the bone-PDL-cementum complex

PubMed Central

Niver, Eric L.; Leong, Narita; Greene, Janelle; Curtis, Donald; Ryder, Mark I.; Ho, Sunita P.

2011-01-01

Background Adaptive properties of the bone-PDL-tooth complex have been identified by changing the magnitude of functional loads using small-scale animal models such as rodents. Reported adaptive responses as a result of lower loads due to softer diet include decreased muscle development, change in structure-function relationship of the cranium, narrowed PDL-space, changes in mineral level of the cortical bone and alveolar jaw bone, and glycosaminoglycans of the alveolar bone. However, the adaptive role of the dynamic bone-PDL-cementum complex due to prolonged reduced loads has not been fully explained to date, especially with regards to concurrent adaptations of bone, PDL and cementum. Hence, the temporal effect of reduced functional loads on physical characteristics such as morphology and mechanical properties, and mineral profiles of the bone-periodontal ligament (PDL)-cementum complex using a rat model was investigated. Materials and Methods Two groups of six-week-old male Sprague-Dawley rats were fed nutritionally identical food with a stiffness range of 127–158N/mm for hard pellet or 0.32–0.47N/mm for soft powder forms. Spatio-temporal adaptation of the bone-PDL-cementum complex was identified by mapping changes in: 1) PDL-collagen orientation and birefringence using polarized light microscopy, bone and cementum adaptation using histochemistry, and bone and cementum morphology using micro X-ray computed tomography, 2) mineral profiles of the PDL-cementum and PDL-bone interfaces by X-ray attenuation, and 3) microhardness of bone and cementum by microindentation of specimens at ages six, eight, twelve, and fifteen weeks. Results Reduced functional loads over prolonged time resulted in 1) altered PDL orientation and decreased PDL collagen birefringence indicating decreased PDL turnover rate and decreased apical cementum resorption; 2) a gradual increase in X-ray attenuation, owing to mineral differences, at the PDL-bone and PDL-cementum interfaces without significant differences in the gradients for either group; 3) significantly (p<0.05) lower microhardness of alveolar bone (0.93±0.16 GPa) and secondary cementum (0.803±0.13 GPa) compared to the higher load group (1.10±0.17 GPa and 0.940±0.15 GPa respectively) at fifteen weeks indicating a temporal effect of loads on local mineralization of bone and cementum. Conclusions Based on the results from this study, the effect of reduced functional loads for a prolonged time could differentially affect morphology and mechanical properties, and mineral variations and of the local load-bearing sites in a bone-PDL-cementum complex. These observed local changes in turn could help explain the overall biomechanical function and adaptations of the tooth-bone joint. From a clinical translation perspective, our study provides an insight into modulation of load on the complex for improved tooth function during periodontal disease, and/or orthodontic and prosthodontic treatments. PMID:21848615

Histological Evidence of the Osseointegration of Fractured Direct Metal Laser Sintering Implants Retrieved after 5 Years of Function.

PubMed

Mangano, Francesco; Mangano, Carlo; Piattelli, Adriano; Iezzi, Giovanna

2017-01-01

Direct metal laser sintering (DMLS) is an additive manufacturing technique that allows the fabrication of dental implants layer by layer through the laser fusion of titanium microparticles. The surface of DMLS implants is characterized by a high open porosity with interconnected pores of different sizes; therefore, it has the potential to enhance and accelerate bone healing. To date, however, there are no histologic/histomorphometric studies in the literature evaluating the interface between bone and DMLS implants in the long-term. To evaluate the interface between bone and DMLS implants retrieved after 5 years of functional loading. Two fractured DMLS implants were retrieved from the human jaws, using a 5 mm trephine bur. Both the implants were clinically stable and functioned regularly before fracture. The specimens were processed for histologic/histomorphometric evaluation; the bone-to-implant contact (BIC%) was calculated. Compact, mature lamellar bone was found over most of the DMLS implants in close contact with the implant surface; the histomorphometric evaluation showed a mean BIC% of 66.1% (±4.5%). The present histologic/histomorphometric study showed that DMLS implants were well integrated in bone, after 5 years of loading, with the peri-implant bone undergoing continuous remodeling at the interface.

Histological Evidence of the Osseointegration of Fractured Direct Metal Laser Sintering Implants Retrieved after 5 Years of Function

PubMed Central

Piattelli, Adriano

2017-01-01

Background Direct metal laser sintering (DMLS) is an additive manufacturing technique that allows the fabrication of dental implants layer by layer through the laser fusion of titanium microparticles. The surface of DMLS implants is characterized by a high open porosity with interconnected pores of different sizes; therefore, it has the potential to enhance and accelerate bone healing. To date, however, there are no histologic/histomorphometric studies in the literature evaluating the interface between bone and DMLS implants in the long-term. Purpose To evaluate the interface between bone and DMLS implants retrieved after 5 years of functional loading. Methods Two fractured DMLS implants were retrieved from the human jaws, using a 5 mm trephine bur. Both the implants were clinically stable and functioned regularly before fracture. The specimens were processed for histologic/histomorphometric evaluation; the bone-to-implant contact (BIC%) was calculated. Results Compact, mature lamellar bone was found over most of the DMLS implants in close contact with the implant surface; the histomorphometric evaluation showed a mean BIC% of 66.1% (±4.5%). Conclusions The present histologic/histomorphometric study showed that DMLS implants were well integrated in bone, after 5 years of loading, with the peri-implant bone undergoing continuous remodeling at the interface. PMID:28929117

Exercise does not enhance aged bone's impaired response to artificial loading in C57Bl/6 mice.

PubMed

Meakin, Lee B; Udeh, Chinedu; Galea, Gabriel L; Lanyon, Lance E; Price, Joanna S

2015-12-01

Bones adapt their structure to their loading environment and so ensure that they become, and are maintained, sufficiently strong to withstand the loads to which they are habituated. The effectiveness of this process declines with age and bones become fragile fracturing with less force. This effect in humans also occurs in mice which experience age-related bone loss and reduced adaptation to loading. Exercise engenders many systemic and local muscular physiological responses as well as engendering local bone strain. To investigate whether these physiological responses influence bones' adaptive responses to mechanical strain we examined whether a period of treadmill exercise influenced the adaptive response to an associated period of artificial loading in young adult (17-week) and old (19-month) mice. After treadmill acclimatization, mice were exercised for 30 min three times per week for two weeks. Three hours after each exercise period, right tibiae were subjected to 40 cycles of non-invasive axial loading engendering peak strain of 2250 με. In both young and aged mice exercise increased cross-sectional muscle area and serum sclerostin concentration. In young mice it also increased serum IGF1. Exercise did not affect bone's adaptation to loading in any measured parameter in young or aged bone. These data demonstrate that a level of exercise sufficient to cause systemic changes in serum, and adaptive changes in local musculature, has no effect on bone's response to loading 3h later. This study provides no support for the beneficial effects of exercise on bone in the elderly being mediated by systemic or local muscle-derived effects rather than local adaptation to altered mechanical strain. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Development of a Portable Knee Rehabilitation Device That Uses Mechanical Loading.

PubMed

Fitzwater, Daric; Dodge, Todd; Chien, Stanley; Yokota, Hiroki; Anwar, Sohel

2013-12-01

Joint loading is a recently developed mechanical modality, which potentially provides a therapeutic regimen to activate bone formation and prevent degradation of joint tissues. To our knowledge, however, few joint loading devices are available for clinical or point-of-care applications. Using a voice-coil actuator, we developed an electromechanical loading system appropriate for human studies and preclinical trials that should prove both safe and effective. Two specific tasks for this loading system were development of loading conditions (magnitude and frequency) suitable for humans, and provision of a convenient and portable joint loading apparatus. Desktop devices have been previously designed to evaluate the effects of various loading conditions using small and large animals. However, a portable knee loading device is more desirable from a usability point of view. In this paper, we present such a device that is designed to be portable, providing a compact, user-friendly loader. The portable device was employed to evaluate its capabilities using a human knee model. The portable device was characterized for force-pulse width modulation duty cycle and loading frequency properties. The results demonstrate that the device is capable of producing the necessary magnitude of forces at appropriate frequencies to promote the stimulation of bone growth and which can be used in clinical studies for further evaluations.

Characterization of drug-release kinetics in trabecular bone from titania nanotube implants

PubMed Central

Aw, Moom Sinn; Khalid, Kamarul A; Gulati, Karan; Atkins, Gerald J; Pivonka, Peter; Findlay, David M; Losic, Dusan

2012-01-01

Purpose The aim of this study was to investigate the application of the three-dimensional bone bioreactor for studying drug-release kinetics and distribution of drugs in the ex vivo cancellous bone environment, and to demonstrate the application of nanoengineered titanium (Ti) wires generated with titania nanotube (TNT) arrays as drug-releasing implants for local drug delivery Methods Nanoengineered Ti wires covered with a layer of TNT arrays implanted in bone were used as a drug-releasing implant. Viable bovine trabecular bone was used as the ex vivo bone substrate embedded with the implants and placed in the bone reactor. A hydrophilic fluorescent dye (rhodamine B) was used as the model drug, loaded inside the TNT–Ti implants, to monitor drug release and transport in trabecular bone. The distribution of released model drug in the bone was monitored throughout the bone structure, and concentration profiles at different vertical (0–5 mm) and horizontal (0–10 mm) distances from the implant surface were obtained at a range of release times from 1 hour to 5 days. Results Scanning electron microscopy confirmed that well-ordered, vertically aligned nanotube arrays were formed on the surface of prepared TNT–Ti wires. Thermogravimetric analysis proved loading of the model drug and fluorescence spectroscopy was used to show drug-release characteristics in-vitro. The drug release from implants inserted into bone ex vivo showed a consistent gradual release of model drug from the TNT–Ti implants, with a characteristic three-dimensional distribution into the surrounding bone, over a period of 5 days. The parameters including the flow rate of bone culture medium, differences in trabecular microarchitecture between bone samples, and mechanical loading were found to have the most significant influence on drug distribution in the bone. Conclusion These results demonstrate the utility of the Zetos™ system for ex vivo drug-release studies in bone, which can be applied to optimize the delivery of specific therapies and to assist in the design of new drug delivery systems. This method has the potential to provide new knowledge to understand drug distribution in the bone environment and to considerably improve existing technologies for local administration in bone, including solving some critical problems in bone therapy and orthopedic implants. PMID:23028217

Characterization of drug-release kinetics in trabecular bone from titania nanotube implants.

PubMed

Aw, Moom Sinn; Khalid, Kamarul A; Gulati, Karan; Atkins, Gerald J; Pivonka, Peter; Findlay, David M; Losic, Dusan

2012-01-01

The aim of this study was to investigate the application of the three-dimensional bone bioreactor for studying drug-release kinetics and distribution of drugs in the ex vivo cancellous bone environment, and to demonstrate the application of nanoengineered titanium (Ti) wires generated with titania nanotube (TNT) arrays as drug-releasing implants for local drug delivery Nanoengineered Ti wires covered with a layer of TNT arrays implanted in bone were used as a drug-releasing implant. Viable bovine trabecular bone was used as the ex vivo bone substrate embedded with the implants and placed in the bone reactor. A hydrophilic fluorescent dye (rhodamine B) was used as the model drug, loaded inside the TNT-Ti implants, to monitor drug release and transport in trabecular bone. The distribution of released model drug in the bone was monitored throughout the bone structure, and concentration profiles at different vertical (0-5 mm) and horizontal (0-10 mm) distances from the implant surface were obtained at a range of release times from 1 hour to 5 days. Scanning electron microscopy confirmed that well-ordered, vertically aligned nanotube arrays were formed on the surface of prepared TNT-Ti wires. Thermogravimetric analysis proved loading of the model drug and fluorescence spectroscopy was used to show drug-release characteristics in-vitro. The drug release from implants inserted into bone ex vivo showed a consistent gradual release of model drug from the TNT-Ti implants, with a characteristic three-dimensional distribution into the surrounding bone, over a period of 5 days. The parameters including the flow rate of bone culture medium, differences in trabecular microarchitecture between bone samples, and mechanical loading were found to have the most significant influence on drug distribution in the bone. These results demonstrate the utility of the Zetos™ system for ex vivo drug-release studies in bone, which can be applied to optimize the delivery of specific therapies and to assist in the design of new drug delivery systems. This method has the potential to provide new knowledge to understand drug distribution in the bone environment and to considerably improve existing technologies for local administration in bone, including solving some critical problems in bone therapy and orthopedic implants.

Biomechanical fatigue analysis of an advanced new carbon fiber/flax/epoxy plate for bone fracture repair using conventional fatigue tests and thermography.

PubMed

Bagheri, Zahra S; El Sawi, Ihab; Bougherara, Habiba; Zdero, Radovan

2014-07-01

The current study is part of an ongoing research program to develop an advanced new carbon fiber/flax/epoxy (CF/flax/epoxy) hybrid composite with a “sandwich structure” as a substitute for metallic materials for orthopedic long bone fracture plate applications. The purpose of this study was to assess the fatigue properties of this composite, since cyclic loading is one of the main types of loads carried by a femur fracture plate during normal daily activities. Conventional fatigue testing, thermographic analysis, and scanning electron microscopy (SEM) were used to analyze the damage progress that occurred during fatigue loading. Fatigue strength obtained using thermography analysis (51% of ultimate tensile strength) was confirmed using the conventional fatigue test (50–55% of ultimate tensile strength). The dynamic modulus (E⁎) was found to stay almost constant at 47 GPa versus the number of cycles, which can be related to the contribution of both flax/epoxy and CF/epoxy laminae to the stiffness of the composite. SEM images showed solid bonding at the CF/epoxy and flax/epoxy laminae, with a crack density of only 0.48% for the plate loaded for 2 million cycles. The current composite plate showed much higher fatigue strength than the main loads experienced by a typical patient during cyclic activities; thus, it may be a potential candidate for bone fracture plate applications. Moreover, the fatigue strength from thermographic analysis was the same as that obtained by the conventional fatigue tests, thus demonstrating its potential use as an alternate tool to rapidly evaluate fatigue strength of composite biomaterials.

Biomechanical fatigue analysis of an advanced new carbon fiber/flax/epoxy plate for bone fracture repair using conventional fatigue tests and thermography.

PubMed

Bagheri, Zahra S; El Sawi, Ihab; Bougherara, Habiba; Zdero, Radovan

2014-07-01

The current study is part of an ongoing research program to develop an advanced new carbon fiber/flax/epoxy (CF/flax/epoxy) hybrid composite with a "sandwich structure" as a substitute for metallic materials for orthopedic long bone fracture plate applications. The purpose of this study was to assess the fatigue properties of this composite, since cyclic loading is one of the main types of loads carried by a femur fracture plate during normal daily activities. Conventional fatigue testing, thermographic analysis, and scanning electron microscopy (SEM) were used to analyze the damage progress that occurred during fatigue loading. Fatigue strength obtained using thermography analysis (51% of ultimate tensile strength) was confirmed using the conventional fatigue test (50-55% of ultimate tensile strength). The dynamic modulus (E(⁎)) was found to stay almost constant at 47GPa versus the number of cycles, which can be related to the contribution of both flax/epoxy and CF/epoxy laminae to the stiffness of the composite. SEM images showed solid bonding at the CF/epoxy and flax/epoxy laminae, with a crack density of only 0.48% for the plate loaded for 2 million cycles. The current composite plate showed much higher fatigue strength than the main loads experienced by a typical patient during cyclic activities; thus, it may be a potential candidate for bone fracture plate applications. Moreover, the fatigue strength from thermographic analysis was the same as that obtained by the conventional fatigue tests, thus demonstrating its potential use as an alternate tool to rapidly evaluate fatigue strength of composite biomaterials. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cortical bone viscoelasticity and fixation strength of press-fit femoral stems: an in-vitro model.

PubMed

Norman, T L; Ackerman, E S; Smith, T S; Gruen, T A; Yates, A J; Blaha, J D; Kish, V L

2006-02-01

Cementless total hip femoral components rely on press-fit for initial stability and bone healing and remodeling for secondary fixation. However, the determinants of satisfactory press-fit are not well understood. In previous studies, human cortical bone loaded circumferentially to simulate press-fit exhibited viscoelastic, or time dependent, behavior. The effect of bone viscoelastic behavior on the initial stability of press-fit stems is not known. Therefore, in the current study, push-out loads of cylindrical stems press-fit into reamed cadaver diaphyseal femoral specimens were measured immediately after assembly and 24 h with stem-bone diametral interference and stem surface treatment as independent variables. It was hypothesized that stem-bone interference would result in a viscoelastic response of bone that would decrease push-out load thereby impairing initial press-fit stability. Results showed that push-out load significantly decreased over a 24 h period due to bone viscoelasticity. It was also found that high and low push-out loads occurred at relatively small amounts of stem-bone interference, but a relationship between stem-bone interference and push-out load could not be determined due to variability among specimens. On the basis of this model, it was concluded that press-fit fixation can occur at relatively low levels of diametral interference and that stem-bone interference elicits viscoelastic response that reduces stem stability over time. From a clinical perspective, these results suggest that there could be large variations in initial press-fit fixation among patients.

Effect of water on nanomechanics of bone is different between tension and compression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samuel, Jitin; Park, Jun-Sang; Almer, Jonathan

Water, an important constituent in bone, resides in different compartments in bone matrix and may impose significant effects on its bulk mechanical properties. However, a clear understanding of the mechanistic role of water in toughening bone is yet to emerge. To address this issue, this study used a progressive loading protocol, coupled with measurements of in situ mineral and collagen fibril deformations using synchrotron X-ray diffraction techniques. Using this unique approach, the contribution of water to the ultrastructural behavior of bone was examined by testing bone specimens in different loading modes (tension and compression) and hydration states (wet and dehydrated).more » The results indicated that the effect of water on the mechanical behavior of mineral and collagen phases at the ultrastructural level was loading mode dependent and correlated with the bulk behavior of bone. Tensile loading elicited a transitional drop followed by an increase in load bearing by the mineral phase at the ultrastructural level, which was correlated with a strain hardening behavior of bone at the bulk level. Compression loading caused a continuous loss of load bearing by the mineral phase, which was reflected at the bulk level as a strain softening behavior. In addition, viscous strain relaxation and pre-strain reduction were observed in the mineral phase in the presence of water. Taken together, the results of this study suggest that water dictates the bulk behavior of bone by altering the interaction between mineral crystals and their surrounding matrix.« less

Skeletal maturation substantially affects elastic tissue properties in the endosteal and periosteal regions of loaded mice tibiae.

PubMed

Checa, Sara; Hesse, Bernhard; Roschger, Paul; Aido, Marta; Duda, Georg N; Raum, Kay; Willie, Bettina M

2015-07-01

Although it is well known that the bone adapts to changes in the mechanical environment by forming and resorbing the bone matrix, little is known about the influence of mechanical loading on tissue material properties of the pre-existing and newly formed bone. In this study, we analyzed the newly formed and pre-existing tissue after two weeks of controlled in vivo axial compressive loading in tibia of young (10 week-old) and adult (26 week-old) female mice and compared to the control contralateral limb, by means of scanning acoustic microscopy. Additionally, we used quantitative backscattered electron imaging to determine the bone mineral density distribution within the newly formed and pre-existing bone of young mice. No significant differences were found in tissue stiffness or mineral density in the pre-existing bone tissue as a result of external loading. In the endosteal region, 10 and 26 week loaded animals showed a 9% reduction in bone tissue stiffness compared to control animals. An increase of 200% in the mineral apposition rate in this region was observed in both age groups. In the periosteal region, the reduction in bone tissue stiffness and the increase in bone mineral apposition rate as a result of loading were two times higher in the 10 compared to the 26 week old animals. These data suggest that, during growth and skeletal maturation, the response of bone to mechanical loading is a deposition of new bone matrix, where the tissue amount but not its mineral or elastic properties are influenced by animal age. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Reduced functional loads alter the physical characteristics of the bone-periodontal ligament-cementum complex.

PubMed

Niver, E L; Leong, N; Greene, J; Curtis, D; Ryder, M I; Ho, S P

2011-12-01

Adaptive properties of the bone-periodontal ligament-tooth complex have been identified by changing the magnitude of functional loads using small-scale animal models, such as rodents. Reported adaptive responses as a result of lower loads due to softer diet include decreased muscle development, change in structure-function relationship of the cranium, narrowed periodontal ligament space, and changes in the mineral level of the cortical bone and alveolar jaw bone and in the glycosaminoglycans of the alveolar bone. However, the adaptive role of the dynamic bone-periodontal ligament-cementum complex to prolonged reduced loads has not been fully explained to date, especially with regard to concurrent adaptations of bone, periodontal ligament and cementum. Therefore, in the present study, using a rat model, the temporal effect of reduced functional loads on physical characteristics, such as morphology and mechanical properties and the mineral profiles of the bone-periodontal ligament-cementum complex was investigated. Two groups of 6-wk-old male Sprague-Dawley rats were fed nutritionally identical food with a stiffness range of 127-158 N/mm for hard pellet or 0.3-0.5 N/mm for soft powder forms. Spatio-temporal adaptation of the bone-periodontal ligament-cementum complex was identified by mapping changes in the following: (i) periodontal ligament collagen orientation and birefringence using polarized light microscopy, bone and cementum adaptation using histochemistry, and bone and cementum morphology using micro-X-ray computed tomography; (ii) mineral profiles of the periodontal ligament-cementum and periodontal ligament-bone interfaces by X-ray attenuation; and (iii) microhardness of bone and cementum by microindentation of specimens at ages 6, 8, 12 and 15 wk. Reduced functional loads over prolonged time resulted in the following adaptations: (i) altered periodontal ligament orientation and decreased periodontal ligament collagen birefringence, indicating decreased periodontal ligament turnover rate and decreased apical cementum resorption; (ii) a gradual increase in X-ray attenuation, owing to mineral differences, at the periodontal ligament-bone and periodontal ligament-cementum interfaces, without significant differences in the gradients for either group; (iii) significantly (p < 0.05) lower microhardness of alveolar bone (0.93 ± 0.16 GPa) and secondary cementum (0.803 ± 0.13 GPa) compared with the higher load group insert bone = (1.10 ± 0.17 and cementum = 0.940 ± 0.15 GPa, respectively) at 15 wk, indicating a temporal effect of loads on the local mineralization of bone and cementum. Based on the results from this study, the effect of reduced functional loads for a prolonged time could differentially affect morphology, mechanical properties and mineral variations of the local load-bearing sites in the bone-periodontal ligament-cementum complex. These observed local changes in turn could help to explain the overall biomechanical function and adaptations of the tooth-bone joint. From a clinical translation perspective, our study provides an insight into modulation of load on the complex for improved tooth function during periodontal disease and/or orthodontic and prosthodontic treatments. © 2011 John Wiley & Sons A/S.

Evaluation of implants coated with recombinant human bone morphogenetic protein-2 and vacuum-dried using the critical-size supraalveolar peri-implant defect model in dogs.

PubMed

Decker, John F; Lee, Jaebum; Cortella, Carlo Alberto; Polimeni, Giuseppe; Rohrer, Michael D; Wozney, John M; Hall, Jan; Susin, Cristiano; Wikesjö, Ulf M E

2010-12-01

Endosseous implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) in a laboratory bench setting and air-dried induce relevant bone formation but also resident bone remodeling. Thus, the objective of this study is to evaluate the effect of implants fully or partially coated with rhBMP-2 and vacuum-dried using an industrial process on local bone formation and resident bone remodeling. Twelve male adult Hound Labrador mongrel dogs were used. Critical-size, supraalveolar, peri-implant defects received titanium porous oxide surface implants coated in their most coronal aspect with rhBMP-2 (coronal-load, six animals), or by immersion of the entire implant in a rhBMP-2 solution (soak-load, six animals) for a total of 30 μg rhBMP-2 per implant. All implants were vacuum-dried. The animals were sacrificed at 8 weeks for histometric evaluation. Clinical healing was unremarkable. Bone formation was not significantly affected by the rhBMP-2 application protocol. New bone height and area averaged (± SE) 3.2 ± 0.5 versus 3.6 ± 0.3 mm, and 2.3 ± 0.5 versus 2.6 ± 0.8 mm(2) for coronal-load and soak-load implants, respectively (P >0.05). The corresponding bone density and bone-implant contact registrations averaged 46.7% ± 5.8% versus 31.6% ± 4.4%, and 28% ± 5.6% versus 36.9% ± 3.4% (P >0.05). In contrast, resident bone remodeling was significantly influenced by the rhBMP-2 application protocol. Peri-implant bone density averaged 72.2% ± 2.1% for coronal-load versus 60.6% ± 4.7% for soak-load implants (P <0.05); the corresponding bone-implant contact averaged 70.7% ± 6.1% versus 47.2% ± 6.0% (P <0.05). Local application of rhBMP-2 and vacuum-drying using industrial process seems to be a viable technology to manufacture implants that support local bone formation and osseointegration. Coronal-load implants obviate resident bone remodeling without compromising local bone formation.

Biomechanical analysis on fracture risk associated with bone deformity

NASA Astrophysics Data System (ADS)

Kamal, Nur Amalina Nadiah Mustafa; Som, Mohd Hanafi Mat; Basaruddin, Khairul Salleh; Daud, Ruslizam

2017-09-01

Osteogenesis Imperfecta (OI) is a disease related to bone deformity and is also known as `brittle bone' disease. Currently, medical personnel predict the bone fracture solely based on their experience. In this study, the prediction for risk of fracture was carried out by using finite element analysis on the simulated OI bone of femur. The main objective of this research was to analyze the fracture risk of OI-affected bone with respect to various loadings. A total of 12 models of OI bone were developed by applying four load cases and the angle of deformation for each of the models was calculated. The models were differentiated into four groups, namely standard, light, mild and severe. The results show that only a small amount of load is required to increase the fracture risk of the bone when the model is tested with hopping conditions. The analysis also shows that the torsional load gives a small effect to the increase of the fracture risk of the bone.

Development of implants composed of bioactive materials for bone repair

NASA Astrophysics Data System (ADS)

Xiao, Wei

The purpose of this Ph.D. research was to address the clinical need for synthetic bioactive materials to heal defects in non-loaded and loaded bone. Hollow hydroxyapatite (HA) microspheres created in a previous study were evaluated as a carrier for controlled release of bone morphogenetic protein-2 (BMP2) in bone regeneration. New bone formation in rat calvarial defects implanted with BMP2-loaded microspheres (43%) was significantly higher than microspheres without BMP2 (17%) at 6 weeks postimplantation. Then hollow HA microspheres with a carbonate-substituted composition were prepared to improve their resorption rate. Hollow HA microspheres with 12 wt. % of carbonate showed significantly higher new bone formation (73 +/- 8%) and lower residual HA (7 +/- 2%) than stoichiometric HA microspheres (59 +/- 2% new bone formation; 21 +/- 3% residual HA). The combination of carbonate-substituted hollow HA microspheres and clinically-safe doses of BMP2 could provide promising implants for healing non-loaded bone defects. Strong porous scaffolds of bioactive silicate (13-93) glass were designed with the aid of finite-element modeling, created by robocasting and evaluated for loaded bone repair. Scaffolds with a porosity gradient to mimic human cortical bone showed a compressive strength of 88 +/- 20 MPa, a flexural strength of 34 +/- 5 MPa and the ability to support bone infiltration in vivo. The addition of a biodegradable polylactic acid (PLA) layer to the external surface of these scaffolds increased their load-bearing capacity in four-point bending by 50% and dramatically enhanced their work of fracture, resulting in a "ductile" mechanical response. These bioactive glass-PLA composites, combining bioactivity, high strength, high work of fracture and an internal architecture conducive to bone infiltration, could provide optimal implants for structural bone repair.

Influence of lactose addition to gentamicin-loaded acrylic bone cement on the kinetics of release of the antibiotic and the cement properties.

PubMed

Frutos, Gloria; Pastor, José Ygnacio; Martínez, Noelia; Virto, María Rosa; Torrado, Susana

2010-03-01

The purpose of this study was to characterize a poly(methyl methacrylate) bone cement that was loaded with the antibiotic gentamicin sulphate (GS) and lactose, which served to modulate the release of GS from cement specimens. The release of GS when the cement specimens were immersed in phosphate-buffered saline at 37 degrees Celsius was determined spectrophotometrically. The microstructure, porosity, density, tensile properties and flexural properties of the cements were determined before and after release of GS. A kinetics model of the release of GS from the cement that involved a coupled mechanism based on dissolution/diffusion processes and an initial burst effect was proposed. Dissolution assay results showed that drug elution was controlled by a diffusion mechanism which can be modulated by lactose addition. Density values and mechanical properties (tensile strength, flexural strength, elastic modulus and fracture toughness) were reduced by the increased porosity resulting from lactose addition, but maintained acceptable values for the structural functions of bone cement. The present results suggest that lactose-modified, gentamicin-loaded acrylic bone cements are potential candidates for use in various orthopaedic and dental applications. Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Mechanical properties of cancellous bone in the human mandibular condyle are anisotropic.

PubMed

Giesen, E B; Ding, M; Dalstra, M; van Eijden, T M

2001-06-01

The objective of the present study was (1) to test the hypothesis that the elastic and failure properties of the cancellous bone of the mandibular condyle depend on the loading direction, and (2) to relate these properties to bone density parameters. Uniaxial compression tests were performed on cylindrical specimens (n=47) obtained from the condyles of 24 embalmed cadavers. Two loading directions were examined, i.e., a direction coinciding with the predominant orientation of the plate-like trabeculae (axial loading) and a direction perpendicular to the plate-like trabeculae (transverse loading). Archimedes' principle was applied to determine bone density parameters. The cancellous bone was in axial loading 3.4 times stiffer and 2.8 times stronger upon failure than in transverse loading. High coefficients of correlation were found among the various mechanical properties and between them and the apparent density and volume fraction. The anisotropic mechanical properties can possibly be considered as a mechanical adaptation to the loading of the condyle in vivo.

Early life vitamin D depletion alters the postnatal response to skeletal loading in growing and mature bone

PubMed Central

Buckley, Harriet; Owen, Robert; Marin, Ana Campos; Lu, Yongtau; Eyles, Darryl; Lacroix, Damien; Reilly, Gwendolen C.; Skerry, Tim M.; Bishop, Nick J.

2018-01-01

There is increasing evidence of persistent effects of early life vitamin D exposure on later skeletal health; linking low levels in early life to smaller bone size in childhood as well as increased fracture risk later in adulthood, independently of later vitamin D status. A major determinant of bone mass acquisition across all ages is mechanical loading. We tested the hypothesis in an animal model system that early life vitamin D depletion results in abrogation of the response to mechanical loading, with consequent reduction in bone size, mass and strength during both childhood and adulthood. A murine model was created in which pregnant dams were either vitamin D deficient or replete, and their offspring moved to a vitamin D replete diet at weaning. Tibias of the offspring were mechanically loaded and bone structure, extrinsic strength and growth measured both during growth and after skeletal maturity. Offspring of vitamin D deplete mice demonstrated lower bone mass in the non loaded limb and reduced bone mass accrual in response to loading in both the growing skeleton and after skeletal maturity. Early life vitamin D depletion led to reduced bone strength and altered bone biomechanical properties. These findings suggest early life vitamin D status may, in part, determine the propensity to osteoporosis and fracture that blights later life in many individuals. PMID:29370213

Drug diffusion, integration, and stability of nanoengineered drug-releasing implants in bone ex-vivo.

PubMed

Rahman, Shafiur; Gulati, Karan; Kogawa, Masakazu; Atkins, Gerald J; Pivonka, Peter; Findlay, David M; Losic, Dusan

2016-03-01

To treat skeletal conditions such as bone infections, osteoporotic fractures, and osteosarcoma, it would be ideal to introduce drugs directly to the affected site. Localized drug delivery from the bone implants is a promising alternative to systemic drug administration. In this study we investigated electrochemically nanoengineered Ti wire implants with titania nanotubes (TNTs), as minimally invasive drug-releasing implants for the delivery of drugs directly into the bone tissue. Since trabecular bone in vivo contains a highly interconnected bone marrow, we sought to determine the influence of marrow on drug release and diffusion. Electrochemical anodization of Ti wires (length 10 mm) was performed to create an oxide layer with TNTs on the surface, followed by loading with a fluorescent model drug, Rhodamine B (RhB). Cores of bovine trabecular bone were generated from the sternum of a young steer, and were processed to have an intact bone marrow, or the marrow was removed. RhB-loaded TNTs/Ti wires were inserted into the bone cores, which were then cultured ex vivo using the ZetOS™ bioreactor system to maintain bone viability. Release and diffusion of RhB inside the bone was monitored using fluorescence imaging and different patterns of drug transport in the presence or absence of marrow were observed. Scanning electron microscopy of the implants after retrieval from bone cores confirmed survival of the TNTs structures. Histological investigation showed the presence of bone cells adherent on the implants. This study shows a potential of Ti drug-releasing implants based on TNTs technology towards localized bone therapy. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 714-725, 2016. © 2015 Wiley Periodicals, Inc.

Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.

PubMed

Oestreich, A K; Carleton, S M; Yao, X; Gentry, B A; Raw, C E; Brown, M; Pfeiffer, F M; Wang, Y; Phillips, C L

2016-01-01

Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates. Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility. Currently, there is no cure, and therapeutic strategies encompass the use of antiresorptive pharmaceuticals and surgical bracing, with limited success and significant potential for adverse effects. Bone, a mechanosensing organ, can respond to high mechanical loads by increasing new bone formation and altering bone geometry to withstand increased forces. Skeletal muscle is a major source of physiological loading on bone, and bone strength is proportional to muscle mass. To test the hypothesis that congenic increases in muscle mass in the osteogenesis imperfecta murine model mouse (oim) will improve their compromised bone quality and strength, heterozygous (+/oim) mice were bred to mice deficient in myostatin (+/mstn), a negative regulator of muscle growth. The resulting adult offspring were evaluated for hindlimb muscle mass, and bone microarchitecture, physiochemistry, and biomechanical integrity. +/oim mice deficient in myostatin (+/mstn +/oim) were generated and demonstrated that myostatin deficiency increased body weight, muscle mass, and biomechanical strength in +/mstn +/oim mice as compared to +/oim mice. Additionally, myostatin deficiency altered the physiochemical properties of the +/oim bone but did not alter bone remodeling. Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.

Static vs dynamic loads as an influence on bone remodelling.

PubMed

Lanyon, L E; Rubin, C T

1984-01-01

Remodelling activity in the avian ulna was assessed under conditions of disuse alone, disuse with a superimposed continuous compressive load, and disuse interrupted by a short daily period of intermittent loading. The ulnar preparation consisted of the 110mm section of the bone shaft between two submetaphyseal osteotomies. Each end of the preparation was transfixed by a stainless steel pin and the shaft either protected from normal functional loading with the pins joined by external fixators, loaded continuously in compression by joining the pins with springs, or loaded intermittently in compression for a single 100s period per day by engaging the pins in an Instron machine. Similar loads (525 N) were used in both static and dynamic cases. The strains engendered were determined by strain gauges, and at their maximum around the bone's midshaft were -0.002. The intermittent load was applied at a frequency of 1 Hz as a ramped square wave, with a rate of change of strain during the ramp of 0.01 s-1. Peak strain at the midshaft of the ulna during wing flapping in the intact bone was recorded from bone bonded strain gauges in vivo as -0.0033 with a maximum rate of change of strain of 0.056 s-1. Examination of bone sections from the midpoint of the preparation after an 8 week period indicated that in both non-loaded and statically loaded bones there was an increase in both endosteal diameter and intra cortical porosity. These changes produced a decrease in cross sectional area which was similar in the two groups (-13%).(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced mechanical load decreases the density, stiffness, and strength of cancellous bone of the mandibular condyle.

PubMed

Giesen, E B W; Ding, M; Dalstra, M; van Eijden, T M G J

2003-05-01

To investigate the influence of decreased mechanical loading on the density and mechanical properties of the cancellous bone of the human mandibular condyle. Destructive compressive mechanical tests were performed on cancellous bone specimens.Background. Reduced masticatory function in edentate people leads to a reduction of forces acting on the mandible. As bone reacts to its mechanical environment a change in its material properties can be expected. Cylindrical bone specimens were obtained from dentate and edentate embalmed cadavers. Mechanical parameters were determined in the axial and in the transverse directions. Subsequently, density parameters were determined according to a method based on Archimedes' principle. The apparent density and volume fraction of the bone were about 18% lower in the edentate group; no age-related effect on density was found. The decrease of bone in the edentate group was associated with a lower stiffness and strength (about 22% and 28%, respectively). The ultimate strain, however, did not differ between the two groups. Both groups had similar mechanical anisotropy; in axial loading the bone was stiffer and stronger than in transverse loading. Reduced mechanical load had affected the density and herewith the mechanical properties of condylar cancellous bone, but not its anisotropy. The change in material properties of the cancellous bone after loss of teeth indicate that the mandibular condyle is sensitive for changes in its mechanical environment. Therefore, changes in mechanical loading of the condyle have to be accounted for in surgical procedures of the mandible.

Bioinspired Design of Polycaprolactone Composite Nanofibers as Artificial Bone Extracellular Matrix for Bone Regeneration Application.

PubMed

Gao, Xiang; Song, Jinlin; Zhang, Yancong; Xu, Xiao; Zhang, Siqi; Ji, Ping; Wei, Shicheng

2016-10-07

The design and development of functional biomimetic systems for programmed stem cell response is a field of topical interest. To mimic bone extracellular matrix, we present an innovative strategy for constructing drug-loaded composite nanofibrous scaffolds in this study, which could integrate multiple cues from calcium phosphate mineral, bioactive molecule, and highly ordered fiber topography for the control of stem cell fate. Briefly, inspired by mussel adhesion mechanism, a polydopamine (pDA)-templated nanohydroxyapatite (tHA) was synthesized and then surface-functionalized with bone morphogenetic protein-7-derived peptides via catechol chemistry. Afterward, the resulting peptide-loaded tHA (tHA/pep) particles were blended with polycaprolactone (PCL) solution to fabricate electrospun hybrid nanofibers with random and aligned orientation. Our research demonstrated that the bioactivity of grafted peptides was retained in composite nanofibers. Compared to controls, PCL-tHA/pep composite nanofibers showed improved cytocompatibility. Moreover, the incorporated tHA/pep particles in nanofibers could further facilitate osteogenic differentiation potential of human mesenchymal stem cells (hMSCs). More importantly, the aligned PCL-tHA/pep composite nanofibers showed more osteogenic activity than did randomly oriented counterparts, even under nonosteoinductive conditions, indicating excellent performance of biomimetic design in cell fate decision. After in vivo implantation, the PCL-tHA/pep composite nanofibers with highly ordered structure could significantly promote the regeneration of lamellar-like bones in a rat calvarial critical-sized defect. Accordingly, the presented strategy in our work could be applied for a wide range of potential applications in not only bone regeneration application but also pharmaceutical science.

Biofunctionalization of Titanium Granules with Simvastatin for Improving Osteogenic Activity and Antibacterial Properties (Ex Vivo Study).

PubMed

Karaji, Zahra Gorgin; Houshmand, Behzad; Abbasi, Shahsanam; Shafiei, Sara; Faghihi, Shahab

Titanium-based biomaterials present good biocompatibility, while their osseointegration and antibacterial properties need to be improved. This study aimed to enhance the bone-bonding ability of titanium-based granules, which are intended to be used as bone graft. The titanium granules were anodized in ethylene glycol-based electrolyte and subsequently annealed to be loaded separately with simvastatin. The samples were then inspected with attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) for drug loading. The release of simvastatin from titanium granule samples was measured after soaking samples in phosphate-buffered saline (PBS) for 30 days using ultraviolet-visible (UV/Vis) spectroscopy. The alkaline phosphatase (ALP) activity of MG63 osteosarcoma-loaded samples was measured, and microbroth dilution assay was performed to evaluate the antibacterial potential of drug-loaded and nonloaded titanium granule samples for bacterial growth. The results expressed the gradual and constant release of simvastatin within the duration of the examination. ALP of the samples showed improved activity of anodized and annealed granules, while the antibacterial test illustrated no significant improvement in their bactericidal effects. However, the simvastatin-loaded samples showed an improved antibacterial effect compared with nonloaded samples. It is assumed that anodizing, annealing, and subsequent simvastatin loading of titanium granules could be used as surface modification to improve osseointegration and restrain bacterial growth and adhesion. It is fair to believe that the results of this study could be used to treat titanium granules as bone graft substitute materials for dental and orthopedic applications.

Advances in imaging: impact on studying craniofacial bone structure.

PubMed

Majumdar, S

2003-01-01

Methods for measuring the structure of craniofacial bones are discussed in this paper. In addition to the three-dimensional macro-structure of the craniofacial skeleton, there is considerable interest in imaging the bone at a microscopic resolution in order to depict the micro-architecture of the trabecular bone itself. In addition to the density of the bone, the microarchitecture reflects bone quality. An understanding of bone quality and density changes has implications for a number of craniofacial pathologies, as well as for implant design and understanding the biomechanical function and loading of the jaw. Trabecular bone micro-architecture has been recently imaged using imaging methods such as micro-computed tomography, magnetic resonance imaging, and the images have been used in finite element models to assess bone mechanical properties. In this paper, some of the recent advances in micro-computed tomography and magnetic resonance imaging are reviewed, and their potential for imaging the trabecular bone in mandibular bones is presented. Examples of in vitro and in vivo images are presented.

The Osteogenesis Effect and Underlying Mechanisms of Local Delivery of gAPN in Extraction Sockets of Beagle Dogs

PubMed Central

Hu, Hongcheng; Pu, Yinfei; Lu, Songhe; Zhang, Kuo; Guo, Yuan; Lu, Hui; Li, Deli; Li, Xuefen; Li, Zichen; Wu, Yuwei; Tang, Zhihui

2015-01-01

A plastic and biodegradable bone substitute consists of poly (l-lactic-co-glycolic) acid and 30 wt % β-tricalcium phosphate has been previously fabricated, but its osteogenic capability required further improvement. We investigated the use of globular adiponectin (gAPN) as an anabolic agent for tissue-engineered bone using this scaffold. A qualitative analysis of the bone regeneration process was carried out using μCT and histological analysis 12 weeks after implantation. CBCT (Cone Beam Computed Tomography) superimposition was used to characterise the effect of the different treatments on bone formation. In this study, we also explored adiponectin’s (APN) influence on primary cultured human jaw bone marrow mesenchymal stem cells gene expressions involved in the osteogenesis. We found that composite scaffolds loaded with gAPN or bone morphogenetic protein 2 (BMP2) exhibited significantly increased bone formation and mineralisation following 12 weeks in the extraction sockets of beagle dogs, as well as enhanced expression of osteogenic markers. In vitro investigation revealed that APN also promoted osteoblast differentiation of primary cultured human jaw bone marrow mesenchymal stem cells (h-JBMMSCs), accompanied by increased activity of alkaline phosphatase, greater mineralisation, and production of the osteoblast-differentiated genes osteocalcin, bone sialoprotein and collagen type I, which was reversed by APPL1 siRNA. Therefore, the composite scaffold loaded with APN exhibited superior activity for guided bone regeneration compared with blank control or Bio-Oss® (a commercially available product). The composite scaffold with APN has significant potential for clinical applications in bone tissue engineering. PMID:26492241

Progressive cell-mediated changes in articular cartilage and bone in mice are initiated by a single session of controlled cyclic compressive loading

PubMed Central

Ko, Frank C.; Dragomir, Cecilia L.; Plumb, Darren A.; Hsia, Allison W.; Adebayo, Olufunmilayo O.; Goldring, Steven R.; Wright, Timothy M.; Goldring, Mary B.; van der Meulen, Marjolein C.H.

2017-01-01

We previously showed that repetitive cyclic loading of the mouse knee joint causes changes that recapitulate the features of osteoarthritis (OA) in humans. By applying a single loading session, we characterized the temporal progression of the structural and compositional changes in subchondral bone and articular cartilage. We applied loading during a single 5-minute session to the left tibia of adult (26-week-old) C57Bl/6 male mice at a peak load of 9.0N for 1200 cycles. Knee joints were collected at times 0, 1, and 2 weeks after loading. The changes in articular cartilage and subchondral bone were analyzed by histology, immunohistochemistry (caspase-3 and cathepsin K), and microcomputed tomography. At time 0, no change was evident in chondrocyte viability or cartilage or subchondral bone integrity. However, cartilage pathology demonstrated by localized thinning and proteoglycan loss occurred at 1 and 2 weeks after the single session of loading. Transient cancellous bone loss was evident at 1 week, associated with increased osteoclast number. Bone loss was reversed to control levels at 2 weeks. We observed formation of fibrous and cartilaginous tissues at the joint margins at 1 and 2 weeks. Our findings demonstrate that a single session of noninvasive loading leads to the development of OA-like morphological and cellular alterations in articular cartilage and subchondral bone. The loss in subchondral trabecular bone mass and thickness returns to control levels at 2 weeks, whereas the cartilage thinning and proteoglycan loss persist. PMID:26896841

Genetic selection to increase bone strength affects prevalence of keel bone damage and egg parameters in commercially housed laying hens.

PubMed

Stratmann, A; Fröhlich, E K F; Gebhardt-Henrich, S G; Harlander-Matauschek, A; Würbel, H; Toscano, M J

2016-05-01

The prevalence of keel bone damage as well as external egg parameters of 2 pure lines divergently selected for high (H) and low (L) bone strength were investigated in 2 aviary systems under commercial conditions. A standard LSL hybrid was used as a reference group. Birds were kept mixed per genetic line (77 hens of the H and L line and 201 or 206 hens of the LSL line, respectively, per pen) in 8 pens of 2 aviary systems differing in design. Keel bone status and body mass of 20 focal hens per line and pen were assessed at 17, 18, 23, 30, 36, 43, 52, and 63 wk of age. External egg parameters (i.e., egg mass, eggshell breaking strength, thickness, and mass) were measured using 10 eggs per line at both 38 and 57 wk of age. Body parameters (i.e. tarsus and third primary wing feather length to calculate index of wing loading) were recorded at 38 wk of age and mortality per genetic line throughout the laying cycle. Bone mineral density (BMD) of 15 keel bones per genetic line was measured after slaughter to confirm assignment of the experimental lines. We found a greater BMD in the H compared with the L and LSL lines. Fewer keel bone fractures and deviations, a poorer external egg quality, as well as a lower index of wing loading were found in the H compared with the L line. Mortality was lower and production parameters (e.g., laying performance) were higher in the LSL line compared with the 2 experimental lines. Aviary design affected prevalence of keel bone damage, body mass, and mortality. We conclude that selection of specific bone traits associated with bone strength as well as the related differences in body morphology (i.e., lower index of wing loading) have potential to reduce keel bone damage in commercial settings. Also, the housing environment (i.e., aviary design) may have additive effects. © 2016 Poultry Science Association Inc.

[Morphological analysis of bone dynamics and metabolic bone disease. Effect of loading on bone tissue].

PubMed

Sakai, Akinori

2011-04-01

We developed a voluntarily climbing animal model to investigate the effect of skeletal loading on bone tissue. At the cross section of the mid-femur, climbing exercise increases outer diameter and area of cortical bone. The mechanical strength of the femur is increased. This change of cortical volume and structure is more marked in anti-gravity exercise, such as climbing and jumping, than aerobic exercise. At the bone marrow area, climbing exercise increases trabecular bone volume and osteoblast number, while it decreases fat volume and adipocyte number. Skeletal loading promotes differentiation from mesenchymal stem cells to osteoblasts and suppresses that to adipocytes by facilitating the signal through PTH÷PTHrP receptor.

Probabilistic Risk Assessment for Astronaut Post Flight Bone Fracture

NASA Technical Reports Server (NTRS)

Lewandowski, Beth; Myers, Jerry; Licata, Angelo

2015-01-01

Introduction: Space flight potentially reduces the loading that bone can resist before fracture. This reduction in bone integrity may result from a combination of factors, the most common reported as reduction in astronaut BMD. Although evaluating the condition of bones continues to be a critical aspect of understanding space flight fracture risk, defining the loading regime, whether on earth, in microgravity, or in reduced gravity on a planetary surface, remains a significant component of estimating the fracture risks to astronauts. This presentation summarizes the concepts, development, and application of NASA's Bone Fracture Risk Module (BFxRM) to understanding pre-, post, and in mission astronaut bone fracture risk. The overview includes an assessment of contributing factors utilized in the BFxRM and illustrates how new information, such as biomechanics of space suit design or better understanding of post flight activities may influence astronaut fracture risk. Opportunities for the bone mineral research community to contribute to future model development are also discussed. Methods: To investigate the conditions in which spaceflight induced changes to bone plays a critical role in post-flight fracture probability, we implement a modified version of the NASA Bone Fracture Risk Model (BFxRM). Modifications included incorporation of variations in physiological characteristics, post-flight recovery rate, and variations in lateral fall conditions within the probabilistic simulation parameter space. The modeled fracture probability estimates for different loading scenarios at preflight and at 0 and 365 days post-flight time periods are compared. Results: For simple lateral side falls, mean post-flight fracture probability is elevated over mean preflight fracture probability due to spaceflight induced BMD loss and is not fully recovered at 365 days post-flight. In the case of more energetic falls, such as from elevated heights or with the addition of lateral movement, the contribution of space flight quality changes is much less clear, indicating more granular assessments, such as Finite Element modeling, may be needed to further assess the risks in these scenarios.

Genomic variation in the MMP-1 promoter influences estrogen receptor mediated activity in a mechanically activated environment: potential implications for microgravity risk assessment

NASA Astrophysics Data System (ADS)

Thaler, John; Myers, Ken; Lu, Ting; Hart, David

Background: Mechanotransduction, the conversion of mechanical forces (tensile, compression, shear etc.) into cellular signals is a significant response mechanism in bone that contributes to the balance between formation and resorption and helps maintain bone density. In microgravity the lack of mechanical signals can lead to a loss of bone density, however the signaling pathways responsible are not well understood. For women, sex-specific hormones are also important in maintaining bone density since estrogen deficiency is a major factor in the etiology of osteoporosis in postmenopausal women. Estrogen Receptors (ERs) are present in human connective tissue cells such as osteoblasts and may play a role in mechanotransduction responses. The two ER isoforms, alpha (ER-α) and beta (ER-β) differentially regulate expression of matrixmetalloproteinases (MMPs) which degrade extracellular matrix components found in connective tissues. Mechanical stimulation is known to affect the expression of MMP-1, a collagenase involved in the bone resorption process. The MMP-1 promoter region contains a single nucleotide polymorphism of an additional guanine (G) at position -1607 bp which creates a binding site for a member of the Ets family of mammalian transcription factors. The 2G allele is known to be present in 45-70% of healthy populations and has been associated with higher MMP-1 expression. The 2G allele has been linked to higher risk of several types of cancer but a link to osteoporosis or microgravity induced bone loss has not been explored. The purpose of the present study was to conduct a case-study to determine whether small genetic variations can influence cellular and tissue responses to mechanical loading. Specifically we examined the potential of the 1G/2G -1607 MMP-1 promoter SNP to alter the interplay between mechanical shear stress and estrogen receptors in controlling MMP-1 expression. Methods: Rabbit synovial cells (HIG-82) were used as an in vitro model system to examine the potential impact of the 1G/2G SNP on the cellular response to mechanical loading. HIG-82 cells are estrogen receptor (ER) negative and were transiently transfected with SV40 expression vectors for either ER-α or ER-β isoforms. Cells grown on glass slides were also co-transfected with either a 1G or 2G MMP-1 promoter-luciferase construct. Transfected cells were subjected to dynamic shear stress in a Flexcell Streamer Shear Stress Device. The dynamic loading regime was 0.5 Hz, 10 dyn/cm2 shear for 1 minute followed by 14 minutes rest and repeated for 8 hrs. A Promega Dual Luciferase Reporter Assay System was used to assess MMP-1 promoter activity. Results: Shear stress loading increased both 1G and 2G MMP-1 promoter activity compared to unloaded controls, however the 2G promoter had significantly higher rates of expression than the 1G promoter across all loading regimes and ER co-transfections. Transfection with ER-β resulted in higher MMP-1 promoter activity than that in cells expressing ER-α or in ER-neg cells. Conclusions: Specific genomic variations can lead to differences in cellular responses to changes in mechanical loading environments such as are encountered in microgravity environments or earth-based analogs. These genomic differences may predispose individuals to greater risk of bone loss. It is important to understand the combined effects of mechanical loading, genetic variation and sex hormones on bone maintenance so that risks can be identified for microgravity or analog environments, and specific interventions developed to counteract such risk or even exclude some individuals from prolonged space environments due to the extent of the risk.

Editorial Commentary: Save the Subchondral Bone in Rotator Cuff Repair Greater Tuberosity Preparation.

PubMed

Brand, Jefferson C

2016-04-01

Results from a recent investigation into the practice of greater tuberosity decortication before rotator cuff repair showed that decortication significantly reduced the ultimate failure load. Although the potential of greater tuberosity treatment for solving the rotator cuff healing quandary still exists, the biomechanics are clear, one should not decorticate the greater tuberosity to cancellous bone. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Controlled release of NELL-1 protein from chitosan/hydroxyapatite-modified TCP particles.

PubMed

Zhang, Yulong; Dong, Rui; Park, Yujin; Bohner, Marc; Zhang, Xinli; Ting, Kang; Soo, Chia; Wu, Benjamin M

2016-09-10

NEL-like molecule-1 (NELL-1) is a novel osteogenic protein that showing high specificity to osteochondral cells. It was widely used in bone regeneration research by loading onto carriers such as tricalcium phosphate (TCP) particles. However, there has been little research on protein controlled release from this material and its potential application. In this study, TCP was first modified with a hydroxyapatite coating followed by a chitosan coating to prepare chitosan/hydroxyapatite-coated TCP particles (Chi/HA-TCP). The preparation was characterized by SEM, EDX, FTIR, XRD, FM and Zeta potential measurements. The NELL-1 loaded Chi/HA-TCP particles and the release kinetics were investigated in vitro. It was observed that the Chi/HA-TCP particles prepared with the 0.3% (wt/wt) chitosan solution were able to successfully control the release of NELL-1 and maintain a slow, steady release for up to 28 days. Furthermore, more than 78% of the loaded protein's bioactivity was preserved in Chi/HA-TCP particles over the period of the investigation, which was significantly higher than that of the protein released from hydroxyapatite coated TCP (HA-TCP) particles. Collectively, this study suggests that the osteogenic protein NELL-1 showed a sustained release pattern after being encapsulated into the modified Chi/HA-TCP particles, and the NELL-1 integrated composite of Chi/HA-TCP showed a potential to function as a protein delivery carrier and as an improved bone matrix for use in bone regeneration research. Copyright © 2016 Elsevier B.V. All rights reserved.

Activation of Wnt Signaling by Mechanical Loading Is Impaired in the Bone of Old Mice

PubMed Central

Holguin, Nilsson; Brodt, Michael D; Silva, Matthew J

2017-01-01

Aging diminishes bone formation engendered by mechanical loads, but the mechanism for this impairment remains unclear. Because Wnt signaling is required for optimal loading-induced bone formation, we hypothesized that aging impairs the load-induced activation of Wnt signaling. We analyzed dynamic histomorphometry of 5-month-old, 12-month-old, and 22-month-old C57Bl/6JN mice subjected to multiple days of tibial compression and corroborated an age-related decline in the periosteal loading response on day 5. Similarly, 1 day of loading increased periosteal and endocortical bone formation in young-adult (5-month-old) mice, but old (22-month-old) mice were unresponsive. These findings corroborated mRNA expression of genes related to bone formation and the Wnt pathway in tibias after loading. Multiple bouts (3 to 5 days) of loading upregulated bone formation–related genes, e.g., Osx and Col1a1, but older mice were significantly less responsive. Expression of Wnt negative regulators, Sost and Dkk1, was suppressed with a single day of loading in all mice, but suppression was sustained only in young-adult mice. Moreover, multiple days of loading repeatedly suppressed Sost and Dkk1 in young-adult, but not in old tibias. The age-dependent response to loading was further assessed by osteocyte staining for Sclerostin and LacZ in tibia of TOPGAL mice. After 1 day of loading, fewer osteocytes were Sclerostin-positive and, corroboratively, more osteocytes were LacZ-positive (Wnt active) in both 5-month-old and 12-month-old mice. However, although these changes were sustained after multiple days of loading in 5-month-old mice, they were not sustained in 12-month-old mice. Last, Wnt1 and Wnt7b were the most load-responsive of the 19 Wnt ligands. However, 4 hours after a single bout of loading, although their expression was upregulated threefold to 10-fold in young-adult mice, it was not altered in old mice. In conclusion, the reduced bone formation response of aged mice to loading may be due to failure to sustain Wnt activity with repeated loading. PMID:27357062

Finite element analysis of a pseudoelastic compression-generating intramedullary ankle arthrodesis nail.

PubMed

Anderson, Ryan T; Pacaccio, Douglas J; Yakacki, Christopher M; Carpenter, R Dana

2016-09-01

Tibio-talo-calcaneal (TTC) arthrodesis is an end-stage treatment for patients with severe degeneration of the ankle joint. This treatment consists of using an intramedullary nail (IM) to fuse the calcaneus, talus, and tibia bones together into one construct. Poor bone quality within the joint prior to surgery is common and thus the procedure has shown complications due to non-union. However, a new FDA-approved IM nail has been released that houses a nickel titanium (NiTi) rod that uses its inherent pseudoelastic material properties to apply active compression across the fusion site. Finite element analysis was performed to model the mechanical response of the NiTi within the device. A bone model was then developed based on a quantitative computed tomography (QCT) image for anatomical geometry and bone material properties. A total bone and device system was modeled to investigate the effect of bone quality change and gather load-sharing properties during gait loading. It was found that during the highest magnitude loading of gait, the load taken by the bone was more than 50% higher than the load taken by the nail. When comparing the load distribution during gait, results from this study would suggest that the device helps to prevent stress shielding by allowing a more even distribution of load between bone and nail. In conditions where bone quality may vary patient-to-patient, the model indicates that a 10% decrease in overall bone modulus (i.e. material stiffness) due to reduced bone mineral density would result in higher stresses in the nail (3.4%) and a marginal decrease in stress for the bone (0.5%). The finite element model presented in this study can be used as a quantitative tool to further understand the stress environment of both bone and device for a TTC fusion. Furthermore, the methodology presented gives insight on how to computationally program and use the unique material properties of NiTi in an active compression state useful for bone fracture healing or fusion treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bone as an ion exchange system: evidence for a link between mechanotransduction and metabolic needs.

PubMed

Rubinacci, A; Covini, M; Bisogni, C; Villa, I; Galli, M; Palumbo, C; Ferretti, M; Muglia, M A; Marotti, G

2002-04-01

To detect whether the mutual interaction occurring between the osteocytes-bone lining cells system (OBLCS) and the bone extracellular fluid (BECF) is affected by load through a modification of the BECF-extracellular fluid (ECF; systemic extracellular fluid) gradient, mice metatarsal bones immersed in ECF were subjected ex vivo to a 2-min cyclic axial load of different amplitudes and frequencies. The electric (ionic) currents at the bone surface were measured by a vibrating probe after having exposed BECF to ECF through a transcortical hole. The application of different loads and different frequencies increased the ionic current in a dose-dependent manner. The postload current density subsequently decayed following an exponential pattern. Postload increment's amplitude and decay were dependent on bone viability. Dummy and static loads did not induce current density modifications. Because BECF is perturbed by loading, it is conceivable that OBLCS tends to restore BECF preload conditions by controlling ion fluxes at the bone-plasma interface to fulfill metabolic needs. Because the electric current reflects the integrated activity of OBLCS, its evaluation in transgenic mice engineered to possess genetic lesions in channels or matrix constituents could be helpful in the characterization of the mechanical and metabolic functions of bone.

Investigation of fatigue crack growth in acrylic bone cement using the acoustic emission technique.

PubMed

Roques, A; Browne, M; Thompson, J; Rowland, C; Taylor, A

2004-02-01

Failure of the bone cement mantle has been implicated in the loosening process of cemented hip stems. Current methods of investigating degradation of the cement mantle in vitro often require sectioning of the sample to confirm failure paths. The present research investigates acoustic emission as a passive experimental method for the assessment of bone cement failure. Damage in bone cement was monitored during four point bending fatigue tests through an analysis of the peak amplitude, duration, rise time (RT) and energy of the events emitted from the damage sections. A difference in AE trends was observed during failure for specimens aged and tested in (i) air and (ii) Ringer's solution at 37 degrees C. It was noted that the acoustic behaviour varied according to applied load level; events of higher duration and RT were emitted during fatigue at lower stresses. A good correlation was observed between crack location and source of acoustic emission, and the nature of the acoustic parameters that were most suited to bone cement failure characterisation was identified. The methodology employed in this study could potentially be used as a pre-clinical assessment tool for the integrity of cemented load bearing implants.

Raloxifene microsphere-embedded collagen/chitosan/β-tricalcium phosphate scaffold for effective bone tissue engineering.

PubMed

Zhang, Ming-Lei; Cheng, Ji; Xiao, Ye-Chen; Yin, Ruo-Feng; Feng, Xu

2017-02-25

Engineering novel scaffolds that can mimic the functional extracellular matrix (ECM) would be a great achievement in bone tissue engineering. This paper reports the fabrication of novel collagen/chitosan/β-tricalcium phosphate (CCTP) based tissue engineering scaffold. In order to improve the regeneration ability of scaffold, we have embedded raloxifene (RLX)-loaded PLGA microsphere in the CCTP scaffold. The average pore of scaffold was in the range of 150-200μm with ideal mechanical strength and swelling/degradation characteristics. The release rate of RLX from the microsphere (MS) embedded scaffold was gradual and controlled. Also a significantly enhanced cell proliferation was observed in RLX-MS exposed cell group suggesting that microsphere/scaffold could be an ideal biomaterial for bone tissue engineering. Specifically, RLX-MS showed a significantly higher Alizarin red staining indicating the higher mineralization capacity of this group. Furthermore, a high alkaline phosphatase (ALP) activity for RLX-MS exposed group after 15days incubation indicates the bone regeneration capacity of MC3T3-E1 cells. Overall, present study showed that RLX-loaded microsphere embedded scaffold has the promising potential for bone tissue engineering applications. Copyright © 2016. Published by Elsevier B.V.

Development of PLGA-coated β-TCP scaffolds containing VEGF for bone tissue engineering.

PubMed

Khojasteh, Arash; Fahimipour, Farahnaz; Eslaminejad, Mohamadreza Baghaban; Jafarian, Mohammad; Jahangir, Shahrbanoo; Bastami, Farshid; Tahriri, Mohammadreza; Karkhaneh, Akbar; Tayebi, Lobat

2016-12-01

Bone tissue engineering is sought to apply strategies for bone defects healing without limitations and short-comings of using either bone autografts or allografts and xenografts. The aim of this study was to fabricate a thin layer poly(lactic-co-glycolic) acid (PLGA) coated beta-tricalcium phosphate (β-TCP) scaffold with sustained release of vascular endothelial growth factor (VEGF). PLGA coating increased compressive strength of the β-TCP scaffolds significantly. For in vitro evaluations, canine mesenchymal stem cells (cMSCs) and canine endothelial progenitor cells (cEPCs) were isolated and characterized. Cell proliferation and attachment were demonstrated and the rate of cells proliferation on the VEGF released scaffold was significantly more than compared to the scaffolds with no VEGF loading. A significant increase in expression of COL1 and RUNX2 was indicated in the scaffolds loaded with VEGF and MSCs compared to the other groups. Consequently, PLGA coated β-TCP scaffold with sustained and localized release of VEGF showed favourable results for bone regeneration in vitro, and this scaffold has the potential to use as a drug delivery device in the future. Copyright © 2016. Published by Elsevier B.V.

Axial load-bearing capacity of an osteochondral autograft stabilized with a resorbable osteoconductive bone cement compared with a press-fit graft in a bovine model.

PubMed

Kiss, Marc-Olivier; Levasseur, Annie; Petit, Yvan; Lavigne, Patrick

2012-05-01

Osteochondral autografts in mosaicplasty are inserted in a press-fit fashion, and hence, patients are kept nonweightbearing for up to 2 months after surgery to allow bone healing and prevent complications. Very little has been published regarding alternative fixation techniques of those grafts. Osteochondral autografts stabilized with a resorbable osteoconductive bone cement would have a greater load-bearing capacity than standard press-fit grafts. Controlled laboratory study. Biomechanical testing was conducted on 8 pairs of cadaveric bovine distal femurs. For the first 4 pairs, 6 single osteochondral autografts were inserted in a press-fit fashion on one femur. On the contralateral femur, 6 grafts were stabilized with a calcium triglyceride osteoconductive bone cement. For the 4 remaining pairs of femurs, 4 groups of 3 adjacent press-fit grafts were inserted on one femur, whereas on the contralateral femur, grafts were cemented. After a maturation period of 48 hours, axial loading was applied on all single grafts and on the middle graft of each 3-in-a-row series. For the single-graft configuration, median loads required to sink the press-fit and cemented grafts by 2 and 3 mm were 281.87 N versus 345.56 N (P = .015) and 336.29 N versus 454.08 N (P = .018), respectively. For the 3-in-a-row configuration, median loads required to sink the press-fit and cemented grafts by 2 and 3 mm were 260.31 N versus 353.47 N (P = .035) and 384.83 N versus 455.68 N (P = .029), respectively. Fixation of osteochondral grafts using bone cement appears to improve immediate stability over the original mosaicplasty technique for both single- and multiple-graft configurations. Achieving greater primary stability of osteochondral grafts could potentially accelerate postoperative recovery, allowing early weightbearing and physical therapy.

Locomotor variation and bending regimes of capuchin limb bones.

PubMed

Demes, Brigitte; Carlson, Kristian J

2009-08-01

Primates are very versatile in their modes of progression, yet laboratory studies typically capture only a small segment of this variation. In vivo bone strain studies in particular have been commonly constrained to linear locomotion on flat substrates, conveying the potentially biased impression of stereotypic long bone loading patterns. We here present substrate reaction forces (SRF) and limb postures for capuchin monkeys moving on a flat substrate ("terrestrial"), on an elevated pole ("arboreal"), and performing turns. The angle between the SRF vector and longitudinal axes of the forearm or leg is taken as a proxy for the bending moment experienced by these limb segments. In both frontal and sagittal planes, SRF vectors and distal limb segments are not aligned, but form discrepant angles; that is, forces act on lever arms and exert bending moments. The positions of the SRF vectors suggest bending around oblique axes of these limb segments. Overall, the leg is exposed to greater moments than the forearm. Simulated arboreal locomotion and turns introduce variation in the discrepancy angles, thus confirming that expanding the range of locomotor behaviors studied will reveal variation in long bone loading patterns that is likely characteristic of natural locomotor repertoires. "Arboreal" locomotion, even on a linear noncompliant branch, is characterized by greater variability of force directions and discrepancy angles than "terrestrial" locomotion (significant for the forearm only), partially confirming the notion that life in trees is associated with greater variation in long bone loading. Directional changes broaden the range of external bending moments even further.

Multiple Small Diameter Drillings Increase Femoral Neck Stability Compared with Single Large Diameter Femoral Head Core Decompression Technique for Avascular Necrosis of the Femoral Head.

PubMed

Brown, Philip J; Mannava, Sandeep; Seyler, Thorsten M; Plate, Johannes F; Van Sikes, Charles; Stitzel, Joel D; Lang, Jason E

2016-10-26

Femoral head core decompression is an efficacious joint-preserving procedure for treatment of early stage avascular necrosis. However, postoperative fractures have been described which may be related to the decompression technique used. Femoral head decompressions were performed on 12 matched human cadaveric femora comparing large 8mm single bore versus multiple 3mm small drilling techniques. Ultimate failure strength of the femora was tested using a servo-hydraulic material testing system. Ultimate load to failure was compared between the different decompression techniques using two paired ANCOVA linear regression models. Prior to biomechanical testing and after the intervention, volumetric bone mineral density was determined using quantitative computed tomography to account for variation between cadaveric samples and to assess the amount of bone disruption by the core decompression. Core decompression, using the small diameter bore and multiple drilling technique, withstood significantly greater load prior to failure compared with the single large bore technique after adjustment for bone mineral density (p< 0.05). The 8mm single bore technique removed a significantly larger volume of bone compared to the 3mm multiple drilling technique (p< 0.001). However, total fracture energy was similar between the two core decompression techniques. When considering core decompression for the treatment of early stage avascular necrosis, the multiple small bore technique removed less bone volume, thereby potentially leading to higher load to failure.

Effect of healing time on bone-implant contact of orthodontic micro-implants: a histologic study.

PubMed

Ramazanzadeh, Barat Ali; Fatemi, Kazem; Dehghani, Mahboobe; Mohtasham, Nooshin; Jahanbin, Arezoo; Sadeghian, Hamed

2014-01-01

Objectives. This study aimed to evaluate the effect of immediate and delayed loading of orthodontic micro-implants on bone-implant contact. Materials and Methods. Sixty four micro-implants were implanted in dog's jaw bone. The micro-implants were divided into loaded and unloaded (control) groups. The control group had two subgroups: four and eight weeks being implanted. The loaded group had two subgroups of immediate loading and delayed (after four weeks healing) loading. Loaded samples were subjected to 200g load for four weeks. After sacrificing the animals micro-implants and surrounding tissues were observed histologically. Bone-implant contact ratios (BIC) were calculated and different groups' results were compared by three-way ANOVA. Results. Mean survival rate was 96.7% in general. Survival rates were 96.7%, 94.4% and 100% for control, immediate and delayed loaded groups, respectively. BIC values were not significantly different in loaded and control groups, immediate and delayed loading groups, and pressure and tension sides. Mandibular micro-implants had significantly higher BIC than maxillary ones in immediate loading, 4-weeks control, and 8-weeks control groups (P = 0.021, P = 0.009, P = 0.003, resp.). Conclusion Immediate or delayed loading of micro-implants in dog did not cause significant difference in Bone-implant contact which could be concluded that healing time had not significant effect on micro-implant stability.

Effect of Healing Time on Bone-Implant Contact of Orthodontic Micro-Implants: A Histologic Study

PubMed Central

Ramazanzadeh, Barat Ali; Fatemi, Kazem; Dehghani, Mahboobe; Mohtasham, Nooshin; Jahanbin, Arezoo; Sadeghian, Hamed

2014-01-01

Objectives. This study aimed to evaluate the effect of immediate and delayed loading of orthodontic micro-implants on bone-implant contact. Materials and Methods. Sixty four micro-implants were implanted in dog's jaw bone. The micro-implants were divided into loaded and unloaded (control) groups. The control group had two subgroups: four and eight weeks being implanted. The loaded group had two subgroups of immediate loading and delayed (after four weeks healing) loading. Loaded samples were subjected to 200g load for four weeks. After sacrificing the animals micro-implants and surrounding tissues were observed histologically. Bone-implant contact ratios (BIC) were calculated and different groups' results were compared by three-way ANOVA. Results. Mean survival rate was 96.7% in general. Survival rates were 96.7%, 94.4% and 100% for control, immediate and delayed loaded groups, respectively. BIC values were not significantly different in loaded and control groups, immediate and delayed loading groups, and pressure and tension sides. Mandibular micro-implants had significantly higher BIC than maxillary ones in immediate loading, 4-weeks control, and 8-weeks control groups (P = 0.021, P = 0.009, P = 0.003, resp.). Conclusion Immediate or delayed loading of micro-implants in dog did not cause significant difference in Bone-implant contact which could be concluded that healing time had not significant effect on micro-implant stability. PMID:25006463

Skeletal Adaptation to Daily Activity: A Biochemical Perspective

NASA Technical Reports Server (NTRS)

Whalen, Robert T.; Dalton, Bonnie (Technical Monitor)

2002-01-01

Musculoskeletal forces generated by normal daily activity on Earth maintain the functional and structural properties of muscle and bone throughout most of one's adult life. A reduction in the level of cumulative daily loading caused by space flight, bed rest or spinal cord injury induces rapid muscle atrophy, functional changes in muscle, and bone resorption in regions subjected to the reduced loading. Bone cells in culture and bone tissue reportedly respond to a wide variety of non-mechanical and mechanical stimuli ranging, from electromagnetic fields, and hormones to small amplitude, high frequency vibrations, fluid flow, strain rate, and stress/strain magnitude. However, neither the transduction mechanism that transforms the mechanical input into a muscle or bone metabolic response nor the characteristics, of the loading history that directly or indirectly stimulates the cell is known. Identifying the factors contributing to the input stimulus will have a major impact on the design of effective countermeasures for long duration space flight. This talk will present a brief overview of current theories of bone remodeling and functional adaptation to mechanical loading. Work from our lab will be presented from the perspective of daily cumulative loading on Earth and its relationship to bone density and structure. Our objective is to use the tibia and calcaneus as model bone sites of cortical and cancellous bone adaptation, loaded daily by musculoskeletal forces in equilibrium with the ground reaction force. All materials that will be discussed are in the open scientific literature.

Knotless anchors with sutures external to the anchor body may be at risk for suture cutting through osteopenic bone.

PubMed

Ono, Y; Woodmass, J M; Nelson, A A; Boorman, R S; Thornton, G M; Lo, I K Y

2016-06-01

This study evaluated the mechanical performance, under low-load cyclic loading, of two different knotless suture anchor designs: sutures completely internal to the anchor body (SpeedScrew) and sutures external to the anchor body and adjacent to bone (MultiFIX P). Using standard suture loops pulled in-line with the rotator cuff (approximately 60°), anchors were tested in cadaveric bone and foam blocks representing normal to osteopenic bone. Mechanical testing included preloading to 10 N and cyclic loading for 500 cycles from 10 N to 60 N at 60 mm/min. The parameters evaluated were initial displacement, cyclic displacement and number of cycles and load at 3 mm displacement relative to preload. Video recording throughout testing documented the predominant source of suture displacement and the distance of 'suture cutting through bone'. In cadaveric bone and foam blocks, MultiFIX P anchors had significantly greater initial displacement, and lower number of cycles and lower load at 3 mm displacement than SpeedScrew anchors. Video analysis revealed 'suture cutting through bone' as the predominant source of suture displacement in cadaveric bone (qualitative) and greater 'suture cutting through bone' comparing MultiFIX P with SpeedScrew anchors in foam blocks (quantitative). The greater suture displacement in MultiFIX P anchors was predominantly from suture cutting through bone, which was enhanced in an osteopenic bone model. Anchors with sutures external to the anchor body are at risk for suture cutting through bone since the suture eyelet is at the distal tip of the implant and the suture directly abrades against the bone edge during cyclic loading. Suture cutting through bone may be a significant source of fixation failure, particularly in osteopenic bone.Cite this article: Y. Ono, J. M. Woodmass, A. A. Nelson, R. S. Boorman, G. M. Thornton, I. K. Y. Lo. Knotless anchors with sutures external to the anchor body may be at risk for suture cutting through osteopenic bone. Bone Joint Res 2016;5:269-275. DOI: 10.1302/2046-3758.56.2000535. © 2016 Lo et al.

Hydroxyapatite/polylactide biphasic combination scaffold loaded with dexamethasone for bone regeneration.

PubMed

Son, Jun-Sik; Kim, Su-Gwan; Oh, Ji-Su; Appleford, Mark; Oh, Sunho; Ong, Joo L; Lee, Kyu-Bok

2011-12-15

This study presents a novel design of a ceramic/polymer biphasic combination scaffold that mimics natural bone structures and is used as a bone graft substitute. To mimic the natural bone structures, the outside cortical-like shells were composed of porous hydroxyapatite (HA) with a hollow interior using a polymeric template-coating technique; the inner trabecular-like core consisted of porous poly(D,L-lactic acid) (PLA) that was loaded with dexamethasone (DEX) and was directly produced using a particle leaching/gas forming technique to create the inner diameter of the HA scaffold. It was observed that the HA and PLA parts of the fabricated HA/PLA biphasic scaffold contained open and interconnected pore structures, and the boundary between both parts was tightly connected without any gaps. It was found that the structure of the combination scaffold was analogous to that of natural bone based on micro-computed tomography analysis. Additionally, the dense, uniform apatite layer was formed on the surface of the HA/PLA biphasic scaffold through a biomimetic process, and DEX was successfully released from the PLA of the biphasic scaffold over a 1-month period. This release caused human embryonic palatal mesenchyme cells to proliferate, differentiate, produce ECM, and form tissue in vitro. Therefore, it was concluded that this functionally graded scaffold is similar to natural bone and represents a potential bone-substitute material. Copyright © 2011 Wiley Periodicals, Inc.

Electric reaction arising in bone subjected to mechanical loadings

NASA Astrophysics Data System (ADS)

Murasawa, Go; Cho, Hideo; Ogawa, Kazuma

2006-03-01

The aim of present study is the investigation of the electric reaction arising in bone subjected to mechanical loadings. Firstly, specimen was fabricated from femur of cow, and ultrasonic propagation in bone was measured by ultrasonic technique. Secondary, 4-point bending test was conducted up to fracture, and electric reaction arising in bone was measured during loading. Thirdly, cyclic 4-point bending test was conducted to investigate the effect of applied displacement speed on electric reaction.

Titanium versus zirconia implants supporting maxillary overdentures: three-dimensional finite element analysis.

PubMed

Osman, Reham B; Elkhadem, Amr H; Ma, Sunyoung; Swain, Michael V

2013-01-01

The purpose of this study was to compare the stress and strain occurring in peri-implant bone and implants used to support maxillary overdentures. Three-dimensional finite element analysis (3D FEA) was used to compare one-piece zirconia and titanium implants. Two types of implants were simulated using a 3D FEA model: one-piece zirconia and titanium implants (diameter, 3.8 × 11.5 mm) with 2.25-mm diameter ball abutments. In each simulation four implants were placed bilaterally in the canine/premolar region of an edentulous maxillary model. Static loads were applied axially and 20 degrees buccolingually on the buccal slope of the lingual cusps of posterior teeth of the first quadrant. Von Mises stresses and equivalent strains generated in peri-implant bone and first principal stresses in the implants were calculated. Comparable stress and strain values were shown in the peri-implant bone for both types of implants. The maximum equivalent strain produced in the peri-implant region was mostly within the range for bone augmentation. Under oblique loading, maximum von Mises stresses and equivalent strain were more evident at the neck of the most distal implant on the loaded side. Under axial load, the stress and strain were transferred to the peri-implant bone around the apex of the implant. Maximum tensile stresses that developed for either material were well below their fracture strength. The highest stresses were mainly located at the distobuccal region of the neck for the two implant materials under both loading conditions. From a biomechanical point of view, ceramic implants made from yttrium-stabilized tetragonal polycrystalline zirconia may be a potential alternative to conventional titanium implants for the support of overdentures. This is particularly relevant for a select group of patients with a proven allergy to titanium. Prospective clinical studies are still required to confirm these in vitro results. Different simulations presenting various cortical bone thicknesses and implant designs are required to provide a better understanding of the biomechanics of zirconia implants.

Callus remodelling model

NASA Astrophysics Data System (ADS)

Miodowska, Justyna; Bielski, Jan; Kromka-Szydek, Magdalena

2018-01-01

The objective of this paper is to investigate the healing process of the callus using bone remodelling approach. A new mathematical model of bone remodelling is proposed including both underload and overload resorption, as well as equilibrium and bone growth states. The created model is used to predict the stress-stimulated change in the callus density. The permanent and intermittent loading programs are considered. The analyses indicate that obtaining a sufficiently high values of the callus density (and hence the elasticity) modulus is only possible using time-varying load parameters. The model predictions also show that intermittent loading program causes delayed callus healing. Understanding how mechanical conditions influence callus remodelling process may be relevant in the bone fracture treatment and initial bone loading during rehabilitation.

Biomechanics and Mechanobiology of Trabecular Bone: A Review

PubMed Central

Oftadeh, Ramin; Perez-Viloria, Miguel; Villa-Camacho, Juan C.; Vaziri, Ashkan; Nazarian, Ara

2015-01-01

Trabecular bone is a highly porous, heterogeneous, and anisotropic material which can be found at the epiphyses of long bones and in the vertebral bodies. Studying the mechanical properties of trabecular bone is important, since trabecular bone is the main load bearing bone in vertebral bodies and also transfers the load from joints to the compact bone of the cortex of long bones. This review article highlights the high dependency of the mechanical properties of trabecular bone on species, age, anatomic site, loading direction, and size of the sample under consideration. In recent years, high resolution micro finite element methods have been extensively used to specifically address the mechanical properties of the trabecular bone and provide unique tools to interpret and model the mechanical testing experiments. The aims of the current work are to first review the mechanobiology of trabecular bone and then present classical and new approaches for modeling and analyzing the trabecular bone microstructure and macrostructure and corresponding mechanical properties such as elastic properties and strength. PMID:25412137

Comparing the influence of crestal cortical bone and sinus floor cortical bone in posterior maxilla bi-cortical dental implantation: a three-dimensional finite element analysis.

PubMed

Yan, Xu; Zhang, Xinwen; Chi, Weichao; Ai, Hongjun; Wu, Lin

2015-05-01

This study aimed to compare the influence of alveolar ridge cortical bone and sinus floor cortical bone in sinus areabi-cortical dental implantation by means of 3D finite element analysis. Three-dimensional finite element (FE) models in a posterior maxillary region with sinus membrane and the same height of alveolar ridge of 10 mm were generated according to the anatomical data of the sinus area. They were either with fixed thickness of crestal cortical bone and variable thickness of sinus floor cortical bone or vice versa. Ten models were assumed to be under immediate loading or conventional loading. The standard implant model based on the Nobel Biocare implant system was created via computer-aided design software. All materials were assumed to be isotropic and linearly elastic. An inclined force of 129 N was applied. Von Mises stress mainly concentrated on the surface of crestal cortical bone around the implant neck. For all the models, both the axial and buccolingual resonance frequencies of conventional loading were higher than those of immediate loading; however, the difference is less than 5%. The results showed that bi-cortical implant in sinus area increased the stability of the implant, especially for immediately loading implantation. The thickness of both crestal cortical bone and sinus floor cortical bone influenced implant micromotion and stress distribution; however, crestal cortical bone may be more important than sinus floor cortical bone.

Progressive cell-mediated changes in articular cartilage and bone in mice are initiated by a single session of controlled cyclic compressive loading.

PubMed

Ko, Frank C; Dragomir, Cecilia L; Plumb, Darren A; Hsia, Allison W; Adebayo, Olufunmilayo O; Goldring, Steven R; Wright, Timothy M; Goldring, Mary B; van der Meulen, Marjolein C H

2016-11-01

We previously showed that repetitive cyclic loading of the mouse knee joint causes changes that recapitulate the features of osteoarthritis (OA) in humans. By applying a single loading session, we characterized the temporal progression of the structural and compositional changes in subchondral bone and articular cartilage. We applied loading during a single 5-minute session to the left tibia of adult (26-week-old) C57Bl/6 male mice at a peak load of 9.0N for 1,200 cycles. Knee joints were collected at times 0, 1, and 2 weeks after loading. The changes in articular cartilage and subchondral bone were analyzed by histology, immunohistochemistry (caspase-3 and cathepsin K), and microcomputed tomography. At time 0, no change was evident in chondrocyte viability or cartilage or subchondral bone integrity. However, cartilage pathology demonstrated by localized thinning and proteoglycan loss occurred at 1 and 2 weeks after the single session of loading. Transient cancellous bone loss was evident at 1 week, associated with increased osteoclast number. Bone loss was reversed to control levels at 2 weeks. We observed formation of fibrous and cartilaginous tissues at the joint margins at 1 and 2 weeks. Our findings demonstrate that a single session of noninvasive loading leads to the development of OA-like morphological and cellular alterations in articular cartilage and subchondral bone. The loss in subchondral trabecular bone mass and thickness returns to control levels at 2 weeks, whereas the cartilage thinning and proteoglycan loss persist. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1941-1949, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Voxel size dependency, reproducibility and sensitivity of an in vivo bone loading estimation algorithm

PubMed Central

Christen, Patrik; Schulte, Friederike A.; Zwahlen, Alexander; van Rietbergen, Bert; Boutroy, Stephanie; Melton, L. Joseph; Amin, Shreyasee; Khosla, Sundeep; Goldhahn, Jörg; Müller, Ralph

2016-01-01

A bone loading estimation algorithm was previously developed that provides in vivo loading conditions required for in vivo bone remodelling simulations. The algorithm derives a bone's loading history from its microstructure as assessed by high-resolution (HR) computed tomography (CT). This reverse engineering approach showed accurate and realistic results based on micro-CT and HR-peripheral quantitative CT images. However, its voxel size dependency, reproducibility and sensitivity still need to be investigated, which is the purpose of this study. Voxel size dependency was tested on cadaveric distal radii with micro-CT images scanned at 25 µm and downscaled to 50, 61, 75, 82, 100, 125 and 150 µm. Reproducibility was calculated with repeated in vitro as well as in vivo HR-pQCT measurements at 82 µm. Sensitivity was defined using HR-pQCT images from women with fracture versus non-fracture, and low versus high bone volume fraction, expecting similar and different loading histories, respectively. Our results indicate that the algorithm is voxel size independent within an average (maximum) error of 8.2% (32.9%) at 61 µm, but that the dependency increases considerably at voxel sizes bigger than 82 µm. In vitro and in vivo reproducibility are up to 4.5% and 10.2%, respectively, which is comparable to other in vitro studies and slightly higher than in other in vivo studies. Subjects with different bone volume fraction were clearly distinguished but not subjects with and without fracture. This is in agreement with bone adapting to customary loading but not to fall loads. We conclude that the in vivo bone loading estimation algorithm provides reproducible, sensitive and fairly voxel size independent results at up to 82 µm, but that smaller voxel sizes would be advantageous. PMID:26790999

The response of bone to unloading

NASA Technical Reports Server (NTRS)

Bikle, D. D.; Halloran, B. P.

1999-01-01

Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During spaceflight bone is lost principally from the bones most loaded in the 1-g environment, and some redistribution of bone from the lower extremities to the head appears to take place. Although changes in calcitropic hormones have been demonstrated during skeletal unloading (PTH and 1,25(OH)2D decrease), it remains unclear whether such changes account for or are in response to the changes in bone formation and resorption. Bed rest studies with human volunteers and hindlimb elevation studies with rats have provided useful data to help explain the changes in bone formation during spaceflight. These models of skeletal unloading reproduce a number of the conditions associated with microgravity, and the findings from such studies confirm many of the observations made during spaceflight. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. Such investigations couple biophysics to biochemistry to cell and molecular biology. Although studies with cell cultures have revealed biochemical responses to mechanical loads comparable to that seen in intact bone, it seems likely that matrix-cell interactions underlie much of the mechanocoupling. The role for systemic hormones such as PTH, GH, and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs, and TGF-beta in modulating the cellular response to load remains unclear. As the mechanism(s) by which bone responds to mechanical load with increased bone formation are further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, with the expectation that such understanding will lead to effective treatment for disuse osteoporosis.

Functional reconstruction of critical-sized load-bearing bone defects using a Sclerostin-targeting miR-210-3p-based construct to enhance osteogenic activity.

PubMed

Hu, Bin; Li, Yan; Wang, Mohan; Zhu, Youming; Zhou, Yong; Sui, Baiyan; Tan, Yu; Ning, Yujie; Wang, Jie; He, Jiacai; Yang, Chi; Zou, Duohong

2018-06-10

A considerable amount of research has focused on improving regenerative therapy strategies for repairing defects in load-bearing bones. The enhancement of tissue regeneration with microRNAs (miRNAs) is being developed because miRNAs can simultaneously regulate multiple signaling pathways in an endogenous manner. In this study, we developed a miR-210-based bone repair strategy. We identified a miRNA (miR-210-3p) that can simultaneously up-regulate the expression of multiple key osteogenic genes in vitro. This process resulted in enhanced bone formation in a subcutaneous mouse model with a miR-210-3p/poly-L-lactic acid (PLLA)/bone marrow-derived stem cell (BMSC) construct. Furthermore, we constructed a model of critical-sized load-bearing bone defects and implanted a miR-210-3p/β-tricalcium phosphate (β-TCP)/bone mesenchymal stem cell (BMSC) construct into the defect. We found that the load-bearing defect was almost fully repaired using the miR-210-3p construct. We also identified a new mechanism by which miR-210-3p regulates Sclerostin protein levels. This miRNA-based strategy may yield novel therapeutic methods for the treatment of regenerative defects in vital load-bearing bones by utilizing miRNA therapy for tissue engineering. The destroyed maxillofacial bone reconstruction is still a real challenge for maxillofacial surgeon, due to that functional bone reconstruction involved load-bearing. Base on the above problem, this paper developed a novel miR-210-3p/β-tricalcium phosphate (TCP)/bone marrow-derived stem cell (BMSC) construct (miR-210-3p/β-TCP/BMSCs), which lead to functional reconstruction of critical-size mandible bone defect. We found that the load-bearing defect was almost fully repaired using the miR-210-3p construct. In addition, we also found the mechanism of how the delivered microRNA activated the signaling pathways of endogenous stem cells, leading to the defect regeneration. This miRNA-based strategy can be used to regenerate defects in vital load-bearing bones, thus addressing a critical challenge in regenerative medicine by utilizing miRNA therapy for tissue engineering. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Biomechanical Analysis of Treadmill Locomotion on the International Space Station

NASA Technical Reports Server (NTRS)

De Witt, J. K.; Fincke, R. S.; Guilliams, M. E.; Ploutz-Snyder, L. L.

2011-01-01

Treadmill locomotion exercise is an important aspect of ISS exercise countermeasures. It is widely believed that an optimized treadmill exercise protocol could offer benefits to cardiovascular and bone health. If training heart rate is high enough, treadmill exercise is expected to lead to improvements in aerobic fitness. If impact or bone loading forces are high enough, treadmill exercise may be expected to contribute to improved bone outcomes. Ground-based research suggests that joint loads increase with increased running speed. However, it is unknown if increases in locomotion speed results in similar increases in joint loads in microgravity. Although data exist regarding the biomechanics of running and walking in microgravity, a majority were collected during parabolic flight or during investigations utilizing a microgravity analog. The Second Generation Treadmill (T2) has been in use on the International Space Station (ISS) and records the ground reaction forces (GRF) produced by crewmembers during exercise. Biomechanical analyses will aid in understanding potential differences in typical gait motion and allow for modeling of the human body to determine joint and muscle forces during exercise. By understanding these mechanisms, more appropriate exercise prescriptions can be developed that address deficiencies. The objective of this evaluation is to collect biomechanical data from crewmembers during treadmill exercise prior to and during flight. The goal is to determine if locomotive biomechanics differ between normal and microgravity environments and to determine how combinations of subject load and speed influence joint loading during in-flight treadmill exercise. Further, the data will be used to characterize any differences in specific bone and muscle loading during locomotion in these two gravitational conditions. This project maps to the HRP Integrated Research Plan risks including Risk of Bone Fracture (Gap B15), Risk of Early Onset Osteoporosis Due to Spaceflight (Gap B15), Risk of Impaired Performance Due to Reduced Muscle Mass, Strength, and Endurance (Gaps M3, M4, M6, Ml, M8, M9) and Risk of reduced Physical Performance Capabilities Due to Reduce Aerobic Capacity (Gaps M7, M8, M9).

Marginal bone levels at single tooth implants with a conical fixture design. The influence of surface macro- and microstructure.

PubMed

Norton, M R

1998-04-01

The concept of a conical implant design to accommodate single tooth replacement, has previously been shown to result in excessive bone loss, around the machined titanium conical collar, usually down to the 1st thread. This unusually aggressive loss of bone was shown to occur within a short period of time, post loading, with greater than 3 mm of bone loss occurring within the 1st 6 months to 1 year. The influence of implant design, surface texture and microleakage have all been highlighted as a potential cause. A modification of the surface structure, both at the macroscopic and microscopic level, as well as an altered fixture-abutment interface design has resulted in the maintenance of marginal bone around a single tooth titanium implant with a similar conical design. The radiographic follow-up of 33 implants loaded for up to 4 years, has revealed, by comparison, a most favourable maintenance of marginal bone around the conical collar, with a mean marginal bone loss of 0.32 mm mesially and 0.34 mm distally for the whole group. The cumulative mean marginal bone loss mesially and distally is 0.42 mm and 0.40 mm from 1 to 2 years, 0.54 mm and 0.43 mm from 2 to 3 years, 0.51 mm and 0.24 mm from 3 to 4 years, and 0.62 mm and 0.60 mm for implants past their 4 year recall.

Mathematical modelling of bone adaptation of the metacarpal subchondral bone in racehorses.

PubMed

Hitchens, Peta L; Pivonka, Peter; Malekipour, Fatemeh; Whitton, R Chris

2018-06-01

In Thoroughbred racehorses, fractures of the distal limb are commonly catastrophic. Most of these fractures occur due to the accumulation of fatigue damage from repetitive loading, as evidenced by microdamage at the predilection sites for fracture. Adaptation of the bone in response to training loads is important for fatigue resistance. In order to better understand the mechanism of subchondral bone adaptation to its loading environment, we utilised a square root function defining the relationship between bone volume fraction [Formula: see text] and specific surface [Formula: see text] of the subchondral bone of the lateral condyles of the third metacarpal bone (MCIII) of the racehorse, and using this equation, developed a mathematical model of subchondral bone that adapts to loading conditions observed in vivo. The model is expressed as an ordinary differential equation incorporating a formation rate that is dependent on strain energy density. The loading conditions applied to a selected subchondral region, i.e. volume of interest, were estimated based on joint contact forces sustained by racehorses in training. For each of the initial conditions of [Formula: see text] we found no difference between subsequent homoeostatic [Formula: see text] at any given loading condition, but the time to reach equilibrium differed by initial [Formula: see text] and loading condition. We found that the observed values for [Formula: see text] from the mathematical model output were a good approximation to the existing data for racehorses in training or at rest. This model provides the basis for understanding the effect of changes to training strategies that may reduce the risk of racehorse injury.

Effect of Immediate and Delayed High-Strain Loading on Tendon-to-Bone Healing After Anterior Cruciate Ligament Reconstruction

PubMed Central

Packer, Jonathan D.; Bedi, Asheesh; Fox, Alice J.; Gasinu, Selom; Imhauser, Carl W.; Stasiak, Mark; Deng, Xiang-Hua; Rodeo, Scott A.

2014-01-01

Background: We previously demonstrated, in a rat anterior cruciate ligament (ACL) graft reconstruction model, that the delayed application of low-magnitude-strain loading resulted in improved tendon-to-bone healing compared with that observed after immediate loading and after prolonged immobilization. The purpose of this study was to determine the effect of higher levels of strain loading on tendon-to-bone healing. Methods: ACL reconstruction was carried out in a rat model in three randomly assigned groups: high-strain daily loading beginning on either (1) postoperative day one (immediate-loading group; n = 7) or (2) postoperative day four (delayed-loading group; n = 11) or (3) after prolonged immobilization (immobilized group; n = 8). Animals were killed two weeks after surgery and micro-computed tomography (micro-CT) and biomechanical testing of the bone-tendon-bone complex were carried out. Results: The delayed-loading group had greater tissue mineral density than either the immediate-loading or immobilized group (mean [and standard deviation], 813.0 ± 24.9 mg/mL compared with 778.4 ± 32.6 mg/mL and 784.9 ± 26.4 mg/mL, respectively; p < 0.05). There was a trend toward greater bone volume per total volume fraction in both the immobilized and the delayed-loading group compared with the immediate-loading group (0.24 ± 0.03 and 0.23 ± 0.06 compared with 0.20 ± 0.05; p = 0.06). Trabecular thickness was greater in the immobilized group compared with the immediate-loading group (106.5 ± 23.0 μm compared with 72.6 ± 10.6 μm; p < 0.01). There were no significant differences in failure load or stiffness between the immobilized group and either high-strain cyclic-loading group. Conclusions: Immediate application of high-strain loading appears to have a detrimental effect on healing in this rat model. Any beneficial effects of delayed loading on the healing tendon-bone interface (after a brief period of immobilization) may be offset by the detrimental effects of excessive strain levels or by the detrimental effects of stress deprivation on the graft. Clinical Relevance: The timing and magnitude of mechanical load on a healing rat ACL reconstruction graft may have important implications for postoperative rehabilitation. Avoidance of exercises that cause high graft strain in the early postoperative period may lead to improved tendon-to-bone healing in humans. PMID:24806014

Quality of Bone Healing: Perspectives and Assessment Techniques

DTIC Science & Technology

2014-01-01

connective tissue specialized for load bearing . Embryologically, the formation of bone occurs via two routes: intramembranous and endochondral ossification.1...primarily suited to load bearing with two distinct configurations: an inner, porous, cancellous architecture and an outer, denser, cortical bone...delineate the multiple functions served by the human skeleton and then evaluate techniques for clinical assessment. Mechanical load bearing and transduction

The Contribution of Experimental in vivo Models to Understanding the Mechanisms of Adaptation to Mechanical Loading in Bone

PubMed Central

Meakin, Lee B.; Price, Joanna S.; Lanyon, Lance E.

2014-01-01

Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones’ strain environment produced by direct, controlled artificial bone loading. Jiri Hert introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gages to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced. Experiments combining strain gage instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats, and mice has yielded significant insight into the control of strain-related adaptive (re)modeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice, which is now the model of choice for many studies. Together such studies have demonstrated that over the physiological strain range, bone’s mechanically adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles, and that these are most effective when interrupted by short periods of rest between them. PMID:25324829

In Vivo Evaluation of Immediately Loaded Stainless Steel and Titanium Orthodontic Screws in a Growing Bone

PubMed Central

Gritsch, Kerstin; Laroche, Norbert; Bonnet, Jeanne-Marie; Exbrayat, Patrick; Morgon, Laurent; Rabilloud, Muriel; Grosgogeat, Brigitte

2013-01-01

The present work intends to evaluate the use of immediate loaded orthodontic screws in a growing model, and to study the specific bone response. Thirty-two screws (half of stainless steel and half of titanium) were inserted in the alveolar bone of 8 growing pigs. The devices were immediately loaded with a 100 g orthodontic force. Two loading periods were assessed: 4 and 12 weeks. Both systems of screws were clinically assessed. Histological observations and histomorphometric analysis evaluated the percent of “bone-to-implant contact” and static and dynamic bone parameters in the vicinity of the devices (test zone) and in a bone area located 1.5 cm posterior to the devices (control zone). Both systems exhibit similar responses for the survival rate; 87.5% and 81.3% for stainless steel and titanium respectively (p = 0.64; 4-week period), and 62.5% and 50.0% for stainless steel and titanium respectively (p = 0.09; 12-week period). No significant differences between the devices were found regarding the percent of “bone-to-implant contact” (p = 0.1) or the static and dynamic bone parameters. However, the 5% threshold of “bone-to-implant contact” was obtained after 4 weeks with the stainless steel devices, leading to increased survival rate values. Bone in the vicinity of the miniscrew implants showed evidence of a significant increase in bone trabecular thickness when compared to bone in the control zone (p = 0.05). In our study, it is likely that increased trabecular thickness is a way for low density bone to respond to the stress induced by loading. PMID:24124540

Deletion of Nrf2 reduces skeletal mechanical properties and decreases load-driven bone formation.

PubMed

Sun, Yong-Xin; Li, Lei; Corry, Kylie A; Zhang, Pei; Yang, Yang; Himes, Evan; Mihuti, Cristina Layla; Nelson, Cecilia; Dai, Guoli; Li, Jiliang

2015-05-01

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor expressed in many cell types, including osteoblasts, osteocytes, and osteoclasts. Nrf2 has been considered a master regulator of cytoprotective genes against oxidative and chemical insults. The lack of Nrf2 can induce pathologies in multiple organs. The aim of this study was to investigate the role of Nrf2 in load-driven bone metabolism using Nrf2 knockout (KO) mice. Compared to age-matched littermate wild-type controls, Nrf2 KO mice have significantly lowered femoral bone mineral density (-7%, p<0.05), bone formation rate (-40%, p<0.05), as well as ultimate force (-11%, p<0.01). The ulna loading experiment showed that Nrf2 KO mice were less responsive than littermate controls, as indicated by reduction in relative mineralizing surface (rMS/BS, -69%, p<0.01) and relative bone formation rate (rBFR/BS, -84%, p<0.01). Furthermore, deletion of Nrf2 suppressed the load-driven gene expression of antioxidant enzymes and Wnt5a in cultured primary osteoblasts. Taken together, the results suggest that the loss-of-function mutation of Nrf2 in bone impairs bone metabolism and diminishes load-driven bone formation. Copyright © 2015 Elsevier Inc. All rights reserved.

Influence of controlled immediate loading and implant design on peri-implant bone formation.

PubMed

Vandamme, Katleen; Naert, Ignace; Geris, Liesbet; Vander Sloten, Jozef; Puers, Robert; Duyck, Joke

2007-02-01

Tissue formation at the implant interface is known to be sensitive to mechanical stimuli. The aim of the study was to compare the bone formation around immediately loaded versus unloaded implants in two different implant macro-designs. A repeated sampling bone chamber with a central implant was installed in the tibia of 10 rabbits. Highly controlled loading experiments were designed for a cylindrical (CL) and screw-shaped (SL) implant, while the unloaded screw-shaped (SU) implant served as a control. An F-statistic model with alpha=5% determined statistical significance. A significantly higher bone area fraction was observed for SL compared with SU (p<0.0001). The mineralized bone fraction was the highest for SL and significantly different from SU (p<0.0001). The chance that osteoid- and bone-to-implant contact occurred was the highest for SL and significantly different from SU (p<0.0001), but not from CL. When bone-to-implant contact was observed, a loading (SL versus SU: p=0.0049) as well as an implant geometry effect (SL versus CL: p=0.01) was found, in favour of the SL condition. Well-controlled immediate implant loading accelerates tissue mineralization at the interface. Adequate bone stimulation via mechanical coupling may account for the larger bone response around the screw-type implant compared with the cylindrical implant.

Platform switching: biomechanical evaluation using three-dimensional finite element analysis.

PubMed

Tabata, Lucas Fernando; Rocha, Eduardo Passos; Barão, Valentim Adelino Ricardo; Assunção, Wirley Goncalves

2011-01-01

The objective of this study was to evaluate, using three-dimensional finite element analysis (3D FEA), the stress distribution in peri-implant bone tissue, implants, and prosthetic components of implant-supported single crowns with the use of the platform-switching concept. Three 3D finite element models were created to replicate an external-hexagonal implant system with peri-implant bone tissue in which three different implant-abutment configurations were represented. In the regular platform (RP) group, a regular 4.1-mm-diameter abutment (UCLA) was connected to regular 4.1-mm-diameter implant. The platform-switching (PS) group was simulated by the connection of a wide implant (5.0 mm diameter) to a regular 4.1-mm-diameter UCLA abutment. In the wide-platform (WP) group, a 5.0-mm-diameter UCLA abutment was connected to a 5.0-mm-diameter implant. An occlusal load of 100 N was applied either axially or obliquely on the models using ANSYS software. Both the increase in implant diameter and the use of platform switching played roles in stress reduction. The PS group presented lower stress values than the RP and WP groups for bone and implant. In the peri-implant area, cortical bone exhibited a higher stress concentration than the trabecular bone in all models and both loading situations. Under oblique loading, higher intensity and greater distribution of stress were observed than under axial loading. Platform switching reduced von Mises (17.5% and 9.3% for axial and oblique loads, respectively), minimum (compressive) (19.4% for axial load and 21.9% for oblique load), and maximum (tensile) principal stress values (46.6% for axial load and 26.7% for oblique load) in the peri-implant bone tissue. Platform switching led to improved biomechanical stress distribution in peri-implant bone tissue. Oblique loads resulted in higher stress concentrations than axial loads for all models. Wide-diameter implants had a large influence in reducing stress values in the implant system.

On the relationship between the dynamic behavior and nanoscale staggered structure of the bone

NASA Astrophysics Data System (ADS)

Qwamizadeh, Mahan; Zhang, Zuoqi; Zhou, Kun; Zhang, Yong Wei

2015-05-01

Bone, a typical load-bearing biological material, composed of ordinary base materials such as organic protein and inorganic mineral arranged in a hierarchical architecture, exhibits extraordinary mechanical properties. Up to now, most of previous studies focused on its mechanical properties under static loading. However, failure of the bone occurs often under dynamic loading. An interesting question is: Are the structural sizes and layouts of the bone related or even adapted to the functionalities demanded by its dynamic performance? In the present work, systematic finite element analysis was performed on the dynamic response of nanoscale bone structures under dynamic loading. It was found that for a fixed mineral volume fraction and unit cell area, there exists a nanoscale staggered structure at some specific feature size and layout which exhibits the fastest attenuation of stress waves. Remarkably, these specific feature sizes and layouts are in excellent agreement with those experimentally observed in the bone at the same scale, indicating that the structural size and layout of the bone at the nanoscale are evolutionarily adapted to its dynamic behavior. The present work points out the importance of dynamic effect on the biological evolution of load-bearing biological materials.

Structural and Mechanical Repair of Diffuse Damage in Cortical Bone in vivo

PubMed Central

Seref-Ferlengez, Zeynep; Basta-Pljakic, Jelena; Kennedy, Oran D.; Philemon, Claudy J.; Schaffler, Mitchell B.

2014-01-01

Physiological wear and tear causes bone microdamage at several hierarchical levels, and these have different biological consequences. Bone remodeling is widely held to be the mechanism by which bone microdamage is repaired. However, recent studies showed that unlike typical linear microcracks, small crack damage, the clusters of submicron-sized matrix cracks also known as diffuse damage (Dif.Dx), does not activate remodeling. Thus, the fate of diffuse damage in vivo is not known. To examine this, we induced selectively Dif.Dx in rat ulnae in vivo by using end-load ulnar bending creep model. Changes in damage content were assessed by histomorphometry and mechanical testing immediately after loading (i.e., acute loaded) or at 14 days after damage induction (i.e., survival ulnae). Dif.Dx area was markedly reduced over the 14-day survival period after loading (p<0.02). We did not observe any intracortical resorption and there was no increase in cortical bone area in survival ulnae. The reduction in whole bone stiffness in acute loaded ulnae was restored to baseline levels in survival ulnae (p>0.6). Microindentation studies showed that Dif.Dx caused a highly localized reduction in elastic modulus in diffuse damage regions of the ulnar cortex. Moduli in these previously damaged bone areas were restored to control values by 14 days after loading. Our current findings indicate that small crack damage in bone can be repaired without bone remodeling, and suggest that alternative repair mechanisms exist in bone to deal with submicron-sized matrix cracks. Those mechanisms are currently unknown and further investigations are needed to elucidate the mechanisms by which this direct repair occurs. PMID:25042459

Using the Enhanced Daily Load Stimulus Model to Quantify the Mechanical Load and Bone Mineral Density Changes Experienced by Crew Members on the International Space Station

NASA Technical Reports Server (NTRS)

Genc, K. O.; Gopalakrishnan, R.; Kuklis, M. M.; Maender, C. C.; Rice, A. J.; Cavanagh, P. R.

2009-01-01

Despite the use of exercise countermeasures during long-duration space missions, bone mineral density (BMD) and predicted bone strength of astronauts continue to show decreases in the lower extremities and spine. This site-specific bone adaptation is most likely caused by the effects of microgravity on the mechanical loading environment of the crew member. There is, therefore, a need to quantify the mechanical loading experienced on Earth and on-orbit to define the effect of a given "dose" of loading on bone homeostasis. Gene et al. recently proposed an enhanced DLS (EDLS) model that, when used with entire days of in-shoe forces, takes into account recently developed theories on the importance of factors such as saturation, recovery, and standing and their effects on the osteogenic response of bone to daily physical activity. This algorithm can also quantify the tinting and type of activity (sit/unload, stand, walk, run or other loaded activity) performed throughout the day. The purpose of the current study was to use in-shoe force measurements from entire typical work days on Earth and on-orbit in order to quantify the type and amount of loading experienced by crew members. The specific aim was to use these measurements as inputs into the EDLS model to determine activity timing/type and the mechanical "dose" imparted on the musculoskeletal system of crew members and relate this dose to changes in bone homeostasis.

Evaluation of BSA protein release from hollow hydroxyapatite microspheres into PEG hydrogel

PubMed Central

Fu, Hailuo; Rahaman, Mohamed N.; Brown, Roger F.; Day, Delbert E.

2013-01-01

Implants that simultaneously function as an osteoconductive matrix and as a device for local drug or growth factor delivery could provide an attractive system for bone regeneration. In our previous work, we prepared hollow hydroxyapatite (abbreviated HA) microspheres with a high surface area, mesoporous shell wall and studied the release of a model protein, bovine serum albumin (BSA), from the microspheres into phosphate-buffered saline (PBS). The present work is an extension of our previous work to study the release of BSA from similar HA microspheres into a biocompatible hydrogel, poly(ethylene glycol) (PEG). BSA-loaded HA microspheres were placed in a PEG solution which was rapidly gelled using ultraviolet radiation. The BSA release rate into the PEG hydrogel, measured using a spectrophotometric method, was slower than into PBS, and it was dependent on the initial BSA loading and on the microstructure of the microsphere shell wall. A total of 35–40% of the BSA initially loaded into the microspheres was released into PEG over ~14 days. The results indicate that these hollow HA microspheres have promising potential as an osteoconductive device for local drug or growth factor delivery in bone regeneration and in the treatment of bone diseases. PMID:23498254

Relationship of obesity with osteoporosis

PubMed Central

Zhao, Lan-Juan; Liu, Yong-Jun; Liu, Peng-Yuan; Hamilton, James; Recker, Robert R.; Deng, Hong-Wen

2007-01-01

Context The relationship between obesity and osteoporosis has been widely studied, and epidemiological evidence shows that obesity is correlated with increased bone mass. Previous analyses, however, did not control for the mechanical loading effects of total body weight on bone mass and may have generated a confounded or even biased relationship between obesity and osteoporosis. Objective To re-evaluate the relationship between obesity and osteoporosis by accounting for the mechanical loading effects of total body weight on bone mass. Methods We measured whole body fat mass, lean mass, percentage fat mass (PFM), body mass index (BMI), and bone mass in two large samples of different ethnicity: 1,988 unrelated Chinese subjects and 4,489 Caucasian subjects from 512 pedigrees. We first evaluated the Pearson correlations among different phenotypes. We then dissected the phenotypic correlations into genetic and environmental components, with bone mass unadjusted, or adjusted, for body weight. This allowed us to compare the results with and without controlling for mechanical loading effects of body weight on bone mass. Results In both Chinese and Caucasians, when the mechanical loading effect of body weight on bone mass was adjusted for, the phenotypic correlation (including its genetic and environmental components) between fat mass (or PFM) and bone mass was negative. Further multivariate analyses in subjects stratified by body weight confirmed the inverse relationship between bone mass and fat mass, after mechanical loading effects due to total body weight was controlled. Conclusions Increasing fat mass may not have a beneficial effect on bone mass. PMID:17299077

Immediate versus conventional loading of implant-supported maxillary overdentures: a finite element stress analysis.

PubMed

Akca, Kivanc; Eser, Atilim; Eckert, Steven; Cavusoglu, Yeliz; Cehreli, Murat Cavit

2013-01-01

To compare biomechanical outcomes of immediately and conventionally loaded bar-retained implant-supported maxillary overdentures using finite element stress analysis. Finite element models were created to replicate the spatial positioning of four 4.1 × 12-mm implants in the completely edentulous maxillae of four cadavers to support bar-retained overdentures with 7-mm distal extension cantilevers. To simulate the bone-implant interface of immediately loaded implants, a contact situation was defined at the interface; conventional loading was simulated by "bonding" the implants to the surrounding bone. The prostheses were loaded with 100 N in the projected molar regions bilaterally, and strain magnitudes were measured at the buccal aspect of bone. The amplitude of axial and lateral strains, the overall strain magnitudes, and the strain magnitudes around anterior and posterior implants in the immediate loading group were comparable to those seen in the conventional loading group, suggesting that the loading regimens created similar stress/strain fields (P > .05). Conventional and immediate loading of maxillary implants supporting bar-retained overdentures resulted in similar bone strains.

In Vivo Bone Formation Within Engineered Hydroxyapatite Scaffolds in a Sheep Model.

PubMed

Lovati, A B; Lopa, S; Recordati, C; Talò, G; Turrisi, C; Bottagisio, M; Losa, M; Scanziani, E; Moretti, M

2016-08-01

Large bone defects still represent a major burden in orthopedics, requiring bone-graft implantation to promote the bone repair. Along with autografts that currently represent the gold standard for complicated fracture repair, the bone tissue engineering offers a promising alternative strategy combining bone-graft substitutes with osteoprogenitor cells able to support the bone tissue ingrowth within the implant. Hence, the optimization of cell loading and distribution within osteoconductive scaffolds is mandatory to support a successful bone formation within the scaffold pores. With this purpose, we engineered constructs by seeding and culturing autologous, osteodifferentiated bone marrow mesenchymal stem cells within hydroxyapatite (HA)-based grafts by means of a perfusion bioreactor to enhance the in vivo implant-bone osseointegration in an ovine model. Specifically, we compared the engineered constructs in two different anatomical bone sites, tibia, and femur, compared with cell-free or static cell-loaded scaffolds. After 2 and 4 months, the bone formation and the scaffold osseointegration were assessed by micro-CT and histological analyses. The results demonstrated the capability of the acellular HA-based grafts to determine an implant-bone osseointegration similar to that of statically or dynamically cultured grafts. Our study demonstrated that the tibia is characterized by a lower bone repair capability compared to femur, in which the contribution of transplanted cells is not crucial to enhance the bone-implant osseointegration. Indeed, only in tibia, the dynamic cell-loaded implants performed slightly better than the cell-free or static cell-loaded grafts, indicating that this is a valid approach to sustain the bone deposition and osseointegration in disadvantaged anatomical sites.

The impact of skeletal unloading on bone formation

NASA Technical Reports Server (NTRS)

Bikle, Daniel D.; Sakata, Takeshi; Halloran, Bernard P.

2003-01-01

Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During space flight bone is lost principally from the bones most loaded in the 1 g environment. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. It seems likely that matrix/cell interactions will underlie much of the mechanocoupling. Integrins are a prime mediator of such interactions. The role for systemic hormones such as PTH, GH and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs and TGF beta in modulating the cellular response to load remains unclear. Our studies demonstrate that skeletal unloading leads to resistance to the anabolic actions of IGF-I on bone as a result of failure of IGF-I to activate its own signaling pathways. This is associated with a reduction in integrin expression, suggesting crosstalk between these two pathways. As the mechanism(s) by which bone responds to changes in mechanical load with changes in bone formation is further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, and that such understanding will lead to effective treatment for disuse osteoporosis in addition to preventive measures for the bone loss that accompanies space travel.

In vivo evaluation of teicoplanin- and calcium sulfate-loaded PMMA bone cement in preventing implant-related osteomyelitis in rats.

PubMed

Tuzuner, T; Sencan, I; Ozdemir, D; Alper, M; Duman, S; Yavuz, T; Yildirim, M

2006-12-01

The objective of this study was to evaluate the efficacy of teicoplanin- and calcium sulphate-loaded polymethylmethacrylate (PMMA) bone cements in preventing experimental implant-related osteomyelitis in rats. Four groups of antibiotic-loaded rods were prepared and were implanted into the lateral condylus of the rat femur after inoculation of Staphylococcus aureus. The effectiveness of these were assessed microbiologically, radiographically, and histopathologically. Radiographic evaluation revealed a significant reduction of periostal reaction and osteolysis in rats that received calcium sulphate- and teicoplanin-loaded rods. Histopathological evaluation confirmed these results. Acute infection and bone necrosis were found to be significantly lower in rats that had received calcium sulphate- and teicoplanin-loaded rods. The addition of calcium sulfate to teicoplanin-loaded PMMA bone cement appeared satisfactory as an antibiotic-carrying system for prophylaxis of experimental implant-related osteomyelitis, but further investigations are needed to reach definitive statements for clinical applications.

The Effects of Partial Mechanical Loading and Ibandronate on Skeletal Tissues in the Adult Rat Hindquarter Suspension Model for Microgravity

NASA Technical Reports Server (NTRS)

Schultheis, Lester W.

1999-01-01

We report initial data from a suspended rat model that quantitatively relates chronic partial weightbearing to bone loss. Chronic partial weightbearing is our simulation of the effect of limited artificial gravity aboard spacecraft or reduced planetary gravity. Preliminary analysis of bone by PQCT, histomorphometry, mechanical testing and biochemistry suggest that chronic exposure to half of Earth gravity is insufficient to prevent severe bone loss. The effect of episodic full weightbearing activity (Earth Gravity) on rats otherwise at 50% weightbearing was also explored. This has similarity to treatment by an Earth G-rated centrifuge on a spacecraft that normally maintained artificial gravity at half of Earth G. Our preliminary evidence, using the above techniques to analyze bone, indicate that 2 hours daily of full weightbearing was insufficient to prevent the bone loss observed in 50% weightbearing animals. The effectiveness of partial weightbearing and episodic full weightbearing as potential countermeasures to bone loss in spaceflight was compared with treatment by ibandronate. Ibandronate, a long-acting potent bisphosphonate proved more effective in preventing bone loss and associated functionality based upon structure than our first efforts at mechanical countermeasures. The effectiveness of ibandronate was notable by each of the testing methods we used to study bone from gross structure and strength to tissue and biochemistry. These results appear to be independent of generalized systemic stress imposed by the suspension paradigm. Preliminary evidence does not suggest that blood levels of vitamin D were affected by our countermeasures. Despite the modest theraputic benefit of mechanical countermeasures of partial weightbearing and episodic full weightbearing, we know that some appropriate mechanical signal maintains bone mass in Earth gravity. Moreover, the only mechanism that correctly assigns bone mass and strength to oppose regionally specific force applied to bone is mechanical, a process based upon bone strain. Substantial evidence indicates that the specifics of dynamic loading i.e. time-varying forces are critical. Bone strain history is a predictor of the effect that mechanical conditions have on bone structure mass and strength. Using servo-controlled force plates on suspended rats with implanted strain gauges we manipulated impact forces of ambulation in the frequency (Fourier) domain. Our results indicate that high frequency components of impact forces are particularly potent in producing bone strain independent of the magnitude of the peak force or peak energy applied to the leg. Because a servo-system responds to forces produced by the rat's own muscle activity during ambulation, the direction of ground-reaction loads act on bone through the rat's own musculature. This is in distinction to passive vibration of the floor where forces reach bone through the natural filters of soft tissue and joints. Passive vibration may also be effective, but it may or may not increase bone in the appropriate architectural pattern to oppose the forces of normal ambulatory activity. Effectiveness of high frequency mechanical stimulation in producing regional (muscle directed) bone response will be limited by 1. the sensitivity of bone to a particular range of frequencies and 2. the inertia of the muscles, limiting their response to external forces by increasing tension along insertions. We have begun mathematical modeling of normal ambulatory activity. Effectiveness of high frequency mechanical stimulation in producing regional (muscle directed) bone response will be limited by 1. the sensitivity of bone to a particular range of frequencies and 2. the inertia of the muscles, limiting their response to external forces by increasing tension along insertions. We have begun mathematical modeling of the rat forelimb as a transfer function between impact force and bone strain to predict optimal dynamic loading conditions for this system. We plan additional studies of mechanical counter-measures that incorporate improved dynamic loading, features relevant to anticipated evaluation of artificial gravity, exercise regimens and exposure to Martian gravity, The combination of mechanical countermeasures with ibandronate will also be investigated for signs of synergy.

Revisiting the Debate: Does Exercise Build Strong Bones in the Mature and Senescent Skeleton?

PubMed Central

Hughes, Julie M.; Charkoudian, Nisha; Barnes, Jill N.; Morgan, Barbara J.

2016-01-01

Traditional exercise programs seem to be less osteogenic in the mature and post-mature skeleton compared to the young skeleton. This is likely because of the decline in sensitivity of bone to mechanical loading that occurs with advancing age. Another factor contributing to the apparently diminished benefit of exercise in older adults is failure of widely used measurement techniques (i.e., DXA) to identify changes in 3-dimensional bone structure, which are important determinants of bone strength. Moreover, although hormonal contributors to bone loss in the elderly are well-recognized, the influence of age-related increases in sympathetic nervous system activity, which impacts bone metabolism, is rarely considered. In this Perspective, we cite evidence from animal and human studies demonstrating anabolic effects of exercise on bone across the lifespan and we discuss theoretical considerations for designing exercise regimens to optimize bone health. We conclude with suggestions for future research that should help define the osteogenic potential of exercise in older individuals. PMID:27679578

Knotless anchors with sutures external to the anchor body may be at risk for suture cutting through osteopenic bone

PubMed Central

Ono, Y.; Woodmass, J. M.; Nelson, A. A.; Boorman, R. S.; Thornton, G. M.

2016-01-01

Objectives This study evaluated the mechanical performance, under low-load cyclic loading, of two different knotless suture anchor designs: sutures completely internal to the anchor body (SpeedScrew) and sutures external to the anchor body and adjacent to bone (MultiFIX P). Methods Using standard suture loops pulled in-line with the rotator cuff (approximately 60°), anchors were tested in cadaveric bone and foam blocks representing normal to osteopenic bone. Mechanical testing included preloading to 10 N and cyclic loading for 500 cycles from 10 N to 60 N at 60 mm/min. The parameters evaluated were initial displacement, cyclic displacement and number of cycles and load at 3 mm displacement relative to preload. Video recording throughout testing documented the predominant source of suture displacement and the distance of ‘suture cutting through bone’. Results In cadaveric bone and foam blocks, MultiFIX P anchors had significantly greater initial displacement, and lower number of cycles and lower load at 3 mm displacement than SpeedScrew anchors. Video analysis revealed ‘suture cutting through bone’ as the predominant source of suture displacement in cadaveric bone (qualitative) and greater ‘suture cutting through bone’ comparing MultiFIX P with SpeedScrew anchors in foam blocks (quantitative). The greater suture displacement in MultiFIX P anchors was predominantly from suture cutting through bone, which was enhanced in an osteopenic bone model. Conclusions Anchors with sutures external to the anchor body are at risk for suture cutting through bone since the suture eyelet is at the distal tip of the implant and the suture directly abrades against the bone edge during cyclic loading. Suture cutting through bone may be a significant source of fixation failure, particularly in osteopenic bone. Cite this article: Y. Ono, J. M. Woodmass, A. A. Nelson, R. S. Boorman, G. M. Thornton, I. K. Y. Lo. Knotless anchors with sutures external to the anchor body may be at risk for suture cutting through osteopenic bone. Bone Joint Res 2016;5:269–275. DOI: 10.1302/2046-3758.56.2000535. PMID:27357383

Fracture characterization of human cortical bone under mode II loading using the end-notched flexure test.

PubMed

Silva, F G A; de Moura, M F S F; Dourado, N; Xavier, J; Pereira, F A M; Morais, J J L; Dias, M I R; Lourenço, P J; Judas, F M

2017-08-01

Fracture characterization of human cortical bone under mode II loading was analyzed using a miniaturized version of the end-notched flexure test. A data reduction scheme based on crack equivalent concept was employed to overcome uncertainties on crack length monitoring during the test. The crack tip shear displacement was experimentally measured using digital image correlation technique to determine the cohesive law that mimics bone fracture behavior under mode II loading. The developed procedure was validated by finite element analysis using cohesive zone modeling considering a trapezoidal with bilinear softening relationship. Experimental load-displacement curves, resistance curves and crack tip shear displacement versus applied displacement were used to validate the numerical procedure. The excellent agreement observed between the numerical and experimental results reveals the appropriateness of the proposed test and procedure to characterize human cortical bone fracture under mode II loading. The proposed methodology can be viewed as a novel valuable tool to be used in parametric and methodical clinical studies regarding features (e.g., age, diseases, drugs) influencing bone shear fracture under mode II loading.

The influence of impact direction and axial loading on the bone fracture pattern.

PubMed

Cohen, Haim; Kugel, Chen; May, Hila; Medlej, Bahaa; Stein, Dan; Slon, Viviane; Brosh, Tamar; Hershkovitz, Israel

2017-08-01

The effect of the direction of the impact and the presence of axial loading on fracture patterns have not yet been established in experimental 3-point bending studies. To reveal the association between the direction of the force and the fracture pattern, with and without axial loading. A Dynatup Model POE 2000 (Instron Co.) low energy pendulum impact machine was utilized to apply impact loading on fresh pig femoral bones (n=50). The bone clamp shaft was adjusted to position the bone for three-point bending with and without additional bone compression. Four different directions of the force were applied: anterior, posterior, lateral, and medial. The impacted aspect can be distinguished from the non-impacted aspects based on the fracture pattern alone (the most fractured one); the impact point can be identified on bare bones (the area from which all oblique lines radiate and/or the presence of a chip fragment). None of our experiments (with and without compression) yielded a "true" butterfly fracture, but instead, oblique radiating lines emerged from the point of impact (also known as "false" butterfly). Impacts on the lateral and anterior aspects of the bones produce more and longer fracture lines than impacts on the contralateral side; bones subjected to an impact with axial loading are significantly more comminuted and fragmented. Under axial loading, the number of fracture lines is independent of the impact direction. Our study presents an experimental model for fracture analysis and shows that the impact direction and the presence of axial loading during impact significantly affect the fracture pattern obtained. Copyright © 2017 Elsevier B.V. All rights reserved.

Finite element modeling of the influence of hand position and bone properties on the Colles' fracture load during a fall.

PubMed

Buchanan, Drew; Ural, Ani

2010-08-01

Distal forearm fracture is one of the most frequently observed osteoporotic fractures, which may occur as a result of low energy falls such as falls from a standing height and may be linked to the osteoporotic nature of the bone, especially in the elderly. In order to prevent the occurrence of radius fractures and their adverse outcomes, understanding the effect of both extrinsic and intrinsic contributors to fracture risk is essential. In this study, a nonlinear fracture mechanics-based finite element model is applied to human radius to assess the influence of extrinsic factors (load orientation and load distribution between scaphoid and lunate) and intrinsic bone properties (age-related changes in fracture properties and bone geometry) on the Colles' fracture load. Seven three-dimensional finite element models of radius were created, and the fracture loads were determined by using cohesive finite element modeling, which explicitly represented the crack and the fracture process zone behavior. The simulation results showed that the load direction with respect to the longitudinal and dorsal axes of the radius influenced the fracture load. The fracture load increased with larger angles between the resultant load and the dorsal axis, and with smaller angles between the resultant load and longitudinal axis. The fracture load also varied as a function of the load ratio between the lunate and scaphoid, however, not as drastically as with the load orientation. The fracture load decreased as the load ratio (lunate/scaphoid) increased. Multiple regression analysis showed that the bone geometry and the load orientation are the most important variables that contribute to the prediction of the fracture load. The findings in this study establish a robust computational fracture risk assessment method that combines the effects of intrinsic properties of bone with extrinsic factors associated with a fall, and may be elemental in the identification of high fracture risk individuals as well as in the development of fracture prevention methods including protective falling techniques. The additional information that this study brings to fracture identification and prevention highlights the promise of fracture mechanics-based finite element modeling in fracture risk assessment.

An extravehicular suit impact load attenuation study to improve astronaut bone fracture prediction.

PubMed

Sulkowski, Christina M; Gilkey, Kelly M; Lewandowski, Beth E; Samorezov, Sergey; Myers, Jerry G

2011-04-01

Understanding the contributions to the risk of bone fracture during spaceflight is essential for mission success. A pressurized extravehicular activity (EVA) suit analogue test bed was developed, impact load attenuation data were obtained, and the load at the hip of an astronaut who falls to the side during an EVA was characterized. Offset (representing the gap between the EVA suit and the astronaut's body), impact load magnitude, and EVA suit operating pressure were factors varied in the study. The attenuation data were incorporated into a probabilistic model of bone fracture risk during spaceflight, replacing the previous load attenuation value that was based on commercial hip protector data. Load attenuation was more dependent on offset than on pressurization or load magnitude, especially at small offset values. Load attenuation factors for offsets between 0.1-1.5 cm were 0.69 +/- 0.15, 0.49 +/- 0.22, and 0.35 +/- 0.18 for mean impact forces of 4827, 6400, and 8467 N, respectively. Load attenuation factors for offsets of 2.8-5.3 cm were 0.93 +/- 0.2, 0.94 +/- 0.1, and 0.84 +/- 0.5 for the same mean impact forces. The mean and 95th percentile bone fracture risk index predictions were each reduced by 65-83%. The mean and 95th percentile bone fracture probability predictions were both reduced approximately 20-50%. The reduction in uncertainty and improved confidence in bone fracture predictions increased the fidelity and credibility of the fracture risk model and its benefit to mission design and in-flight operational decisions.

High-strength mineralized collagen artificial bone

NASA Astrophysics Data System (ADS)

Qiu, Zhi-Ye; Tao, Chun-Sheng; Cui, Helen; Wang, Chang-Ming; Cui, Fu-Zhai

2014-03-01

Mineralized collagen (MC) is a biomimetic material that mimics natural bone matrix in terms of both chemical composition and microstructure. The biomimetic MC possesses good biocompatibility and osteogenic activity, and is capable of guiding bone regeneration as being used for bone defect repair. However, mechanical strength of existing MC artificial bone is too low to provide effective support at human load-bearing sites, so it can only be used for the repair at non-load-bearing sites, such as bone defect filling, bone graft augmentation, and so on. In the present study, a high strength MC artificial bone material was developed by using collagen as the template for the biomimetic mineralization of the calcium phosphate, and then followed by a cold compression molding process with a certain pressure. The appearance and density of the dense MC were similar to those of natural cortical bone, and the phase composition was in conformity with that of animal's cortical bone demonstrated by XRD. Mechanical properties were tested and results showed that the compressive strength was comparable to human cortical bone, while the compressive modulus was as low as human cancellous bone. Such high strength was able to provide effective mechanical support for bone defect repair at human load-bearing sites, and the low compressive modulus can help avoid stress shielding in the application of bone regeneration. Both in vitro cell experiments and in vivo implantation assay demonstrated good biocompatibility of the material, and in vivo stability evaluation indicated that this high-strength MC artificial bone could provide long-term effective mechanical support at human load-bearing sites.

Reinforced Portland cement porous scaffolds for load-bearing bone tissue engineering applications.

PubMed

Higuita-Castro, Natalia; Gallego-Perez, Daniel; Pelaez-Vargas, Alejandro; García Quiroz, Felipe; Posada, Olga M; López, Luis E; Sarassa, Carlos A; Agudelo-Florez, Piedad; Monteiro, Fernando J; Litsky, Alan S; Hansford, Derek J

2012-02-01

Modified Portland cement porous scaffolds with suitable characteristics for load-bearing bone tissue engineering applications were manufactured by combining the particulate leaching and foaming methods. Non-crosslinked polydimethylsiloxane was evaluated as a potential reinforcing material. The scaffolds presented average porosities between 70 and 80% with mean pore sizes ranging from 300 μm up to 5.0 mm. Non-reinforced scaffolds presented compressive strengths and elastic modulus values of 2.6 and 245 MPa, respectively, whereas reinforced scaffolds exhibited 4.2 and 443 MPa, respectively, an increase of ∼62 and 80%. Portland cement scaffolds supported human osteoblast-like cell adhesion, spreading, and propagation (t = 1-28 days). Cell metabolism and alkaline phosphatase activity were found to be enhanced at longer culture intervals (t ≥ 14 days). These results suggest the possibility of obtaining strong and biocompatible scaffolds for bone repair applications from inexpensive, yet technologically advanced materials such as Portland cement. Copyright © 2011 Wiley Periodicals, Inc.

Improvement of mechanical and biological properties of Polycaprolactone loaded with Hydroxyapatite and Halloysite nanotubes.

PubMed

Torres, E; Fombuena, V; Vallés-Lluch, A; Ellingham, T

2017-06-01

Hydroxyapatite (HA) and Halloysite nanotubes (HNTs) percentages have been optimized in Polycaprolactone (PCL) polymeric matrices to improve mechanical, thermal and biological properties of the composites, thus, to be applied in bone tissue engineering or as fixation plates. Addition of HA guarantees a proper compatibility with human bone due to its osteoconductive and osteoinductive properties, facilitating bone regeneration in tissue engineering applications. Addition of HNTs ensures the presence of tubular structures for subsequent drug loading in their lumen, of molecules such as curcumin, acting as controlled drug delivery systems. The addition of 20% of HA and different amounts of HNTs leads to a substantial improvement in mechanical properties with values of flexural strength up to 40% over raw PCL, with an increase in degradation temperature. DMA analyses showed stability in mechanical and thermal properties, having as a result a potential composite to be used as tissue engineering scaffold or resorbable fixation plate. Copyright © 2017 Elsevier B.V. All rights reserved.

Regional variation of bone density, microarchitectural parameters, and elastic moduli in the ultradistal tibia of young black and white men and women.

PubMed

Unnikrishnan, Ginu; Xu, Chun; Popp, Kristin L; Hughes, Julie M; Yuan, Amy; Guerriere, Katelyn I; Caksa, Signe; Ackerman, Kathryn E; Bouxsein, Mary L; Reifman, Jaques

2018-07-01

Whole-bone analyses can obscure regional heterogeneities in bone characteristics. Quantifying these heterogeneities might improve our understanding of the etiology of injuries, such as lower-extremity stress fractures. Here, we performed regional analyses of high-resolution peripheral quantitative computed tomography images of the ultradistal tibia in young, healthy subjects (age range, 18 to 30 years). We quantified bone characteristics across four regional sectors of the tibia for the following datasets: white women (n = 50), black women (n = 51), white men (n = 50), black men (n = 34), and all subjects (n = 185). After controlling for potentially confounding variables, we observed statistically significant variations in most of the characteristics across sectors (p < 0.05). Most of the bone characteristics followed a similar trend for all datasets but with different magnitudes. Regardless of race or sex, the anterior sector had the lowest trabecular and total volumetric bone mineral density and highest trabecular separation (p < 0.001), while cortical thickness was lowest in the medial sector (p < 0.05). Accordingly, the anterior sector also had the lowest elastic modulus in the anterior-posterior and superior-inferior directions (p < 0.001). In all sectors, the mean anisotropy was ~3, suggesting cross-sector similarity in the ratios of loading in these directions. In addition, the bone characteristics from regional and whole-bone analyses differed in all datasets (p < 0.05). Our findings on the heterogeneous nature of bone microarchitecture in the ultradistal tibia may reflect an adaptation of the bone to habitual loading conditions. Published by Elsevier Inc.

A New Bone Substitute Developed from 3D-Prints of Polylactide (PLA) Loaded with Collagen I: An In Vitro Study.

PubMed

Ritz, Ulrike; Gerke, Rebekka; Götz, Hermann; Stein, Stefan; Rommens, Pol Maria

2017-11-29

Although a lot of research has been performed, large segmental bone defects caused by trauma, infection, bone tumors or revision surgeries still represent big challenges for trauma surgeons. New and innovative bone substitutes are needed. Three-dimensional (3D) printing is a novel procedure to create 3D porous scaffolds that can be used for bone tissue engineering. In the present study, solid discs as well as porous cage-like 3D prints made of polylactide (PLA) are coated or filled with collagen, respectively, and tested for biocompatibility and endotoxin contamination. Microscopic analyses as well as proliferation assays were performed using various cell types on PLA discs. Stromal-derived factor (SDF-1) release from cages filled with collagen was analyzed and the effect on endothelial cells tested. This study confirms the biocompatibility of PLA and demonstrates an endotoxin contamination clearly below the FDA (Food and Drug Administration) limit. Cells of various cell types (osteoblasts, osteoblast-like cells, fibroblasts and endothelial cells) grow, spread and proliferate on PLA-printed discs. PLA cages loaded with SDF-1 collagen display a steady SDF-1 release, support cell growth of endothelial cells and induce neo-vessel formation. These results demonstrate the potential for PLA scaffolds printed with an inexpensive desktop printer in medical applications, for example, in bone tissue engineering.

A New Bone Substitute Developed from 3D-Prints of Polylactide (PLA) Loaded with Collagen I: An In Vitro Study

PubMed Central

Gerke, Rebekka; Götz, Hermann; Rommens, Pol Maria

2017-01-01

Although a lot of research has been performed, large segmental bone defects caused by trauma, infection, bone tumors or revision surgeries still represent big challenges for trauma surgeons. New and innovative bone substitutes are needed. Three-dimensional (3D) printing is a novel procedure to create 3D porous scaffolds that can be used for bone tissue engineering. In the present study, solid discs as well as porous cage-like 3D prints made of polylactide (PLA) are coated or filled with collagen, respectively, and tested for biocompatibility and endotoxin contamination. Microscopic analyses as well as proliferation assays were performed using various cell types on PLA discs. Stromal-derived factor (SDF-1) release from cages filled with collagen was analyzed and the effect on endothelial cells tested. This study confirms the biocompatibility of PLA and demonstrates an endotoxin contamination clearly below the FDA (Food and Drug Administration) limit. Cells of various cell types (osteoblasts, osteoblast-like cells, fibroblasts and endothelial cells) grow, spread and proliferate on PLA-printed discs. PLA cages loaded with SDF-1 collagen display a steady SDF-1 release, support cell growth of endothelial cells and induce neo-vessel formation. These results demonstrate the potential for PLA scaffolds printed with an inexpensive desktop printer in medical applications, for example, in bone tissue engineering. PMID:29186036

The synergistic effect of VEGF and biomorphic silicon carbides topography on in vivo angiogenesis and human bone marrow derived mesenchymal stem cell differentiation.

PubMed

Díaz-Rodríguez, P; Gómez-Amoza, J L; Landin, M

2015-08-04

Topographical features of biomaterials are able to modulate cell attachment, spreading and differentiation. The addition of growth factors to implantable biomaterials can modify these cellular responses, enhancing their therapeutic potential. The aim of this research is to establish the influence of biomorphic silicon carbide ceramics (bioSiCs) surface topography on the proliferation and osteoblastic differentiation of mesenchymal stem cells and the potential synergistic effect of the ceramic porous structure together with vascular endothelial growth factor loading (VEGF) on the surface mediated osteoblastic differentiation. Three porous bioSiCs with important differences in their microstructure were obtained from different natural precursors. Samples loaded with or without VEGF through ionic interactions were cultured with human umbilical vein endothelial cells (HUVEC) or bone marrow derived mesenchymal stem cells (hMSCs). Cell behaviour and protein activity with regard to bioSiC porous structure and surface properties were analysed. An in vivo model (Chick Chorioallantoic Membrane; CAM) was used to assess the capability of the VEGF loaded systems to promote angiogenesis. Experimental data show that loaded systems were able to control the release of VEGF for up to 15 d ensuring the activity of the protein, increasing the proliferation of HUVECs and the formation of new blood vessels in the CAM. It was found that the selection of bioSiCs with a higher pore size promoted a higher concentration of osteoblastic differentiation markers of MSCs cultured on the surface of bioSiCs. Furthermore, the addition of VEGF to the systems was able to promote a faster osteoblastic differentiation according to the qPCR results, suggesting a synergy between both the surface properties and the controlled release of the growth factor. The VEGF loaded sapelli bioSiC was found to be the most promising material for bone tissue engineering applications.

Load-sharing through elastic micro-motion accelerates bone formation and interbody fusion.

PubMed

Ledet, Eric H; Sanders, Glenn P; DiRisio, Darryl J; Glennon, Joseph C

2018-02-13

Achieving a successful spinal fusion requires the proper biological and biomechanical environment. Optimizing load-sharing in the interbody space can enhance bone formation. For anterior cervical discectomy and fusion (ACDF), loading and motion are largely dictated by the stiffness of the plate, which can facilitate a balance between stability and load-sharing. The advantages of load-sharing may be substantial for patients with comorbidities and in multilevel procedures where pseudarthrosis rates are significant. We aimed to evaluate the efficacy of a novel elastically deformable, continuously load-sharing anterior cervical spinal plate for promotion of bone formation and interbody fusion relative to a translationally dynamic plate. An in vivo animal model was used to evaluate the effects of an elastically deformable spinal plate on bone formation and spine fusion. Fourteen goats underwent an ACDF and received either a translationally dynamic or elastically deformable plate. Animals were followed up until 18 weeks and were evaluated by plain x-ray, computed tomography scan, and undecalcified histology to evaluate the rate and quality of bone formation and interbody fusion. Animals treated with the elastically deformable plate demonstrated statistically significantly superior early bone formation relative to the translationally dynamic plate. Trends in the data from 8 to 18 weeks postoperatively suggest that the elastically deformable implant enhanced bony bridging and fusion, but these enhancements were not statistically significant. Load-sharing through elastic micro-motion accelerates bone formation in the challenging goat ACDF model. The elastically deformable implant used in this study may promote early bony bridging and increased rates of fusion, but future studies will be necessary to comprehensively characterize the advantages of load-sharing through micro-motion. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

In vitro modeling of human tibial strains during exercise in micro-gravity

NASA Technical Reports Server (NTRS)

Peterman, M. M.; Hamel, A. J.; Cavanagh, P. R.; Piazza, S. J.; Sharkey, N. A.

2001-01-01

Prolonged exposure to micro-gravity causes substantial bone loss (Leblanc et al., Journal of Bone Mineral Research 11 (1996) S323) and treadmill exercise under gravity replacement loads (GRLs) has been advocated as a countermeasure. To date, the magnitudes of GRLs employed for locomotion in space have been substantially less than the loads imposed in the earthbound 1G environment, which may account for the poor performance of locomotion as an intervention. The success of future treadmill interventions will likely require GRLs of greater magnitude. It is widely held that mechanical tissue strain is an important intermediary signal in the transduction pathway linking the external loading environment to bone maintenance and functional adaptation; yet, to our knowledge, no data exist linking alterations in external skeletal loading to alterations in bone strain. In this preliminary study, we used unique cadaver simulations of micro-gravity locomotion to determine relationships between localized tibial bone strains and external loading as a means to better predict the efficacy of future exercise interventions proposed for bone maintenance on orbit. Bone strain magnitudes in the distal tibia were found to be linearly related to ground reaction force magnitude (R(2)>0.7). Strain distributions indicated that the primary mode of tibial loading was in bending, with little variation in the neutral axis over the stance phase of gait. The greatest strains, as well as the greatest strain sensitivity to altered external loading, occurred within the anterior crest and posterior aspect of the tibia, the sites furthest removed from the neutral axis of bending. We established a technique for estimating local strain magnitudes from external loads, and equations for predicting strain during simulated micro-gravity walking are presented.

Comparison of three methods of calculating strain in the mouse ulna in exogenous loading studies.

PubMed

Norman, Stephanie C; Wagner, David W; Beaupre, Gary S; Castillo, Alesha B

2015-01-02

Axial compression of mouse limbs is commonly used to induce bone formation in a controlled, non-invasive manner. Determination of peak strains caused by loading is central to interpreting results. Load-strain calibration is typically performed using uniaxial strain gauges attached to the diaphyseal, periosteal surface of a small number of sacrificed animals. Strain is measured as the limb is loaded to a range of physiological loads known to be anabolic to bone. The load-strain relationship determined by this subgroup is then extrapolated to a larger group of experimental mice. This method of strain calculation requires the challenging process of strain gauging very small bones which is subject to variability in placement of the strain gauge. We previously developed a method to estimate animal-specific periosteal strain during axial ulnar loading using an image-based computational approach that does not require strain gauges. The purpose of this study was to compare the relationship between load-induced bone formation rates and periosteal strain at ulnar midshaft using three different methods to estimate strain: (A) Nominal strain values based solely on load-strain calibration; (B) Strains calculated from load-strain calibration, but scaled for differences in mid-shaft cross-sectional geometry among animals; and (C) An alternative image-based computational method for calculating strains based on beam theory and animal-specific bone geometry. Our results show that the alternative method (C) provides comparable correlation between strain and bone formation rates in the mouse ulna relative to the strain gauge-dependent methods (A and B), while avoiding the need to use strain gauges. Published by Elsevier Ltd.

Modulation of Stromal Cell-Derived Factor-1/CXC Chemokine Receptor 4 Axis Enhances rhBMP-2-Induced Ectopic Bone Formation

PubMed Central

Wise, Joel K.; Sumner, Dale Rick

2012-01-01

Enhancement of in vivo mobilization and homing of endogenous mesenchymal stem cells (MSCs) to an injury site is an innovative strategy for improvement of bone tissue engineering and repair. The present study was designed to determine whether mobilization by AMD3100 and/or local homing by delivery of stromal cell-derived factor-1 (SDF-1) enhances recombinant human bone morphogenetic protein-2 (rhBMP-2) induced ectopic bone formation in an established rat model. Rats received an injection of either saline or AMD3100 treatment 1 h before harvesting of bone marrow for in vitro colony-forming unit-fibroblasts (CFU-F) culture or the in vivo subcutaneous implantation of absorbable collagen sponges (ACSs) loaded with saline, recombinant human bone morphogenetic protein-2 (rhBMP-2), SDF-1, or the combination of SDF-1 and rhBMP-2. AMD3100 treatment resulted in a significant decrease in CFU-F number, compared with saline, which confirmed that a single systemic AMD3100 treatment rapidly mobilized MSCs from the bone marrow. At 28 and 56 days, bone formation in the explanted ACS was assessed by microcomputed tomography (μCT) and histology. At 28 days, AMD3100 and/or SDF-1 had no statistically significant effect on bone volume (BV) or bone mineral content (BMC), but histology revealed more active bone formation with treatment of AMD3100, loading of SDF-1, or the combination of both AMD3100 and SDF-1, compared with saline-treated rhBMP-2 loaded ACS. At 56 days, the addition of AMD3100 treatment, loading of SDF-1, or the combination of both resulted in a statistically significant stimulatory effect on BV and BMC, compared with the saline-treated rhBMP-2 loaded ACS. Histology of the 56-day ACS were consistent with the μCT analysis, exhibiting more mature and mineralized bone formation with AMD3100 treatment, SDF-1 loading, or the combination of both, compared with the saline-treated rhBMP-2 loaded ACS. The present study is the first that provides evidence of the efficacy of AMD3100 and SDF-1 treatment to stimulate trafficking of MSCs to an ectopic implant site, in order to ultimately enhance rhBMP-2 induced long-term bone formation. PMID:22035136

Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

NASA Technical Reports Server (NTRS)

Westerlind, K. C.; Wronski, T. J.; Ritman, E. L.; Luo, Z. P.; An, K. N.; Bell, N. H.; Turner, R. T.

1997-01-01

Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.

Quantification of Cyclic Ground Reaction Force Histories During Daily Activity in Humans

NASA Technical Reports Server (NTRS)

Breit, G. A.; Whalen, R. T.; Wade, Charles E. (Technical Monitor)

1994-01-01

Theoretical models and experimental studies of bone remodeling suggest that bone density and structure are influenced by local cyclic skeletal tissue stress and strain histories. Estimation of long-term loading histories in humans is usually achieved by assessment of physical activity level by questionnaires, logbooks, and pedometers, since the majority of lower limb cyclic loading occurs during walking and running. These methods provide some indication of the mechanical loading history, but fail to consider the true magnitude of the lower limb skeletal forces generated by various daily activities. These techniques cannot account for individual gait characteristics, gait speed, and unpredictable high loading events that may influence bone mass significantly. We have developed portable instrumentation to measure and record the vertical component of the ground reaction force (GRFz) during normal daily activity. This equipment allows long-term quantitative monitoring of musculoskeletal loads, which in conjunction with bone mineral density assessments, promises to elucidate the relationship between skeletal stresses and bone remodeling.

Damage accumulation of bovine bone under variable amplitude loads.

PubMed

Campbell, Abbey M; Cler, Michelle L; Skurla, Carolyn P; Kuehl, Joseph J

2016-12-01

Stress fractures, a painful injury, are caused by excessive fatigue in bone. This study on damage accumulation in bone sought to determine if the Palmgren-Miner rule (PMR), a well-known linear damage accumulation hypothesis, is predictive of fatigue failure in bone. An electromagnetic shaker apparatus was constructed to conduct cyclic and variable amplitude tests on bovine bone specimens. Three distinct damage regimes were observed following fracture. Fractures due to a low cyclic amplitude loading appeared ductile ( 4000 μ ϵ ), brittle due to high cyclic amplitude loading (> 9000 μ ϵ ), and a combination of ductile and brittle from mid-range cyclic amplitude loading (6500 -6750 μ ϵ ). Brittle and ductile fracture mechanisms were isolated and mixed, in a controlled way, into variable amplitude loading tests. PMR predictions of cycles to failure consistently over-predicted fatigue life when mixing isolated fracture mechanisms. However, PMR was not proven ineffective when used with a single damage mechanism.

3D finite element analysis of changes in stress levels and distributions for an osseointegrated implant after vertical bone loss.

PubMed

Yoon, Kyung-Ho; Kim, Su-Gwan; Lee, Jeong-Hoon; Suh, Seung-Woo

2011-10-01

The effect of stress levels and distributions around the internal nonsubmerged type implants after vertical bone resorption was investigated in this study. An HSII implant was placed in 4 cylindrical alveolar bone models with differing degrees of thread exposures. The load applied to each implant was von Mises stress and principal stress, 250 N in axial direction and 30 degrees lateral pressure. The difference in the load between the bone and the connective portion of the implant was obtained using ANSYS analysis. Bone loss in the cervical area of the implant was more obvious under lateral pressure. When more threads were exposed, bone level decreased and the maximum load applied on the fixture increased. It was concluded that higher bone level has a biomechanical advantage with respect to stress concentration.

Investigating the mechanical response of paediatric bone under bending and torsion using finite element analysis.

PubMed

Altai, Zainab; Viceconti, Marco; Offiah, Amaka C; Li, Xinshan

2018-03-10

Fractures of bone account 25% of all paediatric injuries (Cooper et al. in J Bone Miner Res 19:1976-1981, 2004. https://doi.org/10.1359/JBMR.040902 ). These can be broadly categorised into accidental or inflicted injuries. The current clinical approach to distinguish between these two is based on the clinician's judgment, which can be subjective. Furthermore, there is a lack of studies on paediatric bone to provide evidence-based information on bone strength, mainly due to the difficulties of obtaining paediatric bone samples. There is a need to investigate the behaviour of children's bones under external loading. Such data will critically enhance our understanding of injury tolerance of paediatric bones under various loading conditions, related to injuries, such as bending and torsional loads. The aim of this study is therefore to investigate the response of paediatric femora under two types of loading conditions, bending and torsion, using a CT-based finite element approach, and to determine a relationship between bone strength and age/body mass of the child. Thirty post-mortem CT scans of children aged between 0 and 3 years old were used in this study. Two different boundary conditions were defined to represent four-point bending and pure torsional loads. The principal strain criterion was used to estimate the failure moment for both loading conditions. The results showed that failure moment of the bone increases with the age and mass of the child. The predicted failure moment for bending, external and internal torsions were 0.8-27.9, 1.0-31.4 and 1.0-30.7 Nm, respectively. To the authors' knowledge, this is the first report on infant bone strength in relation to age/mass using models developed from modern medical images. This technology may in future help advance the design of child, car restrain system, and more accurate computer models of children.

Influence of rhBMP-2 on Guided Bone Regeneration for Placement and Functional Loading of Dental Implants: A Radiographic and Histologic Study in Dogs.

PubMed

Ben Amara, Heithem; Lee, Jung-Won; Kim, Jung-Ju; Kang, Yun-Mi; Kang, Eun-Jung; Koo, Ki-Tae

Evidence on the outcomes of functional loading placed in recombinant human bone morphogenetic protein 2 (rhBMP-2)/acellular collagen sponge (ACS)-induced bone is lacking. The aim of this study was to verify whether guided bone regeneration (GBR) with rhBMP-2/ACS enhances regeneration of missing bone and osseointegration of dental implants subject to functional loading. Two bilateral standardized large saddle-type defects (≈10 × 10 × 6 mm) were surgically created in each mandible of seven beagle dogs 2 months after tooth extraction. Defects were immediately reconstructed randomly using rhBMP-2 (O-BMP or InFuse) soaked in ACS, deproteinized bovine bone mineral (DBBM) granules, or ACS alone as surgical control and subsequently covered with collagen membrane. Screw-type sand-blasted, acid-etched dental implants were placed 3 months later into the reconstructed defects and into adjacent bone. Osseointegration was allowed to progress for 3 months before functional loading of 3 months until sacrifice. Significantly more bone fill was radiographically observed for GBR with rhBMP-2/ACS (O-BMP: 92.5%, InFuse: 79%) in comparison to the DBBM (52%) and ACS alone groups (56.6%). Osseointegration was achieved and maintained in all experimental defects challenged by prostheses-driven functional load. The bone density ranged from 37.49% in the ACS group to 64.9% in the rhBMP-2/ACS (InFuse) group with no significance. The highest mean percentage of BIC was found in rhBMP-2/ACS (InFuse: 52.98%) with no statistical difference. Crestal bone resorption was observed around implants placed in reconstructed areas without any significant difference. GBR with rhBMP-2/ACS provided the greatest bone fill among the three treatment procedures. GBR with rhBMP-2/ACS showed efficacy for placement, osseointegration, and functional loading of titanium implants in alveolar ridge defects.

Effects of lateral cortical anchorage on the primary stability of implants subjected to controlled loads: an in vitro study.

PubMed

Xiao, Jian-rui; Li, Yong-Qi; Guan, Su-Min; Kong, Liang; Liu, Baolin; Li, Dehua

2012-03-01

Our aim was to evaluate the effects of lateral cortical anchorage on the primary stability of implants subjected to immediate loading. Implants were placed into bovine bones with monocortical anchorage (implant placed through the cortical bone of the crest) and bicortical anchorage (the crest cortical bone plus one cortical bone on the lateral side). Loads of 25N and 50N were applied to the implants in different cycles. The implant stability quotient (ISQ) was measured before and after the cyclic loadings. Under 25N load there was no difference in ISQ between 1800 cyclic loading and preloading, but the values decreased significantly after 3600 cyclic loading in both groups (p<0.05). Under a 50N load the ISQ value after 1800 and 3600 cyclic loading decreased in the monocortical group (p<0.05), but there was no difference between 1800 cyclic loading and preloading in the bicortical group, and the ISQ in the bicortical group was higher than in the monocortical group after 1800 cyclic loading (p<0.05). Our results suggest that the stability of implants with bicortical anchorage decreased more slowly under higher loads. Copyright © 2011 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Titanium-Enriched Hydroxyapatite–Gelatin Scaffolds with Osteogenically Differentiated Progenitor Cell Aggregates for Calvaria Bone Regeneration

PubMed Central

Padilla, Ricardo; Urkasemsin, Ganokon; Yoon, Kun; Goeckner, Kelly; Hu, Wei-Shou

2013-01-01

Adequate bony support is the key to re-establish both function and esthetics in the craniofacial region. Autologous bone grafting has been the gold standard for regeneration of problematic large bone defects. However, poor graft availability and donor-site complications have led to alternative bone tissue-engineering approaches combining osteoinductive biomaterials and three-dimensional cell aggregates in scaffolds or constructs. The goal of the present study was to generate novel cell aggregate-loaded macroporous scaffolds combining the osteoinductive properties of titanium dioxide (TiO2) with hydroxyapatite–gelatin nanocomposites (HAP-GEL) for regeneration of craniofacial defects. Here we investigated the in vivo applicability of macroporous (TiO2)-enriched HAP-GEL scaffolds with undifferentiated and osteogenically differentiated multipotent adult progenitor cell (MAPC and OD-MAPC, respectively) aggregates for calvaria bone regeneration. The silane-coated HAP-GEL with and without TiO2 additives were polymerized and molded to produce macroporous scaffolds. Aggregates of the rat MAPC were precultured, loaded into each scaffold, and implanted to rat calvaria critical-size defects to study bone regeneration. Bone autografts were used as positive controls and a poly(lactic-co-glycolic acid) (PLGA) scaffold for comparison purposes. Preimplanted scaffolds and calvaria bone from pig were tested for ultimate compressive strength with an Instron 4411® and for porosity with microcomputerized tomography (μCT). Osteointegration and newly formed bone (NFB) were assessed by μCT and nondecalcified histology, and quantified by calcium fluorescence labeling. Results showed that the macroporous TiO2-HAP-GEL scaffold had a comparable strength relative to the natural calvaria bone (13.8±4.5 MPa and 24.5±8.3 MPa, respectively). Porosity was 1.52±0.8 mm and 0.64±0.4 mm for TiO2-HAP-GEL and calvaria bone, respectively. At 8 and 12 weeks postimplantation into rat calvaria defects, greater osteointegration and NFB were significantly present in the TiO2-enriched HAP-GEL constructs with OD-MAPCs, compared to the undifferentiated MAPC-loaded constructs, cell-free HAP-GEL with and without titanium, and PLGA scaffolds. The tissue-engineered TiO2-enriched HAP-GEL constructs with OD-MAPC aggregates present a potential useful therapeutic approach for calvaria bone regeneration. PMID:23495972

Mechanical loading increases detection of estrogen receptor-alpha in osteocytes and osteoblasts despite chronic energy restriction.

PubMed

Swift, Sibyl N; Swift, Joshua M; Bloomfield, Susan A

2014-12-01

Estrogen receptor-α (ER-α) is an important mediator of the bone response to mechanical loading. We sought to determine whether restricting dietary energy intake by 40% limits the bone formation rate (BFR) response to mechanical loading (LOAD) by downregulating ER-α-expressing osteocytes, or osteoblasts, or both. Female rats (n = 48, 7 mo old) were randomized to ADLIB-SHAM and ADLIB-LOAD groups fed AIN-93M purified diet ad libitum or to ER40-SHAM and ER40-LOAD groups fed modified AIN-93M with 40% less energy (100% of all other nutrients). After 12 wk, LOAD rats were subjected to a muscle contraction protocol three times every third day. ER40 produced lower proximal tibia bone volume (-22%), trabecular thickness (-14%), and higher trabecular separation (+127%) in SHAM but not LOAD rats. ER40 rats exhibited reductions in mineral apposition rate, but not percent mineralizing surface or BFR. LOAD induced similar relative increases in these kinetic measures of osteoblast activity/recruitment in both diet groups., but absolute values for ER40 LOAD rats were lower vs. ADLIB-LOAD. There were fourfold and eightfold increases in proportion of estrogen receptor-α protein-positive osteoblast and osteocytes, respectively, in LOAD vs. SHAM rats, with no effect of ER40. These data suggest that a brief period of mechanical loading significantly affects estrogen receptor-α in cancellous bone osteoblasts and osteocytes. Chronic energy restriction does result in lower absolute values in indices of osteoblast activity after mechanical loading, but not by a smaller increment relative to unloaded bones; this change is not explained by an associated downregulation of ER-α in osteoblasts or osteocytes.

The influence of different loads on the remodeling process of a bone and bioresorbable material mixture with voids

NASA Astrophysics Data System (ADS)

Giorgio, Ivan; Andreaus, Ugo; Madeo, Angela

2016-03-01

A model of a mixture of bone tissue and bioresorbable material with voids was used to numerically analyze the physiological balance between the processes of bone growth and resorption and artificial material resorption in a plate-like sample. The adopted model was derived from a theory for the behavior of porous solids in which the matrix material is linearly elastic and the interstices are void of material. The specimen—constituted by a region of bone living tissue and one of bioresorbable material—was acted by different in-plane loading conditions, namely pure bending and shear. Ranges of load magnitudes were identified within which physiological states become possible. Furthermore, the consequences of applying different loading conditions are examined at the end of the remodeling process. In particular, maximum value of bone and material mass densities, and extensions of the zones where bone is reconstructed were identified and compared in the two different load conditions. From the practical view point, during surgery planning and later rehabilitation, some choice of the following parameters is given: porosity of the graft, material characteristics of the graft, and adjustment of initial mixture tissue/bioresorbable material and later, during healing and remodeling, optimal loading conditions.

No influence of simultaneous bone-substitute application on the success of immediately loaded dental implants: a retrospective cohort study.

PubMed

Kopp, Sigmar; Behrend, Detlef; Kundt, Günther; Ottl, Peter; Frerich, Bernhard; Warkentin, Mareike

2013-06-01

To examine the influence of bone-substitute application during implantation on the success of immediately placed and loaded dental implants. A total of 147 consecutive patients (age, 16.5-80.4 years) were provided with 696 immediately loaded implants. The mean follow-up time was 34.1 months. Of these implants, 50.4% (n=351) were immediately placed into extraction sockets. A total of 119 implants were added by simultaneous bone-substitute application (NanoBone, Artoss GmbH, Rostock Germany), whereas the other implants were placed in healed bone. Univariate and multivariate analysis was performed using IBM SPSS V.20. The overall implant success rate was 96.1%. Implants with simultaneous bone replacement had a hazard ratio of 0.877 (p=0.837); 95% CI, 0.253-3.04). Factors found to be statistically significant modifiers of success on multivariate analysis (p<0.05) included type of superstructure (p<0.001), implant-abutment connection (p<0.001), membrane use (p=0.010), and jaw (p=0.026). None of the other factors investigated were significant modifiers. The present study demonstrates high success rates for immediately loaded implants and their superstructures independent of the simultaneous application of bone substitute. The declared aim of socket preservation, the prevention avoiding bone loss, is achieved in the immediate implant placement scenario under immediate-loading conditions.

Guiding bone formation in a critical-sized defect and assessments.

PubMed

Jannetty, Joseph; Kolb, Eric; Boxberger, John; Deslauriers, Richard; Ganey, Timothy

2010-11-01

Development of alternatives to autologous bone has been served by many hypotheses and developments. Favorable properties of synthetic materials used currently in bone grafting support tissue differentiation without shielding capacity for integrated modeling. Ideally, new materials provide tissue compatibility and minimize patient morbidity and are attractive because of potential for in situ delivery, isothermal polymerization, porous structure, and nontoxic chemistry. For application in cranial bone, ability for materials to be laid adjacent to brain and offer postsurgical protection without neural risk is a critical asset. Kryptonite Bone Cement (KBC) meets the property criteria for cranial bone repair with regard to adhesive, conductive, and biologic transparency and US Food and Drug Administration approval for cranial bone void repair. To better delineate the morphology effective in cranial bone repair, a comparison was made between KBC and BoneSource, another material approved for the same indication. After Institutional Animal Care and Use Committee approval, the study assessed 24 rabbits, each with 2 separate cranial implants, to evaluate integration and absorption of the biomaterial at defined time points of 12, 18, 24, and 36 weeks. The 36-week assessment demonstrated near-complete resorption/integration of the BoneSource graft material. Bone was present within the biomaterial as well as independent of contact. The KBC was similarly integrated throughout the mass of the material, and new bone was in contact with the grafting material and also seen as separate islands of new bone. The bone demonstrated lamellar bone architecture with clear trabecular morphology. At higher magnification, the bone architecture can be clearly delineated, and comparison between the graft fillers is not obvious relative to the bone that has formed. Despite microscopic similarities, the most striking difference was maintenance of scaffold anatomy during bone regeneration. Kryptonite Bone Cement meets the criteria described in the introduction; properties of biologic transparency, osteoconductivity, and ergonomic utility offer other potential uses in bone repair. Key tenets of bone tissue regeneration observed in this analysis included adequate cell differentiation and tissue support. Bone that formed demonstrated lamellar rather than woven bone to suggest response to loading strain rather than merely biochemical precipitation. Over the 36-week study, the graft showed progressive bioabsorbable potential with calibrated replacement.

Regional Variation of Bone Tissue Properties at the Human Mandibular Condyle

PubMed Central

Kim, Do-Gyoon; Jeong, Yong-Hoon; Kosel, Erin; Agnew, Amanda M.; McComb, David W.; Bodnyk, Kyle; Hart, Richard T.; Kim, Min Kyung; Han, Sang Yeun; Johnston, William M.

2015-01-01

The temporomandibular joint (TMJ) bears different types of static and dynamic loading during occlusion and mastication. As such, characteristics of mandibular condylar bone tissue play an important role in determining the mechanical stability of the TMJ under the macro-level loading. Thus, the objective of this study was to examine regional variation of the elastic, plastic, and viscoelastic mechanical properties of human mandibular condylar bone tissue using nanoindentation. Cortical and trabecular bone were dissected from mandibular condyles of human cadavers (9 males, 54 to 96 years). These specimens were scanned using microcomputed tomography to obtain bone tissue mineral distribution. Then, nanoindentation was conducted on the surface of the same specimens in hydration. Plastic hardness (H) at a peak load, viscoelastic creep (Creep/Pmax), viscosity (η), and tangent delta (tan δ) during a 30 second hold period, and elastic modulus (E) during unloading were obtained by a cycle of indentation at the same site of bone tissue. The tissue mineral and nanoindentation parameters were analyzed for the periosteal and endosteal cortex, and trabecular bone regions of the mandibular condyle. The more mineralized periosteal cortex had higher mean values of elastic modulus, plastic hardness, and viscosity but lower viscoelastic creep and tan δ than the less mineralized trabecular bone of the mandibular condyle. These characteristics of bone tissue suggest that the periosteal cortex tissue may have more effective properties to resist elastic, plastic, and viscoelastic deformation under static loading, and the trabecular bone tissue to absorb and dissipate time-dependent viscoelastic loading energy at the TMJ during static occlusion and dynamic mastication. PMID:25913634

Pullout strength of bone-patellar tendon-bone allograft bone plugs: a comparison of cadaver tibia and rigid polyurethane foam.

PubMed

Barber, F Alan

2013-09-01

To compare the load-to-failure pullout strength of bone-patellar tendon-bone (BPTB) allografts in human cadaver tibias and rigid polyurethane foam blocks. Twenty BPTB allografts were trimmed creating 25 mm × 10 mm × 10 mm tibial plugs. Ten-millimeter tunnels were drilled in 10 human cadaver tibias and 10 rigid polyurethane foam blocks. The BPTB anterior cruciate ligament allografts were inserted into these tunnels and secured with metal interference screws, with placement of 10 of each type in each material. After preloading (10 N), cyclic loading (500 cycles, 10 to 150 N at 200 mm/min) and load-to-failure testing (200 mm/min) were performed. The endpoints were ultimate failure load, cyclic loading elongation, and failure mode. No difference in ultimate failure load existed between grafts inserted into rigid polyurethane foam blocks (705 N) and those in cadaver tibias (669 N) (P = .69). The mean rigid polyurethane foam block elongation (0.211 mm) was less than that in tibial bone (0.470 mm) (P = .038), with a smaller standard deviation (0.07 mm for foam) than tibial bone (0.34 mm). All BPTB grafts successfully completed 500 cycles. The rigid polyurethane foam block showed less variation in test results than human cadaver tibias. Rigid polyurethane foam blocks provide an acceptable substitute for human cadaver bone tibia for biomechanical testing of BPTB allografts and offer near-equivalent results. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Influence of abutment screw preload on stress distribution in marginal bone.

PubMed

Khraisat, Ameen

2012-01-01

Changes in an implant assembly after abutment connection might possibly cause deformation in the implant/abutment joint and even in the marginal bone. The aim of this study was to evaluate the influence of abutment screw preload through the implant collar on marginal bone stress without external load application. Models of three implant parts made of titanium (implant, abutment, and abutment screw) and cortical bone were built and positioned with computer-aided design software. Meshing and generation of boundary conditions, loads, and interactions were performed. Each part was meshed independently. The sole load applied to the model was a torque of 32 Ncm on the abutment screw about its axis of rotation. The implant collar was deformed axially after the screw was tightened (3 μm). This deformation resulted in 60 MPa of stress in the marginal bone. Moreover, pressure on the marginal bone in a radial direction was observed. It can be concluded that, without any external load application, abutment screw preload exerts stresses on the implant collar and the marginal bone. These findings should help guide the development of new implant/abutment joint designs that exert less stress on the marginal bone.

[Remodeling simulation of human femur under bed rest and spaceflight circumstances based on three dimensional finite element analysis].

PubMed

Yang, Wenting; Wang, Dongmei; Lei, Zhoujixin; Wang, Chunhui; Chen, Shanguang

2017-12-01

Astronauts who are exposed to weightless environment in long-term spaceflight might encounter bone density and mass loss for the mechanical stimulus is smaller than normal value. This study built a three dimensional model of human femur to simulate the remodeling process of human femur during bed rest experiment based on finite element analysis (FEA). The remodeling parameters of this finite element model was validated after comparing experimental and numerical results. Then, the remodeling process of human femur in weightless environment was simulated, and the remodeling function of time was derived. The loading magnitude and loading cycle on human femur during weightless environment were increased to simulate the exercise against bone loss. Simulation results showed that increasing loading magnitude is more effective in diminishing bone loss than increasing loading cycles, which demonstrated that exercise of certain intensity could help resist bone loss during long-term spaceflight. At the end, this study simulated the bone recovery process after spaceflight. It was found that the bone absorption rate is larger than bone formation rate. We advise that astronauts should take exercise during spaceflight to resist bone loss.

Effects of deletion of ER-alpha in osteoblast-lineage cells on bone mass and adaptation to mechanical loading differs in female and male mice

PubMed Central

Melville, Katherine M.; Kelly, Natalie H.; Surita, Gina; Buchalter, Daniel B.; Schimenti, John C.; Main, Russell P.; Ross, F. Patrick; van der Meulen, Marjolein C. H.

2015-01-01

Estrogen receptor alpha (ERα) has been implicated in bone’s response to mechanical loading in both males and females. ERα in osteoblast lineage cells is important for determining bone mass, but results depend on animal sex and the cellular stage at which ERα is deleted. We demonstrated previously that when ERα is deleted from mature osteoblasts and osteocytes in mixed background female mice, bone mass and strength are decreased. However, few studies exist examining the skeletal response to loading in bone cell-specific ERαKO mice. Therefore, we crossed ERα floxed (ERαfl/fl) and osteocalcin-Cre (OC-Cre) mice to generate animals lacking ERα in mature osteoblasts and osteocytes (pOC-ERαKO) and littermate controls (LC). At 10 weeks of age the left tibia was loaded in vivo for two weeks. We analyzed bone mass through microCT, bone formation rate by dynamic histomorphometry, bone strength from mechanical testing, and osteoblast and osteoclast activity by serum chemistry and immunohistochemistry. ERα in mature osteoblasts differentially regulated bone mass in males and females. Compared to LC, female pOC-ERαKO mice had decreased cortical and cancellous bone mass, while male pOC-ERαKO mice had equal or greater bone mass than LC. Bone mass results correlated with decreased compressive strength in pOC-ERαKO female L5 vertebrae, and with increased maximum moment in pOC-ERαKO male femora. Female pOC-ERαKO mice responded more to mechanical loading, while the response of pOC-ERαKO male animals was similar to their littermate controls. PMID:25707500

Aging and loading rate effects on the mechanical behavior of equine bone

NASA Astrophysics Data System (ADS)

Kulin, Robb M.; Jiang, Fengchun; Vecchio, Kenneth S.

2008-06-01

Whether due to a sporting accident, high-speed impact, fall, or other catastrophic event, the majority of clinical bone fractures occur under dynamic loading conditions. However, although extensive research has been performed on the quasi-static fracture and mechanical behavior of bone to date, few high-quality studies on the fracture behavior of bone at high strain rates have been performed. Therefore, many questions remain regarding the material behavior, including not only the loading-rate-dependent response of bone, but also how this response varies with age. In this study, tests were performed on equine femoral bone taken post-mortem from donors 6 months to 28 years of age. Quasi-static and dynamic tests were performed to determine the fracture toughness and compressive mechanical behavior as a function of age at varying loading rates. Fracture paths were then analyzed using scanning confocal and scanning-electron microscopy techniques to assess the role of various microstructural features on toughening mechanisms.

Ex vivo and in vitro synchrotron-based micro-imaging of biocompatible materials applied in dental surgery

NASA Astrophysics Data System (ADS)

Rack, A.; Stiller, M.; Nelson, K.; Knabe, C.; Rack, T.; Zabler, S.; Dalügge, O.; Riesemeier, H.; Cecilia, A.; Goebbels, J.

2010-09-01

Biocompatible materials such as porous bioactive calcium phosphate ceramics or titanium are regularly applied in dental surgery: ceramics are used to support the local bone regeneration in a given defect, afterwards titanium implants replace lost teeth. The current gold standard for bone reconstruction in implant dentistry is the use of autogenous bone grafts. But the concept of guided bone regeneration (GBR) has become a predictable and well documented surgical approach using biomaterials (bioactive calcium phosphate ceramics) which qualify as bone substitutes for this kind of application as well. We applied high resolution synchrotron microtomography and subsequent 3d image analysis in order to investigate bone formation and degradation of the bone substitute material in a three-dimensional manner, extending the knowledge beyond the limits of classical histology. Following the bone regeneration, titanium-based implants to replace lost teeth call for high mechanical precision, especially when two-piece concepts are used in order to guaranty leak tightness. Here, synchrotron-based radiography in comparison with classical laboratory radiography yields high spatial resolution in combination with high contrast even when exploiting micro-sized features in these kind of highly attenuating objects. Therefore, we could study micro-gap formation at interfaces in two-piece dental implants with the specimen under different mechanical load. We could prove the existence of micro-gaps for implants with conical connections as well as to study the micromechanical behavior of the mating zone of conical implants during loading. The micro-gap is a potential issue of failure, i. e. bacterial leakage which can induce an inflammatory process.

Bioactive Molecule-loaded Drug Delivery Systems to Optimize Bone Tissue Repair.

PubMed

Oshiro, Joao Augusto; Sato, Mariana Rillo; Scardueli, Cassio Rocha; Lopes de Oliveira, Guilherme Jose Pimentel; Abucafy, Marina Paiva; Chorilli, Marlus

2017-01-01

Bioactive molecules such as peptides and proteins can optimize the repair of bone tissue; however, the results are often unpredictable when administered alone, owing to their short biological half-life and instability. Thus, the development of bioactive molecule-loaded drug delivery systems (DDS) to repair bone tissue has been the subject of intense research. DDS can optimize the repair of bone tissue owing to their physicochemical properties, which improve cellular interactions and enable the incorporation and prolonged release of bioactive molecules. These characteristics are fundamental to favor bone tissue homeostasis, since the biological activity of these factors depends on how accessible they are to the cell. Considering the importance of these DDS, this review aims to present relevant information on DDS when loaded with osteogenic growth peptide and bone morphogenetic protein. These are bioactive molecules that are capable of modulating the differentiation and proliferation of mesenchymal cells in bone tissue cells. Moreover, we will present different approaches using these peptide and protein-loaded DDS, such as synthetic membranes and scaffolds for bone regeneration, synthetic grafts, bone cements, liposomes, and micelles, which aim at improving the therapeutic effectiveness, and we will compare their advantages with commercial systems. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A study of the progression of damage in an axially loaded Branta leucopsis femur using X-ray computed tomography and digital image correlation.

PubMed

Mustansar, Zartasha; McDonald, Samuel A; Sellers, William Irvin; Manning, Phillip Lars; Lowe, Tristan; Withers, Philip J; Margetts, Lee

2017-01-01

This paper uses X-ray computed tomography to track the mechanical response of a vertebrate (Barnacle goose) long bone subjected to an axial compressive load, which is increased gradually until failure. A loading rig was mounted in an X-ray computed tomography system so that a time-lapse sequence of three-dimensional (3D) images of the bone's internal (cancellous or trabecular) structure could be recorded during loading. Five distinct types of deformation mechanism were observed in the cancellous part of the bone. These were (i) cracking, (ii) thinning (iii) tearing of cell walls and struts, (iv) notch formation, (v) necking and (vi) buckling. The results highlight that bone experiences brittle (notch formation and cracking), ductile (thinning, tearing and necking) and elastic (buckling) modes of deformation. Progressive deformation, leading to cracking was studied in detail using digital image correlation. The resulting strain maps were consistent with mechanisms occurring at a finer-length scale. This paper is the first to capture time-lapse 3D images of a whole long bone subject to loading until failure. The results serve as a unique reference for researchers interested in how bone responds to loading. For those using computer modelling, the study not only provides qualitative information for verification and validation of their simulations but also highlights that constitutive models for bone need to take into account a number of different deformation mechanisms.

The osteoporotic vertebral structure is well adapted to the loads of daily life, but not to infrequent "error" loads.

PubMed

Homminga, J; Van-Rietbergen, B; Lochmüller, E M; Weinans, H; Eckstein, F; Huiskes, R

2004-03-01

Osteoporotic vertebral fractures typically have a gradual onset, frequently remain clinically undetected, and do not seem to be related to traumatic events. The osteoporotic vertebrae may therefore be expected to display a less "optimal" bone architecture, leading to an uneven load distribution over the bone material. We evaluated the trabecular load distribution in an osteoporotic and a healthy vertebra under normal daily loading by combining three recent innovations: high resolution computed tomography (microCT) of entire bones, microfinite element analyses (microFEA), and parallel supercomputers. Much to our surprise, the number of highly loaded trabeculae was not higher in the osteoporotic vertebra than in the healthy one under normal daily loads (8% and 9%, respectively). The osteoporotic trabeculae were more oriented in the longitudinal direction, compensating for effects of bone loss and ensuring adequate stiffness for normal daily loading. The increased orientation did, however, make the osteoporotic structure less resistant against collateral "error" loads. In this case, the number of overloaded trabeculae in the osteoporotic vertebra was higher than in the healthy one (13% and 4%, respectively). These results strengthen the paradigm of a strong relationship between bone morphology and external loads applied during normal daily life. They also indicate that vertebral fractures result from actions like forward flexion or lifting, loads that may not be "daily" but are normally not traumatic either. If future clinical imaging techniques would enable such high-resolution images to be obtained in vivo, the combination of microCT and microFEA would produce a powerful tool to diagnose osteoporosis.

Bone and Skeletal Muscle: Key Players in Mechanotransduction and Potential Overlapping Mechanisms

PubMed Central

Goodman, Craig A.; Hornberger, Troy A.; Robling, Alexander G.

2015-01-01

The development and maintenance of skeletal muscle and bone mass is critical for movement, health and issues associated with the quality of life. Skeletal muscle and bone mass are regulated by a variety of factors that include changes in mechanical loading. Moreover, bone mass is, in large part, regulated by muscle-derived mechanical forces and thus by changes in muscle mass/strength. A thorough understanding of the cellular mechanism(s) responsible for mechanotransduction in bone and skeletal muscle is essential for the development of effective exercise and pharmaceutical strategies aimed at increasing, and/or preventing the loss of, mass in these tissues. Thus, in this review we will attempt to summarize the current evidence for the major molecular mechanisms involved in mechanotransduction in skeletal muscle and bone. By examining the differences and similarities in mechanotransduction between these two tissues, it is hoped that this review will stimulate new insights and ideas for future research and promote collaboration between bone and muscle biologists. PMID:26453495

Clinical and Radiographic Assessment of Three-Implant-Supported Fixed-Prosthesis Rehabilitation of the Edentulous Mandible: Immediate Versus Delayed Loading.

PubMed

Primo, Bruno Tochetto; Mezzari, Leonardo Marcos; da Fontoura Frasca, Luís Carlos; Linderman, Raquel; Rivaldo, Elken Gomes

To evaluate and compare the clinical and radiographic outcomes of mandibular rehabilitation with fixed prostheses on three implants with immediate versus delayed loading. The sample comprised 21 patients who underwent treatment with immediate loading and 23 who received delayed loading. All had worn their prostheses for at least 18 months. Radiographic evaluation of bone loss was carried out in Adobe Photoshop CS5 by a single calibrated examiner using digitized panoramic radiographs. Clinical examination of the technical conditions of the prosthetic device assessed the condition of the acrylic resin base, dental occlusion, metal framework, presence of cover screws, screw fixation of the prosthesis and abutments, length of cantilever (effort) and resistance arms, presence of plaque on prosthetic abutments, and hygiene of the prosthesis. One implant failed in each group, resulting in a 95.23% treatment success rate with immediate loading and 95.65% with delayed loading (no statistically significant between-group difference). In the immediate-loading group, the mean bone loss was 1.96 ± 0.73 mm around central implants and 1.64 ± 0.84 mm at distal implants. In the delayed-loading group, the mean bone loss was 1.85 ± 0.67 mm around central implants and 1.70 ± 0.77 mm at distal implants. According to Student t test, there was no significant within-group difference in bone loss and no difference between the immediate-loading and delayed-loading groups. The only prosthesis-related complications that differed significantly between groups were "condition of the acrylic base," "occlusion," and "presence of right cover screw." There was no statistically significant association of lever arm ratio with peri-implant bone loss or bone loss on the mesial surfaces compared to the distal surfaces of the distal implants. The three-implant-supported fixed prosthesis protocol tested in this study proved to be a viable therapeutic strategy for mandibular edentulous patients with maxillary complete dentures, regardless of whether loading was immediate or delayed, with no difference in peri-implant bone loss.

In situ intracellular calcium oscillations in osteocytes in intact mouse long bones under dynamic mechanical loading

PubMed Central

Jing, Da; Baik, Andrew D.; Lu, X. Lucas; Zhou, Bin; Lai, Xiaohan; Wang, Liyun; Luo, Erping; Guo, X. Edward

2014-01-01

Osteocytes have been hypothesized to be the major mechanosensors in bone. How in situ osteocytes respond to mechanical stimuli is still unclear because of technical difficulties. In vitro studies have shown that osteocytes exhibited unique calcium (Ca2+) oscillations to fluid shear. However, whether this mechanotransduction phenomenon holds for in situ osteocytes embedded within a mineralized bone matrix under dynamic loading remains unknown. Using a novel synchronized loading/imaging technique, we successfully visualized in real time and quantified Ca2+ responses in osteocytes and bone surface cells in situ under controlled dynamic loading on intact mouse tibia. The resultant fluid-induced shear stress on the osteocyte in the lacunocanalicular system (LCS) was also quantified. Osteocytes, but not surface cells, displayed repetitive Ca2+ spikes in response to dynamic loading, with spike frequency and magnitude dependent on load magnitude, tissue strain, and shear stress in the LCS. The Ca2+ oscillations were significantly reduced by endoplasmic reticulum (ER) depletion and P2 purinergic receptor (P2R)/phospholipase C (PLC) inhibition. This study provides direct evidence that osteocytes respond to in situ mechanical loading by Ca2+ oscillations, which are dependent on the P2R/PLC/inositol trisphosphate/ER pathway. This study develops a novel approach in skeletal mechanobiology and also advances our fundamental knowledge of bone mechanotransduction.—Jing, D., Baik, A. D., Lu, X. L., Zhou, B., Lai, X., Wang, L., Luo, E., Guo, X. E. In situ intracellular calcium oscillations in osteocytes in intact mouse long bones under dynamic mechanical loading. PMID:24347610

Spatial relationship between bone formation and mechanical stimulus within cortical bone: Combining 3D fluorochrome mapping and poroelastic finite element modelling.

PubMed

Carrieroa, A; Pereirab, A F; Wilson, A J; Castagno, S; Javaheri, B; Pitsillides, A A; Marenzana, M; Shefelbine, S J

2018-06-01

Bone is a dynamic tissue and adapts its architecture in response to biological and mechanical factors. Here we investigate how cortical bone formation is spatially controlled by the local mechanical environment in the murine tibia axial loading model (C57BL/6). We obtained 3D locations of new bone formation by performing 'slice and view' 3D fluorochrome mapping of the entire bone and compared these sites with the regions of high fluid velocity or strain energy density estimated using a finite element model, validated with ex-vivo bone surface strain map acquired ex-vivo using digital image correlation. For the comparison, 2D maps of the average bone formation and peak mechanical stimulus on the tibial endosteal and periosteal surface across the entire cortical surface were created. Results showed that bone formed on the periosteal and endosteal surface in regions of high fluid flow. Peak strain energy density predicted only the formation of bone periosteally. Understanding how the mechanical stimuli spatially relates with regions of cortical bone formation in response to loading will eventually guide loading regime therapies to maintain or restore bone mass in specific sites in skeletal pathologies.

Preparation of a new composite combining strengthened β-tricalcium phosphate with platelet-rich plasma as a potential scaffold for the repair of bone defects

PubMed Central

WANG, CHENGGONG; ZHONG, DA; ZHOU, XING; YIN, KE; LIAO, QIANDE; KONG, LINGYU; LIU, ANSONG

2014-01-01

β-tricalcium phosphate (β-TCP) and platelet-rich plasma (PRP) are commonly used in bone tissue engineering. In the present study, a new composite combining strengthened β-TCP and PRP was prepared and its morphological and mechanical properties were investigated by scanning electron microscopy (SEM) and material testing. The biocompatibility was evaluated by measuring the adhesion rate and cytotoxicity of bone marrow stromal cells (BMSCs). The strengthened β-TCP/PRP composite had an appearance like the fungus Boletus kermesinus with the PRP gel distributed on the surface of the micropores. The maximum load and load intensity were 945.6±86.4 N and 13.1±0.5 MPa, which were significantly higher than those of β-TCP (110.1±14.3 N and 1.6±0.2 MPa; P<0.05). The BMSC adhesion rate on the strengthened β-TCP/PRP composite was >96% after 24 h, with a cell cytotoxicity value of zero. SEM micrographs revealed that following seeding of BMSCs onto the composite in high-glucose Dulbecco’s modified Eagle’s medium culture for two weeks, the cells grew well and exhibited fusiform, spherical and polygonal morphologies, as well as pseudopodial connections. The strengthened β-TCP/PRP composite has the potential to be used as a scaffold in bone tissue engineering due to its effective biocompatibility and mechanical properties. PMID:25187800

The orthotropic elastic properties of fibrolamellar bone tissue in juvenile white-tailed deer femora

PubMed Central

Barrera, John W.; Le Cabec, Adeline; Barak, Meir M.

2017-01-01

Fibrolamellar bone is a transient primary bone tissue found in fast growing juvenile mammals, several species of birds and large dinosaurs. Despite the fact that this bone tissue is prevalent in many species, the vast majority of bone structural and mechanical studies are focused on humans osteonal bone tissue. Previous research revealed the orthotropic structure of fibrolamellar bone, but only a handful of experiments investigated its elastic properties, mostly in the axial direction. Here we have performed for the first time an extensive biomechanical study to determine the elastic properties of fibrolamellar bone in all three orthogonal directions. We have tested 30 fibrolamellar bone cubes (2×2×2mm) from the femora of five juvenile white-tailed deer (Odocoileus virginianus) in compression. Each bone cube was compressed iteratively, within its elastic region, in the axial, transverse and radial directions and bone stiffness (Young’s modulus) was recorded. Next, the cubes were kept for seven days at 4°C and then compressed again to test whether bone stiffness had significantly deteriorated. Our results demonstrated that bone tissue in the deer femora has orthotropic elastic behavior where the highest stiffness was in the axial direction followed by the transverse and the radial directions respectively (21.6±3.3 GPa, 17.6±3.0 GPa and 14.9±1.9 GPa respectively). Our results also revealed a slight non-significant decrease in bone stiffness after seven days. Finally, our sample size allowed us to establish that population variance was much bigger in the axial direction compared to the radial direction which potentially reflects bone adaptation to the large diversity in loading activity between individuals in the loading direction (axial) compared to the normal (radial) direction. This study confirms that the well mechanically-studied human transverse-isotropic osteonal bone is just one possible functional adaptation of bone tissue and that other vertebrate species use an orthotropic bone tissue structure which is more suitable for their mechanical requirements. PMID:27231028

Osteocyte calcium signals encode strain magnitude and loading frequency in vivo.

PubMed

Lewis, Karl J; Frikha-Benayed, Dorra; Louie, Joyce; Stephen, Samuel; Spray, David C; Thi, Mia M; Seref-Ferlengez, Zeynep; Majeska, Robert J; Weinbaum, Sheldon; Schaffler, Mitchell B

2017-10-31

Osteocytes are considered to be the major mechanosensory cells of bone, but how osteocytes in vivo process, perceive, and respond to mechanical loading remains poorly understood. Intracellular calcium (Ca 2+ ) signaling resulting from mechanical stimulation has been widely studied in osteocytes in vitro and in bone explants, but has yet to be examined in vivo. This is achieved herein by using a three-point bending device which is capable of delivering well-defined mechanical loads to metatarsal bones of living mice while simultaneously monitoring the intracellular Ca 2+ responses of individual osteocytes by using a genetically encoded fluorescent Ca 2+ indicator. Osteocyte responses are imaged by using multiphoton fluorescence microscopy. We investigated the in vivo responses of osteocytes to strains ranging from 250 to 3,000 [Formula: see text] and frequencies from 0.5 to 2 Hz, which are characteristic of physiological conditions reported for bone. At all loading frequencies examined, the number of responding osteocytes increased strongly with applied strain magnitude. However, Ca 2+ intensity within responding osteocytes did not change significantly with physiological loading magnitudes. Our studies offer a glimpse into how these critical bone cells respond to mechanical load in vivo, as well as provide a technique to determine how the cells encode magnitude and frequency of loading. Published under the PNAS license.

Preventing Cartilage Degeneration in Warfighters by Elucidating Novel Mechanisms Regulating Osteocyte-Mediated Perilacunar Bone Remodeling

DTIC Science & Technology

2015-10-01

quality, and cartilage health in post-traumatic osteoarthritis (PTOA). Few molecular details are known about the regulation of PLR or bone quality...degeneration. 15. SUBJECT TERMS Osteocyte, remodeling, bone, bone quality, post-traumatic osteoarthritis , TGF-beta, mechanical load, matrix...joint health, and their contribution to post-traumatic osteoarthritis (PTOA). Osteocytes sense and respond to mechanical loads, and they are also

Time Course of Peri-Implant Bone Regeneration around Loaded and Unloaded Implants in a Rat Model

PubMed Central

Jariwala, Shailly H.; Wee, Hwabok; Roush, Evan P.; Whitcomb, Tiffany L.; Murter, Christopher; Kozlansky, Gery; Lakhtakia, Akhlesh; Kunselman, Allen R.; Donahue, Henry J.; Armstrong, April D.; Lewis, Gregory S.

2018-01-01

The time-course of cancellous bone regeneration surrounding mechanically loaded implants affects implant fixation, and is relevant to determining optimal rehabilitation protocols following orthopaedic surgeries. We investigated the influence of controlled mechanical loading of titanium-coated polyether-ether ketone (PEEK) implants on osseointegration using time-lapsed, non-invasive, in vivo micro-computed tomography (micro-CT) scans. Implants were inserted into proximal tibial metaphyses of both limbs of eight female Sprague-Dawley rats. External cyclic loading (60 μm or 100 μm displacement, 1 Hz, 60 seconds) was applied every other day for 14 days to one implant in each rat, while implants in contralateral limbs served as the unloaded controls. Hind limbs were imaged with high-resolution micro-CT (12.5 μm voxel size) at 2, 5, 9, and 12 days post-surgery. Trabecular changes over time were detected by 3D image registration allowing for measurements of bone-formation rate (BFR) and bone-resorption rate (BRR). At day 9, mean %BV/TV for loaded and unloaded limbs were 35.5 ± 10.0 % and 37.2 ± 10.0 %, respectively, and demonstrated significant increases in bone volume compared to day 2. BRR increased significantly after day 9. No significant differences between bone volumes, BFR, and BRR were detected due to implant loading. Although not reaching significance (p = 0.16), an average 119 % increase in pull-out strength was measured in the loaded implants. PMID:27381807

Responds of Bone Cells to Microgravity: Ground-Based Research

NASA Astrophysics Data System (ADS)

Zhang, Jian; Li, Jingbao; Xu, Huiyun; Yang, Pengfei; Xie, Li; Qian, Airong; Zhao, Yong; Shang, Peng

2015-11-01

Severe loss of bone occurs due to long-duration spaceflight. Mechanical loading stimulates bone formation, while bone degradation happens under mechanical unloading. Bone remodeling is a dynamic process in which bone formation and bone resorption are tightly coupled. Increased bone resorption and decreased bone formation caused by reduced mechanical loading, generally result in disrupted bone remodeling. Bone remodeling is orchestrated by multiple bone cells including osteoblast, osteocyte, osteoclast and mesenchymal stem cell. It is yet not clear that how these bone cells sense altered gravity, translate physical stimulus into biochemical signals, and then regulate themselves structurally and functionally. In this paper, studies elucidating the bioeffects of microgravity on bone cells (osteoblast, osteocyte, osteoclast, mesenchymal stem cell) using various platforms including spaceflight and ground-based simulated microgravity were summarized. Promising gravity-sensitive signaling pathways and protein molecules were proposed.

Evaluation of the protective effects of curcuminoid (curcumin and bisdemethoxycurcumin)-loaded liposomes against bone turnover in a cell-based model of osteoarthritis.

PubMed

Yeh, Chih-Chang; Su, Yu-Han; Lin, Yu-Jhe; Chen, Pin-Jyun; Shi, Chung-Sheng; Chen, Cheng-Nan; Chang, Hsin-I

2015-01-01

Curcumin (Cur) and bisdemethoxycurcumin (BDMC), extracted from Curcuma longa, are poorly water-soluble polyphenol compounds that have shown anti-inflammatory potential for the treatment of osteoarthritis. To increase cellular uptake of Cur and BDMC in bone tissue, soybean phosphatidylcholines were used for liposome formulation. In this study, curcuminoid (Cur and BDMC)-loaded liposomes were characterized in terms of particle size, encapsulation efficiency, liposome stability, and cellular uptake. The results show that there is about 70% entrapment efficiency of Cur and BDMC in liposomes and that particle sizes are stable after liposome formation. Both types of liposome can inhibit macrophage inflammation and osteoclast differential activities. In comparison with free drugs (Cur and BDMC), curcuminoid-loaded liposomes were less cytotoxic and expressed high cellular uptake of the drugs. Of note is that Cur-loaded liposomes can prevent liposome-dependent inhibition of osteoblast differentiation and mineralization, but BDMC-loaded liposomes could not. With interleukin (IL)-1β stimulation, curcuminoid-loaded liposomes can successfully downregulate the expression of inflammatory markers on osteoblasts, and show a high osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) ratio to prevent osteoclastogenesis. In the present study, we demonstrated that Cur and BDMC can be successfully encapsulated in liposomes and can reduce osteoclast activity and maintain osteoblast functions. Therefore, curcuminoid-loaded liposomes may slow osteoarthritis progression.

[Numeric simulation of functional remodeling of the anterior alveolar bone].

PubMed

Wang, Wei-feng; Xin, Hai-tao; Zang, Shun-lai; Ding, Jie

2012-04-01

To study the remodeling of the anterior alveolar bone with parodontium under physiology loading using finite element method (FEM) and theory of bone remodeling. A FEM model of the maxillary central incisor with parodontium was established, and the change of bone density during the remodeling of alveolar bone was investigated under physiology loading (60 - 150 N) based on the theory of bone remodeling about strain energy density (SED). The finite element analysis software Abaqus user material subroutine (UMAT) were used. With the increase of physiology loading, the pressure stress on the buccal cervical margin increased gradually while the density was decreased gradually. The cortical bone was lower than its initial density 1.74 g/cm(3), which was 1.74 - 1.63 g/cm(3). The density of cancellous bone was 0.90 - 0.77 g/cm(3), which was lower than its intial density 0.90 g/cm(3). The lingual cervical margin was under tensile stress which also increased with loading, the density had no significant change. When the achieve to 120 N, the density of cortical bone was 1.74 - 1.73 g/cm(3). No significant change was found in the cancellous bone. The simulation of the perodontium remodeling is achieved and proved to be effective by the relevant research based on the method of the study. And the result will be helpful to form the basis of analysis bone remodeling process and predict the results in the clinical work.

A mathematical multiscale model of bone remodeling, accounting for pore space-specific mechanosensation.

PubMed

Pastrama, Maria-Ioana; Scheiner, Stefan; Pivonka, Peter; Hellmich, Christian

2018-02-01

While bone tissue is a hierarchically organized material, mathematical formulations of bone remodeling are often defined on the level of a millimeter-sized representative volume element (RVE), "smeared" over all types of bone microstructures seen at lower observation scales. Thus, there is no explicit consideration of the fact that the biological cells and biochemical factors driving bone remodeling are actually located in differently sized pore spaces: active osteoblasts and osteoclasts can be found in the vascular pores, whereas the lacunar pores host osteocytes - bone cells originating from former osteoblasts which were then "buried" in newly deposited extracellular bone matrix. We here propose a mathematical description which considers size and shape of the pore spaces where the biological and biochemical events take place. In particular, a previously published systems biology formulation, accounting for biochemical regulatory mechanisms such as the rank-rankl-opg pathway, is cast into a multiscale framework coupled to a poromicromechanical model. The latter gives access to the vascular and lacunar pore pressures arising from macroscopic loading. Extensive experimental data on the biological consequences of this loading strongly suggest that the aforementioned pore pressures, together with the loading frequency, are essential drivers of bone remodeling. The novel approach presented here allows for satisfactory simulation of the evolution of bone tissue under various loading conditions, and for different species; including scenarios such as mechanical dis- and overuse of murine and human bone, or in osteocyte-free bone. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative limb bone loading in the humerus and femur of the tiger salamander: testing the 'mixed-chain' hypothesis for skeletal safety factors.

PubMed

Kawano, Sandy M; Economy, D Ross; Kennedy, Marian S; Dean, Delphine; Blob, Richard W

2016-02-01

Locomotion imposes some of the highest loads upon the skeleton, and diverse bone designs have evolved to withstand these demands. Excessive loads can fatally injure organisms; however, bones have a margin of extra protection, called a 'safety factor' (SF), to accommodate loads that are higher than normal. The extent to which SFs might vary amongst an animal's limb bones is unclear. If the limbs are likened to a chain composed of bones as 'links', then similar SFs might be expected for all limb bones because failure of the system would be determined by the weakest link, and extra protection in other links could waste energetic resources. However, Alexander proposed that a 'mixed-chain' of SFs might be found amongst bones if: (1) their energetic costs differ, (2) some elements face variable demands, or (3) SFs are generally high. To test whether such conditions contribute to diversity in limb bone SFs, we compared the biomechanical properties and locomotor loading of the humerus and femur in the tiger salamander (Ambystoma tigrinum). Despite high SFs in salamanders and similar sizes of the humerus and femur that would suggest similar energetic costs, the humerus had lower bone stresses, higher mechanical hardness and larger SFs. SFs were greatest in the anatomical regions where yield stresses were highest in the humerus and lowest in the femur. Such intraspecific variation between and within bones may relate to their different biomechanical functions, providing insight into the emergence of novel locomotor capabilities during the invasion of land by tetrapods. © 2016. Published by The Company of Biologists Ltd.

Integration of a Finite Element Model with the DAP Bone Remodeling Model to Characterize Bone Response to Skeletal Loading

NASA Technical Reports Server (NTRS)

Werner, Christopher R.; Mulugeta, Lealem; Myers, J. G.; Pennline, J. A.

2015-01-01

NASA's Digital Astronaut Project (DAP) has developed a bone remodeling model that has been validated for predicting volumetric bone mineral density (vBMD) changes of trabecular and cortical bone in the absence of mechanical loading. The model was recently updated to include skeletal loading from exercise and free living activities to maintain healthy bone using a new daily load stimulus (DLS). This new formula was developed based on an extensive review of existing DLS formulas, as discussed in the abstract by Pennline et al. The DLS formula incorporated into the bone remodeling model utilizes strains and stress calculated from finite element model (FEM) of the bone region of interest. The proximal femur was selected for the initial application of the DLS formula, with a specific focus on the femoral neck. METHODS: The FEM was generated from CAD geometry of a femur using de-identified CT data. The femur was meshed using linear tetrahedral elements Figure (1) with higher mesh densities in the femoral neck region, which is the primary region of interest for the initial application of the DLS formula in concert with the DAP bone remodeling model. Nodal loads were applied to the femoral head and the greater trochanter and the base of the femur was held fixed. An L2 norm study was conducted to reduce the length of the femoral shaft without significantly impacting the stresses in the femoral neck. The material properties of the FEM of the proximal femur were separated between cortical and trabecular regions to work with the bone remodeling model. Determining the elements with cortical material properties in the FEM was based off of publicly available CT hip scans [4] that were segmented, cleaned, and overlaid onto the FEM.

Pressure and shear stress in trabecular bone marrow during whole bone loading.

PubMed

Metzger, Thomas A; Schwaner, Stephen A; LaNeve, Anthony J; Kreipke, Tyler C; Niebur, Glen L

2015-09-18

Skeletal adaptation to mechanical loading is controlled by mechanobiological signaling. Osteocytes are highly responsive to applied strains, and are the key mechanosensory cells in bone. However, many cells residing in the marrow also respond to mechanical cues such as hydrostatic pressure and shear stress, and hence could play a role in skeletal adaptation. Trabecular bone encapsulates marrow, forming a poroelastic solid. According to the mechanical theory, deformation of the pores induces motion in the fluid-like marrow, resulting in pressure and velocity gradients. The latter results in shear stress acting between the components of the marrow. To characterize the mechanical environment of trabecular bone marrow in situ, pore pressure within the trabecular compartment of whole porcine femurs was measured with miniature pressure transducers during stress-relaxation and cyclic loading. Pressure gradients ranging from 0.013 to 0.46 kPa/mm were measured during loading. This range was consistent with calculated pressure gradients from continuum scale poroelastic models with the same permeability. Micro-scale computational fluid dynamics models created from computed tomography images were used to calculate the micromechanical stress in the marrow using the measured pressure differentials as boundary conditions. The volume averaged shear stress in the marrow ranged from 1.67 to 24.55 Pa during cyclic loading, which exceeds the mechanostimulatory threshold for mesenchymal lineage cells. Thus, the loading of bone through activities of daily living may be an essential component of bone marrow health and mechanobiology. Additional studies of cell-level interactions during loading in healthy and disease conditions will provide further incite into marrow mechanobiology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Estradiol-loaded PLGA nanoparticles for improving low bone mineral density of cancellous bone caused by osteoporosis: Application of enhanced charged nanoparticles with iontophoresis.

PubMed

Takeuchi, Issei; Kobayashi, Shiori; Hida, Yukari; Makino, Kimiko

2017-07-01

Postmenopausal osteoporosis among older women, which occurs by an ovarian hormone deficiency, is one of the major public health problems. 17 β-estradiol (E2) is used to prevent and treat this disease as a drug of hormone replacement therapy. In oral administration, E2 is significantly affected by first-pass hepatic metabolism, and high dose administration must be needed to obtain drug efficacy. Therefore, alternative administration route is needed, and we have focused on the transdermal drug delivery system. In this study, we have prepared E2-loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles for osteoporosis by using a combination of an antisolvent diffusion method with preferential solvation. The average particle diameter of the nanoparticles was 110.0±41.0nm and the surface charge number density was 82 times higher than that of conventional E2-loaded PLGA nanoparticles. Therapeutic evaluation of E2-loaded PLGA nanoparticles was carried out using ovariectomized female rats. Therapeutic efficacy was evaluated to measure bone mineral density of cancellous bone using an X-ray CT system. When the E2-loaded PLGA nanoparticles were administrated once a week, bone mineral density was significantly higher than that of the non-treated group at 60days after the start of treatment. Also, in the group administered this nanoparticle twice a week, the bone mineral density increased significantly at 45days after the start of treatment. From these results, it was revealed that E2-loaded PLGA nanoparticles with iontophoresis were useful to recover bone mineral density of cancellous bone, and it was also suggested that they extend the dosing interval of E2. Copyright © 2017 Elsevier B.V. All rights reserved.

Associations of physical activity duration, frequency, and load with volumetric BMD, geometry, and bone strength in young girls

PubMed Central

Farr, Joshua N.; Blew, Robert M.; Lee, Vinson R.; Lohman, Timothy G.; Going, Scott B.

2011-01-01

Purpose This study evaluated the associations of physical activity (PA) duration, frequency, load, and their interaction (total PA score = duration × frequency × load) with volumetric bone mineral density, geometry, and indices of bone strength in young girls. Methods 465 girls (aged 8–13 years) completed a past year physical activity questionnaire (PYPAQ) which inquires about the frequency (days/week) and duration (average minutes/session) of leisure-time PA and sports. Load (peak strain score) values were assigned to each activity based on ground reaction forces. Peripheral quantitative computed tomography was used to assess bone parameters at metaphyseal and diaphyseal sites of the femur and tibia of the non-dominant leg. Results Correlations across all skeletal sites between PA duration, frequency, load and periosteal circumference (PC), bone strength index (BSI), and strength-strain index (SSI) were significant (p ≤ 0.05), although low (0.10–0.17). A 2.7–3.7% greater PC across all skeletal sites was associated with a high compared to a low PYPAQ score. Also, a high PYPAQ score was associated with greater BSI (6.5–8.7%) at metaphyseal sites and SSI (7.5–8.1%) at diaphyseal sites of the femur and tibia. The effect of a low PYPAQ score on bone geometric parameters and strength was greater than a high PYPAQ score. Conclusions PA duration, frequency, and load were all associated with bone geometry and strength, although their independent influences were modest and site specific. Low levels of PA may compromise bone development whereas high levels have only a small benefit over more average levels. PMID:20694457

Mechanical Signaling for Bone Modeling and Remodeling

PubMed Central

Robling, Alexander G.; Turner, Charles H.

2012-01-01

Proper development of the skeleton in utero and during growth requires mechanical stimulation. Loading results in adaptive changes in bone that strengthen bone structure. Bone’s adaptive response is regulated by the ability of resident bone cells to perceive and translate mechanical energy into a cascade of structural and biochemical changes within the cells — a process known as mechanotransduction. Mechanotransduction pathways are among the most anabolic in bone, and consequently, there is great interest in elucidating how mechanical loading produces its observed effects, including increased bone formation, reduced bone loss, changes in bone cell differentiation and lifespan, among others. A molecular understanding of these processes is developing, and with it comes a profound new insight into the biology of bone. In this article, we review the nature of the physical stimulus to which bone cells mount an adaptive response, including the identity of the sensor cells, their attributes and physical environment, and putative mechanoreceptors they express. Particular attention is allotted to the focal adhesion and Wnt signaling, in light of their emerging role in bone mechanotransduction. The cellular mechanisms for increased bone loss during disuse, and reduced bone loss during loading are considered. Finally, we summarize the published data on bone cell accommodation, whereby bone cells stop responding to mechanical signaling events. Collectively, these data highlight the complex yet finely orchestrated process of mechanically regulated bone homeostasis. PMID:19817708

Electromechanical Properties of Bone Tissue.

NASA Astrophysics Data System (ADS)

Regimbal, Raymond L.

Discrepancies between calculated and empirical properties of bone are thought to be due to a general lack of consideration for the extent and manner(s) with which bone components interact at the molecular level. For a bone component in physiological fluid or whenever two phases are in contact, there is a region between the bulk phases called the electrical double layer which is marked by a separation of electric charges. For the purpose of studying electrical double layer interactions, the method of particle microelectrophoresis was used to characterize bone and its major constituents on the basis of the net charge they bear when suspended in ionic media of physiological relevance. With the data presented as pH versus zeta (zeta ) potential, the figures reveal an isoelectric point (IEP) for bone mineral near pH 8.6, whereas intact and EDTA demineralized bone tissue both exhibit IEPs near pH 5.1. While these data demonstrate the potential for a significant degree of coulombic interaction between the bone mineral and organic constituent double layers, it was also observed that use of inorganic phosphate buffers, as a specific marker for bone mineral, resulted in (1) an immediate reversal, from positive to negative, of the bone mineral zeta potential (2) rendered the zeta potential of intact bone more negative in a manner linearly dependent on both time and temperature and (3) had no affect on demineralized bone (P < 0.01). In agreement with that shown in model protein-hydroxyapatite systems, it is suggested here that inorganic phosphate ions in solution compete with organic acid groups (e.g. carboxyl and phosphate of collagen, sialoprotein, ...) for positively charged sites on the bone mineral surface and effectively uncouple the bone mineral and organic phase double layers. Mechanically, this uncoupling is manifested as a loss of tissue rigidity when monitoring the midspan deflection of bone beams subject to constant load for a 3 day period. While it is thus demonstrated that the major inorganic and organic phases of bone are electromechanically coupled, a thermodynamic consideration of the data suggests that the nature of the bond is to preserve mineral and organic phase electroneutralities by participating in electrical double layer interactions. The results are discussed in terms of bone mechanical modeling, electrokinetic properties, aging, tissue-implant compatibility and the etiologies of bone pathologic conditions.

Skeletal Geometry and Indices of Bone Strength in Artistic Gymnasts

PubMed Central

Dowthwaite, Jodi N.; Scerpella, Tamara A.

2010-01-01

This review addresses bone geometry and indices of skeletal strength associated with exposure to gymnastic loading during growth. A brief background characterizes artistic gymnastics as a mechanical loading model and outlines densitometric techniques, skeletal outcomes and challenges in assessment of skeletal adaptation. The literature on bone geometric adaptation to gymnastic loading is sparse and consists of results for disparate skeletal sites, maturity phases, gender compositions and assessment methods, complicating synthesis of an overriding view. Furthermore, most studies assess only females, with little information on males and adults. Nonetheless, gymnastic loading during growth appears to yield significant enlargement of total and cortical bone geometry (+10 to 30%) and elevation of trabecular density (+20%) in the forearm, yielding elevated indices of skeletal strength (+20 to +50%). Other sites exhibit more moderate geometric and densitometric adaptations (5 to 15%). Mode of adaptation appears to be site-specific; some sites demonstrate marked periosteal and endosteal expansion, whereas other sites exhibit negligible or moderate periosteal expansion coupled with endocortical contraction. Further research is necessary to address sex-, maturity- and bone tissue-specific adaptation, as well as maintenance of benefits beyond loading cessation. PMID:19949278

Mechanical basis of bone strength: influence of bone material, bone structure and muscle action.

PubMed

Hart, N H; Nimphius, S; Rantalainen, T; Ireland, A; Siafarikas, A; Newton, R U

2017-09-01

This review summarises current understanding of how bone is sculpted through adaptive processes, designed to meet the mechanical challenges it faces in everyday life and athletic pursuits, serving as an update for clinicians, researchers and physical therapists. Bone's ability to resist fracture under the large muscle and locomotory forces it experiences during movement and in falls or collisions is dependent on its established mechanical properties, determined by bone's complex and multidimensional material and structural organisation. At all levels, bone is highly adaptive to habitual loading, regulating its structure according to components of its loading regime and mechanical environment, inclusive of strain magnitude, rate, frequency, distribution and deformation mode. Indeed, the greatest forces habitually applied to bone arise from muscular contractions, and the past two decades have seen substantial advances in our understanding of how these forces shape bone throughout life. Herein, we also highlight the limitations of in vivo methods to assess and understand bone collagen, and bone mineral at the material or tissue level. The inability to easily measure or closely regulate applied strain in humans is identified, limiting the translation of animal studies to human populations, and our exploration of how components of mechanical loading regimes influence mechanoadaptation.

A Flexible Method for Producing F.E.M. Analysis of Bone Using Open-Source Software

NASA Technical Reports Server (NTRS)

Boppana, Abhishektha; Sefcik, Ryan; Myers, Jerry G.; Lewandowski, Beth

2016-01-01

Individuals who experience decreases in load-bearing bone densities can be subject to a higher risk of bone fracture during daily activity. Astronauts may lose up to nine percent of their load-bearing bone density for every month they spend in space [1]. Because of this, specialized countermeasures reduce percent loss in bone density and reduce fracture risk upon returning to Earth. Astronauts will typically not be at risk for fracture during spaceflight, because of the lesser loads experienced in microgravity conditions. However, once back on Earth, astronauts have an increased risk for bone fracture as a result of weakened bone and return to 1G conditions [2]. It is therefore important to understand the significance of any bone density loss in addition to developing exercises in an attempt to limit losses in bone strength. NASA seeks to develop a deeper understanding of fracture risk through the development of a computational bone strength model to assess the bone fracture risk of astronauts pre-flight and post-flight. This study addresses the several key processes needed to develop such strength analyses using medical image processing and finite element modeling.

In vivo evaluation of a novel nanocomposite porous 3D scaffold in a rabbit model: histological analysis

PubMed Central

Mahmood, Saffanah Khuder; Razak, Intan-Shameha Abdul; Ghaji, Mustafa Saddam; Yusof, Loqman Mohamed; Mahmood, Zaid Khudhur; Rameli, Mohd Adha Bin P; Zakaria, Zuki Abu Bakar

2017-01-01

The healing of load-bearing segmental defects in long bones is a challenge due to the complex nature of the weight that affects the bone part and due to bending, shearing, axial, and torsional forces. An innovative porous 3D scaffolds implant of CaCO3 aragonite nanocomposite derived from cockle shell was advanced for substitute bone solely for load-bearing cases. The biomechanical characteristics of such materials were designed to withstand cortical bone strength. In promoting bone growth to the implant material, an ideal surface permeability was formed by means of freeze drying and by adding copolymers to the materials. The properties of coating and copolymers supplement were also assessed for bone-implant connection resolutions. To examine the properties of the material in advanced biological system, an experimental trial in an animal model was carried out. Critical sized defect of bone was created in rabbit’s radial bone to assess the material for a load-bearing application with a short and extended period assessment with histological evaluation of the incorporated implanted material to the bone of the host. Trials in animal models proved that the material has the capability of enduring load-bearing conditions for long-term use devoid of breaking or generating stress that affects the host bone. Histological examination further confirmed the improved integration of the implanted materials to the host bone with profound bone development into and also above the implanted scaffold, which was attained with negligible reaction of the tissues to a foreign implanted material. PMID:29238193

[Research advances of fluid bio-mechanics in bone].

PubMed

Chen, Zebin; Huo, Bo

2017-04-01

It has been found for more than one century that when experiencing mechanical loading, the structure of bone will adapt to the changing mechanical environment, which is called bone remodeling. Bone remodeling is charaterized as two processes of bone formation and bone resorption. A large number of studies have confirmed that the shear stress is resulted from interstitial fluid flow within bone cavities under mechanical loading and it is the key factor of stimulating the biological responses of bone cells. This review summarizes the major research progress during the past years, including the biological response of bone cells under fluid flow, the pressure within bone cavities, the theoretical modeling, numerical simulation and experiments about fluid flow within bone, and finally analyzes and predicts the possible tendency in this field in the future.

Bone Marrow Mesenchymal Stem Cells Loaded With an Oncolytic Adenovirus Suppress the Anti-adenoviral Immune Response in the Cotton Rat Model

PubMed Central

Ahmed, Atique U; Rolle, Cleo E; Tyler, Matthew A; Han, Yu; Sengupta, Sadhak; Wainwright, Derek A; Balyasnikova, Irina V; Ulasov, Ilya V; Lesniak, Maciej S

2010-01-01

Oncolytic adenoviral virotherapy is an attractive treatment modality for cancer. However, following intratumoral injections, oncolytic viruses fail to efficiently migrate away from the injection site and are rapidly cleared by the immune system. We have previously demonstrated enhanced viral delivery and replicative persistence in vivo using human bone marrow–derived mesenchymal stem cells (MSCs) as delivery vehicles. In this study, we evaluated the immune response to adenovirus (Ad)-loaded MSCs using the semipermissive cotton rat (CR) model. First, we isolated MSCs from CR bone marrow aspirates. Real-time quantitative PCR analysis revealed that CR MSCs supported the replication of Ads in vitro. Moreover, we observed similar levels of suppression of T-cell proliferation in response to mitogenic stimulation, by MSCs alone and virus-loaded MSCs. Additionally, we found that MSCs suppressed the production of interferon-γ (IFN-γ) by activated T cells. In our in vivo model, CR MSCs enhanced the dissemination and persistence of Ad, compared to virus injection alone. Collectively, our data suggest that the use of MSCs as a delivery strategy for oncolytic Ad potentially offers a myriad of benefits, including improved delivery, enhanced dissemination, and increased persistence of viruses via suppression of the antiviral immune response. PMID:20588259

Load Bearing Equipment for Bone and Muscle

NASA Technical Reports Server (NTRS)

Shackelford, Linda; Griffith, Bryan

2015-01-01

Resistance exercise on ISS has proven effective in maintaining bone mineral density and muscle mass. Exploration missions require exercise with similar high loads using equipment with less mass and volume and greater safety and reliability than resistance exercise equipment used on ISS (iRED, ARED, FWED). Load Bearing Equipment (LBE) uses each exercising person to create and control the load to the partner.

In Vivo Axial Loading of the Mouse Tibia

PubMed Central

Melville, Katherine M.; Robling, Alexander G.

2015-01-01

Summary Non-invasive methods to apply controlled, cyclic loads to the living skeleton are used as an anabolic agent to stimulate new bone formation in adults and enhance bone mass accrual in growing animals. These methods are also invaluable for understanding bone signaling pathways. Our focus here is on a particular loading model: in vivo axial compression of the mouse tibia. An advantage of loading the tibia is that changes are present in both the cancellous envelope of the proximal tibia and the cortical bone of the tibial diaphysis. To load the tibia of the mouse axially in vivo, a cyclic compressive load is applied up to five times a week to a single tibia per mouse for a duration lasting from 1 day to 6 weeks. With the contralateral limb as an internal control, the anabolic response of the skeleton to mechanical stimuli can be studied in a pairwise experimental design. Here, we describe the key parameters that must be considered before beginning an in vivo mouse tibial loading experiment, including methods for in vivo strain gauging of the tibial midshaft, and then we describe general methods for loading the mouse tibia for an experiment lasting multiple days. PMID:25331046

Effects of immediate and delayed loading on peri-implant trabecular structures: a cone beam CT evaluation.

PubMed

Huang, Yan; Van Dessel, Jeroen; Liang, Xin; Depypere, Maarten; Zhong, Weijian; Ma, Guowu; Lambrichts, Ivo; Maes, Frederik; Jacobs, Reinhilde

2014-12-01

To develop a method for characterizing trabecular bone microarchitecture using cone beam computed tomography (CBCT) and to evaluate trabecular bone changes after rehabilitation using immediate versus delayed implant protocols. Six mongrel dogs randomly received 27 titanium implants in the maxillary incisor or mandibular premolar areas, following one of four protocols: (1) normal extraction socket healing; (2) immediate implant placement and immediate loading; (3) delayed implant placement and delayed loading; (4) delayed implant placement and immediate loading. The animals were euthanized at 8 weeks, and block biopsies were scanned using high resolution CBCT. Standard bone structural variables were assessed in coronal, middle, and apical levels. Coronal and middle regions had more compact, more platelike, and thicker trabeculae. Protocols (2), (3), and (4) had significantly higher values (p < 0.001) than protocol (1) for bone surface density, bone surface volume ratio, and connectivity density, while significantly lower values (p < 0.001) were found for trabecular separation and fractal dimension. However, protocols (2), (3), and (4) did not show significantly different bone remodeling. Compared with normal extraction healing, the implant protocols have an improved bone structural integration. Results do not suggest a different bone remodeling pattern when a delayed versus an immediate implant protocol is used. © 2013 Wiley Periodicals, Inc.

Bone and hormonal changes induced by skeletal unloading in the mature male rat

NASA Technical Reports Server (NTRS)

Dehority, W.; Halloran, B. P.; Bikle, D. D.; Curren, T.; Kostenuik, P. J.; Wronski, T. J.; Shen, Y.; Rabkin, B.; Bouraoui, A.; Morey-Holton, E.

1999-01-01

To determine whether the rat hindlimb elevation model can be used to study the effects of spaceflight and loss of gravitational loading on bone in the adult animal, and to examine the effects of age on bone responsiveness to mechanical loading, we studied 6-mo-old rats subjected to hindlimb elevation for up to 5 wk. Loss of weight bearing in the adult induced a mild hypercalcemia, diminished serum 1,25-dihydroxyvitamin D, decreased vertebral bone mass, and blunted the otherwise normal increase in femoral mass associated with bone maturation. Unloading decreased osteoblast numbers and reduced periosteal and cancellous bone formation but had no effect on bone resorption. Mineralizing surface, mineral apposition rate, and bone formation rate decreased during unloading. Our results demonstrate the utility of the adult rat hindlimb elevation model as a means of simulating the loss of gravitational loading on the skeleton, and they show that the effects of nonweight bearing are prolonged and have a greater relative effect on bone formation in the adult than in the young growing animal.

Identification of a constitutive law for trabecular bone samples under remodeling in the framework of irreversible thermodynamics

NASA Astrophysics Data System (ADS)

Louna, Zineeddine; Goda, Ibrahim; Ganghoffer, Jean-François

2018-01-01

We construct in the present paper constitutive models for bone remodeling based on micromechanical analyses at the scale of a representative unit cell (RUC) including a porous trabecular microstructure. The time evolution of the microstructure is simulated as a surface remodeling process by relating the surface growth remodeling velocity to a surface driving force incorporating a (surface) Eshelby tensor. Adopting the framework of irreversible thermodynamics, a 2D constitutive model based on the setting up of the free energy density and a dissipation potential is identified from FE simulations performed over a unit cell representative of the trabecular architecture obtained from real bone microstructures. The static and evolutive effective properties of bone at the scale of the RUC are obtained by combining a methodology for the evaluation of the average kinematic and static variables over a prototype unit cell and numerical simulations with controlled imposed first gradient rates. The formulated effective growth constitutive law at the scale of the homogenized set of trabeculae within the RUC is of viscoplastic type and relates the average growth strain rate to the homogenized stress tensor. The postulated model includes a power law function of an effective stress chosen to depend on the first and second stress invariants. The model coefficients are calibrated from a set of virtual testing performed over the RUC subjected to a sequence of loadings. Numerical simulations show that overall bone growth does not show any growth kinematic hardening. The obtained results quantify the strength and importance of different types of external loads (uniaxial tension, simple shear, and biaxial loading) on the overall remodeling process and the development of elastic deformations within the RUC.

Parafunctional loading and occlusal device on stress distribution around implants: A 3D finite element analysis.

PubMed

Borges Radaelli, Manuel Tomás; Idogava, Henrique Takashi; Spazzin, Aloisio Oro; Noritomi, Pedro Yoshito; Boscato, Noéli

2018-04-30

An occlusal device is frequently recommended for patients with bruxism to protect implant-supported restorations and prevent marginal bone loss. Scientific evidence to support this treatment is lacking. The purpose of this 3-dimensional (3D) finite element study was to evaluate the influence of an acrylic resin occlusal device, implant length, and insertion depth on stress distribution with functional and parafunctional loadings. Computer-aided design software was used to construct 8 models. The models were composed of a mandibular bone section including the second premolar and first and second molars. Insertion depths (bone level and 2 mm subcrestal) were simulated at the first molar. Three natural antagonist maxillary teeth and the placement or not of an occlusal device were simulated. Functional (200-N axial and 10-N oblique) and parafunctional (1000-N axial and 25-N oblique) forces were applied. Finite element analysis (FEA) was used to determine the maximum principal stress for the cortical and trabecular bone and von Mises for implant and prosthetic abutment. Stress concentration was observed at the abutment-implant and the implant-bone interfaces. Occlusal device placement changed the pattern of stress distribution and reduced stress levels from parafunctional loading in all structures, except in the trabecular bone. Implants with subcrestal insertion depths had reduced stress at the implant-abutment interface and cortical bone around the implant abutment, while the stress increased in the bone in contact with the implant. Parafunctional loading increased the stress levels in all structures when compared with functional loading. An occlusal device resulted in the lowest stress levels at the abutment and implant and the most favorable stress distribution between the cortical and trabecular bone. Under parafunctional loading, an occlusal device was more effective in reducing stress distribution for longer implants inserted at bone level. Subcrestally, implant insertion yielded the most favorable biomechanical conditions at the abutment-implant interface and at the coronal surface of the cortical bone, mainly when there was no occlusal device. Copyright © 2018 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Mechanical torque measurement in the proximal femur correlates to failure load and bone mineral density ex vivo.

PubMed

Grote, Stefan; Noeldeke, Tatjana; Blauth, Michael; Mutschler, Wolf; Bürklein, Dominik

2013-06-07

Knowledge of local bone quality is essential for surgeons to determine operation techniques. A device for intraoperative measurement of local bone quality has been developed by the AO-Research Foundation (Densi - Probe®). We used this device to experimentally measure peak breakaway torque of trabecular bone in the proximal femur and correlated this with local bone mineral density (BMD) and failure load. Bone mineral density of 160 cadaver femurs was measured by ex situ dualenergy X-ray absorptiometry. The failure load of all femurs was analyzed by side-impact analysis. Femur fractures were fixed and mechanical peak torque was measured with the DensiProbe® device. Correlation was calculated whereas correlation coefficient and significance was calculated by Fisher's Ztransformation. Moreover, linear regression analysis was carried out. The unpaired Student's t-test was used to assess the significance of differences. The Ward triangle region had the lowest BMD with 0.511 g/cm(2) (±0.17 g/cm(2)), followed by the upper neck region with 0.546 g/cm(2) (±0.16 g/cm(2)), trochanteric region with 0.685 g/cm(2) (±0.19 g/cm(2)) and the femoral neck with 0.813 g/cm(2) (±0.2 g/cm(2)). Peak torque of DensiProbe® in the femoral head was 3.48 Nm (±2.34 Nm). Load to failure was 4050.2 N (±1586.7 N). The highest correlation of peak torque measured by Densi Probe® and load to failure was found in the femoral neck (r=0.64, P<0.001). The overall correlation of mechanical peak torque with T-score was r=0.60 (P<0.001). A correlation was found between mechanical peak torque, load to failure of bone and BMD in vitro. Trabecular strength of bone and bone mineral density are different aspects of bone strength, but a correlation was found between them. Mechanical peak torque as measured may contribute additional information about bone strength, especially in the perioperative testing.

Design of calcium phosphate ceramics for drug delivery applications in bone diseases: A review of the parameters affecting the loading and release of the therapeutic substance.

PubMed

Parent, Marianne; Baradari, Hiva; Champion, Eric; Damia, Chantal; Viana-Trecant, Marylène

2017-04-28

Effective treatment of critical-size defects is a key challenge in restorative surgery of bone. The strategy covers the implantation of biocompatible, osteoconductive, bioactive and biodegradable devices which (1) well interact with native tissue, mimic multi-dimensional and hierarchical structure of bone and (2) are able to enhance bone repair, treating post implantation pathologies or bone diseases by local delivery of therapeutic agents. Among different options, calcium phosphate biomaterials are found to be attractive choices, due to their excellent biocompatibility, customisable bioactivity and biodegradability. Several approaches have been established to enhance this material ability to be loaded with a therapeutic agent, in order to obtain an in situ controlled release that meets the clinical needs. This article reviews the most important factors influencing on both drug loading and release capacity of porous calcium phosphate bone substitutes. Characteristics of the carrier, drug/carrier interactions, experimental conditions of drug loading and evaluation of drug delivery are considered successively. Copyright © 2017 Elsevier B.V. All rights reserved.

Measurement of Strain Distributions in Mouse Femora with 3D-Digital Speckle Pattern Interferometry

PubMed Central

Yang, Lianxiang; Zhang, Ping; Liu, Sheng; Samala, Praveen R; Su, Min; Yokota, Hiroki

2007-01-01

Bone is a mechanosensitive tissue that adapts its mass, architecture and mechanical properties to external loading. Appropriate mechanical loads offer an effective means to stimulate bone remodeling and prevent bone loss. A role of in situ strain in bone is considered essential in enhancement of bone formation, and establishing a quantitative relationship between 3D strain distributions and a rate of local bone formation is important. Digital speckle pattern interferometry (DSPI) can achieve whole-field, non-contacting measurements of microscopic deformation for high-resolution determination of 3D strain distributions. However, the current system does not allow us to derive accurate strain distributions because of complex surface contours inherent to biological samples. Through development of a custom-made piezoelectric loading device as well as a new DSPI-based force calibration system, we built an advanced DSPI system and integrated local contour information to deformation data. Using a mouse femur in response to a knee loading modality as a model system, we determined 3D strain distributions and discussed effectiveness and limitations of the described system. PMID:18670581

Fiber glass-bioactive glass composite for bone replacing and bone anchoring implants.

PubMed

Vallittu, Pekka K; Närhi, Timo O; Hupa, Leena

2015-04-01

Although metal implants have successfully been used for decades, devices made out of metals do not meet all clinical requirements, for example, metal objects may interfere with some new medical imaging systems, while their stiffness also differs from natural bone and may cause stress-shielding and over-loading of bone. Peer-review articles and other scientific literature were reviewed for providing up-dated information how fiber-reinforced composites and bioactive glass can be utilized in implantology. There has been a lot of development in the field of composite material research, which has focused to a large extent on biodegradable composites. However, it has become evident that biostable composites may also have several clinical benefits. Fiber reinforced composites containing bioactive glasses are relatively new types of biomaterials in the field of implantology. Biostable glass fibers are responsible for the load-bearing capacity of the implant, while the dissolution of the bioactive glass particles supports bone bonding and provides antimicrobial properties for the implant. These kinds of combination materials have been used clinically in cranioplasty implants and they have been investigated also as oral and orthopedic implants. The present knowledge suggests that by combining glass fiber-reinforced composite with particles of bioactive glass can be used in cranial implants and that the combination of materials may have potential use also as other types of bone replacing and repairing implants. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

New methodology for evaluating osteoclastic activity induced by orthodontic load

PubMed Central

ARAÚJO, Adriele Silveira; FERNANDES, Alline Birra Nolasco; MACIEL, José Vinicius Bolognesi; NETTO, Juliana de Noronha Santos; BOLOGNESE, Ana Maria

2015-01-01

Orthodontic tooth movement (OTM) is a dynamic process of bone modeling involving osteoclast-driven resorption on the compression side. Consequently, to estimate the influence of various situations on tooth movement, experimental studies need to analyze this cell. Objectives The aim of this study was to test and validate a new method for evaluating osteoclastic activity stimulated by mechanical loading based on the fractal analysis of the periodontal ligament (PDL)-bone interface. Material and Methods The mandibular right first molars of 14 rabbits were tipped mesially by a coil spring exerting a constant force of 85 cN. To evaluate the actual influence of osteoclasts on fractal dimension of bone surface, alendronate (3 mg/Kg) was injected weekly in seven of those rabbits. After 21 days, the animals were killed and their jaws were processed for histological evaluation. Osteoclast counts and fractal analysis (by the box counting method) of the PDL-bone interface were performed in histological sections of the right and left sides of the mandible. Results An increase in the number of osteoclasts and in fractal dimension after OTM only happened when alendronate was not administered. Strong correlation was found between the number of osteoclasts and fractal dimension. Conclusions Our results suggest that osteoclastic activity leads to an increase in bone surface irregularity, which can be quantified by its fractal dimension. This makes fractal analysis by the box counting method a potential tool for the assessment of osteoclastic activity on bone surfaces in microscopic examination. PMID:25760264

The Extravehicular Suit Impact Load Attenuation Study for Use in Astronaut Bone Fracture Prediction

NASA Technical Reports Server (NTRS)

Lewandowski, Beth E.; Gilkey, Kelly M.; Sulkowski, Christina M.; Samorezov, Sergey; Myers, Jerry G.

2011-01-01

The NASA Integrated Medical Model (IMM) assesses the risk, including likelihood and impact of occurrence, of all credible in-flight medical conditions. Fracture of the proximal femur is a traumatic injury that would likely result in loss of mission if it were to happen during spaceflight. The low gravity exposure causes decreases in bone mineral density which heightens the concern. Researchers at the NASA Glenn Research Center have quantified bone fracture probability during spaceflight with a probabilistic model. It was assumed that a pressurized extravehicular activity (EVA) suit would attenuate load during a fall, but no supporting data was available. The suit impact load attenuation study was performed to collect analogous data. METHODS: A pressurized EVA suit analog test bed was used to study how the offset, defined as the gap between the suit and the astronaut s body, impact load magnitude and suit operating pressure affects the attenuation of impact load. The attenuation data was incorporated into the probabilistic model of bone fracture as a function of these factors, replacing a load attenuation value based on commercial hip protectors. RESULTS: Load attenuation was more dependent on offset than on pressurization or load magnitude, especially at small offsets. Load attenuation factors for offsets between 0.1 - 1.5 cm were 0.69 +/- 0.15, 0.49 +/- 0.22 and 0.35 +/- 0.18 for mean impact forces of 4827, 6400 and 8467 N, respectively. Load attenuation factors for offsets of 2.8 - 5.3 cm were 0.93 +/- 0.2, 0.94 +/- 0.1 and 0.84 +/- 0.5, for the same mean impact forces. Reductions were observed in the 95th percentile confidence interval of the bone fracture probability predictions. CONCLUSIONS: The reduction in uncertainty and improved confidence in bone fracture predictions increased the fidelity and credibility of the fracture risk model and its benefit to mission design and operational decisions.

Proliferation, differentiation and gene expression of osteoblasts in boron-containing associated with dexamethasone deliver from mesoporous bioactive glass scaffolds.

PubMed

Wu, Chengtie; Miron, Richard; Sculean, Anton; Kaskel, Stefan; Doert, Thomas; Schulze, Renate; Zhang, Yufeng

2011-10-01

Boron is one of the trace elements in the human body which plays an important role in bone growth. Porous mesopore bioactive glass (MBG) scaffolds are proposed as potential bone regeneration materials due to their excellent bioactivity and drug-delivery ability. The aims of the present study were to develop boron-containing MBG (B-MBG) scaffolds by sol-gel method and to evaluate the effect of boron on the physiochemistry of B-MBG scaffolds and the response of osteoblasts to these scaffolds. Furthermore, the effect of dexamethasone (DEX) delivery in B-MBG scaffold system was investigated on the proliferation, differentiation and bone-related gene expression of osteoblasts. The composition, microstructure and mesopore properties (specific surface area, nano-pore volume and nano-pore distribution) of B-MBG scaffolds have been characterized. The effect of boron contents and large-pore porosity on the loading and release of DEX in B-MBG scaffolds were also investigated. The results have shown that the incorporation of boron into MBG scaffolds slightly decreases the specific surface area and pore volume, but maintains well-ordered mesopore structure and high surface area and nano-pore volume compared to non-mesopore bioactive glass. Boron contents in MBG scaffolds did not influence the nano-pore size distribution or the loading and release of DEX. B-MBG scaffolds have the ability to maintain a sustained release of DEX in a long-term span. Incorporating boron into MBG glass scaffolds led to a controllable release of boron ions and significantly improved the proliferation and bone-related gene expression (Col I and Runx2) of osteoblasts. Furthermore, the sustained release of DEX from B-MBG scaffolds significantly enhanced alkaline phosphatase (ALP) activity and gene expressions (Col I, Runx2, ALP and BSP) of osteoblasts. These results suggest that boron plays an important role in enhancing osteoblast proliferation in B-MBG scaffold system and DEX-loaded B-MBG scaffolds show great potential as a release system to enhance osteogenic property for bone tissue engineering application. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

In situ femoral dual-energy X-ray absorptiometry related to ash weight, bone size and density, and its relationship with mechanical failure loads of the proximal femur.

PubMed

Lochmüller, E M; Miller, P; Bürklein, D; Wehr, U; Rambeck, W; Eckstein, F

2000-01-01

The objective of this study was to directly compare in situ femoral dual-energy X-ray absorptiometry (DXA) and in vitro chemical analysis (ash weight and calcium) with mechanical failure loads of the proximal femur, and to determine the influence of bone size (volume) and density on mechanical failure and DXA-derived areal bone mineral density (BMD, in g/cm2). We performed femoral DXA in 52 fixed cadavers (age 82.1 +/- 9.7 years; 30 male, 22 female) with intact skin and soft tissues. The femora were then excised, mechanically loaded to failure in a stance phase configuration, their volume measured with a water displacement method (proximal neck to lesser trochanter), and the ash weight and calcium content of this region determined by chemical analysis. The correlation coefficient between the bone mineral content (measured in situ with DXA) and the ash weight was r = 0.87 (standard error of the estimate = 16%), the ash weight allowing for a better prediction of femoral failure loads (r = 0.78; p < 0.01) than DXA (r = 0.67; p < 0.01). The femoral volume (r = 0.61; p < 0.01), but not the volumetric bone density (r = 0.26), was significantly associated with the failure load. The femoral bone volume had a significant impact (r = 0.35; p < 0.01) on the areal BMD (DXA), and only 63% of the variability of bone volume could be predicted (based on the basis of body height, weight and femoral projectional bone area. The results suggest that accuracy errors of femoral DXA limit the prediction of mechanical failure loads, and that the influence of bone size on areal BMD cannot be fully corrected by accounting for body height, weight and projected femoral area.

Effects of age and loading rate on equine cortical bone failure.

PubMed

Kulin, Robb M; Jiang, Fengchun; Vecchio, Kenneth S

2011-01-01

Although clinical bone fractures occur predominantly under impact loading (as occurs during sporting accidents, falls, high-speed impacts or other catastrophic events), experimentally validated studies on the dynamic fracture behavior of bone, at the loading rates associated with such events, remain limited. In this study, a series of tests were performed on femoral specimens obtained post-mortem from equine donors ranging in age from 6 months to 28 years. Fracture toughness and compressive tests were performed under both quasi-static and dynamic loading conditions in order to determine the effects of loading rate and age on the mechanical behavior of the cortical bone. Fracture toughness experiments were performed using a four-point bending geometry on single and double-notch specimens in order to measure fracture toughness, as well as observe differences in crack initiation between dynamic and quasi-static experiments. Compressive properties were measured on bone loaded parallel and transverse to the osteonal growth direction. Fracture propagation was then analyzed using scanning electron and scanning confocal microscopy to observe the effects of microstructural toughening mechanisms at different strain rates. Specimens from each horse were also analyzed for dry, wet and mineral densities, as well as weight percent mineral, in order to investigate possible influences of composition on mechanical behavior. Results indicate that bone has a higher compressive strength, but lower fracture toughness when tested dynamically as compared to quasi-static experiments. Fracture toughness also tends to decrease with age when measured quasi-statically, but shows little change with age under dynamic loading conditions, where brittle "cleavage-like" fracture behavior dominates. Copyright © 2010 Elsevier Ltd. All rights reserved.

Lower body negative pressure treadmill exercise as a countermeasure for bed rest-induced bone loss in female identical twins.

PubMed

Zwart, Sara R; Hargens, Alan R; Lee, Stuart M C; Macias, Brandon R; Watenpaugh, Donald E; Tse, Kevin; Smith, Scott M

2007-02-01

Supine weight-bearing exercise within lower body negative pressure (LBNP) alleviates some of the skeletal deconditioning induced by simulated weightlessness in men. We examined this potential beneficial effect in women. Because dietary acid load affected the degree of bone resorption in men during bed rest, we also investigated this variable in women. Subjects were 7 pairs of female identical twins assigned at random to 2 groups, sedentary bed rest (control) or bed rest with supine treadmill exercise within LBNP. Dietary intake was controlled and monitored. Urinary calcium and markers of bone resorption were measured before bed rest and on bed rest days 5/6, 12/13, 19/20, and 26/27. Bone mineral content was assessed by dual-energy X-ray absorptiometry before and after bed rest. Data were analyzed by repeated-measures two-way analysis of variance. Pearson correlation coefficients were used to define the relationships between diet and markers of bone metabolism and to estimate heritability of markers. During bed rest, all markers of bone resorption and urinary calcium and phosphorus increased (P<0.001); parathyroid hormone (P=0.06), bone-specific alkaline phosphatase (P=0.06), and 1,25-dihydroxyvitamin D (P=0.09) tended to decrease. LBNP exercise tended to mitigate bone density loss. The ratio of dietary animal protein to potassium was positively correlated with urinary calcium excretion for all weeks of bed rest in the control group, but only during weeks 1 and 3 in the exercise group. Pre-bed rest data suggested that many markers of bone metabolism have strong genetic determinants. Treadmill exercise within LBNP had less of a protective effect on bone resorption during bed rest in women than previously published results had shown for its effect in men, but the same trends were observed for both sexes. Dietary acid load of these female subjects was significantly correlated with calcium excretion but not with other bone resorption markers.

Differentiating zones at periodontal ligament-bone and periodontal ligament-cementum entheses.

PubMed

Lee, J-H; Pryce, B A; Schweitzer, R; Ryder, M I; Ho, S P

2015-12-01

The structural and functional integrity of bone-periodontal ligament (PDL)-cementum complex stems from the load-bearing attachment sites (entheses) between soft (PDL) and hard (bone, cementum) tissues. These attachment sites are responsible for the maintenance of a bone-PDL-cementum complex biomechanical function. The objective was to investigate changes in spatiotemporal expression of key biomolecules in developing and functionally active entheses. Multilabeling technique was performed on hemimandibles of 3 wk and 3 mo-old scleraxis-GFP transgenic mice for CD146, CD31, NG2, osterix and bone sialoprotein. Regions of dominant stretch within the PDL were evaluated by identifying directionality of collagen fibrils, PDL fibroblasts and PDL cell cytoskeleton. CD146+ cells adjacent to CD31+ vasculature were identified at PDL-bone enthesis. NG2+ cells were located at coronal bone-PDL and apical cementum-PDL entheses in the 3-wk-old group, but at 3 mo, NG2 was positive at the entheses of the apical region and alveolar crest. NG2 and osterix were colocalized at the osteoid and cementoid regions of the PDL-bone and PDL-cementum entheses. Bone sialoprotein was prominent at the apical region of 3-wk-old mice. The directionality of collagen fibers, fibroblasts and their cytoskeleton overlapped, except in the apical region of 3 wk. Colocalization of biomolecules at zones of the PDL adjacent to attachment sites may be essential for the formation of precementum and osteoid interfaces at a load-bearing bone-PDL-tooth fibrous joint. Biophysical cues resulting from development and function can regulate recruitment and differentiation of stem cells potentially from a vascular origin toward osteo- and cemento-blastic lineages at the PDL-bone and PDL-cementum entheses. Investigating the coupled effect of biophysical and biochemical stimuli leading to cell differentiation at the functional attachment sites is critical for developing regeneration strategies to enable functional reconstruction of the periodontal complex. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Lower body negative pressure treadmill exercise as a countermeasure for bed rest-induced bone loss in female identical twins

PubMed Central

Zwart, Sara R.; Hargens, Alan R.; Lee, Stuart M. C.; Macias, Brandon R.; Watenpaugh, Donald E.; Tse, Kevin; Smith, Scott M.

2007-01-01

Supine weight-bearing exercise within lower body negative pressure (LBNP) alleviates some of the skeletal deconditioning induced by simulated weightlessness in men. We examined the potential beneficial effect in women. Because dietary acid load affected the degree of bone resorption in men during bed rest, we also investigated this variable in women. Subjects were 7 pairs of female identical twins assigned at random to 2 groups, sedentary bed rest (control) or bed rest with supine treadmill exercise within LBNP. Dietary intake was controlled and monitored. Urinary calcium and markers of bone resorption were measured before bed rest (BR) and on BR days 5/6, 12/13, 19/20, and 26/27. Bone mineral content was assessed by dual-energy X-ray absorptiometry before and after bed rest. Data were analyzed by repeated measures two-way analysis of variance. Pearson correlation coefficients were used to define the relationships between diet and markers of bone metabolism, and to estimate heritability of markers. During bed rest, all markers of bone resorption and urinary calcium and phosphorus increased (P < 0.001); parathyroid hormone (P = 0.06), bone-specific alkaline phosphatase (P = 0.06), and 1,25-dihydroxyvitamin D (P = 0.09) tended to decrease. LBNP exercise tended to mitigate bone density loss. The ratio of dietary animal protein to potassium was positively correlated with urinary calcium excretion for all weeks of bed rest in the control group, but only during weeks 1 and 3 for the exercise group. Pre-bed rest data suggested that many markers of bone metabolism have strong genetic determinants. Treadmill exercise within LBNP had less of a protective effect on bone resorption during bed rest in women than previously-published results had shown for its effect in men, but the same trends were observed for both sexes. Dietary acid load of these female subjects was significantly correlated with calcium excretion but not with other bone resorption markers. PMID:17070743

Stress Distribution Around Single Short Dental Implants: A Finite Element Study.

PubMed

Vidya Bhat, S; Premkumar, Priyanka; Kamalakanth Shenoy, K

2014-12-01

Bone height restrictions are more common in the posterior regions of the mandible, because of either bone resorption resulting from tooth loss or even anatomic limitations, such as the position of the inferior alveolar nerve. In situations where adequate bone height is not available in the posterior mandible region, smaller lengths of implants may have to be used but it has been reported that the use of long implants (length ≥10 mm) is a positive factor in osseointegration and authors have reported failures with short implants. Hence knowledge about the stress generated on the bone with different lengths of implants needs scientific evaluation. The purpose of this study was to compare and evaluate the influence of different lengths of implants on stress upon bone in mandibular posterior area. A 3 D finite element model was made of the posterior mandible using the details from a CT scan, using computer software (ANSYS 12). Four simulated implants with lengths 6 mm, 8 mm, 10 mm and 13 mm were placed in the centre of the bone. A static vertical force of 250 N and a static horizontal force of 100 N were applied. The stress generated in the cortical and cancellous bone around the implant were recorded and evaluated with the help of ANSYS. In this study, Von Mises stress on a 6 mm implant under a static vertical load of 250 N appeared to be almost in the same range of 8 and 10 mm implant which were more as compared to 13 mm implant. Von Mises stress on a 6mm implant under a static horizontal load of 100 N appeared to be less when compared to 8, 10 and 13 mm implants. From the results obtained it may be inferred that under static horizontal loading conditions, shorter implants receive lesser load and thus may tend to transfer more stresses to the surrounding bone. While under static vertical loading the shorter implants bear more loads and comparatively transmit lesser load to the surrounding bone.

Estimation of Local Bone Loads for the Volume of Interest.

PubMed

Kim, Jung Jin; Kim, Youkyung; Jang, In Gwun

2016-07-01

Computational bone remodeling simulations have recently received significant attention with the aid of state-of-the-art high-resolution imaging modalities. They have been performed using localized finite element (FE) models rather than full FE models due to the excessive computational costs of full FE models. However, these localized bone remodeling simulations remain to be investigated in more depth. In particular, applying simplified loading conditions (e.g., uniform and unidirectional loads) to localized FE models have a severe limitation in a reliable subject-specific assessment. In order to effectively determine the physiological local bone loads for the volume of interest (VOI), this paper proposes a novel method of estimating the local loads when the global musculoskeletal loads are given. The proposed method is verified for the three VOI in a proximal femur in terms of force equilibrium, displacement field, and strain energy density (SED) distribution. The effect of the global load deviation on the local load estimation is also investigated by perturbing a hip joint contact force (HCF) in the femoral head. Deviation in force magnitude exhibits the greatest absolute changes in a SED distribution due to its own greatest deviation, whereas angular deviation perpendicular to a HCF provides the greatest relative change. With further in vivo force measurements and high-resolution clinical imaging modalities, the proposed method will contribute to the development of reliable patient-specific localized FE models, which can provide enhanced computational efficiency for iterative computing processes such as bone remodeling simulations.

Subchondral bone density distribution of the talus in clinically normal Labrador Retrievers.

PubMed

Dingemanse, W; Müller-Gerbl, M; Jonkers, I; Vander Sloten, J; van Bree, H; Gielen, I

2016-03-15

Bones continually adapt their morphology to their load bearing function. At the level of the subchondral bone, the density distribution is highly correlated with the loading distribution of the joint. Therefore, subchondral bone density distribution can be used to study joint biomechanics non-invasively. In addition physiological and pathological joint loading is an important aspect of orthopaedic disease, and research focusing on joint biomechanics will benefit veterinary orthopaedics. This study was conducted to evaluate density distribution in the subchondral bone of the canine talus, as a parameter reflecting the long-term joint loading in the tarsocrural joint. Two main density maxima were found, one proximally on the medial trochlear ridge and one distally on the lateral trochlear ridge. All joints showed very similar density distribution patterns and no significant differences were found in the localisation of the density maxima between left and right limbs and between dogs. Based on the density distribution the lateral trochlear ridge is most likely subjected to highest loads within the tarsocrural joint. The joint loading distribution is very similar between dogs of the same breed. In addition, the joint loading distribution supports previous suggestions of the important role of biomechanics in the development of OC lesions in the tarsus. Important benefits of computed tomographic osteoabsorptiometry (CTOAM), i.e. the possibility of in vivo imaging and temporal evaluation, make this technique a valuable addition to the field of veterinary orthopaedic research.

Three-dimensional polycaprolactone-hydroxyapatite scaffolds combined with bone marrow cells for cartilage tissue engineering.

PubMed

Wei, Bo; Yao, Qingqiang; Guo, Yang; Mao, Fengyong; Liu, Shuai; Xu, Yan; Wang, Liming

2015-08-01

The goal of this study was to investigate the chondrogenic potential of three-dimensional polycaprolactone-hydroxyapatite (PCL-HA) scaffolds loaded with bone marrow cells in vitro and the effect of PCL-HA scaffolds on osteochondral repair in vivo. Here, bone marrow was added to the prepared PCL-HA scaffolds and cultured in chondrogenic medium for 10 weeks. Osteochondral defects were created in the trochlear groove of 29 knees in 17 New Zealand white rabbits, which were then divided into four groups that underwent: implantation of PCL-HA scaffolds (left knee, n = 17; Group 1), microfracture (right knee, n = 6; Group 2), autologous osteochondral transplantation (right knee, n = 6; Group 3), and no treatment (right knee, n = 5; Control). Extracellular matrix produced by bone marrow cells covered the surface and filled the pores of PCL-HA scaffolds after 10 weeks in culture. Moreover, many cell-laden cartilage lacunae were observed, and cartilage matrix was concentrated in the PCL-HA scaffolds. After a 12-week repair period, Group 1 showed excellent vertical and lateral integration with host bone, but incomplete cartilage regeneration and matrix accumulation. An uneven surface of regenerated cartilage and reduced distribution of cartilage matrix were observed in Group 2. In addition, abnormal bone growth and unstable integration between repaired and host tissues were detected. For Group 3, the integration between transplanted and host cartilage was interrupted. Our findings indicate that the PCL-HA scaffolds loaded with bone marrow cells improved chondrogenesis in vitro and implantation of PCL-HA scaffolds for osteochondral repairenhanced integration with host bone. However, cartilage regeneration remained unsatisfactory. The addition of trophic factors or the use of precultured cell-PCL-HA constructs for accelerated osteochondral repair requires further investigation. © The Author(s) 2015.

Cyclic load testing of biodegradable suture anchors containing 2 high-strength sutures.

PubMed

Barber, F Alan; Coons, David A; Ruiz-Suarez, Michell

2007-04-01

The purpose of this study was to test 4 different biodegradable suture anchors threaded with 2 high-strength sutures under cyclic loading conditions in humeral cadaveric specimens divided into 2 different age groups. Thirty-two paired human cadaveric humeri were stripped of all soft tissue. Two groups were studied: group 1, in which the mean age was 54 years, and group 2, in which the mean age was 70 years. We placed 1 suture anchor at 3 humeral sites per bone (anterior, middle, and posterior greater tuberosity). We tested 24 specimens using each of 4 anchors: TwinFix AB (Smith & Nephew Endoscopy, Andover, MA), BioZip (Stryker Endoscopy, San Jose, CA), Bio-Corkscrew FT (Arthrex, Naples, FL), and SpiraLok (DePuy Mitek, Raynham, MA). The anchor's sutures were grasped with an Instron clamp (Instron, Canton, MA), preloaded, and cycled from 10 to 60 N 500 times, followed by destructive testing. The mean displacement at 500 cycles, yield loads, failure modes, and ultimate loads were recorded. Most cyclic motion occurred during the first 100 cycles. More motion occurred in older bones than in younger bones (P < .05). The mean yield loads were greater for the young group for the SpiraLok anchors than for Bio-Corkscrew FT anchors in the young and old groups (P < .001), TwinFix anchors in the old group (P < .05), and BioZip anchors in the old group (P < .05). The ultimate failure loads for SpiraLok anchors in the young group were greater than for Bio-Corkscrew FT anchors in the young and old groups and BioZip anchors in the old group (P < .05). In group 1 TwinFix AB (P = .01) and BioZip (P = .02) ultimate loads were statistically greater than that for Bio-Corkscrew FT. The TwinFix AB failed by anchor pullout. The Bio-Corkscrew FT failed by eyelet pullout. The BioZip and SpiraLok pulled out in older bone and experienced eyelet breakage in younger bone. None of the 4 anchors reached 5 mm of displacement even after 500 loading cycles. Most of the displacement occurred in the first 100 cycles. Of all anchors tested, the Bio-Corkscrew FT recorded the lowest displacement after 500 cycles (P < .05). The SpiraLok had the highest ultimate load of all anchors tested (P < .01). Rotator cuff anchors perform differently in younger humeral bone than in older humeral bone. Most displacement with cyclic loading occurring between the anchor and bone takes place in the first 100 cycles. Anchors in older bones can be expected to fail at lower loads.

Theoretical effects of fully ductile versus fully brittle behaviors of bone tissue on the strength of the human proximal femur and vertebral body.

PubMed

Nawathe, Shashank; Yang, Haisheng; Fields, Aaron J; Bouxsein, Mary L; Keaveny, Tony M

2015-05-01

The influence of the ductility of bone tissue on whole-bone strength represents a fundamental issue of multi-scale biomechanics. To gain insight, we performed a computational study of 16 human proximal femurs and 12 T9 vertebral bodies, comparing the whole-bone strength for the two hypothetical bounding cases of fully brittle versus fully ductile tissue-level failure behaviors, all other factors, including tissue-level elastic modulus and yield stress, held fixed. For each bone, a finite element model was generated (60-82 μm element size; up to 120 million elements) and was virtually loaded in habitual (stance for femur, compression for vertebra) and non-habitual (sideways fall, only for femur) loading modes. Using a geometrically and materially non-linear model, the tissue was assumed to be either fully brittle or fully ductile. We found that, under habitual loading, changing the tissue behavior from fully ductile to fully brittle reduced whole-bone strength by 38.3±2.4% (mean±SD) and 39.4±1.9% for the femur and vertebra, respectively (p=0.39 for site difference). These reductions were remarkably uniform across bones, but (for the femur) were greater for non-habitual (57.1±4.7%) than habitual loading (p<0.001). At overall structural failure, there was 5-10-fold less failed tissue for the fully brittle than fully ductile cases. These theoretical results suggest that the whole-bone strength of the proximal femur and vertebra can vary substantially between fully brittle and fully ductile tissue-level behaviors, an effect that is relatively insensitive to bone morphology but greater for non-habitual loading. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inhibition of TGF–β signaling in subchondral bone mesenchymal stem cells attenuates osteoarthritis

PubMed Central

Zhen, Gehua; Wen, Chunyi; Jia, Xiaofeng; Li, Yu; Crane, Janet L.; Mears, Simon C.; Askin, Frederic B.; Frassica, Frank J.; Chang, Weizhong; Yao, Jie; Nayfeh, Tariq; Johnson, Carl; Artemov, Dmitri; Chen, Qianming; Zhao, Zhihe; Zhou, Xuedong; Cosgarea, Andrew; Carrino, John; Riley, Lee; Sponseller, Paul; Wan, Mei; Lu, William Weijia; Cao, Xu

2013-01-01

Osteoarthritis is a highly prevalent and debilitating joint disorder. There is no effective medical therapy for osteoarthritis due to limited understanding of osteoarthritis pathogenesis. We show that TGF–β1 is activated in the subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) osteoarthritis mouse model. TGF–β1 concentrations also increased in human osteoarthritis subchondral bone. High concentrations of TGF–β1 induced formation of nestin+ mesenchymal stem cell (MSC) clusters leading to aberrant bone formation accompanied by increased angiogenesis. Transgenic expression of active TGF–β1 in osteoblastic cells induced osteoarthritis. Inhibition of TGF–β activity in subchondral bone attenuated degeneration of osteoarthritis articular cartilage. Notably, knockout of the TGF–β type II receptor (TβRII) in nestin+ MSCs reduced development of osteoarthritis in ACLT mice. Thus, high concentrations of active TGF–β1 in the subchondral bone initiated the pathological changes of osteoarthritis, inhibition of which could be a potential therapeutic approach. PMID:23685840

Tensile loading modulates bone marrow stromal cell differentiation and the development of engineered fibrocartilage constructs.

PubMed

Connelly, John T; Vanderploeg, Eric J; Mouw, Janna K; Wilson, Christopher G; Levenston, Marc E

2010-06-01

Mesenchymal progenitors such as bone marrow stromal cells (BMSCs) are an attractive cell source for fibrocartilage tissue engineering, but the types or combinations of signals required to promote fibrochondrocyte-specific differentiation remain unclear. The present study investigated the influences of cyclic tensile loading on the chondrogenesis of BMSCs and the development of engineered fibrocartilage. Cyclic tensile displacements (10%, 1 Hz) were applied to BMSC-seeded fibrin constructs for short (24 h) or extended (1-2 weeks) periods using a custom loading system. At early stages of chondrogenesis, 24 h of cyclic tension stimulated both protein and proteoglycan synthesis, but at later stages, tension increased protein synthesis only. One week of intermittent cyclic tension significantly increased the total sulfated glycosaminoglycan and collagen contents in the constructs, but these differences were lost after 2 weeks of loading. Constraining the gels during the extended culture periods prevented contraction of the fibrin matrix, induced collagen fiber alignment, and increased sulfated glycosaminoglycan release to the media. Cyclic tension specifically stimulated collagen I mRNA expression and protein synthesis, but had no effect on collagen II, aggrecan, or osteocalcin mRNA levels. Overall, these studies suggest that the combination of chondrogenic stimuli and tensile loading promotes fibrochondrocyte-like differentiation of BMSCs and has the potential to direct fibrocartilage development in vitro.

Development of an injectable pseudo-bone thermo-gel for application in small bone fractures.

PubMed

Kondiah, Pariksha J; Choonara, Yahya E; Kondiah, Pierre P D; Kumar, Pradeep; Marimuthu, Thashree; du Toit, Lisa C; Pillay, Viness

2017-03-30

A pseudo-bone thermo-gel was synthesized and evaluated for its physicochemical, mechanical and rheological properties, with its application to treat small bone fractures. The pseudo-bone thermo-gel was proven to have thermo-responsive properties, behaving as a solution in temperatures below 25°C, and forming a gelling technology when maintained at physiological conditions. Poly propylene fumerate (PPF), Pluronic F127 and PEG-PCL-PEG were strategically blended, obtaining a thermo-responsive delivery system, to mimic the mechanical properties of bone with sufficient matrix hardness and resilience. A Biopharmaceutics Classification System (BCS) class II drug, simvastatin, was loaded in the pseudo-bone thermo-gel, selected for its bone healing properties. In vitro release analysis was undertaken on a series of experimental formulations, with the ideal formulations obtaining its maximum controlled drug release profile up to 14days. Ex vivo studies were undertaken on an induced 4mm diameter butterfly-fractured osteoporotic human clavicle bone samples. X-ray, ultrasound as well as textural analysis, undertaken on the fractured bones before and after treatment displayed significant bone filling, matrix hardening and matrix resilience properties. These characteristics of the pseudo-bone thermo-gel thus proved significant potential for application in small bone fractures. Copyright © 2017 Elsevier B.V. All rights reserved.

Physical Activity and Bone Density in Women

NASA Technical Reports Server (NTRS)

Bowley, Susan M.; Whalen, R. T.

2000-01-01

A mathematical model of bone density regulation as a function of the daily tissue "effective" stress has been derived. Using the model, the influence of daily activity in the form of a daily loading history has been related to bone density of the calcaneus. The theory incorporates a stress exponent m to account for differences in the importance of magnitude and number of load cycles experienced during daily activity. We have derived a parameter from the model, the "Bone Density Index" (BDI). We have developed a method of collecting daily habitual loading histories using an insole force sensor interfaced to a portable digital data logger carried in a fanny pack. Our goal for this study was to determine a stress exponent, m, relating GRFz history to Calcaneal Bone Mineral Density (CBMD).

Modular adaptive implant based on smart materials.

PubMed

Bîzdoacă, N; Tarniţă, Daniela; Tarniţă, D N

2008-01-01

Applications of biological methods and systems found in nature to the study and design of engineering systems and modern technology are defined as Bionics. The present paper describes a bionics application of shape memory alloy in construction of orthopedic implant. The main idea of this paper is related to design modular adaptive implants for fractured bones. In order to target the efficiency of medical treatment, the implant has to protect the fractured bone, for the healing period, undertaking much as is possible from the daily usual load of the healthy bones. After a particular stage of healing period is passed, using implant modularity, the load is gradually transferred to bone, assuring in this manner a gradually recover of bone function. The adaptability of this design is related to medical possibility of the physician to made the implant to correspond to patient specifically anatomy. Using a CT realistic numerical bone models, the mechanical simulation of different types of loading of the fractured bones treated with conventional method are presented. The results are commented and conclusions are formulated.

The effects of vibration loading on adipose stem cell number, viability and differentiation towards bone-forming cells

PubMed Central

Tirkkonen, Laura; Halonen, Heidi; Hyttinen, Jari; Kuokkanen, Hannu; Sievänen, Harri; Koivisto, Anna-Maija; Mannerström, Bettina; Sándor, George K. B.; Suuronen, Riitta; Miettinen, Susanna; Haimi, Suvi

2011-01-01

Mechanical stimulation is an essential factor affecting the metabolism of bone cells and their precursors. We hypothesized that vibration loading would stimulate differentiation of human adipose stem cells (hASCs) towards bone-forming cells and simultaneously inhibit differentiation towards fat tissue. We developed a vibration-loading device that produces 3g peak acceleration at frequencies of 50 and 100 Hz to cells cultured on well plates. hASCs were cultured using either basal medium (BM), osteogenic medium (OM) or adipogenic medium (AM), and subjected to vibration loading for 3 h d–1 for 1, 7 and 14 day. Osteogenesis, i.e. differentiation of hASCs towards bone-forming cells, was analysed using markers such as alkaline phosphatase (ALP) activity, collagen production and mineralization. Both 50 and 100 Hz vibration frequencies induced significantly increased ALP activity and collagen production of hASCs compared with the static control at 14 day in OM. A similar trend was detected for mineralization, but the increase was not statistically significant. Furthermore, vibration loading inhibited adipocyte differentiation of hASCs. Vibration did not affect cell number or viability. These findings suggest that osteogenic culture conditions amplify the stimulatory effect of vibration loading on differentiation of hASCs towards bone-forming cells. PMID:21613288

Biomechanical investigation of thread designs and interface conditions of zirconia and titanium dental implants with bone: three-dimensional numeric analysis.

PubMed

Fuh, Lih-Jyh; Hsu, Jui-Ting; Huang, Heng-Li; Chen, Michael Y C; Shen, Yen-Wen

2013-01-01

Bone stress and interfacial sliding at the bone-implant interface (BII) were analyzed in zirconia and titanium implants with various thread designs and interface conditions (bonded BII and contact BIIs with different frictional coefficients) for both conventional and immediately loaded treatments. A total of 18 finite element models comprising two implant materials (zirconia and titanium), three thread designs (different shapes and pitches), and three interface conditions (bonded and contact BIIs) were analyzed to assess the effects on bone stresses and on sliding at the BII. The material properties of the bone model were anisotropic, and a lateral force of 130 N was applied as the loading condition. In the immediately loaded implant, the stress was highly concentrated at one site of the peri-implant bone. The peak bone stress was more than 20% lower in zirconia implants than in titanium implants for a bonded BII and 14% to 20% lower for a contact BII. The bone stresses did not differ significantly between implants with V-shaped threads and square threads. However, sliding at the BII was more than 25% lower with square-thread implants than with V-shaped-thread implants for titanium implants and 36% lower for zirconia implants. Reducing the thread size and pitch in cortical bone (via two V-shaped threads with different pitches) decreased the bone stress by 13%. Increasing the frictional coefficient reduced sliding at the BII in both zirconia and titanium implants. As an implant material, zirconia can reduce the bone stress in the crestal cortical region. Bone stress and sliding at the BII are heavily dependent on the thread design and the frictional coefficient at the BII of immediately loaded implants.

Influence of implant collar design on stress and strain distribution in the crestal compact bone: a three-dimensional finite element analysis.

PubMed

Shen, Wan-Ling; Chen, Chen-Sheng; Hsu, Ming-Lun

2010-01-01

To evaluate the influence of implant collar geometry on the distribution of stress and strain in the crestal compact bone contiguous to an implant collar for four types of bone under axial and oblique loads. Finite element models of threaded implants with three kinds of implant collar designs (divergent, straight, and convergent) with their corresponding suprastructures embedded in the posterior mandible were created with ANSYS software. Eight different test conditions incorporating four types of bone (orthotropic and effectively isotropic in part 1 and high and low densities in part 2) under separate 100-N axial and 35.6-degree oblique forces were created to investigate the stress and strain distributions in the crestal compact bone around the implant collars. In all eight conditions, the divergent collar demonstrated the lowest maximum von Mises and principal stresses and strains in the crestal compact bone contiguous to the implant collar, followed by the straight and convergent collars. The oblique load induced higher peak values than the axial load. The orthotropic design amplified and increased the pathologic microstrains and tensile stresses in the crestal compact bone compared to the effectively isotropic design, especially in models with a convergent collar design. In part 2 of the study, the maximum von Mises stresses and strains increased with a decrease in the cancellous bone density. Under oblique loading, the convergent and straight collars showed pathologic microstrain values as well as excessive ultimate tensile stresses in the orthotropic bone model with low-density cancellous bone. Within the limitations, it was concluded that stress and strain distributions in the adjacent compact bone are influenced by the implant collar design. The divergent implant collar design was associated with the lowest stress and strain concentrations in the crestal compact bone.

The effects of simulated bone loss on the implant-abutment assembly and likelihood of fracture: an in vitro study.

PubMed

Manzoor, Behzad; Suleiman, Mahmood; Palmer, Richard M

2013-01-01

The crestal bone level around a dental implant may influence its strength characteristics by offering protection against mechanical failures. Therefore, the present study investigated the effect of simulated bone loss on modes, loads, and cycles to failure in an in vitro model. Different amounts of bone loss were simulated: 0, 1.5, 3.0, and 4.5 mm from the implant head. Forty narrow-diameter (3.0-mm) implant-abutment assemblies were tested using compressive bending and cyclic fatigue testing. Weibull and accelerated life testing analysis were used to assess reliability and functional life. Statistical analyses were performed using the Fisher-Exact test and the Spearman ranked correlation. Compressive bending tests showed that the level of bone loss influenced the load-bearing capacity of implant-abutment assemblies. Fatigue testing showed that the modes, loads, and cycles to failure had a statistically significant relationship with the level of bone loss. All 16 samples with bone loss of 3.0 mm or more experienced horizontal implant body fractures. In contrast, 14 of 16 samples with 0 and 1.5 mm of bone loss showed abutment and screw fractures. Weibull and accelerated life testing analysis indicated a two-group distribution: the 0- and 1.5-mm bone loss samples had better functional life and reliability than the 3.0- and 4.5-mm samples. Progressive bone loss had a significant effect on modes, loads, and cycles to failure. In addition, bone loss influenced the functional life and reliability of the implant-abutment assemblies. Maintaining crestal bone levels is important in ensuring biomechanical sustainability and predictable long-term function of dental implant assemblies.

Three-Dimensional Finite Element Analysis of Varying Diameter and Connection Type in Implants with High Crown-Implant Ratio.

PubMed

Moraes, Sandra Lúcia Dantas de; Verri, Fellippo Ramos; Santiago, Joel Ferreira; Almeida, Daniel Augusto de Faria; Lemos, Cleidiel Aparecido Araujo; Gomes, Jéssica Marcela de Luna; Pellizzer, Eduardo Piza

2018-01-01

The aim of this study was to evaluate the effect of varying the diameter, connection type and loading on stress distribution in the cortical bone for implants with a high crown-implant ratio. Six 3D models were simulated with the InVesalius, Rhinoceros 3D 4.0 and SolidWorks 2011 software programs. Models were composed of bone from the posterior mandibular region; they included an implant of 8.5 mm length, diameter Ø 3.75 mm or Ø 5.00 mm and connection types such as external hexagon (EH), internal hexagon (IH) and Morse taper (MT). Models were processed using the Femap 11.2 and NeiNastran 11.0 programs and by using an axial force of 200 N and oblique force of 100 N. Results were recorded in terms of the maximum principal stress. Oblique loading showed high stress in the cortical bone compared to that shown by axial loading. The results showed that implants with a wide diameter showed more favorable stress distribution in the cortical bone region than regular diameter, regardless of the connection type. Morse taper implants showed better stress distribution compared to other connection types, especially in the oblique loading. Thus, oblique loading showed higher stress concentration in cortical bone tissue when compared with axial loading. Wide diameter implant was favorable for improved stress distribution in the cortical bone region, while Morse taper implants showed lower stress concentration than other connections.

A study of the progression of damage in an axially loaded Branta leucopsis femur using X-ray computed tomography and digital image correlation

PubMed Central

Manning, Phillip Lars; Lowe, Tristan; Withers, Philip J.

2017-01-01

This paper uses X-ray computed tomography to track the mechanical response of a vertebrate (Barnacle goose) long bone subjected to an axial compressive load, which is increased gradually until failure. A loading rig was mounted in an X-ray computed tomography system so that a time-lapse sequence of three-dimensional (3D) images of the bone’s internal (cancellous or trabecular) structure could be recorded during loading. Five distinct types of deformation mechanism were observed in the cancellous part of the bone. These were (i) cracking, (ii) thinning (iii) tearing of cell walls and struts, (iv) notch formation, (v) necking and (vi) buckling. The results highlight that bone experiences brittle (notch formation and cracking), ductile (thinning, tearing and necking) and elastic (buckling) modes of deformation. Progressive deformation, leading to cracking was studied in detail using digital image correlation. The resulting strain maps were consistent with mechanisms occurring at a finer-length scale. This paper is the first to capture time-lapse 3D images of a whole long bone subject to loading until failure. The results serve as a unique reference for researchers interested in how bone responds to loading. For those using computer modelling, the study not only provides qualitative information for verification and validation of their simulations but also highlights that constitutive models for bone need to take into account a number of different deformation mechanisms. PMID:28652932

Experimental pre-clinical assessment of the primary stability of two cementless femoral knee components.

PubMed

Berahmani, Sanaz; Hendriks, Maartje; Wolfson, David; Wright, Abraham; Janssen, Dennis; Verdonschot, Nico

2017-11-01

To achieve long-lasting fixation of cementless implants, an adequate primary stability is required. We aimed to compare primary stability of a new cementless femoral knee component (Attune®) against a conventional implant (LCS®) under different loading conditions. Six pairs of femora were prepared following the normal surgical procedure. Calibrated CT-scans and 3D-optical scans of the bones were obtained to measure bone mineral density (BMD) and cut accuracy, respectively. Micromotions were measured in nine regions of interest at the bone-implant interface using digital image correlation. The reconstructions were subjected to the implant-specific's peak tibiofemoral load of gait and a deep knee bend loading profiles. Afterwards, the implants were pushed-off at a flexion angle of 150°. Micromotions of Attune were significantly lower than LCS under both loading conditions (P ≤ 0.001). Cut accuracy did not affect micromotions, and BMD was only a significant factor affecting the micromotions under simplified gait loading. No significant difference was found in high-flex push-off force, but Attune required a significantly higher load to generate excessive micromotions during push-off. Parallel anterior and posterior bone cuts in the LCS versus the tapered bone cuts of the Attune may explain the difference between the two designs. Additionally, the rims at the borders of the LCS likely reduced the area of contact with the bone for the LCS, which may have affected the initial fixation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Micro finite element analysis of dental implants under different loading conditions.

PubMed

Marcián, Petr; Wolff, Jan; Horáčková, Ladislava; Kaiser, Jozef; Zikmund, Tomáš; Borák, Libor

2018-05-01

Osseointegration is paramount for the longevity of dental implants and is significantly influenced by biomechanical stimuli. The aim of the present study was to assess the micro-strain and displacement induced by loaded dental implants at different stages of osseointegration using finite element analysis (FEA). Computational models of two mandible segments with different trabecular densities were constructed using microCT data. Three different implant loading directions and two osseointegration stages were considered in the stress-strain analysis of the bone-implant assembly. The bony segments were analyzed using two approaches. The first approach was based on Mechanostat strain intervals and the second approach was based on tensile/compression yield strains. The results of this study revealed that bone surrounding dental implants is critically strained in cases when only a partial osseointegration is present and when an implant is loaded by buccolingual forces. In such cases, implants also encounter high stresses. Displacements of partially-osseointegrated implant are significantly larger than those of fully-osseointegrated implants. It can be concluded that the partial osseointegration is a potential risk in terms of implant longevity. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Role of GH/IGF-I Axis in Muscle Homeostasis During Weightlessness

NASA Technical Reports Server (NTRS)

Schwartz, Robert J.

1997-01-01

Exposure to reduced gravity during space travel profoundly alters the loads placed on bone and muscle. Astronauts suffer significant losses of muscle and bone strength during weightlessness. Exercise as a countermeasure is only partially effective in remedying severe muscle atrophy and bone demineralization. Similar wasting of muscles and bones affects people on Earth during prolonged bed rest or immobilization due to injury. In the absence of weight bearing activity, atrophy occurs primarily in the muscles that act in low power, routine movements and in maintaining posture. Hormonal disfunction could contribute in part to the loss of muscle and bone during spaceflight. Reduced levels of human Growth Hormone (hGH) were found in astronauts during space flight, as well as reduced GH secretory activity was observed from the anterior pituitary in 7-day space flight rats. Growth hormone has been shown to be required for maintenance of muscle mass and bone mineralization, in part by mediating the biosynthesis IGF-I, a small polypeptide growth factor. IGF biosynthesis and secretion plays an important role in potentiating muscle cell differentiation and has been shown to drive the expression of myogenin, a myogenic specific basic helix-loop-helix factor. IGF-I has also been shown to have an important role in potentiating muscle regeneration, repair and adult muscle hypertrophy.

Mechanical Vibration Mitigates the Decrease of Bone Quantity and Bone Quality of Leptin Receptor-Deficient Db/Db Mice by Promoting Bone Formation and Inhibiting Bone Resorption.

PubMed

Jing, Da; Luo, Erping; Cai, Jing; Tong, Shichao; Zhai, Mingming; Shen, Guanghao; Wang, Xin; Luo, Zhuojing

2016-09-01

Leptin, a major hormonal product of adipocytes, is involved in regulating appetite and energy metabolism. Substantial studies have revealed the anabolic actions of leptin on skeletons and bone cells both in vivo and in vitro. Growing evidence has substantiated that leptin receptor-deficient db/db mice exhibit decreased bone mass and impaired bone microstructure despite several conflicting results previously reported. We herein systematically investigated bone microarchitecture, mechanical strength, bone turnover and its potential molecular mechanisms in db/db mice. More importantly, we also explored an effective approach for increasing bone mass in leptin receptor-deficient animals in an easy and noninvasive manner. Our results show that deterioration of trabecular and cortical bone microarchitecture and decreases of skeletal mechanical strength-including maximum load, yield load, stiffness, energy, tissue-level modulus and hardness-in db/db mice were significantly ameliorated by 12-week, whole-body vibration (WBV) with 0.5 g, 45 Hz via micro-computed tomography (μCT), three-point bending, and nanoindentation examinations. Serum biochemical analysis shows that WBV significantly decreased serum tartrate-resistant acid phosphatase 5b (TRACP5b) and CTx-1 levels and also mitigated the reduction of serum osteocalcin (OCN) in db/db mice. Bone histomorphometric analysis confirmed that decreased bone formation-lower mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone-in db/db mice were suppressed by WBV. Real-time PCR assays show that WBV mitigated the reductions of tibial alkaline phosphatase (ALP), OCN, Runt-related transcription factor 2 (RUNX2), type I collagen (COL1), BMP2, Wnt3a, Lrp6, and β-catenin mRNA expression, and prevented the increases of tibial sclerostin (SOST), RANK, RANKL, RANL/osteoprotegerin (OPG) gene levels in db/db mice. Our results show that WBV promoted bone quantity and quality in db/db mice with obvious anabolic and anticatabolic effects. This study not only enriches our basic knowledge about bone quality and bone turnover mechanisms in leptin receptor-deficient animals, but also advances our understanding of the skeletal sensitivity of leptin-resistant db/db mice in response to external mechanical stimulation. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Fatigue of immature baboon cortical bone.

PubMed

Keller, T S; Lovin, J D; Spengler, D M; Carter, D R

1985-01-01

Strain-controlled uniaxial fatigue and monotonic tensile tests were conducted on turned femoral cortical bone specimens obtained from baboons at various ages of maturity. Fatigue loading produced a progressive loss in stiffness and an increase in hysteresis prior to failure, indicating that immature primate cortical bone responds to repeated loading in a fashion similar to that previously observed for adult human cortical bone. Bone fatigue resistance under this strain controlled testing decreased during maturation. Maturation was also associated with an increase in bone dry density, ash fraction and elastic modulus. The higher elastic modulus of more mature bone meant that these specimens were subjected to higher stress levels during testing than more immature bone specimens. Anatomical regions along the femoral shaft exhibited differences in strength and fatigue resistance.

The Implications of Reduced Ground Reaction Forces During Space Flight for Bone Strains

NASA Technical Reports Server (NTRS)

Peterman, Marc M.; Hamel, Andrew J.; Sharkey, Neil A.; Piazza, Stephen J.; Cavanagh, Peter R.

1998-01-01

The specific mechanisms regulating bone mass are not known, but most investigators agree that bone maintenance is largely dependent upon mechanical demand and the resultant local bone strains. During space flight, bone loss such as that reported by LeBlanc et al. may result from failure to effectively load the skeleton and generate sufficient localized bone strains. In microgravity, a gravity replacement system can be used to tether an exercising subject to a treadmill. It follows that the ability to prevent bone loss is critically dependent upon the external ground reaction forces (GRFs) and skeletal loads imparted by the tethering system. To our knowledge, the loads during orbital flight have been measured only once (on STS 81). Based on these data and data from ground based experiments, it appears likely that interventions designed to prevent bone loss in micro-gravity generate GRFs substantially less than body weight. It is unknown to what degree reductions in external GRFs will affect internal bone strain and thus the bone maintenance response. To better predict the efficacy of treadmill exercise in micro-gravity we used a unique cadaver model to measure localized bone strains under conditions representative of those that might be produced by a gravity replacement system in space.

3D Printing and Biofabrication for Load Bearing Tissue Engineering.

PubMed

Jeong, Claire G; Atala, Anthony

2015-01-01

Cell-based direct biofabrication and 3D bioprinting is becoming a dominant technological platform and is suggested as a new paradigm for twenty-first century tissue engineering. These techniques may be our next step in surpassing the hurdles and limitations of conventional scaffold-based tissue engineering, and may offer the industrial potential of tissue engineered products especially for load bearing tissues. Here we present a topically focused review regarding the fundamental concepts, state of the art, and perspectives of this new technology and field of biofabrication and 3D bioprinting, specifically focused on tissue engineering of load bearing tissues such as bone, cartilage, osteochondral and dental tissue engineering.

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

PubMed Central

Liu, Jinsong; Zeng, Youyun; Shi, Shuai; Xu, Lihua; Zhang, Hualin; Pathak, Janak L; Pan, Yihuai

2017-01-01

Treatment of cancer metastasized to bone is still a challenge due to hydrophobicity, instability, and lack of target specificity of anticancer drugs. Poly (ethylene glycol)-poly (ε-caprolactone) polymer (PEG-PCL) is an effective, biodegradable, and biocompatible hydrophobic drug carrier, but lacks bone specificity. Polyaspartic acid with eight peptide sequences, that is, (Asp)8, has a strong affinity to bone surface. The aim of this study was to synthesize (Asp)8-PEG-PCL nanoparticles as a bone-specific carrier of hydrophobic drugs to treat cancer metastasized to bone. 1H nuclear magnetic resonance, Fourier transform infrared spectroscopy, and transmission electron microscopy data showed that (Asp)8-PEG-PCL nanoparticles (size 100 nm) were synthesized successfully. (Asp)8-PEG-PCL nanoparticles did not promote erythrocyte aggregation. Fluorescence microscopy showed clear uptake of Nile red-loaded (Asp)8-PEG-PCL nanoparticles by cancer cells. (Asp)8-PEG-PCL nanoparticles did not show cytotoxic effect on MG63 and human umbilical vein endothelial cells at the concentration of 10–800 μg/mL. (Asp)8-PEG-PCL nanoparticles bound with hydroxyapatite 2-fold more than PEG-PCL. Intravenously injected (Asp)8-PEG-PCL nanoparticles accumulated 2.7-fold more on mice tibial bone, in comparison to PEG-PCL. Curcumin is a hydrophobic anticancer drug with bone anabolic properties. Curcumin was loaded in the (Asp)8-PEG-PCL. (Asp)8-PEG-PCL showed 11.07% loading capacity and 95.91% encapsulation efficiency of curcumin. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles gave sustained release of curcumin in high dose for >8 days. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles showed strong antitumorigenic effect on MG63, MCF7, and HeLa cancer cells. In conclusion, (Asp)8-PEG-PCL nanoparticles were biocompatible, permeable in cells, a potent carrier, and an efficient releaser of hydrophobic anticancer drug and were bone specific. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles showed strong antitumorigenic ability in vitro. Therefore, (Asp)8-PEG-PCL nanoparticles could be a potent carrier of hydrophobic anticancer drugs to treat the cancer metastasized to bone. PMID:28507436

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone.

PubMed

Liu, Jinsong; Zeng, Youyun; Shi, Shuai; Xu, Lihua; Zhang, Hualin; Pathak, Janak L; Pan, Yihuai

2017-01-01

Treatment of cancer metastasized to bone is still a challenge due to hydrophobicity, instability, and lack of target specificity of anticancer drugs. Poly (ethylene glycol)-poly (ε-caprolactone) polymer (PEG-PCL) is an effective, biodegradable, and biocompatible hydrophobic drug carrier, but lacks bone specificity. Polyaspartic acid with eight peptide sequences, that is, (Asp) 8 , has a strong affinity to bone surface. The aim of this study was to synthesize (Asp) 8 -PEG-PCL nanoparticles as a bone-specific carrier of hydrophobic drugs to treat cancer metastasized to bone. 1 H nuclear magnetic resonance, Fourier transform infrared spectroscopy, and transmission electron microscopy data showed that (Asp) 8 -PEG-PCL nanoparticles (size 100 nm) were synthesized successfully. (Asp) 8 -PEG-PCL nanoparticles did not promote erythrocyte aggregation. Fluorescence microscopy showed clear uptake of Nile red-loaded (Asp) 8 -PEG-PCL nanoparticles by cancer cells. (Asp) 8 -PEG-PCL nanoparticles did not show cytotoxic effect on MG63 and human umbilical vein endothelial cells at the concentration of 10-800 μg/mL. (Asp) 8 -PEG-PCL nanoparticles bound with hydroxyapatite 2-fold more than PEG-PCL. Intravenously injected (Asp) 8 -PEG-PCL nanoparticles accumulated 2.7-fold more on mice tibial bone, in comparison to PEG-PCL. Curcumin is a hydrophobic anticancer drug with bone anabolic properties. Curcumin was loaded in the (Asp) 8 -PEG-PCL. (Asp) 8 -PEG-PCL showed 11.07% loading capacity and 95.91% encapsulation efficiency of curcumin. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles gave sustained release of curcumin in high dose for >8 days. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles showed strong antitumorigenic effect on MG63, MCF7, and HeLa cancer cells. In conclusion, (Asp) 8 -PEG-PCL nanoparticles were biocompatible, permeable in cells, a potent carrier, and an efficient releaser of hydrophobic anticancer drug and were bone specific. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles showed strong antitumorigenic ability in vitro. Therefore, (Asp) 8 -PEG-PCL nanoparticles could be a potent carrier of hydrophobic anticancer drugs to treat the cancer metastasized to bone.

Anatomic and Biomechanical Comparison of Traditional Bankart Repair With Bone Tunnels and Bankart Repair Utilizing Suture Anchors

PubMed Central

Judson, Christopher H.; Charette, Ryan; Cavanaugh, Zachary; Shea, Kevin P.

2016-01-01

Background: Traditional Bankart repair using bone tunnels has a reported failure rate between 0% and 5% in long-term studies. Arthroscopic Bankart repair using suture anchors has become more popular; however, reported failure rates have been cited between 4% and 18%. There have been no satisfactory explanations for the differences in these outcomes. Hypothesis: Bone tunnels will provide increased coverage of the native labral footprint and demonstrate greater load to failure and stiffness and decreased cyclic displacement in biomechanical testing. Study Design: Controlled laboratory study. Methods: Twenty-two fresh-frozen cadaveric shoulders were used. For footprint analysis, the labral footprint area was marked and measured using a Microscribe technique in 6 specimens. A 3-suture anchor repair was performed, and the area of the uncovered footprint was measured. This was repeated with traditional bone tunnel repair. For the biomechanical analysis, 8 paired specimens were randomly assigned to bone tunnel or suture anchor repair with the contralateral specimen assigned to the other technique. Each specimen underwent cyclic loading (5-25 N, 1 Hz, 100 cycles) and load to failure (15 mm/min). Displacement was measured using a digitized video recording system. Results: Bankart repair with bone tunnels provided significantly more coverage of the native labral footprint than repair with suture anchors (100% vs 27%, P < .001). Repair with bone tunnels (21.9 ± 8.7 N/mm) showed significantly greater stiffness than suture anchor repair (17.1 ± 3.5 N/mm, P = .032). Mean load to failure and gap formation after cyclic loading were not statistically different between bone tunnel (259 ± 76.8 N, 0.209 ± 0.064 mm) and suture anchor repairs (221.5 ± 59.0 N [P = .071], 0.161 ± 0.51 mm [P = .100]). Conclusion: Bankart repair with bone tunnels completely covered the footprint anatomy while suture anchor repair covered less than 30% of the native footprint. Repair using bone tunnels resulted in significantly greater stiffness than repair with suture anchors. Load to failure and gap formation were not significantly different. PMID:26779555

Anatomic and Biomechanical Comparison of Traditional Bankart Repair With Bone Tunnels and Bankart Repair Utilizing Suture Anchors.

PubMed

Judson, Christopher H; Charette, Ryan; Cavanaugh, Zachary; Shea, Kevin P

2016-01-01

Traditional Bankart repair using bone tunnels has a reported failure rate between 0% and 5% in long-term studies. Arthroscopic Bankart repair using suture anchors has become more popular; however, reported failure rates have been cited between 4% and 18%. There have been no satisfactory explanations for the differences in these outcomes. Bone tunnels will provide increased coverage of the native labral footprint and demonstrate greater load to failure and stiffness and decreased cyclic displacement in biomechanical testing. Controlled laboratory study. Twenty-two fresh-frozen cadaveric shoulders were used. For footprint analysis, the labral footprint area was marked and measured using a Microscribe technique in 6 specimens. A 3-suture anchor repair was performed, and the area of the uncovered footprint was measured. This was repeated with traditional bone tunnel repair. For the biomechanical analysis, 8 paired specimens were randomly assigned to bone tunnel or suture anchor repair with the contralateral specimen assigned to the other technique. Each specimen underwent cyclic loading (5-25 N, 1 Hz, 100 cycles) and load to failure (15 mm/min). Displacement was measured using a digitized video recording system. Bankart repair with bone tunnels provided significantly more coverage of the native labral footprint than repair with suture anchors (100% vs 27%, P < .001). Repair with bone tunnels (21.9 ± 8.7 N/mm) showed significantly greater stiffness than suture anchor repair (17.1 ± 3.5 N/mm, P = .032). Mean load to failure and gap formation after cyclic loading were not statistically different between bone tunnel (259 ± 76.8 N, 0.209 ± 0.064 mm) and suture anchor repairs (221.5 ± 59.0 N [P = .071], 0.161 ± 0.51 mm [P = .100]). Bankart repair with bone tunnels completely covered the footprint anatomy while suture anchor repair covered less than 30% of the native footprint. Repair using bone tunnels resulted in significantly greater stiffness than repair with suture anchors. Load to failure and gap formation were not significantly different.

Ready to Use Tissue Construct for Military Bone & Cartilage Trauma

DTIC Science & Technology

2014-10-01

during nail introduction and reaming. In the present study, we examined the load - bearing capacity and optimal internal fixation of a bone/poly-ε...segmental defect, (a) axial loading via ball bearing , (b) torsional loading via square clamp allowing axial displacement, (c) three-point bending of tibia...knee joints by simulating loads seen during ambulation and knee range of motion. Our central hypothesis is that an anatomically and

Combination of bone morphogenetic protein-2 plasmid DNA with chemokine CXCL12 creates an additive effect on bone formation onset and volume.

PubMed

Wegman, F; Poldervaart, M T; van der Helm, Y J; Oner, F C; Dhert, W J; Alblas, J

2015-07-27

Bone morphogenetic protein-2 (BMP-2) gene delivery has shown to induce bone formation in vivo in cell-based tissue engineering. In addition, the chemoattractant stromal cell-derived factor-1α (SDF-1α, also known as CXCL12) is known to recruit multipotent stromal cells towards its release site where it enhances vascularisation and possibly contributes to osteogenic differentiation. To investigate potential cooperative behaviour for bone formation, we investigated combined release of BMP-2 and SDF-1α on ectopic bone formation in mice. Multipotent stromal cell-seeded and cell-free constructs with BMP-2 plasmid DNA and /or SDF-1α loaded onto gelatin microparticles, were implanted subcutaneously in mice for a period of 6 weeks. Histological analysis and histomorphometry revealed that the onset of bone formation and the formed bone volume were both enhanced by the combination of BMP-2 and SDF-1α compared to controls in cell-seeded constructs. Samples without seeded multipotent stromal cells failed to induce any bone formation. We conclude that the addition of stromal cell-derived factor-1α to a cell-seeded alginate based bone morphogenetic protein-2 plasmid DNA construct has an additive effect on bone formation and can be considered a promising combination for bone regeneration.

Creep of trabecular bone from the human proximal tibia

PubMed Central

Novitskaya, Ekaterina; Zin, Carolyn; Chang, Neil; Cory, Esther; Chen, Peter; D'Lima, Darryl; Sah, Robert L.; McKittrick, Joanna

2014-01-01

Creep is the deformation that occurs under a prolonged, sustained load and can lead to permanent damage in bone. Creep in bone is a complex phenomenon and varies with type of loading and local mechanical properties. Human trabecular bone samples from proximal tibia were harvested from a 71-year old female cadaver with osteoporosis. The samples were initially subjected to one cycle load up to 1% strain to determine the creep load. Samples were then loaded in compression under a constant stress for two hours and immediately unloaded. All tests were conducted with the specimens soaked in phosphate buffered saline with proteinase inhibitors at 37°C. Steady state creep rate and final creep strain were estimated from mechanical testing and compared with published data. The steady state creep rate correlated well with values obtained from bovine tibial and human vertebral trabecular bone, and was higher for lower density samples. Tissue architecture was analyzed by micro-computed tomography (μCT) both before and after creep testing to assess creep deformation and damage accumulated. Quantitative morphometric analysis indicated that creep induced changes in trabecular separation and the structural model index. A main mode of deformation was bending of trabeculae. PMID:24857486

Increased resistance during jump exercise does not enhance cortical bone formation.

PubMed

Boudreaux, Ramon D; Swift, Joshua M; Gasier, Heath G; Wiggs, Michael P; Hogan, Harry A; Fluckey, James D; Bloomfield, Susan A

2014-01-01

This study sought to elucidate the effects of a low- and high-load jump resistance exercise (RE) training protocol on cortical bone of the tibia and femur mid-diaphyses. Sprague-Dawley rats (male, 6 months old) were randomly assigned to high-load RE (HRE; n = 16), low-load RE (LRE; n = 15), or cage control (CC; n = 11) groups. Animals in the HRE and LRE groups performed 15 sessions of jump RE for 5 wk. Load in the HRE group was progressively increased from 80 g added to a weighted vest (50 repetitions) to 410 g (16 repetitions). The LRE rats completed the same protocol as the HRE group (same number of repetitions), with only a 30-g vest applied. Low- and high-load jump RE resulted in 6%-11% higher cortical bone mineral content and cortical bone area compared with controls, as determined by in vivo peripheral quantitative computed tomography measurements. In the femur, however, only LRE demonstrated improvements in cortical volumetric bone mineral density (+11%) and cross-sectional moment of inertia (+20%) versus the CC group. The three-point bending to failure revealed a marked increase in tibial maximum force (25%-29%), stiffness (19%-22%), and energy to maximum force (35%-55%) and a reduction in elastic modulus (-11% to 14%) in both LRE and HRE compared with controls. Dynamic histomorphometry assessed at the tibia mid-diaphysis determined that both LRE and HRE resulted in 20%-30% higher periosteal mineralizing surface versus the CC group. Mineral apposition rate and bone formation rate were significantly greater in animals in the LRE group (27%, 39%) than those in the HRE group. These data demonstrate that jump training with minimal loading is equally, and sometimes more, effective at augmenting cortical bone integrity compared with overload training in skeletally mature rats.

Three-Dimensional Mechanical Loading Modulates the Osteogenic Response of Mesenchymal Stem Cells to Tumor-Derived Soluble Signals.

PubMed

Lynch, Maureen E; Chiou, Aaron E; Lee, Min Joon; Marcott, Stephen C; Polamraju, Praveen V; Lee, Yeonkyung; Fischbach, Claudia

2016-08-01

Dynamic mechanical loading is a strong anabolic signal in the skeleton, increasing osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) and increasing the bone-forming activity of osteoblasts, but its role in bone metastatic cancer is relatively unknown. In this study, we integrated a hydroxyapatite-containing three-dimensional (3D) scaffold platform with controlled mechanical stimulation to investigate the effects of cyclic compression on the interplay between breast cancer cells and BM-MSCs as it pertains to bone metastasis. BM-MSCs cultured within mineral-containing 3D poly(lactide-co-glycolide) (PLG) scaffolds differentiated into mature osteoblasts, and exposure to tumor-derived soluble factors promoted this process. When BM-MSCs undergoing osteogenic differentiation were exposed to conditioned media collected from mechanically loaded breast cancer cells, their gene expression of osteopontin was increased. This was further enhanced when mechanical compression was simultaneously applied to BM-MSCs, leading to more uniformly deposited osteopontin within scaffold pores. These results suggest that mechanical loading of 3D scaffold-based culture models may be utilized to evaluate the role of physiologically relevant physical cues on bone metastatic breast cancer. Furthermore, our data imply that cyclic mechanical stimuli within the bone microenvironment modulate interactions between tumor cells and BM-MSCs that are relevant to bone metastasis.

Finite element analysis of functionally graded bone plate at femur bone fracture site

NASA Astrophysics Data System (ADS)

Satapathy, Pravat Kumar; Sahoo, Bamadev; Panda, L. N.; Das, S.

2018-03-01

This paper focuses on the analysis of fractured Femur bone with functionally graded bone plate. The Femur bone is modeled by using the data from the CT (Computerized Tomography) scan and the material properties are assigned using Mimics software. The fracture fixation plate used here is composed of Functionally Graded Material (FGM). The functionally graded bone plate is considered to be composed of different layers of homogeneous materials. Finite element method approach is adopted for analysis. The volume fraction of the material is calculated by considering its variation along the thickness direction (z) according to a power law and the effective properties of the homogeneous layers are estimated. The model developed is validated by comparing numerical results available in the literature. Static analysis has been performed for the bone plate system by considering both axial compressive load and torsional load. The investigation shows that by introducing FG bone plate instead of titanium, the stress at the fracture site increases by 63 percentage and the deformation decreases by 15 percentage, especially when torsional load is taken into consideration. The present model yields better results in comparison with the commercially available bone plates.

Primary stability, insertion torque and bone density of cylindric implant ad modum Branemark: is there a relationship? An in vitro study.

PubMed

Trisi, Paolo; De Benedittis, Simona; Perfetti, Giorgio; Berardi, Davide

2011-05-01

Protocols of immediate loading have been reported in several studies. It has also been demonstrated that the cause of failure of immediate loaded implants is due to the micromotion on the bone-implant interface induced by immediate loading. There should be a minimum gap between the implant and the peri-implant bone, without micromotions occurring above a definite threshold risk as they induce bone resorption and fibrosis around the implant. Measurement of the torque necessary to insert an implant in the bone is a parameter for measuring initial stability. The higher the implant insertion torque, the higher the initial stability attained. The aim of this study was to evaluate in vitro the correlation between the micromotion of cylindric screw implants ad modum Branemark and the insertion torque in bone of different densities. The test was carried out on 2 × 2 cm samples of fresh bovine bone of three different densities: hard (H), medium (M) and soft (S). One hundred and fifty hexa implants ad modum Branemark were used, 3.75 mm in diameter and 9 mm long. To screw in the implants, a customized manual key was used, controlled digitally to evaluate the peak insertion torques. Ten implants were prepared for each torque (20, 35, 45, 70 and 100 N/cm). The bone sample was then fixed on a loading device, which allowed evaluating the micromotion. On each sample, we applied a 25 N horizontal force. The results indicate that the peak insertion torque and the implant micromotion are statistically correlated, and statistically significant differences in H and M bone were found compared with S bone. In S bone, we noted a micromotion significantly higher than the risk threshold, and it was not possible to reach peak insertion torque above 35 N/cm. In H and M bone, the micromotion is below the threshold of all insertion torques. Increasing the peak insertion torque, we can reduce the extent of the micromotion between the implant and the bone when submitted to lateral forces in vitro. In soft bone, the micromotion was always high; hence, immediate loading of implants in low-density bone should be evaluated with care. © 2010 John Wiley & Sons A/S.

Evaluation of rhBMP-2/collagen/TCP-HA bone graft with and without bone marrow cells in the canine femoral multi defect model.

PubMed

Luangphakdy, V; Shinohara, K; Pan, H; Boehm, C; Samaranska, A; Muschler, G F

2015-01-12

Recombinant human bone morphogenetic protein-2, when applied to an absorbable type 1 bovine collagen sponge (rhBMP-2/ACS) is an effective therapy in many bone grafting settings. Bone marrow aspirate (BMA) has also been used as a source of transplantable osteogenic connective tissue progenitors. This study was designed to characterize the performance of a scaffold comprising rhBMP-2/ACS in which the sponge wraps around tri-calcium phosphate hydroxyapatite granules (rhBMP-2/ACS/TCP-HA) and to test the hypothesis that addition of BMA will improve the performance of this construct in the Canine Femoral Multi Defect Model. In each subject, two sites were grafted with rhBMP-2/ACS/TCP-HA scaffold loaded with BMA clot and two other sites with rhBMP-2/ACS/TCP-HA scaffold loaded with wound blood (WB). After correction for unresorbed TCP-HA granules, sites grafted with rhBMP-2/ACS/TCP-HA+BMA and rhBMP-2/ACS/TCP-HA+WB were similar, with mean percent bone volumes of 10.9 %±1.2 and 11.2 %±1.2, respectively. No differences were seen in quantitative histomorphometry. While bone formation using both constructs was robust, this study did not support the hypothesis that the addition of unprocessed bone marrow aspirate clot improved bone regeneration in a site engrafted with rhBMP-2/ACS/TCP-HA+BMA. In contrast to prior studies using this model, new bone formation was greater at the center of the defect where TCP-HA was distributed. This finding suggests a potential synergy between rhBMP-2 and the centrally placed ceramic and cellular components of the graft construct. Further optimization may also require more uniform distribution of TCP-HA, alternative cell delivery strategies, and a more rigorous large animal segmental defect model.

A method for continuous monitoring of the Ground Reaction Force during daily activity

NASA Technical Reports Server (NTRS)

Whalen, Robert; Quintana, Jason; Emery, Jeff

1993-01-01

Theoretical models and experimental studies of bone remodeling have identified peak cyclic force levels (or cyclic tissue strain energy density), number of daily loading cycles, and load (strain) rate as possible contributors to bone modeling and remodeling stimulus. To test our theoretical model and further investigate the influence of mechanical forces on bone density, we have focused on the calcaneus as a model site loaded by calcaneal surface tractions which are predominantly determined by the magnitude of the external ground reaction force (GRF).

Mechanical, material, and antimicrobial properties of acrylic bone cement impregnated with silver nanoparticles.

PubMed

Slane, Josh; Vivanco, Juan; Rose, Warren; Ploeg, Heidi-Lynn; Squire, Matthew

2015-03-01

Prosthetic joint infection is one of the most serious complications that can lead to failure of a total joint replacement. Recently, the rise of multidrug resistant bacteria has substantially reduced the efficacy of antibiotics that are typically incorporated into acrylic bone cement. Silver nanoparticles (AgNPs) are an attractive alternative to traditional antibiotics resulting from their broad-spectrum antimicrobial activity and low bacterial resistance. The purpose of this study, therefore, was to incorporate metallic silver nanoparticles into acrylic bone cement and quantify the effects on the cement's mechanical, material and antimicrobial properties. AgNPs at three loading ratios (0.25, 0.5, and 1.0% wt/wt) were incorporated into a commercial bone cement using a probe sonication technique. The resulting cements demonstrated mechanical and material properties that were not substantially different from the standard cement. Testing against Staphylococcus aureus and Staphylococcus epidermidis using Kirby-Bauer and time-kill assays demonstrated no antimicrobial activity against planktonic bacteria. In contrast, cements modified with AgNPs significantly reduced biofilm formation on the surface of the cement. These results indicate that AgNP-loaded cement is of high potential for use in primary arthroplasty where prevention of bacterial surface colonization is vital. Copyright © 2014 Elsevier B.V. All rights reserved.

Multi-scale osteointegration and neovascularization of biphasic calcium phosphate bone scaffolds

NASA Astrophysics Data System (ADS)

Lan, Sheeny K.

Bone grafts are utilized clinically to guide tissue regeneration. Autologous bone and allogeneic bone are the current clinical standards. However, there are significant limitations to their use. To address the need for alternatives to autograft and allograft, researchers have worked to develop synthetic grafts, also referred to as scaffolds. Despite extensive efforts in this area, a gap persists between basic research and clinical application. In particular, solutions for repairing critical size and/or load-bearing defects are lacking. The aim of this thesis work was to address two critical barriers preventing design of successful tissue engineering constructs for bone regeneration within critical size and/or load-bearing defects. Those barriers are insufficient osteointegration and slow neovascularization. In this work, the effects of scaffold microporosity, recombinant human bone morphogenetic protein-2 delivery and endothelial colony forming cell vasculogenesis were evaluated in the context of bone formation in vivo. This was accomplished to better understand the role of these factors in bone regeneration, which may translate to improvements in tissue engineering construct design. Biphasic calcium phosphate (BCP) scaffolds with controlled macro- and microporosity were implanted in porcine mandibular defects. Evaluation of the BCP scaffolds after in vivo implantation showed, for the first time, osteocytes embedded in bone within scaffold micropores (< 10 microm) as well as the most extensive bone growth into micropores to date with bone penetration throughout rods 394 microm in diameter. The result is the first truly osteointegrated bone scaffolds with integration occurring at both the macro and micro length scales, leaving no "dead space" or discontinuities of bone in the defect site. The scaffold forms a living composite upon integration with regenerating bone and this has significant implications with regard to improved scaffold mechanical properties. The presence of osteocytes within scaffold micropores is an indication of scaffold osteoinductivity because a chemotactic factor must be present to induce cell migration into pores on the order of the cell diameter. It is likely that the scaffold undergoes in vivo modifications involving formation of a biological apatite layer within scaffold micropores and possibly co-precipitation of endogenous osteoinductive proteins. To further investigate the effects of scaffold osteoinductivity, BCP scaffolds were implanted in porcine mandibular defects with rhBMP-2, which was partially sequestered in the micropores. Cell migration into osteoinductive scaffold micropores can be enhanced through the delivery of exogenous rhBMP-2 further promoting multi-scale osteointegration. Finally, endothelial colony forming cells (ECFCs) isolated from human umbilical cord blood (UCB) were evaluated in terms of their in vivo vasculogenic potential in the context of bone formation. This work was completed to determine if ECFCs could be utilized in a bone tissue engineering construct to promote neovascularization. ECFCs were combined with a BCP scaffold and rhBMP-2 and implanted subcutaneously on the abdominal wall of NOD/SCID mice. The result was formation of perfused human vessels within BCP scaffold macropores that were present at 4 weeks. The high density and persistence of human vessels at four weeks indicates that human UCB ECFCs exceed their reported in vivo vasculogenic potential when combined with rhBMP-2 and a BCP scaffold. This shows a dual role for BMP-2 in the context of bone regeneration. Collectively, the thesis demonstrates that (1) the design of synthetic bone scaffolds should include controlled multi-scale porosity to promote multi-scale osteointegration, which may significantly improve scaffold mechanical properties and (2) human umbilical cord blood-derived endothelial colony forming cells have potential for promoting neovascularization in a bone defect when combined with rhBMP-2.

Analysis of multiple bone responses to graded strains above functional levels, and to disuse, in mice in vivo show that the human Lrp5 G171V High Bone Mass mutation increases the osteogenic response to loading but that lack of Lrp5 activity reduces it

PubMed Central

Saxon, Leanne K.; Jackson, Brendan F.; Sugiyama, Toshihiro; Lanyon, Lance E.; Price, Joanna S.

2011-01-01

Introduction To investigate the role of the low-density lipoprotein receptor-related protein 5 (Lrp5) in bones' responses to loading, we analysed changes in multiple measures of bone architecture in tibias subjected to loading or disuse in male and female mice with the Lrp5 loss of function mutation (Lrp5−/−) or heterozygous for the Lrp5 G171V High Bone Mass (HBM) mutation (Lrp5HBM+). Materials and methods The right tibias of these 17 week old male and female mice and their Wild Type (WT) littermates were subjected to short periods of loading three days a week for two weeks. Each tibia was loaded for 40 cycles, to produce peak strains at the midshaft within the low, medium or high physiological range (~ 1500, 2400 and 3000 microstrain, respectively). In similar groups of mice the right sciatic nerve was severed causing disuse of the right tibia for 3 weeks. Data from microCT of loaded, neurectomised and contra-lateral control tibias were analysed to quantify changes in the cortical and cancellous regions of the bone in the absence of functional strains and in response to graded strains in addition to those derived from function. Results and conclusion Male WT+/+ controls showed significant strain:response curves for cortical area and trabecular thickness, but Lrp5−/− mice showed no detectable strain:response in those same outcomes. Female mice of either WT+/+ or Lrp5−/− genotype did not show significant strain:response curves for cortical or trabecular parameters, the one exception being Tb.Th in Lrp5−/− mice. Since female WT+/+ mice did not respond to loading in a significant dose:responsive manner, the similar lack of responsiveness of the Lrp5−/− females could not be ascribed to their Lrp5 status. Cortical bone loss associated with disuse showed no differences between Lrp5−/− mice and WT+/+ controls, but in cancellous bone of both male and females of these mice, there was a greater loss than in WT+/+ controls. In contrast, the tibias of male and female mice heterozygous for the Lrp5 G171V HBM mutation showed greater osteogenic responsiveness to loading and less bone loss associated with disuse than their WTHBM− controls. These data indicate that the presence of the Lrp5 G171V HBM mutation is associated with an increased osteogenic response to loading but support only a marginal gender-related role for normal Lrp5 function in this loading-related response. PMID:21419885

Biomechanics and strain mapping in bone as related to immediately-loaded dental implants

PubMed Central

Du, Jing; Lee, Jihyun; Jang, Andrew; Gu, Allen; Hossaini-Zadeh, Mehran; Prevost, Richard; Curtis, Don; Ho, Sunita

2015-01-01

The effects of alveolar bone socket geometry and bone-implant contact on implant biomechanics, and resulting strain distributions in bone were investigated. Following extraction of lateral incisors on a cadaver mandible, immediate implants were placed and bone-implant contact area, stability and bone strain were measured. In situ biomechanical testing coupled with micro X-ray microscope (μ-XRM) illustrated less stiff bone-implant complexes (701-822 N/mm) compared with bone-periodontal ligament (PDL)-tooth complexes (791-913 N/mm). X-ray tomograms illustrated that the cause of reduced stiffness was due to reduced and limited bone-implant contact. Heterogeneous elemental composition of bone was identified by using energy dispersive X-ray spectroscopy (EDS). The novel aspect of this study was the application of a new experimental mechanics method, that is, digital volume correlation, which allowed mapping of strains in volumes of alveolar bone in contact with a loaded implant. The identified surface and subsurface strain concentrations were a manifestation of load transferred to bone through bone-implant contact based on bone-implant geometry, quality of bone, implant placement, and implant design. 3D strain mapping indicated that strain concentrations are not exclusive to the bone-implant contact regions, but also extend into bone not directly in contact with the implant. The implications of the observed strain concentrations are discussed in the context of mechanobiology. Although a plausible explanation of surgical complications for immediate implant treatment is provided, extrapolation of results is only warranted by future systematic studies on more cadaver specimens and/or in vivo small scale animal models. PMID:26162549

Effects of mechanical loading on the degradability and mechanical properties of the nanocalcium-deficient hydroxyapatite–multi(amino acid) copolymer composite membrane tube for guided bone regeneration

PubMed Central

Duan, Hong; Yang, Hongsheng; Xiong, Yan; Zhang, Bin; Ren, Cheng; Min, Li; Zhang, Wenli; Yan, Yonggang; Li, Hong; Pei, Fuxing; Tu, Chongqi

2013-01-01

Background and methods Guided bone regeneration (GBR) is a new treatment for bone defects, and the property of membrane is critical to the success of GBR. This study focuses on a novel membrane tube for GBR, which was prepared by a nanocalcium-deficient hydroxyapatite–multi(amino acid) copolymer (n-CDHA-MAC) composite. The biomechanical strength and degradability of this membrane tube under mechanical loading after immersion in phosphate-buffered solution were investigated to evaluate the effects of mechanical loading on the membrane tube. The membrane-tube group with no mechanical loading and femora bone were used as controls. Results The compressive strength and bending strength of n-CDHA-MAC membrane tubes were 66.4 ± 10.2 MPa and 840.7 ± 12.1 MPa, which were lower than those of the goats’ femoral bones (69.0 ± 5.5 MPa and 900.2 ± 17.3 MPa), but there were no significant (P > 0.05) differences. In the in vitro degradability experiment, all membrane tubes were degradable and showed a surface-erosion degradation model. The PH of solution fluctuated from 7.2 to 7.5. The weight and mechanical strength of loaded tubes decreased more quickly than nonloaded ones, with significant differences (P < 0.05). However, the strength of the loaded group after degradation achieved 20.4 ± 1.2 MPa, which was greater than the maximum mechanical strength of 4.338 MPa based on goat femoral middle stationary state by three-dimensional finite-element analysis. Conclusions n-CDHA-MAC membrane tubes have good biomechanical strength during degradation under mechanical loading. Therefore, this membrane tube is an ideal GBR membrane for critical size defects of long bones in goats for animal experiments. PMID:23946651

Diet-dependent net endogenous acid load of vegan diets in relation to food groups and bone health-related nutrients: results from the German Vegan Study.

PubMed

Ströhle, Alexander; Waldmann, Annika; Koschizke, Jochen; Leitzmann, Claus; Hahn, Andreas

2011-01-01

Dietary composition has been shown to affect acid-base homeostasis and bone health in humans. We investigated the potential renal acid load (PRAL) and the estimated diet-dependent net acid load (net endogenous acid production, NEAP) in adult vegans and evaluated the relationships between NEAP, food groups and intake of bone health-related nutrients. The German Vegan Study (GVS) is a cross-sectional study. Data from healthy men (n = 67) and women (n = 87), aged 21-75 years, who fulfilled the study criteria (vegan diet for ≥1 year prior to study start; age ≥18 years, and no pregnancy/childbirth during the last 12 months) were included in the analysis. NEAP values were calculated from diet composition using two models: one based on the protein/potassium quotient and another taking into account an anthropometry-based loss of urinary organic anions. Mean daily intakes of phosphorus, potassium, sodium, magnesium and vitamin C were above, and vitamin D and calcium below Dietary Reference Intake (DRI). Regardless of the model used, the diet in the GVS was characterized by a nearly neutral NEAP. A strong correlation was observed between the NEAP values of the two models (r(s) = 0.873, p < 0.001). Only the consumption of fruits decreased constantly across the increasing quartiles of NEAP. It can be hypothesized that vegan diets do not affect acid-base homeostasis. With respect to bone health, the significance of this finding needs further investigation. Copyright © 2011 S. Karger AG, Basel.

Inbred Strain-Specific Effects of Exercise in Wild Type and Biglycan Deficient Mice

PubMed Central

Wallace, Joseph M.; Golcuk, Kurtulus; Morris, Michael D.; Kohn, David H.

2010-01-01

Biglycan (bgn)-deficient mice (KO) have defective osteoblasts which lead to changes in the amount and quality of bone. Altered tissue strength in C57BL6/129 (B6;129) KO mice, a property which is independent of tissue quantity, suggests that deficiencies in tissue quality are responsible. However, the response to bgn-deficiency is inbred strain-specific. Mechanical loading influences bone matrix quality in addition to any increase in bone mass or change in bone formation activity. Since many diseases influence the mechanical integrity of bone through altered tissue quality, loading may be a way to prevent and treat extracellular matrix deficiencies. C3H/He (C3H) mice consistently have a less vigorous response to mechanical loading vs. other inbred strains. It was therefore hypothesized that the bones from both wild type (WT) and KO B6;129 mice would be more responsive to exercise than the bones from C3H mice. To test these hypotheses at 11 weeks of age, following 21 consecutive days of exercise, we investigated cross-sectional geometry, mechanical properties, and tissue composition in the tibiae of male mice bred on B6;129 and C3H backgrounds. This study demonstrated inbred strain-specific compositional and mechanical changes following exercise in WT and KO mice, and showed evidence of genotype-specific changes in bone in response to loading in a gene disruption model. This study further shows that exercise can influence bone tissue composition and/or mechanical integrity without changes in bone geometry. Together, these data suggest that exercise may represent a possible means to alter tissue quality and mechanical deficiencies caused by many diseases of bone. PMID:20033775

Histologic and histomorphometric evaluation of peri-implant bone of immediate or delayed occlusal-loaded non-splinted implants in the posterior mandible--an experimental study in monkeys.

PubMed

Stokholm, Rie; Isidor, Flemming; Nyengaard, Jens R

2014-11-01

The primary aim of this study was to compare the bone reaction around immediate-loaded non-splinted single implants vs. delayed loaded non-splinted single implants placed in healed ridges in the posterior mandible. Six adult Macaca Fascicularis monkeys were used in this study. The first and second premolars and the first molar were extracted in both sides of the mandible. After 3 months of healing, four implants (Replace Select Tapered; Nobel Biocare, Gothenburg, Sweden) with a moderately rough surface (TiUnite, Nobel Biocare) were placed in the edentulous areas of each monkey, two in each side. The implants had a length of 10 mm and a diameter of 3.5 mm. Four groups of varying time and occlusal loading aspects were created: (i) control group: implant placed non-loaded for 3 months; (ii) immediate loaded: implant placed and loaded immediately for 3 months; (iii) immediate loaded: implant placed and loaded immediately for 6 months; and (iv) delayed loaded: implant placed submerged for 3 months and then loaded for 3 months. At the loaded implants, after a second stage surgery, a composite crown was made directly on an abutment mounted on the implant reinsuring simultaneous occlusal contact on the implant crown and the neighboring teeth. After euthanization of the animals, histologic specimens were quantified in the light microscope. All implants were clinically, radiographically, and histologically osseointegrated at the time of euthanization and with only mild signs of inflammation in the peri-implant mucosa. The histologic marginal bone level was located on average 1.14-1.74 mm apical to the margin of the implants in the various groups. The average bone-to-implant contact (BIC) varied between 55% and 65% and the average bone density (i.e., the proportion of mineralized bone tissue from the implant surface and to a distance of 1 mm lateral to the implant) varied between 30.6% and 34.2%. No statistical significant differences between groups were observed in the above-stated histomorphometric parameters. Similar histologic and histomorphometric findings were observed in immediately and delayed loaded non-splinted implants placed in the posterior mandible of macaque monkeys. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Loading-related regulation of gene expression in bone in the contexts of estrogen deficiency, lack of estrogen receptor α and disuse

PubMed Central

Zaman, Gul; Saxon, Leanne K.; Sunters, Andrew; Hilton, Helen; Underhill, Peter; Williams, Debbie; Price, Joanna S.; Lanyon, Lance E.

2010-01-01

Loading-related changes in gene expression in resident cells in the tibia of female mice in the contexts of normality (WT), estrogen deficiency (WT-OVX), absence of estrogen receptor α (ERα−/−) and disuse due to sciatic neurectomy (WT-SN) were established by microarray. Total RNA was extracted from loaded and contra-lateral non-loaded tibiae at selected time points after a single, short period of dynamic loading sufficient to engender an osteogenic response. There were marked changes in the expression of many genes according to context as well as in response to loading within those contexts. In WT mice at 3, 8, 12 and 24 h after loading the expression of 642, 341, 171 and 24 genes, respectively, were differentially regulated compared with contra-lateral bones which were not loaded. Only a few of the genes differentially regulated by loading in the tibiae of WT mice have recognized roles in bone metabolism or have been linked previously to osteogenesis (Opn, Sost, Esr1, Tgfb1, Lrp1, Ostn, Timp, Mmp, Ctgf, Postn and Irs1, BMP and DLX5). The canonical pathways showing the greatest loading-related regulation were those involving pyruvate metabolism, mitochondrial dysfunction, calcium-induced apoptosis, glycolysis/gluconeogenesis, aryl hydrocarbon receptor and oxidative phosphorylation. In the tibiae from WT-OVX, ERα−/− and WT-SN mice, 440, 439 and 987 genes respectively were differentially regulated by context alone compared to WT. The early response to loading in tibiae of WT-OVX mice involved differential regulation compared to their contra-lateral non-loaded pair of fewer genes than in WT, more down-regulation than up-regulation and a later response. This was shared by WT-SN. In tibiae of ERα−/− mice, the number of genes differentially regulated by loading was markedly reduced at all time points. These data indicate that in resident bone cells, both basal and loading-related gene expression is substantially modified by context. Many of the genes differentially regulated by the earliest loading-related response were primarily involved in energy metabolism and were not specific to bone. PMID:19857613

Experimental and numerical investigation into the influence of loading conditions in biomechanical testing of locking plate fracture fixation devices

PubMed Central

MacLeod, A.; Simpson, A. H. R. W.

2018-01-01

Objectives Secondary fracture healing is strongly influenced by the stiffness of the bone-fixator system. Biomechanical tests are extensively used to investigate stiffness and strength of fixation devices. The stiffness values reported in the literature for locked plating, however, vary by three orders of magnitude. The aim of this study was to examine the influence that the method of restraint and load application has on the stiffness produced, the strain distribution within the bone, and the stresses in the implant for locking plate constructs. Methods Synthetic composite bones were used to evaluate experimentally the influence of four different methods of loading and restraining specimens, all used in recent previous studies. Two plate types and three screw arrangements were also evaluated for each loading scenario. Computational models were also developed and validated using the experimental tests. Results The method of loading was found to affect the gap stiffness strongly (by up to six times) but also the magnitude of the plate stress and the location and magnitude of strains at the bone-screw interface. Conclusions This study demonstrates that the method of loading is responsible for much of the difference in reported stiffness values in the literature. It also shows that previous contradictory findings, such as the influence of working length and very large differences in failure loads, can be readily explained by the choice of loading condition. Cite this article: A. MacLeod, A. H. R. W. Simpson, P. Pankaj. Experimental and numerical investigation into the influence of loading conditions in biomechanical testing of locking plate fracture fixation devices. Bone Joint Res 2018;7:111–120. DOI: 10.1302/2046-3758.71.BJR-2017-0074.R2. PMID:29363522

Repair of diaphyseal bone defects with calcitriol-loaded PLGA scaffolds and marrow stromal cells.

PubMed

Yoon, Sun Jung; Park, Ki Suk; Kim, Moon Suk; Rhee, John M; Khang, Gilson; Lee, Hai Bang

2007-05-01

Calcitriol (1,25(OH)2D3)-loaded porous poly(D,L-lactide-co-glycolide) (PLGA) scaffolds prepared by solvent casting/salt leaching method were used to repair a 1.5 cm diaphyseal segmental bone defect as a fully absorbable osteogenic biomaterial. The in vitro release of sulforhodamine B (SRB) from PLGA scaffold was measured using spectrophotometer, considering SRB as a model drug. The SRB released from SRB-incorporated PLGA scaffold during 3 months was with relatively low initial burst. The calcitriol-loaded PLGA scaffolds with or without marrow stromal cells (MSCs) were implanted in a critical-sized intercalated bone defect in rabbit femur. Defects were assessed by radiographs until 9 weeks. The bony union of the defect was observed only in the calcitriol-loaded groups. RT-PCR results indicated that MSCs, which were seeded into calcitriol-loaded scaffold, expressed an increased level of alkaline phosphatase, osteonectin, and type I collagen mRNA at day 10. After 2 and 4 weeks, the implanted scaffolds were evaluated by histology. New osteoid matrix and direct calcium deposits were more evident in calcitriol/PLGA/MSC group. Three-dimensional computed tomography and frontal tomographic images of repaired femur showed that normal femur anatomy had been restored with cortical bone with no implanted PLGA remnants at 20 weeks. It can be concluded that the porous calcitriol-loaded PLGA scaffold combined with MSCs may be a novel method for repairing the large loaded bone defect.

Mechanical evaluation of external skeletal fixator-intramedullary pin tie-in configurations applied to cadaveral humeri from red-tailed hawks (Buteo jamaicensis).

PubMed

Van Wettere, Arnaud J; Redig, Patrick T; Wallace, Larry J; Bourgeault, Craig A; Bechtold, Joan E

2009-12-01

Use of external skeletal fixator-intramedullary pin (ESF-IM) tie-in fixators is an adjustable and effective method of fracture fixation in birds. The objective of this study was to determine the contribution of each of the following parameters to the compressive and torsional rigidity of an ESF-IM pin tie-in applied to avian bones with an osteotomy gap: (1) varying the fixation pin position in the proximal bone segment and (2) increasing the number of fixation pins in one or both bone segments. ESF-IM pin tie-in constructs were applied to humeri harvested from red-tailed hawks (Buteo jamaicensis) (n=24) that had been euthanatized for clinical reasons. Constructs with a variation in the placement of the proximal fixation pin and with 2, 3, or 4 fixation pins applied to avian bone with an osteotomy gap were loaded to a defined displacement in torque and axial compression. Response variables were determined from resulting load-displacement curves (construct stiffness, load at 1-mm displacement). Increasing the number of fixation pins from 1 to 2 per bone segment significantly increased the stiffness in torque (110%) and compression (60%), and the safe load in torque (107%) and compression (50%). Adding a fixation pin to the distal bone segment to form a 3-pin fixator significantly increased the stiffness (27%) and safe load (20%) in torque but not in axial compression. In the configuration with 2 fixation pins, placing the proximal pin distally in the proximal bone segment significantly increased the stiffness in torque (28%), and the safe load in torque (23%) and in axial compression (32%). Results quantified the relative importance of specific parameters affecting the rigidity of ESF-IM pin tie-in constructs as applied to unstable bone fracture models in birds.

High-density human mesenchymal stem cell rings with spatiotemporally-controlled morphogen presentation as building blocks for engineering bone diaphyseal tissue

PubMed Central

Herberg, Samuel; Varghai, Daniel; Cheng, Yuxuan; Dikina, Anna D.; Dang, Phuong N.; Rolle, Marsha W.; Alsberg, Eben

2018-01-01

Emerging biomimetic tissue engineering strategies aim to partially recapitulate fundamental events that transpire during embryonic skeletal development; namely, cellular self-organization and targeted morphogenetic pathway activation. Here, we describe self-assembled, scaffold-free human mesenchymal stem cell (hMSC) rings featuring microparticle-mediated presentation of transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2). We tested the hypothesis that spatiotemporally-controlled dual presentation of TGF-β1 and BMP-2 is superior in modulating in vitro endochondral ossification of high-density cellular constructs compared to single morphogen delivery. hMSC rings were engineered by seeding cells with microparticles presenting (1) TGF-β1, (2) BMP-2, or (3) TGF-β1 + BMP-2 in custom agarose wells to facilitate self-assembly within 2 d, followed by horizontal culture on glass tubes for 5 weeks. At day 2, hMSC rings across groups revealed homogenous cellular organization mimetic of early mesenchymal condensation with no evidence of new matrix or mineral deposition. Significant early chondrogenic and osteogenic priming occurred with TGF-β1 + BMP-2 presentation compared to single morphogen-loaded groups. By week 5, TGF-β1-loaded hMSC rings had undergone chondrogenesis, while presentation of BMP-2 alone or in conjunction with TGF-β1 stimulated chondrogenesis, chondrocyte hypertrophy, and osteogenesis indicative of endochondral ossification. Importantly, tissue mineralization was most compelling with TGF-β1 + BMP-2 loading. Lastly, hMSC ring 'building blocks' were shown to efficiently fuse into tubes within 6 d post self-assembly. The resulting tubular tissue units exhibited structural integrity, highlighting the translational potential of this advanced biomimetic technology for potential early implantation in long bone defects. PMID:29577017

Advanced immediate functional loading: requirements for long-term success in modern implant dentistry.

PubMed

Romanos, Georgios E

2014-01-01

There are benefits to be derived from the use of advanced surgical protocols in conjunction with immediate functional loading using various dental implant designs and implant-abutment connections. Clinical protocols with simultaneous bone grafting, immediate implant placement, and/or sinus augmentations when a shortened treatment period is needed are included in this report, with the aim of providing understanding of the main protocol characteristics and prerequisites for long-term success in implant dentistry. This article presents three clinical cases that illustrate possibilities for advanced immediate loading using different implant designs. It demonstrates treatment of severe bone defects and the facilitation of placing implants in regenerated bone that can be immediately loaded.

Skeletal adaptation to external loads optimizes mechanical properties: fact or fiction

NASA Technical Reports Server (NTRS)

Turner, R. T.

2001-01-01

The skeleton adapts to a changing mechanical environment but the widely held concept that bone cells are programmed to respond to local mechanical loads to produce an optimal mechanical structure is not consistent with the high frequency of bone fractures. Instead, the author suggests that other important functions of bone compete with mechanical adaptation to determine structure. As a consequence of competing demands, bone architecture never achieves an optimal mechanical structure. c2001 Lippincott Williams & Wilkins, Inc.

Strain gauges used in the mechanical testing of bones. Part II: "In vitro" and "in vivo" technique.

PubMed

Cordey, J; Gautier, E

1999-01-01

How to choose and prepare the strain gauges for bonding on bones "in vitro" and "in vivo"? This communication aims to elucidate technical details and some applications: direct assessment of the axial load, the bending moment, and the torque applied to long bones by the physiological loads. As a typical example of application, we will show the assessment of stress protection due to plates on the bones in the sheep tibia.

Regional responsiveness of the tibia to intermittent administration of parathyroid hormone as affected by skeletal unloading

NASA Technical Reports Server (NTRS)

Halloran, B. P.; Bikle, D. D.; Harris, J.; Tanner, S.; Curren, T.; Morey-Holton, E.

1997-01-01

To determine whether the acute inhibition of bone formation and deficit in bone mineral induced by skeletal unloading can be prevented, we studied the effects of intermittent parathyroid hormone (PTH) administration (8 micrograms/100 g/day) on growing rats submitted to 8 days of skeletal unloading. Loss of weight bearing decreased periosteal bone formation by 34 and 51% at the tibiofibular junction and tibial midshaft, respectively, and reduced the normal gain in tibial mass by 35%. Treatment with PTH of normally loaded and unloaded animals increased mRNA for osteocalcin (+58 and +148%, respectively), cancellous bone volume in the proximal tibia (+41 and +42%, respectively), and bone formation at the tibiofibular junction (+27 and +27%, respectively). Formation was also stimulated at the midshaft in unloaded (+47%, p < 0.05), but not loaded animals (-3%, NS). Although cancellous bone volume was preserved in PTH-treated, unloaded animals, PTH did not restore periosteal bone formation to normal nor prevent the deficit in overall tibial mass induced by unloading. We conclude that the effects of PTH on bone formation are region specific and load dependent. PTH can prevent the decrease in cancellous bone volume and reduce the decrement in cortical bone formation induced by loss of weight bearing.

Expression of Novel Gene Products Upregulated by Disuse is Normalized by an Osteogenic Mechanical Stimulus: Evidence for the Molecular Basis of a Low Level Biomechanical Countermeasure for Osteoporosis?

NASA Technical Reports Server (NTRS)

Rubin, C.; Zhi, J.; Xu, G.; Cute, M.; McLeod, K.; Hadjiargyrou, M.

1999-01-01

The National Research Council's report entitled: A Strategy for Space Biology and Medical Science, highlighted several areas of fundamental scientific investigation which must be addressed to make long-term space exploration not only feasible, but safe. This "Goldberg Strategy," as well as several subsequent reports published by the NRC's Space Studies Board (e.g., Assessment of Programs in Space Biology and Medicine, Smith et. al., 1991), suggests that the principal hurdle to man's extended presence in space is the osteopenia which parallels reduced gravity. Ironically, the most significant risk to the skeleton may only be realized on return to normal gravitational fields, and full recovery of bone mass may never occur. Effective counter-measures to this microgravity induced bone loss are thus essential. Considering the similarities of space and aging induced osteopenia, an indisputable benefit of such a prophylaxis would be its potential as a treatment for the bone loss which plagues over 25 million people in the U.S. The osteogenic potential of mechanical strain is strongly frequency dependent, with sensitivity increasing up through at least 60 Hz (cycles per second). One hundred seconds per day of a 1 Hz cyclic loading will inhibit disuse osteopenia only if sufficient in magnitude to engender 1000 microstrain (mu(epsilon)) in the tissue. When loading is applied at 30 Hz, however, mechanical strains on the order of 5O mu(epsilon) (approx. 1% of the peak strains which occur in bone during vigorous functional activity), can stimulate bone formation in a duration dependent manner. In longer term animal studies, strains of less than 10 mu(epsilon), induced non-invasively via a whole body vibration, will stimulate bone formation on the surfaces of trabeculae, increase bone density, and improve strength. Finally, preliminary results from a double blind prospective clinical trial shows promise in inhibiting the bone loss which parallels the menopause. Based on these observations, we propose that these high frequency, low magnitude, mechanical strains effectively serve as a "surrogate" for musculoskeletal ground reaction forces, and thus represent an ideal countermeasure to the osteopenia which parallels microgravity conditions. The specific goal of this NASA funded work is to identify genes in bone upregulated by disuse, and to determine the efficacy of an osteogenic mechanical stimulus to downregulate their expression.

In vitro and in vivo investigation of bisphosphonate-loaded hydroxyapatite particles for peri-implant bone augmentation.

PubMed

Kettenberger, Ulrike; Luginbuehl, Vera; Procter, Philip; Pioletti, Dominique P

2017-07-01

Locally applied bisphosphonates, such as zoledronate, have been shown in several studies to inhibit peri-implant bone resorption and recently to enhance peri-implant bone formation. Studies have also demonstrated positive effects of hydroxyapatite (HA) particles on peri-implant bone regeneration and an enhancement of the anti-resorptive effect of bisphosphonates in the presence of calcium. In the present study, both hydroxyapatite nanoparticles (nHA) and zoledronate were combined to achieve a strong reinforcing effect on peri-implant bone. The nHA-zoledronate combination was first investigated in vitro with a pre-osteoclastic cell assay (RAW 264.7) and then in vivo in a rat model of postmenopausal osteoporosis. The in vitro study confirmed that the inhibitory effect of zoledronate on murine osteoclast precursor cells was enhanced by loading the drug on nHA. For the in vivo investigation, either zoledronate-loaded or pure nHA were integrated in hyaluronic acid hydrogel. The gels were injected in screw holes that had been predrilled in rat femoral condyles before the insertion of miniature screws. Micro-CT-based dynamic histomorphometry and histology revealed an unexpected rapid mineralization of the hydrogel in vivo through formation of granules, which served as scaffold for new bone formation. The delivery of zoledronate-loaded nHA further inhibited a degradation of the mineralized hydrogel as well as a resorption of the peri-implant bone as effectively as unbound zoledronate. Hyaluronic acid with zoledronate-loaded nHA, thanks to its dual effect on inducing a rapid mineralization and preventing resorption, is a promising versatile material for bone repair and augmentation. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis.

PubMed

Goldring, Mary B; Goldring, Steven R

2010-03-01

The articular surface plays an essential role in load transfer across the joint, and conditions that produce increased load transfer or altered patterns of load distribution accelerate the development of osteoarthritis (OA). Current knowledge segregates the risk factors into two fundamental mechanisms related to the adverse effects of "abnormal" loading on normal cartilage or "normal" loading on abnormal cartilage. Although chondrocytes can modulate their functional state in response to loading, their capacity to repair and modify the surrounding extracellular matrix is limited in comparison to skeletal cells in bone. This differential adaptive capacity underlies the more rapid appearance of detectable skeletal changes, especially after acute injuries that alter joint mechanics. The imbalance in the adaptation of the cartilage and bone disrupts the physiological relationship between these tissues and further contributes to OA pathology. This review focuses on the specific articular cartilage and skeletal features of OA and the putative mechanisms involved in their pathogenesis.

Implant-bone interface stress distribution in immediately loaded implants of different diameters: a three-dimensional finite element analysis.

PubMed

Ding, Xi; Zhu, Xing-Hao; Liao, Sheng-Hui; Zhang, Xiu-Hua; Chen, Hong

2009-07-01

To establish a 3D finite element model of a mandible with dental implants for immediate loading and to analyze stress distribution in bone around implants of different diameters. Three mandible models, embedded with thread implants (ITI, Straumann, Switzerland) with diameters of 3.3, 4.1, and 4.8 mm, respectively, were developed using CT scanning and self-developed Universal Surgical Integration System software. The von Mises stress and strain of the implant-bone interface were calculated with the ANSYS software when implants were loaded with 150 N vertical or buccolingual forces. When the implants were loaded with vertical force, the von Mises stress concentrated on the mesial and distal surfaces of cortical bone around the neck of implants, with peak values of 25.0, 17.6 and 11.6 MPa for 3.3, 4.1, and 4.8 mm diameters, respectively, while the maximum strains (5854, 4903, 4344 muepsilon) were located on the buccal cancellous bone around the implant bottom and threads of implants. The stress and strain were significantly lower (p < 0.05) with the increased diameter of implant. When the implants were loaded with buccolingual force, the peak von Mises stress values occurred on the buccal surface of cortical bone around the implant neck, with values of 131.1, 78.7, and 68.1 MPa for 3.3, 4.1, and 4.8 mm diameters, respectively, while the maximum strains occurred on the buccal surface of cancellous bone adjacent to the implant neck, with peak values of 14,218, 12,706, and 11,504 microm, respectively. The stress of the 4.1-mm diameter implants was significantly lower (p < 0.05) than those of 3.3-mm diameter implants, but not statistically different from that of the 4.8 mm implant. With an increase of implant diameter, stress and strain on the implant-bone interfaces significantly decreased, especially when the diameter increased from 3.3 to 4.1 mm. It appears that dental implants of 10 mm in length for immediate loading should be at least 4.1 mm in diameter, and uniaxial loading to dental implants should be avoided or minimized.

A micromechanical model to explain the mechanical properties of bovine cortical bone in tension: In vitro fluoride ion effects

NASA Astrophysics Data System (ADS)

Kotha, Shiva Prasad

Bone mineral and bone organic are assumed to be a linearly elastic, brittle material. A simple micromechanical model based on the shear lag theory is developed to model the stress transfer between the mineral platelets of bone. The bone mineral platelets carry most of the applied load while the organic primarily serves to transfer load between the overlapped mineral platelets by shear. Experiments were done to elucidate the mechanism of failure in bovine cortical bone and to decrease the mineral content of control bone with in-vitro fluoride ion treatments. It was suggested that the failure at the ultrastructural level is due to the transverse failure of bonds between the collagen microfibrils in the organic matrix. However, the shear stress transfer and the axial load bearing capacity of the organic is not impaired. Hence, it is assumed that the shear strain in the matrix increases while the shear stress remains constant at the shear yield stress once the matrix starts yielding at the ends of the bone mineral. When the shear stress over the length of the mineral platelet reaches the shear yield stress, no more applied stress is carried by the bone mineral platelets while the organic matrix carries the increased axial load. The bone fails when the axial stress in the organic reaches its ultimate stress. The bone mineral is assumed to dissolve due to in-vitro fluoride ion treatments and precipitate calcium fluoride or fluoroapatite like material. The amount of dissolution is estimated based on 19F Nuclear Magnetic Resonance or a decrease in the carbonate content of bone. The dissolution of bone mineral is assumed to increase the porosity in the organic. We assume that the elastic modulus and the ultimate strength of the organic decrease due to the increased porosity. A simple empirical model is used to model the decrease in the elastic modulus. The strength is modeled to decrease based on an increase in the cross-sectional area occupied by the porosity. The precipitate is assumed to contribute to the mechanical properties of bone due to friction generated by the poisson's contraction of the organic as it carries axial loads. The resulting stress-strain curve predicted by the model resembles the stress-strain curves obtained in the experiments.

Feasibility of detecting orthopaedic screw overtightening using acoustic emission.

PubMed

Pullin, Rhys; Wright, Bryan J; Kapur, Richard; McCrory, John P; Pearson, Matthew; Evans, Sam L; Crivelli, Davide

2017-03-01

A preliminary study of acoustic emission during orthopaedic screw fixation was performed using polyurethane foam as the bone-simulating material. Three sets of screws, a dynamic hip screw, a small fragment screw and a large fragment screw, were investigated, monitoring acoustic-emission activity during the screw tightening. In some specimens, screws were deliberately overtightened in order to investigate the feasibility of detecting the stripping torque in advance. One set of data was supported by load cell measurements to directly measure the axial load through the screw. Data showed that acoustic emission can give good indications of impending screw stripping; such indications are not available to the surgeon at the current state of the art using traditional torque measuring devices, and current practice relies on the surgeon's experience alone. The results suggest that acoustic emission may have the potential to prevent screw overtightening and bone tissue damage, eliminating one of the commonest sources of human error in such scenarios.

Cryogenic 3D printing for producing hierarchical porous and rhBMP-2-loaded Ca-P/PLLA nanocomposite scaffolds for bone tissue engineering.

PubMed

Wang, Chong; Zhao, Qilong; Wang, Min

2017-06-07

The performance of bone tissue engineering scaffolds can be assessed through cell responses to scaffolds, including cell attachment, infiltration, morphogenesis, proliferation, differentiation, etc, which are determined or heavily influenced by the composition, structure, mechanical properties, and biological properties (e.g. osteoconductivity and osteoinductivity) of scaffolds. Although some promising 3D printing techniques such as fused deposition modeling and selective laser sintering could be employed to produce biodegradable bone tissue engineering scaffolds with customized shapes and tailored interconnected pores, effective methods for fabricating scaffolds with well-designed hierarchical porous structure (both interconnected macropores and surface micropores) and tunable osteoconductivity/osteoinductivity still need to be developed. In this investigation, a novel cryogenic 3D printing technique was investigated and developed for producing hierarchical porous and recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded calcium phosphate (Ca-P) nanoparticle/poly(L-lactic acid) nanocomposite scaffolds, in which the Ca-P nanoparticle-incorporated scaffold layer and rhBMP-2-encapsulated scaffold layer were deposited alternatingly using different types of emulsions as printing inks. The mechanical properties of the as-printed scaffolds were comparable to those of human cancellous bone. Sustained releases of Ca 2+ ions and rhBMP-2 were achieved and the biological activity of rhBMP-2 was well-preserved. Scaffolds with a desirable hierarchical porous structure and dual delivery of Ca 2+ ions and rhBMP-2 exhibited superior performance in directing the behaviors of human bone marrow-derived mesenchymal stem cells and caused improved cell viability, attachment, proliferation, and osteogenic differentiation, which has suggested their great potential for bone tissue engineering.

In vivo study of magnesium plate and screw degradation and bone fracture healing.

PubMed

Chaya, Amy; Yoshizawa, Sayuri; Verdelis, Kostas; Myers, Nicole; Costello, Bernard J; Chou, Da-Tren; Pal, Siladitya; Maiti, Spandan; Kumta, Prashant N; Sfeir, Charles

2015-05-01

Each year, millions of Americans suffer bone fractures, often requiring internal fixation. Current devices, like plates and screws, are made with permanent metals or resorbable polymers. Permanent metals provide strength and biocompatibility, but cause long-term complications and may require removal. Resorbable polymers reduce long-term complications, but are unsuitable for many load-bearing applications. To mitigate complications, degradable magnesium (Mg) alloys are being developed for craniofacial and orthopedic applications. Their combination of strength and degradation make them ideal for bone fixation. Previously, we conducted a pilot study comparing Mg and titanium devices with a rabbit ulna fracture model. We observed Mg device degradation, with uninhibited healing. Interestingly, we observed bone formation around degrading Mg, but not titanium, devices. These results highlighted the potential for these fixation devices. To better assess their efficacy, we conducted a more thorough study assessing 99.9% Mg devices in a similar rabbit ulna fracture model. Device degradation, fracture healing, and bone formation were evaluated using microcomputed tomography, histology and biomechanical tests. We observed device degradation throughout, and calculated a corrosion rate of 0.40±0.04mm/year after 8 weeks. In addition, we observed fracture healing by 8 weeks, and maturation after 16 weeks. In accordance with our pilot study, we observed bone formation surrounding Mg devices, with complete overgrowth by 16 weeks. Bend tests revealed no difference in flexural load of healed ulnae with Mg devices compared to intact ulnae. These data suggest that Mg devices provide stabilization to facilitate healing, while degrading and stimulating new bone formation. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Constant strain rate and peri-implant bone modeling: an in vivo longitudinal micro-CT analysis.

PubMed

De Smet, Els; Jaecques, Siegfried V N; Wevers, Martine; Sloten, Jos Vander; Naert, Ignace E

2013-06-01

Strain, frequency, loading time, and strain rate, among others, determine mechanical parameters in osteogenic loading. We showed a significant osteogenic effect on bone mass (BM) by daily peri-implant loading at 1.600µε.s(-1) after 4 weeks. To study the peri-implant osteogenic effect of frequency and strain in the guinea pig tibia by in vivo longitudinal micro-computed tomography (CT) analysis. One week after implant installation in both hind limb tibiae, one implant was loaded daily for 10' during 4 weeks, while the other served as control. Frequencies (3, 10, and 30Hz) and strains varied alike in the three series to keep the strain rate constant at 1.600µε.s(-1) . In vivo micro-CT scans were taken of both tibiae: 1 week after implantation but before loading (v1) and after 2 (v2) and 4 weeks (v3) of loading as well as postmortem (pm). BM (BM (%) bone-occupied area fraction) was calculated as well as the difference between test and control sides (delta BM) RESULTS: All implants (n=78) were clinically stable at 4 weeks. Significant increase in BM was measured between v1 and v2 (p<.0001) and between v1 and v3 (p<.0001). A significant positive effect of loading on delta BM was observed in the distal peri-implant marrow 500 Region of Interest already 2 weeks after loading (p=.01) and was significantly larger (11%) in series 1 compared with series 2 (p=.006) and 3 (p=.016). Within the constraints of constant loading time and strain rate, the effect of early implant loading on the peri-implant bone is strongly dependent on strain and frequency. This cortical bone model has shown to be most sensitive for high force loading at low frequency. © 2011 Wiley Periodicals, Inc.

Comparing PMMA and calcium sulfate as carriers for the local delivery of antibiotics to infected surgical sites.

PubMed

McConoughey, Stephen J; Howlin, Robert P; Wiseman, Jessica; Stoodley, Paul; Calhoun, Jason H

2015-05-01

Antibiotic-loaded bone cement is a primary option for treatment of orthopedic infections. Poly(methyl methacrylate) (PMMA) is a widely used cement that, when loaded with antibiotics in spacer or bead form, has been shown to reduce infection rates. However, PMMA is not resorbable and requires a second surgery for removal, while also acting as a potential foreign body for bacterial colonization. Alternatively, resorbable bone cements, such as calcium sulfate, have been proposed and present the advantage of being completely reabsorbed. It is unknown whether the antibiotic elution characteristics of absorbable bone cements are similar to PMMA. This study (1) characterized antibiotic elution from synthetic, highly purified calcium sulfate cement beads of varying sizes against pathogenic bacteria both in liquid culture and seeded on agar plates, (2) tested calcium sulfate beads against PMMA beads loaded with the same antibiotics, and (3) analyzed the structural differences between how PMMA and calcium sulfate bind to antibiotics. In every assay, the calcium sulfate beads performed as well as, or better than, the PMMA beads in inhibition of bacterial growth and elution of vancomycin in vitro with complete elution observed from calcium sulfate within three days. These data suggest that calcium sulfate, functions, as well as PMMA in the patient setting for infection control. © 2014 Wiley Periodicals, Inc.

Assessing the local mechanical environment in medial opening wedge high tibial osteotomy using finite element analysis.

PubMed

Pauchard, Yves; Ivanov, Todor G; McErlain, David D; Milner, Jaques S; Giffin, J Robert; Birmingham, Trevor B; Holdsworth, David W

2015-03-01

High-tibial osteotomy (HTO) is a surgical technique aimed at shifting load away from one tibiofemoral compartment, in order the reduce pain and progression of osteoarthritis (OA). Various implants have been designed to stabilize the osteotomy and previous studies have been focused on determining primary stability (a global measure) that these designs provide. It has been shown that the local mechanical environment, characterized by bone strains and segment micromotion, is important in understanding healing and these data are not currently available. Finite element (FE) modeling was utilized to assess the local mechanical environment provided by three different fixation plate designs: short plate with spacer, long plate with spacer and long plate without spacer. Image-based FE models of the knee were constructed from healthy individuals (N = 5) with normal knee alignment. An HTO gap was virtually added without changing the knee alignment and HTO implants were inserted. Subsequently, the local mechanical environment, defined by bone compressive strain and wedge micromotion, was assessed. Furthermore, implant stresses were calculated. Values were computed under vertical compression in zero-degree knee extension with loads set at 1 and 2 times the subject-specific body weight (1 BW, 2 BW). All studied HTO implant designs provide an environment for successful healing at 1 BW and 2 BW loading. Implant von Mises stresses (99th percentile) were below 60 MPa in all experiments, below the material yield strength and significantly lower in long spacer plates. Volume fraction of high compressive strain ( > 3000 microstrain) was below 5% in all experiments and no significant difference between implants was detected. Maximum vertical micromotion between bone segments was below 200 μm in all experiments and significantly larger in the implant without a tooth. Differences between plate designs generally became apparent only at 2 BW loading. Results suggest that with compressive loading of 2 BW, long spacer plates experience the lowest implant stresses, and spacer plates (long or short) result in smaller wedge micromotion, potentially beneficial for healing. Values are sensitive to subject bone geometry, highlighting the need for subject-specific modeling. This study demonstrates the benefits of using image-based FE modeling and bone theory to fine-tune HTO implant design.

Development and validation of a canine radius replica for mechanical testing of orthopedic implants.

PubMed

Little, Jeffrey P; Horn, Timothy J; Marcellin-Little, Denis J; Harrysson, Ola L A; West, Harvey A

2012-01-01

To design and fabricate fiberglass-reinforced composite (FRC) replicas of a canine radius and compare their mechanical properties with those of radii from dog cadavers. Replicas based on 3 FRC formulations with 33%, 50%, or 60% short-length discontinuous fiberglass by weight (7 replicas/group) and 5 radii from large (> 30-kg) dog cadavers. Bones and FRC replicas underwent nondestructive mechanical testing including 4-point bending, axial loading, and torsion and destructive testing to failure during 4-point bending. Axial, internal and external torsional, and bending stiffnesses were calculated. Axial pullout loads for bone screws placed in the replicas and cadaveric radii were also assessed. Axial, internal and external torsional, and 4-point bending stiffnesses of FRC replicas increased significantly with increasing fiberglass content. The 4-point bending stiffness of 33% and 50% FRC replicas and axial and internal torsional stiffnesses of 33% FRC replicas were equivalent to the cadaveric bone stiffnesses. Ultimate 4-point bending loads did not differ significantly between FRC replicas and bones. Ultimate screw pullout loads did not differ significantly between 33% or 50% FRC replicas and bones. Mechanical property variability (coefficient of variation) of cadaveric radii was approximately 2 to 19 times that of FRC replicas, depending on loading protocols. Within the range of properties tested, FRC replicas had mechanical properties equivalent to and mechanical property variability less than those of radii from dog cadavers. Results indicated that FRC replicas may be a useful alternative to cadaveric bones for biomechanical testing of canine bone constructs.

Sost, independent of the non-coding enhancer ECR5, is required for bone mechanoadaptation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robling, Alexander G.; Kang, Kyung Shin; Bullock, Whitney A.

Here, sclerostin ( Sost) is a negative regulator of bone formation that acts upon the Wnt signaling pathway. Sost is mechanically regulated at both mRNA and protein level such that loading represses and unloading enhances Sost expression, in osteocytes and in circulation. The non-coding evolutionarily conserved enhancer ECR5 has been previously reported as a transcriptional regulatory element required for modulating Sost expression in osteocytes. Here we explored the mechanisms by which ECR5, or several other putative transcriptional enhancers regulate Sost expression, in response to mechanical stimulation. We found that in vivo ulna loading is equally osteoanabolic in wildtype and Sostmore » –/– mice, although Sost is required for proper distribution of load-induced bone formation to regions of high strain. Using Luciferase reporters carrying the ECR5 non-coding enhancer and heterologous or homologous h SOST promoters, we found that ECR5 is mechanosensitive in vitro and that ECR5-driven Luciferase activity decreases in osteoblasts exposed to oscillatory fluid flow. Yet, ECR5–/– mice showed similar magnitude of load-induced bone formation and similar periosteal distribution of bone formation to high-strain regions compared to wildtype mice. Further, we found that in contrast to Sost–/– mice, which are resistant to disuse-induced bone loss, ECR5–/– mice lose bone upon unloading to a degree similar to wildtype control mice. ECR5 deletion did not abrogate positive effects of unloading on Sost, suggesting that additional transcriptional regulators and regulatory elements contribute to load-induced regulation of Sost.« less

Sost, independent of the non-coding enhancer ECR5, is required for bone mechanoadaptation

DOE PAGES

Robling, Alexander G.; Kang, Kyung Shin; Bullock, Whitney A.; ...

2016-09-04

Here, sclerostin ( Sost) is a negative regulator of bone formation that acts upon the Wnt signaling pathway. Sost is mechanically regulated at both mRNA and protein level such that loading represses and unloading enhances Sost expression, in osteocytes and in circulation. The non-coding evolutionarily conserved enhancer ECR5 has been previously reported as a transcriptional regulatory element required for modulating Sost expression in osteocytes. Here we explored the mechanisms by which ECR5, or several other putative transcriptional enhancers regulate Sost expression, in response to mechanical stimulation. We found that in vivo ulna loading is equally osteoanabolic in wildtype and Sostmore » –/– mice, although Sost is required for proper distribution of load-induced bone formation to regions of high strain. Using Luciferase reporters carrying the ECR5 non-coding enhancer and heterologous or homologous h SOST promoters, we found that ECR5 is mechanosensitive in vitro and that ECR5-driven Luciferase activity decreases in osteoblasts exposed to oscillatory fluid flow. Yet, ECR5–/– mice showed similar magnitude of load-induced bone formation and similar periosteal distribution of bone formation to high-strain regions compared to wildtype mice. Further, we found that in contrast to Sost–/– mice, which are resistant to disuse-induced bone loss, ECR5–/– mice lose bone upon unloading to a degree similar to wildtype control mice. ECR5 deletion did not abrogate positive effects of unloading on Sost, suggesting that additional transcriptional regulators and regulatory elements contribute to load-induced regulation of Sost.« less

The response of equine cortical bone to loading at strain rates experienced in vivo by the galloping horse.

PubMed

Evans, G P; Behiri, J C; Vaughan, L C; Bonfield, W

1992-03-01

The behaviour of cortical bone under load is strain rate-dependent, i.e. it is dependent on the rate at which the load is applied. This is particularly relevant in the galloping horse since the strain rates experienced by the bone are far in excess of those recorded for any other species. In this study the effect of strain rates between 0.0001 and 1 sec-1 on the mechanical properties of equine cortical bone were assessed. Initially, increasing strain rates resulted in increased mechanical properties. Beyond a critical value, however, further increases in strain rate resulted in lower strain to failure and energy absorbing capacity. This critical rate occurred around 0.1 sec-1 which is within the in vivo range for a galloping racehorse. Analysis of the stress-strain curves revealed a transition in the type of deformation at this point from pseudo-ductile to brittle. Bones undergoing brittle deformation are more likely to fail under load, leading to catastrophic fracture and destruction of the animal.

Influence of exercise mode and osteogenic index on bone biomarker responses during short-term physical training.

PubMed

Lester, Mark E; Urso, Maria L; Evans, Rachel K; Pierce, Joseph R; Spiering, Barry A; Maresh, Carl M; Hatfield, Disa L; Kraemer, William J; Nindl, Bradley C

2009-10-01

Prescribing exercise based on intensity, frequency, and duration of loading may maximize osteogenic responses in bone, but a model of the osteogenic potential of exercise has not been established in humans. In rodents, an osteogenic index (OI) has been used to predict the osteogenic potential of exercise. The current study sought to determine whether aerobic, resistance, or combined aerobic and resistance exercise programs conducted over eight weeks and compared to a control group could produce changes in biochemical markers of bone turnover indicative of bone formation. We further sought to determine whether an OI could be calculated for each of these programs that would reflect observed biochemical changes. We collected serum biomarkers [bone-specific alkaline phosphatase (BAP), osteocalcin, tartrate-resistant acid phosphatase (TRAP), C-terminal telopeptide fragment of type I collagen (CTx), deoxypyridinoline (DPD), 25-hydroxy vitamin D (25(OH)D), and parathyroid hormone (PTH)] in 56 women (20.3+/-1.8 years) before, during and after eight weeks of training. We also measured bone mineral density (BMD) at regional areas of interest using DXA and pQCT. Biomarkers of bone formation (BAP and osteocalcin) increased in the Resistance and Combined groups (p<0.05), while biomarkers of bone resorption (TRAP and DPD) decreased and increased, respectively, after training (p<0.05) in all groups. Small changes in volumetric and areal BMD (p<0.05) were observed in the distal tibia in the Aerobic and Combined groups, respectively. Mean weekly OIs were 16.0+/-1.9, 20.6+/-2.2, and 36.9+/-5.2 for the Resistance, Aerobic, and Combined groups, respectively. The calculated osteogenic potential of our programs did not correlate with the observed changes in biomarkers of bone turnover. The results of the present study demonstrate that participation in an eight week physical training program that incorporates a resistance component by previously inactive young women results in alterations in biomarkers of bone remodeling indicative of increased formation without substantial alterations in markers of resorption.

Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonuria

PubMed Central

Stroup, Bridget M.; Sawin, Emily A.; Murali, Sangita G.; Binkley, Neil; Hansen, Karen E.

2017-01-01

Background. Skeletal fragility is a complication of phenylketonuria (PKU). A diet containing amino acids compared with glycomacropeptide reduces bone size and strength in mice. Objective. We tested the hypothesis that amino acid medical foods (AA-MF) provide a high dietary acid load, subsequently increasing urinary excretion of renal net acid, calcium, and magnesium, compared to glycomacropeptide medical foods (GMP-MF). Design. In a crossover design, 8 participants with PKU (16–35 y) provided food records and 24-hr urine samples after consuming a low-Phe diet in combination with AA-MF and GMP-MF for 1–3 wks. We calculated potential renal acid load (PRAL) of AA-MF and GMP-MF and determined bone mineral density (BMD) measurements using dual X-ray absorptiometry. Results. AA-MF provided 1.5–2.5-fold higher PRAL and resulted in 3-fold greater renal net acid excretion compared to GMP-MF (p = 0.002). Dietary protein, calcium, and magnesium intake were similar. GMP-MF significantly reduced urinary excretion of calcium by 40% (p = 0.012) and magnesium by 30% (p = 0.029). Two participants had low BMD-for-age and trabecular bone scores, indicating microarchitectural degradation. Urinary calcium with AA-MF negatively correlated with L1–L4 BMD. Conclusion. Compared to GMP-MF, AA-MF increase dietary acid load, subsequently increasing urinary calcium and magnesium excretion, and likely contributing to skeletal fragility in PKU. The trial was registered at clinicaltrials.gov as NCT01428258. PMID:28546877

In vivo dynamic compression has less detrimental effect than static compression on newly formed bone of a rat caudal vertebra

PubMed Central

Benoit, A.; Mustafy, T.; Londono, I.; Grimard, G.; Aubin, C-E.; Villemure, I.

2016-01-01

Fusionless devices are currently designed to treat spinal deformities such as scoliosis by the application of a controlled mechanical loading. Growth modulation by dynamic compression was shown to preserve soft tissues. The objective of this in vivo study was to characterize the effect of static vs. dynamic loading on the bone formed during growth modulation. Controlled compression was applied during 15 days on the 7th caudal vertebra (Cd7) of rats during growth spurt. The load was sustained in the “static” group and sinusoidally oscillating in the “dynamic” group. The effect of surgery and of the device was investigated using control and sham (operated on but no load applied) groups. A high resolution CT-scan of Cd7 was acquired at days 2, 8 and 15 of compression. Growth rates, histomorphometric parameters and mineral density of the newly formed bone were quantified and compared. Static and dynamic loadings significantly reduced the growth rate by 20% compared to the sham group. Dynamic loading preserved newly formed bone histomorphometry and mineral density whereas static loading induced thicker (+31%) and more mineralized (+12%) trabeculae. A significant sham effect was observed. Growth modulation by dynamic compression constitutes a promising way to develop new treatment for skeletal deformities. PMID:27609036

[Tibial press-fit fixation of flexor tendons for reconstruction of the anterior cruciate ligament].

PubMed

Ettinger, M; Liodakis, E; Haasper, C; Hurschler, C; Breitmeier, D; Krettek, C; Jagodzinski, M

2012-09-01

Press-fit fixation of hamstring tendon autografts for anterior cruciate ligament reconstruction is an interesting technique because no hardware is necessary. This study compares the biomechanical properties of press-fit fixations to an interference screw fixation. Twenty-eight human cadaveric knees were used for hamstring tendon explantation. An additional bone block was harvested from the tibia. We used 28 porcine femora for graft fixation. Constructs were cyclically stretched and then loaded until failure. Maximum load to failure, stiffness and elongation during failure testing and cyclic loading were investigated. The maximum load to failure was 970±83 N for the press-fit tape fixation (T), 572±151 N for the bone bridge fixation (TS), 544±109 N for the interference screw fixation (I), 402±77 N for the press-fit suture fixation (S) and 290±74 N for the bone block fixation technique (F). The T fixation had a significantly better maximum load to failure compared to all other techniques (p<0.001). This study demonstrates that a tibial press-fit technique which uses an additional bone block has better maximum load to failure results compared to a simple interference screw fixation.

Partial Reductions in Mechanical Loading Yield Proportional Changes in Bone Density, Bone Architecture, and Muscle Mass

PubMed Central

Ellman, Rachel; Spatz, Jordan; Cloutier, Alison; Palme, Rupert; Christiansen, Blaine A; Bouxsein, Mary L

2014-01-01

Although the musculoskeletal system is known to be sensitive to changes in its mechanical environment, the relationship between functional adaptation and below-normal mechanical stimuli is not well defined. We investigated bone and muscle adaptation to a range of reduced loading using the partial weight suspension (PWS) system, in which a two-point harness is used to offload a tunable amount of body weight while maintaining quadrupedal locomotion. Skeletally mature female C57Bl/6 mice were exposed to partial weight bearing at 20%, 40%, 70%, or 100% of body weight for 21 days. A hindlimb unloaded (HLU) group was included for comparison in addition to age-matched controls in normal housing. Gait kinematics was measured across the full range of weight bearing, and some minor alterations in gait from PWS were identified. With PWS, bone and muscle changes were generally proportional to the degree of unloading. Specifically, total body and hindlimb bone mineral density, calf muscle mass, trabecular bone volume of the distal femur, and cortical area of the femur midshaft were all linearly related to the degree of unloading. Even a load reduction to 70% of normal weight bearing was associated with significant bone deterioration and muscle atrophy. Weight bearing at 20% did not lead to better bone outcomes than HLU despite less muscle atrophy and presumably greater mechanical stimulus, requiring further investigation. These data confirm that the PWS model is highly effective in applying controllable, reduced, long-term loading that produces predictable, discrete adaptive changes in muscle and bone of the hindlimb. PMID:23165526

Age-related mechanical strength evolution of trabecular bone under fatigue damage for both genders: Fracture risk evaluation.

PubMed

Ben Kahla, Rabeb; Barkaoui, Abdelwahed; Merzouki, Tarek

2018-08-01

Bone tissue is a living composite material, providing mechanical and homeostatic functions, and able to constantly adapt its microstructure to changes in long term loading. This adaptation is conducted by a physiological process, known as "bone remodeling". This latter is manifested by interactions between osteoclasts and osteoblasts, and can be influenced by many local factors, via effects on bone cell differentiation and proliferation. In the current work, age and gender effects on damage rate evolution, throughout life, have been investigated using a mechanobiological finite element modeling. To achieve the aim, a mathematical model has been developed, coupling both cell activities and mechanical behavior of trabecular bone, under cyclic loadings. A series of computational simulations (ABAQUS/UMAT) has been performed on a 3D human proximal femur, allowing to investigate the effects of mechanical and biological parameters on mechanical strength of trabecular bone, in order to evaluate the fracture risk resulting from fatigue damage. The obtained results revealed that mechanical stimulus amplitude affects bone resorption and formation rates, and indicated that age and gender are major factors in bone response to the applied loadings. Copyright © 2018 Elsevier Ltd. All rights reserved.

Novel approach to the fabrication of an artificial small bone using a combination of sponge replica and electrospinning methods

NASA Astrophysics Data System (ADS)

Kim, Yang-Hee; Lee, Byong-Taek

2011-06-01

In this study, a novel artificial small bone consisting of ZrO2-biphasic calcium phosphate/polymethylmethacrylate-polycaprolactone-hydroxyapatite (ZrO2-BCP/PMMA-PCL-HAp) was fabricated using a combination of sponge replica and electrospinning methods. To mimic the cancellous bone, the ZrO2/BCP scaffold was composed of three layers, ZrO2, ZrO2/BCP and BCP, fabricated by the sponge replica method. The PMMA-PCL fibers loaded with HAp powder were wrapped around the ZrO2/BCP scaffold using the electrospinning process. To imitate the Haversian canal region of the bone, HAp-loaded PMMA-PCL fibers were wrapped around a steel wire of 0.3 mm diameter. As a result, the bundles of fiber wrapped around the wires imitated the osteon structure of the cortical bone. Finally, the ZrO2/BCP scaffold was surrounded by HAp-loaded PMMA-PCL composite bundles. After removal of the steel wires, the ZrO2/BCP scaffold and bundles of HAp-loaded PMMA-PCL formed an interconnected structure resembling the human bone. Its diameter, compressive strength and porosity were approximately 12 mm, 5 MPa and 70%, respectively, and the viability of MG-63 osteoblast-like cells was determined to be over 90% by the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. This artificial bone shows excellent cytocompatibility and is a promising bone regeneration material.

Novel approach to the fabrication of an artificial small bone using a combination of sponge replica and electrospinning methods

PubMed Central

Kim, Yang-Hee; Lee, Byong-Taek

2011-01-01

In this study, a novel artificial small bone consisting of ZrO2-biphasic calcium phosphate/polymethylmethacrylate-polycaprolactone-hydroxyapatite (ZrO2-BCP/PMMA-PCL-HAp) was fabricated using a combination of sponge replica and electrospinning methods. To mimic the cancellous bone, the ZrO2/BCP scaffold was composed of three layers, ZrO2, ZrO2/BCP and BCP, fabricated by the sponge replica method. The PMMA-PCL fibers loaded with HAp powder were wrapped around the ZrO2/BCP scaffold using the electrospinning process. To imitate the Haversian canal region of the bone, HAp-loaded PMMA-PCL fibers were wrapped around a steel wire of 0.3 mm diameter. As a result, the bundles of fiber wrapped around the wires imitated the osteon structure of the cortical bone. Finally, the ZrO2/BCP scaffold was surrounded by HAp-loaded PMMA-PCL composite bundles. After removal of the steel wires, the ZrO2/BCP scaffold and bundles of HAp-loaded PMMA-PCL formed an interconnected structure resembling the human bone. Its diameter, compressive strength and porosity were approximately 12 mm, 5 MPa and 70%, respectively, and the viability of MG-63 osteoblast-like cells was determined to be over 90% by the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. This artificial bone shows excellent cytocompatibility and is a promising bone regeneration material. PMID:27877406

Numerical study of effect of elastomeric stress absorbers on stress reduction in bone-dental implant interface.

PubMed

Mehdi, Ghalem; Belarbi, Abderrahmane; Mansouri, Bensmaine; Azari, Zitouni

2015-01-01

This paper focused on optimal stress distribution in the mandibular bone surrounding a dental implant and is devoted to the development of a modified Osteoplant® implant type in order to minimize stress concentration in the bone-implant interface. This study investigated 0.4 mm thick layers of two elastomeric stress barriers incorporated into the dental implant using 3-D finite element analysis. Overall, this proposed implant provoked lower load transfer in bone-implant interface due to the effect of the elastomers as stress absorbers. The stress level in the bone was reduced between 28% and 42% for three load cases: 75 N, 60 N and 27 N in corono-apical, linguo-buccal and disto-mesial direction, respectively. The proposed model provided an acceptable solution for load transfer reduction to the mandible. This investigation also permitted to choose how to incorporate two elastomers into the Osteoplant® implant system.

Design and Fabrication of 3D printed Scaffolds with a Mechanical Strength Comparable to Cortical Bone to Repair Large Bone Defects

PubMed Central

Roohani-Esfahani, Seyed-Iman; Newman, Peter; Zreiqat, Hala

2016-01-01

A challenge in regenerating large bone defects under load is to create scaffolds with large and interconnected pores while providing a compressive strength comparable to cortical bone (100–150 MPa). Here we design a novel hexagonal architecture for a glass-ceramic scaffold to fabricate an anisotropic, highly porous three dimensional scaffolds with a compressive strength of 110 MPa. Scaffolds with hexagonal design demonstrated a high fatigue resistance (1,000,000 cycles at 1–10 MPa compressive cyclic load), failure reliability and flexural strength (30 MPa) compared with those for conventional architecture. The obtained strength is 150 times greater than values reported for polymeric and composite scaffolds and 5 times greater than reported values for ceramic and glass scaffolds at similar porosity. These scaffolds open avenues for treatment of load bearing bone defects in orthopaedic, dental and maxillofacial applications. PMID:26782020

Design and Fabrication of 3D printed Scaffolds with a Mechanical Strength Comparable to Cortical Bone to Repair Large Bone Defects

NASA Astrophysics Data System (ADS)

Roohani-Esfahani, Seyed-Iman; Newman, Peter; Zreiqat, Hala

2016-01-01

A challenge in regenerating large bone defects under load is to create scaffolds with large and interconnected pores while providing a compressive strength comparable to cortical bone (100-150 MPa). Here we design a novel hexagonal architecture for a glass-ceramic scaffold to fabricate an anisotropic, highly porous three dimensional scaffolds with a compressive strength of 110 MPa. Scaffolds with hexagonal design demonstrated a high fatigue resistance (1,000,000 cycles at 1-10 MPa compressive cyclic load), failure reliability and flexural strength (30 MPa) compared with those for conventional architecture. The obtained strength is 150 times greater than values reported for polymeric and composite scaffolds and 5 times greater than reported values for ceramic and glass scaffolds at similar porosity. These scaffolds open avenues for treatment of load bearing bone defects in orthopaedic, dental and maxillofacial applications.

Modeling Vascularized Bone Regeneration Within a Porous Biodegradable CaP Scaffold Loaded with Growth Factors

PubMed Central

Sun, X; Kang, Y; Bao, J; Zhang, Y; Yang, Y; Zhou, X

2013-01-01

Osteogenetic microenvironment is a complex constitution in which extracellular matrix (ECM) molecules, stem cells and growth factors each interact to direct the coordinate regulation of bone tissue development. Importantly, angiogenesis improvement and revascularization are critical for osteogenesis during bone tissue regeneration processes. In this study, we developed a three-dimensional (3D) multi-scale system model to study cell response to growth factors released from a 3D biodegradable porous calcium phosphate (CaP) scaffold. Our model reconstructed the 3D bone regeneration system and examined the effects of pore size and porosity on bone formation and angiogenesis. The results suggested that scaffold porosity played a more dominant role in affecting bone formation and angiogenesis compared with pore size, while the pore size could be controlled to tailor the growth factor release rate and release fraction. Furthermore, a combination of gradient VEGF with BMP2 and Wnt released from the multi-layer scaffold promoted angiogenesis and bone formation more readily than single growth factors. These results demonstrated that the developed model can be potentially applied to predict vascularized bone regeneration with specific scaffold and growth factors. PMID:23566802

PHOSPHO1 is essential for mechanically competent mineralization and the avoidance of spontaneous fractures

PubMed Central

Huesa, Carmen; Yadav, Manisha C.; Finnilä, Mikko A.J.; Goodyear, Simon R.; Robins, Simon P.; Tanner, K. Elizabeth; Aspden, Richard M.; Millán, José Luis; Farquharson, Colin

2011-01-01

Phosphatases are essential for the mineralization of the extracellular matrix within the skeleton. Their precise identities and functions however remain unclear. PHOSPHO1 is a phosphoethanolamine/phosphocholine phosphatase involved in the generation of inorganic phosphate for bone mineralization. It is highly expressed at sites of mineralization in bone and cartilage. The bones of Phospho1−/− mice are hypomineralized, bowed and present with spontaneous greenstick fractures at birth. In this study we show that PHOSPHO1 is essential for mechanically competent mineralization that is able to withstand habitual load. Long bones from Phospho1−/− mice did not fracture during 3- point bending but deformed plastically. With dynamic loading nanoindentation the elastic modulus and hardness of Phospho1−/− tibiae were significantly lower than wild-type tibia. Raman microscopy revealed significantly lower mineral:matrix ratios and lower carbonate substitutions in Phospho1−/− tibia. The altered dihydroxylysinonorleucine/hydroxyllysinonorleucine and pyridoline/deoxypyridinoline collagen crosslink ratios indicated possible changes in lysyl hydroxylase-1 activity and/or bone mineralization status. The bone formation and resorption markers, N-terminal propeptide and C-terminal telopeptide of Type I collagen, were both increased in Phospho1−/− mice and this we associated with increased bone remodelling during fracture repair or an attempt to remodel a mechanically competent bone capable of withstanding physiological load. In summary these data indicate that Phospho1−/− bones are hypomineralized and, consequently, are softer and more flexible. An inability to withstand physiological loading may explain the deformations noted. We hypothesize that this phenotype is due to the reduced availability of inorganic phosphate to form hydroxyapatite during mineralization, creating an undermineralized yet active bone. PMID:21272676

Effect of micromorphology of cortical bone tissue on crack propagation under dynamic loading

NASA Astrophysics Data System (ADS)

Wang, Mayao; Gao, Xing; Abdel-Wahab, Adel; Li, Simin; Zimmermann, Elizabeth A.; Riedel, Christoph; Busse, Björn; Silberschmidt, Vadim V.

2015-09-01

Structural integrity of bone tissue plays an important role in daily activities of humans. However, traumatic incidents such as sports injuries, collisions and falls can cause bone fracture, servere pain and mobility loss. In addition, ageing and degenerative bone diseases such as osteoporosis can increase the risk of fracture [1]. As a composite-like material, a cortical bone tissue is capable of tolerating moderate fracture/cracks without complete failure. The key to this is its heterogeneously distributed microstructural constituents providing both intrinsic and extrinsic toughening mechanisms. At micro-scale level, cortical bone can be considered as a four-phase composite material consisting of osteons, Haversian canals, cement lines and interstitial matrix. These microstructural constituents can directly affect local distributions of stresses and strains, and, hence, crack initiation and propagation. Therefore, understanding the effect of micromorphology of cortical bone on crack initiation and propagation, especially under dynamic loading regimes is of great importance for fracture risk evaluation. In this study, random microstructures of a cortical bone tissue were modelled with finite elements for four groups: healthy (control), young age, osteoporosis and bisphosphonate-treated, based on osteonal morphometric parameters measured from microscopic images for these groups. The developed models were loaded under the same dynamic loading conditions, representing a direct impact incident, resulting in progressive crack propagation. An extended finite-element method (X-FEM) was implemented to realize solution-dependent crack propagation within the microstructured cortical bone tissues. The obtained simulation results demonstrate significant differences due to micromorphology of cortical bone, in terms of crack propagation characteristics for different groups, with the young group showing highest fracture resistance and the senior group the lowest.

Early Loading of Fluoridated Implants Placed in Fresh Extraction Sockets and Healed Bone: A 3- to 5-Year Clinical and Radiographic Follow-Up Study of 39 Consecutive Patients.

PubMed

Oxby, Gert; Oxby, Fredrik; Oxby, Johan; Saltvik, Tomas; Nilsson, Peter

2015-10-01

Immediate placement of implants in extraction sockets for early loading is an attractive treatment modality due to reduced treatment time. However, the outcome of fluoridated implants in this situation with regard to bone levels and health of soft tissues is not well documented. To evaluate the outcome of early loading of OsseoSpeed(™) dental implants placed into fresh extraction sockets and healed bone in consecutive patients treated in a private clinic. A total of 182 OsseoSpeed(™) implants (Astra Tech Implant System, DENTSPLY Implants, Mölndal, Sweden), 72 in immediate extraction sockets and 110 in healed sites, were placed in 39 consecutive patients. The implants were loaded with permanent restorations within 60 days (average 31 days). Clinical and radiographic follow-up examinations were performed annually for at least 3 years (mean 55 months). An aesthetic index was used to evaluate the soft tissues adjacent to the prosthetic restorations. No implant was lost during the observation period, giving a survival rate of 100%. Bone level changes during the observation period were minimal, with a mean marginal bone loss of 0.3 ± 0.9 mm around the delayed implants and a mean marginal bone gain of 0.3 ± 1.4 mm around the immediate implants (p = .0036). The frequency distribution of bone level revealed that 85% of implants placed in fresh extraction sockets and 84% of implants in healed bone did not show any loss of bone level during follow-up (p = NS). Soft tissue complications were observed at two immediate implant sites in one patient. The remaining 180 implants received the highest aesthetic score. Moreover, no signs of peri-implant purulent infection or aggressive bone loss were found during the follow-up period. Early loading of fluoridated implants with permanent constructions appears to be a viable therapy for implants placed immediately in extraction sites and in healed bone. © 2014 Wiley Periodicals, Inc.

BMP delivery complements the guiding effect of scaffold architecture without altering bone microstructure in critical-sized long bone defects: A multiscale analysis.

PubMed

Cipitria, A; Wagermaier, W; Zaslansky, P; Schell, H; Reichert, J C; Fratzl, P; Hutmacher, D W; Duda, G N

2015-09-01

Scaffold architecture guides bone formation. However, in critical-sized long bone defects additional BMP-mediated osteogenic stimulation is needed to form clinically relevant volumes of new bone. The hierarchical structure of bone determines its mechanical properties. Yet, the micro- and nanostructure of BMP-mediated fast-forming bone has not been compared with slower regenerating bone without BMP. We investigated the combined effects of scaffold architecture (physical cue) and BMP stimulation (biological cue) on bone regeneration. It was hypothesized that a structured scaffold directs tissue organization through structural guidance and load transfer, while BMP stimulation accelerates bone formation without altering the microstructure at different length scales. BMP-loaded medical grade polycaprolactone-tricalcium phosphate scaffolds were implanted in 30mm tibial defects in sheep. BMP-mediated bone formation after 3 and 12 months was compared with slower bone formation with a scaffold alone after 12 months. A multiscale analysis based on microcomputed tomography, histology, polarized light microscopy, backscattered electron microscopy, small angle X-ray scattering and nanoindentation was used to characterize bone volume, collagen fiber orientation, mineral particle thickness and orientation, and local mechanical properties. Despite different observed kinetics in bone formation, similar structural properties on a microscopic and sub-micron level seem to emerge in both BMP-treated and scaffold only groups. The guiding effect of the scaffold architecture is illustrated through structural differences in bone across different regions. In the vicinity of the scaffold increased tissue organization is observed at 3 months. Loading along the long bone axis transferred through the scaffold defines bone micro- and nanostructure after 12 months. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Three-Dimensional Mechanical Loading Modulates the Osteogenic Response of Mesenchymal Stem Cells to Tumor-Derived Soluble Signals

PubMed Central

Lynch, Maureen E.; Chiou, Aaron E.; Lee, Min Joon; Marcott, Stephen C.; Polamraju, Praveen V.; Lee, Yeonkyung

2016-01-01

Dynamic mechanical loading is a strong anabolic signal in the skeleton, increasing osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs) and increasing the bone-forming activity of osteoblasts, but its role in bone metastatic cancer is relatively unknown. In this study, we integrated a hydroxyapatite-containing three-dimensional (3D) scaffold platform with controlled mechanical stimulation to investigate the effects of cyclic compression on the interplay between breast cancer cells and BM-MSCs as it pertains to bone metastasis. BM-MSCs cultured within mineral-containing 3D poly(lactide-co-glycolide) (PLG) scaffolds differentiated into mature osteoblasts, and exposure to tumor-derived soluble factors promoted this process. When BM-MSCs undergoing osteogenic differentiation were exposed to conditioned media collected from mechanically loaded breast cancer cells, their gene expression of osteopontin was increased. This was further enhanced when mechanical compression was simultaneously applied to BM-MSCs, leading to more uniformly deposited osteopontin within scaffold pores. These results suggest that mechanical loading of 3D scaffold-based culture models may be utilized to evaluate the role of physiologically relevant physical cues on bone metastatic breast cancer. Furthermore, our data imply that cyclic mechanical stimuli within the bone microenvironment modulate interactions between tumor cells and BM-MSCs that are relevant to bone metastasis. PMID:27401765

Ionic liquid as a potential solvent for preparation of collagen-alginate-hydroxyapatite beads as bone filler.

PubMed

Iqbal, Bushra; Sarfaraz, Zenab; Muhammad, Nawshad; Ahmad, Pervaiz; Iqbal, Jibran; Khan, Zia Ul Haq; Gonfa, Girma; Iqbal, Farasat; Jamal, Arshad; Rahim, Abdur

2018-07-01

In this study, collagen/alginate/hydroxyapatite beads having different proportions were prepared as bone fillers for the restoration of osteological defects. Ionic liquid was used to dissolve the collagen and subsequently the solution was mixed with sodium alginate solution. Hydroxyapatite was added in different proportions, with the rationale to enhance mechanical as well as biological properties. The prepared solutions were given characteristic bead shapes by dropwise addition into calcium chloride solution. The prepared beads were characterized using FTIR, XRD, TGA and SEM analysis. Microhardness testing was used to evaluate the mechanical properties. The prepared beads were investigated for water adsorption behavior to ascertain its ability for body fluid uptake and adjusted accordingly to the bone cavity. Drug loading and subsequently the antibacterial activity was investigated for the prepared beads. The biocompatibility was assessed using the hemolysis testing and cell proliferation assay. The prepared collagen-alginate-HA beads, having biocompatibility and good mechanical properties, have showed an option of promising biologically active bone fillers for bone regeneration.

Porous stable poly(lactic acid)/ethyl cellulose/hydroxyapatite composite scaffolds prepared by a combined method for bone regeneration.

PubMed

Mao, Daoyong; Li, Qing; Bai, Ningning; Dong, Hongzhou; Li, Daikun

2018-01-15

A major challenge in bone tissue engineering is the development of biomimetic scaffolds which should simultaneously meet mechanical strength and pore structure requirements. Herein, we combined technologies of high concentration solvent casting, particulate leaching, and room temperature compression molding to prepare a novel poly(lactic acid)/ethyl cellulose/hydroxyapatite (PLA/EC/HA) scaffold. The functional, structural and mechanical properties of the obtained porous scaffolds were characterized. The results indicated that the PLA/EC/HA scaffolds at the 20wt% HA loading level showed optimal mechanical properties and desired porous structure. Its porosity, contact angle, compressive yield strength and weight loss after 56days were 84.28±7.04%, 45.13±2.40°, 1.57±0.09MPa and 4.77±0.32%, respectively, which could satisfy the physiological demands to guide bone regeneration. Thus, the developed scaffolds have potential to be used as a bone substitute material for bone tissue engineering application. Copyright © 2017. Published by Elsevier Ltd.

Structural and mechanical implications of PMMA implant shape and interface geometry in cranioplasty--A finite element study.

PubMed

Ridwan-Pramana, Angela; Marcián, Petr; Borák, Libor; Narra, Nathaniel; Forouzanfar, Tim; Wolff, Jan

2016-01-01

This computational study investigates the effect of shape (defect contour curvature) and bone-implant interface (osteotomy angle) on the stress distribution within PMMA skull implants. Using finite element methodology, 15 configurations--combinations of simplified synthetic geometric shapes (circular, square, triangular, irregular) and interface angulations--were simulated under 50N static loads. Furthermore, the implant fixation devices were modelled and analysed in detail. Negative osteotomy configurations demonstrated the largest stresses in the implant (275 MPa), fixation devices (1258 MPa) and bone strains (0.04). The circular implant with zero and positive osteotomy performed well with maximum observed magnitudes of--implant stress (1.2 MPa and 1.2 MPa), fixation device stress (11.2 MPa and 2.2 MPa), bone strain (0.218e-3 and 0.750e-4). The results suggest that the preparation of defect sites is a critical procedure. Of the greatest importance is the angle at which the edges of the defect are sawed. If under an external load, the implant has no support from the interface and the stresses are transferred to the fixation devices. This can endanger their material integrity and lead to unphysiological strains in the adjacent bone, potentially compromising the bone morphology required for anchoring. These factors can ultimately weaken the stability of the entire implant assembly. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Effects of exercise on bone mass in young women with anorexia nervosa.

PubMed

Waugh, Esther J; Woodside, D Blake; Beaton, Dorcas E; Coté, Pierre; Hawker, Gillian A

2011-05-01

The response of bone to exercise in women with anorexia nervosa (AN) is unclear. We investigated the associations between bone mineral density (BMD) and exercise performed while ill and while recovered in women with a history of AN. A cross-sectional study was conducted with 141 women with AN (85 ill; 56 recovered), aged 17-40 yr. BMD at the lumbar spine (LS), femoral neck (FN), and total body (TB) was measured by dual-energy x-ray absorptiometry. Life History Calendar and Minnesota Leisure Time Physical Activity interviews were used to collect lifetime illness and exercise histories (amount and bone loading type). Average hours per week of each of moderate (MOD) and high (HI) bone loading exercise were determined for three illness phases: "before ill," "while ill," and "while recovered." Participants were categorized into four exercise groups for each phase: MOD-ONLY, HI-ONLY, BOTH, and NEITHER (reference group). Weight-adjusted BMD z-scores were compared in the exercise groups by multivariable linear regression, adjusting for illness duration and severity, and exercise during the other illness phases. In ill participants, MOD-ONLY "while ill" had lower BMD at LS (β = -0.69, 95% confidence interval (CI) = -1.02 to -0.05) and TB (β = -0.73, 95% CI = -1.31 to -0.15) than the NEITHER group. In recovered participants, HI-ONLY "while recovered" had higher BMD at FN (β = 0.95, 95% CI = 0.15-1.75) and TB (β = 0.79, 95% CI = 0.07-1.51) than the NEITHER group. The effect of exercise on bone in AN patients is dependent on both the type of mechanical loading and the phase of illness during which it was performed. Excessive moderate loading exercise while ill may put patients at higher risk of low bone mass, but high bone loading activities may provoke bone accrual during recovery. © 2011 by the American College of Sports Medicine

Maximum load to failure and tensile displacement of an all-suture glenoid anchor compared with a screw-in glenoid anchor.

PubMed

Dwyer, Tim; Willett, Thomas L; Dold, Andrew P; Petrera, Massimo; Wasserstein, David; Whelan, Danny B; Theodoropoulos, John S

2016-02-01

The purpose of this study was to evaluate the biomechanical behavior of an all-suture glenoid anchor in comparison with a more conventional screw-in glenoid anchor, with regard to maximum load to failure and tensile displacement. All mechanical testing was performed using an Instron ElectroPuls E1000 mechanical machine, with a 10 N pre-load and displacement rate of 10 mm/min. Force-displacement curves were generated, with calculation of maximum load, maximum displacement, displacement at 50 N and stiffness. Pretesting of handset Y-Knots in bone analog models revealed low force displacement below 60 N of force. Subsequently, three groups of anchors were tested for pull out strength in bovine bone and cadaver glenoid bone: a bioabsorbable screw-in anchor (Bio Mini-Revo, ConMed Linvatec), a handset all-suture anchor (Y-Knot, ConMed Linvatec) and a 60 N pre-tensioned all-suture anchor (Y-Knot). A total of 8 anchors from each group was tested in proximal tibia of bovine bone and human glenoids (age range 50-90). In bovine bone, the Bio Mini-Revo displayed greater maximum load to failure (206 ± 77 N) than both the handset (140 ± 51 N; P = 0.01) and the pre-tensioned Y-Knot (135 ± 46 N; P = 0.001); no significant difference was seen between the three anchor groups in glenoid bone. Compared to the screw-in anchors, the handset all-suture anchor displayed inferior fixation, early displacement and greater laxity in the bovine bone and cadaveric bone (P < 0.05). Pre-tensioning the all-suture anchor to 60 N eliminated this behavior in all bone models. Handset Y-Knots display low force anchor displacement, which is likely due to slippage in the pilot hole. Pre-tensioning the Y-Knot to 60 N eliminates this behavior. I.

Implant-Supported Fixed Partial Prostheses With Different Prosthetic Materials: A Three-Dimensional Finite Element Stress Analysis.

PubMed

Arinc, Hakan

2018-06-01

To evaluate the effects of prosthetic material on the degree of stress to the cortical bone, trabecular bone, framework, and implants using finite element analysis (FEA). A mandibular implant-supported fixed prosthesis was designed. Different prosthetic materials [cobalt-chromium-supported ceramic, zirconia-supported ceramic, and zirconia-reinforced polymethyl methacrylate (ZRPMMA)-supported resin] were used. FEA was used to evaluate stress under different loading conditions. Maximum principal (σmax), minimum principal (σmin), and von Mises (σvM) stress values were obtained. Similar σmax, σmin, and σvM values were observed in the cortical and trabecular bones and in implants under both loading conditions, with the exception of the ZRPMMA model, which showed the highest σmax, σmin, and σvM values in oblique loading. The ZRPMMA model had the lowest σvM value in the framework under both loading conditions. ZRPMMA had the lowest stress values in the framework, with increased stress values in the implants and bone tissue. Framework and veneering materials may influence stress values under different loading conditions.

The role of low acid load in vegetarian diet on bone health: a narrative review.

PubMed

Burckhardt, Peter

2016-01-01

Vegetarian and vegan diets contain low amounts of protein and calcium. For this reason they are supposed to cause low bone mineral density (BMD) and osteoporosis. But this is not the case, except for vegans with a particularly low calcium intake. The absence of osteoporosis or low BMD can be explained by the low acid load of these diets. Nutritional acid load is negatively correlated with bone mineral density (BMD) and positively with fracture risk. Low acid load is correlated with lower bone resorption and higher BMD. It is linked to high intake of potassium-rich nutrients, such as fruits and vegetables, as found in vegetarian diets. The total nutritional acid load, which not only depends on the potassium content of the nutrition, was recently assessed in several studies on vegetarian and vegan diets and was found to be very low or absent, while the diet of Western-style omnivores produces daily 50 to 70 mEq of acid. This might be an important factor for the protection of vegetarians from osteoporosis.

Mechanical basis of bone strength: influence of bone material, bone structure and muscle action

PubMed Central

Hart, N.H.; Nimphius, S.; Rantalainen, T.; Ireland, A.; Siafarikas, A.; Newton, R.U.

2017-01-01

This review summarises current understanding of how bone is sculpted through adaptive processes, designed to meet the mechanical challenges it faces in everyday life and athletic pursuits, serving as an update for clinicians, researchers and physical therapists. Bone’s ability to resist fracture under the large muscle and locomotory forces it experiences during movement and in falls or collisions is dependent on its established mechanical properties, determined by bone’s complex and multidimensional material and structural organisation. At all levels, bone is highly adaptive to habitual loading, regulating its structure according to components of its loading regime and mechanical environment, inclusive of strain magnitude, rate, frequency, distribution and deformation mode. Indeed, the greatest forces habitually applied to bone arise from muscular contractions, and the past two decades have seen substantial advances in our understanding of how these forces shape bone throughout life. Herein, we also highlight the limitations of in vivo methods to assess and understand bone collagen, and bone mineral at the material or tissue level. The inability to easily measure or closely regulate applied strain in humans is identified, limiting the translation of animal studies to human populations, and our exploration of how components of mechanical loading regimes influence mechanoadaptation. PMID:28860414

Immediate versus early non-occlusal loading of dental implants placed flapless in partially edentulous patients: a 3-year randomized clinical trial.

PubMed

Merli, Mauro; Moscatelli, Marco; Mariotti, Giorgia; Piemontese, Matteo; Nieri, Michele

2012-02-01

To compare immediate versus early non-occlusal loading of dental implants placed flapless in a 3-year, parallel group, randomized clinical trial. The study was conducted in a private dental clinic between July 2005 and July 2010. Patients 18 years or older were randomized to receive implants for fixed partial dentures in cases of partial edentulism. The test group was represented by immediate non-occlusal implant loading, whereas the control group was represented by early non-occlusal implant loading. The outcome variables were implant failure, complications and radiographic bone level at implant sites 3 years after loading, measured from the implant-abutment junction to the most coronal point of bone-to-implant contact. Randomization was computer-generated with allocation concealment by opaque sequentially numbered sealed envelopes, and the measurer was blinded to group assignment. Sixty patients were randomized: 30 to the immediately loaded group and 30 to the early loaded group. Four patients dropped out; however, the data of all patients were included in the analysis. No implant failure occurred. Two complications occurred in the control group and one in the test group. The mean bone level at 3 years was 1.91 mm for test group and 1.59 mm for control group. The adjusted difference in bone level was 0.26 mm (CI 95% -0.08 to 0.59, p = 0.1232). The null hypothesis of no difference in failure rates, complications and bone level between implants that were loaded immediately or early at 3 years cannot be rejected in this randomized clinical trial. © 2011 John Wiley & Sons A/S.

Physical characterization and osteogenic activity of the quaternized chitosan-loaded PMMA bone cement.

PubMed

Tan, Honglue; Guo, Shengrong; Yang, Shengbing; Xu, Xiaofen; Tang, Tingting

2012-07-01

Gentamicin-loaded polymethylmethacrylate (PMMA), widely used for primary cemented arthroplasty and revision surgery for preventing or treating infections, may lead to the evolution of antibiotic-resistant bacteria and dysfunction of osteogenic cells, which further influence the osteointegration of bone cement. In a previous study, we reported that a new quaternized chitosan derivative (hydroxypropyltrimethyl ammonium chloride chitosan, HACC) that was loaded into PMMA significantly inhibited the formation of biofilms caused by methicillin-resistant Staphylococcus strains. In the present study, we further investigated the surface morphology, hydrophilicity, apatite formation ability and osteogenic activity of HACC-loaded PMMA. Chitosan-loaded PMMA, gentamicin-loaded PMMA and PMMA without antibiotic were also investigated and compared. The results showed that, compared to other PMMA-based cements, HACC-loaded PMMA had improved properties such as a lower polymerization temperature, prolonged setting time, porous structures after immersion in phosphate-buffered saline, higher hydrophilicity, more apatite formation on the surface after immersion in simulated body fluid, and better attachment and spreading of the human-marrow-derived mesenchymal stem cells. We also found better stem cell proliferation, osteogenic differentiation, and osteogenesis-associated genes expression on the surface of the HACC-loaded PMMA compared to the gentamicin-loaded PMMA. Therefore, this new anti-infective bone cement had improved physical properties and osteogenic activity, which may lead to better osteointegration of the bone cement in cemented arthroplasty. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Quantitative computed tomography-based predictions of vertebral strength in anterior bending.

PubMed

Buckley, Jenni M; Cheng, Liu; Loo, Kenneth; Slyfield, Craig; Xu, Zheng

2007-04-20

This study examined the ability of QCT-based structural assessment techniques to predict vertebral strength in anterior bending. The purpose of this study was to compare the abilities of QCT-based bone mineral density (BMD), mechanics of solids models (MOS), e.g., bending rigidity, and finite element analyses (FE) to predict the strength of isolated vertebral bodies under anterior bending boundary conditions. Although the relative performance of QCT-based structural measures is well established for uniform compression, the ability of these techniques to predict vertebral strength under nonuniform loading conditions has not yet been established. Thirty human thoracic vertebrae from 30 donors (T9-T10, 20 female, 10 male; 87 +/- 5 years of age) were QCT scanned and destructively tested in anterior bending using an industrial robot arm. The QCT scans were processed to generate specimen-specific FE models as well as trabecular bone mineral density (tBMD), integral bone mineral density (iBMD), and MOS measures, such as axial and bending rigidities. Vertebral strength in anterior bending was poorly to moderately predicted by QCT-based BMD and MOS measures (R2 = 0.14-0.22). QCT-based FE models were better strength predictors (R2 = 0.34-0.40); however, their predictive performance was not statistically different from MOS bending rigidity (P > 0.05). Our results suggest that the poor clinical performance of noninvasive structural measures may be due to their inability to predict vertebral strength under bending loads. While their performance was not statistically better than MOS bending rigidities, QCT-based FE models were moderate predictors of both compressive and bending loads at failure, suggesting that this technique has the potential for strength prediction under nonuniform loads. The current FE modeling strategy is insufficient, however, and significant modifications must be made to better mimic whole bone elastic and inelastic material behavior.

Microstructure and Cross-Sectional Shape of Limb Bones in Great Horned Owls and Red-Tailed Hawks: How Do These Features Relate to Differences in Flight and Hunting Behavior?

PubMed Central

Marelli, Crystal A.; Simons, Erin L. R.

2014-01-01

The Red-tailed Hawk and Great Horned Owl are two species of raptor that are similar in body size, diet, and habitat. Both species use their hindlimbs during hunting, but differ in foot morphology, how they approach and immobilize prey, and the average size of prey captured. They also differ in primary flight style: the Red-tailed Hawk uses static soaring and the Great Horned Owl uses flap-gliding. The objectives of this study were to characterize the microstructure and cross-sectional shape of limb bones of these species and examine the relationship with flight and hunting behaviors. The mid-shaft of six limb bones from six individuals of each species was sampled. The degree of bone laminarity (proportion of circular primary vascular canals) and cross-sectional geometric parameters were calculated. In both species, the humerus and femur exhibited features that suggest high resistance to torsional loading, whereas the tibiotarsus and phalanges had a shape more likely to resist compression and bending in a specific plane. The femur of the Red-tailed Hawk exhibited higher laminarity and larger polar moment of area than that of the Great Horned Owl. The tibiotarsus was more elliptical than that of the Great Horned Owl. The hawk approaches prey from a more horizontal axis, takes prey of greater mass, and is more likely to pursue prey on the ground, which could potentially be causing more torsional loads on the femur and bending loads on the tibiotarsus. In addition, differences in polar moment of area of the phalanges between the species could relate to differences in foot morphology or digit length. The humerus and ulna of the flap-gliding Great Horned Owl are more elliptical than the static soaring Red-tailed Hawk, a shape that may better resist the bending loads associated with a larger amount of flapping. PMID:25162595

Microstructure and cross-sectional shape of limb bones in Great Horned Owls and Red-tailed Hawks: how do these features relate to differences in flight and hunting behavior?

PubMed

Marelli, Crystal A; Simons, Erin L R

2014-01-01

The Red-tailed Hawk and Great Horned Owl are two species of raptor that are similar in body size, diet, and habitat. Both species use their hindlimbs during hunting, but differ in foot morphology, how they approach and immobilize prey, and the average size of prey captured. They also differ in primary flight style: the Red-tailed Hawk uses static soaring and the Great Horned Owl uses flap-gliding. The objectives of this study were to characterize the microstructure and cross-sectional shape of limb bones of these species and examine the relationship with flight and hunting behaviors. The mid-shaft of six limb bones from six individuals of each species was sampled. The degree of bone laminarity (proportion of circular primary vascular canals) and cross-sectional geometric parameters were calculated. In both species, the humerus and femur exhibited features that suggest high resistance to torsional loading, whereas the tibiotarsus and phalanges had a shape more likely to resist compression and bending in a specific plane. The femur of the Red-tailed Hawk exhibited higher laminarity and larger polar moment of area than that of the Great Horned Owl. The tibiotarsus was more elliptical than that of the Great Horned Owl. The hawk approaches prey from a more horizontal axis, takes prey of greater mass, and is more likely to pursue prey on the ground, which could potentially be causing more torsional loads on the femur and bending loads on the tibiotarsus. In addition, differences in polar moment of area of the phalanges between the species could relate to differences in foot morphology or digit length. The humerus and ulna of the flap-gliding Great Horned Owl are more elliptical than the static soaring Red-tailed Hawk, a shape that may better resist the bending loads associated with a larger amount of flapping.

Tensile Loading Modulates Bone Marrow Stromal Cell Differentiation and the Development of Engineered Fibrocartilage Constructs

PubMed Central

Connelly, John T.; Vanderploeg, Eric J.; Mouw, Janna K.; Wilson, Christopher G.

2010-01-01

Mesenchymal progenitors such as bone marrow stromal cells (BMSCs) are an attractive cell source for fibrocartilage tissue engineering, but the types or combinations of signals required to promote fibrochondrocyte-specific differentiation remain unclear. The present study investigated the influences of cyclic tensile loading on the chondrogenesis of BMSCs and the development of engineered fibrocartilage. Cyclic tensile displacements (10%, 1 Hz) were applied to BMSC-seeded fibrin constructs for short (24 h) or extended (1–2 weeks) periods using a custom loading system. At early stages of chondrogenesis, 24 h of cyclic tension stimulated both protein and proteoglycan synthesis, but at later stages, tension increased protein synthesis only. One week of intermittent cyclic tension significantly increased the total sulfated glycosaminoglycan and collagen contents in the constructs, but these differences were lost after 2 weeks of loading. Constraining the gels during the extended culture periods prevented contraction of the fibrin matrix, induced collagen fiber alignment, and increased sulfated glycosaminoglycan release to the media. Cyclic tension specifically stimulated collagen I mRNA expression and protein synthesis, but had no effect on collagen II, aggrecan, or osteocalcin mRNA levels. Overall, these studies suggest that the combination of chondrogenic stimuli and tensile loading promotes fibrochondrocyte-like differentiation of BMSCs and has the potential to direct fibrocartilage development in vitro. PMID:20088686

Differentiation potentials of perivascular cells in the bone tissue remodeling zones under microgravity

NASA Astrophysics Data System (ADS)

Rodionova, Natalia; Katkova, Olena

Adaptive remodeling processes in the skeleton bones occur in the close topographical interconnection with blood capillaries followed by perivascular cells. Radioautographic studies with 3H- thymidine (Kimmel D.B., Fee W.S., 1980; Rodionova N.V., 1989, 2006) has shown that in osteogenesis zones there is sequential differentiation process of the perivascular cells into osteogenic ones. Using electron microscopy and cytochemistry we studied perivsacular cells in metaphysis of the rats femoral bones under conditions of modeling microgravity (28 days duration) and in femoral bones metaphyses of rats flown on board of the space laboratory (Spacelab - 2) It was revealed that population of the perivascular cells is not homogeneous in adaptive zones of the remodeling in both control and test groups (lowering support loading). This population comprises adjacent to endothelium little differentiated forms and isolated cells with differentiation features (specific volume of rough endoplasmic reticulum in cytoplasm is increased). Majority of the perivascular cells in the control group reveals reaction to alkaline phosphatase (marker of the osteogenic differentiation). In little differentiated cells this reaction is registered in nucleolus, nucleous and cytoplasm. In differentiating cells activity of the alkaline phosphatase is also detected on the outer surface of the cellular membrane. Unlike the control group in the bones of animals under microgravitaty reaction to the alkaline phosphatase is registered not for all cells of perivascular population. Part of the differentiating perivascular cells does not contain a product of the reaction. There is also visible trend of individual alkaline phosphatase containing perivascular cells amounts decrease (i.e. osteogenic cells-precursors). Under microgravity some little differentiated perivascular cells reveal destruction signs. Found decrease trend of the alkaline phosphatase containing cells (i.e. osteogenic cells) number in perivascular cells population. It is one of the mechanisms of the osteogenic process intensity decrease in bones due to lowering support loading on the bone skeleton. In particular this is confirmed by the fact that in the zones of adaptive remodeling we found fibroblasts and fibrosis zones - areas filled with non mineralized collagen fibrils on the bones surfaces. Hence it should be considered that lowering (removal) support loading slows down (or blocks) osteogenic differentiation of the perivascular cells part and stimulates differentiation of the fibroblast cells. Obtained data considered as one of the cellular mechanisms of the adaptive reactions development in spongy bone under microgravity which could lead to the bone mass loss.

Influence of different peg length in glenoid bone loss: A biomechanical analysis regarding primary stability of the glenoid baseplate in reverse shoulder arthroplasty.

PubMed

Königshausen, M; Jettkant, B; Sverdlova, N; Ehlert, C; Gessmann, J; Schildhauer, T A; Seybold, D

2015-01-01

There is no biomechanical basis to determine the influence of different length of the central peg of the baseplate anchored within the native scapula in glenoid defect reconstruction in cases of degenerative or posttraumatic glenoid bone loss in reversed shoulder arthroplasty. The purpose of this study was to analyse the stability of different peg lengths used in glenoid bone loss in reversed shoulder arthroplasty. Different lengths of metaglene pegs with different depths of peg anchorage performed with or without metaglene screws in sawbone foam blocks were loaded in vertical and horizontal directions for differentiating load capacities. Simulated physiological loadings were then applied to the peg implants to determine the limits of loading in each depth of anchorage. The loading capacity of the implant was reduced as less of the peg was anchored. The vertically loaded implants showed a significantly higher stability, in contrast to those loaded horizontally at a corresponding peg length and depth of anchorage (p < 0.05). The tests revealed that the metaglene screws are more essential for primary stability than is the peg particularly in the vertically directed loadings (2/3 anchored: peg contributed to 28% of the stability, 1/3 anchorage: peg contributed to 12%). Under the second test conditions, the lowest depth of peg anchorage (1/3) resulted in 322 Newtons [N] in the long peg with a vertical loading direction, and in 130 N in the long peg with a horizontal loading direction (p < 0.05). The pegs should be anchored as deeply as possible into the native scapula bone stock. The metaglene screws play a major role in the initial stability, in contrast to the peg, and they become more important when the depth of the peg anchorage is reduced. If possible, four metaglene screws should be used in cases of uncontained bone loss to guarantee the highest stability.

Tension degradation of anterior cruciate ligament grafts with dynamic flexion-extension loading: a biomechanical model in porcine knees.

PubMed

Dargel, Jens; Koebke, Jürgen; Brüggemann, Gert-Peter; Pennig, Dietmar; Schmidt-Wiethoff, Rüdiger

2009-10-01

This study investigates the influence of various femoral anterior cruciate ligament graft fixation methods on the amount of tension degradation and the initial fixation strength after cyclic flexion-extension loading in a porcine knee model. One hundred twenty porcine digital extensor tendons, used as 4-stranded free tendon grafts, were fixated within porcine femoral bone tunnels by use of extracortical button, cross-pin, or interference screw fixation. One hundred twenty porcine patellar tendon-bone grafts were fixated by use of cross-pin, interference screw, or press-fit fixation. Each femur-graft complex was submitted to cyclic flexion-extension loading for 1,000 cycles throughout different loading ranges, and the total loss of tension was determined. After cyclic testing, the grafts were loaded to failure, and the data were compared with a pullout series without cyclic loading. Tension degradation after 1,000 cycles of flexion-extension loading averaged 62.6% +/- 10.0% in free tendon grafts and 48.9% +/- 13.35% in patellar tendon-bone grafts. There was no influence of the loading range on the total amount of tension degradation. The total amount of tension degradation was the highest with interference screw fixation of free tendon and patellar tendon-bone grafts. Despite excessive loss of tension, the initial fixation strength of the femur-graft complex was not reduced. The method of femoral graft fixation significantly influenced tension degradation during dynamic flexion-extension loading. Femoral graft fixation methods that secure the graft close to the tunnel entrance and that displace the graft substance from the center of the bone tunnel show the largest amount of tension degradation during cyclic flexion-extension loading. The graft substance, not the fixation site, was the weakest link of the graft complex within this investigation. We believe that the graft fixation method should be considered when aiming to improve the precision of femoral graft placement in anterior cruciate ligament reconstruction.

Effects of Imbalanced Muscle Loading on Hip Joint Development and Maturation

PubMed Central

Ford, Caleb A.; Nowlan, Niamh C.; Thomopoulos, Stavros; Killian, Megan L.

2017-01-01

The mechanical loading environment influences the development and maturation of joints. In this study, the influence of imbalanced muscular loading on joint development was studied using localized chemical denervation of hip stabilizing muscle groups in neonatal mice. It was hypothesized that imbalanced muscle loading, targeting either gluteal muscles or quadriceps muscles, would lead to bilateral hip joint asymmetry, as measured by acetabular coverage, femoral head volume and bone morphometry, and femoral-acetabular shape. The contralateral hip joints as well as age-matched, uninjected mice were used as controls. Altered bone development was analyzed using micro-computed tomography, histology, and image registration techniques at postnatal days (P) 28, 56, and 120. This study found that unilateral muscle unloading led to reduced acetabular coverage of the femoral head, lower total volume, lower bone volume ratio, and lower mineral density, at all three time points. Histologically, the femoral head was smaller in unloaded hips, with thinner triradiate cartilage at P28 and thinner cortical bone at P120 compared to contralateral hips. Morphological shape changes were evident in unloaded hips at P56. Unloaded hips had lower trabecular thickness and increased trabecular spacing of the femoral head compared to contralateral hips. The present study suggests that decreased muscle loading of the hip leads to altered bone and joint shape and growth during postnatal maturation. Statement of Clinical Significance: Adaptations from altered muscle loading during postnatal growth investigated in this study have implications on developmental hip disorders that result from asymmetric loading, such as patients with limb-length inequality or dysplasia. PMID:27391299

Establishing Biomechanical Mechanisms in Mouse Models: Practical Guidelines for Systematically Evaluating Phenotypic Changes in the Diaphyses of Long Bones

PubMed Central

Jepsen, Karl J; Silva, Matthew J; Vashishth, Deepak; Guo, X Edward; van der Meulen, Marjolein CH

2016-01-01

Mice are widely used in studies of skeletal biology, and assessment of their bones by mechanical testing is a critical step when evaluating the functional effects of an experimental perturbation. For example, a gene knockout may target a pathway important in bone formation and result in a “low bone mass” phenotype. But how well does the skeleton bear functional loads; eg, how much do bones deform during loading and how resistant are bones to fracture? By systematic evaluation of bone morphological, densitometric, and mechanical properties, investigators can establish the “biomechanical mechanisms” whereby an experimental perturbation alters whole-bone mechanical function. The goal of this review is to clarify these biomechanical mechanisms and to make recommendations for systematically evaluating phenotypic changes in mouse bones, with a focus on long-bone diaphyses and cortical bone. Further, minimum reportable standards for testing conditions and outcome variables are suggested that will improve the comparison of data across studies. Basic biomechanical principles are reviewed, followed by a description of the cross-sectional morphological properties that best inform the net cellular effects of a given experimental perturbation and are most relevant to biomechanical function. Although morphology is critical, whole-bone mechanical properties can only be determined accurately by a mechanical test. The functional importance of stiffness, maximum load, postyield displacement, and work-to-fracture are reviewed. Because bone and body size are often strongly related, strategies to adjust whole-bone properties for body mass are detailed. Finally, a comprehensive framework is presented using real data, and several examples from the literature are reviewed to illustrate how to synthesize morphological, tissue-level, and whole-bone mechanical properties of mouse long bones. PMID:25917136

Structural Analysis and Optimization of the Support Device Used for a Proximal Fracture of the Femur

DTIC Science & Technology

2008-12-01

support system and bone , the models were considered under two different load conditions. From these results, a recommendation can be made to the...support system and bone , the models were considered under two different load conditions. From these results, a recommendation can be made to the...nail with coordinate reference ............................................................30  Figure 27.  Model with bone and Nail

Stiffness and ultimate load of osseointegrated prosthesis fixations in the upper and lower extremity.

PubMed

Welke, Bastian; Hurschler, Christof; Föller, Marie; Schwarze, Michael; Calliess, Tilman

2013-07-11

Techniques for the skeletal attachment of amputation-prostheses have been developed over recent decades. This type of attachment has only been performed on a small number of patients. It poses various potential advantages compared to conventional treatment with a socket, but is also associated with an increased risk of bone or implant-bone interface fracture in the case of a fall. We therefore investigated the bending stiffness and ultimate bending moment of such devices implanted in human and synthetic bones. Eight human specimens and 16 synthetic models of the proximal femora were implanted with lower extremity prostheses and eight human specimens and six synthetic humeri were implanted with upper extremity prostheses. They were dissected according to typical amputation levels and underwent loading in a material testing machine in a four-point bending setup. Bending stiffness, ultimate bending moment and fracture modes were determined in a load to failure experiment. Additionally, axial pull-out was performed on eight synthetic specimens of the lower extremity. Maximum bending moment of the synthetic femora was 160.6±27.5 Nm, the flexural rigidity of the synthetic femora was 189.0±22.6 Nm2. Maximum bending moment of the human femora was 100.4±38.5 Nm, and the flexural rigidity was 137.8±29.4 Nm2. The maximum bending moment of the six synthetic humeri was 104.9±19.0 Nm, and the flexural rigidity was 63.7±3.6 Nm2. For the human humeri the maximum bending moment was 36.7±11.0 Nm, and the flexural rigidity at was 43.7±10.5 Nm2. The maximum pull-out force for the eight synthetic femora was 3571±919 N. Significant differences were found between human and synthetic specimens of the lower and upper extremity regarding maximum bending moment, bending displacement and flexural rigidity. The results of this study are relevant with respect to previous finding regarding the load at the interfaces of osseointegrated prosthesis fixation devices and are crucial for the development of safety devices intended to protect the bone-implant interface from damaging loadings.

Stiffness and ultimate load of osseointegrated prosthesis fixations in the upper and lower extremity

PubMed Central

2013-01-01

Background Techniques for the skeletal attachment of amputation-prostheses have been developed over recent decades. This type of attachment has only been performed on a small number of patients. It poses various potential advantages compared to conventional treatment with a socket, but is also associated with an increased risk of bone or implant-bone interface fracture in the case of a fall. We therefore investigated the bending stiffness and ultimate bending moment of such devices implanted in human and synthetic bones. Methods Eight human specimens and 16 synthetic models of the proximal femora were implanted with lower extremity prostheses and eight human specimens and six synthetic humeri were implanted with upper extremity prostheses. They were dissected according to typical amputation levels and underwent loading in a material testing machine in a four-point bending setup. Bending stiffness, ultimate bending moment and fracture modes were determined in a load to failure experiment. Additionally, axial pull-out was performed on eight synthetic specimens of the lower extremity. Results Maximum bending moment of the synthetic femora was 160.6±27.5 Nm, the flexural rigidity of the synthetic femora was 189.0±22.6 Nm2. Maximum bending moment of the human femora was 100.4±38.5 Nm, and the flexural rigidity was 137.8±29.4 Nm2. The maximum bending moment of the six synthetic humeri was 104.9±19.0 Nm, and the flexural rigidity was 63.7±3.6 Nm2. For the human humeri the maximum bending moment was 36.7±11.0 Nm, and the flexural rigidity at was 43.7±10.5 Nm2. The maximum pull-out force for the eight synthetic femora was 3571±919 N. Conclusion Significant differences were found between human and synthetic specimens of the lower and upper extremity regarding maximum bending moment, bending displacement and flexural rigidity. The results of this study are relevant with respect to previous finding regarding the load at the interfaces of osseointegrated prosthesis fixation devices and are crucial for the development of safety devices intended to protect the bone-implant interface from damaging loadings. PMID:23844992

Effects of age-related differences in femoral loading and bone mineral density on strains in the proximal femur during controlled walking.

PubMed

Anderson, Dennis E; Madigan, Michael L

2013-10-01

Maintenance of healthy bone mineral density (BMD) is important for preventing fractures in older adults. Strains experienced by bone in vivo stimulate remodeling processes, which can increase or decrease BMD. However, there has been little study of age differences in bone strains. This study examined the relative contributions of age-related differences in femoral loading and BMD to age-related differences in femoral strains during walking using gait analysis, static optimization, and finite element modeling. Strains in older adult models were similar or larger than in young adult models. Reduced BMD increased strains in a fairly uniform manner, whereas older adult loading increased strains in early stance but decreased strains in late stance. Peak ground reaction forces, hip joint contact forces, and hip flexor forces were lower in older adults in late stance phase, and this helped older adults maintain strains similar to those of young adults despite lower BMD. Because walking likely represents a "baseline" level of stimulus for bone remodeling processes, increased strains during walking in older adults might indicate the extent of age-related impairment in bone remodeling processes. Such a measure might be clinically useful if it could be accurately determined with age-appropriate patient-specific loading, geometry, and BMD.

Fabrication and characterization of a novel carbon fiber-reinforced calcium phosphate silicate bone cement with potential osteo-inductivity.

PubMed

Zheng, Jiangjiang; Xiao, Yu; Gong, Tianxing; Zhou, Shuxin; Troczynski, Tom; Yang, Quanzu; Bao, Chongyun; Xu, Xiaoming

2015-12-23

The repair of bone defects is still a pressing challenge in clinics. Injectable bone cement is regarded as a promising material to solve this problem because of its special self-setting property. Unfortunately, its poor mechanical conformability, unfavorable osteo-genesis ability and insufficient osteo-inductivity seriously limit its clinical application. In this study, novel experimental calcium phosphate silicate bone cement reinforced by carbon fibers (CCPSC) was fabricated and characterized. First, a compressive strength test and cell culture study were carried out. Then, the material was implanted into the femoral epiphysis of beagle dogs to further assess its osteo-conductivity using a micro-computed tomography scan and histological analysis. In addition, we implanted CCPSC into the beagles' intramuscular pouches to perform an elementary investigation of its osteo-inductivity. The results showed that incorporation of carbon fibers significantly improved its mechanical properties. Meanwhile, CCPSC had better biocompatibility to activate cell adhesion as well as proliferation than poly-methyl methacrylate bone cement based on the cell culture study. Moreover, pronounced biodegradability and improved osteo-conductivity of CCPSC could be observed through the in vivo animal study. Finally, a small amount of osteoid was found at the heterotopic site one month after implantation which indicated potential osteo-inductivity of CCPSC. In conclusion, the novel CCPSC shows promise as a bioactive bone substitute in certain load-bearing circumstances.

Two-time scale fatigue modelling: application to damage

NASA Astrophysics Data System (ADS)

Devulder, Anne; Aubry, Denis; Puel, Guillaume

2010-05-01

A temporal multiscale modelling applied to fatigue damage evolution in cortical bone is presented. Microdamage accumulation in cortical bone, ensued from daily activities, leads to impaired mechanical properties, in particular by reducing the bone stiffness and inducing fatigue. However, bone damage is also known as a stimulus to bone remodelling, whose aim is to repair and generate new bone, adapted to its environment. This biological process by removing fatigue damage seems essential to the skeleton lifetime. As daily activities induce high frequency cycles (about 10,000 cycles a day), identifying two-time scale is very fruitful: a fast one connected with the high frequency cyclic loading and a slow one related to a quasi-static loading. A scaling parameter is defined between the intrinsic time (bone lifetime of several years) and the high frequency loading (few seconds). An asymptotic approach allows to decouple the two scales and to take into account history effects (Guennouni and Aubry in CR Acad Sci Paris Ser II 20:1765-1767, 1986). The method is here applied to a simple case of fatigue damage and a real cortical bone microstructure. A significant reduction in the amount of computation time in addition to a small computational error between time homogenized and non homogenized models are obtained. This method seems thus to give new perspectives to assess fatigue damage and, with regard to bone, to give a better understanding of bone remodelling.

Surface structural damage study in cortical bone due to medical drilling.

PubMed

Tavera R, Cesar G; De la Torre-I, Manuel H; Flores-M, Jorge M; Hernandez M, Ma Del Socorro; Mendoza-Santoyo, Fernando; Briones-R, Manuel de J; Sanchez-P, Jorge

2017-05-01

A bone's fracture could be produced by an excessive, repetitive, or sudden load. A regular medical practice to heal it is to fix it in two possible ways: external immobilization, using a ferule, or an internal fixation, using a prosthetic device commonly attached to the bone by means of surgical screws. The bone's volume loss due to this drilling modifies its structure either in the presence or absence of a fracture. To observe the bone's surface behavior caused by the drilling effects, a digital holographic interferometer is used to analyze the displacement surface's variations in nonfractured post-mortem porcine femoral bones. Several nondrilled post-mortem bones are compressed and compared to a set of post-mortem bones with a different number of cortical drillings. During each compression test, a series of digital interferometric holograms were recorded using a high-speed CMOS camera. The results are presented as pseudo 3D mesh displacement maps for comparisons in the physiological range of load (30 and 50 lbs) and beyond (100, 200, and 400 lbs). The high resolution of the optical phase gives a better understanding about the bone's microstructural modifications. Finally, a relationship between compression load and bone volume loss due to the drilling was observed. The results prove that digital holographic interferometry is a viable technique to study the conditions that avoid the surgical screw from loosening in medical procedures of this kind.

Effect of a freeze-dried CMC/PLGA microsphere matrix of rhBMP-2 on bone healing.

PubMed

Schrier, J A; Fink, B F; Rodgers, J B; Vasconez, H C; DeLuca, P P

2001-10-07

The hypothesis of this research was that implants of poly(lactide-co-glycolide) (PLGA) microspheres loaded with bone morphogenetic protein-2 (rhBMP-2) and distributed in a freeze-dried carboxymethylcellulose (CMC) matrix would produce more new bone than would matrix implants of non-protein-loaded microspheres or matrix implants of only CMC. To test this hypothesis it was necessary to fashion microsphere-loaded CMC implants that were simple to insert, fit precisely into a defect, and would not elicit swelling. Microspheres were produced via a water-in-oil-in-water double-emulsion system and were loaded with rhBMP-2 by soaking them in a buffered solution of the protein at a concentration of 5.4 mg protein per gram of PLGA. Following recovery of the loaded microspheres by lyophilization, matrices for implantation were prepared by lyophilizing a suspension of the microspheres in 2% CMC in flat-bottom tissue culture plates. Similar matrices were made with 2% CMC and with 2% CMC containing blank microspheres. A full-thickness calvarial defect model in New Zealand white rabbits was used to assess bone growth. Implants fit the defect well, allowing for direct application. Six weeks postsurgery, defects were collected and processed for undecalcified histology. In vitro, 60% of the loaded rhBMP-2 released from devices or microspheres in 5 to 7 days, with the unembedded microspheres releasing faster than those embedded in CMC. In vivo, the rhBMP-2 microspheres greatly enhanced bone healing, whereas nonloaded PLGA microspheres in the CMC implants had little effect. The results showed that a lyophilized device of rhBMP-2/PLGA microspheres in CMC was an effective implantable protein-delivery system for use in bone repair.

Effect of Integration Patterns Around Implant Neck on Stress Distribution in Peri-Implant Bone: A Finite Element Analysis.

PubMed

Han, Jingyun; Sun, Yuchun; Wang, Chao

2017-08-01

To investigate the biomechanical performance of different osseointegration patterns between cortical bone and implants using finite element analysis. Fifteen finite element models were constructed of the mandibular fixed prosthesis supported by implants. Masticatory loads (200 N axial, 100 N oblique, 40 N horizontal) were applied. The cortical bone/implant interface was divided equally into four layers: upper, upper-middle, lower-middle, and lower. The bone stress and implant displacement were calculated for 5 degrees of uniform integration (0, 20%, 40%, 60%, and 100%) and 10 integration patterns. The stress was concentrated in the bone margin and gradually decreased as osseointegration progressed, when the integrated and nonintegrated areas were alternated on the bone-implant surface. Compared with full integration, the integration of only the lower-middle layer or lower half layers significantly decreased von Mises, tensile, and compressive stresses in cortical bone under oblique and horizontal loads, and these patterns did not induce higher stress in the cancellous bone. For the integration of only the upper or upper-middle layer, stress in the cortical and cancellous bones significantly increased and was considerably higher than in the case of nonintegration. In addition, the maximum stress in the cortical bone was sensitive to the quantity of integrated nodes at the bone margin; lower quantity was associated with higher stress. There was no significant difference in the displacement of implants among 15 models. Integration patterns of cortical bone significantly affect stress distribution in peri-implant bone. The integration of only the lower-middle or lower half layers helps to increase the load-bearing capacity of peri-implant bone and decrease the risk of overloading, while upper integration may further increase the risk of bone resorption. © 2016 by the American College of Prosthodontists.

Increased Resistance during Jump Exercise Does Not Enhance Cortical Bone Formation

PubMed Central

Boudreaux, Ramon D.; Swift, Joshua M.; Gasier, Heath G.; Wiggs, Michael P.; Hogan, Harry A.; Fluckey, James D.; Bloomfield, Susan A.

2014-01-01

PURPOSE This study sought to elucidate the effects of a low- and high-load jump resistance exercise (RE) training protocol on cortical bone of the tibia and femur mid-diaphyses. METHODS Sprague-Dawley rats (male, 6-mos-old) were randomly assigned to high-load RE (HRE; n = 16), low-load RE (LRE; n = 15) or cage control (CC; n = 11) groups. Animals in the HRE and LRE groups performed 15 sessions of jump RE for 5 weeks. Load in the HRE group was progressively increased from 80g added to a weighted vest (50 repetitions) to 410g (16 repetitions). The LRE rats completed the same protocol as the HRE group (same number of repetitions) with only a 30g vest applied. RESULTS Low- and high-load jump RE resulted in 6–11% higher cortical bone mineral content (BMC) and cortical bone area compared to controls as determined by in vivo pQCT measurements. In the femur, however, only LRE demonstrated improvements in cortical volumetric bone mineral density (vBMD; +11%) and cross-sectional moment of inertia (CSMI; +20%) versus CC group. Three-point bending to failure revealed a marked increase in tibial max force (25–29%), stiffness (19–22%), and energy to max force (35–55%), and a reduction in elastic modulus (−11–14%) in both LRE and HRE compared to controls. Dynamic histomorphometry assessed at the tibia mid-diaphysis determined that both LRE and HRE resulted in 20–30% higher periosteal mineralizing surface versus CC group. Mineral apposition rate (MAR) and bone formation rate (BFR) were significantly greater in LRE animals (27%, 39%) than in the HRE group. CONCLUSION These data demonstrate that jump training with minimal loading is equally, and sometimes more, effective at augmenting cortical bone integrity compared to overload training in skeletally mature rats. PMID:24743108

Radiographic and clinical outcomes of implants placed in ridge preserved sites: a 12-month post-loading follow-up.

PubMed

Patel, K; Mardas, N; Donos, N

2013-06-01

The aim of this clinical study was to evaluate the interproximal radiographic bone levels and the survival/success rate of dental implants placed in alveolar ridges previously preserved with a synthetic bone substitute or a bovine xenograft. Alveolar ridge preservation was performed in 27 patients who were randomly assigned in two groups. In the test group (n = 14), the extraction socket was treated with a synthetic bone graft Straumann Bone Ceramic; SBC and a collagen barrier, whereas in the control group (n = 13) a deproteinized bovine bone mineral (DBBM) and the same collagen barrier were used. After 8 months of healing, titanium dental implants with a hydrophilic surface were placed in the preserved ridges. During surgery, 9/13 implants in the SBC group and 8/12 implants in the DBBM group presented with either dehiscence or fenestration defects and required additional bone augmentation. The implants were loaded at 4 months following placement and were followed up for 1 year post-loading. Interproximal radiographic bone levels were evaluated in standardized periapical radiographs at loading and 1 year post-loading. Probing pocket depth, gingival recession and bleeding upon probing were recorded at implants and neighbouring teeth. The success rate of the implants was evaluated according to criteria set by Albrektsson et al. (1986). The survival rate of the implants in both groups was 100% at 1-year post-loading. No statistically significant differences in any of the clinical and radiographic measurements were detected between the two groups (P < 0.05). The success rate of the implants was 84.6% (11/13) in the SBC group and 83.3% (10/12) in the DBBM group. Equivalent success and survival rates (as well as similar radiographic changes) of dental implants placed in alveolar ridges previously preserved with SBC or DBBM should be anticipated. © 2012 John Wiley & Sons A/S.

Influence of fine threads and platform-switching on crestal bone stress around implant-a three-dimensional finite element analysis.

PubMed

Khurana, Pardeep; Sharma, Arun; Sodhi, Kiranmeet Kaur

2013-12-01

The aims of this study were to investigate the effect of implant fine threads on crestal bone stress compared to a standard smooth implant collar and to analyze how different abutment diameters influenced the crestal bone stress level. Three-dimensional finite element imaging was used to create a cross-sectional model in SolidWorks 2007 software of an implant (5-mm platform and 10 mm in length) placed in the premolar region of the mandible. The implant model was created to resemble a commercially available fine thread implant. Abutments of different diameters (5.0 mm: standard, 4.5 mm, 4.0 mm, and 3.5 mm) were loaded with a force of 100 N at 90° vertical and 40° oblique angles. Finite element analysis was done in COSMOSWorks software, which was used to analyze the stress patterns in bone, especially in the crestal region. Upon loading, the fine thread implant model had greater stress at the crestal bone adjacent to the implant than the smooth neck implant in both vertical and oblique loading. When the abutment diameter decreased progressively from 5.0 mm to 4.5 mm to 4 mm and to 3.5 mm the thread model showed a reduction of stress at the crestal bone level from 23.2 MPa to 15.02 MPa for fine thread and from 22.7 to 13.5 MPa for smooth collar implant group after vertical loading and from 43.7 MPa to 33.1 MPa in fine thread model and from 36.9 to 20.5 MPa in smooth collar implant model after oblique loading. Fine threads increase crestal stress upon loading. Reduced abutment diameter that is platform switching resulted in less stress translated to the crestal bone in the fine thread and smooth neck.

Effect of long-term impact-loading on mass, size, and estimated strength of humerus and radius of female racquet-sports players: a peripheral quantitative computed tomography study between young and old starters and controls.

PubMed

Kontulainen, Saija; Sievänen, Harri; Kannus, Pekka; Pasanen, Matti; Vuori, Ilkka

2002-12-01

Bone characteristics of the humeral shaft and distal radius were measured from 64 female tennis and squash players and their 27 age-, height-, and weight-matched controls with peripheral quantitative tomography (pQCT) and DXA. The players were divided into two groups according to the starting age of their tennis or squash training (either before or after menarche) to examine the possible differences in the loading-induced changes in bone structure and volumetric density. The used pQCT variables were bone mineral content (BMC), total cross-sectional area (TotA) of bone, cross-sectional area of the marrow cavity (CavA) and that of the cortical bone (CoA), cortical wall thickness (CWT), volumetric density of the cortical bone (CoD) and trabecular bone (TrD), and torsional bone strength index (BSIt) for the shaft, and compressional bone strength index (BSIc) for the bone end. These bone strength indices were compared with the DXA-derived areal bone mineral density (aBMD) to assess how well the latter represents the effect of mechanical loading on apparent bone strength. At the humeral shaft, the loaded arm's greater BMC (an average 19% side-to-side difference in young starters and 9% in old starters) was caused by an enlarged cortex (CoA; side-to-side differences 20% and 9%, respectively). The loaded humerus seemed to have grown periosteally (the CavA did not differ between the sites) leading to 26% and 11% side-to-side BSIt difference in the young and old starters, respectively. CoD was equal between the arms (-1% difference in both player groups). The side-to-side differences in the young starters' BMC, CoA, TotA, CWT, and BSIt were 8-22% higher than those of the controls and 8-14% higher than those of the old starters. Old starters' BMC, CoA, and BSIt side-to-side differences were 6-7% greater than those in the controls. The DXA-derived side-to-side aBMD difference was 7% greater in young starters compared with that of the old starters and 14% compared with that in controls, whereas the difference between old starters and controls was 6%, in favor of the former. All these between-group differences were statistically significant. At the distal radius, the player groups differed significantly from controls in the side-to-side BMC, TrD, and aBMD differences only; the young starters' BMC difference was 9% greater, TrD and aBMD differences were 5% greater than those in the controls, and the old starters' TrD and aBMD differences were both 7% greater than those in the controls. In summary, in both of the female player groups the structural adaptation of the humeral shaft to long-term loading seemed to be achievedthrough periosteal enlargement of the bone cortex although this adaptation was clearly better in the young starters. Exercise-induced cortical enlargement was not so clear at the distal radius (a trabecular bone site), and the study suggested that at long bone ends also the TrD could be a modifiable factor to build a stronger bone structure. The conventional DXA-based aBMD measurement detected the intergroup differences in the exercise-induced bone gains, although, measuring two dimensions of bone only, it seemed to underestimate the effect of exercise on the apparent bone strength, especially if the playing had been started during the growing years.

Assessment of bone healing ability of calcium phosphate cements loaded with platelet lysate in rat calvarial defects.

PubMed

Babo, Pedro S; Carvalho, Pedro P; Santo, Vítor E; Faria, Susana; Gomes, Manuela E; Reis, Rui L

2016-11-01

Injectable calcium phosphate cements have been used as a valid alternative to autologous bone grafts for bone augmentation with the additional advantage of enabling minimally invasive implantation procedures and for perfectly fitting the tissue defect. Nevertheless, they have low biodegradability and lack adequate biochemical signaling to promote bone healing and remodeling. In previous in vitro studies, we observed that the incorporation of platelet lysate directly into the cement paste or loaded in hyaluronic acid microspheres allowed to modulate the cement degradation and the in vitro expression of osteogenic markers in seeded human adipose derived stem cells. The present study aimed at investigating the possible effect of this system in new bone formation when implanted in calvarial bilateral defects in rats. Different formulations were assessed, namely plain calcium phosphate cements, calcium phosphate cements loaded with human platelet lysate, hybrid injectable formulations composed of the calcium phosphate cement incorporating hyaluronin acid non-loaded microparticles (20% hyaluronin acid) or with particles loaded with platelet lysate. The degradability and new bone regrowth were evaluated in terms of mineral volume in the defect, measured by micro-computed tomography and histomorphometric analysis upon 4, 8 and 12 weeks of implantation. We observed that the incorporation of hyaluronin acid microspheres induced an overly rapid cement degradation, impairing the osteoconductive properties of the cement composites. Moreover, the incorporation of platelet lysate induced higher bone healing than the materials without platelet lysate, up to four weeks after surgery. Nevertheless, this effect was not found to be significant when compared to the one observed in the sham-treated group. © The Author(s) 2016.

Influence of surgical and prosthetic techniques on marginal bone loss around titanium implants. Part I: immediate loading in fresh extraction sockets.

PubMed

Berberi, Antoine N; Tehini, Georges E; Noujeim, Ziad F; Khairallah, Alexandre A; Abousehlib, Moustafa N; Salameh, Ziad A

2014-10-01

Delayed placement of implant abutments has been associated with peri-implant marginal bone loss; however, long-term results obtained by modifying surgical and prosthetic techniques after implant placement are still lacking. This study aimed to evaluate the marginal bone loss around titanium implants placed in fresh extraction sockets using two loading protocols after a 5-year follow-up period. A total of 36 patients received 40 titanium implants (Astra Tech) intended for single-tooth replacement. Implants were immediately placed into fresh extraction sockets using either a one-stage (immediate loading by placing an interim prosthesis into functional occlusion) or a two-stage prosthetic loading protocol (insertion of abutments after 8 weeks of healing time). Marginal bone levels relative to the implant reference point were evaluated at four time intervals using intraoral radiographs: at time of implant placement, and 1, 3, and 5 years after implant placement. Measurements were obtained from mesial and distal surfaces of each implant (α = 0.05). One-stage immediate implant placement into fresh extraction sockets resulted in a significant reduction in marginal bone loss (p < 0.002) compared to the traditional two-stage technique. Whereas mesial surfaces remained stable for the 5-year observation period, significant marginal bone loss was observed on distal surfaces of implants after cementation of interim prostheses (p < 0.007) and after 12 months (p < 0.034). Within the limitations of this study, immediate loading of implants placed into fresh extraction sockets reduced marginal bone loss and did not compromise the success rate of the restorations. © 2014 by the American College of Prosthodontists.

Highly aligned porous Ti scaffold coated with bone morphogenetic protein-loaded silica/chitosan hybrid for enhanced bone regeneration.

PubMed

Jung, Hyun-Do; Yook, Se-Won; Han, Cheol-Min; Jang, Tae-Sik; Kim, Hyoun-Ee; Koh, Young-Hag; Estrin, Yuri

2014-07-01

Porous Ti has been widely investigated for orthopedic and dental applications on account of their ability to promote implant fixation via bone ingrowth into pores. In this study, highly aligned porous Ti scaffolds coated with a bone morphogenetic protein (BMP)-loaded silica/chitosan hybrid were produced, and their bone regeneration ability was evaluated by in vivo animal experiments. Reverse freeze casting allowed for the creation of highly aligned pores, resulting in a high compressive strength of 254 ± 21 MPa of the scaffolds at a porosity level of ∼51 vol %. In addition, a BMP-loaded silica/chitosan hybrid coating layer with a thickness of ∼1 μm was uniformly deposited on the porous Ti scaffold, which enabled the sustained release of the BMP over a prolonged period of time up to 26 days. The cumulative amount of the BMP released was ∼4 μg, which was much higher than that released from the specimen without a hybrid coating layer. In addition, the bone regeneration ability of the porous Ti scaffold with a BMP-loaded silica/chitosan coating layer was examined by in vivo animal testing using a rabbit calvarial defect model and compared with those of the as-produced porous Ti scaffold and porous Ti scaffold with a silica/chitosan coating layer. After 4 weeks of healing, the specimen coated with a BMP-loaded silica/chitosan hybrid showed a much higher bone regeneration volume (∼36%) than the as-produced specimen (∼15%) (p < 0.005) and even the specimen coated with a silica/chitosan hybrid (∼25%) (p < 0.05). © 2013 Wiley Periodicals, Inc.

Finite element analysis of maxillary bone stress caused by Aramany Class IV obturator prostheses.

PubMed

Miyashita, Elcio Ricardo; Mattos, Beatriz Silva Câmara; Noritomi, Pedro Yoshito; Navarro, Hamilton

2012-05-01

The retention of an Aramany Class IV removable partial dental prosthesis can be compromised by a lack of support. The biomechanics of this obturator prosthesis result in an unusual stress distribution on the residual maxillary bone. This study evaluated the biomechanics of an Aramany Class IV obturator prosthesis with finite element analysis and a digital 3-dimensional (3-D) model developed from a computed tomography scan; bone stress was evaluated according to the load placed on the prosthesis. A 3-D model of an Aramany Class IV maxillary resection and prosthesis was constructed. This model was used to develop a finite element mesh. A 120 N load was applied to the occlusal and incisal platforms corresponding to the prosthetic teeth. Qualitative analysis was based on the scale of maximum principal stress; values obtained through quantitative analysis were expressed in MPa. Under posterior load, tensile and compressive stresses were observed; the tensile stress was greater than the compressive stress, regardless of the bone region, and the greatest compressive stress was observed on the anterior palate near the midline. Under an anterior load, tensile stress was observed in all of the evaluated bone regions; the tensile stress was greater than the compressive stress, regardless of the bone region. The Aramany Class IV obturator prosthesis tended to rotate toward the surgical resection when subjected to posterior or anterior loads. The amount of tensile and compressive stress caused by the Aramany Class IV obturator prosthesis did not exceed the physiological limits of the maxillary bone tissue. (J Prosthet Dent 2012;107:336-342). Copyright © 2012 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

Virtual stress testing of fracture stability in soldiers with severely comminuted tibial fractures.

PubMed

Petfield, Joseph L; Hayeck, Garry T; Kopperdahl, David L; Nesti, Leon J; Keaveny, Tony M; Hsu, Joseph R

2017-04-01

Virtual stress testing (VST) provides a non-invasive estimate of the strength of a healing bone through a biomechanical analysis of a patient's computed tomography (CT) scan. We asked whether VST could improve management of patients who had a tibia fracture treated with external fixation. In a retrospective case-control study of 65 soldier-patients who had tibia fractures treated with an external fixator, we performed VST utilizing CT scans acquired prior to fixator removal. The strength of the healing bone and the amount of tissue damage after application of an overload were computed for various virtual loading cases. Logistic regression identified computed outcomes with the strongest association to clinical events related to nonunion within 2 months after fixator removal. Clinical events (n = 9) were associated with a low tibial strength for compression loading (p < 0.05, AUC = 0.74) or a low proportion of failed cortical bone tissue for torsional loading (p < 0.005, AUC = 0.84). Using post-hoc thresholds of a compressive strength of four times body-weight and a proportional of failed cortical bone tissue of 5%, the test identified all nine patients who failed clinically (100% sensitivity; 40.9% positive predictive value) and over three fourths of those (43 of 56) who progressed to successful healing (76.8% specificity; 100% negative predictive value). In this study, VST identified all patients who progressed to full, uneventful union after fixator removal; thus, we conclude that this new test has the potential to provide a quantitative, objective means of identifying tibia-fracture patients who can safely resume weight bearing. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:805-811, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Musculoskeletal phenotype through the life course: the role of nutrition.

PubMed

Ward, Kate

2012-02-01

This review considers the definition of a healthy bone phenotype through the life course and the modulating effects of muscle function and nutrition. In particular, it will emphasise that optimal bone strength (and how that is regulated) is more important than simple measures of bone mass. The forces imposed on bone by muscle loading are the primary determinants of musculoskeletal health. Any factor that changes muscle loading on the bone, or the response of bone to loading results in alterations of bone strength. Advances in technology have enhanced the understanding of a healthy bone phenotype in different skeletal compartments. Multiple components of muscle strength can also be quantified. The critical evaluation of emerging technologies for assessment of bone and muscle phenotype is vital. Populations with low and moderate/high daily Ca intakes and/or different vitamin D status illustrate the importance of nutrition in determining musculoskeletal phenotype. Changes in mass and architecture maintain strength despite low Ca intake or vitamin D status. There is a complex interaction between body fat and bone which, in addition to protein intake, is emerging as a key area of research. Muscle and bone should be considered as an integrative unit; the role of body fat requires definition. There remains a lack of longitudinal evidence to understand how nutrition and lifestyle define musculoskeletal health. In conclusion, a life-course approach is required to understand the definition of healthy skeletal phenotype in different populations and at different stages of life.

Modulation of release kinetics by plasma polymerization of ampicillin-loaded β-TCP ceramics

NASA Astrophysics Data System (ADS)

Labay, C.; Buxadera-Palomero, J.; Avilés, M.; Canal, C.; Ginebra, M. P.

2016-08-01

Beta-tricalcium phosphate (β-TCP) bioceramics are employed in bone repair surgery. Their local implantation in bone defects puts them in the limelight as potential materials for local drug delivery. However, obtaining suitable release patterns fitting the required therapeutics is a challenge. Here, plasma polymerization of ampicillin-loaded β-TCP is studied for the design of a novel antibiotic delivery system. Polyethylene glycol-like (PEG-like) coating of β-TCP by low pressure plasma polymerization was performed using diglyme as precursor, and nanometric PEG-like layers were obtained by simple and double plasma polymerization processes. A significant increase in hydrophobicity, and the presence of plasma polymer was visible on the surface by SEM and quantified by XPS. As a main consequence of the plasma polymerisation, the release kinetics were successfully modified, avoiding burst release, and slowing down the initial rate of release leading to a 4.5 h delay in reaching the same antibiotic release percentage, whilst conservation of the activity of the antibiotic was simultaneously maintained. Thus, plasma polymerisation on the surface of bioceramics may be a good strategy to design controlled drug delivery matrices for local bone therapies.

Single-screw Fixation of Adolescent Salter-II Proximal Humeral Fractures: Biomechanical Analysis of the "One Pass Door Lock" Technique.

PubMed

Miller, Mark Carl; Redman, Christopher N; Mistovich, R Justin; Muriuki, Muturi; Sangimino, Mark J

2017-09-01

Pin fixation of Salter-II proximal humeral fractures in adolescents approaching skeletal maturity has potential complications that can be avoided with single-screw fixation. However, the strength of screw fixation relative to parallel and diverging pin fixation is unknown. To compare the biomechanical fixation strength between these fixation modalities, we used synthetic composite humeri, and then compared these results in composite bone with cadaveric humeri specimens. Parallel pinning, divergent pinning, and single-screw fixation repairs were performed on synthetic composite humeri with simulated fractures. Six specimens of each type were tested in axial loading and other 6 were tested in torsion. Five pair of cadaveric humeri were tested with diverging pins and single screws for comparison. Single-screw fixation was statistically stronger than pin fixation in axial and torsional loading in both composite and actual bone. There was no statistical difference between composite and cadaveric bone specimens. Single-screw fixation can offer greater stability to adolescent Salter-II fractures than traditional pinning. Single-screw fixation should be considered as a viable alternative to percutaneous pin fixation in transitional patients with little expected remaining growth.

In vitro evaluation of electrospun PLGA/PLLA/PDLLA blend fibers loaded with naringin for guided bone regeneration.

PubMed

Guo, Zhenzhao; Wu, Shuai; Li, Hong; Li, Qiyan; Wu, Gang; Zhou, Changren

2018-03-30

The present study was to evaluate fiber mesh loaded with naringin via electrospinning to guide bone regeneration in vitro. The naringin-loaded fiber mesh was prepared via elctrospinning of PLGA, PLLA, PDLLA blending solution with naringin. SEM showed that naringin decreased the fiber's diameter according to the concentration of naringin. After 20 days' degradation in PBS, the drug-loaded fiber meshes still kept their stability with about 10% decrease in tensile strength. In vitro release experiments showed a sustained and steady naringin releasing profile with little initial burst releasing. Compared to the mats without naringin, the fiber mats loaded with naringin showed the most pronounced enhancement of cell growth when MC3T3-E1 cells were cultured on the fiber mats. The blend fiber loaded with naringin has optimized physical properties and sustained release profile in vitro. The study presents a promising fibrous mesh material for guided bone regeneration therapy.

Biomechanical characterization of double-bundle femoral press-fit fixation techniques.

PubMed

Ettinger, M; Haasper, C; Hankemeier, S; Hurschler, C; Breitmeier, D; Krettek, C; Jagodzinski, M

2011-03-01

Press-fit fixation of patellar tendon bone anterior cruciate ligament autografts is an interesting technique because no hardware is necessary. To date, no biomechanical data exist describing an implant-free double-bundle press-fit procedure. The purpose of this study was to characterize the biomechanical properties of three double-bundle press-fit fixations. In a controlled laboratory study, the patellar-, quadriceps- and hamstring tendons of 10 human cadavers (age: 49.2 ± 18.5 years) were used. An inside out press-fit fixation with a knot in the semitendinosus and gracilis tendons (SG) combined with an additional bone block, with two quadriceps tendon bone block grafts (QU) was compared with press-fit fixation of two bone patellar tendon bone block (PT) grafts in 30 porcine femora. Constructs were cyclically stretched and then loaded until failure. Maximum load to failure, stiffness and elongation during failure testing and cyclical loading were investigated. The maximum load to failure was 703 ± 136 N for SG fixation, 632 ± 130 N for QU and 656 ± 127 N for PT fixation. Stiffness of the constructs averaged 138 ± 26 N/mm for SG, 159 ± 74 N/mm for QU, and 154 ± 50 N/mm for PT fixation. Elongation during initial cyclical loading was 1.2 ± 1.4 mm for SG, 2.0 ± 1.4 mm for QU, and 1.0 ± 0.6 mm for PT (significantly larger for PT and QU between the first 5 cycles compared with cycles 15-20th, P < 0.01). All investigated double-bundle fixation techniques were equal in terms of maximum load to failure, stiffness, and elongation. Unlike with single-bundle press-fit fixation techniques that have been published, no difference was observed between pure tendon combined with an additional bone block and tendon bone grafts. All techniques exhibited larger elongation during initial cyclical loading. All three press-fit fixation techniques that were investigated exhibit comparable biomechanical properties. Preconditioning of the constructs is critical.

Mechanical torque measurement predicts load to implant cut-out: a biomechanical study investigating DHS anchorage in femoral heads.

PubMed

Suhm, Norbert; Hengg, Clemens; Schwyn, Ronald; Windolf, Markus; Quarz, Volker; Hänni, Markus

2007-08-01

Bone strength plays an important role in implant anchorage. Bone mineral density (BMD) is used as surrogate parameter to quantify bone strength and to predict implant anchorage. BMD can be measured by means of quantitative computer tomography (QCT) or dual energy X-ray absorptiometry (DXA). These noninvasive methods for BMD measurement are not available pre- or intra-operatively. Instead, the surgeon could determine bone strength by direct mechanical measurement. We have evaluated mechanical torque measurement for (A) its capability to quantify local bone strength and (B) its predictive value towards load at implant cut-out. Our experimental study was performed using sixteen paired human cadaver proximal femurs. BMD was determined for all specimens by QCT. The torque to breakaway of the cancellous bone structure (peak torque) was measured by means of a mechanical probe at the exact position of subsequent DHS placement. The fixation strength of the DHS achieved was assessed by cyclic loading in a stepwise protocol beginning with 1,500 N increasing 500 N every 5,000 cycles until 4,000 N. A highly significant correlation of peak torque with BMD (QCT) was found (r = 0.902, r (2) = 0.814, P < 0.001). Peak torque correlated highly significant with the load at implant cut-out (r = 0.795, P < 0.001). All specimens with a measured peak torque below 6.79 Nm failed at the first load level of 1,500 N. The specimens with a peak torque above 8.63 Nm survived until the last load level of 4,000 N. Mechanical peak torque measurement is able to quantify bone strength. In an experimental setup, peak torque identifies those specimens that are likely to fail at low load. In clinical routine, implant migration and cut-out depend on several parameters, which are difficult to control, such as fracture type, fracture reduction achieved, and implant position. The predictive value of peak torque towards cut-out in a clinical set-up therefore has to be carefully validated.

Implementation and Integration of a Finite Element Model into the Bone Remodeling Model to Characterize Skeletal Loading

NASA Technical Reports Server (NTRS)

Werner, C. R.; Lewandowski, B.; Boppana, A.; Pennline, J. A.

2017-01-01

NASA's Digital Astronaut Project is developing a bone physiology model to predict changes in bone mineral density over the course of a space mission. The model intends to predict bone loss due to exposure in microgravity as well as predicting bone maintenance due to mechanical stimulus generated by exercise countermeasures. These predictions will be used to inform exercise device efficacy and to help design exercise protocols that will maintain bone mineral density during long exposures to microgravity during spaceflight. The mechanical stimulus and the stresses that are exhibited on the bone are important factors for bone remodeling. These stresses are dependent on the types of exercise that are performed and vary throughout the bone due to the geometry. A primary area of focus for bone health is the proximal femur. This location is critical in transmitting loads between the upper and lower body and have been known to be a critical failure point in older individuals with conditions like osteoporosis.

Radiographic evaluation of marginal bone level around implants with different neck designs after 1 year.

PubMed

Shin, Young-Kyu; Han, Chong-Hyun; Heo, Seong-Joo; Kim, Sunjai; Chun, Heoung-Jae

2006-01-01

To evaluate the influence of macro- and microstructure of the implant surface at the marginal bone level after functional loading. Sixty-eight patients were randomly assigned to 1 of 3 groups. The first group received 35 implants with a machined neck (Ankylos); the second group, 34 implants with a rough-surfaced neck (Stage 1); and the third, 38 implants with a rough-surfaced neck with microthreads (Oneplant). Clinical and radiographic examinations were conducted at baseline (implant loading) and 3, 6, and 12 months postloading. Two-way repeated analysis of variance (ANOVA) was used to test the significance of marginal bone change of each tested group at baseline, 3, 6, and 12 month follow-ups and 1-way ANOVA was also used to compare the bone loss of each time interval within the same implant group (P < .05). At 12 months, significant differences were noted in the amount of alveolar bone loss recorded for the 3 groups (P < .05). The group with the rough-surfaced microthreaded neck had a mean crestal bone loss of 0.18 +/- 0.16 mm; the group with the rough-surfaced neck, 0.76 +/- 0.21 mm; and the group with the machined neck, 1.32 +/- 0.27 mm. In the rough-surfaced group and the rough-surfaced microthreaded group, no statistically significant changes were observed after 3 months, whereas the machined-surface group showed significant bone loss for every interval (P < .05). To minimize marginal bone loss, in addition to the use of a rough surface at the marginal bone level, a macroscopic modification such as the addition of microthreads could be recommended. A rough surface and microthreads at the implant neck not only reduce crestal bone loss but also help with early biomechanical adaptation against loading in comparison to the machined neck design. A rough surface with microthreads at the implant neck was the most effective design to maintain the marginal bone level against functional loading.

Correlation of cervical endplate strength with CT measured subchondral bone density

PubMed Central

Ordway, Nathaniel R.; Lu, Yen-Mou; Zhang, Xingkai; Cheng, Chin-Chang; Fang, Huang

2007-01-01

Cervical interbody device subsidence can result in screw breakage, plate dislodgement, and/or kyphosis. Preoperative bone density measurement may be helpful in predicting the complications associated with anterior cervical surgery. This is especially important when a motion preserving device is implanted given the detrimental effect of subsidence on the postoperative segmental motion following disc replacement. To evaluate the structural properties of the cervical endplate and examine the correlation with CT measured trabecular bone density. Eight fresh human cadaver cervical spines (C2–T1) were CT scanned and the average trabecular bone densities of the vertebral bodies (C3–C7) were measured. Each endplate surface was biomechanically tested for regional yield load and stiffness using an indentation test method. Overall average density of the cervical vertebral body trabecular bone was 270 ± 74 mg/cm3. There was no significant difference between levels. The yield load and stiffness from the indentation test of the endplate averaged 139 ± 99 N and 156 ± 52 N/mm across all cervical levels, endplate surfaces, and regional locations. The posterior aspect of the endplate had significantly higher yield load and stiffness in comparison to the anterior aspect and the lateral aspect had significantly higher yield load in comparison to the midline aspect. There was a significant correlation between the average yield load and stiffness of the cervical endplate and the trabecular bone density on regression analysis. Although there are significant regional variations in the endplate structural properties, the average of the endplate yield loads and stiffnesses correlated with the trabecular bone density. Given the morbidity associated with subsidence of interbody devices, a reliable and predictive method of measuring endplate strength in the cervical spine is required. Bone density measures may be used preoperatively to assist in the prediction of the strength of the vertebral endplate. A threshold density measure has yet to be established where the probability of endplate fracture outweighs the benefit of anterior cervical procedure. PMID:17712574

Finite element simulation of Reference Point Indentation on bone.

PubMed

Idkaidek, Ashraf; Agarwal, Vineet; Jasiuk, Iwona

2017-01-01

Reference Point Indentation (RPI) is a novel technique aimed to assess bone quality. Measurements are recorded by the BioDent instrument that applies multiple indents to the same location of cortical bone. Ten RPI parameters are obtained from the resulting force-displacement curves. Using the commercial finite element analysis software Abaqus, we assess the significance of the RPI parameters. We create an axisymmetric model and employ an isotropic viscoelastic-plastic constitutive relation with damage to simulate indentations on a human cortical bone. Fracture of bone tissue is not simulated for simplicity. The RPI outputs are computed for different simulated test cases and then compared with experimental results, measured using the BioDent, found in literature. The number of cycles, maximum indentation load, indenter tip radius, and the mechanical properties of bone: Young׳s modulus, compressive yield stress, and viscosity and damage constants, are varied. The trends in the RPI parameters are then investigated. We find that the RPI parameters are sensitive to the mechanical properties of bone. An increase in Young׳s modulus of bone causes the force-displacement loading and unloading slopes to increase and the total indentation distance (TID) to decrease. The compressive yield stress is inversely proportional to a creep indentation distance (CID1) and the TID. The viscosity constant is proportional to the CID1 and an average of the energy dissipated (AvED). The maximum indentation load is proportional to the TID, CID1, loading and unloading slopes, and AvED. The damage parameter is proportional to the TID, but it is inversely proportional to both the loading and unloading slopes and the AvED. The value of an indenter tip radius is proportional to the CID1 and inversely proportional to the TID. The number of load cycles is inversely proportional to an average of a creep indentation depth (AvCID) and the AvED. The indentation distance increase (IDI) is strongly inversely proportional to the compressive yield stress, and strongly proportional to the viscosity constant and maximum applied load, but has weak relation with the damage parameter, indenter tip radius, and elastic modulus. This computational study advances our understanding of the RPI outputs and provides a starting point for more comprehensive computational studies of the RPI technique. Copyright © 2016 Elsevier Ltd. All rights reserved.

3D Printing Surgical Implants at the clinic: A Experimental Study on Anterior Cruciate Ligament Reconstruction

PubMed Central

Liu, An; Xue, Guang-huai; Sun, Miao; Shao, Hui-feng; Ma, Chi-yuan; Gao, Qing; Gou, Zhong-ru; Yan, Shi-gui; Liu, Yan-ming; He, Yong

2016-01-01

Desktop three-dimensional (3D) printers (D3DPs) have become a popular tool for fabricating personalized consumer products, favored for low cost, easy operation, and other advantageous qualities. This study focused on the potential for using D3DPs to successfully, rapidly, and economically print customized implants at medical clinics. An experiment was conducted on a D3DP-printed anterior cruciate ligament surgical implant using a rabbit model. A well-defined, orthogonal, porous PLA screw-like scaffold was printed, then coated with hydroxyapatite (HA) to improve its osteoconductivity. As an internal fixation as well as an ideal cell delivery system, the osteogenic scaffold loaded with mesenchymal stem cells (MSCs) were evaluated through both in vitro and in vivo tests to observe bone-ligament healing via cell therapy. The MSCs suspended in Pluronic F-127 hydrogel on PLA/HA screw-like scaffold showed the highest cell proliferation and osteogenesis in vitro. In vivo assessment of rabbit anterior cruciate ligament models for 4 and 12 weeks showed that the PLA/HA screw-like scaffold loaded with MSCs suspended in Pluronic F-127 hydrogel exhibited significant bone ingrowth and bone-graft interface formation within the bone tunnel. Overall, the results of this study demonstrate that fabricating surgical implants at the clinic (fab@clinic) with D3DPs can be feasible, effective, and economical. PMID:26875826

Insights into the effects of tensile and compressive loadings on human femur bone.

PubMed

Havaldar, Raviraj; Pilli, S C; Putti, B B

2014-01-01

Fragile fractures are most likely manifestations of fatigue damage that develop under repetitive loading conditions. Numerous microcracks disperse throughout the bone with the tensile and compressive loads. In this study, tensile and compressive load tests are performed on specimens of both the genders within 19 to 83 years of age and the failure strength is estimated. Fifty five human femur cortical samples are tested. They are divided into various age groups ranging from 19-83 years. Mechanical tests are performed on an Instron 3366 universal testing machine, according to American Society for Testing and Materials International (ASTM) standards. The results show that stress induced in the bone tissue depends on age and gender. It is observed that both tensile and compression strengths reduces as age advances. Compressive strength is more than tensile strength in both the genders. The compression and tensile strength of human femur cortical bone is estimated for both male and female subjecting in the age group of 19-83 years. The fracture toughness increases till 35 years in male and 30 years in female and reduces there after. Mechanical properties of bone are age and gender dependent.

Analysis of Bone Height Changes after Maxillary Sinus Augmentation with Simultaneous and Delayed Placement of Dental Implants: A Clinical and Radiographic Study.

PubMed

Yin, Lihua; Yu, Zhanhai; Chen, Zhuofan; Huang, Baoxin; Zhang, Kailiang; Zhou, Ailing; Li, Xiangxin

2016-08-01

To retrospectively assess the changes of the vertical height of the maxillary sinus floor after augmentation with simultaneous and delayed placement of implants. In total, 38 patients with 76 implants were involved; vertical bone height of the sinus floor was radiographically measured at different stages including preoperation, immediately postsurgery, 6 and 12 months postsurgery, and 6 and 24 months postfunctional loading. Sinus augmentation significantly increased vertical bone height of the sinus floor for both the simultaneous and delayed groups. The survival rate was 100% in the simultaneous group and 95.46% in the delayed group. For simultaneous placement, the vertical bone height of the sinus floor at 6 and 12 months postsurgery was significantly less than that immediately postsurgery. For both groups, augmented bone height of the sinus floor showed significant decrease from 6 months to 24 months postfunctional loading. The mean value of final bone augmentation was 5.85 mm for simultaneous placement and 5.80 mm for delayed placements. Sinus augmentation with simultaneous and delayed placement of implants led to similar survival rates and bone augmentation. Resorption of augmentative bone was evident at 24 months postfunctional loading in both cases. © 2015 by the American College of Prosthodontists.

Numerical investigation of bone remodelling around immediately loaded dental implants using sika deer (Cervus nippon) antlers as implant bed.

PubMed

He, Yun; Hasan, Istabrak; Keilig, Ludger; Fischer, Dominik; Ziegler, Luisa; Abboud, Marcus; Wahl, Gerhard; Bourauel, Christoph

2018-03-01

This study combines finite element method and animal studies, aiming to investigate tissue remodelling processes around dental implants inserted into sika deer antler and to develop an alternative animal consuming model for studying bone remodelling around implants. Implants were inserted in the antlers and loaded immediately via a self-developed loading device. After 3, 4, 5 and 6 weeks, implants and surrounding tissue were taken out. Specimens were scanned by μCT scanner and finite element models were generated. Immediate loading and osseointegration conditions were simulated at the implant-tissue interface. A vertical force of 10 N was applied on the implant. During the healing time, density and Young's modulus of antler tissue around the implant increased significantly. For each time point, the values of displacement, stresses and strains in the osseointegration model were lower than those of the immediate loading model. As the healing time increased, the displacement of implants was reduced. The 3-week immediate loading model (9878 ± 1965 μstrain) illustrated the highest strains in the antler tissue. Antler tissue showed similar biomechanical properties as human bone in investigating the bone remodelling around implants, therefore the use of sika deer antler model is a promising alternative in implant biomechanical studies.

In vivo tibial stiffness is maintained by whole bone morphology and cross-sectional geometry in growing female mice

PubMed Central

Main, Russell P.; Lynch, Maureen E.; van der Meulen, Marjolein C.H.

2010-01-01

Whole bone morphology, cortical geometry, and tissue material properties modulate skeletal stresses and strains that in turn influence skeletal physiology and remodeling. Understanding how bone stiffness, the relationship between applied load and tissue strain, is regulated by developmental changes in bone structure and tissue material properties is important in implementing biophysical strategies for promoting healthy bone growth and preventing bone loss. The goal of this study was to relate developmental patterns of in vivo whole bone stiffness to whole bone morphology, cross-sectional geometry, and tissue properties using a mouse axial loading model. We measured in vivo tibial stiffness in three age groups (6wks, 10wks, 16wks old) of female C57Bl/6 mice during cyclic tibial compression. Tibial stiffness was then related to cortical geometry, longitudinal bone curvature, and tissue mineral density using microcomputed tomography (microCT). Tibial stiffness and the stresses induced by axial compression were generally maintained from 6 to 16wks of age. Growth-related increases in cortical cross-sectional geometry and longitudinal bone curvature had counteracting effects on induced bone stresses and, therefore, maintained tibial stiffness similarly with growth. Tissue mineral density increased slightly from 6 to 16wks of age, and although the effects of this increase on tibial stiffness were not directly measured, its role in the modulation of whole bone stiffness was likely minor over the age range examined. Thus, whole bone morphology, as characterized by longitudinal curvature, along with cortical geometry, plays an important role in modulating bone stiffness during development and should be considered when evaluating and designing in vivo loading studies and biophysical skeletal therapies. PMID:20673665

2D FEA of evaluation of micromovements and stresses at bone-implant interface in immediately loaded tapered implants in the posterior maxilla.

PubMed

Desai, Shrikar R; Singh, Rika; Karthikeyan, I

2013-09-01

The aim of the study is to evaluate the influence implant length on stress distribution at bone implant interface in single immediately loaded implants when placed in D4 bone quality. A 2-dimensional finite element models were developed to simulate two types of implant designs, standard 3.75 mm-diameter tapered body implants of 6 and 10 mm lengths. The implants were placed in D4 bone quality with a cortical bone thickness of 0.5 mm. The implant design incorporated microthreads at the crestal part and the rest of the implant body incorporated Acme threads. The Acme thread form has a 29° thread angle with a thread height half of the pitch; the apex and valley are flat. A 100 N of force was applied vertically and in the oblique direction (at an angle of 45°) to the long axis of the implants. The respective material properties were assigned. Micro-movements and stresses at the bone implant interface were evaluated. The results of total deformation (micro-movement) and Von mises stress were found to be lower for tapered long implant (10 mm) than short implant (6 mm) while using both vertical as well as oblique loading. Short implants can be successfully placed in poor bone quality under immediate loading protocol. The novel approach of the combination of microthreads at the crestal portion and acme threads for body portion of implant fixture gave promising results.

Effect of long-term impact-loading on mass, size, and estimated strength of humerus and radius of female racquet-sports players: a peripheral quantitative computed tomography study between young and old starters and controls.

PubMed

Kontulainen, Saija; Sievänen, Harri; Kannus, Pekka; Pasanen, Matti; Vuori, Ilkka

2003-02-01

Bone characteristics of the humeral shaft and distal radius were measured from 64 female tennis and squash players and their 27 age-, height-, and weight-matched controls with peripheral quantitative tomography (pQCT) and dual energy X-ray absorptiometry (DXA). The players were divided into two groups according to the starting age of their tennis or squash training (either before or after menarche) to examine the possible differences in the loading-induced changes in bone structure and volumetric density. The following pQCT variables were used: bone mineral content, total cross-sectional area of bone (TotA), cross-sectional area of the marrow cavity (CavA) and that of the cortical bone (CoA), cortical wall thickness (CWT), volumetric density of the cortical bone (CoD) and trabecular bone (TrD), and torsional bone strength index for the shaft (BSIt) and compressional bone strength index for the bone end (BSIc). These bone strength indices were compared with the DXA-derived areal bone mineral density (aBMD) to assess how well the latter represents the effect of mechanical loading on apparent bone strength. At the humeral shaft, the loaded arm's greater bone mineral content (an average 19% side-to-side difference in young starters and 9% in old starters), was caused by an enlarged cortex (CoA; side-to-side differences 20% and 9%, respectively). The loaded humerus seemed to have grown periosteally (the CavA did not differ between the sites), leading to 26% and 11% side-to-side BSIt differences in the young and old starters, respectively. CoD was equal between the arms (-1% difference in both player groups). The side-to-side differences in the young starters' bone mineral content, CoA, TotA, CWT, and BSIt were 8-22% higher than those of the controls and 8-14% higher than those of the old starters. Old starters' bone mineral content, CoA, and BSIt side-to-side differences were 6-7% greater than those in the controls. The DXA-derived side-to-side aBMD difference was 7% greater in young starters compared with that of the old starters and 14% compared with that in controls, whereas the difference between old starters and controls was 6%, in favor of the former. All these between-group differences were statistically significant. At the distal radius, the player groups differed significantly from controls in the side-to-side bone mineral content, TrD, and aBMD differences only: the young starters' bone mineral content difference was 9% greater, TrD and aBMD differences were 5% greater than those in the controls, and the old starters' TrD and aBMD differences were both 7% greater than those in the controls. In summary, in both of the female player groups, the structural adaptation of the humeral shaft to long-term loading seemed to be achieved through periosteal enlargement of the bone cortex, although this adaptation was clearly better in the young starters. Exercise-induced cortical enlargement was not so clear at the distal radius (a trabecular bone site), and the study suggested that at long bone ends, the trabecular density could be a modifiable factor to built a stronger bone structure. Conventional DXA-based aBMD measurement detected the intergroup differences in the exercise-induced bone gains, although, because it measured two dimensions of bone only, it seemed to underestimate the effect of exercise on the apparent bone strength, especially if the playing had been started during the growing years.

Instrumentation and Methods to Measure Dynamic Forces During Exercise Using the Horizontal Exercise Machine

NASA Technical Reports Server (NTRS)

Figueroa, Fernando

1999-01-01

It is hypothesized that bone loss experienced by astronauts in zero gravity conditions may be curtailed by appropriate exercise. According to Wolf's law, bone regenerates when muscles produce stresses by pulling on the bone during daily activity and/or exercise on Earth. To use this theory to prevent or decrease bone loss, one needs to quantify musculoskeletal loads and relate them to bone density changes. In the context of the space program, it is desirable to determine musculoskeletal loads during exercise so that one may make similar measurements on Earth and in space. In this manner, load measurements on Earth may be used as reference to generate similar loads during exercise in space. A research project to investigate the effects of high-resistive exercise to decrease bone density loss underzero-gravity conditions is being carried out in Life Sciences Research Laboratories at NASA JSC. The project consists of a bed-rest study whereby subjects remain in horizontal position for seventeen weeks. During the study, a subset of those subjects executes a regime of resistive exercises in the horizontal exercise machine (HEM). The HEM was designed so that subjects remain horizontal while exercising to minimize gravity loading even during exercise. Bone density of each subject is measured throughout the duration of their participation. The objective of the study is to determine if the resistive exercises are effective in diminishing or eliminating bone loss. My participation in this project relates to instrumentation, measurement, and processing of signals from displacement sensors (optical encoders) and load-cells. Measurement of displacements will be used to determine the motion of the body during exercise, and load measurements will be used (along with displacement data) to determine forces and torques exerted on each section of the body during exercise. Further, I have assisted in specifying new sensors to be added to the HEM and to a new prototype resistive exercise machine called the Interim Resistive Exercise Device (IRED). New load cells and encoders should be mounted in these devices to obtain more complete kineto-dynamic information. This report includes a description of the instrumentation that was built to perform measurements in the HEM and the IRED, along with the software that was developed to collect the measurements. It also includes examples of measurements taken in the HEM. Finally, a plan is laid out that describes how these measurements may be used to determine forces exerted by muscles for each exercise.

Marrow fat may distribute the energy of impact loading throughout subchondral bone

PubMed Central

Simkin, Peter A

2018-01-01

Abstract Most students of articular mechanics consider impact loads to be compressive forces that are borne by an intraosseous, trabecular scaffold. The possible role of marrow fat, which comprises about 75% of the structure, is generally ignored, and the potential contribution of type 1 collagen, the prototypic tensile protein, is not considered. Here, I question the evidence underlying these omissions and reject the conclusion of exclusive trabecular compression. Instead, I suggest that impact loading pressurizes the fat in subchondral compartments, and those pressures stretch the elastic trabecular walls, which are thereby subjected to tensile loading. The load-driven pressure pulses then diminish as they pass from each compartment to its adjoining neighbours. The resulting pressure gradient distributes the burden throughout the subchondrium, stores energy for ensuing recovery and subjects individual trabeculae only to the net pressure differences between adjacent compartments. PMID:28977578

Fabrication and in vitro biological properties of piezoelectric bioceramics for bone regeneration

PubMed Central

Tang, Yufei; Wu, Cong; Wu, Zixiang; Hu, Long; Zhang, Wei; Zhao, Kang

2017-01-01

The piezoelectric effect of biological piezoelectric materials promotes bone growth. However, the material should be subjected to stress before it can produce an electric charge that promotes bone repair and reconstruction conducive to fracture healing. A novel method for in vitro experimentation of biological piezoelectric materials with physiological load is presented. A dynamic loading device that can simulate the force of human motion and provide periodic load to piezoelectric materials when co-cultured with cells was designed to obtain a realistic expression of piezoelectric effect on bone repair. Hydroxyapatite (HA)/barium titanate (BaTiO3) composite materials were fabricated by slip casting, and their piezoelectric properties were obtained by polarization. The d33 of HA/BaTiO3 piezoelectric ceramics after polarization was 1.3 pC/N to 6.8 pC/N with BaTiO3 content ranging from 80% to 100%. The in vitro biological properties of piezoelectric bioceramics with and without cycle loading were investigated. When HA/BaTiO3 piezoelectric bioceramics were affected by cycle loading, the piezoelectric effect of BaTiO3 promoted the growth of osteoblasts and interaction with HA, which was better than the effect of HA alone. The best biocompatibility and bone-inducing activity were demonstrated by the 10%HA/90%BaTiO3 piezoelectric ceramics. PMID:28240268

Fabrication and in vitro biological properties of piezoelectric bioceramics for bone regeneration.

PubMed

Tang, Yufei; Wu, Cong; Wu, Zixiang; Hu, Long; Zhang, Wei; Zhao, Kang

2017-02-27

The piezoelectric effect of biological piezoelectric materials promotes bone growth. However, the material should be subjected to stress before it can produce an electric charge that promotes bone repair and reconstruction conducive to fracture healing. A novel method for in vitro experimentation of biological piezoelectric materials with physiological load is presented. A dynamic loading device that can simulate the force of human motion and provide periodic load to piezoelectric materials when co-cultured with cells was designed to obtain a realistic expression of piezoelectric effect on bone repair. Hydroxyapatite (HA)/barium titanate (BaTiO 3 ) composite materials were fabricated by slip casting, and their piezoelectric properties were obtained by polarization. The d 33 of HA/BaTiO 3 piezoelectric ceramics after polarization was 1.3 pC/N to 6.8 pC/N with BaTiO 3 content ranging from 80% to 100%. The in vitro biological properties of piezoelectric bioceramics with and without cycle loading were investigated. When HA/BaTiO 3 piezoelectric bioceramics were affected by cycle loading, the piezoelectric effect of BaTiO 3 promoted the growth of osteoblasts and interaction with HA, which was better than the effect of HA alone. The best biocompatibility and bone-inducing activity were demonstrated by the 10%HA/90%BaTiO 3 piezoelectric ceramics.

Fabrication and in vitro biological properties of piezoelectric bioceramics for bone regeneration

NASA Astrophysics Data System (ADS)

Tang, Yufei; Wu, Cong; Wu, Zixiang; Hu, Long; Zhang, Wei; Zhao, Kang

2017-02-01

The piezoelectric effect of biological piezoelectric materials promotes bone growth. However, the material should be subjected to stress before it can produce an electric charge that promotes bone repair and reconstruction conducive to fracture healing. A novel method for in vitro experimentation of biological piezoelectric materials with physiological load is presented. A dynamic loading device that can simulate the force of human motion and provide periodic load to piezoelectric materials when co-cultured with cells was designed to obtain a realistic expression of piezoelectric effect on bone repair. Hydroxyapatite (HA)/barium titanate (BaTiO3) composite materials were fabricated by slip casting, and their piezoelectric properties were obtained by polarization. The d33 of HA/BaTiO3 piezoelectric ceramics after polarization was 1.3 pC/N to 6.8 pC/N with BaTiO3 content ranging from 80% to 100%. The in vitro biological properties of piezoelectric bioceramics with and without cycle loading were investigated. When HA/BaTiO3 piezoelectric bioceramics were affected by cycle loading, the piezoelectric effect of BaTiO3 promoted the growth of osteoblasts and interaction with HA, which was better than the effect of HA alone. The best biocompatibility and bone-inducing activity were demonstrated by the 10%HA/90%BaTiO3 piezoelectric ceramics.

The combination of ultrasound with antibiotics released from bone cement decreases the viability of planktonic and biofilm bacteria: an in vitro study with clinical strains.

PubMed

Ensing, Geert T; Neut, Daniëlle; van Horn, Jim R; van der Mei, Henny C; Busscher, Henk J

2006-12-01

Antibiotic-loaded bone cements are used for the permanent fixation of joint prostheses. Antibiotic-loaded cements significantly decrease the incidence of infection. The objective of this study was to investigate whether the viability of bacteria derived from patients with a prosthesis-related infection could be further decreased when antibiotic release from bone cements was combined with application of pulsed ultrasound. Escherichia coli ATCC 10798, Staphylococcus aureus 7323, coagulase-negative staphylococci (CoNS 7368 and CoNS 7391) and Pseudomonas aeruginosa 5148 were grown planktonically in suspension and as a biofilm on three different bone cements: Palacos R without gentamicin as control, gentamicin-loaded Palacos R-G and gentamicin/clindamycin-loaded Copal. The viability of planktonic and biofilm bacteria was measured in the absence and presence of pulsed ultrasound for 40 h. Ultrasound itself did not affect bacterial viability. However, application of pulsed ultrasound in combination with antibiotic release by antibiotic-loaded bone cements yielded a reduction of both planktonic and biofilm bacterial viability compared with antibiotic release without application of ultrasound. This study shows that antibiotic release in combination with ultrasound increases the antimicrobial efficacy further than antibiotic release alone against a variety of clinical isolates. Application of ultrasound in combination with antibiotic release in clinical practice could therefore lead to better prevention or treatment of prosthesis-related infections.

Osteocyte viability and regulation of osteoblast function in a 3D trabecular bone explant under dynamic hydrostatic pressure.

PubMed

Takai, Erica; Mauck, Robert L; Hung, Clark T; Guo, X Edward

2004-09-01

A new trabecular bone explant model was used to examine osteocyte-osteoblast interactions under DHP loading. DHP loading enhanced osteocyte viability as well as osteoblast function measured by osteoid formation. However, live osteocytes were necessary for osteoblasts to form osteoids in response to DHP, which directly show osteoblast-osteocyte interactions in this in vitro culture. A trabecular bone explant model was characterized and used to examine the effect of osteocyte and osteoblast interactions and dynamic hydrostatic pressure (DHP) loading on osteocyte viability and osteoblast function in long-term culture. Trabecular bone cores obtained from metacarpals of calves were cleaned of bone marrow and trabecular surface cells and divided into six groups, (1) live cores + dynamic hydrostatic pressure (DHP), (2) live cores + sham, (3) live cores + osteoblast + DHP, (4) live cores + osteoblast + sham, (5) devitalized cores + osteoblast + DHP, and (6) devitalized cores + osteoblast + sham, with four culture durations (2, 8, 15, and 22 days; n = 4/group). Cores from groups 3-6 were seeded with osteoblasts, and cores from groups 5 and 6 were devitalized before seeding. Groups 1, 3, and 5 were subjected to daily DHP loading. Bone histomorphometry was performed to quantify osteocyte viability based on morphology and to assess osteoblast function based on osteoid surface per bone surface (Os/Bs). TUNEL staining was performed to evaluate the mode of osteocyte death under various conditions. A portion of osteocytes remained viable for the duration of culture. DHP loading significantly enhanced osteocyte viability up to day 8, whereas the presence of seeded osteoblasts significantly decreased osteocyte viability. Cores with live osteocytes showed higher Os/Bs compared with devitalized cores, which reached significant levels over a greater range of time-points when combined with DHP loading. DHP loading did not increase Os/Bs in the absence of live osteocytes. The percentage of apoptotic cells remained the same regardless of treatment or culture duration. Enhanced osteocyte viability with DHP suggests the necessity of mechanical stimulation for osteocyte survival in vitro. Furthermore, osteocytes play a critical role in the transmission of signals from DHP loading to modulate osteoblast function. This explant culture model may be used for mechanotransduction studies in long-term cultures.

Loading of Hip Measured by Hip Contact Forces at Different Speeds of Walking and Running.

PubMed

Giarmatzis, Georgios; Jonkers, Ilse; Wesseling, Mariska; Van Rossom, Sam; Verschueren, Sabine

2015-08-01

Exercise plays a pivotal role in maximizing peak bone mass in adulthood and maintaining it through aging, by imposing mechanical loading on the bone that can trigger bone mineralization and growth. The optimal type and intensity of exercise that best enhances bone strength remains, however, poorly characterized, partly because the exact peak loading of the bone produced by the diverse types of exercises is not known. By means of integrated motion capture as an input to dynamic simulations, contact forces acting on the hip of 20 young healthy adults were calculated during walking and running at different speeds. During walking, hip contact forces (HCFs) have a two-peak profile whereby the first peak increases from 4.22 body weight (BW) to 5.41 BW and the second from 4.37 BW to 5.74 BW, by increasing speed from 3 to 6 km/h. During running, there is only one peak HCF that increases from 7.49 BW to 10.01 BW, by increasing speed from 6 to 12 km/h. Speed related profiles of peak HCFs and ground reaction forces (GRFs) reveal a different progression of the two peaks during walking. Speed has a stronger impact on peak HCFs rather than on peak GRFs during walking and running, suggesting an increasing influence of muscle activity on peak HCF with increased speed. Moreover, results show that the first peak of HCF during walking can be predicted best by hip adduction moment, and the second peak of HCF by hip extension moment. During running, peak HCF can be best predicted by hip adduction moment. The present study contributes hereby to a better understanding of musculoskeletal loading during walking and running in a wide range of speeds, offering valuable information to clinicians and scientists exploring bone loading as a possible nonpharmacological osteogenic stimulus. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.

Simulated Microgravity Regulates Gene Transcript Profiles of 2T3 Preosteoblasts: Comparison of the Random Positioning Machine and the Rotating Wall Vessel Bioreactor

NASA Technical Reports Server (NTRS)

Patel, Mamta J.; Liu, Wenbin; Sykes, Michelle C.; Ward, Nancy E.; Risin, Semyon A.; Risin, Diana; Hanjoong, Jo

2007-01-01

Microgravity of spaceflight induces bone loss due in part to decreased bone formation by osteoblasts. We have previously examined the microgravity-induced changes in gene expression profiles in 2T3 preosteoblasts using the Random Positioning Machine (RPM) to simulate microgravity conditions. Here, we hypothesized that exposure of preosteoblasts to an independent microgravity simulator, the Rotating Wall Vessel (RWV), induces similar changes in differentiation and gene transcript profiles, resulting in a more confined list of gravi-sensitive genes that may play a role in bone formation. In comparison to static 1g controls, exposure of 2T3 cells to RWV for 3 days inhibited alkaline phosphatase activity, a marker of differentiation, and downregulated 61 genes and upregulated 45 genes by more than two-fold as shown by microarray analysis. The microarray results were confirmed with real time PCR for downregulated genes osteomodulin, bone morphogenic protein 4 (BMP4), runx2, and parathyroid hormone receptor 1. Western blot analysis validated the expression of three downregulated genes, BMP4, peroxiredoxin IV, and osteoglycin, and one upregulated gene peroxiredoxin I. Comparison of the microarrays from the RPM and the RWV studies identified 14 gravi-sensitive genes that changed in the same direction in both systems. Further comparison of our results to a published database showing gene transcript profiles of mechanically loaded mouse tibiae revealed 16 genes upregulated by the loading that were shown to be downregulated by RWV and RPM. These mechanosensitive genes identified by the comparative studies may provide novel insights into understanding the mechanisms regulating bone formation and potential targets of countermeasure against decreased bone formation both in astronauts and in general patients with musculoskeletal disorders.

In vitro and in vivo evaluation of the marine sponge skeleton as a bone mimicking biomaterial.

PubMed

Nandi, Samit K; Kundu, Biswanath; Mahato, Arnab; Thakur, Narsinh L; Joardar, Siddhartha N; Mandal, Biman B

2015-02-01

This investigation was carried out to identify and characterize marine sponges as potential bioscaffolds in bone tissue engineering. The marine sponge (Biemna fortis) samples were collected from the rocky intertidal region of Anjuna, Goa, India, freeze-dried and converted to pure cristobalite at low temperature. After thorough evaluation of sponge samples by DTA-TGA thermography, XRD, FTIR, SEM and cell cytotoxicity by MTT assay, bare sponge scaffolds were fabricated by firing at 1190 °C. These scaffolds were loaded with growth factors (IGF-1 and BMP-2), checked for quasi-dynamic in vitro release kinetics and finally implanted into femoral bone defects in rabbits for up to 90 days, by keeping an empty defect as a control. The in vivo bone healing process was evaluated and compared using chronological radiology, histology, SEM and fluorochrome labeling studies. SEM revealed that the sponge skeleton possesses a collagenous fibrous network consisting of highly internetworked porosity in the size range of 10-220 μm. XRD and FTIR analysis showed a cristobalite phase with acicular crystals of high aspect ratio, and crystallinity was found to increase from 725 to 1190 °C. MTT assay demonstrated the non-cytotoxicity of the samples. A combination of burst and sustained release profile was noticed for both the growth factors and about 74.3% and 83% total release at day 28. In the radiological, histological, scanning electron microscopy and fluorochrome labeling analysis, the IGF-1 impregnated converted sponge scaffold promoted excellent osseous tissue formation followed by the BMP-2 loaded and bare one. These observations suggest that the marine sponge alone and in combination with growth factors is a promising biomaterial for bone repair and bone augmentation.

Insulin-like growth factor-1 receptor in mature osteoblasts is required for periosteal bone formation induced by reloading

NASA Astrophysics Data System (ADS)

Kubota, Takuo; Elalieh, Hashem Z.; Saless, Neema; Fong, Chak; Wang, Yongmei; Babey, Muriel; Cheng, Zhiqiang; Bikle, Daniel D.

2013-11-01

Skeletal loading and unloading has a pronounced impact on bone remodeling, a process also regulated by insulin-like growth factor-1 (IGF-1) signaling. Skeletal unloading leads to resistance to the anabolic effect of IGF-1, while reloading after unloading restores responsiveness to IGF-1. However, a direct study of the importance of IGF-1 signaling in the skeletal response to mechanical loading remains to be tested. In this study, we assessed the skeletal response of osteoblast-specific Igf-1 receptor deficient (Igf-1r-/-) mice to unloading and reloading. The mice were hindlimb unloaded for 14 days and then reloaded for 16 days. Igf-1r-/- mice displayed smaller cortical bone and diminished periosteal and endosteal bone formation at baseline. Periosteal and endosteal bone formation decreased with unloading in Igf-1r+/+ mice. However, the recovery of periosteal bone formation with reloading was completely inhibited in Igf-1r-/- mice, although reloading-induced endosteal bone formation was not hampered. These changes in bone formation resulted in the abolishment of the expected increase in total cross-sectional area with reloading in Igf-1r-/- mice compared to the control mice. These results suggest that the Igf-1r in mature osteoblasts has a critical role in periosteal bone formation in the skeletal response to mechanical loading.

The Role of Trabecular Microarchitecture in the Formation, Accumulation, and Morphology of Microdamage in Human Cancellous Bone

PubMed Central

Karim, Lamya; Vashishth, Deepak

2011-01-01

Alterations in microdamage morphology and accumulation are typically attributed to impaired remodeling, but may also result from changes in microdamage initiation and propagation. Such alterations are relevant for cancellous bone with high metabolic activity and numerous bone quality changes. This study investigates the role of trabecular microarchitecture on morphology and accumulation of microdamage in human cancellous bone. Trabecular bone cores from donors of varying ages and bone volume fraction (BV/TV) were separated into high and low BV/TV groups. Samples were subjected to no load or uniaxial compression to 0.6% (pre-yield) or 1.1% (post-yield) strain. Microdamage was stained with lead uranyl acetate and specimens were imaged via microcomputed tomography to quantify microdamage and determine its morphology in three-dimensions (3D). Donors with high BV/TV had greater post yield strain and were tougher than low BV/TV donors. High BV/TV bone had less microdamage than low BV/TV bone under post- but not pre-yield loading. Microdamage under both loading conditions showed significant correlations with microarchitecture and BV/TV, but the key predictor was structure model index (SMI). As SMI increased (more trabecular rods), microdamage morphology became crack-like. Thus, low BV/TV and increased SMI have strong influences on microdamage accumulation in bone through altered initiation. PMID:21538510

Low dose PTH improves metaphyseal bone healing more when muscles are paralyzed.

PubMed

Sandberg, Olof; Macias, Brandon R; Aspenberg, Per

2014-06-01

Stimulation of bone formation by PTH is related to mechanosensitivity. The response to PTH treatment in intact bone could therefore be blunted by unloading. We studied the effects of mechanical loading on the response to PTH treatment in bone healing. Most fractures occur in the metaphyses, therefor we used a model for metaphyseal bone injury. One hind leg of 20 male SD rats was unloaded via intramuscular botulinum toxin injections. Two weeks later, the proximal unloaded tibia had lost 78% of its trabecular contents. At this time-point, the rats received bilateral proximal tibiae screw implants. Ten of the 20 rats were given daily injections of 5 μg/kg PTH (1-34). After two weeks of healing, screw fixation was measured by pull-out, and microCT of the distal femur cancellous compartment was performed. Pull-out force provided an estimate for cancellous bone formation after trauma. PTH more than doubled the pull-out force in the unloaded limbs (from 14 to 30 N), but increased it by less than half in the loaded ones (from 30 to 44 N). In relative terms, PTH had a stronger effect on pull-out force in unloaded bone than in loaded bone (p=0.03). The results suggest that PTH treatment for stimulation of bone healing does not require simultaneous mechanical stimulation. Copyright © 2014 Elsevier Inc. All rights reserved.

Differences in trabecular bone of leptin-deficient ob/ob mice in response to biomechanical loading.

PubMed

Heep, Hansjoerg; Wedemeyer, Christian; Wegner, Alexander; Hofmeister, Sebastian; von Knoch, Marius

2008-06-15

It is known that bone mineral density (BMD) and the strength of bone is predicted by body mass. Fat mass is a significant predictor of bone mineral density which correlates with body weight. This suggests that body fat regulates bone metabolism first by means of hormonal factors and second that the effects of muscle and loading are signaling factors in mechanotransduction. Leptin, a peptide hormone produced predominantly by white fat cells, is one of these hormonal factors. The aim of this study was to investigate and measure by micro-CT the different effects of weight-bearing on trabecular bone formation in mice without the stimulation of leptin. Animals with an ad-libitum-diet (Group A) were found to increase body weight significantly at the age of six weeks in comparison with lean mice (Group B). From this point on, the difference increased constantly. At the age of twenty weeks the obese mice were almost twice as heavy as the lean mice. Significant statistical differences are shown between the two groups for body weight and bone mineral density. Examination of trabecular bone (BV/TV, trabecular number (Tb.N.), trabecular thickness (Tb.Th.)) revealed that the only statistically significant difference between the two groups was the Tb.N. for the proximal femur. High weight-bearing insignificantly improved all trabecular bone parameters in the obese mice. Compared with the control-diet Group B, the BV/TV and Tb.N. were slightly higher in the controlled-diet Group A, but not the Tb.Th.. However, correlation was found between Tb.N. and BMD on the one hand and body weight on the other hand. biomechanical loading led to decreased bone mineral density by a decrease in the number of trabeculae. Trabecular thickness was not increased by biomechanical loading in growing mice. Decreased body weight in leptin-deficient mice protects against bone loss. This finding is consistent with the principle of light-weight construction of bone. Differences in cortical and trabecular bone will be examined in later studies. It is not possible to conclude that these results also apply to human beings.

Influence of implant number on the biomechanical behaviour of mandibular implant-retained/supported overdentures: a three-dimensional finite element analysis.

PubMed

Liu, Jingyin; Pan, Shaoxia; Dong, Jing; Mo, Zhongjun; Fan, Yubo; Feng, Hailan

2013-03-01

The aim of this study was to evaluate strain distribution in peri-implant bone, stress in the abutments and denture stability of mandibular overdentures anchored by different numbers of implants under different loading conditions, through three-dimensional finite element analysis (3D FEA). Four 3D finite element models of mandibular overdentures were established, using between one and four Straumann implants with Locator attachments. Three types of load were applied to the overdenture in each model: 100N vertical and inclined loads on the left first molar and a 100N vertical load on the lower incisors. The biomechanical behaviours of peri-implant bone, implants, abutments and overdentures were recorded. Under vertical load on the lower incisors, the single-implant overdenture rotated over the implant from side to side, and no obvious increase of strain was found in peri-implant bone. Under the same loading conditions, the two-implant-retained overdenture showed more apparent rotation around the fulcrum line passing through the two implants, and the maximum equivalent stress in the abutments was higher than in the other models. In the three-implant-supported overdenture, no strain concentration was found in cortical bone around the middle implant under three loading conditions. Single-implant-retained mandibular overdentures do not show damaging strain concentration in the bone around the only implant and may be a cost-effective treatment option for edentulous patients. A third implant can be placed between the original two when patients rehabilitated by two-implant overdentures report constant and obvious denture rotation around the fulcrum line. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effects of imbalanced muscle loading on hip joint development and maturation.

PubMed

Ford, Caleb A; Nowlan, Niamh C; Thomopoulos, Stavros; Killian, Megan L

2017-05-01

The mechanical loading environment influences the development and maturation of joints. In this study, the influence of imbalanced muscular loading on joint development was studied using localized chemical denervation of hip stabilizing muscle groups in neonatal mice. It was hypothesized that imbalanced muscle loading, targeting either gluteal muscles or quadriceps muscles, would lead to bilateral hip joint asymmetry, as measured by acetabular coverage, femoral head volume and bone morphometry, and femoral-acetabular shape. The contralateral hip joints as well as age-matched, uninjected mice were used as controls. Altered bone development was analyzed using micro-computed tomography, histology, and image registration techniques at postnatal days (P) 28, 56, and 120. This study found that unilateral muscle unloading led to reduced acetabular coverage of the femoral head, lower total volume, lower bone volume ratio, and lower mineral density, at all three time points. Histologically, the femoral head was smaller in unloaded hips, with thinner triradiate cartilage at P28 and thinner cortical bone at P120 compared to contralateral hips. Morphological shape changes were evident in unloaded hips at P56. Unloaded hips had lower trabecular thickness and increased trabecular spacing of the femoral head compared to contralateral hips. The present study suggests that decreased muscle loading of the hip leads to altered bone and joint shape and growth during postnatal maturation. Statement of Clinical Significance: Adaptations from altered muscle loading during postnatal growth investigated in this study have implications on developmental hip disorders that result from asymmetric loading, such as patients with limb-length inequality or dysplasia. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1128-1136, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Comparative biomechanical evaluation of a pin-sleeve transfixation system in cadaveric calf metacarpal bones.

PubMed

Brianza, Stefano; Vogel, Susan; Rothstock, Stephan; Thalhauser, Martin; Desrochers, Andrè; Boure, Ludovic

2013-01-01

To compare proximal fragment displacement and the peri-implant strain using a pin-sleeve cast (PSC) system and a transfixation pin cast (TPC) system on a cadaveric calf metacarpal bone fracture model. Experimental. Cadaveric calf metacarpal bones (n = 6 pairs). Paired samples were instrumented with either the TPC or the PSC systems. Strain gauges were applied proximal to the transfixation implants and the bones encased in cast material. The distal part of the construct was removed to mimic an unstable distal comminuted fracture. Constructs were fixed to the material testing machine and initially loaded in axial compression in their elastic range to determine construct stiffness. Constructs were loaded cyclically with a sinusoidal curve that increased until failure. Variables compared statistically between constructs were the initial construct stiffness and, at given load points, the mean metacarpal axial displacement in loading and unloading condition and mean axial strain. Initial construct mean ± SD axial stiffness was not significantly different between constructs (PSC: 689 ± 258; TPC: 879 ± 306 N/mm). There was no significant difference between either investigated displacements of metacarpal bones transfixed with PSC and those transfixed with TPC at all load points. The PSC constructs had a significant decrease in the recorded mean strain (502 ± 340 μstrain) compared to the TPC construct (1738 ± 2218 μstrain). The PSC significantly reduced peri-implant strain with comparable axial displacement to the TPC in cadaveric calf metacarpal bones. © Copyright 2012 by The American College of Veterinary Surgeons.

Hydroxyapatite-coated double network hydrogel directly bondable to the bone: Biological and biomechanical evaluations of the bonding property in an osteochondral defect.

PubMed

Wada, Susumu; Kitamura, Nobuto; Nonoyama, Takayuki; Kiyama, Ryuji; Kurokawa, Takayuki; Gong, Jian Ping; Yasuda, Kazunori

2016-10-15

We have developed a novel hydroxyapatite (HAp)-coated double-network (DN) hydrogel (HAp/DN gel). The purpose of this study was to determine details of the cell and tissue responses around the implanted HAp/DN gel and to determine how quickly and strongly the HAp/DN gel bonds to the bone in a rabbit osteochondral defect model. Immature osteoid tissue was formed in the space between the HAp/DN gel and the bone at 2weeks, and the osteoid tissue was mineralized at 4weeks. The push-out load of the HAp/DN gel averaged 37.54N and 42.15N at 4 and 12weeks, respectively, while the push-out load of the DN gel averaged less than 5N. The bonding area of the HAp/DN gel to the bone was above 80% by 4weeks, and above 90% at 12weeks. This study demonstrated that the HAp/DN gel enhanced osseointegration at an early stage after implantation. The presence of nanoscale structures in addition to osseointegration of HAp promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage. Recent studies have reported the development of various hydrogels that are sufficiently tough for application as soft supporting tissues. However, fixation of hydrogels on bone surfaces with appropriate strength is a great challenge. We have developed a novel, tough hydrogel hybridizing hydroxyapatite (HAp/DN gel), which is directly bondable to the bone. The present study demonstrated that the HAp/DN gel enhanced osseointegration in the early stage after implantation. The presence of nanoscale structures in addition to the osseointegration ability of hydroxyapatite promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Desalted Duck Egg White Peptides Promote Calcium Uptake and Modulate Bone Formation in the Retinoic Acid-Induced Bone Loss Rat and Caco-2 Cell Model.

PubMed

Hou, Tao; Liu, Yanshuang; Kolba, Nikolai; Guo, Danjun; He, Hui

2017-05-12

Desalted duck egg white peptides (DPs) have been proven to promote calcium uptake in Caco-2 cells and rats treated with a calcium-deficient diet. The retinoic acid-induced bone loss model was used to evaluate the effect of DPs on calcium absorption and bone formation. Three-month-old Wistar female rats were treated with 0.9% saline, DPs (800 mg/kg), or alendronate (5 mg/kg) for three weeks immediately after retinoic acid treatment (80 mg/kg) once daily for two weeks. The model group was significantly higher in serum bone alkaline phosphatase than the other three groups ( p < 0.05), but lower in calcium absorption rate, serum osteocalcin, bone weight index, bone calcium content, bone mineral density, and bone max load. After treatment with DPs or alendronate, the absorption rate increased and some serum and bone indices recovered. The morphology results indicated bone tissue form were ameliorated and numbers of osteoclasts decreased after supplementation with DPs or alendronate. The in vitro study showed that the transient receptor potential vanilloid 6 (TRPV6) calcium channel was the main transport pathway of both DPs and Val-Ser-Glu-Glu peptitde (VSEE), which was identified from DPs. Our results indicated that DPs could be a promising alternative to current therapeutic agents for bone loss because of the promotion of calcium uptake and regulation of bone formation.

Stress distribution of the foot during mid-stance to push-off in barefoot gait: a 3-D finite element analysis.

PubMed

Chen, W P; Tang, F T; Ju, C W

2001-08-01

To quantify stress distribution of the foot during mid-stance to push-off in barefoot gait using 3-D finite element analysis. To simulate the foot structure and facilitate later consideration of footwear. Finite element model was generated and loading condition simulating barefoot gait during mid-stance to push-off was used to quantify the stress distributions. A computational model can provide overall stress distributions of the foot subject to various loading conditions. A preliminary 3-D finite element foot model was generated based on the computed tomography data of a male subject and the bone and soft tissue structures were modeled. Analysis was performed for loading condition simulating barefoot gait during mid-stance to push-off. The peak plantar pressure ranged from 374 to 1003 kPa and the peak von Mises stress in the bone ranged from 2.12 to 6.91 MPa at different instants. The plantar pressure patterns were similar to measurement result from previous literature. The present study provides a preliminary computational model that is capable of estimating the overall plantar pressure and bone stress distributions. It can also provide quantitative analysis for normal and pathological foot motion. This model can identify areas of increased pressure and correlate the pressure with foot pathology. Potential applications can be found in the study of foot deformities, footwear, surgical interventions. It may assist pre-treatment planning, design of pedorthotic appliances, and predict the treatment effect of foot orthosis.

Mechanics of limb bone loading during terrestrial locomotion in the green iguana (Iguana iguana) and American alligator (Alligator mississippiensis).

PubMed

Blob, R W; Biewener, A A

2001-03-01

In vivo measurements of strain in the femur and tibia of Iguana iguana (Linnaeus) and Alligator mississippiensis (Daudin) have indicated three ways in which limb bone loading in these species differs from patterns observed in most birds and mammals: (i) the limb bones of I. iguana and A. mississippiensis experience substantial torsion, (ii) the limb bones of I. iguana and A. mississippiensis have higher safety factors than those of birds or mammals, and (iii) load magnitudes in the limb bones of A. mississippiensis do not decrease uniformly with the use of a more upright posture. To verify these patterns, and to evaluate the ground and muscle forces that produce them, we collected three-dimensional kinematic and ground reaction force data from subadult I. iguana and A. mississippiensis using a force platform and high-speed video. The results of these force/kinematic studies generally confirm the loading regimes inferred from in vivo strain measurements. The ground reaction force applies a torsional moment to the femur and tibia in both species; for the femur, this moment augments the moment applied by the caudofemoralis muscle, suggesting large torsional stresses. In most cases, safety factors in bending calculated from force/video data are lower than those determined from strain data, but are as high or higher than the safety factors of bird and mammal limb bones in bending. Finally, correlations between limb posture and calculated stress magnitudes in the femur of I. iguana confirm patterns observed during direct bone strain recordings from A. mississippiensis: in more upright steps, tensile stresses on the anterior cortex decrease, but peak compressive stresses on the dorsal cortex increase. Equilibrium analyses indicate that bone stress increases as posture becomes more upright in saurians because the ankle and knee extensor muscles exert greater forces during upright locomotion. If this pattern of increased bone stress with the use of a more upright posture is typical of taxa using non-parasagittal kinematics, then similar increases in load magnitudes were probably experienced by lineages that underwent evolutionary shifts to a non-sprawling posture. High limb bone safety factors and small body size in these lineages could have helped to accommodate such increases in limb bone stress.

Biomechanical optimization of implant diameter and length for immediate loading: a nonlinear finite element analysis.

PubMed

Kong, Liang; Gu, Zexu; Li, Tao; Wu, Junjie; Hu, Kaijin; Liu, Yanpu; Zhou, Hongzhi; Liu, Baolin

2009-01-01

A nonlinear finite element method was applied to examine the effects of implant diameter and length on the maximum von Mises stresses in the jaw, and to evaluate the maximum displacement of the implant-abutment complex in immediate-loading models. The implant diameter (D) ranged from 3.0 to 5.0 mm and implant length (L) ranged from 6.0 to 16.0 mm. The results showed that the maximum von Mises stress in cortical bone was decreased by 65.8% under a buccolingual load with an increase in D. In cancellous bone, it was decreased by 71.5% under an axial load with an increase in L. The maximum displacement in the implant-abutment complex decreased by 64.8% under a buccolingual load with an increase in D. The implant was found to be more sensitive to L than to D under axial loads, while D played a more important role in enhancing its stability under buccolingual loads. When D exceeded 4.0 mm and L exceeded 11.0 mm, both minimum stress and displacement were obtained. Therefore, these dimensions were the optimal biomechanical selections for immediate-loading implants in type B/2 bone.

Experimental and numeric stress analysis of titanium and zirconia one-piece dental implants.

PubMed

Mobilio, Nicola; Stefanoni, Filippo; Contiero, Paolo; Mollica, Francesco; Catapano, Santo

2013-01-01

To compare the stress in bone around zirconia and titanium implants under loading. A one-piece zirconia implant and a replica of the same implant made of commercially pure titanium were embedded in two self-curing acrylic resin blocks. To measure strain, a strain gauge was applied on the surface of the two samples. Loads of 50, 100, and 150 N, with orientations of 30, 45, and 60 degrees with respect to the implant axis were applied on the implant. Strain under all loading conditions on both samples was measured. Three-dimensional virtual replicas of both the implants were reproduced using the finite element method and inserted into a virtual acrylic resin block. All the materials were considered isotropic, linear, and elastic. The same geometry and loading conditions of the experimental setup were used to realize two new models, with the implants embedded within a virtual bone block. Very close values of strain in the two implants embedded in acrylic resin were obtained both experimentally and numerically. The stress states generated by the implants embedded in virtual bone were also very similar, even if the two implants moved differently. Moreover, the stress levels were higher on cortical bone than on trabecular bone. The stress levels in bone, generated by the two implants, appeared to be very similar. From a mechanical point of view, zirconia is a feasible substitute for titanium.

Predicting the bending properties of long bones: Insights from an experimental mouse model.

PubMed

Peacock, Sarah J; Coats, Brittney R; Kirkland, J Kyle; Tanner, Courtney A; Garland, Theodore; Middleton, Kevin M

2018-03-01

Analyses of bone cross-sectional geometry are frequently used by anthropologists and paleontologists to infer the loading histories of past populations. To address some underlying assumptions, we investigated the relative roles of genetics and exercise on bone cross-sectional geometry and bending mechanics in three mouse strains: high bone density (C3H/He), low bone density (C57BL/6), and a high-runner strain homozygous for the Myh4 Minimsc allele (MM). Weanlings of each strain were divided into exercise (wheel) or control (sedentary) treatment groups for a 7-week experimental period. Morphometrics of the femoral mid-diaphysis and mechanical testing were used to assess both theoretical and ex vivo bending mechanics. Across all measured morphological and bending traits, we found relatively small effects of exercise treatment compared to larger and more frequent interstrain differences. In the exercised group, total distance run over the experimental period was not a predictor of any morphological or bending traits. Cross-sectional geometry did not accurately predict bone response to loading. Results from this experimental model do not support hypothesized associations among extreme exercise, cross-sectional geometry, and bending mechanics. Our results suggest that analysis of cross-sectional geometry alone is insufficient to predict loading response, and questions the common assumption that cross-sectional geometry differences are indicative of differential loading history. © 2017 Wiley Periodicals, Inc.

Biomechanical effects of two different collar implant structures on stress distribution under cantilever fixed partial dentures.

PubMed

Merıç, Gökçe; Erkmen, Erkan; Kurt, Ahmet; Eser, Atilim; özden, Ahmet Utku

2011-11-01

The purpose of the study was to compare the effects of two distinct collar geometries of implants on stress distribution in the bone around the implants supporting cantilever fixed partial dentures (CFPDs) as well as in the implant-abutment complex and superstructures. The three-dimensional finite element method was selected to evaluate the stress distribution. CFPDs which was supported by microthread collar structured (MCS) and non-microthread collar structured (NMCS) implants was modeled; 300 N vertical, 150 N oblique and 60 N horizontal forces were applied to the models separately. The stress values in the bone, implant-abutment complex and superstructures were calculated. In the MCS model, higher stresses were located in the cortical bone and implant-abutment complex in the case of vertical load while decreased stresses in cortical bone and implant-abutment complex were noted within horizontal and oblique loading. In the case of vertical load, decreased stresses have been noted in cancellous bone and framework. Upon horizontal and oblique loading, a MCS model had higher stress in cancellous bone and framework than the NMCS model. Higher von Mises stresses have been noted in veneering material for NMCS models. It has been concluded that stress distribution in implant-supported CFPDs correlated with the macro design of the implant collar and the direction of applied force.

Load Bearing Equipment for Bone and Muscle Project

NASA Technical Reports Server (NTRS)

Terrier, Douglas; Clayton, Ronald G.; Shackelford, Linda

2015-01-01

Axial skeletal loads coupled with muscle torque forces around joints maintain bone. Astronauts working in pairs to exercise can provide high eccentric loads for each other that are most effective. A prototype of load bearing equipment that will allow astronauts to perform exercises using each other for counter force generation in a controlled fashion and provide eccentric overload is proposed. A frame and attachments that can be rapidly assembled for use and easily stored will demonstrate feasibility of a design that can be adapted for ISS testing and Orion use.

Simulated Space Radiation: Murine Skeletal Responses During Recovery and with Mechanical Stimulation

NASA Technical Reports Server (NTRS)

Shirazi-Fard, Yasaman; Zaragoza, Josergio; Schreurs, Ann-Sofie; Truong, Tiffany; Tahimic, Candice; Alwood, Joshua S.; Castillo, Alesha B.; Globus, R. K.

2016-01-01

Simulated space radiation at doses similar to those of solar particle events or a round-trip sojourn to Mars (1-2Gy) may cause skeletal tissue degradation and deplete stem/progenitor cell pools throughout the body. We hypothesized that simulated space radiation (SSR) causes late, time-dependent deficits in bone structure and bone cell function reflected by changes in gene expression in response to anabolic stimuli. We used a unique sequential dual ion exposure (proton and iron) for SSR to investigate time-dependence of responses in gene expression, cell function, and microarchitecture with respect to radiation and an anabolic stimulus of axial loading (AL). Male 16-wk C57BL6/J mice (n=120 total) were exposed to 0Gy (Sham, n=10), 56Fe (2Gy, positive control dose, n=10), or sequential ions for SSR (1Gy 1H/56Fe/1H, n=10) by total body irradiation (IR), and the tissues were harvested 2 or 6 mo. later. Further, to assess the response to anabolic stimuli, we subjected additional Sham-AL (n=15) and SSR-AL (n=15) groups to rest-inserted tibial axial loading (AL) starting at 1 and 5 months post-IR (-9N, 60 cycles/day, 3 days/wk, 4 wks). Exposure to 56Fe caused a significant reduction in cancellous bone volume fraction (BV/TV) compared to Sham (-34%) and SSR (-20%) in the proximal tibia metaphysis at 2-months post-IR; however BV/TV for SSR group was not different than Sham. Both 56Fe and SSR caused significant reduction in trabecular number (Tb.N) compared to Sham (-33% and -16%, respectively). Further, Tb.N for 56Fe (2Gy) was significantly lower than SSR (-21%). Ex vivo culture of marrow cells to assess growth and differentiation of osteoblast lineage cells 6 months post-IR showed that both 56Fe and SSR exposures significantly impaired colony formation compared to Sham (-66% and -54%, respectively), as well as nodule mineralization (-90% and -51%, respectively). Two-way analysis of variance showed that both mechanical loading and radiation reduced BV/TV, mechanical loading reduced trabecular thickness (Tb.Th), and radiation reduced Tb.N, at both time points. To assess acute response to mechanical stimuli, samples were harvested from a subset of Sham-AL (n=5) and SSR-AL (n=5) to measure changes in gene expression levels. Preliminary results indicate that axial loading increased expression of the antioxidant response gene Nfe2l2 and the osteoprogenitor-associated marker Runx2 in the bone marrow cells, and there was an interaction effect between axial loading and radiation at 2-months post-IR. Additional analyses of gene expression levels in the mineralized tissue are in progress. Results indicate that SSR caused persistent impairment of osteoblast colony formation and nodule mineralization 6-mo post-IR. Contrary to our hypothesis, simulated space radiation did not impair the ability of cancellous bone to respond to a mechanical anabolic stimulus, consistent with our previous findings [1]. Hence, compressive loading may be a potential countermeasure against spaceflight-induced bone loss.

Simulated Space Radiation: Murine Skeletal Responses During Recovery and with Mechanical Stimulation

NASA Technical Reports Server (NTRS)

Shirazi-Fard, Yasaman; Zaragoza, Josergio; Schreurs, Ann-Sofie; Truong, Tiffany; Tahimic, Candice; Alwood, Joshua S.; Globus, R. K.

2016-01-01

Simulated space radiation at doses similar to those of solar particle events or a round-trip sojourn to Mars (1-2Gy) may cause skeletal tissue degradation and deplete stem/progenitor cell pools throughout the body. We hypothesized that simulated space radiation (SSR) causes late, time-dependent deficits in bone structure and bone cell function reflected by changes in gene expression in response to anabolic stimuli. We used a unique sequential dual ion exposure (proton and iron) for SSR to investigate time-dependence of responses in gene expression, cell function, and microarchitecture with respect to radiation and an anabolic stimulus of axial loading (AL). Male 16-wk C57BL6/J mice (n=120 total) were exposed to 0Gy (Sham, n=10), 56Fe (2Gy, positive control dose, n=10), or sequential ions for SSR (1Gy 1H/56Fe/1H, n=10) by total body irradiation (IR), and the tissues were harvested 2 or 6 mo. later. Further, to assess the response to anabolic stimuli, we subjected additional Sham-AL (n=15) and SSR-AL (n=15) groups to rest-inserted tibial axial loading (AL) starting at 1 and 5 months post-IR (-9N, 60 cycles/day, 3 days/wk, 4 wks). Exposure to 56Fe caused a significant reduction in cancellous bone volume fraction (BV/TV) compared to Sham (-34%) and SSR (-20%) in the proximal tibia metaphysis at 2-months post-IR; however BV/TV for SSR group was not different than Sham. Both 56Fe and SSR caused significant reduction in trabecular number (Tb.N) compared to Sham (-33% and -16%, respectively). Further, Tb.N for 56Fe (2Gy) was significantly lower than SSR (-21%). Ex vivo culture of marrow cells to assess growth and differentiation of osteoblast lineage cells 6 months post-IR showed that both 56Fe and SSR exposures significantly impaired colony formation compared to Sham (-66% and -54%, respectively), as well as nodule mineralization (-90% and -51%, respectively). Two-way analysis of variance showed that both mechanical loading and radiation reduced BV/TV, mechanical loading reduced trabecular thickness (Tb.Th), and radiation reduced Tb.N, at both time points. To assess acute response to mechanical stimuli, samples were harvested from a subset of Sham-AL (n=5) and SSR-AL (n=5) to measure changes in gene expression levels. Preliminary results indicate that axial loading increased expression of the antioxidant response gene Nfe2l2 and the osteoprogenitor-associated marker Runx2 in the bone marrow cells, and there was an interaction effect between axial loading and radiation at 2-months post-IR. Additional analyses of gene expression levels in the mineralized tissue are in progress. Results indicate that SSR caused persistent impairment of osteoblast colony formation and nodule mineralization 6-mo post-IR. Contrary to our hypothesis, simulated space radiation did not impair the ability of cancellous bone to respond to a mechanical anabolic stimulus, consistent with our previous findings. Hence, compressive loading may be a potential countermeasure against spaceflight-induced bone loss.

Bone tissue engineering: the role of interstitial fluid flow

NASA Technical Reports Server (NTRS)

Hillsley, M. V.; Frangos, J. A.

1994-01-01

It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.

Myo-conductive and osteo-inductive free-standing polysaccharide membranes

PubMed Central

Caridade, Sofia G.; Monge, Claire; Almodóvar, Jorge; Guillot, Raphael; Lavaud, Jonathan; Josserand, Véronique; Coll, Jean-Luc; Mano, João F.; Picart, Catherine

2015-01-01

Free-standing (FS) membranes have increasing applications in the biomedical field as drug delivery systems for wound healing and tissue engineering. Here, we studied the potential of free-standing membranes made by the layer-by-layer assembly of chitosan and alginate to be used as a simple biomimetic system of the periosteum. The design of a periosteum-like membrane implies the elaboration of a thick membrane suitable for both muscle and bone formation. Our aim was to produce well defined ~50 μm thick polysaccharide membranes that could be easily manipulated, be mechanically resistant, and enable both myogenesis and osteogenesis in vitro and in vivo. The membranes were chemically crosslinked to improve their mechanical properties. Crosslinking chemistry was followed via FTIR and the mechanical properties of the membranes were assessed using dynamic mechanical analysis. The loading and release of the potent osteoinductive growth factor bone morphogenetic protein 2 (BMP-2) inside and outside of the FS membrane was followed by fluorescence spectroscopy in a physiological buffer over one month. The myogenic and osteogenic potential of the membranes in vitro was assessed using BMP-2 responsive skeletal myoblasts. Finally, their osteoinductive properties in vivo were studied in a preliminary experiment using a mouse ectopic model. Our results showed that the more crosslinked FS membranes enabled a more efficient myoblast differentiation in myotubes. In addition, we showed that a tunable amount of BMP-2 can be loaded in and subsequently released from the membranes depending on the crosslinking degree and BMP-2 initial concentration in solution. Only the more crosslinked membranes were found to be osteoinductive in vivo. These polysaccharide-based membranes have strong potential as a periosteum-mimetic scaffold for bone tissue regeneration. PMID:25575853

[Development, physiology, and cell activity of bone].

PubMed

de Baat, P; Heijboer, M P; de Baat, C

2005-07-01

Bones are of crucial importance for the human body, providing skeletal support, serving as a home for the formation of haematopoietic cells, and reservoiring calcium and phosphate. Long bones develop by endochondral ossification. Flat bones develop by intramembranous ossification. Bone tissue contains hydroxyapatite and various extracellular proteins, producing bone matrix. Two biological mechanisms, determining the strength of bone, are modelling and remodelling. Modelling can change bone shape and size through bone formation by osteoblasts at some sites and through bone destruction by osteoclasts at other sites. Remodelling is bone turnover, also performed by osteoclasts and osteoblasts. The processes of modelling and remodelling are induced by mechanical loads, predominantly muscle loads. Osteoblasts develop from mesenchymal stem cells. Many stimulating factors are known to activate the differentiation. Mature osteoblasts synthesize bone matrix and may further differentiate into osteocytes. Osteocytes maintain structural bone integrity and allow bone to adapt to any mechanical and chemical stimulus. Osteoclasts derive from haematopoietic stem cells. A number of transcription and growth factors have been identified essential for osteoclast differentiation and function. Finally, there is a complex interaction between osteoblasts and osteoclasts. Bone destruction starts by attachment of osteoclasts to the bone surface. Following this, osteoclasts undergo specific morphological changes. The process of bone destruction starts by acid dissolution of hydroxyapatite. After that osteoclasts start to destruct the organic matrix.

Mechanical signaling in the development of postmenopausal osteoporosis

NASA Technical Reports Server (NTRS)

Turner, R. T.

1999-01-01

Estrogen deficiency results in increased bone turnover and net bone loss in rats as well as humans. The respective roles of bone turnover and mechanical strain in mediating estrogen deficiency-induced cancellous bone loss were investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in long bones. However, cancellous bone was preferentially lost in the metaphysis, a site that experiences low strain energy during normal physical activity. No bone loss was observed in the epiphysis, a site experiencing higher strain energy, despite a similar increase in bone turnover. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased or decreased in long bones of ovariectomized rats by treadmill exercise or functional unloading, respectively. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing weight bearing accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in unloaded limbs and prevented bone loss in the loaded limbs. These results suggest that estrogen alters the mechanosensory (mechanostat) set point for skeletal adaptation, effectively reducing the minimum strain energy levels at which bone is added. Additionally, these studies suggest that physical activity as well as endocrine status play an important role in maintenance of the female skeleton during aging.

Bone regeneration in strong porous bioactive glass (13–93) scaffolds with an oriented microstructure implanted in rat calvarial defects

PubMed Central

Liu, Xin; Rahaman, Mohamed N.; Fu, Qiang

2012-01-01

There is a need for synthetic bone graft substitutes to repair large bone defects resulting from trauma, malignancy, and congenital diseases. Bioactive glass has attractive properties as a scaffold material but factors that influence its ability to regenerate bone in vivo are not well understood. In the present work, the ability of strong porous scaffolds of 13–93 bioactive glass with an oriented microstructure to regenerate bone was evaluated in vivo using a rat calvarial defect model. Scaffolds with an oriented microstructure of columnar pores (porosity = 50%; pore diameter = 50–150 µm) showed mostly osteoconductive bone regeneration, and new bone formation, normalized to the available pore area (volume) of the scaffolds, increased from 37% at 12 weeks to 55% at 24 weeks. Scaffolds of the same glass with a trabecular microstructure (porosity = 80%; pore width = 100–500 µm), used as the positive control, showed bone regeneration in the pores of 25% and 46% at 12 and 24 weeks, respectively. The brittle mechanical response of the as-fabricated scaffolds changed markedly to an elasto-plastic response in vivo at both implantation times. These results indicate that both groups of 13–93 bioactive glass scaffolds could potentially be used to repair large bone defects, but scaffolds with the oriented microstructure could also be considered for the repair of loaded bone. PMID:22922251

Bone Strength Estimated by Micro-Finite Element Analysis (µFEA) Is Heritable and Shares Genetic Predisposition With Areal BMD: The Framingham Study.

PubMed

Karasik, David; Demissie, Serkalem; Lu, Darlene; Broe, Kerry E; Boyd, Steven K; Liu, Ching-Ti; Hsu, Yi-Hsiang; Bouxsein, Mary L; Kiel, Douglas P

2017-11-01

Genetic factors contribute to the risk of bone fractures, partly because of effects on bone strength. High-resolution peripheral quantitative computed tomography (HR-pQCT) estimates bone strength using micro-finite element analysis (µFEA). The goal of this study was to investigate if the bone failure load estimated by HR-pQCT-based µFEA is heritable and to what extent it shares genetic regulation with areal bone mineral density (aBMD). Bone microarchitecture was measured by HR-pQCT at the ultradistal tibia and ultradistal radius in adults from the Framingham Heart Study (n = 1087, mean age 72 years; 57% women). Radial and tibial failure load in compression were estimated by µFEA. Femoral neck (FN) and ultradistal forearm (UD) aBMD were measured by dual-energy X-ray absorptiometry (DXA). Heritability (h 2 ) of failure load and aBMD and genetic correlations between them was estimated adjusting for covariates (age and sex). Failure load values at the non-weight-bearing ultradistal radius and at the weight-bearing ultradistal tibia were highly correlated (r = 0.906; p < 0.001). Estimates of h 2 adjusted for covariates were 0.522 for the radius and 0.497 for the tibia. Additional adjustment for height did not impact on the h 2 results, but adjustment for aBMD at the UD and FN somewhat decreased h 2 point estimates: 0.222 and 0.380 for radius and tibia, respectively. In bivariate analysis, there was a high phenotypic and genetic correlation between covariate-adjusted failure load at the radius and UD aBMD (ρ P  = 0.826, ρ G  = 0.954, respectively), whereas environmental correlations were lower (ρ E  = 0.696), all highly significant (p < 0.001). Similar correlations were observed between tibial failure load and femoral neck aBMD (ρ P  = 0.577, ρ G  = 0.703, both p < 0.001; ρ E  = 0.432, p < 0.05). These data from adult members of families from a population-based cohort suggest that bone strength of distal extremities estimated by micro-finite element analysis is heritable and shares some genetic composition with areal BMD, regardless of the skeletal site. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Biomechanical evaluation of fixation of intra-articular fractures of the distal part of the radius in cadavera: Kirschner wires compared with calcium-phosphate bone cement.

PubMed

Yetkinler, D N; Ladd, A L; Poser, R D; Constantz, B R; Carter, D

1999-03-01

The purpose of this study was to compare the biomechanical efficacy of an injectable calcium-phosphate bone cement (Skeletal Repair System [SRS]) with that of Kirschner wires for the fixation of intraarticular fractures of the distal part of the radius. Colles fractures (AO pattern, C2.1) were produced in ten pairs of fresh-frozen human cadaveric radii. One radius from each pair was randomly chosen for stabilization with SRS bone cement. These ten radii were treated with open incision, impaction of loose cancellous bone with use of a Freer elevator, and placement of the SRS bone cement by injection. In the ten control specimens, the fracture was stabilized with use of two horizontal and two oblique Kirschner wires. The specimens were cyclically loaded to a peak load of 200 newtons for 2000 cycles to evaluate the amount of settling, or radial shortening, under conditions simulating postoperative loading with the limb in a cast. Each specimen then was loaded to failure to determine its ultimate strength. The amount of radial shortening was highly variable among the specimens, but it was consistently higher in the Kirschner-wire constructs than in the bone fixed with SRS bone cement within each pair of radii. The range of shortening for all twenty specimens was 0.18 to 4.51 millimeters. The average amount of shortening in the SRS constructs was 50 percent of that in the Kirschner-wire constructs (0.51+/-0.34 compared with 1.01+/-1.23 millimeters; p = 0.015). With the numbers available, no significant difference in ultimate strength was detected between the two fixation groups. This study showed that fixation of an intra-articular fracture of the distal part of a cadaveric radius with biocompatible calcium-phosphate bone cement produced results that were biomechanically comparable with those produced by fixation with Kirschner wires. However, the constructs that were fixed with calcium-phosphate bone cement demonstrated less shortening under simulated cyclic load-bearing.

Calcium ions and osteoclastogenesis initiate the induction of bone formation by coral-derived macroporous constructs

PubMed Central

Klar, Roland M; Duarte, Raquel; Dix-Peek, Therese; Dickens, Caroline; Ferretti, Carlo; Ripamonti, Ugo

2013-01-01

Coral-derived calcium carbonate/hydroxyapatite macroporous constructs of the genus Goniopora with limited hydrothermal conversion to hydroxyapatite (7% HA/CC) initiate the induction of bone formation. Which are the molecular signals that initiate pattern formation and the induction of bone formation? To evaluate the role of released calcium ions and osteoclastogenesis, 7% HA/CC was pre-loaded with either 500 μg of the calcium channel blocker, verapamil hydrochloride, or 240 μg of the osteoclast inhibitor, biphosphonate zoledronate, and implanted in the rectus abdominis muscle of six adult Chacma baboons Papio ursinus. Generated tissues on days 15, 60 and 90 were analysed by histomorphometry and qRT-PCR. On day 15, up-regulation of type IV collagen characterized all the implanted constructs correlating with vascular invasion. Zoledronate-treated specimens showed an important delay in tissue patterning and morphogenesis with limited bone formation. Osteoclastic inhibition yielded minimal, if any, bone formation by induction. 7% HA/CC pre-loaded with the Ca++ channel blocker verapamil hydrochloride strongly inhibited the induction of bone formation. Down-regulation of bone morphogenetic protein-2 (BMP-2) together with up-regulation of Noggin genes correlated with limited bone formation in 7% HA/CC pre-loaded with either verapamil or zoledronate, indicating that the induction of bone formation by coral-derived macroporous constructs is via the BMPs pathway. The spontaneous induction of bone formation is initiated by a local peak of Ca++ activating stem cell differentiation and the induction of bone formation. PMID:24106923

Anterior Cruciate Ligament-Derived Stem Cells Transduced With BMP2 Accelerate Graft-Bone Integration After ACL Reconstruction.

PubMed

Kawakami, Yohei; Takayama, Koji; Matsumoto, Tomoyuki; Tang, Ying; Wang, Bing; Mifune, Yutaka; Cummins, James H; Warth, Ryan J; Kuroda, Ryosuke; Kurosaka, Masahiro; Fu, Freddie H; Huard, Johnny

2017-03-01

Strong graft-bone integration is a prerequisite for successful graft remodeling after reconstruction of the anterior cruciate ligament (ACL) using soft tissue grafts. Novel strategies to accelerate soft tissue graft-bone integration are needed to reduce the need for bone-tendon-bone graft harvest, reduce patient convalescence, facilitate rehabilitation, and reduce total recovery time after ACL reconstruction. The application of ACL-derived stem cells with enhanced expression of bone morphogenetic protein 2 (BMP2) onto soft tissue grafts in the form of cell sheets will both accelerate and improve the quality of graft-bone integration after ACL reconstruction in a rat model. Controlled laboratory study. ACL-derived CD34+ cells were isolated from remnant human ACL tissues, virally transduced to express BMP2, and embedded within cell sheets. In a rat model of ACL injury, bilateral single-bundle ACL reconstructions were performed, in which cell sheets were wrapped around tendon autografts before reconstruction. Four groups containing a total of 48 rats (96 knees) were established (n = 12 rats; 24 knees per group): CD34+BMP2 (100%), CD34+BMP2 (25%), CD34+ (untransduced), and a control group containing no cells. Six rats from each group were euthanized 2 and 4 weeks after surgery, and each graft was harvested for immunohistochemical and histological analyses. The remaining 6 rats in each group were euthanized at 4 and 8 weeks to evaluate in situ tensile load to failure in each femur-graft-tibia complex. In vitro, BMP2 transduction promoted the osteogenic differentiation of ACL-derived CD34+ cells while retaining their intrinsic multipotent capabilities. Osteoblast densities were greatest in the BMP2 (100%) and BMP2 (25%) groups. Bone tunnels in the CD34+BMP2 (100%) and CD34+BMP2 (25%) groups had the smallest cross-sectional areas according to micro-computed tomography analyses. Graft-bone integration occurred most rapidly in the CD34+BMP2 (25%) group. Tensile load to failure was significantly greater in the groups containing stem cells at 4 and 8 weeks after surgery. Tensile strength was greatest in the CD34+BMP2 (100%) group at 4 weeks, and in the CD34+BMP2 (25%) group at 8 weeks. ACL-derived CD34+ cells transduced with BMP2 accelerated graft-bone integration after ACL reconstruction using soft tissue autografts in a rat model, as evidenced by improved histological appearance and graft-bone interface biology along with tensile load to failure at each time point up to 8 weeks after surgery. A primary disadvantage of using soft tissue grafts for ACL reconstruction is the prolonged time required for bony ingrowth, which delays the initiation of midsubstance graft remodeling. The lack of consistent correlation between the appearance of a "healed" ACL on postoperative magnetic resonance imaging and readiness to return to sport results in athletes being released to sport before the graft is ready to handle high-intensity loading. Therefore, it is desirable to identify strategies that accelerate graft-bone integration, which would reduce the time to biologic fixation, improve the reliability of biologic fixation, allow for accelerated rehabilitation, and potentially reduce the incidence of early graft pullout and late midsubstance failure.

Multiscale imaging of bone microdamage

PubMed Central

Poundarik, Atharva A.; Vashishth, Deepak

2015-01-01

Bone is a structural and hierarchical composite that exhibits remarkable ability to sustain complex mechanical loading and resist fracture. Bone quality encompasses various attributes of bone matrix from the quality of its material components (type-I collagen, mineral and non-collagenous matrix proteins) and cancellous microarchitecture, to the nature and extent of bone microdamage. Microdamage, produced during loading, manifests in multiple forms across the scales of hierarchy in bone and functions to dissipate energy and avert fracture. Microdamage formation is a key determinant of bone quality, and through a range of biological and physical mechanisms, accumulates with age and disease. Accumulated microdamage in bone decreases bone strength and increases bone’s propensity to fracture. Thus, a thorough assessment of microdamage, across the hierarchical levels of bone, is crucial to better understand bone quality and bone fracture. This review article details multiple imaging modalities that have been used to study and characterize microdamage; from bulk staining techniques originally developed by Harold Frost to assess linear microcracks, to atomic force microscopy, a modality that revealed mechanistic insights into the formation diffuse damage at the ultrastructural level in bone. New automated techniques using imaging modalities such as microcomputed tomography are also presented for a comprehensive overview. PMID:25664772

Numerical assessment of bone remodeling around conventionally and early loaded titanium and titanium-zirconium alloy dental implants.

PubMed

Akça, Kıvanç; Eser, Atılım; Çavuşoğlu, Yeliz; Sağırkaya, Elçin; Çehreli, Murat Cavit

2015-05-01

The aim of this study was to investigate conventionally and early loaded titanium and titanium-zirconium alloy implants by three-dimensional finite element stress analysis. Three-dimensional model of a dental implant was created and a thread area was established as a region of interest in trabecular bone to study a localized part of the global model with a refined mesh. The peri-implant tissues around conventionally loaded (model 1) and early loaded (model 2) implants were implemented and were used to explore principal stresses, displacement values, and equivalent strains in the peri-implant region of titanium and titanium-zirconium implants under static load of 300 N with or without 30° inclination applied on top of the abutment surface. Under axial loading, principal stresses in both models were comparable for both implants and models. Under oblique loading, principal stresses around titanium-zirconium implants were slightly higher in both models. Comparable stress magnitudes were observed in both models. The displacement values and equivalent strain amplitudes around both implants and models were similar. Peri-implant bone around titanium and titanium-zirconium implants experiences similar stress magnitudes coupled with intraosseous implant displacement values under conventional loading and early loading simulations. Titanium-zirconium implants have biomechanical outcome comparable to conventional titanium implants under conventional loading and early loading.

The Effect of Polymethyl Methacrylate Augmentation on the Primary Stability of Cannulated Bone Screws in an Anterolateral Plate in Osteoporotic Vertebrae: A Human Cadaver Study

PubMed Central

Rüger, Matthias; Sellei, Richard M.; Stoffel, Marcus; von Rüden, Christian

2015-01-01

Study Design Cohort study. Objective Expandable anterolateral plates facilitate the reduction of posttraumatic deformities of thoracolumbar spine injuries and are commonly used in cases of unstable injuries or compromised bone quality. In this in vitro study, the craniocaudal yield load of the osseous fixation of an anterior angular stable plate fixation system and the effect of polymethyl methacrylate (PMMA) screw augmentation on the primary stability of the screw–bone interface during kyphosis reduction was evaluated in 12 osteoporotic human thoracolumbar vertebrae. Methods The anterolateral stabilization device used for this study is comprised of two swiveling flanges and an expandable midsection. It facilitates the controlled reduction of kyphotic deformities in situ with a geared distractor. Single flanges were attached to 12 thoracolumbar vertebrae. Six specimens were augmented with PMMA by means of cannulated bone screws. The constructs were subjected to static, displacement-controlled craniocaudal loading to failure in a servohydraulic testing machine. Results The uncemented screws cut out at a mean 393 ± 66 N, whereas the cemented screws showed significantly higher yield load of 966 ± 166 N (p < 0.02). We detected no significant correlation between bone mineral density and yield load in this setting. Conclusion Our results indicate that PMMA augmentation is an effective method to increase two- to threefold the primary stability of the screw–bone interface of an anterolateral spine stabilization system in osteoporotic bone. We recommend it in cases of severely compromised bone quality to reduce the risk of screw loosening during initial kyphosis correction and to increase long-term construct stability. PMID:26835201

Simulation of peri-implant bone healing due to immediate loading in dental implant treatments.

PubMed

Chou, Hsuan-Yu; Müftü, Sinan

2013-03-15

The goal of this work was to investigate the role of immediate loading on the peri-implant bone healing in dental implant treatments. A mechano-regulatory tissue differentiation model that takes into account the stimuli through the solid and the fluid components of the healing tissue, and the diffusion of pluripotent stem cells into the healing callus was used. A two-dimensional axisymmetric model consisting of a dental implant, the healing callus tissue and the host bone tissue was constructed for the finite element analysis. Poroelastic material properties were assigned to the healing callus and the bone tissue. The effects of micro-motion, healing callus size, and implant thread design on the length of the bone-to-implant contact (BIC) and the bone volume (BV) formed in the healing callus were investigated. In general, the analysis predicted formation of a continuous layer of soft tissue along the faces of the implant which are parallel to the loading direction. This was predicted to be correlated with the high levels of distortional strain transferred through the solid component of the stimulus. It was also predicted that the external threads on the implant, redistribute the interfacial load, thus help reduce the high distortional stimulus and also help the cells to differentiate to bone tissue. In addition, the region underneath the implant apex was predicted to experience high fluid stimulus that results in the development of soft tissue. The relationship between the variables considered in this study and the outcome measures, BV and BIC, was found to be highly nonlinear. A three-way analysis of variance (ANOVA) of the results was conducted and it showed that micro-motion presents the largest hindrance to bone formation during healing. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Effect of Polymethyl Methacrylate Augmentation on the Primary Stability of Cannulated Bone Screws in an Anterolateral Plate in Osteoporotic Vertebrae: A Human Cadaver Study.

PubMed

Rüger, Matthias; Sellei, Richard M; Stoffel, Marcus; von Rüden, Christian

2016-02-01

Study Design Cohort study. Objective Expandable anterolateral plates facilitate the reduction of posttraumatic deformities of thoracolumbar spine injuries and are commonly used in cases of unstable injuries or compromised bone quality. In this in vitro study, the craniocaudal yield load of the osseous fixation of an anterior angular stable plate fixation system and the effect of polymethyl methacrylate (PMMA) screw augmentation on the primary stability of the screw-bone interface during kyphosis reduction was evaluated in 12 osteoporotic human thoracolumbar vertebrae. Methods The anterolateral stabilization device used for this study is comprised of two swiveling flanges and an expandable midsection. It facilitates the controlled reduction of kyphotic deformities in situ with a geared distractor. Single flanges were attached to 12 thoracolumbar vertebrae. Six specimens were augmented with PMMA by means of cannulated bone screws. The constructs were subjected to static, displacement-controlled craniocaudal loading to failure in a servohydraulic testing machine. Results The uncemented screws cut out at a mean 393 ± 66 N, whereas the cemented screws showed significantly higher yield load of 966 ± 166 N (p < 0.02). We detected no significant correlation between bone mineral density and yield load in this setting. Conclusion Our results indicate that PMMA augmentation is an effective method to increase two- to threefold the primary stability of the screw-bone interface of an anterolateral spine stabilization system in osteoporotic bone. We recommend it in cases of severely compromised bone quality to reduce the risk of screw loosening during initial kyphosis correction and to increase long-term construct stability.

Physical activity effects on bone metabolism.

PubMed

Smith, E L; Gilligan, C

1991-01-01

The incidence of osteoporotic fractures rises exponentially with age and is increasing faster than the demographic increase in the aging population. Physical activity has great potential to reduce the risk for osteoporotic fractures. Three independent but interactive factors contribute to the risk of fractures: bone strength, the risk of falling, and the effectiveness of neuromuscular response that protects the skeleton from injury. Exercise can reduce fracture risk not only by preventing bone loss, but by decreasing the risk of falling and the force of impact by improving strength, flexibility, balance, and reaction time. Extreme inactivity causes rapid bone loss of up to 40%, while athletic activity results in bone hypertrophy of up to 40%. Exercise intervention programs have reduced bone loss or increased bone mass in both men and women of various ages and initial bone status. These benefits have been shown for arm bone mineral content, total body calcium, spine, calcium bone index, tibia, and calcaneus. In both middle-aged and elderly women, physical activity intervention reduced bone loss or increased bone mass. The mechanisms for maintenance of skeletal integrity rely on a cellular response to hormonal and mechanical load stimuli. Studies in animal models show that training affects cellular activity. In osteoporotics, cellular erosion is increased and mineral apposition rate (MAR) decreased compared with normal age-matched controls. In contrast to this, sows trained on a treadmill 20 min per day for 20 weeks had greater active periosteal surface, periosteal MAR, and osteonal MAR than untrained sows.

A Comparative Analysis on Two Types of Oral Implants, Bone-Level and Tissue-Level, with Different Cantilever Lengths of Fixed Prosthesis.

PubMed

Mosavar, Alireza; Nili, Monireh; Hashemi, Sayed Raouf; Kadkhodaei, Mahmoud

2017-06-01

Depending on esthetic, anatomical, and functional aspects, in implant-prosthetic restoration of a completely edentulous jaw, the selection of implant type is highly important; however, bone- and tissue-level implants and their stress distribution in bone have not yet been comparatively investigated. Hence, finite element analysis was used to study the influence of cantilever length in a fixed prosthesis on stress distribution in peri-implant bone around these two types of oral implants. A 3D edentulous mandible was modeled. In simulations, a framework with four posterior cantilever lengths and two types of implants, bone-level and tissue-level, was considered. A compressive load was applied to the distal regions of the cantilevers, and the von-Mises stress of peri-implant bone was investigated. The independent t-test and the Pearson correlation coefficient analyzed the results (α = 0.05). Stresses in the cortical bone around the bone-level implants were greater than those in the tissue-level implants with the same cantilever length. In addition, by extending the cantilever length, the stress values in peri-implant bone increased. Therefore, when the cantilever was at its maximum length, the maximum stress was in cortical bone and around the bone-level distal implants. The results of the present study indicate that treatment with tissue-level implants is potentially more advantageous than with bone-level implants for implant-supported fixed prostheses. © 2015 by the American College of Prosthodontists.

Cortical Structure of Hallucal Metatarsals and Locomotor Adaptations in Hominoids

PubMed Central

Jashashvili, Tea; Dowdeswell, Mark R.; Lebrun, Renaud; Carlson, Kristian J.

2015-01-01

Diaphyseal morphology of long bones, in part, reflects in vivo loads experienced during the lifetime of an individual. The first metatarsal, as a cornerstone structure of the foot, presumably expresses diaphyseal morphology that reflects loading history of the foot during stance phase of gait. Human feet differ substantially from those of other apes in terms of loading histories when comparing the path of the center of pressure during stance phase, which reflects different weight transfer mechanisms. Here we use a novel approach for quantifying continuous thickness and cross-sectional geometric properties of long bones in order to test explicit hypotheses about loading histories and diaphyseal structure of adult chimpanzee, gorilla, and human first metatarsals. For each hallucal metatarsal, 17 cross sections were extracted at regularly-spaced intervals (2.5% length) between 25% and 65% length. Cortical thickness in cross sections was measured in one degree radially-arranged increments, while second moments of area were measured about neutral axes also in one degree radially-arranged increments. Standardized thicknesses and second moments of area were visualized using false color maps, while penalized discriminant analyses were used to evaluate quantitative species differences. Humans systematically exhibit the thinnest diaphyseal cortices, yet the greatest diaphyseal rigidities, particularly in dorsoplantar regions. Shifts in orientation of maximum second moments of area along the diaphysis also distinguish human hallucal metatarsals from those of chimpanzees and gorillas. Diaphyseal structure reflects different loading regimes, often in predictable ways, with human versus non-human differences probably resulting both from the use of arboreal substrates by non-human apes and by differing spatial relationships between hallux position and orientation of the substrate reaction resultant during stance. The novel morphological approach employed in this study offers the potential for transformative insights into form-function relationships in additional long bones, including those of extinct organisms (e.g., fossils). PMID:25635768

Long-term antibiotic delivery by chitosan-based composite coatings with bone regenerative potential

NASA Astrophysics Data System (ADS)

Ordikhani, F.; Simchi, A.

2014-10-01

Composite coatings with bone-bioactivity and drug-eluting capacity are considered as promising materials for titanium bone implants. In this work, drug-eluting chitosan-bioactive glass coatings were fabricated by a single-step electrophoretic deposition technique. Drug-loading and -releasing capacity of the composite coatings were carried out using the vancomycin antibiotic. Uniform coatings with a thickness of ∼55 μm containing 23.7 wt% bioactive glass particles and various amounts of the antibiotic (380-630 μg/cm2) were produced. The coatings were bioactive in terms of apatite-forming ability in simulated body fluid and showed favorable cell adhesion and growth. In vitro biological tests also indicated that the composite coatings had better cellular affinity than pristine chitosan coatings. The in vitro elution kinetics of the composite coating revealed an initial burst release of around 40% of the drug within the first elution step of 1 h and following by a continuous eluting over 4 weeks, revealing long-term drug-delivering potential. Antibacterial tests using survival assay against Gram-positive Staphylococcus aureus bacteria determined the effect of vancomycin release on reduction of infection risk. Almost no bacteria were survived on the coatings prepared from the EPD suspension containing ≥0.5 g/l vancomycin. The developed chitosan-based composite coatings with bone bioactivity and long-term drug-delivery ability may be potentially useful for metallic implants to reduce infection risk.

Food and Your Bones

MedlinePlus

... Loading ... Nutritional Guide View Now Food and Your Bones — Osteoporosis Nutrition Guidelines The food that you eat ... by taking multivitamins or supplements . Good-for-Your-Bones Foods Food Nutrient Dairy products such as low- ...

The Mechanics of Long Bone Fractures.

DTIC Science & Technology

1981-01-31

r = .99) between wet density and ultimate bending strength for 37 specimens of human femoral bone. Evans (1973) studied embalmed human tibial...Work 2 2.2 Methods 6 2.2.1 Torsional Loading 6 2.2.2 The Effects of Combined Loading 10 2.2.3 Cancellous Bone Effects 11 2.3 Results 11 2.3.1...PROPERTIES 21 3.1 Previous Work 22 3.2 Methods 26 3.2.1 Cross Sectional Property Software 26 3.2.2 CT Scanning Procedure 28 3.2.3 Linear Dependency of

American Society of Biomechanics Journal of Biomechanics Award 2013: Cortical bone tissue mechanical quality and biological mechanisms possibly underlying atypical fractures

PubMed Central

Geissler, Joseph R.; Bajaj, Devendra; Fritton, J. Christopher

2015-01-01

The biomechanics literature contains many well-understood mechanisms behind typical fracture types that have important roles in treatment planning. The recent association of “atypical” fractures with long-term use of drugs designed to prevent osteoporosis has renewed interest in the effects of agents on bone tissue-level quality. While this class of fracture was recognized prior to the introduction of the anti-resorptive bisphosphonate drugs and recently likened to stress fractures, the mechanism(s) that lead to atypical fractures have not been definitively identified. Thus, a causal relationship between these drugs and atypical fracture has not been established. Physicians, bioengineers and others interested in the biomechanics of bone are working to improve fracture-prevention diagnostics, and the design of treatments to avoid this serious side-effect in the future. This review examines the mechanisms behind the bone tissue damage that may produce the atypical fracture pattern observed increasingly with long-term bisphosphonate use. Our recent findings and those of others reviewed support that the mechanisms behind normal, healthy excavation and tunnel filling by bone remodeling units within cortical tissue strengthen mechanical integrity. The ability of cortical bone to resist the damage induced during cyclic loading may be altered by the reduced remodeling and increased tissue age resulting from long-term bisphosphonate treatment. Development of assessments for such potential fractures would restore confidence in pharmaceutical treatments that have the potential to spare millions in our aging population from the morbidity and death that often follow bone fracture. PMID:25683519

2D FEA of evaluation of micromovements and stresses at bone-implant interface in immediately loaded tapered implants in the posterior maxilla

PubMed Central

Desai, Shrikar R.; Singh, Rika; Karthikeyan, I.

2013-01-01

Aim: The aim of the study is to evaluate the influence implant length on stress distribution at bone implant interface in single immediately loaded implants when placed in D4 bone quality. Materials and Methods: A 2-dimensional finite element models were developed to simulate two types of implant designs, standard 3.75 mm–diameter tapered body implants of 6 and 10 mm lengths. The implants were placed in D4 bone quality with a cortical bone thickness of 0.5 mm. The implant design incorporated microthreads at the crestal part and the rest of the implant body incorporated Acme threads. The Acme thread form has a 29° thread angle with a thread height half of the pitch; the apex and valley are flat. A 100 N of force was applied vertically and in the oblique direction (at an angle of 45°) to the long axis of the implants. The respective material properties were assigned. Micro-movements and stresses at the bone implant interface were evaluated. Results: The results of total deformation (micro-movement) and Von mises stress were found to be lower for tapered long implant (10 mm) than short implant (6 mm) while using both vertical as well as oblique loading. Conclusion: Short implants can be successfully placed in poor bone quality under immediate loading protocol. The novel approach of the combination of microthreads at the crestal portion and acme threads for body portion of implant fixture gave promising results. PMID:24174759

Non-enzymatic glycation alters microdamage formation in human cancellous bone⋆

PubMed Central

Tang, S.Y.; Vashishth, D.

2015-01-01

Introduction The accumulation of advanced glycation end-products (AGEs) in bone has been suggested to adversely affect the fracture resistance of bone with aging, diabetes, and pharmacological treatments. The formation of AGEs increases crosslinking in the organic matrix of bone but it is unknown how elevated levels of AGEs affect the mechanisms of fracture resistance such as microdamage formation. Methods Human tibial cancellous bone cores were subjected to non-enzymatic glycation (NEG) by in vitro ribosylation and were mechanically loaded to pre- (0.6%) and post- (1.1%) yield apparent level strains. Loaded specimens were stained with lead–uranyl acetate and subjected to microCT-based 3D quantification and characterization of microdamage as either diffuse damage and linear microcracks. Damaged volume per bone volume (DV/BV) and damaged surface per damaged volume (DS/DV) ratios were used to quantify the volume and morphology of the detected microdamage, respectively. Results In vitro ribosylation increased the microdamage morphology parameter (DS/DV) under both pre-(p<0.05; +51%) and post-yield loading (p<0.001; +38%), indicating that the alteration of bone matrix by NEG caused the formation of crack-like microdamage morphologies. Under post-yield loading, the NEG-mediated increase in DS/DV was coupled with the reductions in microdamage formation (DV/BV; p<0.001) and toughness (p<0.001). Discussion Using a novel microCT technique to characterize and quantify microdamage, this study shows that the accumulation of AGEs in the bone matrix significantly alters the quantity and morphology of microdamage production and results in reduced fracture resistance. PMID:19747573

β-Ecdysone Augments Peak Bone Mass in Mice of Both Sexes.

PubMed

Dai, Weiwei; Zhang, HongLiang; Zhong, Zhendong A; Jiang, Li; Chen, Haiyan; Lay, Yu-An Evan; Kot, Alexander; Ritchie, Robert O; Lane, Nancy E; Yao, Wei

2015-08-01

One of the strongest predictors for osteoporosis is peak bone mass. Interventions to augment peak bone mass have yet to be developed. β-Ecdysone (βEcd), a natural steroid-like compound produced by arthropods to initiate metamorphosis, is believed to have androgenic effects and so may be used to augment bone mass. The purpose of this study was to use both male and female (1) gonadal-sufficient; and (2) -insufficient mice to investigate sex differences in terms of bone development and structure after βEcd administration. Two-month-old male and female Swiss-Webster mice were randomized to receive either vehicle or βEcd (0.5 mg/kg) for 3 weeks. In a separate experiment to evaluate the effects of βEcd on sex hormone-deficient mice, gonadectomy was performed in male (orchiectomy [ORX]) and female mice (ovariectomy [OVX]). Sham-operated and the ORX/OVX mice were then treated for 3 weeks with βEcd. Primary endpoints for the study were trabecular bone structure and bone strength. In male mice, the trabecular bone volume was 0.18±0.02 in the placebo-treated (PL) and 0.23±0.02 in the βEcd-treated group (p<0.05 versus PL); and 0.09±0.01 in the ORX group (p<0.05 versus PL) and 0.12±0.01 in the ORX+βEcd group. Vertebral bone strength (maximum load) was 43±2 in PL and 51±1 in the βEcd-treated group (p<0.05 versus PL); and 30±4 in the ORX group (p<0.05 versus PL) and 37±3 in the ORX+βEcd group. In female mice, trabecular bone volume was 0.23±0.02 in PL and 0.26±0.02 in the βEcd-treated group (p<0.05 versus PL); and 0.15±0.01 in the OVX group (p<0.05 versus PL) and 0.14±0.01 in the OVX+βEcd group. Maximum load of the vertebrae was 45±2 in PL and 48±4 in the βEcd-treated group; and 39±4 in the OVX group (p<0.05 versus PL) and 44±4 in the OVX+βEcd group. These findings suggest the potential use of βEcd in the augmentation of bone mass in growing male and female mice. It may also partially prevent the detrimental effects of gonadectomy on trabecular bone. Our results support the potential use of βEcd or nature products that are rich in βEcd to augment peak bone mass. βEcd may differ from the other anabolic hormone treatments that may have severe side effects such as serious cardiac complications. However, its effects on humans remain to be determined.

Effects of lead shot ingestion on bone mineralization in a population of red-legged partridge (Alectoris rufa).

PubMed

Álvarez-Lloret, Pedro; Rodríguez-Navarro, Alejandro B; Romanek, Christopher S; Ferrandis, Pablo; Martínez-Haro, Mónica; Mateo, Rafael

2014-01-01

The effect of lead (Pb) toxicity on bone mineralization was investigated in a wild population of red-legged partridge (Alectoris rufa) inhabiting a farmland area contaminated with Pb-shot from recreational hunting activities in Albacete, a southeastern province of Spain. Femora from 40 specimens of red-legged partridge were analyzed for Pb by graphite furnace atomic absorption spectroscopy (GF-AAS), and for bone composition by Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD). The FTIR and DRX data of bone were analyzed in detail to determine possible alterations in bone mineral chemistry and crystallinity due to Pb toxicity. Results showed a marked decrease in the degree of mineralization as Pb concentrations in bone tissue increased while XRD analyses showed that the crystallinity of apatite crystals increased with the Pb load in bone. These load-dependent effects are indicative that Pb contamination altered bone remodeling by reducing new bone mineral formation and demonstrate that bone quality is a sensitive indicator of adverse effects on wild bird populations exposed to Pb pollution. © 2013 Elsevier B.V. All rights reserved.

High Dietary Protein Intake and Protein-Related Acid Load on Bone Health.

PubMed

Cao, Jay J

2017-12-01

Consumption of high-protein diets is increasingly popular due to the benefits of protein on preserving lean mass and controlling appetite and satiety. The paper is to review recent clinical research assessing dietary protein on calcium metabolism and bone health. Epidemiological studies show that long-term, high-protein intake is positively associated with bone mineral density and reduced risk of bone fracture incidence. Short-term interventional studies demonstrate that a high-protein diet does not negatively affect calcium homeostasis. Existing evidence supports that the negative effects of the acid load of protein on urinary calcium excretion are offset by the beneficial skeletal effects of high-protein intake. Future research should focus on the role and the degree of contribution of other dietary and physiological factors, such as intake of fruits and vegetables, in reducing the acid load and further enhancing the anabolic effects of protein on the musculoskeletal system.

A gelatin composite scaffold strengthened by drug-loaded halloysite nanotubes.

PubMed

Ji, Lijun; Qiao, Wei; Zhang, Yuheng; Wu, Huayu; Miao, Shiyong; Cheng, Zhilin; Gong, Qianming; Liang, Ji; Zhu, Aiping

2017-09-01

Mechanical properties and anti-infection are two of the most concerned issues for artificial bone grafting materials. Bone regeneration porous scaffolds with sustained drug release were developed by freeze-drying the mixture of nanosized drug-loaded halloysite nanotubes (HNTs) and gelatin. The scaffolds showed porous structure and excellent biocompatibility. The mechanical properties of the obtained composite scaffolds were enhanced significantly by HNTs to >300%, comparing to those of gelatin scaffold, and match to those of natural cancellous bones. The ibuprofen-loaded HNTs incorporated in the scaffolds allowed extended drug release over 100h, comparing to 8h when directly mixed the drug into the gelatin scaffold. The biological properties of the composite scaffolds were investigated by culturing MG63 cells on them. The HNTs/gelatin scaffolds with excellent mechanical properties and sustained drug release could be a promising artificial bone grating material. Copyright © 2017 Elsevier B.V. All rights reserved.

The influence of the cumulated deformation energy in the measurement by the DSI method on the selected mechanical properties of bone tissues.

PubMed

Makuch, Anna M; Skalski, Konstanty R; Pawlikowski, Marek

2017-01-01

The goal of the study was to determine the influence of DSI test conditions, i.e., loading/unloading rates, hold time, and the value of the maximum loading force on selected mechanical properties of trabecular bone tissue. The test samples were resected from a femoral head of a patient qualified for a hip replacement surgery. During the DSI tests hardness (HV, HM, HIT) and elastic modulus (EIT) of trabecular bone tissue were measured using the Micro Hardness Tester (MHT, CSEM). The analysis of the results of measurements and the calculations of total energy, i.e., elastic and inelastic (Wtotal, Welastic, Winelastic) and those of hardness and elasticity made it possible to assess the impact of the process parameters (loading velocity, force and hold time) on mechanical properties of bone structures at a microscopic level. The coefficient k dependent on the EIT/HIT ratio and on the stored energy (ΔW = Wtotal - Welastic) is a measure of the material reaction to the loading and the deformation of tissue.

An in vitro biomechanical comparison of two fixation methods for transverse osteotomies of the medial proximal forelimb sesamoid bones in horses.

PubMed

Wilson, D A; Keegan, K G; Carson, W L

1999-01-01

This study compared the mechanical properties of the normal intact suspensory apparatus and two methods of fixation for repair of transverse, midbody fractures of the proximal sesamoid bones of adult horses: transfixation wiring (TW) and screws placed in lag fashion (LS). An in vitro, paired study using equine cadaver limbs mounted in a loading apparatus was used to test the mechanical properties of TW and LS. Seventeen paired (13 repaired, 4 normal) equine cadaver limbs consisting of the suspensory apparatus third metacarpal bone, and first and second phalanges. The two methods of repair and normal intact specimens were evaluated in single cycle-to-failure loading. Yield failure was defined to occur at the first notable discontinuity (>50 N) in the load-displacement curve, the first visible failure as evident on the videotape, or a change in the slope of the moment-fetlock angle curve. Ultimate failure was defined to occur at the highest load resisted by the specimen. Corresponding resultant force and force per kg of body weight on the suspensory apparatus, fetlock joint moment, and angle of fetlock dorsiflexion were calculated by use of specimen dimensions and applied load. These were compared along with specimen stiffness, and ram displacement. Load on the suspensory apparatus, load on the suspensory apparatus per kg of body weight, moment, applied load, and angle of fetlock dorsiflexion at yield failure were significantly greater for the TW-repaired than for the LS-repaired specimens. A 3 to 5 mm gap was observed before yield failure in most TW-repaired osteotomies. Transfixation wiring provided greater strength to yield failure than screws placed in lag fashion in single cycle load-to-failure mechanical testing of repaired transverse osteotomized specimens of the medial proximal forelimb sesamoid bone.

Fiber-enriched double-setting calcium phosphate bone cement.

PubMed

dos Santos, Luís Alberto; Carrodéguas, Raúl Garcia; Boschi, Anselmo Ortega; Fonseca de Arruda, Antônio Celso

2003-05-01

Calcium phosphate bone cements are useful in orthopedics and traumatology, their main advantages being their biocompatibility and bioactivity, which render bone tissue osteoconductive, providing in situ hardening and easy handling. However, their low mechanical strength, which, in the best of cases, is equal to the trabecular bone, and their very low toughness are disadvantages. Calcium phosphate cement compositions with mechanical properties more closely resembling those of human bone would broaden the range of applications, which is currently limited to sites subjected to low loads. This study investigated the influence of added polypropylene, nylon, and carbon fibers on the mechanical properties of double setting alpha-tricalcium phosphate-based cement, using calcium phosphate cement added to an in situ polymerizable acrylamide-based system recently developed by the authors. Although the addition of fibers was found to reduce the compression strength of the double-setting calcium phosphate cement because of increased porosity, it strongly increased the cement's toughness (J(IC)) and tensile strength. The composites developed in this work, therefore, have a potential application in shapes subjected to flexure. Copyright 2003 Wiley Periodicals, Inc.

Therapeutic efficacy of intra-articular hyaluronan derivative and platelet-rich plasma in mice following axial tibial loading

PubMed Central

Duan, Xin; Sandell, Linda J.; Chinzei, Nobuaki; Holguin, Nilsson; Silva, Matthew J.; Schiavinato, Antonella

2017-01-01

Objective To investigate the therapeutic potential of intra-articular hyaluronan-derivative HYADD® 4-G and/or platelet-rich plasma (PRP) in a mouse model of non-invasive joint injury. Methods Non-invasive axial tibial loading was used to induce joint injury in 10-week-old C57BL/6J mice (n = 86). Mice underwent a single loading of either 6 Newton (N) or 9N axial tibial compression. HYADD® 4-G was injected intra-articularly at 8 mg/mL or 15 mg/mL either before or after loading with or without PRP. Phosphate-buffered-saline was injected as control. Knee joints were harvested at 5 or 56 days post-loading and prepared for micro-computed tomography scanning and subsequently processed for histology. Immunostaining was performed for aggrecan to monitor its distribution, for CD44 to monitor chondrocyte reactive changes and for COMP (cartilage oligomeric matrix protein) as an index for cartilage matrix changes related to loading and cartilage injury. TUNEL assay was performed to identify chondrocyte apoptosis. Results Loading initiated cartilage proteoglycan loss and chondrocyte apoptosis within 5 days with slowly progressive post-traumatic osteoarthritis (no cartilage degeneration, but increased synovitis and ectopic calcification after 9N loading) at 56 days. Mice treated with repeated HYADD® 4-G (15 mg/mL) or HYADD® 4-G (8 mg/mL) ± PRP or PRP alone exhibited no significant improvement in the short-term (5 days) and long-term (56 days) consequences of joint loading except for a trend for improved bone changes compared to non-loaded joints. Conclusion While we failed to show an overall effect of intra-articular delivery of hyaluronan-derivative and/or PRP in reversing/protecting the pathological events in cartilage and synovium following joint injury, some bone alterations were relatively less severe with hyaluronan-derivative at higher concentration or in association with PRP. PMID:28406954

Analysis of crack propagation in human long bone by using finite element modeling

NASA Astrophysics Data System (ADS)

Salim, Mohammad Shahril; Salleh, Ahmad Faizal; Daud, Ruslizam

2017-12-01

The aim of this research is to present a numerical modeling of crack for human long bone specifically on femur shaft bone under mode I loading condition. Two - dimensional model (2D) of long bone was developed based on past research study. The finite element analysis and construction of the model are done using Mechanical APDL (ANSYS) v14.0 software. The research was conducted mainly based on two conditions that were at different crack lengths and different loading forces for male and female. In order to evaluate the stress intensity factor (KI) of the femur shaft of long bone, this research employed finite element method to predict the brittle fracture loading by using three-point bending test. The result of numerical test found that the crack was formed when the crack length reached 0.0022 m where KI values are proportional with the crack's length. Also, various loading forces in range of 400 N to 1000 N were applied in an attempt to study their effect on stress intensity factor and it was found that the female dimension has higher KI values compared to male. It was also observed that K values found by this method have good agreement with theoretical results based on previous research.

Bone Graft Substitute Provides Metaphyseal Fixation for a Stemless Humeral Implant.

PubMed

Kim, Myung-Sun; Kovacevic, David; Milks, Ryan A; Jun, Bong-Jae; Rodriguez, Eric; DeLozier, Katherine R; Derwin, Kathleen A; Iannotti, Joseph P

2015-07-01

Stemless humeral fixation has become an alternative to traditional total shoulder arthroplasty, but metaphyseal fixation may be compromised by the quality of the trabecular bone that diminishes with age and disease, and augmentation of the fixation may be desirable. The authors hypothesized that a bone graft substitute (BGS) could achieve initial fixation comparable to polymethylmethacrylate (PMMA) bone cement. Fifteen fresh-frozen human male humerii were randomly implanted using a stemless humeral prosthesis, and metaphyseal fixation was augmented with either high-viscosity PMMA bone cement (PMMA group) or a magnesium-based injectable BGS (OsteoCrete; Bone Solutions Inc, Dallas, Texas) (OC group). Both groups were compared with a control group with no augmentation. Initial stiffness, failure load, failure displacement, failure cycle, and total work were compared among groups. The PMMA and OC groups showed markedly higher failure loads, failure displacements, and failure cycles than the control group (P<.01). There were no statistically significant differences in initial stiffness, failure load, failure displacement, failure cycle, or total work between the PMMA and OC groups. The biomechanical properties of magnesium-based BGS fixation compared favorably with PMMA bone cement in the fixation of stemless humeral prostheses and may provide sufficient initial fixation for this clinical application. Future work will investigate the long-term remodeling characteristics and bone quality at the prosthetic-bone interface in an in vivo model to evaluate the clinical efficacy of this approach. Copyright 2015, SLACK Incorporated.

Effect on Bone Architecture of Marginal Grooves in Dental Implants Under Occlusal Loaded Conditions in Beagle Dogs.

PubMed

Kato, Hatsumi; Kuroshima, Shinichiro; Inaba, Nao; Uto, Yusuke; Sawase, Takashi

2018-02-01

The aim of this study was to clarify whether marginal grooves on dental implants affect osseointegration, bone structure, and the alignment of collagen fibers to determine bone quality under loaded conditions. Anodized Ti-6Al-4V alloy dental implants, with and without marginal grooves (test and control implants, respectively), were used (3.7 × 8.0 mm). Fourth premolars and first molars of 6 beagle mandibles were extracted. Two control and test implants were placed in randomly selected healed sites at 12 weeks after tooth extraction. Screw-retained single crowns for first molars were fabricated. Euthanasia was performed at 8 weeks after the application of occlusal forces. Implant marginal bone level, bone to implant contact (BIC), bone structure around dental implants, and the alignment of collagen fibers determining bone quality were analyzed. The marginal bone level in test implants was significantly higher than that in control implants. Occlusal forces significantly increased BIC in test implants ( P = .007), whereas BIC did not change in control implants, irrespective of occlusal forces ( P = .303). Moreover, occlusal forces significantly increased BIC in test implants compared with control implants ( P = .032). Additionally, occlusal forces preferentially aligned collagen fibers in test implants, but not control implants. Hence, marginal grooves on dental implants have positive effects on increased osseointegration and adapted bone quality based on the preferential alignment of collagen fibers around dental implants under loaded conditions.

Rapid prototyped porous nickel–titanium scaffolds as bone substitutes

PubMed Central

Hoffmann, Waldemar; Bormann, Therese; Rossi, Antonella; Müller, Bert; Schumacher, Ralf; Martin, Ivan; Wendt, David

2014-01-01

While calcium phosphate–based ceramics are currently the most widely used materials in bone repair, they generally lack tensile strength for initial load bearing. Bulk titanium is the gold standard of metallic implant materials, but does not match the mechanical properties of the surrounding bone, potentially leading to problems of fixation and bone resorption. As an alternative, nickel–titanium alloys possess a unique combination of mechanical properties including a relatively low elastic modulus, pseudoelasticity, and high damping capacity, matching the properties of bone better than any other metallic material. With the ultimate goal of fabricating porous implants for spinal, orthopedic and dental applications, nickel–titanium substrates were fabricated by means of selective laser melting. The response of human mesenchymal stromal cells to the nickel–titanium substrates was compared to mesenchymal stromal cells cultured on clinically used titanium. Selective laser melted titanium as well as surface-treated nickel–titanium and titanium served as controls. Mesenchymal stromal cells had similar proliferation rates when cultured on selective laser melted nickel–titanium, clinically used titanium, or controls. Osteogenic differentiation was similar for mesenchymal stromal cells cultured on the selected materials, as indicated by similar gene expression levels of bone sialoprotein and osteocalcin. Mesenchymal stromal cells seeded and cultured on porous three-dimensional selective laser melted nickel–titanium scaffolds homogeneously colonized the scaffold, and following osteogenic induction, filled the scaffold’s pore volume with extracellular matrix. The combination of bone-related mechanical properties of selective laser melted nickel–titanium with its cytocompatibility and support of osteogenic differentiation of mesenchymal stromal cells highlights its potential as a superior bone substitute as compared to clinically used titanium. PMID:25383165

Evaluation of bone surrogates for indirect and direct ballistic fractures.

PubMed

Bir, Cynthia; Andrecovich, Chris; DeMaio, Marlene; Dougherty, Paul J

2016-04-01

The mechanism of injury for fractures to long bones has been studied for both direct ballistic loading as well as indirect. However, the majority of these studies have been conducted on both post-mortem human subjects (PMHS) and animal surrogates which have constraints in terms of storage, preparation and testing. The identification of a validated bone surrogate for use in forensic, medical and engineering testing would provide the ability to investigate ballistic loading without these constraints. Two specific bone surrogates, Sawbones and Synbone, were evaluated in comparison to PMHS for both direct and indirect ballistic loading. For the direct loading, the mean velocity to produce fracture was 121 ± 19 m/s for the PMHS, which was statistically different from the Sawbones (140 ± 7 m/s) and Synbone (146 ± 3 m/s). The average distance to fracture in the indirect loading was .70 cm for the PMHS. The Synbone had a statistically similar average distance to fracture (.61 cm, p=0.54) however the Sawbones average distance to fracture was statistically different (.41 cm, p<0.05). Fractures patterns were found to be comparable to the PMHS for tests conducted with Synbones, however the input parameters were slightly varied to produce similar results. The fractures patterns with the Sawbones were not found to be as comparable to the PMHS. An ideal bone surrogate for ballistic testing was not identified and future work is warranted. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Influence of bicortical techniques in internal connection placed in premaxillary area by 3D finite element analysis.

PubMed

Verri, Fellippo Ramos; Cruz, Ronaldo Silva; Lemos, Cleidiel Aparecido Araújo; de Souza Batista, Victor Eduardo; Almeida, Daniel Augusto Faria; Verri, Ana Caroline Gonçales; Pellizzer, Eduardo Piza

2017-02-01

The aim of study was to evaluate the stress distribution in implant-supported prostheses and peri-implant bone using internal hexagon (IH) implants in the premaxillary area, varying surgical techniques (conventional, bicortical and bicortical in association with nasal floor elevation), and loading directions (0°, 30° and 60°) by three-dimensional (3D) finite element analysis. Three models were designed with Invesalius, Rhinoceros 3D and Solidworks software. Each model contained a bone block of the premaxillary area including an implant (IH, Ø4 × 10 mm) supporting a metal-ceramic crown. 178 N was applied in different inclinations (0°, 30°, 60°). The results were analyzed by von Mises, maximum principal stress, microstrain and displacement maps including ANOVA statistical test for some situations. Von Mises maps of implant, screws and abutment showed increase of stress concentration as increased loading inclination. Bicortical techniques showed reduction in implant apical area and in the head of fixation screws. Bicortical techniques showed slight increase stress in cortical bone in the maximum principal stress and microstrain maps under 60° loading. No differences in bone tissue regarding surgical techniques were observed. As conclusion, non-axial loads increased stress concentration in all maps. Bicortical techniques showed lower stress for implant and screw; however, there was slightly higher stress on cortical bone only under loads of higher inclinations (60°).

Pulsatile Fluid Shear in Bone Remodeling

NASA Technical Reports Server (NTRS)

Frangos, John A.

1997-01-01

The objective of this investigation was to elucidate the sensitivity to transients in fluid shear stress in bone remodeling. Bone remodeling is clearly a function of the local mechanical environment which includes interstitial fluid flow. Traditionally, load-induced remodeling has been associated with low frequency (1-2 Hz) signals attributed to normal locomotion. McLeod and Rubin, however, demonstrated in vivo remodeling events associated with high frequency (15-30 Hz) loading. Likewise, other in vivo studies demonstrated that slowly applied strains did not trigger remodeling events. We therefore hypothesized that the mechanosensitive pathways which control bone maintenance and remodeling are differentially sensitive to varying rates of applied fluid shear stress.

Loading and Skeletal Development and Maintenance

PubMed Central

Bergmann, P.; Body, J. J.; Boonen, S.; Boutsen, Y.; Devogelaer, J. P.; Goemaere, S.; Kaufman, J.; Reginster, J. Y.; Rozenberg, S.

2011-01-01

Mechanical loading is a major regulator of bone mass and geometry. The osteocytes network is considered the main sensor of loads, through the shear stress generated by strain induced fluid flow in the lacuno-canalicular system. Intracellular transduction implies several kinases and phosphorylation of the estrogen receptor. Several extra-cellular mediators, among which NO and prostaglandins are transducing the signal to the effector cells. Disuse results in osteocytes apoptosis and rapid imbalanced bone resorption, leading to severe osteoporosis. Exercising during growth increases peak bone mass, and could be beneficial with regards to osteoporosis later in life, but the gain could be lost if training is abandoned. Exercise programs in adults and seniors have barely significant effects on bone mass and geometry at least at short term. There are few data on a possible additive effect of exercise and drugs in osteoporosis treatment, but disuse could decrease drugs action. Exercise programs proposed for bone health are tedious and compliance is usually low. The most practical advice for patients is to walk a minimum of 30 to 60 minutes per day. Other exercises like swimming or cycling have less effect on bone, but could reduce fracture risk indirectly by maintaining muscle mass and force. PMID:21209784

Does bone cement in percutaneous vertebroplasty act as a stress riser?

PubMed

Aquarius, René; van der Zijden, Astrid Maria; Homminga, Jasper; Verdonschot, Nico; Tanck, Esther

2013-11-15

An in vitro cadaveric study. To determine whether percutaneous vertebroplasty (PVP) with a clinically relevant amount of bone cement is capable of causing stress peaks in adjacent-level vertebrae. It is often suggested that PVP of a primary spinal fracture causes stress peaks in adjacent vertebrae, thereby leading to additional fractures. The in vitro studies that demonstrated this relationship, however, use bigger volumes of bone cement used clinically. Ten fresh-frozen vertebrae were loaded until failure, while registering force and displacement as well as the pressure under the lower endplate. After failure, the vertebrae were augmented with clinically relevant amounts of bone cement and then again loaded until failure. The force, displacement, and pressure under the lower endplate were again registered. Stress peaks were not related to the location of the injected bone cement. Both failure load and stiffness were significantly lower after augmentation. On the basis of our findings, we conclude that vertebral augmentation with clinically relevant amounts of bone cement does not lead to stress peaks under the endplate. It is therefore unlikely that PVP, in itself, causes detrimental stresses in the adjacent vertebrae, leading to new vertebral fractures. N/A.

Teicoplanin-loaded borate bioactive glass implants for treating chronic bone infection in a rabbit tibia osteomyelitis model.

PubMed

Zhang, Xin; Jia, Weitao; Gu, Yifei; Xiao, Wei; Liu, Xin; Wang, Deping; Zhang, Changqing; Huang, Wenhai; Rahaman, Mohamed N; Day, Delbert E; Zhou, Nai

2010-08-01

The treatment of chronic osteomyelitis (bone infection) remains a clinical challenge. In this work, pellets composed of a chitosan-bonded mixture of borate bioactive glass particles (<50microm) and teicoplanin powder (antibiotic), were evaluated in vitro and in vivo for treating chronic osteomyelitis induced by methicillin-resistant Staphylococcus aureus (MRSA) in a rabbit model. When immersed in phosphate-buffered saline, the pellets showed sustained release of teicoplanin over 20-30 days, while the bioactive glass converted to hydroxyapatite (HA) within 7 days, eventually forming a porous HA structure. Implantation of the teicoplanin-loaded pellets in a rabbit tibia osteomyelitis model resulted in the detection of teicoplanin in the blood for about 9 days. The implants converted to a bone-like HA graft, and supported the ingrowth of new bone into the tibia defects within 12 weeks of implantation. Microbiological, histological and scanning electron microscopy techniques showed that the implants provided a cure for the bone infection. The results indicate that the teicoplanin-loaded borate bioactive glass implant, combining sustained drug release with the ability to support new bone ingrowth, could provide a method for treating chronic osteomyelitis. Copyright 2010 Elsevier Ltd. All rights reserved.

The relationship between loading history and proximal femoral diaphysis cross-sectional geometry.

PubMed

Niinimäki, Sirpa; Narra, Nathaniel; Härkönen, Laura; Abe, Shinya; Nikander, Riku; Hyttinen, Jari; Knüsel, Christopher; Sievänen, Harri

2017-07-08

We investigated the relationship between loading history and bone biomechanical properties used in physical activity reconstructions. These bone properties included bone bending and torsional strength (J), cortical area (CA), the direction of the major axis (theta angle), and element shape ratios determined from cross sections of standardized bone length. In addition, we explored the applicability of anatomically determined cross sections. Our material consisted of hip and proximal thigh magnetic resonance images of Finnish female athletes (N = 91) engaged in high-jump, triple-jump, endurance running, swimming, power-lifting, soccer and squash; along with a group of active non-athlete individuals (N = 20). We used regression analysis for size-adjustment, and the extracted residuals were then used to compare differences in the bone properties between groups. We found that triple-jumpers, soccer players, and squash players had the greatest values in CA and J, swimmers and non-athletes had the smallest, whereas high-jumpers, power-lifters, and endurance runners exhibited interim values. No between-the-group differences in element shape ratios or theta angles were found. We found that influences of activity were similar regardless of whether standardized length or anatomically determined cross sections were used. Extreme (triple-jump) and directionally inconsistent loading (soccer and squash) necessitate a more robust skeleton compared to directionally consistent loading (high-jump, power-lifting, and endurance running) or non-impact loading (swimming and non-athletes). However, not all of these relationships were statistically significant. Thus, information gained about physical activity using bone properties is informative but limited. Accounting for the limitations, the method is applicable on fragmented skeletal material as anatomically determined cross sections can be used. © 2017 Wiley Periodicals, Inc.

Finite element analysis on the biomechanical stability of open porous titanium scaffolds for large segmental bone defects under physiological load conditions.

PubMed

Wieding, Jan; Souffrant, Robert; Mittelmeier, Wolfram; Bader, Rainer

2013-04-01

Repairing large segmental defects in long bones caused by fracture, tumour or infection is still a challenging problem in orthopaedic surgery. Artificial materials, i.e. titanium and its alloys performed well in clinical applications, are plenary available, and can be manufactured in a wide range of scaffold designs. Although the mechanical properties are determined, studies about the biomechanical behaviour under physiological loading conditions are rare. The goal of our numerical study was to determine the suitability of open-porous titanium scaffolds to act as bone scaffolds. Hence, the mechanical stability of fourteen different scaffold designs was characterized under both axial compression and biomechanical loading within a large segmental distal femoral defect of 30mm. This defect was stabilized with an osteosynthesis plate and physiological hip reaction forces as well as additional muscle forces were implemented to the femoral bone. Material properties of titanium scaffolds were evaluated from experimental testing. Scaffold porosity was varied between 64 and 80%. Furthermore, the amount of material was reduced up to 50%. Uniaxial compression testing revealed a structural modulus for the scaffolds between 3.5GPa and 19.1GPa depending on porosity and material consumption. The biomechanical testing showed defect gap alterations between 0.03mm and 0.22mm for the applied scaffolds and 0.09mm for the intact bone. Our results revealed that minimizing the amount of material of the inner core has a smaller influence than increasing the porosity when the scaffolds are loaded under biomechanical loading. Furthermore, an advanced scaffold design was found acting similar as the intact bone. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved.

Geometry Design Optimization of Functionally Graded Scaffolds for Bone Tissue Engineering: A Mechanobiological Approach.

PubMed

Boccaccio, Antonio; Uva, Antonio Emmanuele; Fiorentino, Michele; Mori, Giorgio; Monno, Giuseppe

2016-01-01

Functionally Graded Scaffolds (FGSs) are porous biomaterials where porosity changes in space with a specific gradient. In spite of their wide use in bone tissue engineering, possible models that relate the scaffold gradient to the mechanical and biological requirements for the regeneration of the bony tissue are currently missing. In this study we attempt to bridge the gap by developing a mechanobiology-based optimization algorithm aimed to determine the optimal graded porosity distribution in FGSs. The algorithm combines the parametric finite element model of a FGS, a computational mechano-regulation model and a numerical optimization routine. For assigned boundary and loading conditions, the algorithm builds iteratively different scaffold geometry configurations with different porosity distributions until the best microstructure geometry is reached, i.e. the geometry that allows the amount of bone formation to be maximized. We tested different porosity distribution laws, loading conditions and scaffold Young's modulus values. For each combination of these variables, the explicit equation of the porosity distribution law-i.e the law that describes the pore dimensions in function of the spatial coordinates-was determined that allows the highest amounts of bone to be generated. The results show that the loading conditions affect significantly the optimal porosity distribution. For a pure compression loading, it was found that the pore dimensions are almost constant throughout the entire scaffold and using a FGS allows the formation of amounts of bone slightly larger than those obtainable with a homogeneous porosity scaffold. For a pure shear loading, instead, FGSs allow to significantly increase the bone formation compared to a homogeneous porosity scaffolds. Although experimental data is still necessary to properly relate the mechanical/biological environment to the scaffold microstructure, this model represents an important step towards optimizing geometry of functionally graded scaffolds based on mechanobiological criteria.

A new approach for the one-step synthesis of bioactive PS vs. PMMA silica hybrid microspheres as potential drug delivery systems.

PubMed

Angelopoulou, A; Efthimiadou, E K; Boukos, N; Kordas, G

2014-05-01

In this work, hybrid microspheres were prepared in a two-step process combining the emulsifier free-emulsion polymerization and the sol-gel coating method. In the first step, polystyrene (St) and poly(methyl methacrylate) (PMMA) microspheres were prepared as sacrificial template and in the second step a silanol shell was fabricated. The functionalized surface of the hybrid microspheres by silane analogs (APTES, TEOS) resulted in enhanced effects. The hollow microspheres were resulted either in an additional step by template dissolution and/or during the coating process. The microspheres' surface interactions and the size distribution were optimized by treatment in simulated body fluids, which resulted in the in vitro prediction of bioactivity. The bioassay test indicated that the induced hydroxyapatite resembled in structure to naturally occurring bone apatite. The drug doxorubicin (DOX) was used as a model entity for the evaluation of drug loading and release. The drug release study was performed in two different pH conditions, at acidic (pH=4.5) close to cancer cell environment and at slightly basic pH (pH=7.4) resembling the orthopedic environment. The results of the present study indicated promising hybrid microspheres for the potential application as drug delivery vehicles, for dual orthopedic functionalities in bone defects, bone inflammation, bone cancer and bone repair. Copyright © 2014 Elsevier B.V. All rights reserved.

Combined VEGF and LMP-1 delivery enhances osteoprogenitor cell differentiation and ectopic bone formation.

PubMed

Wang, Xiuli; Cui, Fuai; Madhu, Vedavathi; Dighe, Abhijit S; Balian, Gary; Cui, Quanjun

2011-02-01

A novel strategy to enhance bone repair is to combine angiogenic factors and osteogenic factors. We combined vascular endothelial growth factor (VEGF) and LIM mineralization protein-1 (LMP-1) by using an internal ribosome entry site to link the genes within a single plasmid. We then evaluated the effects on osteoblastic differentiation in vitro and ectopic bone formation in vivo with a subcutaneously placed PLAGA scaffold loaded with a cloned mouse osteoprogenitor cell line, D1, transfected with plasmids containing VEGF and LMP-1 genes. The cells expressing both genes elevated mRNA expression of RunX2 and β-catenin and alkaline phosphatase activity compared to cells from other groups. In vivo, X-ray and micro-CT analysis of the retrieved implants revealed more ectopic bone formation at 2 and 3 weeks but not at 4 weeks compared to other groups. The results indicate that the combination of the therapeutic growth factors potentiates cell differentiation and may promote osteogenesis.

Exercise Countermeasures for Bone Loss During Space Flight: A Method for the Study of Ground Reaction Forces and their Implications for Bone Strain

NASA Technical Reports Server (NTRS)

Peterman, M.; McCrory, J. L.; Sharkey, N. A.; Piazza, S.; Cavanagh, P. R.

1999-01-01

Effective countermeasures to prevent loss of bone mineral during long duration space flight remain elusive. Despite an exercise program on MIR flights, the data from LeBlanc et al. (1996) indicated that there was still a mean rate of loss of bone mineral density in the proximal femur of 1.58% per month (n=18, flight duration 4 - 14.4 months). The specific mechanisms regulating bone mass are not known, but most investigators agree that bone maintenance is largely dependent upon mechanical demand and the resultant local bone strains. A plausible hypothesis is that bone loss during space flight, such as that reported by LeBlanc et al. (1996), may result from failure to effectively load the skeleton in order to generate localized bone strains of sufficient magnitude to prevent disuse osteoporosis. A variety of methods have been proposed to simulate locomotor exercise in reduced gravity. In such simulations, and in an actual microgravity environment, a gravity replacement load (GRL) must always be added to return the exercising subject to the support surface and the resulting skeletal load is critically dependent upon the magnitude of the GRL. To our knowledge, GRLs during orbital flight have only been measured once (on STS 81) and it is likely that most or all prior treadmill exercise in space has used GRLs that were less than one body weight. McCrory (1997) has shown that subjects walking and running in simulated zero-G can tolerate GRLs of 1 if an appropriate harness is used. Several investigators have attempted to measure in vivo strains and forces in the bones of humans, but have faced ethical and technical limitations. The anteromedial aspect of the tibial midshaft has been a common site for the placement of strain gauges; one reason to measure strains in the anterior tibia is that this region is surgically accessible. Aamodt et al. (1997) were able to measure strains on the lateral surface of the proximal femur only because their experimental subjects were already scheduled for hip surgery. Lu et al. (1997) used an instrumented massive proximal femoral prosthesis along with electromyographic measurements to demonstrate that femoral forces depend on muscular activity. These analyses of in vivo bone mechanics are valuable. The invasive nature of the procedures involved, however, limits both the number of subjects and the number of strain gauge locations. Further, the results of these studies may be confounded by the inclusion of subjects with pathological conditions. Gross et al. (1992) measured strain at three locations on the equine third metacarpal and used those data to construct a computer model of the internal strain environment of the bone. An analogous placement of multiple gauges in living humans would be difficult and potentially hazardous because of the depth of soft tissue overlying the tibia and femur.

Controlled delivery of icariin on small intestine submucosa for bone tissue engineering.

PubMed

Li, Mei; Gu, Qiaoqiao; Chen, Mengjie; Zhang, Chi; Chen, Songdi; Zhao, Jiyuan

2017-02-01

Small intestine submucosa (SIS) has been reported as an excellent biomaterial for tissue engineering because of its naturally occurring collagenous extracellular matrix property with growth factors. However, SIS from submucosal layer of intestine provides different microenvironment from bone tissue, which limits its application to bone regeneration. The object of this study was to improve osteoinductivity of SIS by controlled local delivery of icariin (Ic), a potent osteogenic compound. Sustained release of icariin from SIS scaffold was achieved for >30days and the loading of icariin on SIS scaffold was uniform as scanned by SEM. In vitro experiments revealed that expression of osteogenic differentiation markers (Alp, Bsp and Ocn) was increased after treatment of Ic-SIS scaffold, without significant cytotoxicity. In an in vivo mouse calvarial defect model, bone regeneration was enhanced by SIS implantation at 8weeks, compared to control defect. New bone formation was further improved by implantation with Ic-SIS (low and high) at both 4 and 8weeks. The results of this study suggest that SIS scaffold has the potential as an icariin delivery carrier for enhancement of bone regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

Laminated electrospun nHA/PHB-composite scaffolds mimicking bone extracellular matrix for bone tissue engineering.

PubMed

Chen, Zhuoyue; Song, Yue; Zhang, Jing; Liu, Wei; Cui, Jihong; Li, Hongmin; Chen, Fulin

2017-03-01

Electrospinning is an effective means to generate nano- to micro-scale polymer fibers resembling native extracellular matrix for tissue engineering. However, a major problem of electrospun materials is that limited pore size and porosity may prevent adequate cellular infiltration and tissue ingrowth. In this study, we first prepared thin layers of hydroxyapatite nanoparticle (nHA)/poly-hydroxybutyrate (PHB) via electrospinning. We then laminated the nHA/PHB thin layers to obtain a scaffold for cell seeding and bone tissue engineering. The results demonstrated that the laminated scaffold possessed optimized cell-loading capacity. Bone marrow mesenchymal stem cells (MSCs) exhibited better adherence, proliferation and osteogenic phenotypes on nHA/PHB scaffolds than on PHB scaffolds. Thereafter, we seeded MSCs onto nHA/PHB scaffolds to fabricate bone grafts. Histological observation showed osteoid tissue formation throughout the scaffold, with most of the scaffold absorbed in the specimens 2months after implantation, and blood vessels ingrowth into the graft could be observed in the graft. We concluded that electrospun and laminated nanoscaled biocomposite scaffolds hold great therapeutic potential for bone regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

Challenges in engineering osteochondral tissue grafts with hierarchical structures.

PubMed

Gadjanski, Ivana; Vunjak-Novakovic, Gordana

2015-01-01

A major hurdle in treating osteochondral (OC) defects is the different healing abilities of two types of tissues involved - articular cartilage and subchondral bone. Biomimetic approaches to OC-construct engineering, based on recapitulation of biological principles of tissue development and regeneration, have potential for providing new treatments and advancing fundamental studies of OC tissue repair. This review on state of the art in hierarchical OC tissue graft engineering is focused on tissue engineering approaches designed to recapitulate the native milieu of cartilage and bone development. These biomimetic systems are discussed with relevance to bioreactor cultivation of clinically sized, anatomically shaped human cartilage/bone constructs with physiologic stratification and mechanical properties. The utility of engineered OC tissue constructs is evaluated for their use as grafts in regenerative medicine, and as high-fidelity models in biological research. A major challenge in engineering OC tissues is to generate a functionally integrated stratified cartilage-bone structure starting from one single population of mesenchymal cells, while incorporating perfusable vasculature into the bone, and in bone-cartilage interface. To this end, new generations of advanced scaffolds and bioreactors, implementation of mechanical loading regimens and harnessing of inflammatory responses of the host will likely drive the further progress.

A 5-year comparison of marginal bone level following immediate loading of single-tooth implants placed in healed alveolar ridges and extraction sockets in the maxilla.

PubMed

Berberi, Antoine N; Sabbagh, Joseph M; Aboushelib, Moustafa N; Noujeim, Ziad F; Salameh, Ziad A

2014-01-01

The aim of present investigation was to evaluate marginal bone level after 5-year follow-up of implants placed in healed ridges and fresh extraction sockets in maxilla with immediate loading protocol. Thirty-six patients in need of a single-tooth replacement in the anterior maxilla received 42 Astra Tech implants (Astra Tech Implant system™, Dentsply Implants, Mölndal, Sweden). Implants were placed either in healed ridges (group I) or immediately into fresh extraction sockets (group II). Implants were restored and placed into functional loading immediately by using a prefabricated abutment. Marginal bone level relative to the implant reference point was recorded at implant placement, crown cementation, 12, 36, and 60 months following loading using intra-oral radiographs. Measurements were made on the mesial and distal sides of each implant. Overall, two implants were lost from the group II, before final crown cementation: they were excluded from the study. The mean change in marginal bone loss (MBL) after implant placement was 0.26 ± 0.161 mm for 1 year, and 0.26 ± 0.171 mm for 3 years, and 0.21 ± 0.185 mm for 5 years in extraction sockets and was 0.26 ± 0.176 mm for 1 year and 0.21 ± 0.175 mm for 3 years, and 0.19 ± 0.172 mm for 5 years in healed ridges group. Significant reduction of marginal bone was more pronounced in implants inserted in healed ridges (P < 0.041) compared to fresh surgical extraction sockets (P < 0.540). Significant MBL was observed on the mesial side of the implant after cementation of the provisional (P < 0.007) and after 12 months (P < 0.034) compared to the distal side which remained stable for 3 and 5 years observation period. Within the limitations of this study, responses of local bone to immediately loaded implants placed either in extraction sockets or healed ridges were similar. Functional loading technique by using prefabricated abutment placed during the surgery time seems to maintain marginal bone around implant in both healed and fresh extraction sites.

Immediately loaded mini dental implants as overdenture retainers: 1-Year cohort study of implant stability and peri-implant marginal bone level.

PubMed

Šćepanović, Miodrag; Todorović, Aleksandar; Marković, Aleksa; Patrnogić, Vesna; Miličić, Biljana; Moufti, Adel M; Mišić, Tijana

2015-05-01

This 1-year cohort study investigated stability and peri-implant marginal bone level of immediately loaded mini dental implants used to retain overdentures. Each of 30 edentulous patients received 4 mini dental implants (1.8 mm × 13 mm) in the interforaminal mandibular region. The implants were immediately loaded with pre-made overdentures. Outcome measures included implant stability and bone resorption. Implant stability was measured using the Periotest Classic(®) device immediately after placement and on the 3rd and 6th weeks and the 4th, 6th and 12th months postoperatively. The peri-implant marginal bone level (PIBL) was evaluated at the implant's mesial and distal sides from the polished platform to the marginal crest. Radiographs were taken using a tailored film holder to reproducibly position the X-ray tube at the 6th week, 4th and 12th months postoperatively. The primary stability (Periotest value, PTV) measured -0.27 ± 3.41 on a scale of -8 to + 50 (lower PTV reflects higher stability). The secondary stability decreased significantly until week 6 (mean PTV = 7.61 ± 7.05) then increased significantly reaching (PTV = 6.17 ± 6.15) at 12 months. The mean PIBL measured -0.40 mm after 1 year of functional loading, with no statistically significant differences at the various follow-ups (p = 0.218). Mini dental implants placed into the interforaminal region could achieve a favorable primary stability for immediate loading. The follow-up Periotest values fluctuated, apparently reflecting the dynamics of bone remodeling, with the implants remaining clinically stable (98.3%) after 1 year of function. The 1-year bone resorption around immediately loaded MDIs is within the clinically acceptable range for standard implants. Copyright © 2014 Elsevier GmbH. All rights reserved.

Improvement in bone properties by using risedronate adsorbed hydroxyapatite novel nanoparticle based formulation in a rat model of osteoporosis.

PubMed

Sahana, H; Khajuria, Deepak Kumar; Razdan, Rema; Mahapatra, D Roy; Bhat, M R; Suresh, Sarasija; Rao, R Ramachandra; Mariappan, L

2013-02-01

A superior drug formulation capable of achieving efficient osteogenesis is in imperative demand for the treatment of osteoporosis. In the present study we investigated the potential of using novel risedronate-hydroxyapatite (HA) nanoparticle based formulation in an animal model of established osteoporosis. Nanoparticles of HA loaded with risedronate (NHLR) of various sizes (80-130 nm) were generated for bone targeted drug delivery. Three months after ovariectomy, 36 ovariectomized (OVX) rats were divided into 6 equal groups and treated with various doses of NHLR (500, 350 and 250 microg/kg intravenous single dose) and sodium risedronate (500 microg/kg, intravenous single dose). Untreated OVX and sham OVX served as controls. One month after drug administration, the left tibia and femur were tested for bone mechanical properties and histology, respectively. In the right femur, bone density was measured by method based on Archimedes principle and bone porosity analyses were performed using X-ray imaging. NHLR (250 microg/kg) showed a significant increase in bone density and reduced bone porosity when compared with OVX control. Moreover, NHLR (250 microg/kg) significantly increased bone mechanical properties and bone quality when compared with OVX control. The results strongly suggest that the NHLR, which is a novel nanoparticle based formulation, has a therapeutic advantage over risedronate sodium monotherapy for the treatment of osteoporosis in a rat model of postmenopausal osteoporosis.

Application of Additive Manufacturing in Oral and Maxillofacial Surgery.

PubMed

Farré-Guasch, Elisabet; Wolff, Jan; Helder, Marco N; Schulten, Engelbert A J M; Forouzanfar, Tim; Klein-Nulend, Jenneke

2015-12-01

Additive manufacturing is the process of joining materials to create objects from digital 3-dimensional (3D) model data, which is a promising technology in oral and maxillofacial surgery. The management of lost craniofacial tissues owing to congenital abnormalities, trauma, or cancer treatment poses a challenge to oral and maxillofacial surgeons. Many strategies have been proposed for the management of such defects, but autogenous bone grafts remain the gold standard for reconstructive bone surgery. Nevertheless, cell-based treatments using adipose stem cells combined with osteoconductive biomaterials or scaffolds have become a promising alternative to autogenous bone grafts. Such treatment protocols often require customized 3D scaffolds that fulfill functional and esthetic requirements, provide adequate blood supply, and meet the load-bearing requirements of the head. Currently, such customized 3D scaffolds are being manufactured using additive manufacturing technology. In this review, 2 of the current and emerging modalities for reconstruction of oral and maxillofacial bone defects are highlighted and discussed, namely human maxillary sinus floor elevation as a valid model to test bone tissue-engineering approaches enabling the application of 1-step surgical procedures and seeding of Good Manufacturing Practice-level adipose stem cells on computer-aided manufactured scaffolds to reconstruct large bone defects in a 2-step surgical procedure, in which cells are expanded ex vivo and seeded on resorbable scaffolds before implantation. Furthermore, imaging-guided tissue-engineering technologies to predetermine the surgical location and to facilitate the manufacturing of custom-made implants that meet the specific patient's demands are discussed. The potential of tissue-engineered constructs designed for the repair of large oral and maxillofacial bone defects in load-bearing situations in a 1-step surgical procedure combining these 2 innovative approaches is particularly emphasized. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Participation in ball sports may represent a prehabilitation strategy to prevent future stress fractures and promote bone health in young athletes.

PubMed

Tenforde, Adam Sebastian; Sainani, Kristin Lynn; Carter Sayres, Lauren; Milgrom, Charles; Fredericson, Michael

2015-02-01

Sports participation has many benefits for the young athlete, including improved bone health. However, a subset of athletes may attain suboptimal bone health and be at increased risk for stress fractures. This risk is greater for female than for male athletes. In healthy children, high-impact physical activity has been shown to improve bone health during growth and development. We offer our perspective on the importance of promoting high-impact, multidirectional loading activities, including ball sports, as a method of enhancing bone quality and fracture prevention based on collective research. Ball sports have been associated with greater bone mineral density and enhanced bone geometric properties compared with participation in repetitive, low-impact sports such as distance running or nonimpact sports such as swimming. Runners and infantry who participated in ball sports during childhood were at decreased risk of future stress fractures. Gender-specific differences, including the coexistence of female athlete triad, may negate the benefits of previous ball sports on fracture prevention. Ball sports involve multidirectional loading with high ground reaction forces that may result in stiffer and more fracture-resistant bones. Encouraging young athletes to participate in ball sports may optimize bone health in the setting of adequate nutrition and in female athletes, eumenorrhea. Future research to determine timing, frequency, and type of loading activity could result in a primary prevention program for stress fracture injuries and improved life-long bone health. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Dependence of Long Bone Flexural Properties on Bone Mineral Distribution

NASA Technical Reports Server (NTRS)

Katz, BethAnn; Cleek, Tammy M.; Whalen, Robert T.; Connolly, James P. (Technical Monitor)

1995-01-01

The objective of this study is to assess whether a non-invasive determination of long bone cross-sectional areal properties using bone densitometry accurately estimates true long bone flexural properties. In this study, section properties of two pairs of human female embalmed tibiae were compared using two methods: special analysis of bone densitometry data, and experimental determination of flexural regidities from bone surface strain measurements during controlled loading.

Fabrication and anti-microbial evaluation of drug loaded polylactide space filler intended for ridge preservation following tooth extraction

PubMed Central

Thomas, Nebu George; Sanil, George P.; Rajmohan, Gopimohan; Prabhakaran, Jayachandran V.; Panda, Amulya K.

2011-01-01

Background: The preservation or reduction of alveolar ridge resorption following tooth extraction is important in patients especially for those intended for implants at a later stage. One way to achieve this is by using membranes, graft materials, and biodegradable space fillers to prevent alveolar bone resorption and promote regeneration. A major attraction for using biodegradable and biocompatible polymers as space fillers for ridge preservation is their safety profile in comparison to xenograft materials like lyophilized bone and collagen. Materials and Methods: Biocompatible polylactide space fillers were fabricated by fusing porous polylactide particles. The sponges were loaded with drugs by placing them in the respective solutions. Pseudomonas aeruginosa was isolated from a chronic periodontitis patient and in vitro anti-microbial evaluation was done with the drug loaded sponges. Results: Chlorhexidine loaded space filler showed significant anti microbial effect against multiple drug resistant Pseudomonas aeruginosa isolated from a patient with chronic periodontitis. Conclusion: The results of this study indicate that biodegradable drug releasing polylactide space fillers has the potential to be used for ridge preservation following tooth extraction. Release of drugs in the socket may prove useful in preventing development of alveolar osteitis post extraction which can interfere with normal healing of the socket. Synthetic biodegradable polymers also exhibit a controlled degradation rate to achieve complete resorption within the intended time. PMID:22028514

Tissue-engineered matrices as functional delivery systems: adsorption and release of bioactive proteins from degradable composite scaffolds.

PubMed

Cushnie, Emily K; Khan, Yusuf M; Laurencin, Cato T

2010-08-01

A tissue-engineered bone graft should imitate the ideal autograft in both form and function. However, biomaterials that have appropriate chemical and mechanical properties for grafting applications often lack biological components that may enhance regeneration. The concept of adding proteins such as growth factors to scaffolds has therefore emerged as a possible solution to improve overall graft design. In this study, we investigated this concept by loading porous hydroxyapatite-poly(lactide-co-glycolide) (HA-PLAGA) scaffolds with a model protein, cytochrome c, and then studying its release in a phosphate-buffered saline solution. The HA-PLAGA scaffold has previously been shown to be bioactive, osteoconductive, and to have appropriate physical properties for tissue engineering applications. The loading experiments demonstrated that the HA-PLAGA scaffold could also function effectively as a substrate for protein adsorption and release. Scaffold protein adsorptive loading (as opposed to physical entrapment within the matrix) was directly related to levels of scaffold HA-content. The HA phase of the scaffold facilitated protein retention in the matrix following incubation in aqueous buffer for periods up to 8 weeks. Greater levels of protein retention time may improve the protein's effective activity by increasing the probability for protein-cell interactions. The ability to control protein loading and delivery simply via composition of the HA-PLAGA scaffold offers the potential of forming robust functionalized bone grafts. (c) 2010 Wiley Periodicals, Inc.

Fortified tuna bone powder supplementation increases bone mineral density of lactating rats and their offspring.

PubMed

Suntornsaratoon, Panan; Charoenphandhu, Narattaphol; Krishnamra, Nateetip

2018-03-01

Breastfeeding leads to bone calcium loss for milk production, resulting in progressive maternal osteopenia. Calcium supplement from natural sources has been postulated to be more beneficial to bone health than purified CaCO 3 because natural sources also contain other nutrients such as certain amino acids that might enhance calcium metabolism. Herein, we examined the effect of calcium supplementation from tuna bone powder and CaCO 3 on bones of dams and the offspring. Both forms of calcium supplement, i.e. tuna bone powder and CaCO 3 , increased maternal bone mineral density (BMD). However, bone histomorphometry revealed that only tuna bone had beneficial effect on maternal bone microstructure, i.e. increased bone formation, decreased bone resorption and increased in bone volume. Regarding the mechanical properties, the decreased ultimate load in non-supplement lactating mothers was restored to the load seen in nulliparous animals by calcium supplementation. Moreover, both tuna bone and CaCO 3 supplementation in mothers led to increased milk calcium concentration and consequently increased BMD in the growing offspring. Calcium supplement from tuna bone powder was effective in preventing maternal osteopenia. Tuna bone, which is a readily available fishing industrial waste, is a good alternative source of calcium supplement that increases BMD in both lactating mothers and the neonates. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Displacement of dental implants in trabecular bone under a static lateral load in fresh bovine bone.

PubMed

Engelke, Wilfried; Müller, Alois; Decco, Oscar A; Rau, María J; Cura, Andrea C; Ruscio, Mara L; Knösel, Michael

2013-04-01

The study aims to provide objective data for the displacement of titanium screw implants in trabecular bone specimens. One hundred Semados implants (Bego, Bremen, Germany) were inserted in bovine type IV bone specimens. All implants had a diameter of 3.75 mm; 50 implants had a length of 8.5 mm and 50 implants had a length of 15 mm. Insertion torque was determined at intervals of 10, 20, and 30 Ncm. Implants were loaded horizontally with 10, 20, and 30 N for 2 seconds. An indicator strip was attached to the implant abutment to allow direct observation of implant movement relative to the bone surface. Horizontal displacement was assessed with an accuracy of measurement of 10 µm. Seven implants got lost by visible loosening. Degree of displacement was subject to evaluation with all others. Those implants showed a mean displacement of 59 µm for 10 N (n = 100), 173 µm for 20 N (n = 99), and 211 µm for 30 N (n = 93). The mean displacement of 15-mm implants (16, 37, 51 µm) was significantly lower compared with 8.5-mm implants (103, 311, 396 µm) corresponding to 10, 20, and 30 N as lateral loads. Displacement of screw implants in trabecular bone can be detected and visualized using commercially available endoscopes with a high magnification. A lateral load of 20 N indicates a mean displacement of over 100 µm and therefore results in a critical displacement. © 2011 Wiley Periodicals, Inc.