Monitoring the mechanical properties of healing bone.

PubMed

Claes, L E; Cunningham, J L

2009-08-01

Fracture healing is normally assessed through an interpretation of radiographs, clinical evaluation, including pain on weight bearing, and a manual assessment of the mobility of the fracture. These assessments are subjective and their accuracy in determining when a fracture has healed has been questioned. Viewed in mechanical terms, fracture healing represents a steady increase in strength and stiffness of a broken bone and it is only when these values are sufficiently high to support unrestricted weight bearing that a fracture can be said to be healed. Information on the rate of increase of the mechanical properties of a healing bone is therefore valuable in determining both the rate at which a fracture will heal and in helping to define an objective and measurable endpoint of healing. A number of techniques have been developed to quantify bone healing in mechanical terms and these are described and discussed in detail. Clinical studies, in which measurements of fracture stiffness have been used to identify a quantifiable end point of healing, compare different treatment methods, predictably determine whether a fracture will heal, and identify factors which most influence healing, are reviewed and discussed.

Fracture healing using degradable magnesium fixation plates and screws.

PubMed

Chaya, Amy; Yoshizawa, Sayuri; Verdelis, Kostas; Noorani, Sabrina; Costello, Bernard J; Sfeir, Charles

2015-02-01

Internal bone fixation devices made with permanent metals are associated with numerous long-term complications and may require removal. We hypothesized that fixation devices made with degradable magnesium alloys could provide an ideal combination of strength and degradation, facilitating fracture fixation and healing while eliminating the need for implant removal surgery. Fixation plates and screws were machined from 99.9% pure magnesium and compared with titanium devices in a rabbit ulnar fracture model. Magnesium device degradation and the effect on fracture healing and bone formation were assessed after 4 weeks. Fracture healing with magnesium device fixation was compared with that of titanium devices using qualitative histologic analysis and quantitative histomorphometry. Micro-computed tomography showed device degradation after 4 weeks in vivo. In addition, 2-dimensional micro-computed tomography slices and histologic staining showed that magnesium degradation did not inhibit fracture healing or bone formation. Histomorphology showed no difference in bone-bridging fractures fixed with magnesium and titanium devices. Interestingly, abundant new bone was formed around magnesium devices, suggesting a connection between magnesium degradation and bone formation. Our results show potential for magnesium fixation devices in a loaded fracture environment. Furthermore, these results suggest that magnesium fixation devices may enhance fracture healing by encouraging localized new bone formation. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Bone Marrow Aspirate Concentrate in Animal Long Bone Healing: An Analysis of Basic Science Evidence.

PubMed

Gianakos, Arianna; Ni, Amelia; Zambrana, Lester; Kennedy, John G; Lane, Joseph M

2016-01-01

Long bone fractures that fail to heal or show a delay in healing can lead to increased morbidity. Bone marrow aspirate concentrate (BMAC) containing bone mesenchymal stem cells (BMSCs) has been suggested as an autologous biologic adjunct to aid long bone healing. The purpose of this study was to systematically review the basic science in vivo evidence for the use of BMAC with BMSCs in the treatment of segmental defects in animal long bones. The PubMed/MEDLINE and EMBASE databases were screened in July 14-25, 2014. The following search criteria were used: [("bmac" OR "bone marrow aspirate concentrate" OR "bmc" OR "bone marrow concentrate" OR "mesenchymal stem cells") AND ("bone" OR "osteogenesis" OR "fracture healing" OR "nonunion" OR "delayed union")]. Three authors extracted data and analyzed for trends. Quality of evidence score was given to each study. Results are presented as Hedge G standardized effect sizes with 95% confidence intervals. The search yielded 35 articles for inclusion. Of studies reporting statistics, 100% showed significant increase in bone formation in the BMAC group on radiograph. Ninety percent reported significant improvement in earlier bone healing on histologic/histomorphometric assessment. Eighty-one percent reported a significant increase in bone area on micro-computed tomography. Seventy-eight percent showed a higher torsional stiffness for the BMAC-treated defects. In the in vivo studies evaluated, BMAC confer beneficial effects on the healing of segmental defects in animal long bone models when compared with a control. Proof-of-concept has been established for BMAC in the treatment of animal segmental bone defects.

Efficacy of Various Analgesics on Shoulder Function and Rotator Cuff Tendon-to-Bone Healing in a Rat (Rattus norvegicus) Model

PubMed Central

Caro, Adam C; Tucker, Jennica J; Yannascoli, Sarah M; Dunkman, Andrew A; Thomas, Stephen J; Soslowsky, Louis J

2014-01-01

Although relief of postoperative pain is an imperative aspect of animal welfare, analgesics that do not interfere with the scientific goals of the study must be used. Here we compared the efficacy of different analgesic agents by using an established rat model of supraspinatus tendon healing and a novel gait-analysis system. We hypothesized that different analgesic agents would all provide pain relief in this model but would cause differences in tendon-to-bone healing and gait parameters. Buprenorphine, ibuprofen, tramadol–gabapentin, and acetaminophen were compared with a no-analgesia control group. Gait measures (stride length and vertical force) on the operative forelimb differed between the control group and both the buprenorphine (2 and 4 d postsurgery) and ibuprofen (2 d postsurgery) groups. Step length was different in the control group as compared with the tramadol–gabapentin (2 d after surgery), buprenorphine (2 and 4 d after surgery), and ibuprofen (2 d after surgery) groups. Regarding tendon-to-bone healing, the ibuprofen group showed less stiffness at the insertion site; no other differences in tendon-to-bone healing were detected. In summary, the analgesics evaluated were associated with differences in both animal gait and tendon-to-bone healing. This information will be useful for improving the management of postsurgical pain without adversely affecting tissue healing. Given its ability to improve gait without impeding healing, we recommend use of buprenorphine for postsurgical pain management in rats. In addition, our gait-analysis system can be used to evaluate new analgesics. PMID:24602546

Use of the Er:YAG laser for improved plating in maxillofacial surgery: comparison of bone healing in laser and drill osteotomies.

PubMed

Lewandrowski, K U; Lorente, C; Schomacker, K T; Flotte, T J; Wilkes, J W; Deutsch, T F

1996-01-01

Surgical reconstruction of bony defects in the maxillofacial region involves fixation of bony fragments with mini and micro plates. Bone stabilization during hole drilling is often challenging due to the need to apply pressure when using a conventional mechanical Hall drill. In addition, fragmentation of the fragile bones may occur and complicate the reconstruction. The pulsed Er:YAG laser offers an attractive alternative drilling modality because it does not require physical contact with the bone in order to drill holes, cuts bone with minimal thermal damage, and allows precise control of bone cutting. The objective of this study was to investigate the pulsed Er:YAG laser as an alternative to the mechanical bur by comparing bone healing using both modalities. Bone healing in an inferior border defect of the rat mandible was examined using either an Er:YAG laser or a mechanical bur for drilling. The healing of osteotomies in facial bones and of screw holes for plate stabilization of free bone fragments was studied. All defects healed by 4 weeks postoperatively. Histologic evaluation demonstrated no difference in the amount of newly formed woven bone at the osteotomy site or screw holes made by either the laser or the drill. The extent of thermal damage at the osteotomy sites was comparable in laser and mechanically cut bone fragments. On the basis of this study we suggest that the Er: YAG laser can be used clinically in thin, fragile bones in the maxillofacial region.

Differences of bone healing in metaphyseal defect fractures between osteoporotic and physiological bone in rats.

PubMed

Thormann, Ulrich; El Khawassna, Thaqif; Ray, Seemun; Duerselen, Lutz; Kampschulte, Marian; Lips, Katrin; von Dewitz, Helena; Heinemann, Sascha; Heiss, Christian; Szalay, Gabor; Langheinrich, Alexander C; Ignatius, Anita; Schnettler, Reinhard; Alt, Volker

2014-03-01

Discrepancies in bone healing between osteoporotic and non-osteoporotic bone remain uncertain. The focus of the current work is to evaluate potential healing discrepancies in a metaphyseal defect model in rat femora. Female Sprague-Dawley rats were either ovariectomized (OVX, n=14) and combined with a calcium-, phosphorus- and vitamin D3-, soy- and phytoestrogen-free diet or received SHAM operation with standard diet rat (SHAM, n=14). Three months post-ovariectomy, DEXA measurement showed a reduction of bone mineral density reflecting an osteoporotic bone status in OVX rats. Rats then underwent a 3 mm wedge-shaped osteotomy at the distal metaphyseal area of the left femur stabilized with a T-shaped mini-plate and allowed to heal for 6 weeks. Biomechanical competence by means of a non-destructive three-point bending test showed significant lower flexural rigidity in the OVX rats at 3 mm lever span compared to SHAM animals (p=0.048) but no differences at 10 mm lever span. Microcomputer tomography (μCT) showed bridging cortices and consolidation of the defect in both groups, however, no measurable differences were found in either total ossified tissue or vascular volume fraction. Furthermore, histology showed healing discrepancies that were characterized by cartilaginous remnant and more unmineralized tissue presence in the OVX rats compared to more mature consolidation appearance in the SHAM group. In summary, bone defect healing in metaphyseal bone slightly differs between osteoporotic and non-osteoporotic bone in the current 3 mm defect model in both 3mm lever span biomechanical testing and histology. Copyright © 2013 Elsevier Ltd. All rights reserved.

Specific Biomimetic Hydroxyapatite Nanotopographies Enhance Osteoblastic Differentiation and Bone Graft Osteointegration

PubMed Central

Loiselle, Alayna E.; Wei, Lai; Faryad, Muhammad; Paul, Emmanuel M.; Lewis, Gregory S.; Gao, Jun; Lakhtakia, Akhlesh

2013-01-01

Impaired healing of cortical bone grafts represents a significant clinical problem. Cadaveric bone grafts undergo extensive chemical processing to decrease the risk of disease transmission; however, these processing techniques alter the bone surface and decrease the osteogenic potential of cells at the healing site. Extensive work has been done to optimize the surface of bone grafts, and hydroxyapatite (HAP) and nanotopography both increase osteoblastic differentiation. HAP is the main mineral component of bone and can enhance osteoblastic differentiation and bone implant healing in vivo, while nanotopography can enhance osteoblastic differentiation, adhesion, and proliferation. This is the first study to test the combined effects of HAP and nanotopographies on bone graft healing. With the goal of identifying the optimized surface features to improve bone graft healing, we tested the hypothesis that HAP-based nanotopographic resurfacing of bone grafts improves integration of cortical bone grafts by enhancing osteoblastic differentiation. Here we show that osteoblastic cells cultured on processed bones coated with specific-scale (50–60 nm) HAP nanotopographies display increased osteoblastic differentiation compared to cells on uncoated bone, bones coated with poly-l-lactic acid nanotopographies, or other HAP nanotopographies. Further, bone grafts coated with 50–60-nm HAP exhibited increased formation of new bone and improved healing, with mechanical properties equivalent to live autografts. These data indicate the potential for specific HAP nanotopographies to not only increase osteoblastic differentiation but also improve bone graft incorporation, which could significantly increase patient quality of life after traumatic bone injuries or resection of an osteosarcoma. PMID:23510012

Bilateral first rib anomalous articulations with pseudarthroses mimicking healing fractures in an infant with abusive head injury.

PubMed

Pasquale-Styles, Melissa A; Crowder, Christian M; Fridie, Jeannette; Milla, Sarah S

2014-11-01

Bilateral symmetric bone nodules were observed in the anterolateral first ribs of an infant with shaking injuries at autopsy. The location prompted diagnostic considerations of healing fractures versus anomalous articulations with pseudarthroses. The forensic pathologist worked with forensic anthropologists and pediatric radiologists to evaluate autopsy findings and compare premortem and postmortem X-rays. Gross examination of the bones by the pathologist and anthropologists confirmed bilateral, callus-like bone nodules in first-rib locations associated with pseudarthroses. Histologic examination of one of the bones further showed features most consistent with pseudarthrosis, not a healing fracture. Radiologists then compared multiple premortem and postmortem radiographs that showed no remodeling of the bone over a 2-week interval between the time of injury and death, which would be unexpected for a healing fracture in an infant. This multidisciplinary approach resulted in the appropriate diagnosis of pseudarthroses due to anomalous articulations, an uncommon finding in forensic pathology. © 2014 American Academy of Forensic Sciences.

Emulating Native Periosteum Cell Population and Subsequent Paracrine Factor Production To Promote Tissue Engineered Periosteum-Mediated Allograft Healing

PubMed Central

Hoffman, Michael D.

2015-01-01

Emulating autograft healing within the context of decellularized bone allografts has immediate clinical applications in the treatment of critical-sized bone defects. The periosteum, a thin, osteogenic tissue that surrounds bone, houses a heterogeneous population of stem cells and osteoprogenitors. There is evidence that periosteum-cell derived paracrine factors, specifically vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2), orchestrate autograft healing through host cell recruitment and subsequent tissue elaboration. In previous work, we demonstrated that the use of poly(ethylene glycol) (PEG) hydrogels as a tissue engineered (T.E.) periosteum to localize mesenchymal stem cells (MSCs) to the surface of decellularized bone enhances allograft healing and integration. Herein, we utilize a mixed population of 50:50 MSCs and osteoprogenitor cells to better mimic native periosteum cell population and paracrine factor production to further promote allograft healing. This mixed cell population was localized to the surface of decellularized allografts within degradable hydrogels and shown to expedite allograft healing. Specifically, bone callus formation and biomechanical graft-host integration are increased as compared to unmodified allografts. These results demonstrate the dual importance of periosteum-mediated paracrine factors orchestrating host cell recruitment as well as new bone formation while developing clinically translatable strategies for allograft healing and integration. PMID:25818449

Spatially offset raman spectroscopy for non-invasive assessment of fracture healing

NASA Astrophysics Data System (ADS)

Ding, Hao; Lu, Guijin; West, Christopher; Gogola, Gloria; Kellam, James; Ambrose, Catherine; Bi, Xiaohong

2016-02-01

Fracture non-unions and bone re-fracture are common challenges for post-fracture management. To achieve better prognosis and treatment evaluation, it is important to be able to assess the quality of callus over the time course of healing. This study evaluated the potential of spatially offset Raman spectroscopy for assessing the fracture healing process in situ. We investigated a rat model of fracture healing at two weeks and 4 weeks post fracture with a fractured femur and a contralateral control in each animal. Raman spectra were collected from the depilated thighs on both sides transcutaneously in situ with various source/detection offsets. Bone signals were recovered from SORS spectra, and then compared with those collected from bare bones. The relative intensity of mineral from fractured bone was markedly decreased compared to the control. The fractured bones demonstrated lower mineral and carbonate level and higher collagen content in the callus at the early time point. Compared to week 2, collagen mineralization and mineral carbonation increased at 4 weeks post fracture. Similarly, the material properties of callus determined by reference point indentation also increased in the 4-week group, indicating improved callus quality with time. The results from Raman analysis are in agreement with radiographic and material testing, indicating the potential of this technique in assessing fracture healing in vivo.

Mechanical induction of critically delayed bone healing in sheep: radiological and biomechanical results.

PubMed

Schell, Hanna; Thompson, Mark S; Bail, Hermann J; Hoffmann, Jan-Erik; Schill, Alexander; Duda, Georg N; Lienau, Jasmin

2008-10-20

This study aimed to mechanically produce a standardized ovine model for a critically delayed bone union. A tibial osteotomy was stabilized with either a rigid (group I) or mechanically critical (group II) external fixator in sheep. Interfragmentary movements and ground reaction forces were monitored throughout the healing period of 9 weeks. After sacrifice at 6 weeks, 9 weeks and 6 months, radiographs were taken and the tibiae were examined mechanically. Interfragmentary movements were considerably larger in group II throughout the healing period. Unlike group I, the operated limb in group II did not return to full weight bearing during the treatment period. Radiographic and mechanical observations showed significantly inferior bone healing in group II at 6 and 9 weeks compared to group I. After 6 months, five sheep treated with the critical fixator showed radiological bridging of the osteotomy, but the biomechanical strength of the repair was still inferior to group I at 9 weeks. The remaining three animals had even developed a hypertrophic non-union. In this study, mechanical instability was employed to induce a critically delayed healing model in sheep. In some cases, this approach even led to the development of a hypertrophic non-union. The mechanical induction of critical bone healing using an external fixation device is a reasonable attempt to investigate the patho-physiological healing cascade without suffering from any biological intervention. Therefore, the presented ovine model provides the basis for a comparative evaluation of mechanisms controlling delayed and standard bone healing.

Comparison of bone healing and outcomes between allogenous bone chip and hydroxyapatite chip grafts in open wedge high tibial osteotomy.

PubMed

Lee, O-Sung; Lee, Kyung Jae; Lee, Yong Seuk

2017-11-03

Allogenous bone chips and hydroxyapatite (HA) chips have been known as good options for filling an inevitable void after open wedge high tibial osteotomy (OWHTO). However, there are concerns regarding bone healing after the use of these grafts. The purpose of this study was to compare the bone healing represented by the osteoconductivity and absorbability between allogenous bone chips and HA chips in OWHTO. The outcomes of bone healing of 53 patients who received an allogenous bone chip graft and 41 patients who received an HA chip graft were retrospectively evaluated, and the results were compared between the two groups. Osteoconductivity and absorbability were serially evaluated for the assessment of bone healing at 6 weeks, 3 months, 6 months, and 1 year postoperatively. The osteoconductivity of the allogenous bone chips was greater than that of the HA chips at 6 weeks postoperatively (p < 0.05). However, there were no statistically significant differences from 3 months to 1 year postoperatively. The absorbability showed no statistically significant differences 6 weeks and 3 months after OWHTO; however, the allogenous bone chip group showed a greater absorbability at 6 months and 1 year postoperatively (42.8 ± 14.2 vs. 34.6 ± 13.8, p = 0.006 at 6 months postoperatively; 54.6 ± 14.4 vs. 43.0 ± 14.0, p < 0.001 at 1 year postoperatively). However, the two graft materials showed similar results of HKA angle, WBL ratio, posterior tibial slope.

Assessment of Regeneration of Bone in the Extracted Third Molar Sockets Augmented Using Xenograft (CollaPlugTN Zimmer) in Comparison with the Normal Healing on the Contralateral Side.

PubMed

Ranganathan, Murugan; Balaji, M; Krishnaraj, R; Narayanan, Vivek; Thangavelu, Annamalai

2017-11-01

Alveolar bone resorption is a significant clinical problem. Bone loss in third molar region following extraction or surgical removal not only leads to periodontal problems in second molar region but also it may lead to some serious problems like increased incidence of angle fractures. In order to reduce the risks following third molar surgery, the socket should be augmented with bone grafts. In recent days guided tissue regeneration is the most accepted and successful technique followed many authors and its efficacy has been proved. Based upon our clinical experience, the use of bio absorbable collagen wound dressing such as CollaPlug TN has achieved quick healing and more primary wound coverage. Amongst the graft materials collagen is preferable due to its high biocompatibility and hemostatic ability. This study was done to assess the regeneration of bone in the extracted third molar sockets using xenograft (CollaPlug TN -Zimmer) which was compared with the normal healing on the contra lateral side. The assessment was done to analyze post-operative healing complications and to compare the bone density formed between control site and implant site radiologically. On this basis of this study, the use of collaplugTN appears to be beneficial to the patient in postoperative wound healing and also for better bone formation. The use of this material was advantageous because of its simplicity of application cost effectiveness and availability. There is enhanced wound healing and early bone formation.

Bone sialoprotein, but not osteopontin, deficiency impairs the mineralization of regenerating bone during cortical defect healing.

PubMed

Monfoulet, Laurent; Malaval, Luc; Aubin, Jane E; Rittling, Susan R; Gadeau, Alain P; Fricain, Jean-Christophe; Chassande, Olivier

2010-02-01

Bone healing is a complex multi-step process, which depends on the position and size of the lesion, and on the mechanical stability of the wounded area. To address more specifically the mechanisms involved in cortical bone healing, we created drill-hole defects in the cortex of mouse femur, a lesion that triggers intramembranous repair, and compared the roles of bone sialoprotein (BSP) and osteopontin (OPN), two proteins of the extracellular matrix, in the repair process. Bone regeneration was analyzed by ex vivo microcomputerized X-ray tomography and histomorphometry of bones of BSP-deficient, OPN-deficient and wild-type mice. In all mouse strains, the cortical gap was bridged with woven bone within 2 weeks and no mineralized tissue was observed in the marrow. Within 3 weeks, lamellar cortical bone filled the gap. The amount and degree of mineralization of the woven bone was not affected by OPN deficiency, but cortical bone healing was delayed in BSP-deficient mice due to delayed mineralization. Gene expression studies showed a higher amount of BSP transcripts in the repair bone of OPN-deficient mice, suggesting a possible compensation of OPN function by BSP in OPN-null mice. Our data suggest that BSP, but not OPN, plays a role in primary bone formation and mineralization of newly formed bone during the process of cortical bone healing. (c) 2009 Elsevier Inc. All rights reserved.

Are bone turnover markers capable of predicting callus consolidation during bone healing?

PubMed

Klein, P; Bail, H J; Schell, H; Michel, R; Amthauer, H; Bragulla, H; Duda, G N

2004-07-01

The aim of this study was to determine the ability of the following bone turnover markers to monitor the course of callus consolidation during bone healing: Carboxy-terminal propeptide of procollagen type I (PICP), skeletal alkaline phosphatase (sALP), and amino-terminal propeptide of type III procollagen (PIlINP). Since interfragmentary movements have been proven to possess the ability to document the progression of bone healing in experimental studies, correlations between bone turnover markers and interfragmentary movements in vivo were investigated. Therefore, two different types of osteosyntheses representing different mechanical situations at the fracture site were compared in an ovine osteotomy model. Blood samples were taken preoperatively and postoperatively in weekly intervals over a nine-week healing period. At the same intervals, interfragmentary movements were measured in all sheep. After nine weeks, animals were sacrificed and the tibiae were evaluated both mechanically and histologically. Wide interindividual ranges were observed for all bone turnover markers. The systemic PICP level did not increase with callus consolidation. The bone-healing model seemed to influence the systemic level of PIIINP and sALP but no general correlation between bone turnover markers and interfragmentary movements could be detected. No differences between the different types of osteosyntheses and thus the different mechanical situations were observed. All analyzed markers failed as general predictors for the course of callus consolidation during bone healing.

Hypochlorhydria-induced calcium malabsorption does not affect fracture healing but increases post-traumatic bone loss in the intact skeleton.

PubMed

Haffner-Luntzer, Melanie; Heilmann, Aline; Heidler, Verena; Liedert, Astrid; Schinke, Thorsten; Amling, Michael; Yorgan, Timur Alexander; Vom Scheidt, Annika; Ignatius, Anita

2016-11-01

Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk because calcium absorption is dependent on gastric pH. We investigated fracture healing and post-traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr-/- mice display hypochlorhydria, calcium malabsorption, and osteopenia. Cckbr-/- and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium-enriched diet. Healed and intact bones were assessed by biomechanical testing, histomorphometry, micro-computed tomography, and quantitative backscattering. Parathyroid hormone (PTH) serum levels were determined by enzyme-linked immunosorbent assay. Fracture healing was unaffected in Cckbr-/- mice. However, Cckbr-/- mice displayed increased calcium mobilization from the intact skeleton during bone healing, confirmed by significantly elevated PTH levels and osteoclast numbers compared to WT mice. Calcium supplementation significantly reduced secondary hyperparathyroidism and bone resorption in the intact skeleton in both genotypes, but more efficiently in WT mice. Furthermore, calcium administration improved bone healing in WT mice, indicated by significantly increased mechanical properties and bone mineral density of the fracture callus, whereas it had no significant effect in Cckbr-/- mice. Therefore, under conditions of hypochlorhydria-induced calcium malabsorption, calcium, which is essential for callus mineralization, appears to be increasingly mobilized from the intact skeleton in favor of fracture healing. Calcium supplementation during fracture healing prevented systemic calcium mobilization, thereby maintaining bone mass and improving fracture healing in healthy individuals whereas the effect was limited by gastric hypochlorhydria. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1914-1921, 2016. © 2016 The Authors. Journal of Orthopaedic Research Published by by Wiley Periodicals, Inc.

A review of the physiological and histological effects of laser osteotomy.

PubMed

Rajitha Gunaratne, G D; Khan, Riaz; Fick, Daniel; Robertson, Brett; Dahotre, Narendra; Ironside, Charlie

2017-01-01

Osteotomy is the surgical cutting of bone. Some obstacles to laser osteotomy have been melting, carbonisation and subsequent delayed healing. New cooled scanning techniques have resulted in effective bone cuts without the strong thermal side effects, which were observed by inappropriate irradiation techniques with continuous wave and long pulsed lasers. With these new techniques, osteotomy gaps histologically healed with new bone formation without any noticeable or minimum thermal damage. No significant cellular differences in bone healing between laser and mechanical osteotomies were noticed. Some studies even suggest that the healing rate may be enhanced following laser osteotomy compared to conventional mechanical osteotomy. Additional research is necessary to evaluate different laser types with appropriate laser setting variables to increase ablation rates, with control of depth, change in bone type and damage to adjacent soft tissue. Laser osteotomy has the potential to become incorporated into the armamentarium of bone surgery.

Analysis of fracture healing in osteopenic bone caused by disuse: experimental study.

PubMed

Paiva, A G; Yanagihara, G R; Macedo, A P; Ramos, J; Issa, J P M; Shimano, A C

2016-03-01

Osteoporosis has become a serious global public health issue. Hence, osteoporotic fracture healing has been investigated in several previous studies because there is still controversy over the effect osteoporosis has on the healing process. The current study aimed to analyze two different periods of bone healing in normal and osteopenic rats. Sixty, 7-week-old female Wistar rats were randomly divided into four groups: unrestricted and immobilized for 2 weeks after osteotomy (OU2), suspended and immobilized for 2 weeks after osteotomy (OS2), unrestricted and immobilized for 6 weeks after osteotomy (OU6), and suspended and immobilized for 6 weeks after osteotomy (OS6). Osteotomy was performed in the middle third of the right tibia 21 days after tail suspension, when the osteopenic condition was already set. The fractured limb was then immobilized by orthosis. Tibias were collected 2 and 6 weeks after osteotomy, and were analyzed by bone densitometry, mechanical testing, and histomorphometry. Bone mineral density values from bony calluses were significantly lower in the 2-week post-osteotomy groups compared with the 6-week post-osteotomy groups (multivariate general linear model analysis, P<0.000). Similarly, the mechanical properties showed that animals had stronger bones 6 weeks after osteotomy compared with 2 weeks after osteotomy (multivariate general linear model analysis, P<0.000). Histomorphometry indicated gradual bone healing. Results showed that osteopenia did not influence the bone healing process, and that time was an independent determinant factor regardless of whether the fracture was osteopenic. This suggests that the body is able to compensate for the negative effects of suspension.

The use of a magnesium-based bone adhesive for flexor tendon-to-bone healing

PubMed Central

Stavros, Thomopoulos; Emmanouil, Zampiakis; Rosalina, Das; Hyun-Min, Kim; J., Silva, Matthew; Necat, Havlioglu; H., Gelberman, Richard

2010-01-01

Purpose Our previous studies in a canine animal model demonstrated that the flexor tendon-to-bone insertion site has a poor capacity to heal. Magnesium based adhesives have the potential to improve tendon-to-bone healing. Therefore, we hypothesized that magnesium based bone adhesive (MBA) will improve the tendon-to-bone biomechanical properties initially and in the early period after repair. Methods Flexor digitorum profundus tendons were injured and repaired into bone tunnels in the distal phalanges of dogs. The bone tunnels were either filled with MBA prior to completing the repair or left empty (CTL). Histologic appearance, tensile properties, range of motion, and bone density were examined at time zero and 21 days after the repair. Results There was no histologic evidence of acute inflammation. There appeared to be more mast cells in the MBA group than in the CTL group. Chronic inflammatory infiltrate and fibrosis was slightly higher in the MBA group compared to the CTL group. Tensile properties at time zero were significantly higher in the MBA group compared to the CTL group. However, tensile properties were significantly lower in the MBA group compared to the CTL group at 21 days. Range of motion and bone density were significantly lower in the MBA and CTL groups compared to normal (i.e., uninjured) at 21 days; no differences were seen when comparing MBA to CTL. Conclusions We found that the initial biomechanical properties of flexor tendon-to-bone repairs can be improved with MBA. However, MBA use in vivo led to a decrease in the biomechanical properties of the repair. There was no effect of MBA on bone density or range of motion in the early period after repair. Our histologic analysis suggests that the poor healing in the MBA group may have been due to an allergic response or to increased chronic inflammation due to the foreign material. PMID:19643291

Healing bone lesion defects using injectable CaSO4 /CaPO4 -TCP bone graft substitute compared to cancellous allograft bone chips in a canine model.

PubMed

Hall, Deborah J; Turner, Thomas M; Urban, Robert M

2018-04-16

CaSO 4 /CaPO 4 -TCP bone graft substitute has been shown to be effective for treatment of bone lesion defects, but its mechanical, histological, and radiographic characteristics have not been studied in direct comparison with a conventional treatment such as cancellous allograft bone. Thirteen canines had a critical-size axial defect created bilaterally into the proximal humerus. CaSO 4 /CaPO 4 -TCP bone graft substitute (PRO-DENSE™, Wright Medical Technology) was injected into the defect in one humerus, and an equal volume of freeze-dried cancellous allograft bone chips was placed in the contralateral defect. The area fraction of new bone, residual graft, and fibrous tissue and the compressive strength and elastic modulus of bone within the defects were determined after 6, 13, or 26 weeks and correlated with radiographic changes. The data were analyzed using Friedman and Mann-Whitney tests. There was more bone in defects treated with the CaSO 4 /CaPO 4 -TCP bone graft substitute compared to defects treated with cancellous bone allograft at all three time points, and the difference at 13 weeks was significant (p = 0.025). The new bone was significantly stronger and stiffer in defects treated with the CaSO 4 /CaPO 4 -TCP bone graft substitute compared to defects treated with cancellous bone allograft at 13 (p = 0.046) and 26 weeks (p = 0.025). At 26 weeks, all defects treated with CaSO 4 /CaPO 4 -TCP bone graft substitute demonstrated complete healing with new bone, whereas healing was incomplete in all defects treated with cancellous allograft chips. The CaSO 4 /CaPO 4 -TCP bone graft substitute could provide faster and significantly stronger healing of bone lesions compared to the conventional treatment using freeze-dried cancellous allograft bone. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc.

Extracorporeal shock wave therapy in treatment of delayed bone-tendon healing.

PubMed

Wang, Lin; Qin, Ling; Lu, Hong-bin; Cheung, Wing-hoi; Yang, Hu; Wong, Wan-nar; Chan, Kai-ming; Leung, Kwok-sui

2008-02-01

Extracorporeal shock wave therapy is indicated for treatment of chronic injuries of soft tissues and delayed fracture healing and nonunion. No investigation has been conducted to study the effect of shock wave on delayed healing at the bone-tendon junction. Shock wave promotes osteogenesis, regeneration of fibrocartilage zone, and remodeling of healing tissue in delayed healing of bone-tendon junction surgical repair. Controlled laboratory study. Twenty-eight mature rabbits were used for establishing a delayed healing model at the patella-patellar tendon complex after partial patellectomy and then divided into control and shock wave groups. In the shock wave group, a single shock wave treatment was given at week 6 postoperatively to the patella-patellar tendon healing complex. Seven samples were harvested at week 8 and 7 samples at week 12 for radiologic, densitometric, histologic, and mechanical evaluations. Radiographic measurements showed 293.4% and 185.8% more new bone formation at the patella-patellar tendon healing junction in the shock wave group at weeks 8 and 12, respectively. Significantly better bone mineral status was found in the week 12 shock wave group. Histologically, the shock wave group showed more advanced remodeling in terms of better alignment of collagen fibers and thicker and more mature regenerated fibrocartilage zone at both weeks 8 and 12. Mechanical testing showed 167.7% and 145.1% higher tensile load and strength in the shock wave group at week 8 and week 12, respectively, compared with controls. Extracorporeal shock wave promotes osteogenesis, regeneration of fibrocartilage zone, and remodeling in the delayed bone-to-tendon healing junction in rabbits. These results provide a foundation for future clinical studies toward establishment of clinical indication for treatment of delayed bone-to-tendon junction healing.

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

Medicarpin, a Natural Pterocarpan, Heals Cortical Bone Defect by Activation of Notch and Wnt Canonical Signaling Pathways

PubMed Central

Gupta, Chandra Prakash; Kureel, Jyoti; Mansoori, Mohd Nizam; Shukla, Priyanka; John, Aijaz A.; Singh, Kavita; Purohit, Dipak; Awasthi, Pallavi; Singh, Divya; Goel, Atul

2015-01-01

We evaluated the bone regeneration and healing effect of Medicarpin (med) in cortical bone defect model that heals by intramembranous ossification. For the study, female Sprague–Dawley rats were ovariectomized and rendered osteopenic. A drill hole injury was generated in mid femoral bones of all the animals. Med treatment was commenced the day after and continued for 15 days. PTH was taken as a reference standard. Fifteen days post-treatment, animals were sacrificed. Bones were collected for histomorphometry studies at the injury site by micro-computed tomography (μCT) and confocal microscopy. RNA and protein was harvested from newly generated bone. For immunohistochemistry, 5μm sections of decalcified femur bone adjoining the drill hole site were cut. By μCT analysis and calcein labeling of newly generated bone it was found that med promotes bone healing and new bone formation at the injury site and was comparable to PTH in many aspects. Med treatment led to increase in the Runx-2 and osteocalcin signals indicating expansion of osteoprogenitors at the injury site as evaluated by qPCR and immunohistochemical localization. It was observed that med promoted bone regeneration by activating canonical Wnt and notch signaling pathway. This was evident by increased transcript and protein levels of Wnt and notch signaling components in the defect region. Finally, we confirmed that med treatment leads to elevated bone healing in pre-osteoblasts by co localization of beta catenin with osteoblast marker alkaline phosphatase. In conclusion, med treatment promotes new bone regeneration and healing at the injury site by activating Wnt/canonical and notch signaling pathways. This study also forms a strong case for evaluation of med in delayed union and non-union fracture cases. PMID:26657206

Medicarpin, a Natural Pterocarpan, Heals Cortical Bone Defect by Activation of Notch and Wnt Canonical Signaling Pathways.

PubMed

Dixit, Manisha; Raghuvanshi, Ashutosh; Gupta, Chandra Prakash; Kureel, Jyoti; Mansoori, Mohd Nizam; Shukla, Priyanka; John, Aijaz A; Singh, Kavita; Purohit, Dipak; Awasthi, Pallavi; Singh, Divya; Goel, Atul

2015-01-01

We evaluated the bone regeneration and healing effect of Medicarpin (med) in cortical bone defect model that heals by intramembranous ossification. For the study, female Sprague-Dawley rats were ovariectomized and rendered osteopenic. A drill hole injury was generated in mid femoral bones of all the animals. Med treatment was commenced the day after and continued for 15 days. PTH was taken as a reference standard. Fifteen days post-treatment, animals were sacrificed. Bones were collected for histomorphometry studies at the injury site by micro-computed tomography (μCT) and confocal microscopy. RNA and protein was harvested from newly generated bone. For immunohistochemistry, 5μm sections of decalcified femur bone adjoining the drill hole site were cut. By μCT analysis and calcein labeling of newly generated bone it was found that med promotes bone healing and new bone formation at the injury site and was comparable to PTH in many aspects. Med treatment led to increase in the Runx-2 and osteocalcin signals indicating expansion of osteoprogenitors at the injury site as evaluated by qPCR and immunohistochemical localization. It was observed that med promoted bone regeneration by activating canonical Wnt and notch signaling pathway. This was evident by increased transcript and protein levels of Wnt and notch signaling components in the defect region. Finally, we confirmed that med treatment leads to elevated bone healing in pre-osteoblasts by co localization of beta catenin with osteoblast marker alkaline phosphatase. In conclusion, med treatment promotes new bone regeneration and healing at the injury site by activating Wnt/canonical and notch signaling pathways. This study also forms a strong case for evaluation of med in delayed union and non-union fracture cases.

Early mechanical stimulation only permits timely bone healing in sheep.

PubMed

Tufekci, Pelin; Tavakoli, Aramesh; Dlaska, Constantin; Neumann, Mirjam; Shanker, Mihir; Saifzadeh, Siamak; Steck, Roland; Schuetz, Michael; Epari, Devakar

2018-06-01

Bone fracture healing is sensitive to the fixation stability. However, it is unclear which phases of healing are mechano-sensitive and if mechanical stimulation is required throughout repair. In this study, a novel bone defect model, which isolates an experimental fracture from functional loading, was applied in sheep to investigate if stimulation limited to the early proliferative phase is sufficient for bone healing. An active fixator controlled motion in the fracture. Animals of the control group were unstimulated. In the physiological-like group, 1 mm axial compressive movements were applied between day 5 and 21, thereafter the movements were decreased in weekly increments and stopped after 6 weeks. In the early stimulatory group, the movements were stopped after 3 weeks. The experimental fractures were evaluated with mechanical and micro-computed tomography methods after 9 weeks healing. The callus strength of the stimulated fractures (physiological-like and early stimulatory) was greater than the unstimulated control group. The control group was characterized by minimal external callus formation and a lack of bone bridging at 9 weeks. In contrast, the stimulated groups exhibited advanced healing with solid bone formation across the defect. This was confirmed quantitatively by a lower bone volume in the control group compared to the stimulated groups.The novel experimental model permits the application of a well-defined load history to an experimental bone fracture. The poor healing observed in the control group is consistent with under-stimulation. This study has shown early mechanical stimulation only is sufficient for a timely healing outcome. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1790-1796, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Effect of simvastatin versus low level laser therapy (LLLT) on bone regeneration in rabbit's tibia

NASA Astrophysics Data System (ADS)

Gheith, Mostafa E.; Khairy, Maggie A.

2014-02-01

Simvastatin is a cholesterol lowering drug which proved effective on promoting bone healing. Recently low level laser therapy (LLLT) proved its effect as a biostimulator promoting bone regeneration. This study aims to compare the effect of both Simvastatin versus low level laser on bone healing in surgically created bone defects in rabbit's tibia. Material and methods: The study included 12 New Zealand white rabbits. Three successive 3mm defects were created in rabbits tibia first defect was left as control, second defect was filled with Simvastatin while the third defect was acted on with Low Level Laser (optical fiber 320micrometer). Rabbits were sacrificed after 48 hours, 1 week and 2 weeks intervals. Histopathology was conducted on the three defects Results: The histopathologic studies showed that the bony defects treated with the Low Level Laser showed superior healing patterns and bone regeneration than those treated with Simvastatin. While the control defect showed the least healing pattern.

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.

Treatment of unicameral bone cyst: systematic review and meta analysis.

PubMed

Kadhim, Muayad; Thacker, Mihir; Kadhim, Amjed; Holmes, Laurens

2014-03-01

Different treatment modalities have been utilized to treat unicameral bone cyst (UBC), but evidence has not been fully described to support one treatment over another and the optimal treatment is controversial. The aim of this quantitative systematic review was to assess the effectiveness of different UBC treatment modalities. We utilized Pubmed to isolate retrospective studies on patients with UBC who received any kind of treatment. The included studies needed to have a minimum sample size of 15 patients, and have provided data on radiographic healing outcome. Sixty-two articles were selected for the meta-analysis from a total of 463 articles. The cumulative sample size was 3,211 patients with 3,217 UBC, and male to female ratio was 2.2:1. The summary or pool estimate of methylprednisolone acetate (MPA) injection resulted in a healing rate of (77.4 %) that was comparable to bone marrow injection (77.9 %). A higher healing rate was observed with MPA injection when inner wall disruption was performed. The pool estimate of bone marrow with demineralized bone matrix injection was high (98.7 %). UBC healing rate after surgical curettage was comparable whether autograft or allograft was utilized (90 %). UBC treatment with flexible intramedullary nails without curettage provided almost 100% healing rate, while continuous decompression with cannulated screws provided 89 % healing rate. Conservative treatment indicated a healing rate of 64.2, 95 % CI (26.7-101.8). Active treatment for UBC provided variable healing rates and the outcomes were favorable relative to conservative treatment. Due to the heterogeneity of the studies and reporting bias, the interpretation of these findings should be handled with caution.

Effect of insertion torque on titanium implant osseointegration: an animal experimental study.

PubMed

Duyck, Joke; Roesems, Rutger; Cardoso, Marcio V; Ogawa, Toru; De Villa Camargos, Germana; Vandamme, Katleen

2015-02-01

To evaluate the effect of implant insertion torque on the peri-implant bone healing and implant osseointegration. Bilaterally in the tibia of five adult New Zealand white rabbits, 20 implants were installed, subdivided into four groups, corresponding to two insertion torque conditions (low, < 10 Ncm vs. high > 50 Ncm) and 2 experimental periods (2 weeks vs. 4 weeks of healing). The implant insertion torque was determined by the surgical drill diameter relative to the implant diameter. Implant osseointegration was evaluated by quantitative histology (bone-to-implant contact with host bone [BIC-host], with neoformed bone [BIC-de novo], with both bone types [BIC-total], and peri-implant bone [BA/TA]). Every response was modelled over time using GEE (general estimation equation) with an unstructured variance-covariance matrix to correct for dependency between the measurements from one animal. The statistical significance level of α = 0.05 was applied. Significantly, more BIC-host and BIC-total were recorded for H implants compared with L implants after 2 week of healing (P = 0.010 and P = 0.0001, respectively). However, this result was no longer found for the extended healing period. Furthermore, BIC-total significantly increased over time for L implants (P < 0.00001). In contrast, the significant increase in BA/TA over time was found for H implants (P < 0.01). Finally, H insertion torque led to an increased BA/TA after 4 week of healing (P < 0.02) compared with the L insertion protocol. L insertion torque implants installed in the rabbit tibial bone osseointegrate with considerable de novo bone formation. This bone neoformation enables L implants to catch up, already during the early osseointegration stage, the initial inferior amount BIC contact compared with that of H implants. A negative impact of the created strain environment accompanying H insertion torque implant installation on the biological process of osseointegration could not be observed, at least not at tissue level. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Novel Therapy for Bone Regeneration in Large Segmental Defects

DTIC Science & Technology

2016-10-01

reamed and nonreamed intrame- dullary nailing on fracture healing. Clin Orthop Relat Res. 1998;355(Suppl):S230–8. 37. Pape HC, Giannoudis PV. Fat embolism ...extension period (Year 4). 15. SUBJECT TERMS Bone healing, bone morphogenetic protein (BMP), thrombopoietin (TPO), therapy, fracture healing, bone...Bone healing, bone morphogenetic protein (BMP), thrombopoietin (TPO), therapy, fracture healing, bone regeneration, minipig, pig 3. OVERALL PROJECT

A randomized comparative prospective study of platelet-rich plasma, platelet-rich fibrin, and hydroxyapatite as a graft material for mandibular third molar extraction socket healing.

PubMed

Dutta, Shubha Ranjan; Passi, Deepak; Singh, Purnima; Sharma, Sarang; Singh, Mahinder; Srivastava, Dhirendra

2016-01-01

The purpose of this study was to compare the efficacy of platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and hydroxyapatite (HA) for reduction of pain and swelling, absence of dry socket, soft tissue healing, and bone regeneration after mandibular third molar extraction in human patients. Forty patients requiring extraction of mandibular third molars were randomly grouped as control, PRP, PRF, and HA-treated. The patients were assessed for postoperative pain, swelling, dry socket, and soft tissue healing on the 3 rd , 7 th , and 14 th day of postoperative periods depending on the standard methods. Radiological assessment of the extraction site was done at 1, 2, and 6 months interval to compare the change in bone density in the sockets in control and treated patients. Pain and swelling were less on PRP and PRF site when compared to HA and control site. PRP and PRF site showed better soft tissue healing when compared to HA and control site. Radiographic assessment showed comparatively lesser bone density values in PRP, PRF, and control site at 1, 2, and 6 months than HA site. Our study showed that PRP and PRF are better graft materials than HA regarding pain, swelling, dry socket, and soft tissue healing. Bone regeneration is induced promptly by HA as compared to other graft materials. However, a more elaborate study with a larger number of clinical cases is very much essential to be more conclusive regarding the efficacy of the graft materials.

A randomized comparative prospective study of platelet-rich plasma, platelet-rich fibrin, and hydroxyapatite as a graft material for mandibular third molar extraction socket healing

PubMed Central

Dutta, Shubha Ranjan; Passi, Deepak; Singh, Purnima; Sharma, Sarang; Singh, Mahinder; Srivastava, Dhirendra

2016-01-01

Aim: The purpose of this study was to compare the efficacy of platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and hydroxyapatite (HA) for reduction of pain and swelling, absence of dry socket, soft tissue healing, and bone regeneration after mandibular third molar extraction in human patients. Materials and Methods: Forty patients requiring extraction of mandibular third molars were randomly grouped as control, PRP, PRF, and HA-treated. The patients were assessed for postoperative pain, swelling, dry socket, and soft tissue healing on the 3rd, 7th, and 14th day of postoperative periods depending on the standard methods. Radiological assessment of the extraction site was done at 1, 2, and 6 months interval to compare the change in bone density in the sockets in control and treated patients. Results: Pain and swelling were less on PRP and PRF site when compared to HA and control site. PRP and PRF site showed better soft tissue healing when compared to HA and control site. Radiographic assessment showed comparatively lesser bone density values in PRP, PRF, and control site at 1, 2, and 6 months than HA site. Conclusion: Our study showed that PRP and PRF are better graft materials than HA regarding pain, swelling, dry socket, and soft tissue healing. Bone regeneration is induced promptly by HA as compared to other graft materials. However, a more elaborate study with a larger number of clinical cases is very much essential to be more conclusive regarding the efficacy of the graft materials. PMID:28163478

Hydroxyapatite-doped polycaprolactone nanofiber membrane improves tendon-bone interface healing for anterior cruciate ligament reconstruction.

PubMed

Han, Fei; Zhang, Peng; Sun, Yaying; Lin, Chao; Zhao, Peng; Chen, Jiwu

2015-01-01

Hamstring tendon autograft is a routine graft for anterior cruciate ligament (ACL) reconstruction. However, ways of improving the healing between the tendon and bone is often overlooked in clinical practice. This issue can be addressed by using a biomimetic scaffold. Herein, a biomimetic nanofiber membrane of polycaprolactone/nanohydroxyapatite/collagen (PCL/nHAp/Col) is fabricated that mimics the composition of native bone tissue for promoting tendon-bone healing. This membrane has good cytocompatibility, allowing for osteoblast cell adhesion and growth and bone formation. As a result, MC3T3 cells reveal a higher mineralization level in PCL/nHAp/Col membrane compared with PCL membrane alone. Further in vivo studies in ACL reconstruction in a rabbit model shows that PCL/nHAp/Col-wrapped tendon may afford superior tissue integration to nonwrapped tendon in the interface between the tendon and host bone as well as improved mechanical strength. This study shows that PCL/nHAp/Col nanofiber membrane wrapping of autologous tendon is effective for improving tendon healing with host bone in ACL reconstruction.

Changes in biochemical markers after lower limb fractures.

PubMed

Stoffel, Karl; Engler, Hanna; Kuster, Markus; Riesen, Walter

2007-01-01

The bone remodeling sequence after bone fracture changes the concentrations of biochemical bone markers, but the relationships of fracture size and of healing time to changes in biomarkers are unclear. The present pilot study was undertaken to determine the changes found in serum bone markers after plate osteosynthesis of closed distal tibial and malleolar fractures during a study period of 24 weeks. We measured tatrate-resistant acid phosphatase (TRACP 5b), collagen type I C-terminal telopeptide (ICTP), bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I C-terminal propeptide (PICP), procollagen type III N-terminal propeptide (PIIINP), and human cartilage glycoprotein 39 (YKL-40) in 20 patients with lower limb fractures (10 malleolar, 10 tibia). A physical examination and radiographs were completed to assess evidence of union. All malleolar fractures healed within 6 weeks, whereas 2 tibial fractures did not show complete bone healing after 24 weeks. Changes were comparable but more pronounced in the tibia group, and marker concentrations remained increased at the end of study (bone ALP, 86 vs 74 U/L; OC, 14.9 vs 7.7 microg/L; ICTP: 5.6 vs 3.3 microg/L at day 84 after osteosynthesis, P <0.05 in tibia; 80 vs 70 U/L, 8 vs 5.2 microg/L, and 3.5 vs 3.2 microg/L, respectively, in the malleolar fracture group). In normal bone healing, changes in bone turnover markers were primarily dependent on the fracture size. Delayed tibia fracture healing may involve a disturbance in bone remodeling.

Is Bone Grafting Necessary in the Treatment of Malunited Distal Radius Fractures?

PubMed Central

Disseldorp, Dominique J. G.; Poeze, Martijn; Hannemann, Pascal F. W.; Brink, Peter R. G.

2015-01-01

Background Open wedge osteotomy with bone grafting and plate fixation is the standard procedure for the correction of malunited distal radius fractures. Bone grafts are used to increase structural stability and to enhance new bone formation. However, bone grafts are also associated with donor site morbidity, delayed union at bone–graft interfaces, size mismatch between graft and osteotomy defect, and additional operation time. Purpose The goal of this study was to assess bone healing and secondary fracture displacement in the treatment of malunited distal radius fractures without the use of bone grafting. Methods Between January 1993 and December 2013, 132 corrective osteotomies and plate fixations without bone grafting were performed for malunited distal radius fractures. The minimum follow-up time was 12 months. Primary study outcomes were time to complete bone healing and secondary fracture displacement. Preoperative and postoperative radiographs during follow-up were compared with each other, as well as with radiographs of the uninjured side. Results All 132 osteotomies healed. In two cases (1.5%), healing took more than 4 months, but reinterventions were not necessary. No cases of secondary fracture displacement or hardware failure were observed. Significant improvements in all radiographic parameters were shown after corrective osteotomy and plate fixation. Conclusion This study shows that bone grafts are not required for bone healing and prevention of secondary fracture displacement after corrective osteotomy and plate fixation of malunited distal radius fractures. Level of evidence Therapeutic, level IV, case series with no comparison group PMID:26261748

Treatment of unicameral bone cyst: a comparative study of selected techniques.

PubMed

Hou, Hsien-Yang; Wu, Karl; Wang, Chen-Ti; Chang, Shun-Min; Lin, Wei-Hsin; Yang, Rong-Sen

2010-04-01

There is a variety of treatment modalities for unicameral bone cysts, with variable outcomes reported in the literature. Although good initial outcomes have been reported, the success rate has often changed with longer-term follow-up. We introduce a novel, minimally invasive treatment method and compare its clinical outcomes with those of other methods of treatment of this lesion. From February 1994 to April 2008, forty patients with a unicameral bone cyst were treated with one of four techniques: serial percutaneous steroid and autogenous bone-marrow injection (Group 1, nine patients); open curettage and grafting with a calcium sulfate bone substitute either without instrumentation (Group 2, twelve patients) or with internal instrumentation (Group 3, seven patients); or minimally invasive curettage, ethanol cauterization, disruption of the cystic boundary, insertion of a synthetic calcium sulfate bone-graft substitute, and placement of a cannulated screw to provide drainage (Group 4, twelve patients). Success was defined as radiographic evidence of a healed cyst or of a healed cyst with some defect according to the modified Neer classification, and failure was defined as a persistent or recurrent cyst that needed additional treatment. Patients who sustained a fracture during treatment were also considered to have had a failure. The outcome parameters included the radiographically determined healing rate, the time to solid union, and the total number of procedures needed. The follow-up time ranged from eighteen to eighty-four months. Group-4 patients had the highest radiographically determined healing rate. Healing was seen in eleven of the twelve patients in that group compared with three of the nine in Group 1, eight of the twelve in Group 2, and six of the seven in Group 3. Group-4 patients also had the shortest mean time to union: 3.7 +/- 2.3 months compared with 23.4 +/- 14.9, 12.2 +/- 8.5, and 6.6 +/- 4.3 months in Groups 1, 2, and 3, respectively. This new minimally invasive method achieved a favorable outcome, with a higher radiographically determined healing rate and a shorter time to union. Thus, it can be considered an option for initial treatment of unicameral bone cysts.

Comparison of platelet rich plasma and synthetic graft material for bone regeneration after third molar extraction.

PubMed

Nathani, Dipesh B; Sequeira, Joyce; Rao, B H Sripathi

2015-01-01

To compare the efficacy of Platelet rich plasma and synthetic graft material for bone regeneration after bilateral third molar extraction. This study was conducted in 10 patients visiting the outpatient department of Oral & Maxillofacial Surgery, Yenepoya Dental College & Hospital. Patients requiring extraction of bilateral mandibular third molars were taken for the study. Following extraction, PRP (Platelet Rich Plasma) was placed in one extraction socket and synthetic graft material in form granules [combination of Hydroxyapatite (HA) and Bioactive glass (BG)] in another extraction socket. The patients were assessed for postoperative pain and soft tissue healing. Radiological assessment of the extraction site was done at 8, 12 and 16 weeks interval to compare the change in bone density in both the sockets. Pain was less on PRP site when compared to HA site. Soft tissue evaluation done using gingival healing index given by Landry et al showed better healing on PRP site when compared to HA site. The evaluation of bone density by radiological assessment showed the grey level values calculated at 4 months at the PRP site were comparatively higher than HA site. The study showed that the platelet rich plasma is a better graft material than synthetic graft material in terms of soft tissue and bone healing. However a more elaborate study with a larger number of clinical cases is very much essential to be more conclusive regarding the efficacy of both the materials.

Effect of diet-induced vitamin D deficiency on rotator cuff healing in a rat model.

PubMed

Angeline, Michael E; Ma, Richard; Pascual-Garrido, Cecilia; Voigt, Clifford; Deng, Xiang Hua; Warren, Russell F; Rodeo, Scott A

2014-01-01

Few studies have considered hormonal influences, particularly vitamin D, on healing. Vitamin D deficiency would have a negative effect on the structure of the healing tendon-bone interface in a rat model and would result in decreased tendon attachment strength. Controlled laboratory study. Vitamin D deficiency was induced in 28 male Sprague-Dawley rats using a specialized vitamin D-deficient diet and ultraviolet light restriction. Serum levels of vitamin D were measured after 6 weeks. These vitamin D-deficient animals (experimental group) plus 32 rats with normal vitamin D levels (controls) underwent unilateral detachment of the right supraspinatus tendon from the greater tuberosity of the humerus, followed by immediate repair using bone tunnel suture fixation. The animals were sacrificed at 2- and 4-week intervals after surgery for biomechanical analysis. A paired t test was used to compare serum vitamin D levels at day 0 and at 6 weeks. A nonparametric Mann-Whitney U test was used to compare load-to-failure and stiffness values between the experimental group and controls. Bone density and new bone formation at the tendon insertion site on the greater tuberosity were assessed with micro-computed tomography (CT). The organization of collagen tissue, new bone formation, vascularity at the tendon-bone interface, fibrocartilage at the tendon-bone interface, and collagen fiber continuity between the tendon and bone tissue were evaluated with safranin O and picrosirius red staining. Blood draws confirmed vitamin D deficiency at 6 weeks compared with time zero/baseline for rats in the experimental group (10.9 ng/mL vs 6.5 ng/mL, respectively; P < .001). Biomechanical testing demonstrated a significant decrease in load to failure in the experimental group compared with controls at 2 weeks (5.8 ± 2.0 N vs 10.5 ± 4.4 N, respectively; P < .006). There was no difference in stiffness at 2 weeks between the control and experimental groups. At 4 weeks, there was no significant difference in load to failure or stiffness between the control and experimental groups. Histological analysis showed less bone formation and less collagen fiber organization in the vitamin D-deficient specimens at 4 weeks as compared with controls. Micro-CT analysis showed no significant difference between groups for total mineral density and bone volume fraction of cortical, whole, or trabecular bone at 4 weeks. The biomechanical and histological data from this study suggest that low vitamin D levels may negatively affect early healing at the rotator cuff repair site. It is estimated that 1 billion people worldwide are vitamin D deficient. In the deficient state, acutely injured rotator cuffs may have a reduced ability for tendon healing. Further studies are needed to determine the exact mechanism by which vitamin D affects tendon healing and whether vitamin D supplementation can improve rotator cuff tendon healing and reduce the incidence of retears.

In vivo study of microarc oxidation coated biodegradable magnesium plate to heal bone fracture defect of 3mm width.

PubMed

Wu, Y F; Wang, Y M; Jing, Y B; Zhuang, J P; Yan, J L; Shao, Z K; Jin, M S; Wu, C J; Zhou, Y

2017-10-01

Microarc oxidation (MAO) coated magnesium (Mg) with improved corrosion resistance appeal increasing interests as a revolutionary biodegradable metal for fractured bone fixing implants application. However, the in vivo corrosion degradation of the implants and bone healing response are not well understood, which is highly required in clinic. In the present work, 10μm and 20μm thick biocompatible MAO coatings mainly composed of MgO, Mg 2 SiO 4 , CaSiO 3 and Mg 3 (PO 4 ) 2 phases were fabricated on AZ31 magnesium alloy. The electrochemical tests indicated an improved corrosion resistance of magnesium by the MAO coatings. The 10μm and 20μm coated and uncoated magnesium plates were separately implanted into the radius bone fracture site of adult New Zealand white rabbits using a 3mm width bone fracture defect model to investigate the magnesium implants degradation and uninhibited bone healing. Taking advantage of the good biocompatibility of the MAO coatings, no adverse effects were detected through the blood test and histological examination. The implantation groups of coated and uncoated magnesium plates were both observed the promoting effect of bone fracture healing compared with the simple fracture group without implant. The releasing Mg 2+ by the degradation of implants into the fracture site improved the bone fracture healing, which is attributed to the magnesium promoting CGRP-mediated osteogenic differentiation. Mg degradation and bone fracture healing promoting must be tailored by microarc oxidation coating with different thickness for potential clinic application. Copyright © 2017. Published by Elsevier B.V.

Partial gravity unloading inhibits bone healing responses in a large animal model.

PubMed

Gadomski, Benjamin C; McGilvray, Kirk C; Easley, Jeremiah T; Palmer, Ross H; Santoni, Brandon G; Puttlitz, Christian M

2014-09-22

The reduction in mechanical loading associated with space travel results in dramatic decreases in the bone mineral density (BMD) and mechanical strength of skeletal tissue resulting in increased fracture risk during spaceflight missions. Previous rodent studies have highlighted distinct bone healing differences in animals in gravitational environments versus those during spaceflight. While these data have demonstrated that microgravity has deleterious effects on fracture healing, the direct translation of these results to human skeletal repair remains problematic due to substantial differences between rodent and human bone. Thus, the objective of this study was to investigate the effects of partial gravitational unloading on long-bone fracture healing in a previously-developed large animal Haversian bone model. In vivo measurements demonstrated significantly higher orthopedic plate strains (i.e. load burden) in the Partial Unloading (PU) Group as compared to the Full Loading (FL) Group following the 28-day healing period due to inhibited healing in the reduced loading environment. DEXA BMD in the metatarsus of the PU Group decreased 17.6% (p<0.01) at the time of the ostectomy surgery. Four-point bending stiffness of the PU Group was 4.4 times lower than that of the FL Group (p<0.01), while µCT and histomorphometry demonstrated reduced periosteal callus area (p<0.05), mineralizing surface (p<0.05), mineral apposition rate (p<0.001), bone formation rate (p<0.001), and periosteal/endosteal osteoblast numbers (p<0.001/p<0.01, respectively) as well as increased periosteal osteoclast number (p<0.05). These data provide strong evidence that the mechanical environment dramatically affects the fracture healing cascade, and likely has a negative impact on Haversian system healing during spaceflight. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of Guided Bone Regeneration around Oral Implants over Different Healing Times Using Two Different Bovine Bone Materials: A Randomized, Controlled Clinical and Histological Investigation.

PubMed

Kohal, Ralf Joachim; Straub, Lisa Marie; Wolkewitz, Martin; Bächle, Maria; Patzelt, Sebastian Berthold Maximilian

2015-10-01

To evaluate the potential of two bone substitute materials and the influence of different healing periods in guided bone regeneration therapy of osseous defects around implants. Twenty-four edentulous patients received implants in the region of the lost lower incisors. Around two standardized osseous defects were created, treated either with a 50:50 mixture of PepGen P-15® and OsteoGraf®/N-700 (test group) or with BioOss® (control group), and covered with titanium membranes. After healing periods of 2, 4, 6, or 9 months, the implants were removed together with the surrounding bone and subsequently prepared for histological evaluations. Defect depths in both groups showed a clinical reduction after intervention. The histologically measured distance from the implant shoulder to the first point of bone-implant contact (BIC) after treatment did not differ between the two groups. The healing time influenced the level of the first point of BIC, with a longer healing period producing a more coronal first point of BIC. A greater percentage BIC and a higher fraction of mineralized bone were found in the pristine bone area compared with the augmented defect area. It can be concluded that in the treatment of osseous defects around oral implants, both materials were equally effective bone substitute materials when used in combination with guided bone regeneration. © 2014 Wiley Periodicals, Inc.

Evaluation of the Effects of Photobiomodulation on Partial Osteotomy in Streptozotocin-Induced Diabetes in Rats.

PubMed

Mostafavinia, Ataroalsadat; Masteri Farahani, Reza; Abdollahifar, Mohammad-Amin; Ghatrehsamani, Mahdi; Ghoreishi, Seyed Kamran; Hajihossainlou, Behnam; Chien, Sufan; Dadras, Sara; Rezaei, Fatemehalsadat; Bayat, Mohammad

2018-05-31

We examined the effects of photobiomodulation (PBM) on stereological parameters, and gene expression of Runt-related transcription factor 2 (RUNX2), osteocalcin, and receptor activator of nuclear factor kappa-B ligand (RANKL) in repairing tissue of tibial bone defect in streptozotocin (STZ)-induced type 1 diabetes mellitus (TIDM) in rats during catabolic response of fracture healing. There were conflicting results regarding the efficacy of PBM on bone healing process in healthy and diabetic animals. Forty-eight rats have been distributed into four groups: group 1 (healthy control, no TIDM and no PBM), group 2 (healthy test, no TIDM and PBM), group 3 (diabetic control, TIDM and no PBM), and group 4 (diabetic test, no TIDM and PBM). TIDM was induced in the groups 3 and 4. A partial bone defect in tibia was made in all groups. The bone defects of groups second and fourth were irradiated by a laser (890 nm, 80 Hz, 1.5 J/cm 2 ). Thirty days after the surgery, all bone defects were extracted and were submitted to stereological examination and real-time polymerase chain reaction (RT-PCR). PBM significantly increased volumes of total callus, total bone, bone marrow, trabecular bone, and cortical bone, and the numbers of osteocytes and osteoblasts of callus in TIDM rats compared to those of callus in diabetic control. In addition, TIDM increased RUNX2, and osteocalcin in callus of tibial bone defect compared to healthy group. PBM significantly decreased osteocalcin gene expression in TIDM rats. PBM significantly increased many stereological parameters of bone repair in an STZ-induced TIDM during catabolic response of fracture healing. Further RT-PCR test demonstrated that bone repair was modulated in diabetic rats during catabolic response of fracture healing by significant increase in mRNA expression of RUNX2, and osteocalcin compared to healthy control rats. PBM also decreased osteocalcin mRNA expression in TIDM rats.

Comparative study on the role of gelatin, chitosan and their combination as tissue engineered scaffolds on healing and regeneration of critical sized bone defects: an in vivo study.

PubMed

Oryan, Ahmad; Alidadi, Soodeh; Bigham-Sadegh, Amin; Moshiri, Ali

2016-10-01

Gelatin and chitosan are natural polymers that have extensively been used in tissue engineering applications. The present study aimed to evaluate the effectiveness of chitosan and gelatin or combination of the two biopolymers (chitosan-gelatin) as bone scaffold on bone regeneration process in an experimentally induced critical sized radial bone defect model in rats. Fifty radial bone defects were bilaterally created in 25 Wistar rats. The defects were randomly filled with chitosan, gelatin and chitosan-gelatin and autograft or left empty without any treatment (n = 10 in each group). The animals were examined by radiology and clinical evaluation before euthanasia. After 8 weeks, the rats were euthanized and their harvested healing bone samples were evaluated by radiology, CT-scan, biomechanical testing, gross pathology, histopathology, histomorphometry and scanning electron microscopy. Gelatin was biocompatible and biodegradable in vivo and showed superior biodegradation and biocompatibility when compared with chitosan and chitosan-gelatin scaffolds. Implantation of both the gelatin and chitosan-gelatin scaffolds in bone defects significantly increased new bone formation and mechanical properties compared with the untreated defects (P < 0.05). Combination of the gelatin and chitosan considerably increased structural and functional properties of the healing bones when compared to chitosan scaffold (P < 0.05). However, no significant differences were observed between the gelatin and gelatin-chitosan groups in these regards (P > 0.05). In conclusion, application of the gelatin alone or its combination with chitosan had beneficial effects on bone regeneration and could be considered as good options for bone tissue engineering strategies. However, chitosan alone was not able to promote considerable new bone formation in the experimentally induced critical-size radial bone defects.

Healing of ungrafted and grafted extraction sockets after 12 weeks: a prospective clinical study.

PubMed

Heberer, Susanne; Al-Chawaf, Bassem; Jablonski, Carlo; Nelson, John J; Lage, Hermann; Nelson, Katje

2011-01-01

In this prospective study, bone formation in human extraction sockets augmented with Bio-Oss Collagen after a 12-week healing period was quantified and compared to bone formation in unaugmented extraction sockets. Selected patients with four-walled extraction sockets were included in this prospective study. After extraction, the sockets were randomly augmented using Bio-Oss Collagen or left to heal unfilled without raising a mucoperiosteal flap. At the time of implant placement, histologic specimens were obtained from the socket and analyzed. Statistical analysis was performed using the Wilcoxon signed-rank test. Twenty-five patients with a total of 39 sockets (20 augmented, 19 unaugmented) were included in the study and the histologic specimens analyzed. All specimens were free of inflammatory cells. The mean overall new bone formation in the augmented sites was 25% (range, 8%-41%) and in the unaugmented sockets it was 44% (range, 3%-79%). There was a significant difference in the rate of new bone formation between the grafted and ungrafted sockets and a significant difference in the bone formation rate in the apical compared to the coronal regions of all sockets, independent of the healing mode. This descriptive study demonstrated that bone formation in Bio-Oss Collagen-grafted human extraction sockets was lower than bone formation in ungrafted sockets. Bone formation occurred in all specimens with varying degrees of maturation independent of the grafting material and was initiated from the apical region.

The effect of mesenchymal stem cells delivered via hydrogel-based tissue engineered periosteum on bone allograft healing

PubMed Central

Hoffman, Michael D.; Xie, Chao; Zhang, Xinping; Benoit, Danielle S.W.

2013-01-01

Allografts remain the clinical “gold standard” for treatment of critical sized bone defects despite minimal engraftment and ~60% long-term failure rates. Therefore, the development of strategies to improve allograft healing and integration are necessary. The periosteum and its associated stem cell population, which are lacking in allografts, coordinate autograft healing. Herein we utilized hydrolytically degradable hydrogels to transplant and localize mesenchymal stem cells (MSCs) to allograft surfaces, creating a periosteum mimetic, termed a ‘tissue engineered periosteum’. Our results demonstrated that this tissue engineering approach resulted in increased graft vascularization (~2.4-fold), endochondral bone formation (~2.8-fold), and biomechanical strength (1.8-fold), as compared to untreated allografts, over 16 weeks of healing. Despite this enhancement in healing, the process of endochondral ossification was delayed compared to autografts, requiring further modifications for this approach to be clinically acceptable. However, this bottom-up biomaterials approach, the engineered periosteum, can be augmented with alternative cell types, matrix cues, growth factors, and/or other small molecule drugs to expedite the process of ossification. PMID:23958029

Effects of Particle Size and Porosity on In Vivo Remodeling of Settable Allograft Bone/Polymer Composites

PubMed Central

Prieto, Edna M.; Talley, Anne D.; Gould, Nicholas R.; Zienkiewicz, Katarzyna J.; Drapeau, Susan J.; Kalpakci, Kerem N.

2014-01-01

Established clinical approaches to treat bone voids include the implantation of autograft or allograft bone, ceramics, and other bone void fillers (BVFs). Composites prepared from lysine-derived polyurethanes and allograft bone can be injected as a reactive liquid and set to yield BVFs with mechanical strength comparable to trabecular bone. In this study, we investigated the effects of porosity, allograft particle size, and matrix mineralization on remodeling of injectable and settable allograft/polymer composites in a rabbit femoral condyle plug defect model. Both low viscosity (LV) and high viscosity (HV) grafts incorporating small (<105 μm) particles only partially healed at 12 weeks, and the addition of 10% demineralized bone matrix did not enhance healing. In contrast, composite grafts with large (105 – 500 μm) allograft particles healed at 12 weeks post-implantation, as evidenced by radial μCT and histomorphometric analysis. This study highlights particle size and surface connectivity as influential parameters regulating the remodeling of composite bone scaffolds. PMID:25581686

Chitosan nanofiber scaffold improves bone healing via stimulating trabecular bone production due to upregulation of the Runx2/osteocalcin/alkaline phosphatase signaling pathway

PubMed Central

Ho, Ming-Hua; Yao, Chih-Jung; Liao, Mei-Hsiu; Lin, Pei-I; Liu, Shing-Hwa; Chen, Ruei-Ming

2015-01-01

Osteoblasts play critical roles in bone formation. Our previous study showed that chitosan nanofibers can stimulate osteoblast proliferation and maturation. This translational study used an animal model of bone defects to evaluate the effects of chitosan nanofiber scaffolds on bone healing and the possible mechanisms. In this study, we produced uniform chitosan nanofibers with fiber diameters of approximately 200 nm. A bone defect was surgically created in the proximal femurs of male C57LB/6 mice, and then the left femur was implanted with chitosan nanofiber scaffolds for 21 days and compared with the right femur, which served as a control. Histological analyses revealed that implantation of chitosan nanofiber scaffolds did not lead to hepatotoxicity or nephrotoxicity. Instead, imaging analyses by X-ray transmission and microcomputed tomography showed that implantation of chitosan nanofiber scaffolds improved bone healing compared with the control group. In parallel, microcomputed tomography and bone histomorphometric assays further demonstrated augmentation of the production of new trabecular bone in the chitosan nanofiber-treated group. Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor. As to the mechanisms, analysis by confocal microscopy showed that implantation of chitosan nanofiber scaffolds increased levels of Runt-related transcription factor 2 (Runx2), a key transcription factor that regulates osteogenesis, in the bone defect sites. Successively, amounts of alkaline phosphatase and osteocalcin, two typical biomarkers that can simulate bone maturation, were augmented following implantation of chitosan nanofiber scaffolds. Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline phosphatase and osteocalcin gene expressions. Our results suggest the potential of chitosan nanofiber scaffolds for therapy of bone diseases, including bone defects and bone fractures. PMID:26451104

Improvement of Bone Healing by Neutralization of microRNA-335-5p, but not by Neutralization of microRNA-92A in Bone Marrow Mononuclear Cells Transplanted into a Large Femur Defect of the Rat.

PubMed

Janko, Maren; Dietz, Konstantin; Rachor, Julia; Sahm, Julian; Schroder, Katrin; Schaible, Alexander; Nau, Christoph; Seebach, Caroline; Marzi, Ingo; Henrich, Dirk

2018-04-23

Transplanted bone marrow mononuclear cells (BMC) support the healing of large bone defects. Neutralization of microRNA (MiR) that negatively affects key processes of the reparative response in BMC might help to further improve the beneficial effect of transplanted BMC in bone healing. Hence, the aim of this study was to evaluate if the neutralization of MiR-92A (vascularization) and MiR-335-5p (osteogenic differentiation) in BMC using specific antiMiRs leads to a further improvement of the BMC-supported therapy of large bone defects. BMC transiently transfected with antiMiR- 92A, antiMiR-335, antiMiR-92A, and antiMiR-355 or control antiMiR were seeded on β-TCP (beta-tricalcium phosphate) and placed in a femoral large bone defect (5 mm) in Sprague-Dawley rats. Ultimate load as well as osseous integration of the β-TCP-scaffolds were significantly improved in the antiMiR-335 group compared to the control group after 8 weeks, whereas neutralization of antiMiR-92A lead to an improvement of early vascularization after 1 week, but not to enhanced bone healing after 8 weeks. We demonstrated that the targeted inhibition of MiRs in transplanted BMC is a new approach that enhances BMC-supported bone healing.

Bone healing in children.

PubMed

Lindaman, L M

2001-01-01

Just as pediatric fractures and bones are basically similar to adult fractures and bones, pediatric bone healing is basically similar to adult bone healing. They both go through the three same phases of inflammation, reparation, and remodeling. It is those differences between pediatric and adult bone, however, that affect the differences in the healing of pediatric bone. Because pediatric bone can fail in compression, less initial stability and less callus formation is required to achieve a clinically stable or healed fracture. The greater subperiosteal hematoma and the stronger periosteum all contribute to a more rapid formation of callous strong enough to render the fracture healed more rapidly than the adult. Genes and hormones that are necessary for the initial formation of the skeleton are the same as, or at least similar in most instances, to those necessary for the healing of fractures. This osteogenic environment of the pediatric bone means that these fracture healing processes are already ongoing in the child at the time of the fracture. In the adult, these factors must be reawakened, leading to the slower healing time in the adult. Once the fracture is healed, the still-growing pediatric bone can correct any "sins" of fracture alignment or angulation leaving the bone with no signs of having ever been broken. The final result is bone that is, in the child's words, "as good as new."

Treatment of unicameral bone cyst: surgical technique.

PubMed

Hou, Hsien-Yang; Wu, Karl; Wang, Chen-Ti; Chang, Shun-Min; Lin, Wei-Hsin; Yang, Rong-Sen

2011-03-01

There is a variety of treatment modalities for unicameral bone cysts, with variable outcomes reported in the literature. Although good initial outcomes have been reported, the success rate has often changed with longer-term follow-up. We introduce a novel, minimally invasive treatment method and compare its clinical outcomes with those of other methods of treatment of this lesion. From February 1994 to April 2008, forty patients with a unicameral bone cyst were treated with one of four techniques: serial percutaneous steroid and autogenous bone-marrow injection (Group 1, nine patients); open curettage and grafting with a calcium sulfate bone substitute either without instrumentation (Group 2, twelve patients) or with internal instrumentation (Group 3, seven patients); or minimally invasive curettage, ethanol cauterization, disruption of the cystic boundary, insertion of a synthetic calcium sulfate bone-graft substitute, and placement of a cannulated screw to provide drainage (Group 4, twelve patients). Success was defined as radiographic evidence of a healed cyst or of a healed cyst with some defect according to the modified Neer classification, and failure was defined as a persistent or recurrent cyst that needed additional treatment. Patients who sustained a fracture during treatment were also considered to have had a failure. The outcome parameters included the radiographically determined healing rate, the time to solid union, and the total number of procedures needed. The follow-up time ranged from eighteen to eighty-four months. Group-4 patients had the highest radiographically determined healing rate. Healing was seen in eleven of the twelve patients in that group compared with three of the nine in Group 1, eight of the twelve in Group 2, and six of the seven in Group 3. Group-4 patients also had the shortest mean time to union: 3.7 ± 2.3 months compared with 23.4 ± 14.9, 12.2 ± 8.5, and 6.6 ± 4.3 months in Groups 1, 2, and 3, respectively. This new minimally invasive method achieved a favorable outcome, with a higher radiographically determined healing rate and a shorter time to union. Thus, it can be considered an option for initial treatment of unicameral bone cysts.

Oxygen as a critical determinant of bone fracture healing-a multiscale model.

PubMed

Carlier, Aurélie; Geris, Liesbet; van Gastel, Nick; Carmeliet, Geert; Van Oosterwyck, Hans

2015-01-21

A timely restoration of the ruptured blood vessel network in order to deliver oxygen and nutrients to the fracture zone is crucial for successful bone healing. Indeed, oxygen plays a key role in the aerobic metabolism of cells, in the activity of a myriad of enzymes as well as in the regulation of several (angiogenic) genes. In this paper, a previously developed model of bone fracture healing is further improved with a detailed description of the influence of oxygen on various cellular processes that occur during bone fracture healing. Oxygen ranges of the cell-specific oxygen-dependent processes were established based on the state-of-the art experimental knowledge through a rigorous literature study. The newly developed oxygen model is compared with previously published experimental and in silico results. An extensive sensitivity analysis was also performed on the newly introduced oxygen thresholds, indicating the robustness of the oxygen model. Finally, the oxygen model was applied to the challenging clinical case of a critical sized defect (3mm) where it predicted the formation of a fracture non-union. Further model analyses showed that the harsh hypoxic conditions in the central region of the callus resulted in cell death and disrupted bone healing thereby indicating the importance of a timely vascularization for the successful healing of a large bone defect. In conclusion, this work demonstrates that the oxygen model is a powerful tool to further unravel the complex spatiotemporal interplay of oxygen delivery, diffusion and consumption with the several healing steps, each occurring at distinct, optimal oxygen tensions during the bone repair process. Copyright © 2014 Elsevier Ltd. All rights reserved.

New bone formation and trabecular bone microarchitecture of highly porous tantalum compared to titanium implant threads: A pilot canine study.

PubMed

Lee, Jin Whan; Wen, Hai Bo; Gubbi, Prabhu; Romanos, Georgios E

2018-02-01

This study evaluated new bone formation activities and trabecular bone microarchitecture within the highly porous region of Trabecular Metal™ Dental Implants (TM) and between the threads of Tapered Screw-Vent® Dental Implants (TSV) in fresh canine extraction sockets. Eight partially edentulated dogs received four implants (4.1 mmD × 13 mmL) bilaterally in mandibular fresh extraction sockets (32 TM, 32 TSV implants), and allowed to heal for 2, 4, 8, and 12 weeks. Calcein was administered to label mineralizing bone at 11 and 4 days before euthanasia for dogs undergoing all four healing periods. Biopsies taken at each time interval were examined histologically. Histomorphometric assay was conducted for 64 unstained and 64 stained slides at the region of interest (ROI) (6 mm long × 0.35 mm deep) in the midsections of the implants. Topographical and chemical analyses were also performed. Histomorphometry revealed significantly more new bone in the TM than in the TSV implants at each healing time (p = .0014, .0084, .0218, and .0251). Calcein-labeled data showed more newly mineralized bone in the TM group than in the TSV group at 2, 8, and 12 weeks (p = .045, .028, .002, respectively) but not at 4 weeks (p = .081). Histologically TM implants exhibited more bone growth and dominant new immature woven bone at an earlier time point than TSV implants. The parameters representing trabecular bone microarchitecture corroborated faster new bone formation in the TM implants when compared to the TSV implants. TM exhibited an irregular faceted topography compared to a relatively uniform microtextured surface for TSV. Chemical analysis showed peaks associated with each implant's composition material, and TSV also showed peaks reflecting the elements of the calcium phosphate blasting media. Results suggest that the healing pathway associated with the highly porous midsection of TM dental implant could enable faster and stronger secondary implant stability than conventional osseointegration alone; however, prospective clinical studies are needed to confirm these potential benefits in patients with low bone density, compromised healing, or prior implant failure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of the Interposition of Calcium Phosphate Materials on Tendon-Bone Healing During Repair of Chronic Rotator Cuff Tear.

PubMed

Zhao, Song; Peng, Lingjie; Xie, Guoming; Li, Dingfeng; Zhao, Jinzhong; Ning, Congqin

2014-08-01

The current nature of tendon-bone healing after rotator cuff (RC) repair is still the formation of granulation tissue at the tendon-bone interface rather than the formation of fibrocartilage, which is the crucial structure in native tendon insertion and can be observed after knee ligament reconstruction. The interposition of calcium phosphate materials has been found to be able to enhance tendon-bone healing in knee ligament reconstruction. However, whether the interposition of these kinds of materials can enhance tendon-bone healing or even change the current nature of tendon-bone healing after RC repair still needs to be explored. The interposition of calcium phosphate materials during RC repair would enhance tendon-bone healing or change its current nature of granulation tissue formation into a more favorable process. Controlled laboratory study. A total of 144 male Sprague-Dawley rats underwent unilateral detachment of the supraspinatus tendon, followed by delayed repair after 3 weeks. The animals were allocated into 1 of 3 groups: (1) repair alone, (2) repair with Ca5(PO4)2SiO4 (CPS) bioceramic interposition, or (3) repair with hydroxyapatite (HA) bioceramic interposition at the tendon-bone interface. Animals were sacrificed at 2, 4, or 8 weeks postoperatively, and microcomputed tomography (micro-CT) was used to quantify the new bone formation at the repair site. New fibrocartilage formation and collagen organization at the tendon-bone interface was evaluated by histomorphometric analysis. Biomechanical testing of the supraspinatus tendon-bone complex was performed. Statistical analysis was performed using 1-way analysis of variance. Significance was set at P < .05. The micro-CT analysis demonstrated remarkable osteogenic activity and osteoconductivity to promote new bone formation and ingrowth of CPS and HA bioceramic, with CPS bioceramic showing better results than HA. Histological observations indicated that CPS bioceramic had excellent biocompatibility and biodegradability. At early time points after the RC repair, CPS bioceramic significantly increased the area of fibrocartilage at the tendon-bone interface compared with the control and HA groups. Moreover, CPS and HA bioceramics had significantly improved collagen organization. Biomechanical tests indicated that the CPS and HA groups have greater ultimate load to failure and stiffness than the control group at 4 and 8 weeks, and the CPS specimens exhibited the maximum ultimate load to failure, stiffness, and stress of the healing enthesis. Both CPS and HA bioceramics aid in cell attachment and proliferation and accelerate new bone formation, and CPS bioceramic has a more prominent effect on tendon-to-bone healing. Local application of CPS and HA bioceramic at the tendon-bone interface shows promise in improving healing after rotator cuff tear repair. © 2014 The Author(s).

Bone implant sockets made using three different procedures: a stability study in dogs

PubMed Central

Campo, Julián

2012-01-01

Objective: This study compared the effects of three different methods of preparing bone implant sockets (drilling, osteotomes, and piezoelectric device) on osseointegration using resonance frequency analysis (RFA). Study Design: An experimental prospective study was designed. Material and Methods: Ten adult beagle dogs were studied. After 5 weeks, 23 out of 28 initially placed implants in the iliac crest were evaluated, comparing these three different procedures of bone implant socket. Student’s t-test (paired, two-tailed) was used to reveal differences among the three groups at each time point (SPSS 16.0, IL, USA). Results: After a 5-week healing period, the implants placed in sockets that were made using an osteotome or piezoelectric device were slightly more stable than those made by drilling. Reduced mechanical and heat injury to the bone is beneficial for maintaining and improving stability during the critical early healing period. Conclusion: Using RFA, there was evidence of a slight increase in implant stability in the iliac crest after 5 weeks of healing when the implant socket was made using a piezoelectric device or expansion procedure as compare with the drilling method. Key words:Bone implant sockets, drilling, osteotomes, piezoelectric, resonance frequency analysis, stability. PMID:24558558

Investigation of a pre-clinical mandibular bone notch defect model in miniature pigs: clinical computed tomography, micro-computed tomography, and histological evaluation.

PubMed

Carlisle, Patricia L; Guda, Teja; Silliman, David T; Lien, Wen; Hale, Robert G; Brown Baer, Pamela R

2016-02-01

To validate a critical-size mandibular bone defect model in miniature pigs. Bilateral notch defects were produced in the mandible of dentally mature miniature pigs. The right mandibular defect remained untreated while the left defect received an autograft. Bone healing was evaluated by computed tomography (CT) at 4 and 16 weeks, and by micro-CT and non-decalcified histology at 16 weeks. In both the untreated and autograft treated groups, mineralized tissue volume was reduced significantly at 4 weeks post-surgery, but was comparable to the pre-surgery levels after 16 weeks. After 16 weeks, CT analysis indicated that significantly greater bone was regenerated in the autograft treated defect than in the untreated defect (P=0.013). Regardless of the treatment, the cortical bone was superior to the defect remodeled over 16 weeks to compensate for the notch defect. The presence of considerable bone healing in both treated and untreated groups suggests that this model is inadequate as a critical-size defect. Despite healing and adaptation, the original bone geometry and quality of the pre-injured mandible was not obtained. On the other hand, this model is justified for evaluating accelerated healing and mitigating the bone remodeling response, which are both important considerations for dental implant restorations.

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.

Novel Therapy for Bone Regeneration in Large Segmental Defects

DTIC Science & Technology

2017-12-01

healing. Clin Orthop Relat Res. 1998;355(Suppl):S230–8. 37. Pape HC, Giannoudis PV. Fat embolism and IM nailing. Injury. 2006;37(Suppl 4):S1–2. 38. Wenda...mechanisms to elicit bone healing. 15. SUBJECT TERMS Bone healing, bone morphogenetic protein (BMP), thrombopoietin (TPO), therapy, fracture healing...thrombopoietin (TPO), therapy, fracture healing, bone regeneration, minipig, pig 3. OVERALL PROJECT SUMMARY: Project start date 30/09/2013 Project end

CD133: Enhancement of Bone Healing by Local Transplantation of Peripheral Blood Cells in a Biologically Delayed Rat Osteotomy Model

PubMed Central

Preininger, Bernd; Duda, Georg; Gerigk, Hinnerk; Bruckner, Jonas; Ellinghaus, Agnes; Sass, F. Andrea; Perka, Carsten; Schmidt-Bleek, Katharina; Dienelt, Anke

2013-01-01

Sufficient angiogenesis is crucial during tissue regeneration and therefore also pivotal in bone defect healing. Recently, peripheral blood derived progenitor cells have been identified to have in addition to their angiogenic potential also osteogenic characteristics, leading to the hypothesis that bone regeneration could be stimulated by local administration of these cells. The aim of this study was to evaluate the angiogenic potential of locally administered progenitor cells to improve bone defect healing. Cells were separated from the peripheral blood of donor animals using the markers CD34 and CD133. Results of the in vitro experiments confirmed high angiogenic potential in the CD133(+) cell group. CD34(+) and CD133(+) cells were tested in an in vivo rat femoral defect model of delayed healing for their positive effect on the healing outcome. An increased callus formation and higher bone mineral density of callus tissue was found after the CD133(+) cell treatment compared to the group treated with CD34(+) cells and the control group without cells. Histological findings confirmed an increase in vessel formation and mineralization at day 42 in the osteotomy gap after CD133(+) cell transplantation. The higher angiogenic potential of CD133(+) cells from the in vitro experients therefore correlates with the in vivo data. This study demonstrates the suitability of angiogenic precursors to further bone healing and gives an indication that peripheral blood is a promising source for progenitor cells circumventing the problems associated with bone marrow extraction. PMID:23457441

Bone-to-bone Fixation Enhances Functional Healing of the Porcine Anterior Cruciate Ligament Using a Collagen-Platelet Composite

PubMed Central

Murray, Martha M.; Magarian, Elise; Zurakowski, David; Fleming, Braden C.

2010-01-01

Purpose The purpose of this study was to determine if providing bony stabilization between the tibia and femur would improve the structural properties of an “enhanced” ACL repair using a collagen-platelet composite when compared to the traditional (Marshall) suture technique. Methods Twelve pigs underwent unilateral ACL transection and were treated with sutures connecting the bony femoral ACL attachment site to the distal ACL stump (LIGAMENT group), or to the tibia via a bone tunnel (TIBIA group). A collagen-platelet composite was placed around the sutures to enhance the biologic repair in both groups. Anteroposterior (AP) knee laxity and the graft structural properties were measured after 15 weeks of healing in both the ACL-repaired and contralateral ACL-intact joints. Results Enhanced ACL repair with bone-to-bone fixation significantly improved yield load and linear stiffness of the ACL repairs (p<0.05) after 15 weeks of healing. However, laxity values of the knees were similar in both groups of repaired knees (p>0.10). Conclusions Using an enhanced ACL suture repair technique that includes bone-to-bone fixation to protect the repair in the initial healing stages resulted in an ACL with improved structural properties after 15 weeks in the porcine model. Clinical Relevance The healing response of an ACL suture repair using a collagen-platelet composite can be enhanced by providing bony stabilization between the tibia and femur to protect the graft during the initial healing process in a translational model. PMID:20810092

Radiographic evaluation of marginal bone levels adjacent to parallel-screw cylinder machined-neck implants and rough-surfaced microthreaded implants using digitized panoramic radiographs.

PubMed

Nickenig, Hans-Joachim; Wichmann, Manfred; Schlegel, Karl Andreas; Nkenke, Emeka; Eitner, Stephan

2009-06-01

The purpose of this split-mouth study was to compare macro- and microstructure implant surfaces at the marginal bone level during a stress-free healing period and under functional loading. From January to February 2006, 133 implants (70 rough-surfaced microthreaded implants and 63 machined-neck implants) were inserted in the mandible of 34 patients with Kennedy Class I residual dentitions and followed until February 2008. The marginal bone level was radiographically determined, using digitized panoramic radiographs, at four time points: at implant placement (baseline level), after the healing period, after 6 months of functional loading, and at the end of follow-up. The median follow-up time was 1.9 (range: 1.9-2.1) years. The machined-neck group had a mean crestal bone loss of 0.5 mm (range: 0-2.3) after the healing period, 0.8 mm after 6 months (range: 0-2.4), and 1.1 mm (range: 0-3) at the end of follow-up. The rough-surfaced microthreaded implant group had a mean bone loss of 0.1 mm (range: -0.4-2) after the healing period, 0.4 mm (range: 0-2.1) after 6 months, and 0.5 mm (range: 0-2.1) at the end of follow-up. The two implant types showed significant differences in marginal bone levels (healing period: P=0.01; end of follow-up: P<0.01). Radiographic evaluation of marginal bone levels adjacent to machined-neck or rough-surfaced microthreaded implants showed that implants with the microthreaded design caused minimal changes in crestal bone levels during healing (stress-free) and under functional loading.

Biomimetics of Bone Implants: The Regenerative Road.

PubMed

Brett, Elizabeth; Flacco, John; Blackshear, Charles; Longaker, Michael T; Wan, Derrick C

2017-01-01

The current strategies for healing bone defects are numerous and varied. At the core of each bone healing therapy is a biomimetic mechanism, which works to enhance bone growth. These range from porous scaffolds, bone mineral usage, collagen, and glycosaminoglycan substitutes to transplanted cell populations. Bone defects face a range of difficulty in their healing, given the composite of dense outer compact bone and blood-rich inner trabecular bone. As such, the tissue possesses a number of inherent characteristics, which may be clinically harnessed as promoters of bone healing. These include mechanical characteristics, mineral composition, native collagen content, and cellular fraction of bone. This review charts multiple biomimetic strategies to help heal bony defects in large and small osseous injury sites, with a special focus on cell transplantation.

Nonsteroidal Anti-Inflammatory Drugs and Bone-Healing: A Systematic Review of Research Quality.

PubMed

Marquez-Lara, Alejandro; Hutchinson, Ian D; Nuñez, Fiesky; Smith, Thomas L; Miller, Anna N

2016-03-15

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often avoided by orthopaedic surgeons because of their possible influence on bone-healing. This belief stems from multiple studies, in particular animal studies, that show delayed bone-healing or nonunions associated with NSAID exposure. The purpose of this review was to critically analyze the quality of published literature that evaluates the impact of NSAIDs on clinical bone-healing. A MEDLINE and Embase search was conducted to identify all articles relating to bone and fracture-healing and the utilization of NSAIDs. All human studies, including review articles, were identified for further analysis. Non-English-language manuscripts and in vitro and animal studies were excluded. A total of twelve clinical articles and twenty-four literature reviews were selected for analysis. The quality of the clinical studies was assessed with a modified Coleman Methodology Score with emphasis on the NSAID utilization. Review articles were analyzed with regard to variability in the cited literature and final conclusions. The mean modified Coleman Methodology Score (and standard deviation) was significantly lower (p = 0.032) in clinical studies that demonstrated a negative effect of NSAIDs on bone-healing (40.0 ± 14.3 points) compared with those that concluded that NSAIDs were safe (58.8 ± 10.3 points). Review articles also demonstrated substantial variability in the number of cited clinical studies and overall conclusions. There were only two meta-analyses and twenty-two narrative reviews. The mean number (and standard deviation) of clinical studies cited was significantly greater (p = 0.008) for reviews that concluded that NSAIDs were safe (8.0 ± 4.8) compared with those that recommended avoiding them (2.1 ± 2.1). Unanimously, all reviews admitted to the need for prospective randomized controlled trials to help clarify the effects of NSAIDs on bone-healing. This systematic literature review highlights the great variability in the interpretation of the literature addressing the impact of NSAIDs on bone-healing. Unfortunately, there is no consensus regarding the safety of NSAIDs following orthopaedic procedures, and future studies should aim for appropriate methodological designs to help to clarify existing discrepancies to improve the quality of care for orthopaedic patients. This systematic review highlights the limitations in the current understanding of the effects of NSAIDs on bone healing. Thus, withholding these medications does not have any proven scientific benefit to patients and may even cause harm by increasing narcotic requirements in cases in which they could be beneficial for pain management. This review should encourage further basic-science and clinical studies to clarify the risks and benefits of anti-inflammatory medications in the postoperative period, with the aim of improving patient outcomes.

Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34).

PubMed

Ren, Yongxin; Liu, Bo; Feng, Yuxu; Shu, Lei; Cao, Xiaojian; Karaplis, Andrew; Goltzman, David; Miao, Dengshun

2011-01-01

Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s) whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH. Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth(-/-)) mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg) for 1-4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth(-/-) mice compared to vehicle-treated wild-type and Pth(-/-) mice. Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing.

Aging Periosteal Progenitor Cells have Reduced Regenerative Responsiveness to Bone Injury and to the Anabolic Actions of PTH 1-34 Treatment

PubMed Central

Yukata, Kiminori; Xie, Chao; Li, Tian-Fang; Takahata, Masahiko; Hoak, Donna; Kondabolu, Sirish; Zhang, Xinping; Awad, Hani A.; Schwarz, Edward M.; Beck, Christopher A.; Jonason, Jennifer H.; O’Keefe, Regis J.

2014-01-01

A stabilized tibia fracture model was used in young (8-week old) and aged (1-year old) mice to define the relative bone regenerative potential and the relative responsiveness of the periosteal progenitor population with aging and PTH 1-34 (PTH) systemic therapy. Bone regeneration was assessed through gene expressions, radiographic imaging, histology/histomorphometry, and biomechanical testing. Radiographs and microCT showed increased calcified callus tissue and enhanced bone healing in young compared to aged mice. A key mechanism involved reduced proliferation, expansion, and differentiation of periosteal progenitor cell populations in aged mice. The experiments showed that PTH increased calcified callus tissue and torsional strength with a greater response in young mice. Histology and quantitative histomorphometry confirmed that PTH increased callus tissue area due primarily to an increase in bone formation, since minimal changes in cartilage and mesenchyme tissue area occurred. Periosteum examined at 3, 5, and 7 days showed that PTH increased cyclin D1 expression, the total number of cells in the periosteum, and width of the periosteal regenerative tissue. Gene expression showed that aging delayed differentiation of both bone and cartilage tissues during fracture healing. PTH resulted in sustained Col10a1 expression consistent with delayed chondrocyte maturation, but otherwise minimally altered cartilage gene expression. In contrast, PTH 1-34 stimulated expression of Runx2 and Osterix, but resulted in reduced Osteocalcin. β-catenin staining was present in mesenchymal chondroprogenitors and chondrocytes in early fracture healing, but was most intense in osteoblastic cells at later times. PTH increased active β-catenin staining in the osteoblast populations of both young and aged mice, but had a lesser effect in cartilage. Altogether the findings show that reduced fracture healing in aging involves decreased proliferation and differentiation of stem cells lining the bone surface. While PTH 1-34 enhances the proliferation and expansion of the periosteal stem cell population and accelerates bone formation and fracture healing, the effects are proportionately reduced in aged mice compared to young mice. β-catenin is induced by PTH in early and late fracture healing and is a potential target of PTH 1-34 effects. PMID:24530870

Microgrooved Polymer Substrates Promote Collective Cell Migration To Accelerate Fracture Healing in an in Vitro Model.

PubMed

Zhang, Qing; Dong, Hua; Li, Yuli; Zhu, Ye; Zeng, Lei; Gao, Huichang; Yuan, Bo; Chen, Xiaofeng; Mao, Chuanbin

2015-10-21

Surface topography can affect cell adhesion, morphology, polarity, cytoskeleton organization, and osteogenesis. However, little is known about the effect of topography on the fracture healing in repairing nonunion and large bone defects. Microgrooved topography on the surface of bone implants may promote cell migration into the fracture gap to accelerate fracture healing. To prove this hypothesis, we used an in vitro fracture (wound) healing assay on the microgrooved polycaprolactone substrates to study the effect of microgroove widths and depths on the osteoblast-like cell (MG-63) migration and the subsequent healing. We found that the microgrooved substrates promoted MG-63 cells to migrate collectively into the wound gap, which serves as a fracture model, along the grooves and ridges as compared with the flat substrates. Moreover, the groove widths did not show obvious influence on the wound healing whereas the smaller groove depths tended to favor the collective cell migration and thus subsequent healing. The microgrooved substrates accelerated the wound healing by facilitating the collective cell migration into the wound gaps but not by promoting the cell proliferation. Furthermore, microgrooves were also found to promote the migration of human mesenchymal stem cells (hMSCs) to heal the fracture model. Though osteogenic differentiation of hMSCs was not improved on the microgrooved substrate, collagen I and minerals deposited by hMSCs were organized in a way similar to those in the extracellular matrix of natural bone. These findings suggest the necessity in using microgrooved implants in enhancing fracture healing in bone repair.

The effect of mesenchymal stem cells delivered via hydrogel-based tissue engineered periosteum on bone allograft healing.

PubMed

Hoffman, Michael D; Xie, Chao; Zhang, Xinping; Benoit, Danielle S W

2013-11-01

Allografts remain the clinical "gold standard" for treatment of critical sized bone defects despite minimal engraftment and ∼60% long-term failure rates. Therefore, the development of strategies to improve allograft healing and integration are necessary. The periosteum and its associated stem cell population, which are lacking in allografts, coordinate autograft healing. Herein we utilized hydrolytically degradable hydrogels to transplant and localize mesenchymal stem cells (MSCs) to allograft surfaces, creating a periosteum mimetic, termed a 'tissue engineered periosteum'. Our results demonstrated that this tissue engineering approach resulted in increased graft vascularization (∼2.4-fold), endochondral bone formation (∼2.8-fold), and biomechanical strength (1.8-fold), as compared to untreated allografts, over 16 weeks of healing. Despite this enhancement in healing, the process of endochondral ossification was delayed compared to autografts, requiring further modifications for this approach to be clinically acceptable. However, this bottom-up biomaterials approach, the engineered periosteum, can be augmented with alternative cell types, matrix cues, growth factors, and/or other small molecule drugs to expedite the process of ossification. Copyright © 2013 Elsevier Ltd. All rights reserved.

The osteo-inductive activity of bone-marrow-derived mononuclear cells resides within the CD14+ population and is independent of the CD34+ population.

PubMed

Henrich, D; Seebach, C; Verboket, R; Schaible, A; Marzi, I; Bonig, H

2018-03-06

Bone marrow mononuclear cells (BMC) seeded on a scaffold of β-tricalcium phosphate (β-TCP) promote bone healing in a critical-size femur defect model. Being BMC a mixed population of predominantly mature haematopoietic cells, which cell type(s) is(are) instrumental for healing remains elusive. Although clinical therapies using BMC are often dubbed as stem cell therapies, whether stem cells are relevant for the therapeutic effects is unclear and, at least in the context of bone repair, seems dubious. Instead, in light of the critical contribution of monocytes and macrophages to tissue development, homeostasis and injury repair, in the current study it was hypothesised that BMC-mediated bone healing derived from the stem cell population. To test this hypothesis, bone remodelling studies were performed in an established athymic rats critical-size femoral defect model, with β-TCP scaffolds augmented with complete BMC or BMC immunomagnetically depleted of stem cells (CD34+) or monocytes/macrophages (CD14+). Bone healing was assessed 8 weeks after transplantation. Compared to BMC-augmented controls, when CD14- BMC, but not CD34- BMC were transplanted into the bone defect, femora possessed dramatically decreased biomechanical stability and new bone formation was markedly reduced, as measured by histology. The degree of vascularisation did not differ between the two groups. It was concluded that the monocyte fraction within the BMC provided critical osteo-inductive cues during fracture healing. Which factors were responsible at the molecular levels remained elusive. However, this study marked a significant progress towards elucidating the mechanisms by which BMC elicit their therapeutic effects, at least in bone regeneration.

The effect of layer-by-layer chitosan-hyaluronic acid coating on graft-to-bone healing of a poly(ethylene terephthalate) artificial ligament.

PubMed

Li, Hong; Ge, Yunsheng; Zhang, Pengyun; Wu, Lingxiang; Chen, Shiyi

2012-01-01

Surface coating with an organic layer-by-layer self-assembled template of chitosan and hyaluronic acid on a poly(ethylene terephthalate) (PET) artificial ligament was designed for the promotion and enhancement of graft-to-bone healing after artificial ligament implantation in a bone tunnel. The results of in vitro culturing of MC3T3-E1 mouse osteoblastic cells supported the hypothesis that the layer-by-layer coating of chitosan and hyaluronic acid could promote the cell compatibility of grafts and could promote osteoblast proliferation. A rabbit extra-articular tendon-to-bone healing model was used to evaluate the effect of this kind of surface-modified stainless artificial ligament in vivo. The final results proved that this organic compound coating could significantly promote and enhance new bone formation at the graft-bone interface histologically and, correspondingly, the experimental group with coating had significantly higher biomechanical properties compared with controls at 8 weeks (P < 0.05).

Comparison of titanium elastic intramedullary nailing versus injection of bone marrow in treatment of simple bone cysts in children: a retrospective study.

PubMed

Li, Wenchao; Xu, Ruijiang; Du, Minghua; Chen, Hui

2016-08-15

Simple bone cysts are common benign lytic bone lesions in children. The main goals of treatment for bone cysts are to prevent pathological fractures, support the healing process, and prevent recurrence. This retrospective study compared fixation with titanium elastic intramedullary nailing (TEN) versus aspiration and injection of autogenous bone marrow (ABM) for the treatment of simple bone cysts in children. Forty-six patients (mean follow-up, 62 months; range, 34-71 months) who presented with bone cysts (30 in the humerus, 16 in the femur) from January 2006 to December 2012 were retrospectively evaluated. Patients were treated with either TEN or ABM injection. Radiographs were evaluated according to previously established criteria. Clinical evaluations of pain, infection, additional fractures, and range of motion were performed. After treatment, all patients were pain-free and had normal range of motion in adjacent joints. In the ABM group, 14 (60.9 %) bone cysts completely healed, six (26.1 %) healed with small residuals after two injections, and three (13.0 %) recurred. In the TEN group, 16 (69.6 %) bone cysts completely healed, four (17.4 %) healed with small residuals, and three (13.0 %) recurred. There were no significant differences in radiographic outcomes between groups at the final follow-up (P > 0.05). Three patients developed skin irritation as a result of the nail ends. Additional fractures occurred in four patients who underwent ABM injection and in two patients who underwent TEN. No significant associations were found between pathological fractures and cyst activity, location, or treatment outcomes in the patients studied. Both TEN and ABM injection are safe and effective treatment for bone cysts. ABM injection promotes osteogenic differentiation of bone marrow stromal cells; multiple injections can reduce the likelihood of recurrence. TEN stabilizes the affected bone and thus allows early limb mobilization. It also reduces pressure in the capsule wall by continuous decompression to promote cyst healing. ABM injections can be used to treat cyst recurrence after previous TEN, with favorable results.

Novel Therapy for Bone Regeneration in Large Segmental Defects

DTIC Science & Technology

2017-12-01

on fracture healing. Clin Orthop Relat Res. 1998;355(Suppl):S230–8. 37. Pape HC, Giannoudis PV. Fat embolism and IM nailing. Injury. 2006;37(Suppl 4...BMP), thrombopoietin (TPO), therapy, fracture healing, bone regeneration, minipig, pig 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT...2, TPO, or saline control. 2. KEYWORDS: Bone healing, bone morphogenetic protein (BMP), thrombopoietin (TPO), therapy, fracture healing, bone

Effects of salmon calcitonin on fracture healing in ovariectomized rats.

PubMed

Li, Xiaolin; Luo, Xinle; Yu, Nansheng; Zeng, Bingfang

2007-01-01

To explore the effects of salmon calcitonin on the healing process of osteoporotic fractures in ovariectomized rats. We performed this study in The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China, during the period March 2002 to December 2004. We used 120 female adult Wistar rats in this experiment, among which 90 underwent ovariectomy (OVX) and the other 30 had sham-operation. All rats had their left tibias fractured 3 months later. The 90 OVX rats were randomly divided into 3 groups with 30 in each, while the 30 sham-operated rats served as control group. After the fracture the rats had subcutaneous injection of normal saline, salmon calcitonin and estrogen, respectively. X-ray film, histological examination, bone mineral density (BMD) measurement and biomechanics testing were carried out to evaluate the fracture healing. Compared with OVX rats treated with normal saline, the rats with salmon calcitonin had significantly higher BMD values in the left tibia, higher max torque, shear stress of the left tibia 8 weeks after fracture (p<0.05), and presented with stronger callus formation, shorter fracture healing time and faster normalization of microstructure of bone trabeculae. Salmon calcitonin can, not only increase BMD in osteoporotic bone, but also enhance the bone biomechanical properties and improve the process of fracture healing in fractured osteoporotic bone.

Rotary self-locking intramedullary nail for long tubular bone fractures.

PubMed

Huang, Zhong-lian; Yang, Hai-long; Xu, Jian-kun; Xia, Xue; Wang, Xin-jia; Song, Jian-xin; Hu, Jun

2013-10-01

Intramedullary nails had been widely used in the treatment of long-bone fractures because of less interference of fractures and center bearing biomechanical advantage. However, it had been also found many shortcomings such as broken nails, delayed healing and was modified in order to achieve better efficacy and reduce complications. The aim of the present study is to compare the efficacy of rotary self-locking intramedullary nails (RSIN) with that of interlocking intramedullary nails (IIN) in the treatment of long-bone fractures. A retrospective study investigated 129 cases with long-bone fractures (36 with femoral fracture, 81 with tibial fracture, and 12 with humeral fracture). The fractures were fixed using either an RSIN or IIN. All patients underwent followup for 12-30 months. All patients in both groups achieved a clinical fracture healing standard and the postoperative affected limb muscle strength and joint function were well restored. The RSIN group required a shorter operative time and the fracture healed faster. There was no significant difference in the hospital stay, intraoperative blood loss or postoperative complications between the two groups. RSIN is used to treat long-bone fractures. Its healing efficacy is equivalent to the IIN. Moreover, the RSIN method is simpler and causes less tissue damage than the IIN, therefore having the advantage of accelerated healing.

Clinical Investigation Program Annual Progress Report

DTIC Science & Technology

1993-09-30

272 93/200A 0 Comparison of Healing Rates of Bones Plated Following Fracture, Among Yucatan Swine Having Open and Closed Physes...Study Objective: Compare two enteral formulas in respect to nutritional aspects. (16) Technical Approach: Protocol will take place in SICU. (17...Protocol #: 93/200A (3) Status: Ongoing (4) Title: Comparison of Healing Rates of Bones Plated Following Fractures, Among Yucatan Swine Having Open and

Inkjet-based biopatterning of SDF-1β augments BMP-2-induced repair of critical size calvarial bone defects in mice

PubMed Central

Herberg, Samuel; Kondrikova, Galina; Periyasamy-Thandavan, Sudharsan; Howie, R. Nicole; Elsalanty, Mohammed E.; Weiss, Lee; Campbell, Phil; Hill, William D.; Cray, James J.

2014-01-01

Background A major problem in craniofacial surgery is non-healing bone defects. Autologous reconstruction remains the standard of care for these cases. Bone morphogenetic protein-2 (BMP-2) therapy has proven its clinical utility, although non-targeted adverse events occur due to the high milligram-level doses used. Ongoing efforts explore the use of different growth factors, cytokines, or chemokines, as well as co-therapy to augment healing. Methods Here we utilize inkjet-based biopatterning to load acellular DermaMatrix delivery matrices with nanogram-level doses of BMP-2, stromal cell-derived factor-1β (SDF-1β), transforming growth factor-β1 (TGF-β1), or co-therapies thereof. We tested the hypothesis that bioprinted SDF-1β co-delivery enhances BMP-2 and TGF-β1-driven osteogenesis both in-vitro and in-vivo using a mouse calvarial critical size defect (CSD) model. Results Our data showed that BMP-2 bioprinted in low-doses induced significant new bone formation by four weeks post-operation. TGF-β1 was less effective compared to BMP-2, and SDF-1β therapy did not enhance osteogenesis above control levels. However, co-delivery of BMP-2 + SDF-1β was shown to augment BMP-2-induced bone formation compared to BMP-2 alone. In contrast, co-delivery of TGF-β1 + SDF-1β decreased bone healing compared to TGF-β1 alone. This was further confirmed in vitro by osteogenic differentiation studies using MC3T3-E1 pre-osteoblasts. Conclusions Our data indicates that sustained release delivery of a low-dose growth factor therapy using biopatterning technology can aid in healing CSD injuries. SDF-1β augments the ability for BMP-2 to drive healing, a result confirmed in vivo and in vitro; however, because SDF-1β is detrimental to TGF-β1-driven osteogenesis, its’ effect on osteogenesis is not universal. PMID:25016095

Modeling Staphylococcus epidermidis-Induced Non-Unions: Subclinical and Clinical Evidence in Rats

PubMed Central

Lovati, Arianna Barbara; Romanò, Carlo Luca; Bottagisio, Marta; Monti, Lorenzo; De Vecchi, Elena; Previdi, Sara; Accetta, Riccardo; Drago, Lorenzo

2016-01-01

S. epidermidis is one of the leading causes of orthopaedic infections associated with biofilm formation on implant devices. Open fractures are at risk of S. epidermidis transcutaneous contamination leading to higher non-union development compared to closed fractures. Although the role of infection in delaying fracture healing is well recognized, no in vivo models investigated the impact of subclinical low-grade infections on bone repair and non-union. We hypothesized that the non-union rate is directly related to the load of this commonly retrieved pathogen and that a low-grade contamination delays the fracture healing without clinically detectable infection. Rat femurs were osteotomized and stabilized with plates. Fractures were infected with a characterized clinical-derived methicillin-resistant S. epidermidis (103, 105, 108 colony forming units) and compared to uninfected controls. After 56 days, bone healing and osteomyelitis were clinically assessed and further evaluated by micro-CT, microbiological and histological analyses. The biofilm formation was visualized by scanning electron microscopy. The control group showed no signs of infection and a complete bone healing. The 103 group displayed variable response to infection with a 67% of altered bone healing and positive bacterial cultures, despite no clinical signs of infection present. The 105 and 108 groups showed severe signs of osteomyelitis and a non-union rate of 83–100%, respectively. The cortical bone reaction related to the periosteal elevation in the control group and the metal scattering detected by micro-CT represented limitations of this study. Our model showed that an intra-operative low-grade S. epidermidis contamination might prevent the bone healing, even in the absence of infectious signs. Our findings also pointed out a dose-dependent effect between the S. epidermidis inoculum and non-union rate. This pilot study identifies a relevant preclinical model to assess the role of subclinical infections in orthopaedic and trauma surgery and to test specifically designed diagnostic, prevention and therapeutic strategies. PMID:26796958

Immediate provisionalization of dental implants placed in healed alveolar ridges and extraction sockets: a 5-year prospective evaluation.

PubMed

Cooper, Lyndon F; Reside, Glenn J; Raes, Filiep; Garriga, Joan Soliva; Tarrida, Luis Giner; Wiltfang, Jörg; Kern, Matthias; De Bruyn, Hugo

2014-01-01

This 5-year prospective multicenter study compared implant survival and success, peri-implant health and soft tissue responses, crestal bone level stability, and complication rates following immediate loading of single OsseoSpeed implants placed in anterior maxillary healed ridges or extraction sockets. Individuals requiring anterior tooth replacement with single implants were treated and immediately provisionalized. Definitive all-ceramic crowns were placed at 12 weeks. Implant survival, bone levels, soft tissue levels, and peri-implant health were monitored for 5 years. One hundred thirteen patients received implants in fresh sockets (55) and healed ridges (58). After 5 years, 45 and 49 patients remained for evaluation, respectively. During the first year, three implants failed in the extraction socket group (94.6% survival) and one implant failed in the healed ridge group (98.3% survival); this difference was not significant. No further implant failures were recorded. After 5 years, the interproximal crestal bone levels were located a mean of 0.43 ± 0.63 mm and 0.38 ± 0.62 mm from the reference points of implants in sockets and healed ridges (not a significant difference). In both groups, papillae increased over time and peri-implant mucosal zenith positions were stable from the time of definitive crown placement in sockets and healed ridges. Compared to flap surgery for implants in healed ridges, flapless surgery resulted in increased peri-implant mucosal tissue dimension (average, 0.78 ± 1.34 mm vs 0.19 ± 0.79 mm). After 5 years, the bone and soft tissue parameters that characterize implant success and contribute to dental implant esthetics were similar following the immediate provisionalization of implants in sockets and healed ridges. The overall tissue responses and reported implant survival support the immediate provisionalization of dental implants in situations involving healed ridges and, under ideal circumstances, extraction sockets.

Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles.

PubMed

Förster, Yvonne; Schmidt, Johannes R; Wissenbach, Dirk K; Pfeiffer, Susanne E M; Baumann, Sven; Hofbauer, Lorenz C; von Bergen, Martin; Kalkhof, Stefan; Rammelt, Stefan

2016-01-01

Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis.

Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles

PubMed Central

Wissenbach, Dirk K.; Pfeiffer, Susanne E. M.; Baumann, Sven; Hofbauer, Lorenz C.; von Bergen, Martin; Kalkhof, Stefan; Rammelt, Stefan

2016-01-01

Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis. PMID:27441377

Exogenous PTHrP Repairs the Damaged Fracture Healing of PTHrP+/− Mice and Accelerates Fracture Healing of Wild Mice

PubMed Central

Wang, Yinhe; Fang, Xin; Wang, Chun; Ding, Congzhu; Lin, Hua; Liu, Anlong; Wang, Lei; Cao, Yang

2017-01-01

Bone fracture healing is a complicated physiological regenerative process initiated in response to injury and is similar to bone development. To demonstrate whether an exogenous supply of parathyroid hormone–related protein (PTHrP) helps in bone fracture healing, closed mid-diaphyseal femur fractures were created and stabilized with intramedullary pins in eight-week-old wild-type (WT) PTHrP+/+ and PTHrP+/− mice. After administering PTHrP for two weeks, callus tissue properties were analyzed at one, two, and four weeks post-fracture (PF) by various methods. Bone formation–related genes and protein expression levels were evaluated by real-time reverse transcriptase–polymerase chain reaction and Western blots. At two weeks PF, mineral density of callus, bony callus areas, mRNA levels of alkaline phosphatase (ALP), type I collagen, Runt-related transcription factor 2 (Runx-2), and protein levels of Runx-2 and insulin-like growth factor-1 decreased in PTHrP+/− mice compared with WT mice. At four weeks PF, total collagen-positive bony callus areas, osteoblast number, ALP-positive areas, and type I collagen-positive areas all decreased in PTHrP+/− mice. At both two and four weeks PF, tartrate-resistant acid phosphatase–positive osteoclast number and surface decreased a little in PTHrP+/− mice. The study indicates that exogenous PTHrP provided by subcutaneous injection could redress impaired bone fracture healing, leading to mutation of activated PTHrP by influencing callus areas, endochondral bone formation, osteoblastic bone formation, and bone turnover. PMID:28178186

Bone Healing and Hormonal Bioassay in Patients with Long-Bone Fractures and Concomitant Head Injury.

PubMed

Khallaf, Fathy G; Kehinde, Elijah O; Hussein, Sundus

The aim of this study is to investigate healing of fractures in patients with concomitant head injuries and to measure blood hormone levels to elucidate the mechanism of a possible accelerated osteogenesis. One hundred and sixty-two patients were included in this study and divided into 3 cohorts: group A with head injuries only (n = 52); group B with head injuries as well as long-bone fractures (n = 50); group C with long-bone fractures only (n = 60). Fracture-healing parameters including time of appearance and thickness of the bridging callus, and blood hormonal assays were measured and compared using Student's t test. The mean time to healing was significantly lower in cohort B (6.9 ± 2.9 weeks) than C (22.4 ± 8.7 weeks; p = 0.001). The mean thickness of the healing callus was significantly higher in cohort B (26.3 ± 9.7 mm) than C (8.1 ± 5.9 mm; p = 0.002). The mean healing rate was also higher in cohort B (4.5 ± 2.3 mm/week) than C (0.38 ± 0.21 mm/week; p = 0.001). Blood hormonal assays in group B showed higher values of parathyroid hormone and growth hormone than in group C. However, adrenaline and noradrenaline values were lower in group B than in group C at all measured time intervals, and correspondingly leptin was lower in all groups (p = 0.001). Corticosteroid values were normal in group B compared to slightly higher values in group C, also at all measured time intervals. In this study, healing of fractures in patients with concomitant head injuries was accelerated, thereby indicating an involvement of a combined neurohormonal mechanism. © 2016 S. Karger AG, Basel.

A unified theory of bone healing and nonunion: BHN theory.

PubMed

Elliott, D S; Newman, K J H; Forward, D P; Hahn, D M; Ollivere, B; Kojima, K; Handley, R; Rossiter, N D; Wixted, J J; Smith, R M; Moran, C G

2016-07-01

This article presents a unified clinical theory that links established facts about the physiology of bone and homeostasis, with those involved in the healing of fractures and the development of nonunion. The key to this theory is the concept that the tissue that forms in and around a fracture should be considered a specific functional entity. This 'bone-healing unit' produces a physiological response to its biological and mechanical environment, which leads to the normal healing of bone. This tissue responds to mechanical forces and functions according to Wolff's law, Perren's strain theory and Frost's concept of the "mechanostat". In response to the local mechanical environment, the bone-healing unit normally changes with time, producing different tissues that can tolerate various levels of strain. The normal result is the formation of bone that bridges the fracture - healing by callus. Nonunion occurs when the bone-healing unit fails either due to mechanical or biological problems or a combination of both. In clinical practice, the majority of nonunions are due to mechanical problems with instability, resulting in too much strain at the fracture site. In most nonunions, there is an intact bone-healing unit. We suggest that this maintains its biological potential to heal, but fails to function due to the mechanical conditions. The theory predicts the healing pattern of multifragmentary fractures and the observed morphological characteristics of different nonunions. It suggests that the majority of nonunions will heal if the correct mechanical environment is produced by surgery, without the need for biological adjuncts such as autologous bone graft. Cite this article: Bone Joint J 2016;98-B:884-91. ©2016 The British Editorial Society of Bone & Joint Surgery.

Effect of Zoledronate on Oral Wound Healing in Rats

PubMed Central

Yamashita, Junro; Koi, Kiyono; Yang, Dong-Ye; McCauley, Laurie K.

2010-01-01

Purpose Osteonecrosis of the jaw (ONJ) is a growing concern in patients who receive bisphosphonates which target osteoclasts. Since osteoclasts play multifunctional roles in the bone marrow, their suppression likely affects bone homeostasis and alters wound healing of the jaw. The objective was to delineate the impact of osteoclast suppression in the bone marrow and wound healing of the jaw. Experimental Design Zoledronate was administered to senile rats for 14 weeks. A portion of the gingiva was removed to denude the palatal bone. Gene expression in the bone marrow was assessed and histologic sections analyzed to determine the wound healing status. Results Angiogenesis-related genes, CD31 and VEGF-A, were not altered by zoledronate. VEGF-C, which plays a role in lymphangiogenesis, was suppressed. There was a decrease in gene expression of Tcirg1 and MMP-13. Bone denudation caused extensive osteocyte death indicative of bone necrosis. In zoledronate-treated rats, the necrotic bone was retained in the wound while, in controls, osteoclastic resorption of the necrotic bone was prominent. Even though large necrotic bone areas existed in zoledronate-treated rats, overlaying soft tissue healed clinically. Immunohistochemical staining showed rich vascularity in the overlaying soft tissue. Conclusions Zoledronate therapy impacts bone marrow by suppressing genes associated with lymphoangiogenesis and tissue remodeling, such as VEGF-C and MMP-13. Zoledronate was associated with impaired osseous wound healing but had no effect on angiogenic markers in the bone marrow or soft tissue wound healing. Zoledronate selectively blunts healing in bone but does not effect soft tissue healing in the oral cavity. PMID:21149614

Smoking cessation and bone healing: optimal cessation timing.

PubMed

Truntzer, Jeremy; Vopat, Bryan; Feldstein, Michael; Matityahu, Amir

2015-02-01

Smoking is a worldwide epidemic. Complications related to smoking behavior generate an economic loss around $193 billion annually. In addition to impacting chronic health conditions, smoking is linked to increased perioperative complications in those with current or previous smoking history. Numerous studies have demonstrated more frequent surgical complications including higher rates of infection, poor wound healing, heightened pain complaints, and increased pulmonary morbidities in patients with a smoking history. Longer preoperative cessation periods also seem to correlate with reduced rates. At roughly 4 weeks of cessation prior to surgery, complication rates more closely reflect individuals without a smoking history in comparison with those that smoke within 4 weeks of surgery. In the musculoskeletal system, a similar trend has been observed in smokers with higher rates of fractures, nonunions, malunions, infections, osteomyelitis, and lower functional scores compared to non-smoking patients. Unfortunately, the present literature lacks robust data suggesting a temporal relationship between smoking cessation and bone healing. In our review, we analyze pseudoarthrosis rates following spinal fusion to suggest that bone healing in the context of smoking behavior follows a similar time sequence as observed in wound healing. We also discuss the implications for further clarity on bone healing and smoking cessation within orthopedics including improved risk stratification and better identification of circumstances where adjunct therapy is appropriate.

Assessment of tricalcium phosphate/collagen (TCP/collagene)nanocomposite scaffold compared with hydroxyapatite (HA) on healing of segmental femur bone defect in rabbits.

PubMed

Mohseni, Mahmoud; Jahandideh, Alireza; Abedi, Gholamreza; Akbarzadeh, Abolfazl; Hesaraki, Saeed

2018-03-01

Bone regeneration is an important objective in clinical practice and has been used for different applications. The aim of this study was to evaluate the effectiveness of nanocomposite tricalcium phosphate (TCP)/collagen scaffolds combined with hydroxyapatite scaffold for bone healing in surgery of femoral defects in rabbits. In this study, 45 mature male New Zealand white rabbits between 6 and 8 months old and weighting between 3 and 3.5 kg were examined. Rabbits were divided into three groups. Surgical procedures were performed after intramuscular injection of Ketamine 10% (ketamine hydrochloride, 50 mg/kg) and Rompun 5% (xylazine, 5 mg/kg). Then an approximately 6 mm diameter-5 mm cylinder bone defect was created in the femur of one of the hind limbs. After inducing the surgical wound, all rabbits were coloured and randomly divided into three experimental groups of 15 animals each. Group 1 received pure medical nanocomposite TCP/collagen granules, group 2 received hydroxyapatite, and third group was a control group which received no treatment. Histopathological evaluation was performed on days 15, 30, and 45 after surgery. On days 15, 30, and 45 after surgery, the quantity and the velocity of stages of bone formation at the healing site in nanocomposite TCP/collagen group were better than HA and control groups and the quantity of newly formed lamellar bone at the healing site in nanocomposite TCP/collagen group were better than onward compared with HA and control groups. In conclusion, it seems that TCP/collagen nanocomposite has a significant role in the reconstruction of bone defects and can be used as scaffold in bone fractures.

T-Lymphocytes Enable Osteoblast Maturation via IL-17F during the Early Phase of Fracture Repair

PubMed Central

Nam, Diane; Mau, Elaine; Wang, Yufa; Wright, David; Silkstone, David; Whetstone, Heather; Whyne, Cari; Alman, Benjamin

2012-01-01

While it is well known that the presence of lymphocytes and cytokines are important for fracture healing, the exact role of the various cytokines expressed by cells of the immune system on osteoblast biology remains unclear. To study the role of inflammatory cytokines in fracture repair, we studied tibial bone healing in wild-type and Rag1−/− mice. Histological analysis, µCT stereology, biomechanical testing, calcein staining and quantitative RNA gene expression studies were performed on healing tibial fractures. These data provide support for Rag1−/− mice as a model of impaired fracture healing compared to wild-type. Moreover, the pro-inflammatory cytokine, IL-17F, was found to be a key mediator in the cellular response of the immune system in osteogenesis. In vitro studies showed that IL-17F alone stimulated osteoblast maturation. We propose a model in which the Th17 subset of T-lymphocytes produces IL-17F to stimulate bone healing. This is a pivotal link in advancing our current understanding of the molecular and cellular basis of fracture healing, which in turn may aid in optimizing fracture management and in the treatment of impaired bone healing. PMID:22768215

The mechanical heterogeneity of the hard callus influences local tissue strains during bone healing: a finite element study based on sheep experiments.

PubMed

Vetter, A; Liu, Y; Witt, F; Manjubala, I; Sander, O; Epari, D R; Fratzl, P; Duda, G N; Weinkamer, R

2011-02-03

During secondary fracture healing, various tissue types including new bone are formed. The local mechanical strains play an important role in tissue proliferation and differentiation. To further our mechanobiological understanding of fracture healing, a precise assessment of local strains is mandatory. Until now, static analyses using Finite Elements (FE) have assumed homogenous material properties. With the recent quantification of both the spatial tissue patterns (Vetter et al., 2010) and the development of elastic modulus of newly formed bone during healing (Manjubala et al., 2009), it is now possible to incorporate this heterogeneity. Therefore, the aim of this study is to investigate the effect of this heterogeneity on the strain patterns at six successive healing stages. The input data of the present work stemmed from a comprehensive cross-sectional study of sheep with a tibial osteotomy (Epari et al., 2006). In our FE model, each element containing bone was described by a bulk elastic modulus, which depended on both the local area fraction and the local elastic modulus of the bone material. The obtained strains were compared with the results of hypothetical FE models assuming homogeneous material properties. The differences in the spatial distributions of the strains between the heterogeneous and homogeneous FE models were interpreted using a current mechanobiological theory (Isakson et al., 2006). This interpretation showed that considering the heterogeneity of the hard callus is most important at the intermediate stages of healing, when cartilage transforms to bone via endochondral ossification. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effect of rhBMP-2 on tibial plateau fractures in a canine model.

PubMed

Schaefer, Susan L; Lu, Yan; Seeherman, Howard; Li, X Jian; Lopez, Mandi J; Markel, Mark D

2009-04-01

This study was to determine the efficacy of recombinant human bone morphogenetic protien-2 (rhBMP-2)/calcium phosphate matrix (CPX) paste to accelerate healing in a canine articular fracture model with associated subchondral defect. rhBMP-2/CPX (BMP), CPX alone (CPX) or autogenous bone graft (ABG) was administered to a canine articular tibial plateau osteotomy with a subchondral defect in each of 21 female dogs. The unoperated contralateral limbs served as controls. Ground reaction forces, synovial fluid, radiographic changes, mechanical testing, bone density, and histology of bone and synovium were analyzed at 6 weeks after surgery. Radiographic analysis demonstrated that the BMP and CPX groups showed improved bony healing compared to the ABG group at week 6. Histomorphometric analysis demonstrated that the BMP group had significantly increased trabecular bone volume compared to the CPX and ABG groups. Mechanical testing revealed that the BMP group had significantly greater maximum failure loads than the ABG group. Histological analysis demonstrated that the BMP group had significantly less sub-synovial inflammation than CPX group. This study demonstrated that rhBMP-2/CPX accelerated healing of articular fractures with subchondral defect compared to ABG in most of the parameters evaluated, and had less subsynovial inflammation than the CPX alone in a canine model.

Alteration of blood clot structures by interleukin-1 beta in association with bone defects healing

PubMed Central

Wang, Xin; Friis, Thor E.; Masci, Paul P.; Crawford, Ross W.; Liao, Wenbo; Xiao, Yin

2016-01-01

The quality of hematomas are crucial for successful early bone defect healing, as the structure of fibrin clots can significantly influence the infiltration of cells, necessary for bone regeneration, from adjacent tissues into the fibrin network. This study investigated if there were structural differences between hematomas from normal and delayed healing bone defects and whether such differences were linked to changes in the expression of IL-1β. Using a bone defect model in rats, we found that the hematomas in the delayed healing model had thinner fibers and denser clot structures. Moreover, IL-1β protein levels were significantly higher in the delayed healing hematomas. The effects of IL-1β on the structural properties of human whole blood clots were evaluated by thrombelastograph (TEG), scanning electronic microscopy (SEM), compressive study, and thrombolytic assays. S-nitrosoglutathione (GSNO) was applied to modulate de novo hematoma structure and the impact on bone healing was evaluated in the delayed healing model. We found that GSNO produced more porous hematomas with thicker fibers and resulted in significantly enhanced bone healing. This study demonstrated that IL-1β and GSNO had opposing effects on clot architecture, the structure of which plays a pivotal role in early bone healing. PMID:27767056

Proteomic Analysis of Gingival Tissue and Alveolar Bone during Alveolar Bone Healing*

PubMed Central

Yang, Hee-Young; Kwon, Joseph; Kook, Min-Suk; Kang, Seong Soo; Kim, Se Eun; Sohn, Sungoh; Jung, Seunggon; Kwon, Sang-Oh; Kim, Hyung-Seok; Lee, Jae Hyuk; Lee, Tae-Hoon

2013-01-01

Bone tissue regeneration is orchestrated by the surrounding supporting tissues and involves the build-up of osteogenic cells, which orchestrate remodeling/healing through the expression of numerous mediators and signaling molecules. Periodontal regeneration models have proven useful for studying the interaction and communication between alveolar bone and supporting soft tissue. We applied a quantitative proteomic approach to analyze and compare proteins with altered expression in gingival soft tissue and alveolar bone following tooth extraction. For target identification and validation, hard and soft tissue were extracted from mini-pigs at the indicated times after tooth extraction. From triplicate experiments, 56 proteins in soft tissue and 27 proteins in alveolar bone were found to be differentially expressed before and after tooth extraction. The expression of 21 of those proteins was altered in both soft tissue and bone. Comparison of the activated networks in soft tissue and alveolar bone highlighted their distinct responsibilities in bone and tissue healing. Moreover, we found that there is crosstalk between identified proteins in soft tissue and alveolar bone with respect to cellular assembly, organization, and communication. Among these proteins, we examined in detail the expression patterns and associated networks of ATP5B and fibronectin 1. ATP5B is involved in nucleic acid metabolism, small molecule biochemistry, and neurological disease, and fibronectin 1 is involved in cellular assembly, organization, and maintenance. Collectively, our findings indicate that bone regeneration is accompanied by a profound interaction among networks regulating cellular resources, and they provide novel insight into the molecular mechanisms involved in the healing of periodontal tissue after tooth extraction. PMID:23824910

Alveolar bone healing process in spontaneously hypertensive rats (SHR). A radiographic densitometry study

PubMed Central

MANRIQUE, Natalia; PEREIRA, Cassiano Costa Silva; GARCIA, Lourdes Maria Gonzáles; MICARONI, Samuel; de CARVALHO, Antonio Augusto Ferreira; PERRI, Sílvia Helena Venturoli; OKAMOTO, Roberta; SUMIDA, Doris Hissako; ANTONIALI, Cristina

2012-01-01

Hypertension is one of the most important public health problems worldwide. If undiagnosed or untreated, this pathology represents a systemic risk factor and offers unfavorable conditions for dental treatments, especially those requiring bone healing. Objectives The purpose of this study was to demonstrate, by analysis of bone mineral density (BMD), that the alveolar bone healing process is altered in spontaneously hypertensive rats (SHRs). Material and Methods Wistar rats and SHRs were submitted to extraction of the upper right incisor and were euthanized 7, 14, 21, 28 and 42 days after surgery. Right maxillae were collected, radiographed and analyzed using Digora software. BMD was expressed as minimum (min), middle (med) and maximum (max) in the medium (MT) and apical (AT) thirds of the dental alveolus. Results The results were compared across days and groups. Wistar showed difference in med and max BMD in the MT between 7 and 28 and also between 14 and 28 days. The AT exhibited significant difference in med and min BMD between 7 and 28 days, as well as difference in min BMD between 28 and 42 days. SHRs showed lower med BMD in the MT at 28 days when compared to 21 and 42 days. Differences were observed across groups in med and min BMD at day 28 in the MT and AT; and in max BMD at 14, 21 and 42 days in the MT. Conclusions These results suggest that the alveolar bone healing process is delayed in SHRs comparing with Wistar rats. PMID:22666841

The dawn of computer-assisted robotic osteotomy with ytterbium-doped fiber laser.

PubMed

Sotsuka, Yohei; Nishimoto, Soh; Tsumano, Tomoko; Kawai, Kenichiro; Ishise, Hisako; Kakibuchi, Masao; Shimokita, Ryo; Yamauchi, Taisuke; Okihara, Shin-ichiro

2014-05-01

Currently, laser radiation is used routinely in medical applications. For infrared lasers, bone ablation and the healing process have been reported, but no laser systems are established and applied in clinical bone surgery. Furthermore, industrial laser applications utilize computer and robot assistance; medical laser radiations are still mostly conducted manually nowadays. The purpose of this study was to compare the histological appearance of bone ablation and healing response in rabbit radial bone osteotomy created by surgical saw and ytterbium-doped fiber laser controlled by a computer with use of nitrogen surface cooling spray. An Ytterbium (Yb)-doped fiber laser at a wavelength of 1,070 nm was guided by a computer-aided robotic system, with a spot size of 100 μm at a distance of approximately 80 mm from the surface. The output power of the laser was 60 W at the scanning speed of 20 mm/s scan using continuous wave system with nitrogen spray level 0.5 MPa (energy density, 3.8 × 10(4) W/cm(2)). Rabbits radial bone osteotomy was performed by an Yb-doped fiber laser and a surgical saw. Additionally, histological analyses of the osteotomy site were performed on day 0 and day 21. Yb-doped fiber laser osteotomy revealed a remarkable cutting efficiency. There were little signs of tissue damage to the muscle. Lased specimens have shown no delayed healing compared with the saw osteotomies. Computer-assisted robotic osteotomy with Yb-doped fiber laser was able to perform. In rabbit model, laser-induced osteotomy defects, compared to those by surgical saw, exhibited no delayed healing response.

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 Central

Berberi, Antoine N.; Sabbagh, Joseph M.; Aboushelib, Moustafa N.; Noujeim, Ziad F.; Salameh, Ziad A.

2014-01-01

Purpose: 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. Materials and Methods: 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. Results: 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. Conclusions: 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. PMID:24550840

Dynamics of bone healing after osteotomy with piezosurgery or conventional drilling – histomorphometrical, immunohistochemical, and molecular analysis

PubMed Central

2013-01-01

Background Piezosurgery is an osteotomy system used in medical and dental surgery. Many studies have proven clinical advantages of piezosurgery in terms of quality of cut, maneuverability, ease of use, and safety. However, few investigations have tested its superiority over the traditional osteotomy systems in terms of dynamics of bone healing. Therefore, the aim of this study was to evaluate the dynamics of bone healing after osteotomies with piezosurgery and to compare them with those associated to traditional bone drilling. Methods One hundred and ten rats were divided into two groups with 55 animals each. The animals were anesthetized and the tibiae were surgically exposed to create defects 2 mm in diameter by using piezosurgery (Piezo group) and conventional drilling (Drill group). Animals were sacrificed at 3, 7, 14, 30 and 60 days post-surgery. Bone samples were collected and processed for histological, histomorphometrical, immunohistochemical, and molecular analysis. The histological analysis was performed at all time points (n = 8) whereas the histomorphometrical analysis was performed at 7, 14, 30 and 60 days post-surgery (n = 8). The immunolabeling was performed to detect Vascular Endothelial Growth Factor (VEGF), Caspase-3 (CAS-3), Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kappa-B Ligand (RANKL), and Osteocalcin (OC) at 3, 7, and 14 days (n = 3). For the molecular analysis, animals were sacrificed at 3, 7 and 14 days, total RNA was collected, and quantification of the expression of 21 genes related to BMP signaling, Wnt signaling, inflammation, osteogenenic and apoptotic pathways was performed by qRT-PCR (n = 5). Results Histologically and histomorphometrically, bone healing was similar in both groups with the exception of a slightly higher amount of newly formed bone observed at 30 days after piezosurgery (p < 0.05). Immunohistochemical and qRT-PCR analyses didn’t detect significant differences in expression of all the proteins and most of the genes tested. Conclusions Based on the results of our study we conclude that in a rat tibial bone defect model the bone healing dynamics after piezosurgery are comparable to those observed with conventional drilling. PMID:24053147

Dynamics of bone healing after osteotomy with piezosurgery or conventional drilling - histomorphometrical, immunohistochemical, and molecular analysis.

PubMed

Esteves, Jônatas Caldeira; Marcantonio, Elcio; de Souza Faloni, Ana Paula; Rocha, Fernanda Regina Godoy; Marcantonio, Rosemary Adriana; Wilk, Katarzyna; Intini, Giuseppe

2013-09-23

Piezosurgery is an osteotomy system used in medical and dental surgery. Many studies have proven clinical advantages of piezosurgery in terms of quality of cut, maneuverability, ease of use, and safety. However, few investigations have tested its superiority over the traditional osteotomy systems in terms of dynamics of bone healing. Therefore, the aim of this study was to evaluate the dynamics of bone healing after osteotomies with piezosurgery and to compare them with those associated to traditional bone drilling. One hundred and ten rats were divided into two groups with 55 animals each. The animals were anesthetized and the tibiae were surgically exposed to create defects 2 mm in diameter by using piezosurgery (Piezo group) and conventional drilling (Drill group). Animals were sacrificed at 3, 7, 14, 30 and 60 days post-surgery. Bone samples were collected and processed for histological, histomorphometrical, immunohistochemical, and molecular analysis. The histological analysis was performed at all time points (n = 8) whereas the histomorphometrical analysis was performed at 7, 14, 30 and 60 days post-surgery (n = 8). The immunolabeling was performed to detect Vascular Endothelial Growth Factor (VEGF), Caspase-3 (CAS-3), Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kappa-B Ligand (RANKL), and Osteocalcin (OC) at 3, 7, and 14 days (n = 3). For the molecular analysis, animals were sacrificed at 3, 7 and 14 days, total RNA was collected, and quantification of the expression of 21 genes related to BMP signaling, Wnt signaling, inflammation, osteogenenic and apoptotic pathways was performed by qRT-PCR (n = 5). Histologically and histomorphometrically, bone healing was similar in both groups with the exception of a slightly higher amount of newly formed bone observed at 30 days after piezosurgery (p < 0.05). Immunohistochemical and qRT-PCR analyses didn't detect significant differences in expression of all the proteins and most of the genes tested. Based on the results of our study we conclude that in a rat tibial bone defect model the bone healing dynamics after piezosurgery are comparable to those observed with conventional drilling.

Advanced age diminishes tendon-to-bone healing in a rat model of rotator cuff repair.

PubMed

Plate, Johannes F; Brown, Philip J; Walters, Jordan; Clark, John A; Smith, Thomas L; Freehill, Michael T; Tuohy, Christopher J; Stitzel, Joel D; Mannava, Sandeep

2014-04-01

Advanced patient age is associated with recurrent tearing and failure of rotator cuff repairs clinically; however, basic science studies have not evaluated the influence of aging on tendon-to-bone healing after rotator cuff repair in an animal model. Hypothesis/ This study examined the effect of aging on tendon-to-bone healing in an established rat model of rotator cuff repair using the aged animal colony from the National Institute on Aging of the National Institutes of Health. The authors hypothesized that normal aging decreases biomechanical strength and histologic organization at the tendon-to-bone junction after acute repair. Controlled laboratory study. In 56 F344xBN rats, 28 old and 28 young (24 and 8 months of age, respectively), the supraspinatus tendon was transected and repaired. At 2 or 8 weeks after surgery, shoulder specimens underwent biomechanical testing to compare load-to-failure and load-relaxation response between age groups. Histologic sections of the tendon-to-bone interface were assessed with hematoxylin and eosin staining, and collagen fiber organization was assessed by semiquantitative analysis of picrosirius red birefringence under polarized light. Peak failure load was similar between young and old animals at 2 weeks after repair (31% vs 26% of age-matched uninjured controls, respectively; P > .05) but significantly higher in young animals compared with old animals 8 weeks after repair (86% vs 65% of age-matched uninjured controls, respectively; P < .01). Eight weeks after repair, fibroblasts appeared more organized and uniformly aligned in young animals on hematoxylin and eosin slides compared with old animals. Collagen birefringence analysis of the tendon-to-bone junction demonstrated that young animals had increased collagen fiber organization and similar histologic structure compared with age-matched controls (53.7 ± 2.4 gray scales; P > .05). In contrast, old animals had decreased collagen fiber organization and altered structure compared with age-matched controls (49.8 ± 3.1 gray scales; P < .01). In a rat model of aging, old animals demonstrated diminished tendon-to-bone healing after rotator cuff injury and repair. Old animals had significantly decreased failure strength and collagen fiber organization at the tendon-to-bone junction compared with young animals. This study implies that animal age may need to be considered in future studies of rotator cuff repair in animal models. With increasing age and activity level of the population, the incidence of rotator cuff tears is predicted to rise. Despite advances in rotator cuff repair technique, the retear rate remains specifically high in elderly patients. The findings of this research suggest that aging negatively influences tendon-to-bone healing after rotator cuff repair in a validated animal model.

Ceramic-polylactide composite material used in a model of healing of osseous defects in rabbits.

PubMed

Myciński, Paweł; Zarzecka, Joanna; Skórska-Stania, Agnieszka; Jelonek, Agnieszka; Okoń, Krzysztof; Wróbel, Maria

The growing demand for various kinds of bone regeneration material has in turn increased the desire to find materials with optimal physical, chemical, and biological properties. The objective of the present study was to identify the proportions of ceramic and polylactide components in a bone substitute material prepared in collaboration with the Crystal Chemistry of Drugs Team of the Faculty of Chemistry at the Jagiellonian University, which would be optimal for bone regeneration processes. Another goal was to provide a histological analysis of the influence of a ceramic-polylactide composite on the healing of osseous defects in rabbits. The study was performed on laboratory animals (18 New Zealand White rabbits). The following study groups were formed: - group A (study group, 9 animals) - in this group we performed a histological analysis of healing with a ceramic-polylactide composite based on an 80/20 mix of hydroxyapatite and polylactide; - group B (study group, 9 animals) - in this group we performed a histological analysis of healing with a ceramic-polylactide composite with a reduced amount of hydroxyapatite compared to the previous group, i.e. in a ratio of 61/39; - group K (control, 18 animals) - the control group comprised self-healing, standardised osseous defects prepared in the calvarial bone of the rabbits on the contralateral side. In the assessment of histological samples, we were also able to eliminate individual influences that might have led to differentiation in wound healing. The material used in the histological analysis took the form of rabbit bone tissue samples, containing both defects, with margins of around 0.5 cm, taken 1, 3, and 6 months after the experiment. The osseous defects from groups A and B filled with ceramic-polylactide material healed with less inflammatory infiltration than was the case with control group K. They were also characterised by faster regression, and no resorption or osteonecrosis, which allowed for better regeneration of the bone tissue. A statistical analysis of the study results revealed the increased resorptive activity of the composite in group B, which may have been due to its higher polylactide content. Simultaneously, we observed that healing of osseous defects filled with ceramic-polylactide composites in 80/20 and 61/39 ratios was comparable.

Bone modelling at fresh extraction sockets: immediate implant placement versus spontaneous healing: an experimental study in the beagle dog.

PubMed

Vignoletti, Fabio; Discepoli, Nicola; Müller, Anna; de Sanctis, Massimo; Muñoz, Fernando; Sanz, Mariano

2012-01-01

The purpose of this investigation is to describe histologically the undisturbed healing of fresh extraction sockets when compared to immediate implant placement. In eight beagle dogs, after extraction of the 3P3 and 4P4, implants were inserted into the distal sockets of the premolars, while the mesial sockets were left to heal spontaneously. Each animal provided four socket sites (control) and four implant sites (test). After 6 weeks, animals were sacrificed and tissue blocks were dissected, prepared for ground sectioning. The relative vertical buccal bone resorption in relation to the lingual bone was similar in both test and control groups. At immediate implant sites, however, the absolute buccal bone loss observed was 2.32 (SD 0.36) mm, what may indicate that while an apical shift of both the buccal and lingual bone crest occurred at the implant sites, this may not happen in naturally healing sockets. The results from this investigation showed that after tooth extraction the buccal socket wall underwent bone resorption at both test and control sites. This resorption appeared to be more pronounced at the implant sites, although the limitations of the histological evaluation method utilized preclude a definite conclusion. © 2011 John Wiley & Sons A/S.

Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal Stem Cells.

PubMed

Thangarajah, Tanujan; Shahbazi, Shirin; Pendegrass, Catherine J; Lambert, Simon; Alexander, Susan; Blunn, Gordon W

2016-01-01

Tendon-bone healing following rotator cuff repairs is mainly impaired by poor tissue quality. Demineralised bone matrix promotes healing of the tendon-bone interface but its role in the treatment of tendon tears with retraction has not been investigated. We hypothesized that cortical demineralised bone matrix used with minimally manipulated mesenchymal stem cells will result in improved function and restoration of the tendon-bone interface with no difference between xenogenic and allogenic scaffolds. In an ovine model, the patellar tendon was detached from the tibial tuberosity and a complete distal tendon transverse defect measuring 1 cm was created. Suture anchors were used to reattach the tendon and xenogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5), or allogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5) were used to bridge the defect. Graft incorporation into the tendon and its effect on regeneration of the enthesis was assessed using histomorphometry. Force plate analysis was used to assess functional recovery. Compared to the xenograft, the allograft was associated with significantly higher functional weight bearing at 6 (P = 0.047), 9 (P = 0.028), and 12 weeks (P = 0.009). In the allogenic group this was accompanied by greater remodeling of the demineralised bone matrix into tendon-like tissue in the region of the defect (p = 0.015), and a more direct type of enthesis characterized by significantly more fibrocartilage (p = 0.039). No failures of tendon-bone healing were noted in either group. Demineralised bone matrix used with minimally manipulated mesenchymal stem cells promotes healing of the tendon-bone interface in an ovine model of acute tendon retraction, with superior mechanical and histological results associated with use of an allograft.

Stress-Shielding Effect of Nitinol Swan-Like Memory Compressive Connector on Fracture Healing of Upper Limb

NASA Astrophysics Data System (ADS)

Fu, Q. G.; Liu, X. W.; Xu, S. G.; Li, M.; Zhang, C. C.

2009-08-01

In this article, the stress-shielding effect of a Nitinol swan-like memory compressive connector (SMC) is evaluated. Patients with fracture healing of an upper limb after SMC internal fixation or stainless steel plate fixation were randomly selected and observed comparatively. With the informed consent of the SMC group, minimal cortical bone under the swan-body and swan-neck was harvested; and in the steel plate fixation group, minimal cortical bone under the steel plate and opposite side to the steel plate was also harvested for observation. Main outcome measurements were taken such as osteocyte morphology, Harversian canal histological observation under light microscope; radiographic observation of fracture healing, and computed tomography quantitative scanning of cortical bone. As a conclusion, SMC has a lesser stress-shielding effect to fixed bone than steel plate. Finally, the mechanism of the lesser stress-shielding effect of SMC is discussed.

Bioelectric modulation of wound healing in a 3D in vitro model of tissue-engineered bone.

PubMed

Sundelacruz, Sarah; Li, Chunmei; Choi, Young Jun; Levin, Michael; Kaplan, David L

2013-09-01

Long-standing interest in bioelectric regulation of bone fracture healing has primarily focused on exogenous stimulation of bone using applied electromagnetic fields. Endogenous electric signals, such as spatial gradients of resting potential among non-excitable cells in vivo, have also been shown to be important in cell proliferation, differentiation, migration, and tissue regeneration, and may therefore have as-yet unexplored therapeutic potential for regulating wound healing in bone tissue. To study this form of bioelectric regulation, there is a need for three-dimensional (3D) in vitro wound tissue models that can overcome limitations of current in vivo models. We present a 3D wound healing model in engineered bone tissue that serves as a pre-clinical experimental platform for studying electrophysiological regulation of wound healing. Using this system, we identified two electrophysiology-modulating compounds, glibenclamide and monensin, that augmented osteoblast mineralization. Of particular interest, these compounds displayed differential effects in the wound area compared to the surrounding tissue. Several hypotheses are proposed to account for these observations, including the existence of heterogeneous subpopulations of osteoblasts that respond differently to bioelectric signals, or the capacity of the wound-specific biochemical and biomechanical environment to alter cell responses to electrophysiological treatments. These data indicate that a comprehensive characterization of the cellular, biochemical, biomechanical, and bioelectrical components of in vitro wound models is needed to develop bioelectric strategies to control cell functions for improved bone regeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

Optimal Treatment of Malignant Long Bone Fracture: Influence of Method of Repair and External Beam Irradiation on the Pathway and Efficacy of Fracture Healing

DTIC Science & Technology

2014-10-01

Long Bone Fracture: Influence of Method of Repair and External Beam Irradiation on the Pathway and Efficacy of Fracture Healing 5a. CONTRACT NUMBER...in the fifth quarter of the award. 15. SUBJECT TERMS Fracture healing , bone healing , endochondral ossification, intramembranous ossification...of radiation on the two pathways of bone healing and propose an optimal method of surgical fracture repair for managing malignant osteoporotic

Enhanced Bone Bonding to Nanotextured Implant Surfaces at a Short Healing Period: A Biomechanical Tensile Testing in the Rat Femur.

PubMed

Coelho, Paulo G; Zavanelli, Ricardo A; Salles, Marcos B; Yeniyol, Sinem; Tovar, Nick; Jimbo, Ryo

2016-06-01

To compare the bone bonding capabilities of 2 different surface treatments at an early healing period. Titanium alloy (Ti6Al4V) custom-made rectangular plates (1.4 × 2.4 × 4 mm) were either dual acid etched (Ti6Al4V-DAE) or DAE/nanotextured blasted (Ti6Al4V-NTB). Implants were placed in the distal femurs of 10 Wistar rats and were allowed to heal for 9 days. After euthanasia, the bone immediately proximal and distal to the implant was removed to test the bone bonding force with a universal testing machine. Ultrastructure of the bone/implant interface was assessed by scanning electron microscopy. Ti6Al4V-NTB samples exhibited significantly greater bond strength than Ti6Al4V-DAE samples. Morphologically, the Ti6Al4V-NTB surfaces presented intimate interaction with bone, whereas little interaction between the Ti6Al4V-DAE surface and bone was observed. The results of this study indicated a significant increase in bone bonding for the DAE/nanotextured blasted surface, which is suggested to be the outcome of the nanotexturing.

Soft tissues healing at immediate transmucosal implants placed into molar extraction sites with buccal self-contained dehiscences. A 12-month controlled clinical trial.

PubMed

Siciliano, V Iorio; Salvi, G E; Matarasso, S; Cafiero, C; Blasi, A; Lang, N P

2009-05-01

To assess soft tissues healing at immediate transmucosal implants placed into molar extraction sites with buccal self-contained dehiscences. For this 12-month controlled clinical trial, 15 subjects received immediate transmucosal tapered-effect (TE) implants placed in molar extraction sockets displaying a buccal bone dehiscence (test sites) with a height and a width of > or =3 mm, respectively. Peri-implant marginal defects were treated according to the principles of Guided Bone Regeneration (GBR) by means of deproteinized bovine bone mineral particles in conjunction with a bioresorbable collagen membrane. Fifteen subjects received implants in healed molar sites (control sites) with intact buccal alveolar walls following tooth extraction. In total, 30 TE implants with an endosseous diameter of 4.8 mm and a shoulder diameter of 6.5 mm were used. Flaps were repositioned and sutured, allowing non-submerged, transmucosal soft tissues healing. At the 12-month follow-up, pocket probing depths (PPD) and clinical attachment levels (CAL) were compared between implants placed in the test and the control sites, respectively. All subjects completed the 12-month follow-up period. All implants healed uneventfully, yielding a survival rate of 100%. After 12 months, statistically significantly higher (P<0.05) PPD and CAL values were recorded around implants placed in the test sites compared with those placed in the control sites. The findings of this controlled clinical trial showed that healing following immediate transmucosal implant installation in molar extraction sites with wide and shallow buccal dehiscences yielded less favorable outcomes compared with those of implants placed in healed sites, and resulted in lack of 'complete' osseointegration.

Characteristics of bone turnover in the long bone metaphysis fractured patients with normal or low Bone Mineral Density (BMD).

PubMed

Wölfl, Christoph; Schweppenhäuser, Daniela; Gühring, Thorsten; Takur, Caner; Höner, Bernd; Kneser, Ulrich; Grützner, Paul Alfred; Kolios, Leila

2014-01-01

The incidence of osteoporotic fractures increases as our population ages. Until now, the exact biochemical processes that occur during the healing of metaphyseal fractures remain unclear. Diagnostic instruments that allow a dynamic insight into the fracture healing process are as yet unavailable. In the present matched pair analysis, we study the time course of the osteoanabolic markers bone specific alkaline phosphatase (BAP) and transforming growth factor β1 (TGFβ1), as well as the osteocatabolic markers crosslinked C-telopeptide of type-I-collagen (β-CTX) and serum band 5 tartrate-resistant acid phosphatase (TRAP5b), during the healing of fractures that have a low level of bone mineral density (BMD) compared with fractures that have a normal BMD. Between March 2007 and February 2009, 30 patients aged older than 50 years who suffered a metaphyseal fracture were included in our study. BMDs were verified by dual energy Xray absorptiometry (DXEA) scans. The levels of BTMs were examined over an 8-week period. Osteoanabolic BAP levels in those with low levels of BMD were significantly different from the BAP levels in those with normal BMD. BAP levels in the former group increased constantly, whereas the latter group showed an initial strong decrease in BAP followed by slowly rising values. Osteocatabolic β-CTX increased in the bone of the normal BMD group constantly, whereas these levels decreased significantly in the bone of the group with low BMD from the first week. TRAP5b was significantly reduced in the low level BMD group. With this work, we conduct first insights into the molecular biology of the fracture healing process in patients with low levels of BMD that explains the mechanism of its fracture healing. The results may be one reason for the reduced healing qualities in bones with low BMD.

Chronic Degeneration Leads to Poor Healing of Repaired Massive Rotator Cuff Tears in Rats.

PubMed

Killian, Megan L; Cavinatto, Leonardo M; Ward, Samuel R; Havlioglu, Necat; Thomopoulos, Stavros; Galatz, Leesa M

2015-10-01

Chronic rotator cuff tears present a clinical challenge, often with poor outcomes after surgical repair. Degenerative changes to the muscle, tendon, and bone are thought to hinder healing after surgical repair; additionally, the ability to overcome degenerative changes after surgical repair remains unclear. The purpose of this study was to evaluate healing outcomes of muscle, tendon, and bone after tendon repair in a model of chronic rotator cuff disease and to compare these outcomes to those of acute rotator cuff injuries and repair. The hypothesis was that degenerative rotator cuff changes associated with chronic multitendon tears and muscle unloading would lead to poor structural and mechanical outcomes after repair compared with acute injuries and repair. Controlled laboratory study. Chronic rotator cuff injuries, induced via detachment of the supraspinatus (SS) and infraspinatus (IS) tendons and injection of botulinum toxin A into the SS and IS muscle bellies, were created in the shoulders of rats. After 8 weeks of injury, tendons were surgically reattached to the humeral head, and an acute, dual-tendon injury and repair was performed on the contralateral side. After 8 weeks of healing, muscles were examined histologically, and tendon-to-bone samples were examined microscopically, histologically, and biomechanically and via micro-computed tomography. All repairs were intact at the time of dissection, with no evidence of gapping or ruptures. Tendon-to-bone healing after repair in our chronic injury model led to reduced bone quality and morphological disorganization at the repair site compared with acute injuries and repair. SS and IS muscles were atrophic at 8 weeks after repair of chronic injuries, indicating incomplete recovery after repair, whereas SS and IS muscles exhibited less atrophy and degeneration in the acute injury group at 8 weeks after repair. After chronic injuries and repair, humeral heads had decreased total mineral density and an altered trabecular structure, and the repair had decreased strength, stiffness, and toughness, compared with the acute injury and repair group. Chronic degenerative changes in rotator cuff muscles, tendons, and bone led to inferior healing characteristics after repair compared with acute injuries and repair. The changes were not reversible after repair in the time course studied, consistent with clinical impressions. High retear rates after rotator cuff repair are associated with tear size and chronicity. Understanding the mechanisms behind this association may allow for targeted tissue therapy for tissue degeneration that occurs in the setting of chronic tears. © 2015 The Author(s).

Chronic Degeneration Leads to Poor Healing of Repaired Massive Rotator Cuff Tears in Rats

PubMed Central

Killian, Megan L.; Cavinatto, Leonardo M.; Ward, Samuel R.; Havlioglu, Necat; Thomopoulos, Stavros; Galatz, Leesa M.

2016-01-01

Background Chronic rotator cuff tears present a clinical challenge, often with poor outcomes after surgical repair. Degenerative changes to the muscle, tendon, and bone are thought to hinder healing after surgical repair; additionally, the ability to overcome degenerative changes after surgical repair remains unclear. Purpose/Hypothesis The purpose of this study was to evaluate healing outcomes of muscle, tendon, and bone after tendon repair in a model of chronic rotator cuff disease and to compare these outcomes to those of acute rotator cuff injuries and repair. The hypothesis was that degenerative rotator cuff changes associated with chronic multitendon tears and muscle unloading would lead to poor structural and mechanical outcomes after repair compared with acute injuries and repair. Study Design Controlled laboratory study. Methods Chronic rotator cuff injuries, induced via detachment of the supraspinatus (SS) and infraspinatus (IS) tendons and injection of botulinum toxin A into the SS and IS muscle bellies, were created in the shoulders of rats. After 8 weeks of injury, tendons were surgically reattached to the humeral head, and an acute, dual-tendon injury and repair was performed on the contralateral side. After 8 weeks of healing, muscles were examined histologically, and tendon-to-bone samples were examined microscopically, histologically, and biomechanically and via micro–computed tomography. Results All repairs were intact at the time of dissection, with no evidence of gapping or ruptures. Tendon-to-bone healing after repair in our chronic injury model led to reduced bone quality and morphological disorganization at the repair site compared with acute injuries and repair. SS and IS muscles were atrophic at 8 weeks after repair of chronic injuries, indicating incomplete recovery after repair, whereas SS and IS muscles exhibited less atrophy and degeneration in the acute injury group at 8 weeks after repair. After chronic injuries and repair, humeral heads had decreased total mineral density and an altered trabecular structure, and the repair had decreased strength, stiffness, and toughness, compared with the acute injury and repair group. Conclusion Chronic degenerative changes in rotator cuff muscles, tendons, and bone led to inferior healing characteristics after repair compared with acute injuries and repair. The changes were not reversible after repair in the time course studied, consistent with clinical impressions. Clinical Relevance High retear rates after rotator cuff repair are associated with tear size and chronicity. Understanding the mechanisms behind this association may allow for targeted tissue therapy for tissue degeneration that occurs in the setting of chronic tears. PMID:26297522

VEGF serum concentrations in patients with long bone fractures: a comparison between impaired and normal fracture healing.

PubMed

Sarahrudi, Kambiz; Thomas, Anita; Braunsteiner, Tomas; Wolf, Harald; Vécsei, Vilmos; Aharinejad, Seyedhossein

2009-10-01

Vascular endothelial growth factor (VEGF) plays an important role in the bone repair process as a potent mediator of angiogenesis and it influences directly osteoblast differentiation. Inhibiting VEGF suppresses angiogenesis and callus mineralization in animals. However, no data exist so far on systemic expression of VEGF with regard to delayed or failed fracture healing in humans. One hundred fourteen patients with long bone fractures were included in the study. Serum samples were collected over a period of 6 months following a standardized time schedule. VEGF serum concentrations were measured. Patients were assigned to one of two groups according to their course of fracture healing. The first group contained 103 patients with physiological fracture healing. Eleven patients with delayed or nonunions formed the second group of the study. In addition, 33 healthy volunteers served as controls. An increase of VEGF serum concentration within the first 2 weeks after fracture in both groups with a following decrease within 6 months after trauma was observed. Serum VEGF concentrations in patients with impaired fracture healing were higher compared to the patients with physiological healing during the entire observation period. However, statistically significant differences were not observed at any time point between both groups. VEGF concentrations in both groups were significantly higher than those in controls. The present results show significantly elevated serum concentrations of VEGF in patients after fracture of long bones especially at the initial healing phase, indicating the importance of VEGF in the process of fracture healing in humans. (c) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Unicameral Bone Cysts in the Humerus: Treatment Outcomes.

PubMed

Kadhim, Muayad; Sethi, Samir; Thacker, Mihir M

2016-06-01

Several treatment modalities have been described for the treatment of unicameral bone cysts (UBC). The aim of this study was to examine the outcome of various treatment modalities of UBC in a specific anatomic location, the humerus. This study is a retrospective case-only study of patients with humeral UBC with minimum follow-up of 1 year. Medical records and radiographs were assessed and UBC healing status was determined based on most recent follow-up radiographs and divided into 3 groups (healed, partially healed, and not healed). Descriptive statistics were utilized to summarize study outcome. Sixty-eight patients (54 boys and 14 girls) with humeral UBC comprised the study population. Sixty-four cases (94.1%) presented with a pathologic fracture. Fifty-one cases were in the proximal metaphysis and 17 were in the diaphysis. Mean age at diagnosis was 9.2±3.7 years, and mean follow-up was 4.0±2.6 years. Twenty-five patients were treated with observation, 38 by injection (27 with steroids and 11 with bone marrow), and 5 by open surgery. Patients who underwent open surgery had relatively larger cyst length, width, and cyst index, and all healed or partially healed at last follow-up. UBC persistence was observed in 29% of diaphyseal and 27.5% of metaphyseal cysts. Of the 19 patients with persistence, 8 were treated with observation, 9 with steroid injection, and 2 with bone marrow injection. Inner wall disruption before injection was performed in 17 patients (24% did not heal), whereas 21 patients did not have inner wall disruption (33% did not heal). Twenty patients received >1 injection. Eleven patients complained of pain at the last visit (8 had a persistent cyst, 2 were partially healed, and 1 had a healed UBC). Complete healing of humeral UBC is challenging to achieve irrespective of treatment modality. UBCs treated with open surgery tended to heal better. Unhealed cysts were more likely to be associated with pain. Level III-a retrospective comparative study.

The roles of cellular and molecular components of a hematoma at early stage of bone healing.

PubMed

Shiu, Hoi Ting; Leung, Ping Chung; Ko, Chun Hay

2018-04-01

Bone healing is a complex repair process that commences with the formation of a blood clot at the injured bone, termed hematoma. It has evidenced that a lack of a stable hematoma causes delayed bone healing or non-union. The hematoma at the injured bone constitutes the early healing microenvironment. It appears to dictate healing pathways that ends in a regenerative bone. However, the hematoma is often clinically removed from the damaged site. Conversely, blood-derived products have been used in bone tissue engineering for treating critical sized defects, including fibrin gels and platelet-rich plasma. A second generation of platelet concentrate that is based on leukocyte and fibrin content has also been developed and introduced in market. Conflicting effect of these products in bone repair are reported. We propose that the bone healing response becomes dysregulated if the blood response and subsequent formation and properties of a hematoma are altered. This review focuses on the central structural, cellular, and molecular components of a fracture hematoma, with a major emphasis on their roles in regulating bone healing mechanism, and their interactions with mesenchymal stem cells. New angles towards a better understanding of these factors and relevant mechanisms involved at the beginning of bone healing may help to clarify limited or adverse effects of blood-derived products on bone repair. We emphasize that the recreation of an early hematoma niche with critical compositions might emerge as a viable therapeutic strategy for enhanced skeletal tissue engineering. Copyright © 2017 John Wiley & Sons, Ltd.

Extended fatigue life of a catalyst-free self-healing acrylic bone cement using microencapsulated 2-octyl cyanoacrylate

PubMed Central

Brochu, Alice B.W.; Matthys, Oriane B.; Craig, Stephen L.; Reichert, William M.

2014-01-01

The tissue adhesive 2-octyl cyanoacrylate (OCA) was encapsulated in polyurethane microshells and incorporated into bone cement to form a catalyst free, self-healing bone cement comprised of all clinically approved components. The bending strength, modulus, and fatigue lifetime were investigated in accordance with ASTM and ISO standards for the testing of PMMA bone cement. The bending strength of bone cement specimens decreased with increasing wt% capsules content for capsules without or with OCA, with specimens of < 5 wt% capsule content showing minimal effect. In contrast, bone cement bending modulus was insensitive to capsule content. Load controlled fatigue testing was performed in air at room temperature on capsule free bone cement (0 wt%), bone cement with 5 wt% OCA-free capsules (5 wt% No OCA), and 5 wt% OCA-containing capsules (5 wt% OCA). Specimens were tested at a frequency of 5 Hz at maximum stresses of 90%, 80%, 70% and 50% of each specimen's bending strength until failure. The 5 wt% OCA exhibited significant self-healing at 70% and 50% of its reference strength (p < 0.05). Fatigue testing of all three specimen types in air at 22 MPa (50% of reference strength of the 5 wt% OCA specimens) showed that the cycles to failure of OCA-containing specimens was increased by two-fold compared to the OCA-free and capsule-free specimens. This study represents the first demonstration of dynamic, catalyst-free self-healing in a biomaterial formulation. PMID:24825796

Contribution of methylglyoxal to delayed healing of bone injury in diabetes.

PubMed

Aikawa, Takao; Matsubara, Hidenori; Ugaji, Shuhei; Shirakawa, Junichi; Nagai, Ryoji; Munesue, Seiichi; Harashima, Ai; Yamamoto, Yasuhiko; Tsuchiya, Hiroyuki

2017-07-01

Patients with diabetes are vulnerable to delayed bone fracture healing or pseudoarthrosis. Chronic sustained hyperglycemia, reactive intermediate derivatives of glucose metabolism, such as methylglyoxal (MGO), and advanced glycation end‑products (AGEs) are implicated in diabetic complications. In the present study, it was examined whether MGO is able to cause disturbed bone healing in diabetes. Diabetes was induced in male mice by injection of streptozotocin (50 mg/kg) for 5 days. A bone defect (1.0‑mm diameter) was created in the left distal femur, and bone repair was assessed from an examination of computed tomography scans. ST2 cells were exposed to MGO (0‑400 µM) to investigate osteoblastic differentiation, cell viability, and damage. Consequently, blood glucose and hemoglobin A1c levels in diabetic mice were determined to be 493±14.1 mg/dl and 8.0±0.05%, respectively. Compared with non‑diabetic control mice, diabetic mice exhibited markedly delayed bone healing, with increased levels of the MGO‑derived AGEs, Nε‑(carboxymethyl)‑lysine and Nδ‑(5‑hydro‑5‑methyl‑4‑imidazolone‑2‑yl)‑ornithine, in the sera and femurs. MGO inhibited the osteoblastic differentiation of ST2 cells in a dose‑dependent manner, and markedly decreased cell proliferation through cytotoxicity. In conclusion, MGO has been demonstrated to cause impaired osteoblastic differentiation and delayed bone repair in diabetes. Therefore, detoxification of MGO may be a potentially useful strategy against bone problems in patients with diabetes.

External fixation of tibial pilon fractures and fracture healing.

PubMed

Ristiniemi, Jukka

2007-06-01

Distal tibial fractures are rare and difficult to treat because the bones are subcutaneous. External fixation is commonly used, but the method often results in delayed union. The aim of the present study was to find out the factors that affect fracture union in tibial pilon fractures. For this purpose, prospective data collection of tibial pilon fractures was carried out in 1998-2004, resulting in 159 fractures, of which 83 were treated with external fixation. Additionally, 23 open tibial fractures with significant > 3 cm bone defect that were treated with a staged method in 2000-2004 were retrospectively evaluated. The specific questions to be answered were: What are the risk factors for delayed union associated with two-ring hybrid external fixation? Does human recombinant BMP-7 accelerate healing? What is the role of temporary ankle-spanning external fixation? What is the healing potential of distal tibial bone loss treated with a staged method using antibiotic beads and subsequent autogenous cancellous grafting compared to other locations of the tibia? The following risk factors for delayed healing after external fixation were identified: post-reduction fracture gap of >3 mm and fixation of the associated fibula fracture. Fracture displacement could be better controlled with initial temporary external fixation than with early definitive fixation, but it had no significant effect on healing time, functional outcome or complication rate. Osteoinduction with rhBMP-7 was found to accelerate fracture healing and to shorten the sick leave. A staged method using antibiotic beads and subsequent autogenous cancellous grafting proved to be effective in the treatment of tibial bone loss. Healing potential of the bone loss in distal tibia was at least equally good as in other locations of the tibia.

rhPDGF-BB promotes early healing in a rat rotator cuff repair model.

PubMed

Kovacevic, David; Gulotta, Lawrence V; Ying, Liang; Ehteshami, John R; Deng, Xiang-Hua; Rodeo, Scott A

2015-05-01

Tendon-bone healing after rotator cuff repair occurs by fibrovascular scar tissue formation, which is weaker than a normal tendon-bone insertion site. Growth factors play a role in tissue formation and have the potential to augment soft tissue healing in the perioperative period. Our study aim was to determine if rhPDGF-BB delivery on a collagen scaffold can improve tendon-to-bone healing after supraspinatus tendon repair compared with no growth factor in rats as measured by (1) gross observations; (2) histologic analysis; and (3) biomechanical testing. Ninety-five male Sprague-Dawley rats underwent acute repair of the supraspinatus tendon. Rats were randomized into one of five groups: control (ie, repair only), scaffold only, and three different platelet-derived growth factor (PDGF) doses on the collagen scaffold. Animals were euthanized 5 days after surgery to assess cellular proliferation and angiogenesis. The remaining animals were analyzed at 4 weeks to assess repair site integrity by gross visualization, fibrocartilage formation with safranin-O staining, and collagen fiber organization with picrosirius red staining, and to determine the biomechanical properties (ie, load-to-failure testing) of the supraspinatus tendon-bone construct. The repaired supraspinatus tendon was in continuity with the bone in all animals. At 5 days, rhPDGF-BB delivery on a scaffold demonstrated a dose-dependent response in cellular proliferation and angiogenesis compared with the control and scaffold groups. At 28 days, with the numbers available, rhPDGF-BB had no effect on increasing fibrocartilage formation or improving collagen fiber maturity at the tendon-bone insertion site compared with controls. The control group had higher tensile loads to failure and stiffness (35.5 ± 8.8 N and 20.3 ± 4.5 N/mm) than all the groups receiving the scaffold, including the PDGF groups (scaffold: 27 ± 6.4 N, p = 0.021 and 13 ± 5.7 N/mm, p = 0.01; 30 µg/mL PDGF: 26.5 ± 7.5 N, p = 0.014 and 13.3 ± 3.2 N/mm, p = 0.01; 100 µg/mL PDGF: 25.7 ± 6.1 N, p = 0.005 and 11.6 ± 3.3 N/mm, p = 0.01; 300 µg/mL PDGF: 27 ± 6.9 N, p = 0.014 and 12.7 ± 4.1 N/mm, p = 0.01). rhPDGF-BB delivery on a collagen scaffold enhanced cellular proliferation and angiogenesis during the early phase of healing, but this did not result in either a more structurally organized or stronger attachment site at later stages of healing. The collagen scaffold had a detrimental effect on healing strength at 28 days, and its relatively larger size compared with the rat tendon may have caused mechanical impingement and extrinsic compression of the healing tendon. Future studies should be performed in larger animal models where healing occurs more slowly. Augmenting the healing environment to improve the structural integrity and to reduce the retear rate after rotator cuff repair may be realized with continued understanding and optimization of growth factor delivery systems.

A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering

PubMed Central

Winkler, T.; Sass, F. A.; Schmidt-Bleek, K.

2018-01-01

Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration. Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge. Bone Joint Res 2018;7:232–243. DOI: 10.1302/2046-3758.73.BJR-2017-0270.R1.

Fractures in geriatric mice show decreased callus expansion and bone volume.

PubMed

Lopas, Luke A; Belkin, Nicole S; Mutyaba, Patricia L; Gray, Chancellor F; Hankenson, Kurt D; Ahn, Jaimo

2014-11-01

Poor fracture healing in geriatric populations is a significant source of morbidity, mortality, and cost to individuals and society; however, a fundamental biologic understanding of age-dependent healing remains elusive. The development of an aged-based fracture model system would allow for a mechanistic understanding that could guide future biologic treatments. Using a small animal model of long-bone fracture healing based on chronologic age, we asked how aging affected (1) the amount, density, and proportion of bone formed during healing; (2) the amount of cartilage produced and the progression to bone during healing; (3) the callus structure and timing of the fracture healing; and (4) the behavior of progenitor cells relative to the observed deficiencies of geriatric fracture healing. Transverse, traumatic tibial diaphyseal fractures were created in 5-month-old (n=104; young adult) and 25-month-old (n=107; which we defined as geriatric, and are approximately equivalent to 70-85 year-old humans) C57BL/6 mice. Fracture calluses were harvested at seven times from 0 to 40 days postfracture for micro-CT analysis (total volume, bone volume, bone volume fraction, connectivity density, structure model index, trabecular number, trabecular thickness, trabecular spacing, total mineral content, bone mineral content, tissue mineral density, bone mineral density, degree of anisotropy, and polar moment of inertia), histomorphometry (total callus area, cartilage area, percent of cartilage, hypertrophic cartilage area, percent of hypertrophic cartilage area, bone and osteoid area, percent of bone and osteoid area), and gene expression quantification (fold change). The geriatric mice produced a less robust healing response characterized by a pronounced decrease in callus amount (mean total volume at 20 days postfracture, 30.08±11.53 mm3 versus 43.19±18.39 mm3; p=0.009), density (mean bone mineral density at 20 days postfracture, 171.14±64.20 mg hydroxyapatite [HA]/cm3 versus 210.79±37.60 mg HA/cm3; p=0.016), and less total cartilage (mean cartilage area at 10 days postfracture, 101,279±46,755 square pixels versus 302,167±137,806 square pixels; p=0.013) and bone content (mean bone volume at 20 days postfracture, 11.68±3.18 mm3 versus 22.34±10.59 mm3; p<0.001) compared with the young adult mice. However, the amount of cartilage and bone relative to the total callus size was similar between the adult and geriatric mice (mean bone volume fraction at 25 days postfracture, 0.48±0.10 versus 0.50±0.13; p=0.793), and the relative expression of chondrogenic (mean fold change in SOX9 at 10 days postfracture, 135+25 versus 90±52; p=0.221) and osteogenic genes (mean fold change in osterix at 20 days postfracture, 22.2±5.3 versus 18.7±5.2; p=0.324) was similar. Analysis of mesenchymal cell proliferation in the geriatric mice relative to adult mice showed a decrease in proliferation (mean percent of undifferentiated mesenchymal cells staining proliferating cell nuclear antigen [PCNA] positive at 10 days postfracture, 25%±6.8% versus 42%±14.5%; p=0.047). Our findings suggest that the molecular program of fracture healing is intact in geriatric mice, as it is in geriatric humans, but callus expansion is reduced in magnitude. Our study showed altered healing capacity in a relevant animal model of geriatric fracture healing. The understanding that callus expansion and bone volume are decreased with aging can help guide the development of targeted therapeutics for these difficult to heal fractures.

In silico Mechano-Chemical Model of Bone Healing for the Regeneration of Critical Defects: The Effect of BMP-2

PubMed Central

2015-01-01

The healing of bone defects is a challenge for both tissue engineering and modern orthopaedics. This problem has been addressed through the study of scaffold constructs combined with mechanoregulatory theories, disregarding the influence of chemical factors and their respective delivery devices. Of the chemical factors involved in the bone healing process, bone morphogenetic protein-2 (BMP-2) has been identified as one of the most powerful osteoinductive proteins. The aim of this work is to develop and validate a mechano-chemical regulatory model to study the effect of BMP-2 on the healing of large bone defects in silico. We first collected a range of quantitative experimental data from the literature concerning the effects of BMP-2 on cellular activity, specifically proliferation, migration, differentiation, maturation and extracellular matrix production. These data were then used to define a model governed by mechano-chemical stimuli to simulate the healing of large bone defects under the following conditions: natural healing, an empty hydrogel implanted in the defect and a hydrogel soaked with BMP-2 implanted in the defect. For the latter condition, successful defect healing was predicted, in agreement with previous in vivo experiments. Further in vivo comparisons showed the potential of the model, which accurately predicted bone tissue formation during healing, bone tissue distribution across the defect and the quantity of bone inside the defect. The proposed mechano-chemical model also estimated the effect of BMP-2 on cells and the evolution of healing in large bone defects. This novel in silico tool provides valuable insight for bone tissue regeneration strategies. PMID:26043112

Sequential healing at implants installed immediately into extraction sockets. An experimental study in dogs.

PubMed

Mainetti, Tomaso; Lang, Niklaus P; Bengazi, Franco; Favero, Vittorio; Soto Cantero, Luis; Botticelli, Daniele

2016-01-01

To compare the sequential healing at implants installed in a healed alveolar bony ridge or immediately after tooth extraction without functional load. In the mandible of 12 dogs, the mesial roots of the first molars were endodontically treated, the tooth hemisected, and the distal roots extracted. After 3 months, the mesial roots of the fourth premolars were endodontically treated, the tooth hemisected, and the distal roots extracted in one side of the mandible. Implants were placed immediately into extraction sockets (IPIES) of the fourth premolar and in the healed sites in the molar regions. Healing abutments were placed, and the flaps were sutured to allow a non-submerged healing. The time of surgery and of sacrifices were planned in such a way to obtain biopsies representing the healing after 1 and 2 weeks and 1 and 3 months, respectively. Ground sections were prepared for histological evaluation of tissues components on the implant surface and the coronal termination level of osseointegration (M-B). New bone apposition on the implant surface was slightly higher at the healed compared to the IPIES sites, being 7.4% and 4.1% after 1 week, and 67.3% and 65.3% after 3 months, respectively. Old bone was progressively resorbed, from 27.0% and 21.9% after 1 week, to 2.5% and 2.0% after 3 months, at healed and IPIES sites, respectively. M-B was 1.4 mm and 2.6 mm after 1 week, 1.2 mm and 1.2 mm after 3 months, at healed and IPIES sites, respectively. Similar patterns of sequential osseointegration were found at implants installed in healed alveolar bone or in alveolar sockets immediately after tooth extraction. The coronal termination level of osseointegration, that was different after 1 week, was found similar at the 3-month observation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Enhancement of healing in osteochondral defects by collagen sponge implants.

PubMed

Speer, D P; Chvapil, M; Volz, R G; Holmes, M D

1979-10-01

Implants of porous, highly cross-linked collagen sponge (CS) were tested for their capacity to enhance the healing of osteochondral defects in rabbits. Comparison was made to the healing of similar defects with polyvinyl alcohol sponge (PVAS) implants and with no implants (CONT). Evaluation was carried out up to 44 weeks following implantation and included observation of host cellular response, biodegradability of implant, gross appearance of restored joint surface, collagenous architecture of repair tissue, and properties of the junctions of implants and host articular cartilage, subchondral bone, and medullary bone. Collagen sponge proved most effective in promoting healing of osteochondral defects with fibrous and fibrocartilaginous tissue over restored subchondral bone. Collagen sponge showed many desirable properties as a potential material for biologic resurfacing of damaged joints. These properties included porosity, biodegradability, biocompatability, ability to mechanically protect cells and matrix while directing cell ingrowth, and an available chemical technology for modifying its biomechanical and biological properties. Comparative analysis of results of healing of CS, PVAS, and CONT osteochondral defects suggest rational design criteria for implant materials to improve their effectiveness in restoration of articular surfaces.

Evaluation of Mandibular Bone After Dental Extraction in Rats Treated With Antiresorptive Drugs.

PubMed

Poubel, Victor Lousan do Nascimento; Capella, Diogo Lenzi; Santos, Adair Roberto Soares; Correa, Márcio; Ruhland, Letícia; Rivero, Elena Riet Correa

2018-03-01

Zoledronic acid (ZOL) and denosumab (Dmab) are commonly used to treat bone pathologies. Because these drugs suppress bone metabolism, this study sought to compare their effect on bone repair after tooth extraction. Four-week-old male Wistar rats were randomly assigned to 1 of 3 groups: ZOL 0.125 mg/kg, Dmab 0.25 mg/kg, or saline solution 10 mL/kg (control). After 1 week of treatment, the first left molar was extracted; the rats were euthanized at 28 days. The jaws were removed and photographed for macroscopic analysis of wound healing and then subjected to tomographic and histologic analyses. Immunohistochemistry was carried out against the receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG). No difference in wound healing, presence of inflammatory infiltrate and bone sequestration, or osteocyte expression of RANKL and OPG was found among groups. Tomographic analysis showed that the ZOL group had less alveolar resorption and more complete alveolar repair compared with the other groups. There was a statistically significant difference in the OPG marker in the control (P = .008) and ZOL (P = .05) groups when comparing the extracted and non-extracted sides. Systemic use of ZOL can improve alveolar bone healing; however, the potential risk for the development of osteonecrosis should be considered. Higher expression of OPG seems to be associated with the control of osteoclastogenesis during bone repair. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Articular Cartilage Increases Transition Zone Regeneration in Bone-tendon Junction Healing

PubMed Central

Qin, Ling; Lee, Kwong Man; Leung, Kwok Sui

2008-01-01

The fibrocartilage transition zone in the direct bone-tendon junction reduces stress concentration and protects the junction from failure. Unfortunately, bone-tendon junctions often heal without fibrocartilage transition zone regeneration. We hypothesized articular cartilage grafts could increase fibrocartilage transition zone regeneration. Using a goat partial patellectomy repair model, autologous articular cartilage was harvested from the excised distal third patella and interposed between the residual proximal two-thirds bone fragment and tendon during repair in 36 knees. We evaluated fibrocartilage transition zone regeneration, bone formation, and mechanical strength after repair at 6, 12, and 24 weeks and compared them with direct repair. Autologous articular cartilage interposition resulted in more fibrocartilage transition zone regeneration (69.10% ± 14.11% [mean ± standard deviation] versus 8.67% ± 7.01% at 24 weeks) than direct repair at all times. There was no difference in the amount of bone formation and mechanical strength achieved. Autologous articular cartilage interposition increases fibrocartilage transition zone regeneration in bone-tendon junction healing, but additional research is required to ascertain the mechanism of stimulation and to establish the clinical applicability. PMID:18987921

On optimization of a composite bone plate using the selective stress shielding approach.

PubMed

Samiezadeh, Saeid; Tavakkoli Avval, Pouria; Fawaz, Zouheir; Bougherara, Habiba

2015-02-01

Bone fracture plates are used to stabilize fractures while allowing for adequate compressive force on the fracture ends. Yet the high stiffness of conventional bone plates significantly reduces compression at the fracture site, and can lead to subsequent bone loss upon healing. Fibre-reinforced composite bone plates have been introduced to address this drawback. However, no studies have optimized their configurations to fulfill the requirements of proper healing. In the present study, classical laminate theory and the finite element method were employed for optimization of a composite bone plate. A hybrid composite made of carbon fibre/epoxy with a flax/epoxy core, which was introduced previously, was optimized by varying the laminate stacking sequence and the contribution of each material, in order to minimize the axial stiffness and maximize the torsional stiffness for a given range of bending stiffness. The initial 14×4(14) possible configurations were reduced to 13 after applying various design criteria. A comprehensive finite element model, validated against a previous experimental study, was used to evaluate the mechanical performance of each composite configuration in terms of its fracture stability, load sharing, and strength in transverse and oblique Vancouver B1 fracture configurations at immediately post-operative, post-operative, and healed bone stages. It was found that a carbon fibre/epoxy plate with an axial stiffness of 4.6 MN, and bending and torsional stiffness of 13 and 14 N·m(2), respectively, showed an overall superiority compared with other laminate configurations. It increased the compressive force at the fracture site up to 14% when compared to a conventional metallic plate, and maintained fracture stability by ensuring the fracture fragments' relative motions were comparable to those found during metallic plate fixation. The healed stage results revealed that implantation of the titanium plate caused a 40.3% reduction in bone stiffness, while the composite plate lowered the stiffness by 32.9% as compared to the intact femur. This study proposed a number of guidelines for the design of composite bone plates. The findings suggest that a composite bone plate could be customized to allow for moderate compressive force on the fracture ends, while remaining relatively rigid in bending and torsion and strong enough to withstand external loads when a fracture gap is present. The results indicate that the proposed composite bone plate could be a potential candidate for bone fracture plate applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Biology of Bone and Ligament Healing.

PubMed

Cottrell, Jessica A; Turner, Jessica Cardenas; Arinzeh, Treena Livingston; O'Connor, J Patrick

2016-12-01

This review describes the normal healing process for bone, ligaments, and tendons, including primary and secondary healing as well as bone-to-bone fusion. It depicts the important mediators and cell types involved in the inflammatory, reparative, and remodeling stages of each healing process. It also describes the main challenges for clinicians when trying to repair bone, ligaments, and tendons with a specific emphasis on Charcot neuropathy, fifth metatarsal fractures, arthrodesis, and tendon sheath and adhesions. Current treatment options and research areas are also reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

Healing of extraction sockets filled with BoneCeramic® prior to implant placement: preliminary histological findings.

PubMed

De Coster, Peter; Browaeys, Hilde; De Bruyn, Hugo

2011-03-01

Various grafting materials have been designed to minimize edentulous ridge volume loss following tooth extraction by encouraging new bone formation in healing sockets. BoneCeramic® is a composite of hydroxyapatite and bèta-tricalcium phosphate with pores of 100-500 microns. The aim of this study was to evaluate bone regeneration in healing sockets substituted with BoneCeramic® prior to implant procedures. Fifteen extraction sockets were substituted with BoneCeramic® and 14 sockets were left to heal naturally in 10 patients (mean age 59.6 years). Biopsies were collected only from the implant recipient sites during surgery after healing periods ranging from 6-74 weeks (mean 22). In total, 24 biopsies were available; 10 from substituted and 14 from naturally healed sites. In one site, the implant was not placed intentionally and, in four substituted sites, implant placement had to be postponed due to inappropriate healing, hence from five sites biopsies were not available. Histological sections were examined by transmitted light microscope. At the time of implant surgery, bone at substituted sites was softer than in controls, compromising initial implant stability. New bone formation at substituted sites was consistently poorer than in controls, presenting predominantly loose connective tissue and less woven bone. The use of BoneCeramic® as a grafting material in fresh extraction sockets appears to interfere with normal healing processes of the alveolar bone. On the basis of the present preliminary findings, its indication as a material for bone augmentation, when implant placement is considered within 6-38 weeks after extraction, should be revised. © 2009, Copyright the Authors. Journal Compilation © 2011, Wiley Periodicals, Inc.

[Polarized microscopic observation of the collagen change in bone healing during bone lengthening].

PubMed

Zou, Pei; Li, Junhui; Li, Zhuyi

2006-01-01

To investigate the feature and regularity of the collagen change in bone healing during bone lengthening. Bone lengthening model was made in the middle segment of the rabbit tibia. Five days after the model was established, the bone was lengthened 1.5 mm per day for 14 days. The rabbits were put to death after elongation, 7, 14, 21, 30, 40, 50, 60 and 70 days after elongation. The distracted area of the bone was imbedded with paraffin. After being stained by the picric acid-sirius red staining, the slice was observed under polarized microscope. The features of the collagen change in the distracted bone were as follows: (1) In the fibrous tissue of the distracted area during lengthening period and the early stage after lengthening, there was not only collagen III but also much collagen I. (2) Collagen I , II and III were observed in the cartilage. (3) Collagen I, II and III were also observed in the pseudo-growth plate. (4) Collagen I took the dominance during lengthening period and the late stage after lengthening. New bone formation in bone lengthening is under the distracted force, so the collagen changes have different features compared with that in fracture healing. Collagen I, II and III can be identified by picric acid-sirius red staining and polarized microscope, so a new method for studying the collagen typing in bone repairing is provided.

A high-fat diet can affect bone healing in growing rats.

PubMed

Yamanaka, Jéssica Suzuki; Yanagihara, Gabriela Rezende; Carlos, Bruna Leonel; Ramos, Júnia; Brancaleon, Brígida Batista; Macedo, Ana Paula; Issa, João Paulo Mardegan; Shimano, Antônio Carlos

2018-05-01

A high-fat diet (HFD) can have a negative effect on bone quality in young and old people. Although bone healing in children is normally efficient, there is no evidence that children who have a diet rich in fat have compromised bone fracture regeneration compared with children with recommended dietary fat levels. The purpose of the present study was to evaluate the effects of an HFD on bone healing in growing female rats. Twenty-six postweaning female Wistar rats were divided into two groups (13 animals per group): a standard diet (SD) group and an HFD (with 60% of energy from fat) group. The rats received the assigned diets for 5 weeks, and in the third week they were submitted to an osteotomy procedure of the left tibia. Body mass and feed intake were recorded during the experiment. One day before euthanasia, an insulin tolerance test was performed. After euthanasia, the tibiae were removed and analyzed by densitometry, mechanical testing, histomorphometry, stereology and immunohistochemistry. An HFD caused an adaptive response to maintain energetic balance by decreasing feed intake and causing insulin insensitivity. There was no change in bone mineral density, collagen amount and immunostaining for bone formation, but maximal load and stiffness were decreased in the HFD group. In addition, bone volume had a tendency to be higher in the SD group than in the HFD group. Compared with rats receiving an SD, growing rats receiving an HFD for 5 weeks had similar bone mineral density but altered mechanical properties at the osteotomy defect site.

Synthetic Parathyroid Hormone May Augment Bone Volume in Autogenous Grafts: A Study in Rats.

PubMed

dos Santos, Rodrigo A B; Ferreira, Marcelo S; Mafra, Carlos Eduardo S; Holzhausen, Marinella; de Lima, Luiz Antônio Pugliesi Alves; Mendes Pannuti, Cláudio; César Neto, João Batista

2016-01-01

Synthetic parathyroid hormone [PTH(1-34)] has been investigated for its benefits on bone healing and osteoporosis treatment; however, there is little information regarding bone grafts. This study therefore investigates the effect of PTH(1-34) on autogenous bone graft healing. Bone grafts were harvested from the calvarium of rats with a trephine bur (3-mm internal diameter) and placed on the cortex near the mandible angle with a titanium screw. Animals were randomly assigned to group 1 (control): subcutaneous injections of saline solution, three times a week (n = 15); group 2: 2 μg/kg PTH(1-34), three times a week (n = 15); and group 3: 40 μg/kg PTH(1-34), three times a week (n = 15). Thirty days postoperatively, the animals were killed, and specimens (implant + bed + graft) were removed and used for undecalcified sections. The following histometric parameters were evaluated: total bone thickness (TT) (bed + gap + graft), graft thickness (GT) (adjacent to the implant), bone-to-implant contact (BIC), and bone area (BA) (within the limits of the threads). Five additional animals were sacrificed immediately after surgery (zero hour) to register bed and graft sizes before healing. Group 3 showed significantly greater bone gain compared with groups 1 and 2 (TT and GT, P <0.05). In relation to initial thickness (zero hour), groups 1 and 2 showed a total decrease in volume of 15.91% and 20.83%, respectively, whereas group 3 showed a slight bone gain (1.21%). Data analysis revealed a significant difference for group 3 compared with groups 1 and 2 (P <0.01). No differences were observed for BIC and BA (P >0.05). Systemic administration of PTH(1-34) augmented bone volume in autogenous grafts.

Influence of bone marrow on osseointegration in long bones: an experimental study in sheep.

PubMed

Morelli, Fabrizio; Lang, Niklaus P; Bengazi, Franco; Baffone, Davide; Vila Morales, C Dadonim; Botticelli, Daniele

2015-03-01

To evaluate the influence of yellow bone marrow on osseointegration of titanium oral implants using a long bone model. The two tibiae of eight sheep were used as experimental sites. Two osteotomies for implant installation were prepared in each tibia. At the control sites, no further treatments were performed while, at the test sites, bone marrow was removed from the osteotomy site with a curette to an extent that exceeded the implant dimensions. As a result, the apical portion of the implants at the control sites was in contact with bone marrow while, at the test sites, it was in contact with the blood clot. After 2 months, the same procedures were performed in the contralateral side. After another month, the animal was sacrificed. Ground sections were obtained for histological analysis. After 1 month of healing, no differences between test and control sites were found in the apical extension of osseointegration and the percentage of new bone-to-implant contact. However, after 3 months of healing, a higher percentage of new bone-to-implant contact was found at the test compared to the control sites in the marrow compartment. The apical extension of osseointegration, however, was similar to that found at the 1-month healing period both for test and control sites. Osseointegration appeared to be favored by the presence of a blood clot when compared to the presence of yellow fatty bone marrow. Moreover, the contact with cortical bone appeared to be a prerequisite for the osseointegration process in the long bone model. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Inflammatory cytokine response to titanium chemical composition and nanoscale calcium phosphate surface modification.

PubMed

Hamlet, Stephen; Ivanovski, Saso

2011-05-01

Nanoscale surface modification of titanium dental implants with calcium phosphate (CaP) has been shown to achieve superior bone wound healing and osseointegration compared with smooth or microrough titanium surfaces alone. As bone healing has been shown to be influenced by the action of cytokines, this study examined whether changes in cytokine gene expression from RAW 264.7 cells cultured on commercially pure and titanium alloy (Ti-6Al-4V) microrough or nanoscale crystalline CaP-modified surfaces, may influence downstream events in bone wound healing and osseointegration. Whilst no significant difference in the attachment or proliferation of RAW 264.7 cells was observed, the nanoscale CaP-modified surface elicited a gene expression profile with marked down-regulation of a number of pro-inflammatory cytokines and chemokines. Inflammatory cytokine gene expression was further influenced by chemical composition, with lower levels of pro-inflammatory markers noted following exposure of the macrophage-like cells to titanium alloy (Ti-6Al-4V) compared with the commercially pure titanium surface. Down-regulation of pro-inflammatory cytokine gene expression (confirmed at the protein level for TNFα and CCL5), may thus facilitate the enhanced bone wound healing and osseointegration observed clinically with nanoscale calcium phosphate-modified implant surfaces. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Formation of blood clot on biomaterial implants influences bone healing.

PubMed

Shiu, Hoi Ting; Goss, Ben; Lutton, Cameron; Crawford, Ross; Xiao, Yin

2014-12-01

The first step in bone healing is forming a blood clot at injured bones. During bone implantation, biomaterials unavoidably come into direct contact with blood, leading to a blood clot formation on its surface prior to bone regeneration. Despite both situations being similar in forming a blood clot at the defect site, most research in bone tissue engineering virtually ignores the important role of a blood clot in supporting healing. Dental implantology has long demonstrated that the fibrin structure and cellular content of a peri-implant clot can greatly affect osteoconduction and de novo bone formation on implant surfaces. This article reviews the formation of a blood clot during bone healing in relation to the use of platelet-rich plasma (PRP) gels. It is implicated that PRP gels are dramatically altered from a normal clot in healing, resulting in conflicting effect on bone regeneration. These results indicate that the effect of clots on bone regeneration depends on how the clots are formed. Factors that influence blood clot structure and properties in relation to bone healing are also highlighted. Such knowledge is essential for developing strategies to optimally control blood clot formation, which ultimately alter the healing microenvironment of bone. Of particular interest are modification of surface chemistry of biomaterials, which displays functional groups at varied composition for the purpose of tailoring blood coagulation activation, resultant clot fibrin architecture, rigidity, susceptibility to lysis, and growth factor release. This opens new scope of in situ blood clot modification as a promising approach in accelerating and controlling bone regeneration.

Inflammatory Microenvironment Persists After Bone Healing in Intra-articular Ankle Fractures.

PubMed

Adams, Samuel B; Leimer, Elizabeth M; Setton, Lori A; Bell, Richard D; Easley, Mark E; Huebner, Janet L; Stabler, Thomas V; Kraus, Virginia B; Olson, Steven A; Nettles, Dana L

2017-05-01

Post-traumatic osteoarthritis (PTOA) is responsible for the majority of cases of ankle arthritis. While acute and end-stage intra-articular inflammation has previously been described, the state of the joint between fracture healing and end-stage PTOA remains undefined. This study characterized synovial fluid (SF) composition of ankles after bone healing of an intra-articular fracture to identify factors that may contribute to the development of PTOA. Of an original 21 patients whose SF was characterized acutely following intra-articular ankle fractures, 7 returned for planned hardware (syndesmotic screw) removal after bone healing (approximately 6 months) and consented to a second bilateral SF collection. SF concentrations of 15 cytokines and matrix metalloproteinases (MMPs) and 2 markers each of cartilage catabolism (CTXII and glycosaminoglycan) and hemarthrosis (biliverdin and bilirubin) were compared for previously fractured and contralateral, uninjured ankles from the same patient. Analysis was also performed to determine the effect of the number of fracture lines and involvement of soft tissue on SF composition. Interleukin (IL)-6, IL-8, MMP-1, MMP-2, and MMP-3 were significantly elevated in the SF from healed ankles compared to matched contralateral uninjured ankles at approximately 6 months after fracture. There were no differences in markers of cartilage catabolism or hemarthrosis. Only IL-1α was affected by the number of fracture lines while differences were not detected for other analytes or with respect to the involvment of soft tissue. Sustained intra-articular inflammation, even after complete bone healing, was suggested by elevations of pro-inflammatory cytokines (IL-6 and IL-8). In addition, elevated concentrations of MMPs were also noted and were consistent with a persistent inflammatory environment. This study suggests new evidence of persistent intra-articular inflammation after intra-articular ankle fracture healing and suggests potential mediators for PTOA development. This work may be relevant to the clinical diagnosis and treatment of post-traumatic osteoarthritis.

Stem cell-mediated accelerated bone healing observed with in vivo molecular and small animal imaging technologies in a model of skeletal injury.

PubMed

Lee, Sheen-Woo; Padmanabhan, Parasuraman; Ray, Pritha; Gambhir, Sanjiv Sam; Doyle, Timothy; Contag, Christopher; Goodman, Stuart B; Biswal, Sandip

2009-03-01

Adult stem cells are promising therapeutic reagents for skeletal regeneration. We hope to validate by molecular imaging technologies the in vivo life cycle of adipose-derived multipotent cells (ADMCs) in an animal model of skeletal injury. Primary ADMCs were lentivirally transfected with a fusion reporter gene and injected intravenously into mice with bone injury or sham operation. Bioluminescence imaging (BLI), [(18)F]FHBG (9-(fluoro-hydroxy-methyl-butyl-guanine)-micro-PET, [(18)F]Fluoride ion micro-PET and micro-CT were performed to monitor stem cells and their effect. Bioluminescence microscopy and immunohistochemistry were done for histological confirmation. BLI showed ADMC's traffic from the lungs then to the injury site. BLI microscopy and immunohistochemistry confirmed the ADMCs in the bone defect. Micro-CT measurements showed increased bone healing in the cell-injected group compared to the noninjected group at postoperative day 7 (p < 0.05). Systemically administered ADMC's traffic to the site of skeletal injury and facilitate bone healing, as demonstrated by molecular and small animal imaging. Molecular imaging technologies can validate the usage of adult adipose tissue-derived multipotent cells to promote fracture healing. Imaging can in the future help establish therapeutic strategies including dosage and administration route. (c) 2008 Orthopaedic Research Society.

Evaluation of an injectable bioactive borate glass cement to heal bone defects in a rabbit femoral condyle model.

PubMed

Cui, Xu; Huang, Wenhai; Zhang, Yadong; Huang, Chengcheng; Yu, Zunxiong; Wang, Lei; Liu, Wenlong; Wang, Ting; Zhou, Jie; Wang, Hui; Zhou, Nai; Wang, Deping; Pan, Haobo; Rahaman, Mohamed N

2017-04-01

There is a need for synthetic biomaterials to heal bone defects using minimal invasive surgery. In the present study, an injectable cement composed of bioactive borate glass particles and a chitosan bonding solution was developed and evaluated for its capacity to heal bone defects in a rabbit femoral condyle model. The injectability and setting time of the cement in vitro decreased but the compressive strength increased (8±2MPa to 31±2MPa) as the ratio of glass particles to chitosan solution increased (from 1.0gml -1 to 2.5gml -1 ). Upon immersing the cement in phosphate-buffered saline, the glass particles reacted and converted to hydroxyapatite, imparting bioactivity to the cement. Osteoblastic MC3T3-E1 cells showed enhanced proliferation and alkaline phosphatase activity when incubated in media containing the soluble ionic product of the cement. The bioactive glass cement showed a better capacity to stimulate bone formation in rabbit femoral condyle defects at 12weeks postimplantation when compared to a commercial calcium sulfate cement. The injectable bioactive borate glass cement developed in this study could provide a promising biomaterial to heal bone defects by minimal invasive surgery. Copyright © 2016 Elsevier B.V. All rights reserved.

Immature myeloid cells are critical for enhancing bone fracture healing through angiogenic cascade

PubMed Central

Levy, Seth; Feduska, Joseph M.; Sawant, Anandi; Gilbert, Shawn; Hensel, Jonathan A.; Ponnazhagan, Selvarangan

2016-01-01

Bone fractures heal with overlapping phases of inflammation, cell proliferation, and bone remodeling. Osteogenesis and angiogenesis work in concert to control many stages of this process, and when one is impaired it leads to failure of bone healing, termed a nonunion. During fracture repair, there is an infiltration of immune cells at the fracture site that not only mediate the inflammatory responses, but we hypothesize they also exert influence on neovasculature. Thus, further understanding the effects of immune cell participation throughout fracture healing will reveal additional knowledge as to why some fractures heal while others form nonunions, and lead to development of novel therapeutics modulating immune cells, to increase fracture healing and prevent nonunions. Using novel femoral segmental and critical-size defect models in mice, we identified a systemic and significant increase in immature myeloid cell (IMC) infiltration during the initial phase of fracture healing until boney union is complete. Using gemcitabine to specifically ablate the IMC population, we confirmed delayed bone healing. Further, adoptive transfer of IMC increased bone growth in a nonunion model, signifying the role of this unique cell population in fracture healing. We also identified IMC post-fracture have the ability to increase endothelial cell migration, and tube formation, signaling the essential communication between the immune system and angiogenesis as a requirement for proper bone healing. Based on this data we propose that IMC may play a significant role in fracture healing and therapeutic targeting of IMC after fracture would minimize the chances of eventual nonunion pathology. PMID:27664567

Immature myeloid cells are critical for enhancing bone fracture healing through angiogenic cascade.

PubMed

Levy, Seth; Feduska, Joseph M; Sawant, Anandi; Gilbert, Shawn R; Hensel, Jonathan A; Ponnazhagan, Selvarangan

2016-12-01

Bone fractures heal with overlapping phases of inflammation, cell proliferation, and bone remodeling. Osteogenesis and angiogenesis work in concert to control many stages of this process, and when one is impaired it leads to failure of bone healing, termed a nonunion. During fracture repair, there is an infiltration of immune cells at the fracture site that not only mediate the inflammatory responses, but we hypothesize they also exert influence on neovasculature. Thus, further understanding the effects of immune cell participation throughout fracture healing will reveal additional knowledge as to why some fractures heal while others form nonunions, and lead to development of novel therapeutics modulating immune cells, to increase fracture healing and prevent nonunions. Using novel femoral segmental and critical-size defect models in mice, we identified a systemic and significant increase in immature myeloid cell (IMC) infiltration during the initial phase of fracture healing until boney union is complete. Using gemcitabine to specifically ablate the IMC population, we confirmed delayed bone healing. Further, adoptive transfer of IMC increased bone growth in a nonunion model, signifying the role of this unique cell population in fracture healing. We also identified IMC post-fracture have the ability to increase endothelial cell migration, and tube formation, signaling the essential communication between the immune system and angiogenesis as a requirement for proper bone healing. Based on this data we propose that IMC may play a significant role in fracture healing and therapeutic targeting of IMC after fracture would minimize the chances of eventual nonunion pathology. Copyright © 2016 Elsevier Inc. All rights reserved.

Hard tissue regeneration using bone substitutes: an update on innovations in materials

PubMed Central

Sarkar, Swapan Kumar

2015-01-01

Bone is a unique organ composed of mineralized hard tissue, unlike any other body part. The unique manner in which bone can constantly undergo self-remodeling has created interesting clinical approaches to the healing of damaged bone. Healing of large bone defects is achieved using implant materials that gradually integrate with the body after healing is completed. Such strategies require a multidisciplinary approach by material scientists, biological scientists, and clinicians. Development of materials for bone healing and exploration of the interactions thereof with the body are active research areas. In this review, we explore ongoing developments in the creation of materials for regenerating hard tissues. PMID:25995658

Hard tissue regeneration using bone substitutes: an update on innovations in materials.

PubMed

Sarkar, Swapan Kumar; Lee, Byong Taek

2015-05-01

Bone is a unique organ composed of mineralized hard tissue, unlike any other body part. The unique manner in which bone can constantly undergo self-remodeling has created interesting clinical approaches to the healing of damaged bone. Healing of large bone defects is achieved using implant materials that gradually integrate with the body after healing is completed. Such strategies require a multidisciplinary approach by material scientists, biological scientists, and clinicians. Development of materials for bone healing and exploration of the interactions thereof with the body are active research areas. In this review, we explore ongoing developments in the creation of materials for regenerating hard tissues.

Histologic healing following tooth extraction with ridge preservation using mineralized versus combined mineralized-demineralized freeze-dried bone allograft: a randomized controlled clinical trial.

PubMed

Borg, Tyler D; Mealey, Brian L

2015-03-01

Mineralized and demineralized freeze-dried bone allografts (FDBAs) are used in alveolar ridge (AR) preservation; however, each material has advantages and disadvantages. Combinations of allografts aimed at capitalizing on the advantages each offers are available. To date, there is no evidence to indicate if a combination allograft is superior in this application. The primary objective of this study is to histologically evaluate and compare healing of non-molar extraction sites grafted with either mineralized FDBA or a 70:30 mineralized:demineralized FDBA combination allograft in AR preservation. The secondary objective is to compare dimensional changes in ridge height and width after grafting with these two materials. Forty-two patients randomized into two equal groups received ridge preservation with either 100% mineralized FDBA (active control group) or the combination 70% mineralized: 30% demineralized allograft (test group). Sites were allowed to heal for 18 to 20 weeks, at which time core biopsies were obtained and dental implants were placed. AR dimensions were evaluated at the time of extraction and at implant placement, including change in ridge width and change in buccal and lingual ridge height. Histomorphometric analysis was performed to determine percentage of vital bone, residual graft, and connective tissue/other non-bone components. There was no significant difference between groups in AR dimensional changes. Combination allograft produced increased vital bone percentage (36.16%) compared to the FDBA group (24.69%; P = 0.0116). The combination allograft also had a significantly lower mean percentage of residual graft particles (18.24%) compared to FDBA (27.04%; P = 0.0350). This study provides the first histologic evidence showing greater new bone formation with a combination mineralized/demineralized allograft compared to 100% mineralized FDBA in AR preservation in humans. Combination allograft results in increased vital bone formation while providing similar dimensional stability of the AR compared to FDBA alone in AR preservation.

[Comparative study on graft of autogeneic iliac bone and tissue engineered bone].

PubMed

Shen, Bing; Xie, Fu-lin; Xie, Qing-fang

2002-11-01

To compare the clinical results of repairing bone defect of limbs with tissue engineering technique and with autogeneic iliac bone graft. From July 1999 to September 2001, 52 cases of bone fracture were randomly divided into two groups (group A and B). Open reduction and internal fixation were performed in all cases as routine operation technique. Autogeneic iliac bone was implanted in group A, while tissue engineered bone was implanted in group B. Routine postoperative treatment in orthopedic surgery was taken. The operation time, bleeding volume, wound healing and drainage volume were compared. The bone union was observed by the X-ray 1, 2, 3, and 5 months after operation. The sex, age and disease type had no obvious difference between groups A and B. all the wounds healed with first intention. The swelling degree of wound and drainage volume had no obvious difference. The operation time in group A was longer than that in group B (25 minutes on average) and bleeding volume in group A was larger than that in group B (150 ml on average). Bone union completed within 3 to 7 months in both groups. But there were 2 cases of delayed union in group A and 1 case in group B. Repair of bone defect with tissue engineered bone has as good clinical results as that with autogeneic iliac bone graft. In aspect of operation time and bleeding volume, tissue engineered bone graft is superior to autogeneic iliac bone.

The effects of photobiomodulation on healing of bone defects in streptozotocin induced diabetic rats

NASA Astrophysics Data System (ADS)

Martinez Costa Lino, Maíra D.; Bastos de Carvalho, Fabíola; Ferreira Moraes, Michel; Augusto Cardoso, José; Pinheiro, Antônio L. B.; Maria Pedreira Ramalho, Luciana

2011-03-01

Previous studies have shown positive effects of Low level laser therapy (LLLT) on the repair of bone defects, but there are only a few that associates bone healing in the presence of a metabolic disorder as Diabetes Melitus and LLLT. The aim of this study was to assess histologically the effect of LLLT (AsGaAl), 780nm, 70mW, CW, Ø~0.4mm, 16J/cm2 per session) on the repair of surgical defects created in the femur of diabetic and non-diabetic Wistar Albinus rats. Surgical bone defects were created in 60 animals divided into four groups of 15 animals each: Group C (non-diabetic - control); Group CL (non-diabetic + LLLT); Group CD (diabetic); Group CDL (diabetic + LLLT). The animals on the irradiated group received 16 J/cm2 per session divided into four points around the defect, being the first irradiation immediately after surgery and repeated every 48h for 14 days. The animals were killed 15, 21 and 30 days after surgery. The results of the present investigation showed histological evidence of improved amount of collagen fibers at early stages of the bone healing (15 days) and increased amount of well organized bone trabeculae at the end of the experimental period (30 days) on irradiated animals, (diabetic and non-diabetic) compared to non irradiated ones. It is concluded that LLLT has a positive biomodulative effect on the healing process of bone defects, even when diabetes mellitus was present.

Biomaterial delivery of morphogens to mimic the natural healing cascade in bone

PubMed Central

Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

2012-01-01

Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. PMID:22626978

[The effect of locally applied Grisaldone or choline salicylate gel on bone healing after tooth extraction in animal experiments].

PubMed

Cendelin, E; Fröhlich, M

1977-01-01

Comparative histological and experimental animal studies of the effects upon bone wound healing of topically applied choline salicylate gel and Grisaldon showed that Grisaldon tends to hinder the course of reparation of bone, whereas choline salicylate gel has no appreciable influence upon the time course of wound healing. This essential difference is considered to be due predominantly to the exactly opposite behavior shown by the two pharmaceutical preparations in regard to their solubility in water. The difficultly watersoluble Grisaldon tends to exert a longer-drawn-out irritant effect upon the tissue and can be detected in alveoli even after twenty-eight days from administration thereof. By contrast, choline salicylate gel, which is known to be readily soluble in water, will be eliminated already after two days from administration thereof.

Factors associated with nonunion, delayed union, and malunion in foot and ankle surgery in diabetic patients.

PubMed

Shibuya, Naohiro; Humphers, Jon M; Fluhman, Benjamin L; Jupiter, Daniel C

2013-01-01

The incidence of bone healing complications in diabetic patients is believed to be high after foot and ankle surgery. Although the association of hyperglycemia with bone healing complications has been well documented, little clinical information is available to show which diabetes-related comorbidities directly affect bone healing. Our goal was to better understand the risk factors associated with poor bone healing in the diabetic population through an exploratory, observational, retrospective, cohort study. To this end, 165 diabetic patients who had undergone arthrodesis, osteotomy, or fracture reduction were enrolled in the study to assess the risk factors associated with nonunion, delayed union, and malunion after elective and nonelective foot and/or ankle surgery. Bivariate analyses showed that a history of foot ulcer, peripheral neuropathy, and surgery duration were statistically significantly associated with bone healing complications. After adjusting for other covariates, only peripheral neuropathy, surgery duration, and hemoglobin A1c levels >7% were significantly associated statistically with bone healing complications. Of the risk factors we considered, peripheral neuropathy had the strongest association with bone healing complications. Copyright © 2013 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Wound healing of osteotomy defects prepared with piezo or conventional surgical instruments: a pilot study in rabbits.

PubMed

Ma, Li; Mattheos, Nikos; Sun, Yan; Liu, Xi Ling; Yip Chui, Ying; Lang, Niklaus Peter

2015-08-01

The aim of the present study was to evaluate and compare the wound-healing process following osteotomies performed with either conventional rotary burs or piezoelectric surgery in a rabbit model. Two types of osteotomy window defects of the nasal cavities were prepared on the nasal bone of 16 adult New Zealand white rabbits with either a conventional rotary bur or piezo surgery. The defects were covered with a resorbable membrane. Four animals were killed at 1, 2, 3, and 5 weeks after the surgical procedure, respectively. Histological and morphometric evaluations were performed to assess the volumetric density of various tissue components: the blood clot, vascularized structures, provisional matrix, osteoid, mineralized bone, bone debris, residual tissue, and old bone. Significantly more bone debris was found at 1 week in the conventionally-prepared defects compared to the piezo surgically-prepared defects. At 2 and 3 weeks, a newly-formed hard tissue bridge, mainly composed of woven bone, was seen; however, no statistically-significant differences were observed. At 5 weeks, the defects were completely filled with newly-formed bone. The defects prepared by piezo surgery showed a significantly decreased proportion of bone debris at 1 week, compared to conventional rotary bur defect. © 2014 Wiley Publishing Asia Pty Ltd.

Novel Therapy for Bone Regeneration in Large Segmental Defects

DTIC Science & Technology

2016-10-01

Giannoudis PV. Fat embolism and IM nailing. Injury. 2006;37(Suppl 4):S1–2. 38. Wenda K, Ritter G, Degreif J, Rudigier J. Pathogenesis of pul- monary... fracture healing, bone regeneration, minipig, pig 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF...saline control. 2. KEYWORDS: Bone healing, bone morphogenetic protein (BMP), thrombopoietin (TPO), therapy, fracture healing, bone regeneration, minipig

Possible benefits of strontium ranelate in complicated long bone fractures.

PubMed

Alegre, Duarte Nuno; Ribeiro, Costa; Sousa, Carlos; Correia, João; Silva, Luís; de Almeida, Luís

2012-02-01

Osteoporosis drugs are prescribed to prevent fragility fractures, which is the principal aim of the management of osteoporosis. However, if fracture does occur, then it is also important to promote a fast and uneventful healing process. Despite this, little is known about the effect of osteoporosis drugs on bone healing in humans. Strontium ranelate is an osteoporosis agent that increases bone formation and reduces bone resorption and may therefore be beneficial in fracture healing. We report four cases of fracture non-union for up to 20 months. Treatment with strontium ranelate (2 g/day) for between 6 weeks and 6 months appeared to contribute to bone consolidation in the four cases. Animal studies support beneficial effects of strontium ranelate on bone healing via improvement of bone material properties and microarchitecture in the vicinity of the fracture. The clinical cases described herein provide new information on these effects, in the absence of randomized controlled studies on the clinical efficacy of pharmacological treatments in osteoporosis in fracture repair. Further studies are necessary. Fracture healing is an important topic in orthopedic research and is also a concern for patients with postmenopausal osteoporosis. Evidence from case reports and animal studies suggests that strontium ranelate improves bone microarchitecture and accelerates fracture healing. A positive effect of osteoporosis treatments on bone healing is an interesting possibility and merits further clinical research.

Histopathological examination of bone debris from reaming of interlocking intra-medullary nail fixation of long bone fractures with concomitant head injury.

PubMed

Khallaf, Fathy G; Kehinde, Elijah O

2015-12-01

The aim of study was to test, for the presence of osteoblasts in the reaming debris of intramedullary nailing of femoral and tibial fracture in patients with and without severe head injury. Two groups of patients were studied. Group A (n = 32) had long bone fractures in addition to having head injuries. Group B (n = 35) had only long bone fractures. The fractures in the 2 groups of patients was treated by inter medullary nailing. Osteoblasts in the debris of the inter medullary nailing was compared between the 2 groups of patients. The results demonstrated that histopathological specimens from reaming debris of fractured femur and tibia in patients with head injury showed osteoblasts in (82.9%) and in (27.5%) of patients with isolated long bone fractures (p < 0.001). Healing indicators in diaphyseal fractures and concomitant head injury confirm fast and adequate healing in these patients and the presence of plenty of osteoblasts in their reaming debris may reflect a proof of accelerated fracture healing environment.

Osthole Promotes Bone Fracture Healing through Activation of BMP Signaling in Chondrocytes.

PubMed

Wang, Pinger; Ying, Jun; Luo, Cheng; Jin, Xing; Zhang, Shanxing; Xu, Taotao; Zhang, Lei; Mi, Meng; Chen, Di; Tong, Peijian; Jin, Hongting

2017-01-01

Osthole is a bioactive coumarin derivative and has been reported to be able to enhance bone formation and improve fracture healing. However, the molecular mechanism of Osthole in bone fracture healing has not been fully defined. In this study we determined if Osthole enhances bone fracture healing through activation of BMP2 signaling in mice. We performed unilateral open transverse tibial fracture procedure in 10-week-old C57BL/6 mice which were treated with or without Osthole. Our previous studies demonstrated that chondrocyte BMP signaling is required for bone fracture healing, in this study we also performed tibial fracture procedure in Cre-negative and Col2-Cre;Bmp2 flox/flox conditional knockout (KO) mice ( Bmp2 Col2Cre ) to determine if Osthole enhances fracture healing in a BMP2-dependent manner. Fracture callus tissues were collected and analyzed by X-ray, micro-CT (μCT), histology, histomorphometry, immunohistochemistry (IHC), biomechanical testing and quantitative gene expression analysis. In addition, mouse chondrogenic ATDC5 cells were cultured with or without Osthole and the expression levels of chondrogenic marker genes were examined. The results demonstrated that Osthole promotes bone fracture healing in wild-type (WT) or Cre - control mice. In contrast, Osthole failed to promote bone fracture healing in Bmp2 Col2Cre conditional KO mice. In the mice receiving Osthole treatment, expression of cartilage marker genes was significantly increased. We conclude that Osthole could promote bone strength and enhance fracture healing by activation of BMP2 signaling. Osthole may be used as an alternative approach in the orthopaedic clinic for the treatment of fracture healing.

Osthole Promotes Bone Fracture Healing through Activation of BMP Signaling in Chondrocytes

PubMed Central

Wang, Pinger; Ying, Jun; Luo, Cheng; Jin, Xing; Zhang, Shanxing; Xu, Taotao; Zhang, Lei; Mi, Meng; Chen, Di; Tong, Peijian; Jin, Hongting

2017-01-01

Osthole is a bioactive coumarin derivative and has been reported to be able to enhance bone formation and improve fracture healing. However, the molecular mechanism of Osthole in bone fracture healing has not been fully defined. In this study we determined if Osthole enhances bone fracture healing through activation of BMP2 signaling in mice. We performed unilateral open transverse tibial fracture procedure in 10-week-old C57BL/6 mice which were treated with or without Osthole. Our previous studies demonstrated that chondrocyte BMP signaling is required for bone fracture healing, in this study we also performed tibial fracture procedure in Cre-negative and Col2-Cre;Bmp2flox/flox conditional knockout (KO) mice (Bmp2Col2Cre) to determine if Osthole enhances fracture healing in a BMP2-dependent manner. Fracture callus tissues were collected and analyzed by X-ray, micro-CT (μCT), histology, histomorphometry, immunohistochemistry (IHC), biomechanical testing and quantitative gene expression analysis. In addition, mouse chondrogenic ATDC5 cells were cultured with or without Osthole and the expression levels of chondrogenic marker genes were examined. The results demonstrated that Osthole promotes bone fracture healing in wild-type (WT) or Cre- control mice. In contrast, Osthole failed to promote bone fracture healing in Bmp2Col2Creconditional KO mice. In the mice receiving Osthole treatment, expression of cartilage marker genes was significantly increased. We conclude that Osthole could promote bone strength and enhance fracture healing by activation of BMP2 signaling. Osthole may be used as an alternative approach in the orthopaedic clinic for the treatment of fracture healing. PMID:28924381

Complex ankle arthrodesis: Review of the literature

PubMed Central

Rabinovich, Remy V; Haleem, Amgad M; Rozbruch, S Robert

2015-01-01

Complex ankle arthrodesis is defined as an ankle fusion that is at high risk of delayed and nonunion secondary to patient comorbidities and/or local ankle/hindfoot factors. Risk factors that contribute to defining this group of patients can be divided into systemic factors and local factors pertaining to co-existing ankle or hindfoot pathology. Orthopaedic surgeons should be aware of these risk factors and their association with patients’ outcomes after complex ankle fusions. Both external and internal fixations have demonstrated positive outcomes with regards to achieving stable fixation and minimizing infection. Recent innovations in the application of biophysical agents and devices have shown promising results as adjuncts for healing. Both osteoconductive and osteoinductive agents have been effectively utilized as biological adjuncts for bone healing with low complication rates. Devices such as pulsed electromagnetic field bone stimulators, internal direct current stimulators and low-intensity pulsed ultrasound bone stimulators have been associated with faster bone healing and improved outcomes scores when compared with controls. The aim of this review article is to present a comprehensive approach to the management of complex ankle fusions, including the use of biophysical adjuncts for healing and a proposed algorithm for their treatment. PMID:26396936

Healing of Postextraction Sockets Preserved With Autologous Platelet Concentrates. A Systematic Review and Meta-Analysis.

PubMed

Del Fabbro, Massimo; Bucchi, Cristina; Lolato, Alessandra; Corbella, Stefano; Testori, Tiziano; Taschieri, Silvio

2017-08-01

The true benefit of autologous platelet concentrates (APCs) for enhancing the healing of postextraction sites is still a matter of debate, and in recent years several clinical trials have addressed this issue. The purpose of this study was to determine the effectiveness of an APC adjunct in the preservation of fresh extraction sockets. An electronic search was performed on Medline, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. Only controlled clinical trials or randomized clinical trials were included. Selected articles underwent risk-of-bias assessment. The outcomes were complications and adverse events, discomfort and quality of life, bone healing and remodeling assessed by histologic and radiographic techniques, and soft tissue healing. Thirty-three comparative studies were included. Nine articles had a parallel design and 24 had a split-mouth design. Twenty studies were considered to have a low risk of bias and 13 were considered to have a high risk. Overall, 1,193 teeth were extracted from 911 patients. Meta-analysis showed that soft tissue healing, probing depth at 3 months, and bone density at 1, 3, and 6 months were statistically better for the APC group. Qualitative analysis suggested that APCs might be associated with a decrease in swelling and trismus. However, no relevant difference among groups was found for probing depth at 1 month, incidence of alveolar osteitis, acute inflammation or infection, percentage of new bone, and indirect measurement of bone metabolism. APCs should be used in postextraction sites to improve clinical and radiographic outcomes such as bone density and soft tissue healing and postoperative symptoms. The actual benefit of APCs on decreasing pain in extraction sockets is still not quantifiable. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Effect of abutment height on interproximal implant bone level in the early healing: A randomized clinical trial.

PubMed

Blanco, Juan; Pico, Alexandre; Caneiro, Leticia; Nóvoa, Lourdes; Batalla, Pilar; Martín-Lancharro, Pablo

2018-01-01

The aim of this randomized clinical trial was to compare the effect on the interproximal implant bone loss (IBL) of two different heights (1 and 3 mm) of definitive abutments placed at bone level implants with a platform switched design. Twenty-two patients received forty-four implants (6.5-10 mm length and 3.5-4 mm diameter) to replace at least two adjacent missing teeth, one bridge set to each patient-two implants per bridge. Patients were randomly allocated, and two different abutment heights, 1 and 3 mm using only one abutment height per bridge, were used. Clinical and radiological measurements were performed at 3 and 6 months after surgery. Interproximal bone level changes were compared between treatment groups. The association between IBL and categorical variables (history of periodontitis, smoking, implant location, implant diameter, implant length, insertion torque, width of keratinized mucosa, bone density, gingival biotype and antagonist) was also performed. At 3 months, implants with a 1-mm abutment had significantly greater IBL (0.83 ± 0.19 mm) compared to implants with a 3-mm abutment (0.14 ± 0.08 mm). At 6 months, a greater IBL was observed at implants with 1-mm abutments compared to implants with 3-mm abutments (0.91 ± 0.19 vs. 0.11 ± 0.09 mm). The analysis of the relation between patient characteristics and clinical variables with IBL revealed no significant differences at any moment except for smoking. Abutment height is an important factor to maintain interproximal implant bone level in early healing. Short abutments led to a greater interproximal bone loss in comparison with long abutments after 6 months. Other variables except smoking showed no relation with interproximal bone loss in early healing. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Application of a novel bone osteotomy plate leads to reduction in heat-induced bone tissue necrosis in sheep.

PubMed

Bekić, Marijo; Davila, Slavko; Hrskanović, Mato; Bekić, Marijana; Seiwerth, Sven; Erdeljić, Viktorija; Capak, Darko; Butković, Vladimir

2008-12-01

Previous studies have shown substantial effect thermal damage can have on new bone formation following osteotomy. In this study we evaluated the extent of thermal damage which occurs in four different methods of osteotomy and the effects it can have on bone healing. We further wanted to test whether a special osteotomy plate we constructed can lead to diminished heat generation during osteotomy and enhanced bone healing. The four methods evaluated included osteotomy performed by chisel, a newly constructed osteotomy plate, Gigly and oscillating saw. Twelve adult sheep underwent osteotomy performed on both tibiae. Bone fragments were stabilized using a fixation plate. Callus size was assessed using standard radiographs. Densitometry and histological evaluation were performed at 8 weeks following osteotomy. Temperature measurements were performed both in vivo during the operation, and ex vivo on explanted tibiae. The defects healed without complications and showed typical course of secondary fracture healing with callus ingrowth into the osteotomy gap. Radiographic examination of bone healing showed a tendency towards more callus formation in bones osteotomized using Gigly and oscillating saw, but this difference lacked significance. Use of Gigly and oscillating saw elicited much higher temperatures at the bone cortex surface, which subsequently lead to slightly impaired bone healing according to histological analysis. BMD was equal among all bones. In conclusion, the time required for complete healing of the defect differed depended greatly on the instruments used. The newly constructed osteotomy plate showed best results based on histological findings of capillary and osteoblast density.

Vitamin E and the Healing of Bone Fracture: The Current State of Evidence

PubMed Central

Borhanuddin, Boekhtiar; Mohd Fozi, Nur Farhana; Naina Mohamed, Isa

2012-01-01

Background. The effect of vitamin E on health-related conditions has been extensively researched, with varied results. However, to date, there was no published review of the effect of vitamin E on bone fracture healing. Purpose. This paper systematically audited past studies of the effect of vitamin E on bone fracture healing. Methods. Related articles were identified from Medline, CINAHL, and Scopus databases. Screenings were performed based on the criteria that the study must be an original study that investigated the independent effect of vitamin E on bone fracture healing. Data were extracted using standardised forms, followed by evaluation of quality of reporting using ARRIVE Guidelines, plus recalculation procedure for the effect size and statistical power of the results. Results. Six animal studies fulfilled the selection criteria. The study methods were heterogeneous with mediocre reporting quality and focused on the antioxidant-related mechanism of vitamin E. The metasynthesis showed α-tocopherol may have a significant effect on bone formation during the normal bone remodeling phase of secondary bone healing. Conclusion. In general, the effect of vitamin E on bone fracture healing remained inconclusive due to the small number of heterogeneous and mediocre studies included in this paper. PMID:23304211

T Lymphocytes Influence the Mineralization Process of Bone

PubMed Central

El Khassawna, Thaqif; Serra, Alessandro; Bucher, Christian H.; Petersen, Ansgar; Schlundt, Claudia; Könnecke, Ireen; Malhan, Deeksha; Wendler, Sebastian; Schell, Hanna; Volk, Hans-Dieter; Schmidt-Bleek, Katharina; Duda, Georg N.

2017-01-01

Bone is a unique organ able to regenerate itself after injuries. This regeneration requires the local interplay between different biological systems such as inflammation and matrix formation. Structural reconstitution is initiated by an inflammatory response orchestrated by the host immune system. However, the individual role of T cells and B cells in regeneration and their relationship to bone tissue reconstitution remain unknown. Comparing bone and fracture healing in animals with and without mature T and B cells revealed the essential role of these immune cells in determining the tissue mineralization and thus the bone quality. Bone without mature T and B cells is stiffer when compared to wild-type bone thus lacking the elasticity that helps to absorb forces, thus preventing fractures. In-depth analysis showed dysregulations in collagen deposition and osteoblast distribution upon lack of mature T and B cells. These changes in matrix deposition have been correlated with T cells rather than B cells within this study. This work presents, for the first time, a direct link between immune cells and matrix formation during bone healing after fracture. It illustrates specifically the role of T cells in the collagen organization process and the lack thereof in the absence of T cells. PMID:28596766

Ozone Therapy Enhances Osseous Healing in Rats With Diabetes With Calvarial Defects: A Morphometric and Immunohistochemical Study.

PubMed

Alpan, Aysan Lektemur; Toker, Hülya; Ozer, Hatice

2016-08-01

Bone healing is impaired in diabetes mellitus (DM) cases. The aim of this study is to investigate, both morphometrically and immunohistochemically, the effect of gaseous ozone on bone healing in diabetic rat calvarial defects treated with xenografts. DM was induced with 50 mg/kg intraperitoneal streptozotocin in 56 male Wistar rats. Study groups were as follows: 1) empty defect (control, n = 14); 2) xenograft (XG, n = 14); 3) empty defect treated with ozone therapy (control + ozone, n = 14); and 4) xenograft and ozone application (XG + ozone, n = 14). Critical-size defects were created in all rats. Bovine-derived xenograft was applied to XG groups. Gaseous ozone was applied on the operation day and daily for 2 weeks (140 ppm at 2 L/d, 2.24 mg). Rats were sacrificed at 4 or 8 weeks post-surgery. Total bone area, newly formed bone, and residual graft material were measured histomorphometrically. Osteocalcin and bone morphogenic protein (BMP)-2 expression was evaluated immunohistochemically. Osteoclast numbers in the XG + ozone group were higher than the other groups at week 4 (P <0.05). XG + ozone group revealed more total bone area and new bone area than the XG group at weeks 4 (P <0.05) and 8 (P >0.05). Residual graft materials were decreased in the XG + ozone group and the same group revealed more BMP-2 positivity compared with other groups. Osteocalcin positivity in XG groups was higher than in control groups. Within the limitations of this DM animal study, gaseous ozone application accelerates xenograft resorption and enhances bone regeneration, especially in the early stages of bone healing.

Growth factors and cytokines in patients with long bone fractures and associated spinal cord injury.

PubMed

Khallaf, Fathy G; Kehinde, Elijah O; Mostafa, Ahmed

2016-06-01

The aim of the study was to test the effect of acute traumatic spinal cord injury of quadriplegia or paraplegia on bone healing in patients with associated long bone fractures and to investigate the molecular and cellular events of the underlying mechanism for a possible acceleration. Healing indicators of long bone fractures and growth factors, IGF-II, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), Activin-A, and cytokine I-L-1, in the patients' blood were calculated and measured for 21 patients with spinal cord injuries and associated long bone fractures in prospective controlled study and compared to 20 patients with only spinal cord injuries, 30 patients with only long bone fractures, and 30 healthy volunteers. The study results showed that long bone fractures in patients with associated acute traumatic spinal cord injury of quadriplegia or paraplegia heal more expectedly, faster, and with exuberant florid union callus (P > 0.001) and show statistically significant higher levels of growth factors like PDGF, VEGF, Activin-A, and cytokine I-L-1, along the 3 weeks of follow-up (P > 0.005). I-IGF-II showed statistically significant subnormal level along the whole follow-up period in the same patients (P > 0.005). We concluded that long bone fractures in spinal cord injury patients heal more expectedly, faster, and with exuberant and florid callus formation; growth factors like IGF-II, PDGF, VEGF, Activin-A, and cytokine I-L-I have roles as mediators, in molecular events and as byproducts of the subtle mechanism of accelerated osteogenesis in these patients and may represent therapeutic potentials to serve as agents to enhance bone repair.

Basic concepts regarding fracture healing and the current options and future directions in managing bone fractures.

PubMed

Bigham-Sadegh, Amin; Oryan, Ahmad

2015-06-01

Fracture healing is a complex physiological process, which involves a well-orchestrated series of biological events. Repair of large bone defects resulting from trauma, tumours, osteitis, delayed unions, non-unions, osteotomies, arthrodesis and multifragmentary fractures is a current challenge of surgeons and investigators. Different therapeutic modalities have been developed to enhance the healing response and fill the bone defects. Different types of growth factors, stem cells, natural grafts (autografts, allografts or xenografts) and biologic- and synthetic-based tissue-engineered scaffolds are some of the examples. Nevertheless, these organic and synthetic materials and therapeutic agents have some significant limitations, and there are still no well-approved treatment modalities to meet all the expected requirements. Bone tissue engineering is a newer option than the traditional grafts and may overcome many limitations of the bone graft. To select an appropriate treatment strategy in achieving a successful and secure healing, more information concerning injuries of bones, their healing process and knowledge of the factors involved are required. The main goals of this work are to present different treatment modalities of the fractured bones and to explain how fractures normally heal and what factors interfere with fracture healing. This study provides an overview of the processes of fracture healing and discusses the current therapeutic strategies that have been claimed to be effective in accelerating fracture healing. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Histologic Evaluation of Critical Size Defect Healing With Natural and Synthetic Bone Grafts in the Pigeon ( Columba livia ) Ulna.

PubMed

Tunio, Ahmed; Jalila, Abu; Goh, Yong Meng; Shameha-Intan; Shanthi, Ganabadi

2015-06-01

Fracture and bone segment loss are major clinical problems in birds. Achieving bone formation and clinical union in a fracture case is important for the survival of the bird. To evaluate the efficacy of bone grafts for defect healing in birds, 2 different bone grafts were investigated in the healing of a bone defect in 24 healthy pigeons ( Columba livia ). In each bird, a 1-cm critical size defect (CSD) was created in the left ulna, and the fracture was stabilized with external skeletal fixation (ESF). A graft of hydroxyapatite (HA) alone (n = 12 birds) or demineralized bone matrix (DBM) combined with HA (n = 12 birds) was implanted in the CSD. The CSD healing was evaluated at 3 endpoints: 3, 6, and 12 weeks after surgery. Four birds were euthanatized at each endpoint from each treatment group, and bone graft healing in the ulna CSD was evaluated by histologic examination. The CSD and graft implants were evaluated for quality of union, cortex development, and bone graft incorporation. Results showed no graft rejection in any bird, and all birds had connective tissue formation in the defect because of the bone graft application. These results suggest that bone defect healing can be achieved by a combination of osteoinductive and osteoconductive bone graft materials for clinical union and new bone regeneration in birds. The combination of DBM and HA resulted in a better quality bone graft (P < .05) than did HA alone, but there was no significant differences in cortex development or bone graft incorporation at 3, 6, or 12 weeks. From the results of this study, we conclude that HA bone grafts, alone or in combination with DBM, with external skeletal fixation is suitable and safe for bone defect and fracture treatment in pigeons.

Influence of Healing Period Upon Bone Turn Over on Maxillary Sinus Floor Augmentation Grafted Solely with Deproteinized Bovine Bone Mineral: A Prospective Human Histological and Clinical Trial.

PubMed

Wang, Feng; Zhou, Wenjie; Monje, Alberto; Huang, Wei; Wang, Yueping; Wu, Yiqun

2017-04-01

To investigate the influence of maturation timing upon histological, histomorphometric and clinical outcomes when deproteinized bovine bone mineral (DBBM) was used as a sole biomaterial for staged maxillary sinus floor augmentation (MSFA). Patients with a posterior edentulous maxillary situation and a vertical bone height ≤ 4 mm were included in this study. A staged MSFA was carried out. After MSFA with DBBM as a sole grafting material, biopsy cores were harvested with simultaneous implant placement followed by a healing period of 5, 8, and 11 months, respectively. Micro-CT, histologic and histomorphometric analyses were performed. Forty-one patients were enrolled and 38 bone core biopsies were harvested. Significantly greater BV/TV was observed between 5- and 8-month healing from micro-CT analysis. Histomorphometric analyses showed the ratio of mineralized newly formed bone increased slightly from 5 to 11 months; however, no statistically significant difference was reached (p = .409). Residual bone substitute decreased from 37.3 ± 5.04% to 20.6 ± 7.45%, achieving a statistical significant difference from of 5 up to 11 months (p < .01). Moreover, no implant failure, biological or technical complication occurred after 12-month follow-up of functional loading. DBBM utilized as sole grafting material in staged MSFA demonstrated to be clinically effective regardless of the healing period. Histomorphometrical and micro-CT assessments revealed that at later stages of healing (8 and 11 months) there is a higher proportion of newly-bone formation compared to earlier stages (5 months). Moreover, the longer the maturation period, the substantially lesser remaining biomaterial could be expected. Even though, these facts did not seem to negatively impact on the implant prognosis 1-year after loading. © 2016 Wiley Periodicals, Inc.

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.

Bringing new life to damaged bone: the importance of angiogenesis in bone repair and regeneration.

PubMed

Stegen, Steve; van Gastel, Nick; Carmeliet, Geert

2015-01-01

Bone has the unique capacity to heal without the formation of a fibrous scar, likely because several of the cellular and molecular processes governing bone healing recapitulate the events during skeletal development. A critical component in bone healing is the timely appearance of blood vessels in the fracture callus. Angiogenesis, the formation of new blood vessels from pre-existing ones, is stimulated after fracture by the local production of numerous angiogenic growth factors. The fracture vasculature not only supplies oxygen and nutrients, but also stem cells able to differentiate into osteoblasts and in a later phase also the ions necessary for mineralization. This review provides a concise report of the regulation of angiogenesis by bone cells, its importance during bone healing and its possible therapeutic applications in bone tissue engineering. This article is part of a Special Issue entitled "Stem Cells and Bone". Copyright © 2014 Elsevier Inc. All rights reserved.

The ameloblastin extracellular matrix molecule enhances bone fracture resistance and promotes rapid bone fracture healing.

PubMed

Lu, Xuanyu; Li, Wenjin; Fukumoto, Satoshi; Yamada, Yoshihiko; Evans, Carla A; Diekwisch, Tom; Luan, Xianghong

2016-01-01

The extracellular matrix (ECM) provides structural support, cell migration anchorage, cell differentiation cues, and fine-tuned cell proliferation signals during all stages of bone fracture healing, including cartilaginous callus formation, callus remodeling, and bony bridging of the fracture gap. In the present study we have defined the role of the extracellular matrix protein ameloblastin (AMBN) in fracture resistance and fracture healing of mouse long bones. To this end, long bones from WT and AMBN(Δ5-6) truncation model mice were subjected to biomechanical analysis, fracture healing assays, and stem cell colony formation comparisons. The effect of exogenous AMBN addition to fracture sites was also determined. Our data indicate that lack of a functional AMBN in the bone matrix resulted in 31% decreased femur bone mass and 40% reduced energy to failure. On a cellular level, AMBN function inhibition diminished the proliferative capacity of fracture repair callus cells, as evidenced by a 58% reduction in PCNA and a 40% reduction in Cyclin D1 gene expression, as well as PCNA immunohistochemistry. In terms of fracture healing, AMBN truncation was associated with an enhanced and prolonged chondrogenic phase, resulting in delayed mineralized tissue gene expression and delayed ossification of the fracture repair callus. Underscoring a role of AMBN in fracture healing, there was a 6.9-fold increase in AMBN expression at the fracture site one week after fracture, and distinct AMBN immunolabeling in the fracture gap. Finally, application of exogenous AMBN protein to bone fracture sites accelerated callus formation and bone fracture healing (33% increase in bone volume and 19% increase in bone mineral density), validating the findings of our AMBN loss of function studies. Together, these data demonstrate the functional importance of the AMBN extracellular matrix protein in bone fracture prevention and rapid fracture healing. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

The Ameloblastin extracellular matrix molecule enhances bone fracture resistance and promotes rapid bone fracture healing

PubMed Central

Lu, Xuanyu; Li, Wenjin; Fukumoto, Satoshi; Yamada, Yoshihiko; Evans, Carla; Diekwisch, Thomas G.H.; Luan, Xianghong

2016-01-01

The extracellular matrix (ECM) provides structural support, cell migration anchorage, cell differentiation cues, and fine-tuned cell proliferation signals during all stages of bone fracture healing, including cartilaginous callus formation, callus remodeling, and bony bridging of the fracture gap. In the present study we have defined the role of the extracellular matrix protein ameloblastin (AMBN) in fracture resistance and fracture healing of mouse long bones. To this end, long bones from WT and AMBNΔ5-6 truncation model mice were subjected to biomechanical analysis, fracture healing assays, and stem cell colony formation comparisons. The effect of exogenous AMBN addition to fracture sites was also determined. Our data indicate that lack of a functional AMBN in the bone matrix resulted in 31% decreased femur bone mass and 40% reduced energy to failure. On a cellular level, AMBN function inhibition diminished the proliferative capacity of fracture repair callus cells, as evidenced by a 58% reduction in PCNA and a 40% reduction in Cyclin D1 gene expression, as well as PCNA immunohistochemistry. In terms of fracture healing, AMBN truncation was associated with an enhanced and prolonged chondrogenic phase, resulting in delayed mineralized tissue gene expression and delayed ossification of the fracture repair callus. Underscoring a role of AMBN in fracture healing, there was a 6.9-fold increase in AMBN expression at the fracture site one week after fracture, and distinct AMBN immunolabeling in the fracture gap. Finally, application of exogenous AMBN protein to bone fracture sites accelerated callus formation and bone fracture healing (33% increase in bone volume and 19% increase in bone mineral density), validating the findings of our AMBN loss of function studies. Together, these data demonstrate the functional importance of the AMBN extracellular matrix protein in bone fracture prevention and rapid fracture healing. PMID:26899203

Excellent healing rates and patient satisfaction after arthroscopic repair of medium to large rotator cuff tears with a single-row technique augmented with bone marrow vents.

PubMed

Dierckman, Brian D; Ni, Jake J; Karzel, Ronald P; Getelman, Mark H

2018-01-01

This study evaluated the repair integrity and patient clinical outcomes following arthroscopic rotator cuff repair of medium to large rotator cuff tears using a single-row technique consisting of medially based, triple-loaded anchors augmented with bone marrow vents in the rotator cuff footprint lateral to the repair. This is a retrospective study of 52 patients (53 shoulders) comprising 36 males and 16 females with a median age of 62 (range 44-82) with more than 24-month follow-up, tears between 2 and 4 cm in the anterior-posterior dimension and utilizing triple-loaded anchors. Mann-Whitney test compared Western Ontario Rotator Cuff (WORC) outcome scores between patients with healed and re-torn cuff repairs. Multivariate logistic regression analysed association of variables with healing status and WORC score. Cuff integrity was assessed on MRI, read by a musculoskeletal fellowship-trained radiologist. Magnetic resonance imaging (MRI) demonstrated an intact repair in 48 of 53 shoulders (91%). The overall median WORC score was 95.7 (range 27.6-100.0). A significant difference in WORC scores were seen between patients with healed repairs 96.7 (range 56.7-100.0) compared with a re-tear 64.6 (27.6-73.8), p < 0.00056. Arthroscopic repair of medium to large rotator cuff tears using a triple-loaded single-row repair augmented with bone marrow vents resulted in a 91% healing rate by MRI and excellent patient reported clinical outcomes comparable to similar reported results in the literature. IV.

Histologic and histomorphometric evaluation of bone regeneration using nanocrystalline hydroxyapatite and human freeze-dried bone graft : An experimental study in rabbit.

PubMed

Sadeghi, Rokhsareh; Najafi, Mohammad; Semyari, Hassan; Mashhadiabbas, Fatemeh

2017-03-01

Bone regeneration is an important concern in periodontal treatment and implant dentistry. Different biomaterials and surgical techniques have been used for this purpose. The aim of the present study was to compare the effect of nanocrystalline hydroxyapatite and human freeze-dried bone graft (FDBG) in regeneration of rabbit calvarium bony defects by histologic and histomorphometric evaluation. In this experimental study, three similar defects, measuring 8 mm in diameter, were created in the calvaria of 16 white New Zealand rabbits. Two defects were filled with FDBG and nanocrystalline hydroxyapatite silica gel, while the other one remained unfilled to be considered as control. All the defects were covered with collagen membranes. During the healing period, two animals perished; so 14 rabbits were divided into two groups: half of them were euthanized after 6 weeks of healing and the other half after 12 weeks. The specimens were subjected to histologic and histomorphometric examinations for assessment of the following variables: percentage of bone formation and residual graft material, inflammation scores, patterns of bone formation and type of newly formed bone. The percentages of new bone formation after 6 weeks were 14.22 ± 7.85, 21.57 ± 6.91, and 20.54 ± 10.07% in FDBG, NanoBone, and control defects. These values were 27.54 ± 20.19, 23.86 ± 6.27, and 26.48 ± 14.18% in 12-week specimens, respectively. No significant differences were found in the amount of bone formation between the groups. With regard to inflammation, the control and NanoBone groups showed significantly less inflammation compared to FDBG at the 6-week healing phase (P = 0.04); this difference was not significant in the 12-week specimens. Based on the results of this experimental study, both NanoBone and FDBG exhibited a similar effect on bone formation.

Bmp2 conditional knockout in osteoblasts and endothelial cells does not impair bone formation after injury or mechanical loading in adult mice

PubMed Central

McKenzie, Jennifer A.; Buettmann, Evan G.; Gardner, Michael J.; Silva, Matthew J.

2015-01-01

Post-natal osteogenesis after mechanical trauma or stimulus occurs through either endochondral healing, intramembranous healing or lamellar bone formation. Bone morphogenetic protein 2 (BMP2) is up-regulated in each of these osteogenic processes and is expressed by a variety of cells including osteoblasts and vascular cells. It is known that genetic knockout of Bmp2 in all cells or in osteo-chondroprogenitor cells completely abrogates endochondral healing after full fracture. However, the importance of BMP2 from differentiated osteoblasts and endothelial cells is not known. Moreover, the importance of BMP2 in non-endochondral bone formation such as intramembranous healing or lamellar bone formation is not known. Using inducible and tissue-specific Cre-lox mediated targeting of Bmp2 in adult (10–24 week old) mice, we assessed the role of BMP2 expression globally, by osteoblasts, and by vascular endothelial cells in endochondral healing, intramembranous healing and lamellar bone formation. These three osteogenic processes were modeled using full femur fracture, ulnar stress fracture, and ulnar non-damaging cyclic loading, respectively. Our results confirmed the requirement of BMP2 for endochondral fracture healing, as mice in which Bmp2 was knocked out in all cells prior to fracture failed to form a callus. Targeted deletion of Bmp2 in osteoblasts (osterix-expressing) or vascular endothelial cells (vascular endothelial cadherin-expressing) did not impact fracture healing in any way. Regarding non-endochondral bone formation, we found that BMP2 is largely dispensable for intramembranous bone formation after stress fracture and also not required for lamellar bone formation induced by mechanical loading. Taken together our results indicate that osteoblasts and endothelial cells are not a critical source of BMP2 in endochondral fracture healing, and that non-endochondral bone formation in the adult mouse is not as critically dependent on BMP2. PMID:26344756

Biomaterial delivery of morphogens to mimic the natural healing cascade in bone.

PubMed

Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

2012-09-01

Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

Is sonic Hedgehog involved in human fracture healing? --a prospective study on local and systemic concentrations of SHH.

PubMed

Eipeldauer, Stefan; Thomas, Anita; Hoechtl-Lee, Leonard; Kecht, Mathias; Binder, Harald; Koettstorfer, Julia; Gregori, Markus; Sarahrudi, Kambiz

2014-01-01

Sonic Hedgehog (SHH) is a new signalling pathway in bone repair. Evidence exist that SHH pathway plays a significant role in vasculogenesis and limb development during embryogenesis. Some in vitro and animal studies has already proven its potential for bone regeneration. However, no data on the role of SHH in the human fracture healing have been published so far. Seventy-five patients with long bone fractures were included into the study and divided in 2 groups. First group contained 69 patients with normal fracture healing. Four patients with impaired fracture healing formed the second group. 34 volunteers donated blood samples as control. Serum samples were collected over a period of 1 year following a standardized time schedule. In addition, SHH levels were measured in fracture haematoma and serum of 16 patients with bone fractures. Fracture haematoma and patients serum both contained lower SHH concentrations compared to control serum. The comparison between the patients' serum SHH level and the control serum revealed lower levels for the patients at all measurement time points. Significantly lower concentrations were observed at weeks 1 and 2 after fracture. SHH levels were slightly decreased in patients with impaired fracture healing without statistical significance. This is the first study to report local and systemic concentration of SHH in human fracture healing and SHH serum levels in healthy adults. A significant reduction of the SHH levels during the inflammatory phase of fracture healing was found. SHH concentrations in fracture haematoma and serum were lower than the concentration in control serum for the rest of the healing period. Our findings indicate that there is no relevant involvement of SHH in human fracture healing. Fracture repair process seem to reduce the SHH level in human. Further studies are definitely needed to clarify the underlying mechanisms.

Interactions between MSCs and Immune Cells: Implications for Bone Healing

PubMed Central

Kovach, Tracy K.; Dighe, Abhijit S.; Lobo, Peter I.; Cui, Quanjun

2015-01-01

It is estimated that, of the 7.9 million fractures sustained in the United States each year, 5% to 20% result in delayed or impaired healing requiring therapeutic intervention. Following fracture injury, there is an initial inflammatory response that plays a crucial role in bone healing; however, prolonged inflammation is inhibitory for fracture repair. The precise spatial and temporal impact of immune cells and their cytokines on fracture healing remains obscure. Some cytokines are reported to be proosteogenic while others inhibit bone healing. Cell-based therapy utilizing mesenchymal stromal cells (MSCs) is an attractive option for augmenting the fracture repair process. Osteoprogenitor MSCs not only differentiate into bone, but they also exert modulatory effects on immune cells via a variety of mechanisms. In this paper, we review the current literature on both in vitro and in vivo studies on the role of the immune system in fracture repair, the use of MSCs in the enhancement of fracture healing, and interactions between MSCs and immune cells. Insight into this paradigm can provide valuable clues in identifying cellular and noncellular targets that can potentially be modulated to enhance both natural bone healing and bone repair augmented by the exogenous addition of MSCs. PMID:26000315

Acute Phosphate Restriction Leads to Impaired Fracture Healing and Resistance to BMP-2

PubMed Central

Wigner, Nathan A; Luderer, Hilary F; Cox, Megan K; Sooy, Karen; Gerstenfeld, Louis C; Demay, Marie B

2010-01-01

Hypophosphatemia leads to rickets and osteomalacia, the latter of which results in decreased biomechanical integrity of bones, accompanied by poor fracture healing. Impaired phosphate-dependent apoptosis of hypertrophic chondrocytes is the molecular basis for rickets. However, the underlying pathophysiology of impaired fracture healing has not been characterized previously. To address the role of phosphate in fracture repair, mice were placed on a phosphate-restricted diet 2 days prior to or 3 days after induction of a mid-diaphyseal femoral fracture to assess the effects of phosphate deficiency on the initial recruitment of mesenchymal stem cells and their subsequent differentiation. Histologic and micro-computed tomographic (µCT) analyses demonstrated that both phosphate restriction models dramatically impaired fracture healing primarily owing to a defect in differentiation along the chondrogenic lineage. Based on Sox9 and Sox5 mRNA levels, neither the initial recruitment of cells to the callus nor their lineage commitment was effected by hypophosphatemia. However, differentiation of these cells was impaired in association with impaired bone morphogenetic protein (BMP) signaling. In vivo ectopic bone-formation assays and in vitro investigations in ST2 stromal cells confirmed that phosphate restriction leads to BMP-2 resistance. Marrow ablation studies demonstrate that hypophosphatemia has different effects on injury-induced intramembranous bone formation compared with endochondral bone formation. Thus phosphate plays an important role in the skeleton that extends beyond mineralized matrix formation and growth plate maturation and is critical for endochondral bone repair. © 2010 American Society for Bone and Mineral Research. PMID:19839770

Evaluation of bone marrow derived mesenchymal stem cells for full-thickness wound healing in comparison to tissue engineered chitosan scaffold in rabbit.

PubMed

Rajabian, Mohammad Hossein; Ghorabi, Gholam Hossein; Geramizadeh, Bita; Sameni, Safoura; Ayatollahi, Maryam

2017-02-01

Chronic wounds present a major challenge in modern medicine. Even under optimal conditions, the healing process may lead to scarring and fibrosis. The ability of mesenchymal stem cells (MSCs) to differentiate into other cell types makes these cells an attractive therapeutic tool for cell transplantation. Both tissue-engineered construct and MSC therapy are among the current wound healing procedures and potential care. Chitosan has been widely applied in tissue engineering because of its biocompatibility and biodegradability. The aim of the current work was to compare the efficiency of MSCs and chitosan dressing, alone or in combination treatment on wound healing. This study was conducted on 15 rabbits, which were randomly divided in 3 groups based on the type of treatment with MSCs, chitosan dressing and combination of both. A full-thickness skin defect was excised from the right and left side of the back of each animals. Defects on right sides were filled with treatments and left side defects were left as control. Evaluation of the therapeutic effectiveness was performed through a variety of clinical and microscopical evaluations and measurements of the process of wound healing on days 7, 14, 21, and 28. Histological evaluation of wound healing was classified by different scoring systems. The data indicated that wounds treated with bone marrow derived MSC had enhanced cellularity and better epidermal regeneration. During the early stages of wound healing, the closure rate of bone marrow derived MSC-treated wounds were significantly higher than other treatments (P<0.05). Although the MSCs in the wound edges enhance the healing of the full-thickness wound, the healing process of chitosan treatment was slower than the control group. This study revealed advanced granulation tissue formation and epithelialization in wounds treated with MSCs, and may suggests this treatment as an effective applicant in wound healing process. Chitosan scaffold dressings, whether alone or in combination with MSCs, have worsened the wound healing as compared to the control group. Copyright © 2016 Elsevier Ltd. All rights reserved.

Structural and ultrastructural analyses of bone regeneration in rabbit cranial osteotomy: Piezosurgery versus traditional osteotomes.

PubMed

Anesi, Alexandre; Ferretti, Marzia; Cavani, Francesco; Salvatori, Roberta; Bianchi, Michele; Russo, Alessandro; Chiarini, Luigi; Palumbo, Carla

2018-01-01

Clinical advantages of piezosurgery have been already proved. However, few investigations have focused on the dynamics of bone healing. The aim of this study was to evaluate, in adult rabbits, bone regeneration after cranial linear osteotomies with two piezoelectrical devices (Piezosurgery ® Medical - PM and Piezosurgery ® Plus - PP), comparing them with conventional rotary osteotomes (RO). PP was characterized by an output power three times higher than PM. Fifteen days after surgery, histomorphometric analyses showed that the osteotomy gap produced with PM and PP was about half the size of that produced by RO, and in a more advanced stage of recovery. Values of regenerated bone area with respect to the total osteotomy area were about double in PM and PP samples compared with RO ones, while the number of TRAP-positive (tartrate-resistant acid phosphatase positive) osteoclasts per linear surface showed a significant increase, suggesting greater bone remodelling. Under scanning electron microscopy, regenerated bone displayed higher cell density and less mineralized matrix compared with pre-existent bone for all devices used. Nanoindentation tests showed no changes in elastic modulus. In conclusion, PM/PP osteotomies can be considered equivalent to each other, and result in more rapid healing compared with those using RO. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Marginal bone loss around non-submerged implants is associated with salivary microbiome during bone healing.

PubMed

Duan, Xiao-Bo; Wu, Ting-Xi; Guo, Yu-Chen; Zhou, Xue-Dong; Lei, Yi-Ling; Xu, Xin; Mo, An-Chun; Wang, Yong-Yue; Yuan, Quan

2017-06-01

Marginal bone loss during bone healing exists around non-submerged dental implants. The aim of this study was to identify the relationship between different degrees of marginal bone loss during bone healing and the salivary microbiome. One hundred patients were recruited, and marginal bone loss around their implants was measured using cone beam computed tomography during a 3-month healing period. The patients were divided into three groups according to the severity of marginal bone loss. Saliva samples were collected from all subjected and were analysed using 16S MiSeq sequencing. Although the overall structure of the microbial community was not dramatically altered, the relative abundance of several taxonomic groups noticeably changed. The abundance of species in the phyla Spirochaeta and Synergistetes increased significantly as the bone loss became more severe. Species within the genus Treponema also exhibited increased abundance, whereas Veillonella, Haemophilus and Leptotrichia exhibited reduced abundances, in groups with more bone loss. Porphyromonasgingivalis, Treponemadenticola and Streptococcus intermedius were significantly more abundant in the moderate group and/or severe group. The severity of marginal bone loss around the non-submerged implant was associated with dissimilar taxonomic compositions. An increased severity of marginal bone loss was related to increased proportions of periodontal pathogenic species. These data suggest a potential role of microbes in the progression of marginal bone loss during bone healing.

Tendon Healing in Bone Tunnel after Human Anterior Cruciate Ligament Reconstruction: A Systematic Review of Histological Results.

PubMed

Lu, Hongbin; Chen, Can; Xie, Shanshan; Tang, Yifu; Qu, Jin

2018-05-21

Most studies concerning to tendon healing and incorporation into bone are mainly based on animal studies due to the invasive nature of the biopsy procedure. The evidence considering tendon graft healing to bone in humans is limited in several case series or case reports, and therefore, it is difficult to understand the healing process. A computerized search using relevant search terms was performed in the PubMed, EMBASE, Scopus, and Cochrane Library databases, as well as a manual search of reference lists. Searches were limited to studies that investigated tendon graft healing to bone by histologic examination after anterior cruciate ligament (ACL) reconstruction with hamstring. Ten studies were determined to be eligible for this systematic review. Thirty-seven cases were extracted from the included studies. Most studies showed that a fibrovascular interface would form at the tendon-bone interface at the early stage and a fibrous indirect interface with Sharpey-like fibers would be expected at the later stage. Cartilage-like tissue at tendon graft-bone interface was reported in three studies. Tendon graft failed to integrate with the surrounding bone in 10 of the 37 cases. Unexpectedly, suspensory type of fixation was used for the above failure cases. An indirect type of insertion with Sharpey-like fibers at tendon-bone interface could be expected after ACL reconstruction with hamstring. Regional cartilage-like tissue may form at tendon-bone interface occasionally. The underlying tendon-to-bone healing process is far from understood in the human hamstring ACL reconstruction. Further human studies are highly needed to understand tendon graft healing in bone tunnel after hamstring ACL reconstruction. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Torque test measurement in segmental bone defects using porous calcium phosphate cement implants.

PubMed

Kroese-Deutman, Henriette C; Wolke, Joop G C; Spauwen, Paul H M; Jansen, John A

2010-10-01

This study was performed to assess the bone healing supporting characteristics of porous calcium phosphate (Ca-P) cement when implanted in a rabbit segmental defect model as well as to determine the reliability of torque testing as a method to verify bone healing. The middiaphyseal radius was chosen as the area to create bilaterally increasing defect sizes (5, 10, and 15 mm), which were either filled with porous Ca-P cement or left open as a control. After 12 weeks of implantation, torque test measurements as well as histological and radiographic evaluation were performed. In two of the open 15 mm control defects, bone bridging was visible at the radiographic and histological evaluation. Bone was observed to be present in all porous Ca-P cement implants (5, 10, and 15 mm defects) after 12 weeks. No significant differences in torque measurements were observed between the 5 and 10 mm filled and open control defects using a t-test. In addition, the mechanical strength of all operated specimens was similar compared with nonoperated bone samples. The torsion data for the 15 mm open defect appeared to be lower compared with the filled 15 mm defect, but no significant difference could be proven. Within the limitation of the study design, porous Ca-P cement implants demonstrated osteoconductive properties and confirmed to be a suitable scaffold material in a weight-bearing situation. Further, the used torque testing method was found to be unreliable for testing the mechanical properties of the healed bone defect.

Local delivery of controlled-release simvastatin to improve the biocompatibility of polyethylene terephthalate artificial ligaments for reconstruction of the anterior cruciate ligament.

PubMed

Zhang, Peng; Han, Fei; Li, Yunxia; Chen, Jiwu; Chen, Tianwu; Zhi, Yunlong; Jiang, Jia; Lin, Chao; Chen, Shiyi; Zhao, Peng

2016-01-01

The Ligament Advanced Reinforcement System has recently been widely used as the primary graft of choice in anterior cruciate ligament (ACL) reconstruction. But the biological graft-bone healing still remains a problem. Previous studies have shown that simvastatin (SIM) stimulates bone formation. The objective of this study was to investigate whether surface coating with collagen containing low-dose SIM microsphere could enhance the surface biocompatibility of polyethylene terephthalate (PET) artificial ligaments to accelerate graft-to-bone healing. The in vitro studies demonstrated that bone marrow stromal cells on the collagen-coated PET scaffolds (COL/PET) and simvastatin/collagen-coated PET scaffolds (SIM/COL/PET) proliferated vigorously. Compared with the PET group and the COL/PET group, SIM could induce bone marrow stromal cells' osteoblastic differentiation, high alkaline phosphatase activity, more mineralization deposition, and more expression of osteoblast-related genes, such as osteocalcin, runt-related transcription factor 2, bone morphogenetic protein-2, and vascular endothelial growth factor, in the SIM/COL/PET group. In vivo, rabbits received ACL reconstruction with different scaffolds. Histological analysis demonstrated that graft-bone healing was significantly greater with angiogenesis and osteogenesis in the SIM/COL/PET group than the other groups. In addition, biomechanical testing at the eighth week demonstrated a significant increase in the ultimate failure load and stiffness in the SIM/COL/PET group. The low dose of SIM-sustained release from SIM/COL/PET promoted the graft-bone healing via its effect on both angiogenesis and osteogenesis. This study suggested that collagen containing low-dose SIM microsphere coating on the surface of PET artificial ligaments could be potentially applied for ACL reconstruction.

Healing properties of implants inserted concomitantly with anorganic bovine bone. A histomorphometric human study.

PubMed

Menicucci, G; Mussano, F; Schierano, G; Rizzati, A; Aimetti, M; Gassino, G; Traini, T; Carossa, S

2013-03-01

The present prospective, randomized, double-blind study evaluated the bone-forming process around implants inserted simultaneously with anorganic bovine bone (ABB) in sinus grafting. A total of 18 threaded mini-implants with Osseotite (O) and Nanotite (N) surfaces were placed in seven patients (nine sites). After 12 months, the implants were retrieved and processed for histological analysis. A total of 18 cutting and grinding sections were investigated with bright-field light microscopy, circularly polarized light microscopy (CPLM), confocal scanning laser microscope (CSLM), and scanning electron microscope (SEM) with energy dispersive spectrometer (EDS). The bone-to-implant contact rate in native crestal bone was 62.6 ± 0.4% for N implants and 54.3 ± 0.5% for the O implants (p = 0.001). The collagen fibre density, as assessed by CPLM, was 79.8 ± 6.0 nm for the N group and 74.6 ± 4.6 nm for the O group (p < 0.05). Line scan EDS starting from ABB to newly formed bone showed a decrease in calcium content and an increase of carbon while phosphorus content was constant. While the N surface improved the peri-implant endosseous healing properties in the native bone, when compared to the O surface, it did not improve the healing properties in the bone-graft area. © 2013 Australian Dental Association.

Continuous decompression with intramedullary nailing for the treatment of unicameral bone cysts.

PubMed

Masquijo, Julio Javier; Baroni, Eduardo; Miscione, Horacio

2008-08-01

To evaluate the efficacy of decompression of unicameral bone cysts (UBCs) of the long bones with intramedullary nailing and to compare responses to treatment according to location. We evaluated 48 consecutive patients treated between January 1988 and June 2000. Mean age was 10.3 years. Mean follow-up was 9.8 years. Evaluation was performed according to the radiographic criteria of Capanna. UBCs were located in the proximal humerus (n = 24), humeral shaft (n = 2), proximal femur (n = 19), distal tibia (n = 2) and fibula (n = 1). A total of 62.5% presented a pathological fracture. Successful results were observed in 89.5% (26 total healing, 17 healing with residual radiolucent areas), and there were four recurrences and, in one case, no response to treatment. There was more healing in the humerus than in the femur (92.3% versus 84.2%), and more tendency to restitution ad integrum, although the difference was not statistically significant (P = 0.1499). Intramedullary nailing is a minimally invasive method, which permits early stability and decompresses the cyst allowing healing. Significant differences were not observed among results from different locations.

Adjustable stiffness, external fixator for the rat femur osteotomy and segmental bone defect models.

PubMed

Glatt, Vaida; Matthys, Romano

2014-10-09

The mechanical environment around the healing of broken bone is very important as it determines the way the fracture will heal. Over the past decade there has been great clinical interest in improving bone healing by altering the mechanical environment through the fixation stability around the lesion. One constraint of preclinical animal research in this area is the lack of experimental control over the local mechanical environment within a large segmental defect as well as osteotomies as they heal. In this paper we report on the design and use of an external fixator to study the healing of large segmental bone defects or osteotomies. This device not only allows for controlled axial stiffness on the bone lesion as it heals, but it also enables the change of stiffness during the healing process in vivo. The conducted experiments have shown that the fixators were able to maintain a 5 mm femoral defect gap in rats in vivo during unrestricted cage activity for at least 8 weeks. Likewise, we observed no distortion or infections, including pin infections during the entire healing period. These results demonstrate that our newly developed external fixator was able to achieve reproducible and standardized stabilization, and the alteration of the mechanical environment of in vivo rat large bone defects and various size osteotomies. This confirms that the external fixation device is well suited for preclinical research investigations using a rat model in the field of bone regeneration and repair.

Balancing the Rates of New Bone Formation and Polymer Degradation Enhances Healing of Weight-Bearing Allograft/Polyurethane Composites in Rabbit Femoral Defects

PubMed Central

Dumas, Jerald E.; Prieto, Edna M.; Zienkiewicz, Katarzyna J.; Guda, Teja; Wenke, Joseph C.; Bible, Jesse; Holt, Ginger E.

2014-01-01

There is a compelling clinical need for bone grafts with initial bone-like mechanical properties that actively remodel for repair of weight-bearing bone defects, such as fractures of the tibial plateau and vertebrae. However, there is a paucity of studies investigating remodeling of weight-bearing bone grafts in preclinical models, and consequently there is limited understanding of the mechanisms by which these grafts remodel in vivo. In this study, we investigated the effects of the rates of new bone formation, matrix resorption, and polymer degradation on healing of settable weight-bearing polyurethane/allograft composites in a rabbit femoral condyle defect model. The grafts induced progressive healing in vivo, as evidenced by an increase in new bone formation, as well as a decrease in residual allograft and polymer from 6 to 12 weeks. However, the mismatch between the rates of autocatalytic polymer degradation and zero-order (independent of time) new bone formation resulted in incomplete healing in the interior of the composite. Augmentation of the grafts with recombinant human bone morphogenetic protein-2 not only increased the rate of new bone formation, but also altered the degradation mechanism of the polymer to approximate a zero-order process. The consequent matching of the rates of new bone formation and polymer degradation resulted in more extensive healing at later time points in all regions of the graft. These observations underscore the importance of balancing the rates of new bone formation and degradation to promote healing of settable weight-bearing bone grafts that maintain bone-like strength, while actively remodeling. PMID:23941405

Diabetes mellitus affects the biomechanical function of the callus and the expression of TGF-beta1 and BMP2 in an early stage of fracture healing.

PubMed

Xu, M T; Sun, S; Zhang, L; Xu, F; Du, S L; Zhang, X D; Wang, D W

2016-01-01

Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) are important regulators of bone repair and regeneration. In this study, we examined whether TGF-β1 and BMP-2 expressions were delayed during bone healing in type 1 diabetes mellitus. Tibial fractures were created in 95 diabetic and 95 control adult male Wistar rats of 10 weeks of age. At 1, 2, 3, 4, and 5 weeks after fracture induction, five rats were sacrificed from each group. The expressions of TGF-β1 and BMP2 in the fractured tibias were measured by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction, weekly for the first 5 weeks post-fracture. Mechanical parameters (bending rigidity, torsional rigidity, destruction torque) of the healing bones were also assessed at 3, 4, and 5 weeks post-fracture, after the rats were sacrificed. The bending rigidity, torsional rigidity and destruction torque of the two groups increased continuously during the healing process. The diabetes group had lower mean values for bending rigidity, torsional rigidity and destruction torque compared with the control group (P<0.05). TGF-β1 and BMP-2 expression were significantly lower (P<0.05) in the control group than in the diabetes group at postoperative weeks 1, 2, and 3. Peak levels of TGF-β1 and BMP-2 expression were delayed by 1 week in the diabetes group compared with the control group. Our results demonstrate that there was a delayed recovery in the biomechanical function of the fractured bones in diabetic rats. This delay may be associated with a delayed expression of the growth factors TGF-β1 and BMP-2.

Osteoporotic Animal Models of Bone Healing: Advantages and Pitfalls.

PubMed

Calciolari, Elena; Donos, Nikolaos; Mardas, Nikos

2017-10-01

The aim of this review was to summarize the advantages and pitfalls of the available osteoporotic animal models of bone healing. A thorough literature search was performed in MEDLINE via OVID and EMBASE to identify animal studies investigating the effect of experimental osteoporosis on bone healing and bone regeneration. The osteotomy model in the proximal tibia is the most popular osseous defect model to study the bone healing process in osteoporotic-like conditions, although other well-characterized models, such as the post-extraction model, might be taken into consideration by future studies. The regenerative potential of osteoporotic bone and its response to biomaterials/regenerative techniques has not been clarified yet, and the critical size defect model might be an appropriate tool to serve this purpose. Since an ideal animal model for simulating osteoporosis does not exist, the type of bone remodeling, the animal lifespan, the age of peak bone mass, and the economic and ethical implications should be considered in our selection process. Furthermore, the influence of animal species, sex, age, and strain on the outcome measurement should be taken into account. In order to make future studies meaningful, standardized international guidelines for osteoporotic animal models of bone healing need to be set up.

Radiographic and Histological Evaluation of the Healing of Extraction Sockets Filled With Bovine-Derived Xenograft: An Experimental Study in Rats.

PubMed

Zhou, Fengjuan; Zheng, Xiaofei; Xie, Meng; Mo, Anchun; Wu, Hongkun

2017-06-01

To evaluate the microenvironment changes in the sockets substituted with bovine-derived xenografts during the early healing period. After extraction of the right maxillary incisor of Sprague Dawley rats, 48 rats were randomly divided into 2 groups. The extraction sockets of the test group were filled with Bio-Oss, whereas the control group was allowed to heal without intervention. The bone quality of the extraction sockets was observed through micro-CT and immunohistochemistry. Micro-CT scanning showed that the bone mineral density in the test group was significantly higher than that in the control group during the early healing period, whereas immunohistochemistry showed that the bone formation-related factors were significantly different between the test and control groups. The bovine-derived xenografts may interfere with the healing process of the extraction socket in the early healing stage. Bone formation of the extraction socket was delayed after grafting with bone substitute.

Short-term effects of teriparatide versus placebo on bone biomarkers, structure, and fracture healing in women with lower-extremity stress fractures: A pilot study.

PubMed

Almirol, Ellen A; Chi, Lisa Y; Khurana, Bharti; Hurwitz, Shelley; Bluman, Eric M; Chiodo, Christopher; Matzkin, Elizabeth; Baima, Jennifer; LeBoff, Meryl S

2016-09-01

In this pilot, placebo-controlled study, we evaluated whether brief administration of teriparatide (TPTD) in premenopausal women with lower-extremity stress fractures would increase markers of bone formation in advance of bone resorption, improve bone structure, and hasten fracture healing according to magnetic resonance imaging (MRI). Premenopausal women with acute lower-extremity stress fractures were randomized to injection of TPTD 20-µg subcutaneous (s.c.) (n = 6) or placebo s.c. (n = 7) for 8 weeks. Biomarkers for bone formation N-terminal propeptide of type I procollagen (P1NP) and osteocalcin (OC) and resorption collagen type-1 cross-linked C-telopeptide (CTX) and collagen type 1 cross-linked N-telopeptide (NTX) were measured at baseline, 4 and 8 weeks. The area between the percent change of P1NP and CTX over study duration is defined as the anabolic window. To assess structural changes, peripheral quantitative computed topography (pQCT) was measured at baseline, 8 and 12 weeks at the unaffected tibia and distal radius. The MRI of the affected bone assessed stress fracture healing at baseline and 8 weeks. After 8 weeks of treatment, bone biomarkers P1NP and OC increased more in the TPTD- versus placebo-treated group (both p ≤ 0.01), resulting in a marked anabolic window (p ≤ 0.05). Results from pQCT demonstrated that TPTD-treated women showed a larger cortical area and thickness compared to placebo at the weight bearing tibial site, while placebo-treated women had a greater total tibia and cortical density. No changes at the radial sites were observed between groups. According to MRI, 83.3% of the TPTD- and 57.1% of the placebo-treated group had improved or healed stress fractures (p = 0.18). In this randomized, pilot study, brief administration of TPTD showed anabolic effects that TPTD may help hasten fracture healing in premenopausal women with lower-extremity stress fractures. Larger prospective studies are warranted to determine the effects of TPTD treatment on stress fracture healing in premenopausal women.

Nutritional Aspects of Bone Health and Fracture Healing

PubMed Central

Karpouzos, Athanasios; Diamantis, Evangelos; Farmaki, Paraskevi

2017-01-01

Introduction Fractures are quite common, especially among the elderly. However, they can increase in prevalence in younger ages too if the bone health is not good. This may happen as a result of bad nutrition. Methods A customized, retrospective review of available literature was performed using the following keywords: bone health, nutrition, and fractures. Results Insufficient intake of certain vitamins, particularly A and D, and other nutrients, such as calcium, may affect bone health or even the time and degree of bone healing in case of fracture. The importance of different nutrients, both dietary and found in food supplements, is discussed concerning bone health and fracture healing. Conclusion A healthy diet with adequate amounts of both macro- and micronutrients is essential, for both decreasing fracture risk and enhancing the healing process after fracture. PMID:29464131

Achilles detachment in rat and stable gastric pentadecapeptide BPC 157: Promoted tendon-to-bone healing and opposed corticosteroid aggravation.

PubMed

Krivic, Andrija; Anic, Tomislav; Seiwerth, Sven; Huljev, Dubravko; Sikiric, Predrag

2006-05-01

Stable gastric pentadecapeptide BPC 157 (BPC 157, as an antiulcer agent in clinical trials for inflammatory bowel disease; PLD-116, PL 14736, Pliva, no toxicity reported) alone (without carrier) ameliorates healing of tendon and bone, respectively, as well as other tissues. Thereby, we focus on Achilles tendon-to-bone healing: tendon to bone could not be healed spontaneously, but it was recovered by this peptide. After the rat's Achilles tendon was sharply transected from calcaneal bone, agents [BPC 157 (10 microg, 10 ng, 10 pg), 6alpha-methylprednisolone (1 mg), 0.9% NaCl (5 mL)] were given alone or in combination [/kg body weight (b.w.) intraperitoneally, once time daily, first 30-min after surgery, last 24 h before analysis]. Tested at days 1, 4, 7, 10, 14, and 21 after Achilles detachment, BPC 157 improves healing functionally [Achilles functional index (AFI) values substantially increased], biomechanically (load to failure, stiffness, and Young elasticity modulus significantly increased), macro/microscopically, immunohistochemistry (better organization of collagen fibers, and advanced vascular appearance, more collagen type I). 6alpha-Methylprednisolone consistently aggravates the healing, while BPC 157 substantially reduces 6alpha-methylprednisolone healing aggravation. Thus, direct tendon-to-bone healing using stabile nontoxic peptide BPC 157 without a carrier might successfully exchange the present reconstructive surgical methods. Copyright 2006 Orthopaedic Research Society.

A Concert between Biology and Biomechanics: The Influence of the Mechanical Environment on Bone Healing

PubMed Central

Glatt, Vaida; Evans, Christopher H.; Tetsworth, Kevin

2017-01-01

In order to achieve consistent and predictable fracture healing, a broad spectrum of growth factors are required to interact with one another in a highly organized response. Critically important, the mechanical environment around the fracture site will significantly influence the way bone heals, or if it heals at all. The role of the various biological factors, the timing, and spatial relationship of their introduction, and how the mechanical environment orchestrates this activity, are all crucial aspects to consider. This review will synthesize decades of work and the acquired knowledge that has been used to develop new treatments and technologies for the regeneration and healing of bone. Moreover, it will discuss the current state of the art in experimental and clinical studies concerning the application of these mechano-biological principles to enhance bone healing, by controlling the mechanical environment under which bone regeneration takes place. This includes everything from the basic principles of fracture healing, to the influence of mechanical forces on bone regeneration, and how this knowledge has influenced current clinical practice. Finally, it will examine the efforts now being made for the integration of this research together with the findings of complementary studies in biology, tissue engineering, and regenerative medicine. By bringing together these diverse disciplines in a cohesive manner, the potential exists to enhance fracture healing and ultimately improve clinical outcomes. PMID:28174539

Mechanical and structural properties of bone in non-critical and critical healing in rat.

PubMed

Hoerth, Rebecca M; Seidt, Britta M; Shah, Miheer; Schwarz, Carolin; Willie, Bettina M; Duda, Georg N; Fratzl, Peter; Wagermaier, Wolfgang

2014-09-01

A fracture in bone results in a dramatic change of mechanical loading conditions at the site of injury. Usually, bone injuries heal normally but with increasing fracture gaps, healing is retarded, eventually leading to non-unions. The clinical situation of these two processes with different outcomes is well described. However, the exact relation between the mechanical environment and characteristics of the tissues at all levels of structural hierarchy remains unclear. Here we studied the differences in material formation of non-critical (1mm) and critical (5mm gap) healing. We employed a rat osteotomy model to explore bone material structure depending upon the different mechanical conditions. In both cases, primary bone formation was followed by secondary bone deposition with mineral particle sizes changing from on average short and thick to long and thin particles. Bony bridging occurred at first in the endosteal callus and the nanostructure and microstructure developed towards cortical ordered material organization. In contrast, in critical healing, instead of bridging, a marrow cavity closure was formed endosteal, exhibiting tissue structure oriented along the curvature and a periosteal callus with less mature material structure. The two healing processes separated between 4 and 6 weeks post-osteotomy. The outcome of healing was determined by the varied geometrical conditions in critical and non-critical healing, inducing completely different mechanical situations. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Changes in PGE2 signaling after submandibulectomy alter post-tooth extraction socket healing.

PubMed

Mohn, Claudia Ester; Troncoso, Gastón Rodolfo; Bozzini, Clarisa; Conti, María Inés; Fernandez Solari, Javier; Elverdin, Juan Carlos

2018-03-10

Saliva is very important to oral health, and a salivary deficit has been shown to bring serious problems to oral health. There is scant information about the mechanisms through which salivary glands participate in post-tooth extraction socket healing. Therefore, the aim of the present study was to investigate the effect of submandibulectomy (SMx), consisting of the ablation of submandibular and sublingual glands (SMG and SLG, respectively), on PGE 2 signaling and other bone regulatory molecules, such as OPG and RANKL, involved in tooth extraction socket healing. Male Wistar rats, 70 g body weight, were assigned to an experimental (subjected to SMx) or a control group (sham operated). One week later, the animals in both groups underwent bilateral extraction of the first mandibular molars. The effect of SMx on different stages of socket healing after tooth extraction (7, 14, and 30 days) was studied by evaluating some parameters of inflammation, including PGE 2 and its receptors, and of bone metabolism, as well as by performing bone biomechanical studies. SMx increased TNFα and PGE 2 content as well as cyclooxygenase-II (COX-II) expression in tooth socket tissue at almost all the studied time points. SMx also had an effect on mRNA expression of PGE 2 receptors at the different time points, but did not significantly alter osteoprotegerin (OPG) and RANKL mRNA expression at any of the studied time points. In addition, an increase in bone mass density was observed in SMx rats compared with matched controls, and the structural and mechanical bone properties of the mandibular socket bone were also affected by SMx. Our results suggest that the SMG/SLG complex regulates cellular activation and differentiation by modulating the production of molecules intervening in tooth extraction socket repair, including the PGE 2 signaling system, which would therefore account for the higher density and resistance of the newly formed bone in SMx rat. © 2018 by the Wound Healing Society.

Ovariectomy-Induced Osteopenia Influences the Middle and Late Periods of Bone Healing in a Mouse Femoral Osteotomy Model.

PubMed

Pang, Jian; Ye, Meina; Gu, Xinfeng; Cao, Yuelong; Zheng, Yuxin; Guo, Hailing; Zhao, Yongfang; Zhan, Hongsheng; Shi, Yinyu

2015-08-01

It is known that bone healing is delayed in the presence of osteoporosis in humans. However, due to the complexities of the healing of osteoporotic fractures, animal models may be more appropriate for studying the effects of osteoporosis in more detail and for testing drugs on the fracture repair process. The purpose of this study was to investigate the influence of ovariectomy-induced osteopenia in bone healing in an open femoral osteotomy model, and to test the feasibility of this model for evaluating the healing process under osteopenic conditions. Ovariectomized (OVX) mouse models were employed to assess the effects of osteopenia on fracture healing, A mid-shaft femur osteotomy model was also established 3 weeks after ovariectomy as an osteopenic fracture group (OVX group). Femurs were then harvested at 2 weeks and 6 weeks after fracture for X-ray radiography, micro-computed tomography (micro-CT), histology, and biomechanical analysis. A sham-operated group (sham group) was used for comparison. The OVX mice had significantly lower bone volume density (BVF), volumetric bone mineral density (vBMD), and tissue mineral density (TMD) in the fracture calluses at 6 weeks (p<0.05), and similar trend was observed in 2 weeks. Additionally, larger calluses in OVX animals were observed via micro-CT and X-ray, but these did not result in better healing outcomes, as determined by biomechanical test at 6 weeks. Histological images of the healing fractures in the OVX mice found hastening of broken end resorption and delay of hard callus remodeling. The impaired biomechanical measurements in the OVX group (p<0.05) were consistent with micro-CT measurements and radiographic scoring, which also indicated delay in fracture healing of the OVX group. This study provided evidence that ovariectomy-induced osteopenia impair the middle and late bone healing process. These data also supported the validity of the mouse femoral osteotomy model in evaluating the process of bone healing under osteopenic conditions.

Bone regeneration by polyhedral microcrystals from silkworm virus

PubMed Central

Matsumoto, Goichi; Ueda, Takayo; Shimoyama, Junko; Ijiri, Hiroshi; Omi, Yasushi; Yube, Hisato; Sugita, Yoshihiko; Kubo, Katsutoshi; Maeda, Hatsuhiko; Kinoshita, Yukihiko; Arias, Duverney Gaviria; Shimabukuro, Junji; Kotani, Eiji; Kawamata, Shin; Mori, Hajime

2012-01-01

Bombyx mori cypovirus is a major pathogen which causes significant losses in silkworm cocoon harvests because the virus particles are embedded in micrometer-sized protein crystals called polyhedra and can remain infectious in harsh environmental conditions for years. But the remarkable stability of polyhedra can be applied on slow-release carriers of cytokines for tissue engineering. Here we show the complete healing in critical-sized bone defects by bone morphogenetic protein-2 (BMP-2) encapsulated polyhedra. Although absorbable collagen sponge (ACS) safely and effectively delivers recombinant human BMP-2 (rhBMP-2) into healing tissue, the current therapeutic regimens release rhBMP-2 at an initially high rate after which the rate declines rapidly. ACS impregnated with BMP-2 polyhedra had enough osteogenic activity to promote complete healing in critical-sized bone defects, but ACS with a high dose of rhBMP-2 showed incomplete bone healing, indicating that polyhedral microcrystals containing BMP-2 promise to advance the state of the art of bone healing. PMID:23226833

Bone morphogenetic proteins: a powerful osteoinductive compound with non-negligible side effects and limitations.

PubMed

Oryan, Ahmad; Alidadi, Soodeh; Moshiri, Ali; Bigham-Sadegh, Amin

2014-01-01

Healing and regeneration of large bone defects leading to non-unions is a great concern in orthopedic surgery. Since auto- and allografts have limitations, bone tissue engineering and regenerative medicine (TERM) has attempted to solve this issue. In TERM, healing promotive factors are necessary to regulate the several important events during healing. An ideal treatment strategy should provide osteoconduction, osteoinduction, osteogenesis, and osteointegration of the graft or biomaterials within the healing bone. Since many materials have osteoconductive properties, only a few biomaterials have osteoinductive properties which are important for osteogenesis and osteointegration. Bone morphogenetic proteins (BMPs) are potent inductors of the osteogenic and angiogenic activities during bone repair. The BMPs can regulate the production and activity of some growth factors which are necessary for the osteogenesis. Since the introduction of BMP, it has added a valuable tool to the surgeon's possibilities and is most commonly used in bone defects. Despite significant evidences suggesting their potential benefit on bone healing, there are some evidences showing their side effects such as ectopic bone formation, osteolysis and problems related to cost effectiveness. Bone tissue engineering may create a local environment, using the delivery systems, which enables BMPs to carry out their activities and to lower cost and complication rate associated with BMPs. This review represented the most important concepts and evidences regarding the role of BMPs on bone healing and regeneration from basic to clinical application. The major advantages and disadvantages of such biologic compounds together with the BMPs substitutes are also discussed. © 2014 International Union of Biochemistry and Molecular Biology.

Histomorphometric Study of New Bone Formation Comparing Defect Healing with Three Bone Grafting Materials: The Effect of Osteoporosis on Graft Consolidation.

PubMed

Zhang, Qiao; Jing, Dai; Zhang, Yufeng; Miron, Richard J

Bone grafting materials are frequently utilized in oral surgery and periodontology to fill bone defects and augment lost or missing bone. The purpose of this study was to compare new bone formation in bone defects created in both normal and osteoporotic animals loaded with three types of bone grafts from different origins. Forty-eight female Wistar rats were equally divided into control normal and ovariectomized animals. Bilateral 2.5-mm femur defects were created and filled with an equal weight of (1) natural bone mineral (NBM, BioOss) of bovine origin, (2) demineralized freeze-dried bone allograft (DFDBA, LifeNet), or (3) biphasic calcium phosphate (BCP, Vivoss). Following 3 and 6 weeks of healing, hematoxylin and eosin and TRAP staining was performed to determine new bone formation, material degradation, and osteoclast activity. All bone substitutes demonstrated osteoconductive potential at 3 and 6 weeks with higher osteoclast numbers observed in all ovariectomized animals. NBM displayed continual new bone formation with little to no sign of particle degradation, even in osteoporotic animals. DFDBA particles showed similar levels of new bone formation but rapid particle degradation rates with lower levels of mineralized tissue. BCP bone grafts demonstrated significantly higher new bone formation when compared with both NBM and DFDBA particles; however, the material was associated with higher osteoclast activity and particle degradation. Interestingly, in osteoporotic animals, BCP displayed synergistically and markedly more rapid rates of particle degradation. Recent modifications to synthetically fabricated materials were shown to be equally or more osteopromotive than NBM and DFDBA. However, the current BCP utilized demonstrated much faster resorption properties in osteoporotic animals associated with a decrease in total bone volume when compared with the slowly/nonresorbing NBM. The results from this study point to the clinical relevance of minimizing fast-resorbing bone grafting materials in osteoporotic phenotypes due to the higher osteoclastic activity and greater material resorption.

Dental Implant Macro-Design Features Can Impact the Dynamics of Osseointegration.

PubMed

Vivan Cardoso, Marcio; Vandamme, Katleen; Chaudhari, Amol; De Rycker, Judith; Van Meerbeek, Bart; Naert, Ignace; Duyck, Joke

2015-08-01

The purpose of this study was to compare the clinical performance of two dental implant types possessing a different macro-design in the in vivo pig model. Titanium Aadva(TM) implants (GC, Tokyo, Japan) were compared with OsseoSpeed(TM) implants (Astra, Mölndal, Sweden), with the Aadva implant displaying significant larger inter-thread dimensions than the OsseoSpeed implant. Implants were installed in the parietal bone of 12 domestic pigs and left for healing for either 1 or 3 months. Implant osseointegration was evaluated by quantitative histology (bone volume relative to the tissue volume [BV/TV]; bone-to-implant contact [BIC]) for distinct implant regions (collar, body, total implant length) with specific implant thread features. The Wilcoxon-Mann-Whitney nonparametric test with α = 0.05 was performed. An inferior amount of bone enveloping the Aadva implant compared with the OsseoSpeed implant was observed, in particular at the implant body part with its considerable inter-thread gaps (p < .05). Concomitantly, the Aadva macro-design negatively affected the amount of bone in direct contact with the implant for this specific implant part (p < .05), and resulted in an overall impaired implant osseointegration at the initial healing stage (total implant length; 1-month healing; p < .05). Although the Aadva implant displayed a clinically acceptable level of osseointegration, the findings demonstrate that implant macro-design features can impact the dynamics of implant osseointegration. Consideration of specific implant macro-design features should be made relative to the biological and mechanical microenvironment. © 2013 Wiley Periodicals, Inc.

ECM Inspired Coating of Embroidered 3D Scaffolds Enhances Calvaria Bone Regeneration

PubMed Central

Rentsch, C.; Rentsch, B.; Heinemann, S.; Bernhardt, R.; Bischoff, B.; Förster, Y.; Scharnweber, D.; Rammelt, S.

2014-01-01

Resorbable polymeric implants and surface coatings are an emerging technology to treat bone defects and increase bone formation. This approach is of special interest in anatomical regions like the calvaria since adults lose the capacity to heal large calvarial defects. The present study assesses the potential of extracellular matrix inspired, embroidered polycaprolactone-co-lactide (PCL) scaffolds for the treatment of 13 mm full thickness calvarial bone defects in rabbits. Moreover the influence of a collagen/chondroitin sulfate (coll I/cs) coating of PCL scaffolds was evaluated. Defect areas filled with autologous bone and empty defects served as reference. The healing process was monitored over 6 months by combining a novel ultrasonographic method, radiographic imaging, biomechanical testing, and histology. The PCL coll I/cs treated group reached 68% new bone volume compared to the autologous group (100%) and the biomechanical stability of the defect area was similar to that of the gold standard. Histological investigations revealed a significantly more homogenous bone distribution over the whole defect area in the PCL coll I/cs group compared to the noncoated group. The bioactive, coll I/cs coated, highly porous, 3-dimensional PCL scaffold acted as a guide rail for new skull bone formation along and into the implant. PMID:25013767

Vitamin D and the immunomodulation of rotator cuff injury

PubMed Central

Dougherty, Kaitlin A; Dilisio, Matthew F; Agrawal, Devendra K

2016-01-01

Tendon-to-bone healing after rotator cuff repair surgery has a failure rate of 20%–94%. There has been a recent interest to determine the factors that act as determinants between successful and unsuccessful rotator cuff repair. Vitamin D level in patients is one of the factors that have been linked to bone and muscle proliferation and healing, and it may have an effect on tendon-to-bone healing. The purpose of this article is to critically review relevant published research that relates to the effect of vitamin D on rotator cuff tears and subsequent healing. A review of the literature was conducted to identify all studies that investigate the relationship between vitamin D and tendon healing, in addition to its mechanism of action. The data were then analyzed in order to summarize what is currently known about vitamin D, rotator cuff pathology, and tendon-to-bone healing. The activated metabolite of vitamin D, 1α,25-dihydroxyvitamin D3, affects osteoblast proliferation and differentiation. Likewise, vitamin D plays a significant role in the tendon-to-bone healing process by increasing the bone mineral density and strengthening the skeletal muscles. The 1α,25-dihydroxyvitamin D3 binds to vitamin D receptors on myocytes to stimulate growth and proliferation. The form of vitamin D produced by the liver, calcifediol, is a key initiator of the myocyte healing process by moving phosphate into myocytes, which improves function and metabolism. Investigation into the effect of vitamin D on tendons has been sparse, but limited studies have been promising. Matrix metalloproteinases play an active role in remodeling the extracellular matrix (ECM) of tendons, particularly deleterious remodeling of the collagen fibers. Also, the levels of transforming growth factor-β3 positively influence the success of the surgery for rotator cuff repair. In the tendon-to-bone healing process, vitamin D has been shown to successfully influence bone and muscle healing, but more research is needed to delve into the mechanisms of vitamin D as a factor in skeletal tendon health and healing. PMID:27366101

Evaluation of a press-fit osteochondral poly(ester-urethane) scaffold in a rabbit defect model.

PubMed

Dresing, Iska; Zeiter, Stephan; Auer, Jörg; Alini, Mauro; Eglin, David

2014-07-01

The purpose of this study was to evaluate the impact on osteochondral healing of press-fitted multiphasic osteochondral scaffolds consisting of poly(ester-urethane) (PUR) and hydroxyapatite into a cylindric osteochondral defect in the distal non-weight bearing femoral trochlear ridge of the rabbit. Two scaffolds were investigated, one with and one without an intermediate microporous membrane between the cartilage and the bone compartment of the scaffold. A control group without a scaffold placed into the defect was included. After 12 weeks macroscopic and histomorphological analyses were performed. The scaffold was easily press-fitted and provided a stable matrix for tissue repair. The membrane did not demonstrate a detrimental effect on tissue healing compared with the scaffold without membrane. However, the control group had statistically superior healing as reflected by histological differences in the cartilage and subchondral bone compartment between control group and each scaffold group. A more detailed analysis revealed that the difference was localized in the bone compartment healing. The present study demonstrates that an elastomeric PUR scaffold can easily be press-fitted into an osteochondral defect and provides a stable matrix for tissue repair. However, the multi-phasic scaffold did not provide a clear advantage for tissue healing. Future investigations should refine especially the bone phase of the implant to increase its stiffness, biocompatibility and osteoconductive activity. A more precise fabrication technique would be necessary for the matching of tissue organisation.

Bone formation in sinus augmentation procedures using autologous bone, porcine bone, and a 50 : 50 mixture: a human clinical and histological evaluation at 2 months.

PubMed

Cassetta, Michele; Perrotti, Vittoria; Calasso, Sabrina; Piattelli, Adriano; Sinjari, Bruna; Iezzi, Giovanna

2015-10-01

The aim of this study was to perform a 2 months clinical and histological comparison of autologous bone, porcine bone, and a 50 : 50 mixture in maxillary sinus augmentation procedures. A total of 10 consecutive patients, undergoing two-stage sinus augmentation procedures using 100% autologous bone (Group A), 100% porcine bone (Group B), and a 50 : 50 mixture of autologous and porcine bone (Group C) were included in this study. After a 2-month healing period, at the time of implant insertion, clinical evaluation was performed and bone core biopsies were harvested and processed for histological analysis. The postoperative healing was uneventful regardless of the materials used for the sinus augmentation procedures. The histomorphometrical analysis revealed comparable percentages of newly formed bone, marrow spaces, and residual grafted material in the three groups. The clinical and histological results of this study indicated that porcine bone alone or in combination with autologous bone are biocompatible and osteoconductive materials and can be successfully used in sinus augmentation procedures. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Enhanced bone-integration capability of alkali- and heat-treated nanopolymorphic titanium in micro-to-nanoscale hierarchy.

PubMed

Ueno, Takeshi; Tsukimura, Naoki; Yamada, Masahiro; Ogawa, Takahiro

2011-10-01

This study introduces nanopolymorphic features of alkali- and heat-treated titanium surfaces, comprising of tuft-like, plate-like, and nodular structures that are smaller than 100 nm and determines whether and how the addition of these nanofeatures to a microroughened titanium surface affects bone-implant integration. A comprehensive assessment of biomechanical, interfacial, and histological analyses in a rat model was performed for machined surfaces without microroughness, sandblasted-microroughened surfaces, and micro-nano hybrid surfaces created by sandblasting and alkali and heat treatment. The microroughened surface accelerated the establishment of implant biomechanical fixation at the early healing stage compared with the non-microroughened surface but did not increase the implant fixation at the late healing stage. The addition of the nanopolymorphic features to the microroughened surface further increased implant fixation throughout the healing time. The area of the new bone within 50 μm proximity of the implant surfaces, which was increased 2-3-fold using microroughened surfaces, was further increased 2-fold using nanopolymorphic surfaces. In contrast, the bone area in a 50-200 μm zone was not influenced by either microroughened or nanopolymorphic surfaces. The percentage of bone-implant contact, which was increased 4-5-fold, using microroughened surfaces, was further increased substantially by over 2-fold throughout the healing period. The percentage of soft tissue intervention between bone and implant surfaces, which was reduced to half by microroughened surfaces, was additionally reduced by the nanopolymorphic surfaces to between one-third and one-fourth, resulting in only 5-7% soft tissue intervention compared with 60-75% for the non-microroughened surface. Thus, using an exemplary alkali- and heat-treated nanopolymorphic surface, this study identified critical parameters necessary to describe the process and consequences of bone-implant integration, for which nanofeatures have specific and substantial roles beyond those of microfeatures. Nanofeature-enhanced osteoconductivity, which resulted in both the acceleration and elevation of bone-implant integration, has clearly been demonstrated. Copyright © 2011 Elsevier Ltd. All rights reserved.

The effect of methotrexate on the bone healing of mandibular condylar process fracture: an experimental study in rats.

PubMed

Cavalcanti, Samantha Cristine Santos X B; Corrêa, Luciana; Mello, Suzana Beatriz Veríssimo; Luz, João Gualberto C

2014-10-01

Methotrexate (MTX) is an anti-metabolite used in rheumatology and oncology. High doses are indicated for oncological treatment, whereas low doses are indicated for chronic inflammatory diseases. This study evaluated the effect of two MTX treatment schedules on the bone healing of the temporomandibular joint fracture in rats. Seventy-five adult male Wistar rats were used to generate an experimental unilateral medially rotated condylar fracture model that allows an evaluation of bone healing and the articular structures. The animals were subdivided into three groups that each received one of the following treatments intraperitoneally: saline (1 mL/week), low-dose MTX (3 mg/kg/week) and high-dose MTX (30 mg/kg). The histological study comprised fracture site and temporomandibular joint evaluations and bone neoformation was evaluated by histomorphometric analysis. A biochemical parameter of bone formation was also assessed. When compared with saline, high-dose MTX delayed bone fracture repairs. In this latter group, after 90 days, the histological analysis revealed atrophy of the fibrocartilage and the presence of fibrous tissue in the joint space. The histomorphometric analysis revealed diminished bone neoformation. The alkaline phosphatase levels also decreased after MTX treatment. It was concluded that high-dose MTX impaired mandibular condyle repair and induced degenerative articular changes. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Comparative study suggests that human bone morphogenetic proteins have no influence on the outcome of operative treatment of aseptic clavicle non-unions.

PubMed

von Rüden, Christian; Morgenstern, Mario; Friederichs, Jan; Augat, Peter; Hackl, Simon; Woltmann, Alexander; Bühren, Volker; Hierholzer, Christian

2016-11-01

The purpose of this study was to evaluate the clinical and radiological outcome following compression plate fixation in combination with autologous bone grafting, with and without additional application of recombinant human bone morphogenetic protein (rhBMP) for treatment of aseptic clavicle non-union. Between April 2004 and April 2015, 82 patients were treated for clavicle fracture and had developed aseptic clavicle non-union. Seventy-three out of 82 patients were available for follow-up at least one year after revision surgery; among them, 27 women and 46 men, with a median age of 49 (range, 19-86) years. Forty-five patients received compression plate osteosynthesis with autologous bone grafting, and 28 patients obtained compression plate fixation with autologous bone grafting and additional application of rhBMP-2 (3/28 patients) or rhBMP-7 (25/28 patients). Seventy out of 73 non-unions (96 %) healed within 12 months after revision surgery. Functional outcome according to the DASH Outcome Measure (with rhBMP, 33.16 ± 1.17 points; without rhBMP, 30.58 ± 2.12 points [mean ± SEM]; p = 0.81), non-union healing (p = 0.86), time interval between revision surgery and bone healing (p = 0.37), as well as post-operative complications, did not demonstrate relevant differences between the treatment groups and were not age-dependent. Functional and radiological results demonstrate that successful healing of aseptic clavicle non-union is dependent on radical resection of non-union tissue, restoration of length of the shoulder girdle and application of stable locking-plate osteosynthesis in combination with autologous bone grafting, but not dependent on application of additional rhBMP.

Histomorphometric study of alveolar bone healing in rats fed a boron-deficient diet.

PubMed

Gorustovich, Alejandro A; Steimetz, Tammy; Nielsen, Forrest H; Guglielmotti, María B

2008-04-01

Bone healing after tooth extraction in rats is a suitable experimental model to study bone formation. Thus, we performed a study to determine the effects of boron (B) deficiency on bone healing by using this model. The first lower right molar of weanling Wistar rats was extracted under anesthesia. The animals were divided into two groups: +B (adequate; 3 mg B/kg diet), and -B (boron-deficient; 0.07 mg/kg diet). The animals in both groups were killed in groups of 10 at 7 and 14 days after surgery. The guidelines of the NIH for the care and use of laboratory animals were observed. The mandibles were resected, fixed, decalcified, and embedded in paraffin. Buccolingually oriented sections were obtained at the level of the mesial alveolus and used for histometric evaluations. Total alveolar volume (TAV) and trabecular bone volume per total volume (BV/TV) in the apical third of the alveolus were determined. Percentages of osteoblast surface (ObS), eroded surface (ES), and quiescent surface (QS) were determined. No statistical significant differences in food intake and body weight were observed. Histomorphometric evaluation found -B rats had 36% and 63% reductions in BV/TV at 7 and 14 days, respectively. When compared with +B rats, -B rats had significant reductions (57% and 87%) in ObS concomitantly with increases (120% and 126%) in QS at 7 and 14 days, respectively. The findings show that boron deficiency results in altered bone healing because of a marked reduction in osteogenesis. 2008 Wiley-Liss, Inc

Effect of platelet-rich plasma on tendon-to-bone healing after rotator cuff repair in rats: an in vivo experimental study.

PubMed

Hapa, Onur; Cakıcı, Hüsamettin; Kükner, Aysel; Aygün, Hayati; Sarkalan, Nazlı; Baysal, Gökhan

2012-01-01

The purpose of this experimental study was to analyze the effects of local autologous platelet-rich plasma (PRP) injection on tendon-to-bone healing in a rotator cuff repair model in rats. Rotator cuff injury was created in 68 left shoulders of rats. PRP was obtained from the blood of an additional 15 rats. The 68 rats were divided into 4 groups with 17 rats in each group; PRP group (Week 2), control group (Week 2), PRP group (Week 4), and control group (Week 4). Platelet-rich plasma or saline was injected to the repair area intraoperatively. Rats were sacrificed 2 and 4 weeks after the surgery. Histological analysis using a semiquantitative scoring was performed on 7 rats per group. Tendon integrity and increases in vascularity and inflammatory cells and the degree of new bone formation were evaluated and compared between the groups. The remaining tendons (n=10) were mechanically tested. Degree of inflammation and vascularity were less in the study group at both time intervals (p<0.05). Tendon continuity was better in the study group at 2 weeks (p<0.05). Obvious new bone formation was detected in the control group at 4 weeks (p<0.05). Biomechanically, platelet-rich plasma-treated specimens were stronger at 2 weeks (p<0.05). Local autologous PRP injection may have beneficial effects on initial rotator cuff tendon-to-bone healing and enhance initial tendon-to-bone healing remodeling. This may represent a clinically important improvement in rotator cuff repair.

Distinct frequency dependent effects of whole-body vibration on non-fractured bone and fracture healing in mice.

PubMed

Wehrle, Esther; Wehner, Tim; Heilmann, Aline; Bindl, Ronny; Claes, Lutz; Jakob, Franz; Amling, Michael; Ignatius, Anita

2014-08-01

Low-magnitude high-frequency vibration (LMHFV) provokes anabolic effects in non-fractured bone; however, in fracture healing, inconsistent results were reported and optimum vibration conditions remain unidentified. Here, we investigated frequency dependent effects of LMHFV on fracture healing. Twelve-week-old, female C57BL/6 mice received a femur osteotomy stabilized using an external fixator. The mice received whole-body vibrations (20 min/day) with 0.3g peak-to-peak acceleration and a frequency of either 35 or 45 Hz. After 10 and 21 days, the osteotomized femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, µ-computed tomography, and histomorphometry. In non-fractured trabecular bone, vibration with 35 Hz significantly increased the relative amount of bone (+28%) and the trabecular number (+29%), whereas cortical bone was not influenced. LMHFV with 45 Hz failed to provoke anabolic effects in trabecular or cortical bone. Fracture healing was not significantly influenced by whole-body vibration with 35 Hz, whereas 45 Hz significantly reduced bone formation (-64%) and flexural rigidity (-34%) of the callus. Although the exact mechanisms remain open, our results suggest that small vibration setting changes could considerably influence LMHFV effects on bone formation in remodeling and repair, and even disrupt fracture healing, implicating caution when treating patients with impaired fracture healing. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Dynamic Stabilization of Simple Fractures With Active Plates Delivers Stronger Healing Than Conventional Compression Plating

PubMed Central

Tsai, Stanley; Bliven, Emily K.; von Rechenberg, Brigitte; Kindt, Philipp; Augat, Peter; Henschel, Julia; Fitzpatrick, Daniel C.; Madey, Steven M.

2017-01-01

Objectives: Active plates dynamize a fracture by elastic suspension of screw holes within the plate. We hypothesized that dynamic stabilization with active plates delivers stronger healing relative to standard compression plating. Methods: Twelve sheep were randomized to receive either a standard compression plate (CP) or an active plate (ACTIVE) for stabilization of an anatomically reduced tibial osteotomy. In the CP group, absolute stabilization was pursued by interfragmentary compression with 6 cortical screws. In the ACTIVE group, dynamic stabilization after bony apposition was achieved with 6 elastically suspended locking screws. Fracture healing was analyzed weekly on radiographs. After sacrifice 9 weeks postsurgery, the torsional strength of healed tibiae and contralateral tibiae was measured. Finally, computed tomography was used to assess fracture patterns and healing modes. Results: Healing in both groups included periosteal callus formation. ACTIVE specimens had almost 6 times more callus area by week 9 (P < 0.001) than CP specimens. ACTIVE specimens recovered on average 64% of their native strength by week 9, and were over twice as strong as CP specimens, which recovered 24% of their native strength (P = 0.008). Microcomputed tomography demonstrated that compression plating induced a combination of primary bone healing and gap healing. Active plating consistently stimulated biological bone healing by periosteal callus formation. Conclusions: Compared with compression plating, dynamic stabilization of simple fractures with active plates delivers significantly stronger healing. PMID:27861456

A Passive and Wireless Sensor for Bone Plate Strain Monitoring.

PubMed

Tan, Yisong; Hu, Jiale; Ren, Limin; Zhu, Jianhua; Yang, Jiaqi; Liu, Di

2017-11-16

This paper reports on a sensor for monitoring bone plate strain in real time. The detected bone plate strain could be used for judging the healing state of fractures in patients. The sensor consists of a magnetoelastic material, which can be wirelessly connected and passively embedded. In order to verify the effectiveness of the sensor, a tibia-bone plate-screw (TBS) model was established using the finite element analysis method. A variation of the bone plate strain was obtained via this model. A goat hindquarter tibia was selected as the bone fracture model in the experiment. The tibia was fixed on a high precision load platform and an external force was applied. Bone plate strain variation during the bone fracture healing process was acquired with sensing coils. Simulation results indicated that bone plate strain decreases as the bone gradually heals, which is consistent with the finite element analysis results. This validated the soundness of the sensor reported here. This sensor has wireless connections, no in vivo battery requirement, and long-term embedding. These results can be used not only for clinical practices of bone fracture healing, but also for bone fracture treatment and rehabilitation equipment design.

Parathyroid hormone and bone healing.

PubMed

Ellegaard, M; Jørgensen, N R; Schwarz, P

2010-07-01

Fracture healing is a complex process, and a significant number of fractures are complicated by impaired healing and non-union. Impaired healing is prevalent in certain risk groups, such as the elderly, osteoporotics, people with malnutrition, and women after menopause. Currently, no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial in the treatment of fractures and could thus be a potentially new treatment option for induction of fracture healing in humans. Furthermore, fractures in animals with experimental conditions of impaired healing such as aging, estrogen withdrawal, and malnutrition can heal in an expedited manner after PTH treatment. Interestingly, fractures occurring at both cancellous and cortical sites can be treated successfully, indicating that both osteoporotic and nonosteoporotic fractures can be the target of PTH-induced healing. Finally, the data suggest that PTH partly prevents the delay in fracture healing caused by aging. Recently, the first randomized, controlled clinical trial investigating the effect of PTH on fracture healing was published, indicating a possible clinical benefit of PTH treatment in inducing fracture healing. The aim of this article is therefore to review the evidence for the potential of PTH in bone healing, including the underlying mechanisms for this, and to provide recommendations for the clinical testing and use of PTH in the treatment of impaired fracture healing in humans.

Changes in bone microstructure and toughness during the healing process of long bones

NASA Astrophysics Data System (ADS)

Ishimoto, T.; Nakano, T.; Umakoshi, Y.; Tabata, Y.

2009-05-01

It is of great importance to understand how bone defects regain the microstructure and mechanical function of bone and how the microstructure affects the mechanical function during the bone healing process. In the present study on long bone defects, we investigated the relationship between the recovery process of fracture toughness and biological apatite (BAp)/collagen (Col) alignment as an index of the bone microstructure to clarify the bone toughening mechanisms. A 5-mm defect introduced in the rabbit ulna was allowed to heal naturally and a three-point bending test was conducted on the regenerated site to assess bone toughness. The bone toughness was quite low at the early stage of bone regeneration but increased during the postoperative period. The change in toughness agreed well with the characteristics of the fracture surface morphology, which reflected the history of the crack propagation. SEM and microbeam X-ray diffraction analyses indicated that the toughness was dominated by the degree and orientation of the preferred BAp/Col alignment, i.e. bundles aligned perpendicular to the crack propagation clearly contributed to the bone toughening owing to extra energy consumption for resistance to crack propagation. In conclusion, regenerated bone improves fracture toughness by reconstructing the preferred BAp/Col alignment along the bone longitudinal axis during the healing process of long bones.

Dual delivery of rhPDGF-BB and bone marrow mesenchymal stromal cells expressing the BMP2 gene enhance bone formation in a critical-sized defect model.

PubMed

Park, Shin-Young; Kim, Kyoung-Hwa; Shin, Seung-Yun; Koo, Ki-Tae; Lee, Yong-Moo; Seol, Yang-Jo

2013-11-01

Bone tissue healing is a dynamic, orchestrated process that relies on multiple growth factors and cell types. Platelet-derived growth factor-BB (PDGF-BB) is released from platelets at wound sites and induces cellular migration and proliferation necessary for bone regeneration in the early healing process. Bone morphogenetic protein-2 (BMP-2), the most potent osteogenic differentiation inducer, directs new bone formation at the sites of bone defects. This study evaluated a combinatorial treatment protocol of PDGF-BB and BMP-2 on bone healing in a critical-sized defect model. To mimic the bone tissue healing process, a dual delivery approach was designed to deliver the rhPDGF-BB protein transiently during the early healing phase, whereas BMP-2 was supplied by rat bone marrow stromal cells (BMSCs) transfected with an adenoviral vector containing the BMP2 gene (AdBMP2) for prolonged release throughout the healing process. In in vitro experiments, the dual delivery of rhPDGF-BB and BMP2 significantly enhanced cell proliferation. However, the osteogenic differentiation of BMSCs was significantly suppressed even though the amount of BMP-2 secreted by the AdBMP2-transfected BMSCs was not significantly affected by the rhPDGF-BB treatment. In addition, dual delivery inhibited the mRNA expression of BMP receptor type II and Noggin in BMSCs. In in vivo experiments, critical-sized calvarial defects in rats showed enhanced bone regeneration by dual delivery of autologous AdBMP2-transfected BMSCs and rhPDGF-BB in both the amount of new bone formed and the bone mineral density. These enhancements in bone regeneration were greater than those observed in the group treated with AdBMP2-transfected BMSCs alone. In conclusion, the dual delivery of rhPDGF-BB and AdBMP2-transfected BMSCs improved the quality of the regenerated bone, possibly due to the modulation of PDGF-BB on BMP-2-induced osteogenesis.

The influence of collagen membrane and autogenous bone chips on bone augmentation in the anterior maxilla: a preclinical study.

PubMed

Janner, Simone F M; Bosshardt, Dieter D; Cochran, David L; Chappuis, Vivianne; Huynh-Ba, Guy; Jones, Archie A; Buser, Daniel

2017-11-01

To evaluate the effect of a resorbable collagen membrane and autogenous bone chips combined with deproteinized bovine bone mineral (DBBM) on the healing of buccal dehiscence-type defects. The second incisors and the first premolars were extracted in the maxilla of eight mongrels. Reduced diameter, bone-level implants were placed 5 weeks later. Standardized buccal dehiscence-type defects were created and grafted at implant surgery. According to an allocation algorithm, the graft composition of each of the four maxillary sites was DBBM + membrane (group D + M), autogenous bone chips + DBBM + membrane (group A + D + M), DBBM alone (group D) or autogenous bone chips + DBBM (group A + D). Four animals were sacrificed after 3 weeks of healing and four animals after 12 weeks. Histological and histomorphometric analyses were performed on oro-facial sections. The pattern of bone formation and resorption within the grafted area showed high variability among the same group and healing time. The histomorphometric analysis of the 3-week specimens showed a positive effect of autogenous bone chips on both implant osseointegration and bone formation into the grafted region (P < 0.05). The presence of the collagen membrane correlated with greater bone formation around the DBBM particles and greater bone formation in the grafted region after 12 weeks of healing (P < 0.05). The oro-facial width of the augmented region at the level of the implant shoulder was significantly reduced in cases where damage of the protection splints occurred in the first week of healing (P < 0.05). The addition of autogenous bone chips and the presence of the collagen membrane increased bone formation around DBBM particles. Wound protection from mechanical noxa during early healing may be critical for bone formation within the grafted area. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A 5-year prospective radiographic evaluation of marginal bone levels adjacent to parallel-screw cylinder machined-neck implants and rough-surfaced microthreaded implants using digitized panoramic radiographs.

PubMed

Nickenig, Hans-Joachim; Wichmann, Manfred; Happe, Arndt; Zöller, Joachim E; Eitner, Stephan

2013-10-01

The purpose of this split-mouth study was to compare macro- and microstructure implant surfaces at the marginal bone level over five years of functional loading. From January to February 2006, 133 implants (70 rough-surfaced microthreaded implants and 63 machined-neck implants) were inserted in the mandible of 34 patients with Kennedy Class I residual dentitions and followed until December 2011. Marginal bone level was radiographically determined at six time points: implant placement (baseline), after the healing period, after six months, and at two years, three years, and five years follow-up. Median follow-up time was 5.2 years (range: 5.1-5.4). The machined-neck group had a mean crestal bone loss of 0.5 mm (0.0-2.3) after the healing period, 1.1 mm (0.0-3.0) at two years follow-up, and 1.4 mm (0.0-2.9) at five years follow-up. The rough-surfaced microthreaded implant group had a mean bone loss of 0.1 mm (-0.4 to 2.0) after the healing period, 0.5 mm (0.0-2.1) at two years follow-up, and 0.7 mm (0.0-2.3) at five years follow-up. The two implant types showed significant differences in marginal bone levels. Rough-surfaced microthreaded design caused significantly less loss of crestal bone levels under long-term functional loading in the mandible when compared to machined-neck implants. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Rapid and reliable healing of critical size bone defects with genetically modified sheep muscle.

PubMed

Liu, F; Ferreira, E; Porter, R M; Glatt, V; Schinhan, M; Shen, Z; Randolph, M A; Kirker-Head, C A; Wehling, C; Vrahas, M S; Evans, C H; Wells, J W

2015-09-21

Large segmental defects in bone fail to heal and remain a clinical problem. Muscle is highly osteogenic, and preliminary data suggest that autologous muscle tissue expressing bone morphogenetic protein-2 (BMP-2) efficiently heals critical size defects in rats. Translation into possible human clinical trials requires, inter alia, demonstration of efficacy in a large animal, such as the sheep. Scale-up is fraught with numerous biological, anatomical, mechanical and structural variables, which cannot be addressed systematically because of cost and other practical issues. For this reason, we developed a translational model enabling us to isolate the biological question of whether sheep muscle, transduced with adenovirus expressing BMP-2, could heal critical size defects in vivo. Initial experiments in athymic rats noted strong healing in only about one-third of animals because of unexpected immune responses to sheep antigens. For this reason, subsequent experiments were performed with Fischer rats under transient immunosuppression. Such experiments confirmed remarkably rapid and reliable healing of the defects in all rats, with bridging by 2 weeks and remodelling as early as 3-4 weeks, despite BMP-2 production only in nanogram quantities and persisting for only 1-3 weeks. By 8 weeks the healed defects contained well-organised new bone with advanced neo-cortication and abundant marrow. Bone mineral content and mechanical strength were close to normal values. These data demonstrate the utility of this model when adapting this technology for bone healing in sheep, as a prelude to human clinical trials.

Models of tibial fracture healing in normal and Nf1-deficient mice.

PubMed

Schindeler, Aaron; Morse, Alyson; Harry, Lorraine; Godfrey, Craig; Mikulec, Kathy; McDonald, Michelle; Gasser, Jürg A; Little, David G

2008-08-01

Delayed union and nonunion are common complications associated with tibial fractures, particularly in the distal tibia. Existing mouse tibial fracture models are typically closed and middiaphyseal, and thus poorly recapitulate the prevailing conditions following surgery on a human open distal tibial fracture. This report describes our development of two open tibial fracture models in the mouse, where the bone is broken either in the tibial midshaft (mid-diaphysis) or in the distal tibia. Fractures in the distal tibial model showed delayed repair compared to fractures in the tibial midshaft. These tibial fracture models were applied to both wild-type and Nf1-deficient (Nf1+/-) mice. Bone repair has been reported to be exceptionally problematic in human NF1 patients, and these patients can also spontaneously develop tibial nonunions (known as congenital pseudarthrosis of the tibia), which are recalcitrant to even vigorous intervention. pQCT analysis confirmed no fundamental differences in cortical or cancellous bone in Nf1-deficient mouse tibiae compared to wild-type mice. Although no difference in bone healing was seen in the tibial midshaft fracture model, the healing of distal tibial fractures was found to be impaired in Nf1+/- mice. The histological features associated with nonunited Nf1+/- fractures were variable, but included delayed cartilage removal, disproportionate fibrous invasion, insufficient new bone anabolism, and excessive catabolism. These findings imply that the pathology of tibial pseudarthrosis in human NF1 is complex and likely to be multifactorial.

Autogenous Partial Bone Chip Grafting on the Exposed Inferior Alveolar Nerve After Cystic Enucleation.

PubMed

Seo, Mi Hyun; Eo, Mi Young; Cho, Yun Ju; Kim, Soung Min; Lee, Suk Keun

2018-03-01

This prospective study evaluated the clinical effectiveness of the new approach of partial autogenous bone chip grafts for the treatment of mandibular cystic lesions related to the inferior alveolar nerve (IAN). A total of 38 patients treated for mandibular cysts or benign tumors were included in this prospective study and subsequently divided into 3 groups depending on the bone grafting method used: cystic enucleation without a bone graft (group 1), partial bone chip graft covering the exposed IAN (group 2), and autogenous bone graft covering the entire defect (group 3). We evaluated the symptoms, clinical signs, and radiographic changes using dental panorama preoperatively, immediate postoperatively, and at 1, 3, 6, and 12 months postoperatively. Radiographic densities were compared using Adobe Photoshop CS5 (Adobe Systems Inc., San Jose, CA). Repeated measures analysis of variance was used for statistical evaluation with SPSS 22.0 (SPSS Inc, Chicago, IL), and P < 0.05 was considered statistically significant.Radiopacities were the most increased at 1 year postoperative in group 3; groups 2 and 3 did not show statistically significant differences, whereas groups 1 and 3 were statistically significant. In terms of radiographic bone healing with clinical regeneration of the exposed IAN, healing occurred in all patients, although the best healing was achieved in group 2.This autogenous partial bone chip grafting procedure to cover the exposed IAN is suggested as a new surgical protocol for the treatment of cystic lesions associated with the IAN.

In vitro characterization of MG-63 osteoblast-like cells cultured on organic-inorganic lyophilized gelatin sponges for early bone healing.

PubMed

Rodriguez, Isaac A; Saxena, Gunjan; Hixon, Katherine R; Sell, Scott A; Bowlin, Gary L

2016-08-01

The development of three-dimensional porous scaffolds with enhanced osteogenic and angiogenic potential would be beneficial for inducing early-stage bone regeneration. Previous studies have demonstrated the advantages of mineralized and nonmineralized acellular 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) cross-linked gelatin sponges enhanced with preparations rich in growth factors, hydroxyapatite, and chitin whiskers. In this study, those same scaffolds were mineralized and dynamically seeded with MG-63 cells. Cell proliferation, protein/cytokine secretion, and compressive mechanical properties of scaffolds were evaluated. It was found that mineralization and the addition of growth factors increased cell proliferation compared to gelatin controls. Cells on all scaffolds responded in an appropriate bone regenerative fashion as shown through osteocalcin secretion and little to no secretion of bone resorbing markers. However, compressive mechanical properties of cellularized scaffolds were not significantly different from acellular scaffolds. The combined results of increased cellular attachment, infiltration, and bone regenerative protein/cytokine secretion on scaffolds support the need for the addition of a bone-like mineral surface. Cellularized scaffolds containing growth factors reported similar advantages and mechanical values in the range of native tissues present in the early stages of bone healing. These results suggest that the developed composite sponges exhibited cellular responses and mechanical properties appropriate for promoting early bone healing in various applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2011-2019, 2016. © 2016 Wiley Periodicals, Inc.

Histopathological evaluation of the effect of locally administered strontium on healing time in mandibular fractures: An experimental study.

PubMed

Durmuş, Kasım; Turgut, Nergiz Hacer; Doğan, Mehtap; Tuncer, Ersin; Özer, Hatice; Altuntaş, Emine Elif; Akyol, Melih

2017-10-01

Mandibular fractures are the most common facial fractures. They can be treated by conservative techniques or by surgery. The authors hypothesized that the application of a single local dose of strontium chloride would accelerate the healing of subcondylar mandibular fractures, shorten the recovery time and prevent complications. The aim of the present pilot study was to evaluate the effects of a single local dose of strontium chloride on the healing of subcondylar mandibular fractures in rats. This randomized experimental study was carried out on 24 male Wistar albino rats. The rats were randomly divided into 3 groups: experimental group 1, receiving 3% strontium chloride; experimental group 2, receiving 5% strontium chloride; and the control group. A full thickness surgical osteotomy was created in the subcondylar area. A single dose of strontium solution (0.3 cc/site) was administered locally by injection on the bone surfaces of the fracture line created. Nothing was administered to the control group. The mandibles were dissected on postoperative day 21. The fractured hemimandibles were submitted to histopathological examination. The median bone fracture healing score was 9 (range: 7-9) in experimental group 1; 8 (range: 7-10) in experimental group 2; and 7.50 (range: 7-8) in the control group. When the groups were compared in terms of bone healing scores, there was a statistically significant difference between experimental group 1 and the control group (p < 0.05). This study is the first to show that local strontium may have positive effects on the healing of subcondylar mandibular fractures. In the authors' opinion, 3% strontium was beneficial for accelerating facial skeleton consolidation and bone regeneration in rat subcondylar mandibular fractures. This treatment procedure may be combined with closed fracture treatment or a conservative approach.

Influence of low-level laser therapy on the healing process of autogenous bone block grafts in the jaws of systemically nicotine-modified rats: A histomorphometric study.

PubMed

de Almeida, Juliano Milanezi; de Moraes, Ricardo Oliveira; Gusman, David Jonathan Rodrigues; Faleiros, Paula Lazilha; Nagata, Maria José Hitomi; Garcia, Valdir Gouveia; Theodoro, Letícia Helena; Bosco, Alvaro Francisco

2017-03-01

To analyze the influence of low-level laser therapy (LLLT) on the bone healing process of autogenous bone block grafts installed in nicotine systemically modified rats. Seventy-two rats (Wistar) were randomly assigned into 4 groups (n=18). SS-BG: saline application+bone graft. SS-BG/LLLT: saline application+bone graft+LLLT. NIC-BG: nicotine application+bone graft. NIC-BG/LLLT: nicotine application+bone graft+LLLT. After 30days of application of solutions, all animals received autogenous bone block graft in the jaw, with the donation from the parietal bone's calvarial area. Treatment with LLLT was in bed-graft interface, after accommodation of the graft. The animals in each group were sacrificed at 7, 14, and 28days after graft surgery. The histologic analyses of NIC-BG group depicted a delay of osteogenic activity in the recipient bed-graft interface and the irradiation of tissue with LLLT provided better bone healing. The histometric analysis revealed that SS-BG/LLLT and NIC-BG/LLLT groups showed increased bone formation compared to BG-SS and NIC-BG groups, after 14days (SS-BG 24.94%±13.06% versus SS-BG/LLLT 27.53%±19.07% and NIC-BG 14.27%±2.22% versus NIC-BG/LLLT 24.37%±11.93%) and 28days (SS-BG 50.31%±2.69% versus SS-BG/LLLT 58 19%±12.32% and NIC-BG 36.89%±8.40% versus NIC-BG/LLLT 45.81%±6.03%). Nicotine harms bone formation in the bed-graft interface and LLLT action can mitigate this. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biglycan potentially regulates angiogenesis during fracture repair by altering expression and function of endostatin

PubMed Central

Myren, Maja; Kirby, David J.; Noonan, Megan L.; Maeda, Azusa; Owens, Rick T.; Ricard-Blum, Sylvie; Kram, Vardit; Kilts, Tina M.; Young, Marian F.

2016-01-01

The small proteoglycan biglycan (Bgn) is highly expressed in the organic matrix of bone and plays a role in bone formation. Previous work implicated Bgn in vessel growth during bone healing (1). By infusing barium sulfate (BaSO4) into WT and Bgn-deficient mice we discovered the positive effect of Bgn in modulating angiogenesis during fracture healing. Using micro-computed tomography angiography we found significant differences in the vessel size and volume among other parameters. To further understand the mechanistic basis for this, we explored the relationship between Bgn and the anti-angiogenic protein endostatin. Immunohistochemistry (IHC) showed co-localization of Bgn and endostatin in regions of bone formation, with increased endostatin staining in Bgn-KO compared to WT at 14 days post-fracture. To further elucidate the relationship between Bgn and endostatin, an endothelial cell tube formation assay was used. This study showed that endothelial cells treated with endostatin had significantly decreased vessel length and vessel branches compared to untreated cells, while cells treated with endostatin and Bgn at a 1:1 molar ratio had vessel length and vessel branches comparable to untreated cells. This indicated that Bgn was able to mitigate the inhibitory effect of endostatin on endothelial cell growth. In summary, these results suggest that Bgn is needed for proper blood vessel formation during fracture healing, and one mechanism by which Bgn impacts angiogenesis is through inhibition of endostatin. PMID:27072616

Determining the Role of Sost and Sostdc1 During Fracture Healing

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

Yee, Cristal Sook Ngei

The bone is a dynamic organ, often changing throughout the course of the human lifespan with its continuous remodeling, laying down new bone and resorbing old bone. With age, the bone becomes increasingly porous and mechanically unstable, leading to the development of osteoporosis in some individuals. Elderly patients with osteoporosis are at an increased risk of fracturing their bones which contributes to a higher mortality rate. Recent studies have revealed that type 1 diabetic mellitus (T1DM) patients also have an osteoporotic bone phenotype and impaired fracture healing, independent of age. Currently, there is a lack of available treatments that canmore » improve impaired healing and directly enhance bone formation. Therefore, there is a great need for developing new therapies that can not only aid type 1 diabetic patients with osteoporosis to improve bone phenotype, but that could also aid patients with difficult or impaired fracture healing. In this thesis, I will be discussing the role of Wnt signaling and Sclerostin, a Wnt antagonist that negatively regulates bone formation, in the content of fracture repair.« less

The Impact of Type 2 Diabetes on Bone Fracture Healing

PubMed Central

Marin, Carlos; Luyten, Frank P.; Van der Schueren, Bart; Kerckhofs, Greet; Vandamme, Katleen

2018-01-01

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease known by the presence of elevated blood glucose levels. Nowadays, it is perceived as a worldwide epidemic, with a very high socioeconomic impact on public health. Many are the complications caused by this chronic disorder, including a negative impact on the cardiovascular system, kidneys, eyes, muscle, blood vessels, and nervous system. Recently, there has been increasing evidence suggesting that T2DM also adversely affects the skeletal system, causing detrimental bone effects such as bone quality deterioration, loss of bone strength, increased fracture risk, and impaired bone healing. Nevertheless, the precise mechanisms by which T2DM causes detrimental effects on bone tissue are still elusive and remain poorly studied. The aim of this review was to synthesize current knowledge on the different factors influencing the impairment of bone fracture healing under T2DM conditions. Here, we discuss new approaches used in recent studies to unveil the mechanisms and fill the existing gaps in the scientific understanding of the relationship between T2DM, bone tissue, and bone fracture healing. PMID:29416527

Forces associated with launch into space do not impact bone fracture healing

NASA Astrophysics Data System (ADS)

Childress, Paul; Brinker, Alexander; Gong, Cynthia-May S.; Harris, Jonathan; Olivos, David J.; Rytlewski, Jeffrey D.; Scofield, David C.; Choi, Sungshin Y.; Shirazi-Fard, Yasaman; McKinley, Todd O.; Chu, Tien-Min G.; Conley, Carolynn L.; Chakraborty, Nabarun; Hammamieh, Rasha; Kacena, Melissa A.

2018-02-01

Segmental bone defects (SBDs) secondary to trauma invariably result in a prolonged recovery with an extended period of limited weight bearing on the affected limb. Soldiers sustaining blast injuries and civilians sustaining high energy trauma typify such a clinical scenario. These patients frequently sustain composite injuries with SBDs in concert with extensive soft tissue damage. For soft tissue injury resolution and skeletal reconstruction a patient may experience limited weight bearing for upwards of 6 months. Many small animal investigations have evaluated interventions for SBDs. While providing foundational information regarding the treatment of bone defects, these models do not simulate limited weight bearing conditions after injury. For example, mice ambulate immediately following anesthetic recovery, and in most cases are normally ambulating within 1-3 days post-surgery. Thus, investigations that combine disuse with bone healing may better test novel bone healing strategies. To remove weight bearing, we have designed a SBD rodent healing study in microgravity (μG) on the International Space Station (ISS) for the Rodent Research-4 (RR-4) Mission, which launched February 19, 2017 on SpaceX CRS-10 (Commercial Resupply Services). In preparation for this mission, we conducted an end-to-end mission simulation consisting of surgical infliction of SBD followed by launch simulation and hindlimb unloading (HLU) studies. In brief, a 2 mm defect was created in the femur of 10 week-old C57BL6/J male mice (n = 9-10/group). Three days after surgery, 6 groups of mice were treated as follows: 1) Vivarium Control (maintained continuously in standard cages); 2) Launch Negative Control (placed in the same spaceflight-like hardware as the Launch Positive Control group but were not subjected to launch simulation conditions); 3) Launch Positive Control (placed in spaceflight-like hardware and also subjected to vibration followed by centrifugation); 4) Launch Positive Experimental (identical to Launch Positive Control group, but placed in qualified spaceflight hardware); 5) Hindlimb Unloaded (HLU, were subjected to HLU immediately after launch simulation tests to simulate unloading in spaceflight); and 6) HLU Control (single housed in identical HLU cages but not suspended). Mice were euthanized 28 days after launch simulation and bone healing was examined via micro-Computed Tomography (μCT). These studies demonstrated that the mice post-surgery can tolerate launch conditions. Additionally, forces and vibrations associated with launch did not impact bone healing (p = .3). However, HLU resulted in a 52.5% reduction in total callus volume compared to HLU Controls (p = .0003). Taken together, these findings suggest that mice having a femoral SBD surgery tolerated the vibration and hypergravity associated with launch, and that launch simulation itself did not impact bone healing, but that the prolonged lack of weight bearing associated with HLU did impair bone healing. Based on these findings, we proceeded with testing the efficacy of FDA approved and novel SBD therapies using the unique spaceflight environment as a novel unloading model on SpaceX CRS-10.

Cellular therapy in bone-tendon interface regeneration

PubMed Central

Rothrauff, Benjamin B; Tuan, Rocky S

2014-01-01

The intrasynovial bone-tendon interface is a gradual transition from soft tissue to bone, with two intervening zones of uncalcified and calcified fibrocartilage. Following injury, the native anatomy is not restored, resulting in inferior mechanical properties and an increased risk of re-injury. Recent in vivo studies provide evidence of improved healing when surgical repair of the bone-tendon interface is augmented with cells capable of undergoing chondrogenesis. In particular, cellular therapy in bone-tendon healing can promote fibrocartilage formation and associated improvements in mechanical properties. Despite these promising results in animal models, cellular therapy in human patients remains largely unexplored. This review highlights the development and structure-function relationship of normal bone-tendon insertions. The natural healing response to injury is discussed, with subsequent review of recent research on cellular approaches for improved healing. Finally, opportunities for translating in vivo findings into clinical practice are identified. PMID:24326955

Platelet-rich plasma for bone healing and regeneration.

PubMed

Oryan, Ahmad; Alidadi, Soodeh; Moshiri, Ali

2016-01-01

Successful healing of large bone defects (LBDs) is a complicated phenomenon because the body's natural ability often fails to effectively repair the LBDs. New modalities should be utilized to increase the quality and accelerate bone healing. Platelet concentrates in different forms can be considered an attractive option for such purpose. Platelets as a natural source of growth factors, cytokines, and other micro and macromolecules are hypothesized to improve bone healing. This review has covered important concepts regarding platelet-rich plasma (PRP) including mechanisms of action, preparation protocols and their differences, and factors affecting the PRP efficacy during bone healing. In addition, the most recent studies in different levels which evaluated the role of PRP on bone repair has been reviewed and discussed to clarify the controversies and conflicts, and to illustrate a future prospective and directions for orthopedic surgeons to overcome current limitations and difficulties. As the efficacy of PRP is dependent on various factors, the outcome of PRP therapy is variable and unpredictable in orthopedic patients. Therefore, it is still too soon to suggest PRP as the first line treatment option in complicated bone injuries such as LBDs and nonunions. However, combination of PRP with natural and synthetic biomaterials can enhance the effectiveness of PRP.

Characterization and evaluation of graphene oxide scaffold for periodontal wound healing of class II furcation defects in dog.

PubMed

Kawamoto, Kohei; Miyaji, Hirofumi; Nishida, Erika; Miyata, Saori; Kato, Akihito; Tateyama, Akito; Furihata, Tomokazu; Shitomi, Kanako; Iwanaga, Toshihiko; Sugaya, Tsutomu

2018-01-01

The 3-dimensional scaffold plays a key role in volume and quality of repair tissue in periodontal tissue engineering therapy. We fabricated a novel 3D collagen scaffold containing carbon-based 2-dimensional layered material, named graphene oxide (GO). The aim of this study was to characterize and assess GO scaffold for periodontal tissue healing of class II furcation defects in dog. GO scaffolds were prepared by coating the surface of a 3D collagen sponge scaffold with GO dispersion. Scaffolds were characterized using cytotoxicity and tissue reactivity tests. In addition, GO scaffold was implanted into dog class II furcation defects and periodontal healing was investigated at 4 weeks postsurgery. GO scaffold exhibited low cytotoxicity and enhanced cellular ingrowth behavior and rat bone forming ability. In addition, GO scaffold stimulated healing of dog class II furcation defects. Periodontal attachment formation, including alveolar bone, periodontal ligament-like tissue, and cementum-like tissue, was significantly increased by GO scaffold implantation, compared with untreated scaffold. The results suggest that GO scaffold is biocompatible and possesses excellent bone and periodontal tissue formation ability. Therefore, GO scaffold would be beneficial for periodontal tissue engineering therapy.

MiR-142-5p promotes bone repair by maintaining osteoblast activity.

PubMed

Tu, Manli; Tang, Juanjuan; He, Hongbo; Cheng, Peng; Chen, Chao

2017-05-01

MicroRNAs play important roles in regulating bone regeneration and remodeling. However, the pathophysiological roles of microRNAs in bone repair remain unclear. Here we identify a significant upregulation of miR-142-5p correlated with active osteoblastogenesis during the bone healing process. In vitro, miR-142-5p promoted osteoblast activity and matrix mineralization by targeting the gene encoding WW-domain-containing E3 ubiquitin protein ligase 1. We also found that the expression of miR-142-5p in the callus of aged mice was lower than that in the callus of young mice and directly correlated with the age-related delay in bone healing. Furthermore, treatment with agomir-142-5p in the fracture areas stimulated osteoblast activity which repaired the bone fractures in aged mice. Thus, our study revealed that miR-142-5p plays a crucial role in healing fractures by maintaining osteoblast activity, and provided a new molecular target therapeutic strategy for bone healing.

In vivo assessment of bone healing following Piezotome® ultrasonic instrumentation.

PubMed

Reside, Jonathan; Everett, Eric; Padilla, Ricardo; Arce, Roger; Miguez, Patricia; Brodala, Nadine; De Kok, Ingeborg; Nares, Salvador

2015-04-01

This pilot study evaluated the molecular, histologic, and radiographic healing of bone to instrumentation with piezoelectric or high speed rotary (R) devices over a 3-week healing period. Fourteen Sprague-Dawley rats (Charles River Laboratories International, Inc., Wilmington, MA, USA) underwent bilateral tibial osteotomies prepared in a randomized split-leg design using Piezotome® (P1) (Satelec Acteon, Merignac, France), Piezotome 2® (P2) (Satelec Acteon), High-speed R instrumentation, or sham surgery (S). At 1 week, an osteogenesis array was used to evaluate differences in gene expression while quantitative analysis assessed percentage bone fill (PBF) and bone mineral density (BMD) in the defect, peripheral, and distant regions at 3 weeks. Qualitative histologic evaluation of healing osteotomies was also performed at 3 weeks. At 1 week, expression of 11 and 18 genes involved in bone healing was significantly (p < .05) lower following P1 and P2 instrumentation, respectively, relative to S whereas 16 and 4 genes were lower relative to R. No differences in PBF or BMD were detected between groups within the osteotomy defect. However, significant differences in PBF (p = .020) and BMD (p = .008) were noted along the peripheral region between P2 and R groups, being R the group with the lowest values. Histologically, smooth osteotomy margins were present following instrumentation using P1 or P2 relative to R. Piezoelectric instrumentation favors preservation of bone adjacent to osteotomies while variations in gene expression suggest differences in healing rates due to surgical modality. Bone instrumented by piezoelectric surgery appears less detrimental to bone healing than high-speed R device. © 2013 Wiley Periodicals, Inc.

Enhancement of Tendon–Bone Healing for Anterior Cruciate Ligament (ACL) Reconstruction Using Bone Marrow-Derived Mesenchymal Stem Cells Infected with BMP-2

PubMed Central

Dong, Yu; Zhang, Qingguo; Li, Yunxia; Jiang, Jia; Chen, Shiyi

2012-01-01

At present, due to the growing attention focused on the issue of tendon–bone healing, we carried out an animal study of the use of genetic intervention combined with cell transplantation for the promotion of this process. Here, the efficacy of bone marrow stromal cells infected with bone morphogenetic protein-2 (BMP-2) on tendon–bone healing was determined. A eukaryotic expression vector containing the BMP-2 gene was constructed and bone marrow-derived mesenchymal stem cells (bMSCs) were infected with a lentivirus. Next, we examined the viability of the infected cells and the mRNA and protein levels of BMP-2-infected bMSCs. Gastrocnemius tendons, gastrocnemius tendons wrapped by bMSCs infected with the control virus (bMSCs+Lv-Control), and gastrocnemius tendons wrapped by bMSCs infected with the recombinant BMP-2 virus (bMSCs+Lv-BMP-2) were used to reconstruct the anterior cruciate ligament (ACL) in New Zealand white rabbits. Specimens from each group were harvested four and eight weeks postoperatively and evaluated using biomechanical and histological methods. The bMSCs were infected with the lentivirus at an efficiency close to 100%. The BMP-2 mRNA and protein levels in bMSCs were significantly increased after lentiviral infection. The bMSCs and BMP-2-infected bMSCs on the gastrocnemius tendon improved the biomechanical properties of the graft in the bone tunnel; specifically, bMSCs infected with BMP-2 had a positive effect on tendon–bone healing. In the four-week and eight-week groups, bMSCs+Lv-BMP-2 group exhibited significantly higher maximum loads of 29.3 ± 7.4 N and 45.5 ± 11.9 N, respectively, compared with the control group (19.9 ± 6.4 N and 21.9 ± 4.9 N) (P = 0.041 and P = 0.001, respectively). In the eight-week groups, the stiffness of the bMSCs+Lv-BMP-2 group (32.5 ± 7.3) was significantly higher than that of the bMSCs+Lv-Control group (22.8 ± 7.4) or control groups (12.4 ± 6.0) (p = 0.036 and 0.001, respectively). Based on the histological findings, there was an increased amount of perpendicular collagen fibers formed between the tendon and bone in the bMSCs+Lv-Control and bMSCs+Lv-BMP-2 group, compared with the gastrocnemius tendons. The proliferation of cartilage-like cells and the formation of fibrocartilage-like tissue were highest within the bone tunnels in the bMSCs+Lv-BMP-2 group. These results suggest that this lentivirus can be used to efficiently infect bMSCs with BMP-2. Furthermore, tendons wrapped by bMSCs+Lv-BMP-2 improved tendon–bone healing. PMID:23202970

Defective Bone Repair in C57Bl6 Mice With Acute Systemic Inflammation.

PubMed

Behrends, D A; Hui, D; Gao, C; Awlia, A; Al-Saran, Y; Li, A; Henderson, J E; Martineau, P A

2017-03-01

Bone repair is initiated with a local inflammatory response to injury. The presence of systemic inflammation impairs bone healing and often leads to malunion, although the underlying mechanisms remain poorly defined. Our research objective was to use a mouse model of cortical bone repair to determine the effect of systemic inflammation on cells in the bone healing microenvironment. QUESTION/PURPOSES: (1) Does systemic inflammation, induced by lipopolysaccharide (LPS) administration affect the quantity and quality of regenerating bone in primary bone healing? (2) Does systemic inflammation alter vascularization and the number or activity of inflammatory cells, osteoblasts, and osteoclasts in the bone healing microenvironment? Cortical defects were drilled in the femoral diaphysis of female and male C57BL/6 mice aged 5 to 9 months that were treated with daily systemic injections of LPS or physiologic saline as control for 7 days. Mice were euthanized at 1 week (Control, n = 7; LPS, n = 8), 2 weeks (Control, n = 7; LPS, n = 8), and 6 weeks (Control, n = 9; LPS, n = 8) after surgery. The quantity (bone volume per tissue volume [BV/TV]) and microarchitecture (trabecular separation and thickness, porosity) of bone in the defect were quantified with time using microCT. The presence or activity of vascular endothelial cells (CD34), macrophages (F4/80), osteoblasts (alkaline phosphatase [ALP]), and osteoclasts (tartrate-resistant acid phosphatase [TRAP]) were evaluated using histochemical analyses. Only one of eight defects was bridged completely 6 weeks after surgery in LPS-injected mouse bones compared with seven of nine defects in the control mouse bones (odds ratio [OR], 0.04; 95% CI, 0.003-0.560; p = 0.007). The decrease in cortical bone in LPS-treated mice was reflected in reduced BV/TV (21% ± 4% vs 39% ± 10%; p < 0.01), increased trabecular separation (240 ± 36 μm vs 171 ± 29 μm; p < 0.01), decreased trabecular thickness (81 ± 18 μm vs 110 ± 22 μm; p = 0.02), and porosity (79% ± 4% vs 60% ± 10%; p < 0.01) at 6 weeks postoperative. Defective healing was accompanied by decreased CD34 (1.1 ± 0.6 vs 3.4 ± 0.9; p < 0.01), ALP (1.9 ± 0.9 vs 6.1 ± 3.2; p = 0.03), and TRAP (3.3 ± 4.7 vs 7.2 ± 4.0; p = 0.01) activity, and increased F4/80 (13 ± 2.6 vs 6.8 ± 1.7; p < 0.01) activity at 2 weeks postoperative. The results indicate that LPS-induced systemic inflammation reduced the amount and impaired the quality of bone regenerated in mouse femurs. The effects were associated with impaired revascularization, decreased bone turnover by osteoblasts and osteoclasts, and by increased catabolic activity by macrophages. Results from this preclinical study support clinical observations of impaired primary bone healing in patients with systemic inflammation. Based on our data, local administration of VEGF in the callus to stimulate revascularization, or transplantation of stem cells to enhance bone turnover represent potentially feasible approaches to improve outcomes in clinical practice.

Potential for Osseous Regeneration of Platelet-Rich Fibrin-A Comparative Study in Mandibular Third Molar Impaction Sockets.

PubMed

Varghese, Mathew P; Manuel, Suvy; Kumar L K, Surej

2017-07-01

This study investigated the potential of platelet-rich fibrin (PRF) for osseous regeneration and soft tissue healing in mandibular third molar impaction sockets. A prospective in vivo study was performed. Randomization was performed after extraction. On one side, the socket was sutured primarily (control site); on the other side, autologous PRF gel was placed and then the socket was sutured (test site). Postoperatively, grid periapical radiographs were obtained at periodic intervals (weeks 1, 4, and 16) and digitalized. Gray-level values were measured at 3 different regions of the socket (for regions of newly formed bone) compared with the natural bone area using HL Image++ software, and the percentage bone fill was measured. Clinical evaluation of soft tissue healing was performed using the healing index of Landry et al (J Periodontol 60:212, 1994) at the specific intervals. Thirty healthy men and women (age range, 18 to 35 yr) with bilaterally impacted mandibular third molars were enrolled in this study. In general, there was markedly greater bone formation in sockets treated with PRF (P < .05). In the PRF group, the average gray-level values at the cervical, middle, and apical regions were 61.85 (standard deviation [SD], ±25.186), 64.54 (SD, ±24.831), and 67.80 (SD, ±23.946), respectively, with a mean value of 64.73 (SD, ±24.411). In the control group, these values were 51.58 (SD, ±15.286), 54.30 (SD, ±16.274), and 57.53 (SD, ±16.187), respectively, with a mean of 53.67 (SD, ±16.528). The average percentage of bone fill in the PRF group was 57.90 (SD, ±26.789) and that of the non-PRF group was 46.74 (SD, ±17.713; P < .05). Soft tissue healing as evaluated by the healing index of Landry et al also was found to be better at the PRF test site and it was statistically significant (P < .05). There was evidence for better osseous regeneration and soft tissue healing in response to PRF. Further investigations to evaluate the application of PRF in other areas of oral and maxillofacial surgery are imperative. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study.

PubMed

Hernigou, Philippe; Flouzat Lachaniette, Charles Henri; Delambre, Jerome; Zilber, Sebastien; Duffiet, Pascal; Chevallier, Nathalie; Rouard, Helene

2014-09-01

The purpose of this study was to evaluate the efficiency of biologic augmentation of rotator cuff repair with iliac crest bone marrow-derived mesenchymal stem cells (MSCs). The prevalence of healing and prevention of re-tears were correlated with the number of MSCs received at the tendon-to-bone interface. Forty-five patients in the study group received concentrated bone marrow-derived MSCs as an adjunct to single-row rotator cuff repair at the time of arthroscopy. The average number of MSCs returned to the patient was 51,000 ± 25,000. Outcomes of patients receiving MSCs during their repair were compared to those of a matched control group of 45 patients who did not receive MSCs. All patients underwent imaging studies of the shoulder with iterative ultrasound performed every month from the first postoperative month to the 24th month. The rotator cuff healing or re-tear was confirmed with MRI postoperatively at three and six months, one and two years and at the most recent follow up MRI (minimum ten-year follow-up). Bone marrow-derived MSC injection as an adjunctive therapy during rotator cuff repair enhanced the healing rate and improved the quality of the repaired surface as determined by ultrasound and MRI. Forty-five (100 %) of the 45 repairs with MSC augmentation had healed by six months, versus 30 (67 %) of the 45 repairs without MSC treatment by six months. Bone marrow concentrate (BMC) injection also prevented further ruptures during the next ten years. At the most recent follow-up of ten years, intact rotator cuffs were found in 39 (87 %) of the 45 patients in the MSC-treated group, but just 20 (44 %) of the 45 patients in the control group. The number of transplanted MSCs was determined to be the most relevant to the outcome in the study group, since patients with a loss of tendon integrity at any time up to the ten-year follow-up milestone received fewer MSCs as compared with those who had maintained a successful repair during the same interval. This study showed that significant improvement in healing outcomes could be achieved by the use of BMC containing MSC as an adjunct therapy in standard of care rotator cuff repair. Furthermore, our study showed a substantial improvement in the level of tendon integrity present at the ten-year milestone between the MSC-treated group and the control patients. These results support the use of bone marrow-derived MSC augmentation in rotator cuff repair, especially due to the enhanced rate of healing and the reduced number of re-tears observed over time in the MSC-treated patients.

Vibration Testing Procedures for Bone Stiffness Assessment in Fractures Treated with External Fixation.

PubMed

Mattei, Lorenza; Longo, Antonia; Di Puccio, Francesca; Ciulli, Enrico; Marchetti, Stefano

2017-04-01

A bone healing assessment is crucial for the successful treatment of fractures, particularly in terms of the timing of support devices. However, in clinical practice, this assessment is only made qualitatively through bone manipulation and X-rays, and hence cannot be repeated as often as might be required. The present study reconsiders the quantitative method of frequency response analysis for healing assessments, and specifically for fractures treated with an external fixator. The novelty consists in the fact that bone excitation and response are achieved through fixator pins, thus overcoming the problem of transmission through soft-tissues and their damping effect. The main objective was to develop and validate a test procedure in order to characterize the treated bone. More than 80 tests were performed on a tibia phantom alone, a phantom with pins, and a phantom with a complete fixator. Different excitation techniques and input-output combinations were compared. The results demonstrated the effectiveness of a procedure based on impact tests using a micro-hammer. Pins and fixator were demonstrated to influence the frequency response of the phantom by increasing the number of resonant frequencies. This procedure will be applied in future studies to monitor healing both in in vitro and in vivo conditions.

Local application of an ibandronate/collagen sponge improves femoral fracture healing in ovariectomized rats

PubMed Central

Liu, Yansong; Hou, Zhiyong; Chen, Wei; Jin, Lin; Tian, Ye; Ju, Linlin; Liu, Bo; Dong, Tianhua; Zhang, Fei

2017-01-01

Non-union is a major clinical problem in the healing of fractures, especially in patients with osteoporosis. The systemic administration of drugs is time consuming and large doses are demanding and act slowly, whereas local release acts rapidly, increases the quality and quantity of the bone tissue. We hypothesize that local delivery demonstrates better therapeutic effects on an osteoporotic fracture. The aim of this paper is to investigate the effect of the local application of ibandronate loaded with a collagen sponge on regulating bone formation and remodeling in an osteoporotic rat model of fracture healing. We found that the local delivery of ibandronate exhibited excellent effects on improving the bone microarchitecture and suppressed effects on bone remodeling. At 4 weeks, more callus formation and improvement of mechanical character and microstructure were observed in a local delivery via μCT, mechanical test, histological research and serum analysis. The suppression of bone remodeling was compared with a systemic treatment at 12 weeks, and the structural mechanical properties and microarchitecture were also improved with local delivery. This research identifies an earlier, safer and integrated approach for local delivery of ibandronate with collagen and provides a better strategy for the treatment of osteoporotic fracture in rats. PMID:29108027

Enhanced Tendon-to-Bone Healing of Chronic Rotator Cuff Tears by Bone Marrow Aspirate Concentrate in a Rabbit Model

PubMed Central

Liu, Xiao Ning; Yang, Cheol-Jung; Kim, Ji Eui; Du, Zhen Wu; Ren, Ming; Zhang, Wei; Zhao, Hong Yu; Kim, Kyung Ok

2018-01-01

Background To evaluate the influence of bone marrow aspirate concentrate (BMAC) on tendon-to-bone healing in a rabbit rotator cuff model and to characterize the composition of growth factors in BMAC. Methods In this in vivo study, 40 rabbits were allocated into five groups: control (C), repair + saline (RS), repair + platelet-rich plasma (PRP; RP), repair + BMAC (RB) and repair + PRP + BMAC (RPB). A tear model was created by supraspinatus tendon transection at the footprint. Six weeks after transection, the torn tendon was repaired along with BMAC or PRP administration. Six weeks after repair, shoulder samples were harvested for biomechanical and histological testing. Ten rabbits were used for processing PRP and BMAC, followed by analysis of blood cell composition and the levels of growth factors in vitro. Results The ultimate load-to-failure was significantly higher in RPB group compared to RS group (p = 0.025). BMAC-treated groups showed higher values of biomechanical properties than RS group. The histology of BMAC-treated samples showed better collagen fiber continuity and orientation than RS group. BMAC contained significantly higher levels of the several growth factors than PRP. Conclusions Locally administered BMAC enhanced tendon-to-bone healing and has potential for clinical applications. PMID:29564054

In Vivo Hypobaric Hypoxia Performed During the Remodeling Process Accelerates Bone Healing in Mice

PubMed Central

Durand, Marjorie; Collombet, Jean-Marc; Frasca, Sophie; Begot, Laurent; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline

2014-01-01

We investigated the effects of respiratory hypobaric hypoxia on femoral bone-defect repair in mice because hypoxia is believed to influence both mesenchymal stromal cell (MSC) and hematopoietic stem cell mobilization, a process involved in the bone-healing mechanism. To mimic conditions of non-weight-bearing limb immobilization in patients suffering from bone trauma, our hypoxic mouse model was further subjected to hind-limb unloading. A hole was drilled in the right femur of adult male C57/BL6J mice. Four days after surgery, mice were subjected to hind-limb unloading for 1 week. Seven days after surgery, mice were either housed for 4 days in a hypobaric room (FiO2 at 10%) or kept under normoxic conditions. Unsuspended control mice were housed in either hypobaric or normoxic conditions. Animals were sacrificed on postsurgery day 11 to allow for collection of both contralateral and lesioned femurs, blood, and spleen. As assessed by microtomography, delayed hypoxia enhanced bone-healing efficiency by increasing the closing of the cortical defect and the newly synthesized bone volume in the cavity by +55% and +35%, respectively. Proteome analysis and histomorphometric data suggested that bone-repair improvement likely results from the acceleration of the natural bone-healing process rather than from extended mobilization of MSC-derived osteoprogenitors. Hind-limb unloading had hardly any effect beyond delayed hypoxia-enhanced bone-healing efficiency. PMID:24944208

The role of bone marrow-derived cells during the bone healing process in the GFP mouse bone marrow transplantation model.

PubMed

Tsujigiwa, Hidetsugu; Hirata, Yasuhisa; Katase, Naoki; Buery, Rosario Rivera; Tamamura, Ryo; Ito, Satoshi; Takagi, Shin; Iida, Seiji; Nagatsuka, Hitoshi

2013-03-01

Bone healing is a complex and multistep process in which the origin of the cells participating in bone repair is still unknown. The involvement of bone marrow-derived cells in tissue repair has been the subject of recent studies. In the present study, bone marrow-derived cells in bone healing were traced using the GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) were transplanted into C57BL/6 J wild mice. After transplantation, bone injury was created using a 1.0-mm drill. Bone healing was histologically assessed at 3, 7, 14, and 28 postoperative days. Immunohistochemistry for GFP; double-fluorescent immunohistochemistry for GFP-F4/80, GFP-CD34, and GFP-osteocalcin; and double-staining for GFP and tartrate-resistant acid phosphatase were performed. Bone marrow transplantation successfully replaced the hematopoietic cells into GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts or osteocytes in the repair stage were GFP-negative, whereas osteoclasts in the repair and remodeling stages and hematopoietic cells were GFP-positive. The results indicated that bone marrow-derived cells might not differentiate into osteoblasts. The role of bone marrow-derived cells might be limited to adjustment of the microenvironment by differentiating into inflammatory cells, osteoclasts, or endothelial cells in immature blood vessels.

Localized rosuvastatin via implantable bioerodible sponge and its potential role in augmenting bone healing and regeneration.

PubMed

Ibrahim, Howida Kamal; Fahmy, Rania Hassan

2016-11-01

Statins proved potential bone healing properties. Rosuvastatin is a synthetic, hydrophilic, potent and highly efficacious statin. In the current work, an attempt was investigated to develop, evaluate various bioerodible composite sponges enclosing rosuvastatin and explore their potential in augmenting bone healing and regeneration. Twelve lyophilized sponge formulae were prepared adapting a 4 1 .3 1 full factorial design. Xanthan gum, polycarbophil, Carbopol® and sodium alginate were investigated as anionic polymers, each at three chitosan:anionic polymer ratios (1:3, 1:1, 3:1). The formula of choice was implanted in fractured rat femora. Visual and microscopic examination showed flexible homogenous porous structures with considerable bending ability. Polyelectrolyte complex formation was proved by DSC and FT-IR for all chitosan/anionic combinations except with xanthan gum where chitosan probably bound to the drug rather than xanthan gum. Statistical analysis proved that anionic polymer type and chitosan: polymer ratio, as well as, their interactions, exhibited significant effects on the release parameters at p ≤ 0.05. The optimum chitosan/anionic polymer complexation ratios were 3:1 for polycarbophil and 1:1 for Carbopol and alginate. The release at these ratios followed Fiction diffusion while other ratios had anomalous diffusion. Imwitor® 900K and HPMC K100M were added as release retarardants for further release optimization. The formula of choice was implanted in fractured rat femora. Histopathological examination revealed advanced stages of healing in treated femora compared to control ones. Biodegradable sponges for local rosuvastatin delivery proved significantly enhanced wound healing and regeneration properties to fractured bones.

The effects of healing abutments of different size and anatomic shape placed immediately in extraction sockets on peri-implant hard and soft tissues. A pilot study in foxhound dogs.

PubMed

López-López, Patricia J; Mareque-Bueno, Javier; Boquete-Castro, Ana; Aguilar-Salvatierra Raya, Antonio; Martínez-González, José M; Calvo-Guirado, José L

2016-01-01

The aim of this animal study was to compare the effects of narrow, concave-straight and wide anatomic healing abutments on changes to soft tissues and crestal bone levels around implants immediately placed into extraction sockets in foxhound dogs. Forty-eight titanium implants (Bredent Medical GMBH, Germany) of the same dimensions were placed in six foxhound dogs. They were divided into two groups (n = 24): test (implants with anatomic abutment) and control (implants with concave-straight abutment). The implants were inserted randomly in the post extraction sockets of P2 , P3 , P4, and M1 bilaterally in six dogs. After eight and twelve weeks, the animals were sacrificed and samples extracted containing the implants and the surrounding soft and hard tissues. Soft tissue and crestal bone loss (CBL) were evaluated by histology and histomorphometry. All implants were clinically and histologically osseointegrated. Healing patterns were examined microscopically at eight and twelve weeks. After eight and twelve weeks, for hard tissues, the distance from the implant shoulder to the first bone-to-implant contact (IS-C) was higher for control group in the lingual aspect with statistical significance (P < 0.05). For soft tissues (STL), the distance from the top of the peri-implant mucosa to the apical portion of the junction epithelium (PM-Je) was significantly less on the lingual aspect in the test group (with wider abutment) at eight and twelve weeks (P < 0.05). The distance from the top of the apical portion of the junction epithelium to the first bone-to-implant contact (Je-C) was significantly higher in the test group (wider abutment) in the lingual aspect at eight and twelve weeks (P < 0.05). There was no connective tissue contact with any abutment surface. Within the limitations of this animal study, anatomic healing abutments protect soft and hard tissues and reduce crestal bone resorption compared with concave-straight healing abutments. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of methotrexate on bone and wound healing.

PubMed

Pountos, Ippokratis; Giannoudis, Peter V

2017-05-01

Methotrexate (MTX) is one of the most commonly used disease modifying drugs administered for wide spectrum of conditions. Through the expansion of the indications of MTX use, an increasing number of patients nowadays attend orthopaedic departments receiving this pharmacological agent. The aim of this manuscript is to present our current understanding on the effect of MTX on bone and wound healing. Areas covered: The authors offer a comprehensive review of the existing literature on the experimental and clinical studies analysing the effect of MTX on bone and wound healing. The authors also analyse the available literature and describe the incidence of complications after elective orthopaedic surgery in patients receiving MTX. Expert opinion: The available experimental data and clinical evidence are rather inadequate to allow any safe scientific conclusions on the effect of MTX on bone healing. Regarding wound healing, in vitro and experimental animal studies suggest that MTX can adversely affect wound healing, whilst the clinical studies show that lose-dose MTX is safe and does not affect the incidence of postoperative wound complications.

Inhibition of GSK-3β Rescues the Impairments in Bone Formation and Mechanical Properties Associated with Fracture Healing in Osteoblast Selective Connexin 43 Deficient Mice

PubMed Central

Loiselle, Alayna E.; Lloyd, Shane A. J.; Paul, Emmanuel M.; Lewis, Gregory S.; Donahue, Henry J.

2013-01-01

Connexin 43 (Cx43) is the most abundant gap junction protein in bone and is required for osteoblastic differentiation and bone homeostasis. During fracture healing, Cx43 is abundantly expressed in osteoblasts and osteocytes, while Cx43 deficiency impairs bone formation and healing. In the present study we selectively deleted Cx43 in the osteoblastic lineage from immature osteoblasts through osteocytes and tested the hypothesis that Cx43 deficiency results in delayed osteoblastic differentiation and impaired restoration of biomechanical properties due to attenuated β-catenin expression relative to wild type littermates. Here we show that Cx43 deficiency results in alterations in the mineralization and remodeling phases of healing. In Cx43 deficient fractures the mineralization phase is marked by delayed expression of osteogenic genes. Additionally, the decrease in the RankL/ Opg ratio, osteoclast number and osteoclast size suggest decreased osteoclast bone resorption and remodeling. These changes in healing result in functional deficits as shown by a decrease in ultimate torque at failure. Consistent with these impairments in healing, β-catenin expression is attenuated in Cx43 deficient fractures at 14 and 21 days, while Sclerostin (Sost) expression, a negative regulator of bone formation is increased in Cx43cKO fractures at 21 days, as is GSK-3β, a key component of the β-catenin proteasomal degradation complex. Furthermore, we show that alterations in healing in Cx43 deficient fractures can be rescued by inhibiting GSK-3β activity using Lithium Chloride (LiCl). Treatment of Cx43 deficient mice with LiCl restores both normal bone formation and mechanical properties relative to LiCl treated WT fractures. This study suggests that Cx43 is a potential therapeutic target to enhance fracture healing and identifies a previously unknown role for Cx43 in regulating β-catenin expression and thus bone formation during fracture repair. PMID:24260576

In vitro migration and proliferation ("wound healing") potential of mesenchymal stromal cells generated from human CD271(+) bone marrow mononuclear cells.

PubMed

Latifi-Pupovci, Hatixhe; Kuçi, Zyrafete; Wehner, Sibylle; Bönig, Halvard; Lieberz, Ralf; Klingebiel, Thomas; Bader, Peter; Kuçi, Selim

2015-09-25

Emerging evidence indicates that mesenchymal stromal cells (MSCs) isolated from different tissue sources may be used in vivo as tissue restorative agents. To date, there is no evidence, however, on migration and proliferation ("wound healing") potential of different subsets of MSCs. The main goal of this study was therefore to compare the in vitro "wound healing" capacity of MSCs generated from positively selected CD271(+) bone marrow mononuclear cells (CD271-MSCs) and MSCs generated by plastic adherence (PA-MSCs). The in vitro model of wound healing (CytoSelect™ 24-Well Wound Healing Assay) was used in order to compare the migration and proliferation potential of CD271-MSCs and PA-MSCs of passage 2 and 4 cultured in presence or absence of growth factors or cytokines. CD271-MSCs of both passages when compared to PA-MSCs demonstrated a significantly higher potential to close the wound 12 and 24 h after initiation of the wound healing assay (P < 0.003 and P < 0.002, respectively). Noteworthy, the migration capacity of PA-MSCs of second passage was significantly improved after stimulation with FGF-2 (P < 0.02), PDGF-BB (P < 0.006), MCP-1 (P < 0.002) and IL-6 (P < 0.03), whereas only TGF-β enhanced significantly migration process of PA-MSCs of P4 12 h after the treatment (P < 0.02). Interestingly, treatment of CD271-MSCs of both passages with growth factors or cytokines did not affect their migratory potential. Our in vitro data provide the first evidence that CD271-MSCs are significantly more potent in "wound healing" than their counterparts PA-MSCs.

Scanning electron microscopy study of new bone formation following small and large defects preserved with xenografts supplemented with pamidronate-A pilot study in Fox-Hound dogs at 4 and 8 weeks.

PubMed

Lozano-Carrascal, Naroa; Satorres-Nieto, Marta; Delgado-Ruiz, Rafael; Maté-Sánchez de Val, José Eduardo; Gehrke, Sergio Alexandre; Gargallo-Albiol, Jorge; Calvo-Guirado, José Luis

2017-01-01

The aim of the present study was to evaluate the feasibility of SEM and EDX microanalysis on evaluating the effect of porcine xenografts (MP3 ® ) supplemented with pamidronate during socket healing. Mandibular second premolars (P2) and first molars (M1) were extracted from six Beagle dogs. P2 were categorized as small defects (SD) and M1 as large defects (LD). Four random groups were created: SC (small control defects with MP3 ® ), ST (small test defects MP3 ® +pamidronate), LC (large control defects with MP3 ® ), and LT (large test defects MP3 ® +pamidronate). At four and eight weeks of healing the samples were evaluated fisically through scanning electron microscopy (SEM), and chemical element mapping was carried out by Energy dispersive X-ray spectroscopy (EDX). After four weeks of healing, SEM and EDX analysis revealed more mineralized bone in ST and LT groups compared with control groups (p<0.05). After eight weeks, Ca/P ratios were slightly higher for small defects (groups SC and ST); in SEM description, in both control and test groups, trabecular bone density was similar to the adjacent mineralized cortical bone. Within the limitations of this experimental study, SEM description and EDX elemental microanalysis have demonstrated to be useful techniques to assess bone remodelling of small and large defects. Both techniques show increased bone formation in test groups (MP3 ® modified with pamidronate) after four and eight weeks of healing. Copyright © 2016 Elsevier GmbH. All rights reserved.

Type 2 Diabetes and Metformin Influence on Fracture Healing in an Experimental Rat Model.

PubMed

La Fontaine, Javier; Chen, Chris; Hunt, Nathan; Jude, Edward; Lavery, Lawrence

2016-01-01

Persons with diabetes have a greater incidence of fractures compared with persons without diabetes. However, very little published information is available concerning the deleterious effect of late-stage diabetes on osseous structure and bone healing. The purpose of the present study was to evaluate the role of diabetes on fracture healing in a rat femur repair model. Thirty-six lean and diabetic Zucker rats were subdivided into 3 groups: (1) 12 lean rats as the control group; (2) 12 diabetic rats without blood glucose control (DM group); and (3) 12 diabetic rats treated with 300 mg/kg metformin to reduce the blood glucose levels (DM + Met group). Radiographs were taken every week to determine the incidence of bone repair and delayed union. All the rats were killed at 6 weeks after surgery. In both the sham-operated and the fractured and repaired femurs, significant decreases in the fracture-load/weight and marginal decreases in the fracture-load between the lean and DM groups were found. Metformin treatment significantly reduced the blood glucose and body weight 12 days postoperatively. Furthermore, a decrease in the fracture-load and fracture-load/weight in the repaired femurs was found in the DM + Met group. Diabetes impairs bone fracture healing. Metformin treatment reduces the blood glucose and body weight but had an adverse effect on fracture repair in diabetic rats. Further investigations are needed to reveal the mechanisms responsible for the effects of type 2 diabetes mellitus on bone and bone quality and the effect of medications such as metformin might have in diabetic bone in the presence of neuropathy and vascular disease. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

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

Yee, Cristal S.; Xie, LiQin; Hatsell, Sarah

Type 1 diabetes mellitus (T1DM) patients have osteopenia and impaired fracture healing due to decreased osteoblast activity. Further, no adequate treatments are currently available that can restore impaired healing in T1DM; hence a significant need exists to investigate new therapeutics for treatment of orthopedic complications. Sclerostin (SOST), a WNT antagonist, negatively regulates bone formation, and SostAb is a potent bone anabolic agent. To determine whether SOST antibody (SostAb) treatment improves fracture healing in streptozotocin (STZ) induced T1DM mice, we administered SostAb twice weekly for up to 21 days post-fracture, and examined bone quality and callus outcomes at 21 days andmore » 42 days post-fracture (11 and 14 weeks of age, respectively). Here we show that SostAb treatment improves bone parameters; these improvements persist after cessation of antibody treatment. Markers of osteoblast differentiation such as Runx2, collagen I, osteocalcin, and DMP1 were reduced, while an abundant number of SP7/osterix-positive early osteoblasts were observed on the bone surface of STZ calluses. These results suggest that STZ calluses have poor osteogenesis resulting from failure of osteoblasts to fully differentiate and produce mineralized matrix, which produces a less mineralized callus. SostAb treatment enhanced fracture healing in both normal and STZ groups, and in STZ + SostAb mice, also reversed the lower mineralization seen in STZ calluses. Micro-CT analysis of calluses revealed improved bone parameters with SostAb treatment, and the mineralized bone was comparable to Controls. Additionally, we found sclerostin levels to be elevated in STZ mice and β-catenin activity to be reduced. Consistent with its function as a WNT antagonist, SostAb treatment enhanced β-catenin activity, but also increased the levels of SOST in the callus and in circulation. Lastly, our results indicate that SostAb treatment rescues the impaired osteogenesis seen in the STZ induced T1DM fracture model by facilitating osteoblast differentiation and mineralization of bone.« less

The local administration of parathyroid hormone encourages the healing of bone defects in the rat calvaria: Micro-computed tomography, histological and histomorphometric evaluation.

PubMed

Auersvald, Caroline Moreira; Santos, Felipe Rychuv; Nakano, Mayara Mytie; Leoni, Graziela Bianchi; de Sousa Neto, Manoel Damião; Scariot, Rafaela; Giovanini, Allan Fernando; Deliberador, Tatiana Miranda

2017-07-01

To evaluate the effect of a single-dose local administration of PTH on bone healing in rat calvarial bone defects by means of micro-computed tomography, histological and histomorphometric analysis. Critical-size cranial osteotomy defects were created in 42 male rats. The animals were randomly divided into 3 groups. In the C Group, the bone defect was only filled with a blood clot. In the S Group, it was filled with a collagen sponge and covered with bovine cortical membrane. In the PTH Group, the defect was filled with a collagen sponge soaked with PTH and covered with bovine cortical membrane. The groups were further split in two for euthanasia 15 and 60days post-surgery. Data was statistically analyzed with t-tests for independent samples or the nonparametric Mann-Whitney test when applicable. Intragroup comparisons were analyzed with paired t-tests (p<0.05). Micro-CT analysis results did not demonstrate statistically significant intergroup differences. At 15days post-surgery, the histomorphometric analysis showed that the PTH Group exhibited a significantly higher percentage of bone formation compared with the S Group. At 60days post-surgery, a higher percentage of new bone was observed in the PTH group. The results suggest that the local administration of PTH encouraged the bone healing in critical-size calvarial defects in rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

A new animal model for bone atrophic nonunion: fixation by external fixator.

PubMed

Kaspar, Katharina; Matziolis, Georg; Strube, Patrick; Sentürk, Ufuk; Dormann, Svenja; Bail, Hermann J; Duda, Georg N

2008-12-01

A new small animal model of bone atrophic nonunion was established for investigating the process of bone regeneration by performing cauterization of the periosteum, removal of the local bone marrow, and stabilization with external fixation. The model allows the creation of an atrophic nonunion without the need for a critical size defect. Furthermore, it provides reproducible, well-defined mechanical conditions and minimized physical interference of the implant with the biological processes in the healing zone. Eighty adult Sprague-Dawley rats received an osteotomy of the left femur, stabilized with an external fixator. In half of the animals, the periosteum proximal and distal to the osteotomy was destroyed by cauterization and the adjacent bone marrow was removed (nonunion group). At 2 and 8 weeks after surgery, radiological, biomechanical, histological, and histomorphometrical analyses showed a typical physiological healing in the control group, while the nonunion group was characterized by resorption of the bone ends with some callus formation distant to the osteotomy. At both time points, the callus was composed of significantly less bone and significantly more connective tissue (p < 0.001). In addition, the torsional strength of the osteotomized femur was significantly less in the nonunion group than in the control group, which was comparable to that of the intact femur (p < 0.001). In conclusion, the present model allows the induction of an atrophic nonunion without the need of a critical size defect. It is reproducible, provides standardized biomechanical conditions, and allows minimized interaction of the implant with the healing zone.

Formononetin, a methoxy isoflavone, enhances bone regeneration in a mouse model of cortical bone defect.

PubMed

Singh, Krishna Bhan; Dixit, Manisha; Dev, Kapil; Maurya, Rakesh; Singh, Divya

2017-06-01

The bone regeneration and healing effect of formononetin was evaluated in a cortical bone defect model that predominantly heals by intramembranous ossification. For this study, female Balb/c mice were ovariectomised (OVx) and a drill-hole injury was generated in the midfemoral bones of all animals. Treatment with formononetin commenced the day after and continued for 21 d. Parathyroid hormone (PTH1-34) was used as a reference standard. Animals were killed at days 10 and 21. Femur bones were collected at the injury site for histomorphometry studies using microcomputed tomography (μCT) and confocal microscopy. RNA and protein were harvested from the region surrounding the drill-hole injury. For immunohistochemistry, 5 µm sections of decalcified femur bone adjoining the drill-hole site were cut. μCT analysis showed that formononetin promoted bone healing at days 10 and 21 and the healing effect observed was significantly better than in Ovx mice and equal to PTH treatment in many aspects. Formononetin also significantly enhanced bone regeneration as assessed by calcein-labelling studies. In addition, formononetin enhanced the expression of osteogenic markers at the injury site in a manner similar to PTH. Formononetin treatment also led to predominant runt-related transcription factor 2 and osteocalcin localisation at the injury site. These results support the potential of formononetin to be a bone-healing agent and are suggestive of its promising role in the fracture-repair process.

Orthobiologics in Pediatric Sports Medicine.

PubMed

Bray, Christopher C; Walker, Clark M; Spence, David D

2017-07-01

Orthobiologics are biological substances that allow injured muscles, tendons, ligaments, and bone to heal more quickly. They are found naturally in the body; at higher concentrations they can aid in the healing process. These substances include autograft bone, allograft bone, demineralized bone matrix, bone morphogenic proteins, growth factors, stem cells, plasma-rich protein, and ceramic grafts. Their use in sports medicine has exploded in efforts to increase graft incorporation, stimulate healing, and get athletes back to sport with problems including anterior cruciate ligament ruptures, tendon ruptures, cartilage injuries, and fractures. This article reviews orthobiologics and their applications in pediatric sports medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

PREVALENCE OF HEALED LONG-BONE FRACTURES IN WILD CARNIVORES FROM THE NORTHEASTERN UNITED STATES.

PubMed

Argyros, George C; Roth, Aaron J

2016-09-01

Museum specimens representing 12 species of terrestrial carnivores from the northeastern United States were inspected for evidence of healed long-bone fractures. Of 413 individuals, 18 (4.4%) exhibited healed fractures. Thirteen (72.2%) occurred in hind limbs; five (27.8%) occurred in forelimbs. Mustelids had the highest prevalence of healed long-bone fractures (38.8%) of all observed fractures. Within family, 5.6% of Canidae and 2.8% of Mustelidae exhibited healed fractures. Bobcats had the highest taxon prevalence of fractures, 18%. Observational data to assess use of and behavior near roads could provide insight to causes of fracture. Capture in combination with noninvasive examination techniques could be employed to determine incidence of healed fractures in wild populations. Individuals with healed fractures could then be tracked via radio telemetry to determine if these animals behave differently than uninjured conspecifics, and assess long-term survivability and fitness.

The use of BMP-2 coupled – Nanosilver-PLGA composite grafts to induce bone repair in grossly infected segmental defects

PubMed Central

Zheng, Zhong; Yin, Wei; Zara, Janette N.; Li, Weiming; Kwak, Jinny; Mamidi, Rachna; Lee, Min; Siu, Ronald K.; Ngo, Richard; Wang, Joyce; Carpenter, Doug; Zhang, Xinli; Wu, Benjamin; Ting, Kang; Soo, Chia

2010-01-01

Healing of contaminated/infected bone defects is a significant clinical challenge. Prevalence of multi-antibiotic resistant organisms has renewed interest in the use of antiseptic silver as an effective, but less toxic antimicrobial with decreased potential for bacterial resistance. In this study, we demonstrated that metallic nanosilver particles (with a size of 20–40 nm)-poly(lactic-co-glycolic acid) (PLGA) composite grafts have strong antibacterial properties. In addition, nanosilver particles-PLGA composite grafts did not inhibit adherence, proliferation, alkaline phosphatase activity, or mineralization of ongrowth MC3T3-E1 pre-osteoblasts compared to PLGA controls. Furthermore, nanosilver particles did not affect the osteoinductivity of bone morphogenetic protein 2 (BMP-2). Infected femoral defects implanted with BMP-2 coupled 2.0% nanosilver particles-PLGA composite grafts healed in 12 weeks without evidence of residual bacteria. In contrast, BMP-2 coupled PLGA control grafts failed to heal in the presence of continued bacterial colonies. Our results indicate that nanosilver of defined particle size is bactericidal without discernable in vitro and in vivo cytotoxicity or negative effects on BMP-2 osteoinductivity, making it an ideal antimicrobial for bone regeneration in infected wounds. PMID:20864167

A new procedure for processing extracted teeth for immediate grafting in post-extraction sockets. An experimental study in American Fox Hound dogs.

PubMed

Calvo-Guirado, José Luis; Cegarra Del Pino, Pilar; Sapoznikov, Lari; Delgado Ruiz, Rafael Arcesio; Fernández-Domínguez, Manuel; Gehrke, Sérgio Alexandre

2018-05-01

To investigate freshly extracted dental particulate used to graft post-extraction sockets in dogs, comparing new bone formation at experimental and control sites. Bilateral premolars P2, P3, P4 and first mandibular molars were extracted atraumatically from six American Fox Hound dogs. The teeth were ground immediately using a 'Smart Dentin Grinder'. The dentin particulate was sieved to ensure a grain size of 300-1200μm and immersed in an alcohol cleanser to dissolve organic debris and bacteria, followed by washing in sterile saline buffer solution. The animals were divided into two groups randomly: group 'A' (control) samples were left to heal without any extraction socket grafting procedure; group 'B' (experimental) sockets were filled with the autogenous dentin particulate graft. The rate of tissue healing and the quantity of bone formation were evaluated using histological and histomorphometric analyses at 60 and 90 days post-grafting. The type of bone generated was categorized as woven (immature bone) or lamellar bone (mature bone). Substantially more bone formation was found in Group B (experimental) than Group A (control) at 60 and 90 days (p<0.05). Less immature bone was identified in the dentin grafted group (25.7%) than the control group (5.9%). Similar differences were also observed at 90 days post grafting. Autogenous dentin particulate grafted immediately after extractions may be considered a useful biomaterial for socket preservation, protecting both buccal and lingual plates, generating large amounts of new woven bone formation after 60 days, and small amounts of lamellar bone after 90 days healing. Copyright © 2018 Elsevier GmbH. All rights reserved.

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.

Injectable Reactive Biocomposites For Bone Healing In Critical-Size Rabbit Calvarial Defects

DTIC Science & Technology

2012-03-29

defects (i.e. be conformable), provide temporary protection to the brain until the bone heals, and enhance tissue regeneration with the delivery of...temporary protection to the brain until the bone heals, and enhance tissue regeneration with the delivery of biologics. In this study, we evaluated the...complex defects (i.e. be conformable), harden to provide temporary protection until tissue remodels (i.e. be settable), and enhance tissue regeneration

Preclinical and clinical studies on the use of growth factors for bone repair: a systematic review.

PubMed

Fisher, Daniel Mark; Wong, James Min-Leong; Crowley, Conor; Khan, Wasim S

2013-05-01

Bone healing is a complex process. Whilst the majority of fractures heal with conventional treatment, open fractures, large bone defects and non unions still provide great challenges to Orthopaedic Surgeons. Whilst autologous bone graft is seen as the gold standard, the use of growth factors is a growing area of research to find an effective alternative with lower side effects such as donor site morbidity and the finite amount available. This systematic review aims to summarize the pre clinical in-vivo studies and examine the clinical studies on the use of growth factors in bone healing. Databases: PubMed, Medline, OVID, and Cochrane library. The following key words and search terms were used: Growth Factors, Bone Healing, Bone Morphogenic Protein, Transforming Growth Factor Beta, Insulin Like Growth Factor, Platelet Derived Growth Factor, Fracture. All articles were screened based on title with abstracts and full text articles reviewed as appropriate. Reference lists were reviewed from relevant articles to ensure comprehensive and systematic review. Three tables of studies were constructed focussing on Bone Morphogenic Proteins, Platelet Rich Plasma and Growth Factors and Tissue Engineering. Bone Morphogenic Proteins and Platelet Rich Plasma, which contains multiple growth factors, have been shown in preclinical and clinical trials to be an effective alternative to autologous bone graft. Bone Morphogenic Proteins have been shown to be effective in fracture non union, and in open tibial fractures. Platelet Rich Plasma has shown promise in preclinical trials and some small clinical trials, however numbers are limited. Bone Morphogenic Proteins have been shown to be superior to Platelet Rich Protein in one trial. Combining these growth factors with tissue engineering techniques is the focus of ongoing research, and through further clinical trials the most effective techniques for enhancing bone healing will be revealed.

Peri-implant soft tissue and marginal bone adaptation on implant with non-matching healing abutments: micro-CT analysis.

PubMed

Finelle, Gary; Papadimitriou, Dimitrios E V; Souza, André B; Katebi, Negin; Gallucci, German O; Araújo, Mauricio G

2015-04-01

To assess (i) the outcome of changing the horizontal-offset dimension on the peri-implant soft tissues and the crestal bone and (ii) the effect of different healing abutments (flared vs. straight) on the marginal peri-implant soft tissues and crestal bone. Two-piece dental implants diameters of 3.5 and 4.5 mm were placed at least 1 mm subcrestal in five beagle dogs. Three different investigational groups: (i) 3.5-mm-diameter implant with narrow healing abutment (3.5N), (ii) 4.5-mm-diameter implant with narrow healing abutment (4.5N), and (iii) 3.5-mm-diameter implant with wide healing abutment (3.5W), were assessed. After 4 months of healing, the vertical distance from the marginal crestal bone (MB) to the implant shoulder (IS); the vertical distance from the IS to the first bone-to-implant contact; and the horizontal distance of bone ingrowth on the implant platform were measured with a high-resolution micro-CT (Xradia MicroXCT-200 system). Implants with a narrow healing caps showed an interproximal MB located between 0 and 1 mm above the implant shoulder, while the 3.5W group exhibits a mean value -0.50 mm. As all implants in group 3.5N presented a fBIC located at the level of the IS. For the 4.5N group, the mean fBIC-IS distance was -0.52 mm apically to the IS. For the 3.5WC group, the mean fBIC-IS distance was -1.42 mm. Horizontal bone apposition was only observed for the 3.5N group and the 4.5N group. The dimension of the horizontal offset would play a minimal role in reducing bone remodeling, whereas the configuration of the transmucosal component would directly influence marginal bone remodeling. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of the Surface Treatment on Bone Healing in a Transmucosal 1-mm Area of Implant Abutment: An Experimental Study in the Rabbit Tibia.

PubMed

Gehrke, Sergio Alexandre; da Silva Neto, Ulisses Tavares

2016-06-01

The objective of the present study was to investigate the effect on bone tissue healing patterns in 1-mm area treated in the transmucosal surface of the abutment in the tibia of rabbits. Forty-six abutments were divided into two groups: control group (CG) with 14 abutments with smooth surface and experimental group (EG) with 32 abutments presenting a 1-mm area of the transmucosal surface treated through sandblasting with microparticles of titanium oxide followed by acid etching. Five samples of each group were analyzed using an optical laser profilometer for surface roughness characterization. Thirty-six Morse taper implants (3.5 mm in diameter and 7 mm in length) were inserted 1.5 mm subcrestal into the tibiae of nine rabbits. The implants were removed after 8, 10, and 12 weeks for histological analysis. The histological slides were prepared and analyzed qualitatively in relation to the new bone at the interface bone-abutment and quantitatively, in relation to bone height from the base of the implant. These data were computed and statistically compared inside the groups using analysis of variance and the U-test between groups for same time. Both groups exhibited bone growth in the direction and over the surface of the abutments, with good healing. However, the EG group showed an increased height of bone formation in the crestal direction, and highly significant differences were observed (p < .001) between these measured values. Under the limitations of the present study, histological follow-up at 8, 10, and 12 weeks showed that transmucosal 1-mm area of implant abutment with treatment of the surface facilitated the maintenance of bone height around the abutment compared with the same abutment with the totally smooth surface. © 2015 Wiley Periodicals, Inc.

Photothermal stress triggered by near infrared-irradiated carbon nanotubes promotes bone deposition in rat calvarial defects.

PubMed

Yanagi, Tsukasa; Kajiya, Hiroshi; Kawaguchi, Minoru; Kido, Hirofumi; Fukushima, Tadao

2015-03-01

The bone regenerative healing process is often prolonged, with a high risk of infection particularly in elderly and diseased patients. A reduction in healing process time usually requires mechanical stress devices, chemical cues, or laser/thermal therapies. Although these approaches have been used extensively for the reduction of bone healing time, the exact mechanisms involved in thermal stress-induced bone regeneration remain unclear. In this study, we investigated the effect of optimal hyperthermia on rat calvarial defects in vivo and on osteogenesis in vitro. Photothermal stress stimulation was carried out using a new photothermal device, composed of an alginate gel including in carbon nanotubes and their irradiator with near-infrared light. Photothermal stress (15 min at 42℃, every day), trigged by near-infrared-induced carbon nanotube, promoted bone deposition in critical-sized calvarial defects compared with nonthermal stress controls. We recently reported that our novel DNA/protamine complex scaffold induces bone regeneration in calvarial defects. In this study, photothermal stress upregulated bone deposition in DNA/protamine-engrafted calvarial defects. Furthermore, photothermal stress significantly induced expression of osteogenic related genes in a time-dependent manner, including alkaline phosphatase, osterix, and osteocalcin. This was observed in DNA/protamine cells, which were expanded from regenerated tissue engrafted into the DNA/protamine scaffold, as well as in human MG63 preosteoblasts. In summary, this novel carbon nanotube-based photothermal stress approach upregulated expression of osteogenic-related genes in preosteoblasts, resulting in promotion of mineral deposition for enhanced bone repair. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Participation of GATA-3 in regulation of bone healing through transcriptional upregulation of bcl-xL expression

PubMed Central

Liao, Mei-Hsiu; Lin, Pei-I; Ho, Wei-Pin; Chan, Wing P; Chen, Ta-Liang; Chen, Ruei-Ming

2017-01-01

We have previously demonstrated the expression of GATA-DNA-binding protein (GATA)-3, a transcription factor, in osteoblasts and have verified its function in transducing cell survival signaling. This translational study was further designed to evaluate the roles of GATA-3 in regulating bone healing and to explore its possible mechanisms. A metaphyseal bone defect was created in the left femurs of male ICR mice. Analysis by micro-computed topography showed that the bone volume, trabecular bone number and trabecular thickness were augmented and that the trabecular pattern factor decreased. Interestingly, immunohistological analyses showed specific expression of GATA-3 in the defect area. In addition, colocalized expression of GATA-3 and alkaline phosphatase was observed at the wound site. As the fracture healed, the amounts of phosphorylated and non-phosphorylated GATA-3 concurrently increased. Separately, GATA-3 mRNA was induced during bone healing, and, levels of Runx2 mRNA and protein were also increased. The results of confocal microscopy and co-immunoprecipitation showed an association between nuclear GATA-3 and Runx2 in the area of insult. In parallel with fracture healing, Bcl-XL mRNA was significantly triggered. A bioinformatic search revealed the existence of a GATA-3-specific DNA-binding element in the promoter region of the bcl-xL gene. Analysis by chromatin immunoprecipitation assays further demonstrated transactivation activity by which GATA-3 regulated bcl-xL gene expression. Therefore, this study shows that GATA-3 participates in the healing of bone fractures via regulating bcl-xL gene expression, owing to its association with Runx2. In the clinic, GATA-3 may be used as a biomarker for diagnoses/prognoses or as a therapeutic target for bone diseases, such as bone fractures. PMID:29170477

Early experience and results of bone graft enriched with autologous platelet gel for recalcitrant nonunions of lower extremity.

PubMed

Chiang, Chao-Ching; Su, Chen-Yao; Huang, Ching-Kuei; Chen, Wei-Ming; Chen, Tain-Hsiung; Tzeng, Yun-Hsuan

2007-09-01

Refractory nonunions of the tibia or femur are physically and mentally devastating conditions for the patients, and the treatment is challenging for orthopedic surgeons. The goal of this study was to assess the feasibility and outcome of surgical treatment in recalcitrant nonunions of a lower extremity with bone graft enriched with autologous platelet gel (APG). Twelve patients with four femoral and eight tibial atrophic nonunions after multiple prior procedures were included. All of them were treated with the bone grafting procedures with autograft complex enriched with APG. They were evaluated with radiographs, bone mineral density for bony healing process, and the Short-Form 36 Health Survey for functional outcome. Of the 12 patients, 11 healed at an average of 19.7 weeks after the first attempt and 1 healed after the second attempt at 21 weeks. The bone mineral density continued to increase steadily from early healing to the remodeling phase. Functional status was greatly improved at an average follow-up of 32.4 months. The results of this preliminary study implied the possible potential of bone graft enriched with APG in the treatment of recalcitrant nonunions of the lower extremity. More research is necessary to clarify its role in augmentation of bone graft to enhance healing of nonunion.

Analysis of socket preservation using polylactide and polyglycolide (PLA-PGA) sponge: a clinical, radiographic, and histologic study.

PubMed

Madan, Rohit; Mohan, Ranjana; Bains, Vivek K; Gupta, Vivek; Singh, G P; Madan, Mani

2014-01-01

The aim of this study was to evaluate the extraction socket healing and dimensional changes following alveolar ridge preservation using polylactide and polyglycolide (PLA-PGA) sponge. Fifteen patients were selected for alveolar socket preservation immediately following tooth extraction. Monoradicular maxillary and mandibular teeth were evaluated. The selected sockets had intact sockets walls with a minimum of 7 mm of residual alveolar bone height. The test sites were thoroughly debrided and grafted with PLA-PGA sponge, while the control sites underwent natural healing. Computed tomography (CT) measurements were taken at baseline and 6 months. After 6 months of healing, final CT measurements were performed, and trephine core biopsy specimens were obtained for histologic analysis. Implants were placed immediately after biopsy harvesting. All subjects completed the study, and all sites healed without adverse events and allowed for implant placement. The mean difference in socket height, width, and density after 6 months was statistically significantly higher in the test sites compared with control sites. Clinical measurement at the midbuccal site of the alveolar socket showed a mean loss of 2.45 ± 0.67 mm in the control group, compared with a mean gain of 1.28 ± 0.58 mm in the test group. All test sites showed minimal ridge alterations, and statistically significant differences were observed between the test and control sites with respect to bone composition and horizontal and vertical bone loss, indicating that PLA-PGA sponge is suitable for alveolar ridge preservation.

Site Specific Effects of Zoledronic Acid during Tibial and Mandibular Fracture Repair

PubMed Central

Yu, Yan Yiu; Lieu, Shirley; Hu, Diane; Miclau, Theodore; Colnot, Céline

2012-01-01

Numerous factors can affect skeletal regeneration, including the extent of bone injury, mechanical loading, inflammation and exogenous molecules. Bisphosphonates are anticatabolic agents that have been widely used to treat a variety of metabolic bone diseases. Zoledronate (ZA), a nitrogen-containing bisphosphonate (N-BP), is the most potent bisphosphonate among the clinically approved bisphosphonates. Cases of bisphosphonate-induced osteonecrosis of the jaw have been reported in patients receiving long term N-BP treatment. Yet, osteonecrosis does not occur in long bones. The aim of this study was to compare the effects of zoledronate on long bone and cranial bone regeneration using a previously established model of non-stabilized tibial fractures and a new model of mandibular fracture repair. Contrary to tibial fractures, which heal mainly through endochondral ossification, mandibular fractures healed via endochondral and intramembranous ossification with a lesser degree of endochondral ossification compared to tibial fractures. In the tibia, ZA reduced callus and cartilage formation during the early stages of repair. In parallel, we found a delay in cartilage hypertrophy and a decrease in angiogenesis during the soft callus phase of repair. During later stages of repair, ZA delayed callus, cartilage and bone remodeling. In the mandible, ZA delayed callus, cartilage and bone remodeling in correlation with a decrease in osteoclast number during the soft and hard callus phases of repair. These results reveal a more profound impact of ZA on cartilage and bone remodeling in the mandible compared to the tibia. This may predispose mandible bone to adverse effects of ZA in disease conditions. These results also imply that therapeutic effects of ZA may need to be optimized using time and dose-specific treatments in cranial versus long bones. PMID:22359627

Clinical factors affecting pathological fracture and healing of unicameral bone cysts

PubMed Central

2014-01-01

Background Unicameral bone cyst (UBC) is the most common benign lytic bone lesion seen in children. The aim of this study is to investigate clinical factors affecting pathological fracture and healing of UBC. Methods We retrospectively reviewed 155 UBC patients who consulted Nagoya musculoskeletal oncology group hospitals in Japan. Sixty of the 155 patients had pathological fracture at presentation. Of 141 patients with follow-up periods exceeding 6 months, 77 were followed conservatively and 64 treated by surgery. Results The fracture risk was significantly higher in the humerus than other bones. In multivariate analysis, ballooning of bone, cyst in long bone, male sex, thin cortical thickness and multilocular cyst were significant adverse prognostic factors for pathological fractures at presentation. The healing rates were 30% and 83% with observation and surgery, respectively. Multivariate analysis revealed that fracture at presentation and history of biopsy were good prognostic factors for healing of UBC in patients under observation. Conclusion The present results suggest that mechanical disruption of UBC such as fracture and biopsy promotes healing, and thus watchful waiting is indicated in these patients, whereas patients with poor prognostic factors for fractures should be considered for surgery. PMID:24884661

Clinical factors affecting pathological fracture and healing of unicameral bone cysts.

PubMed

Urakawa, Hiroshi; Tsukushi, Satoshi; Hosono, Kozo; Sugiura, Hideshi; Yamada, Kenji; Yamada, Yoshihisa; Kozawa, Eiji; Arai, Eisuke; Futamura, Naohisa; Ishiguro, Naoki; Nishida, Yoshihiro

2014-05-17

Unicameral bone cyst (UBC) is the most common benign lytic bone lesion seen in children. The aim of this study is to investigate clinical factors affecting pathological fracture and healing of UBC. We retrospectively reviewed 155 UBC patients who consulted Nagoya musculoskeletal oncology group hospitals in Japan. Sixty of the 155 patients had pathological fracture at presentation. Of 141 patients with follow-up periods exceeding 6 months, 77 were followed conservatively and 64 treated by surgery. The fracture risk was significantly higher in the humerus than other bones. In multivariate analysis, ballooning of bone, cyst in long bone, male sex, thin cortical thickness and multilocular cyst were significant adverse prognostic factors for pathological fractures at presentation. The healing rates were 30% and 83% with observation and surgery, respectively. Multivariate analysis revealed that fracture at presentation and history of biopsy were good prognostic factors for healing of UBC in patients under observation. The present results suggest that mechanical disruption of UBC such as fracture and biopsy promotes healing, and thus watchful waiting is indicated in these patients, whereas patients with poor prognostic factors for fractures should be considered for surgery.

Early healing in alveolar sockets grafted with titanium granules. An experimental study in a dog model.

PubMed

Arruda, Thiago; Sukekava, Flávia; de Souza, André B; Rasmusson, Lars; Araújo, Maurício G

2013-07-01

The aim of the present study was to evaluate the effect of the placement of titanium granules in fresh extraction sockets on early bone formation. The mesial roots of the third maxillary premolars of five adult beagle dogs were removed. On one side of the maxilla (Test group) the fresh extraction socket was grafted with titanium granules, while the contra-lateral socket was left non-grafted (Control group). After 1 month of healing, the dogs were euthanized and biopsies were obtained. The healing tissues were described, and histometric measurements were performed to obtain the percentage area occupied by connective tissue, new mineralized bone, bone marrow, and biomaterial particles. After 1 month of healing the findings from the histological examination revealed the titanium graft to be well incorporated into the provisional connective tissue or newly formed woven bone. The histometric measurements showed, however, that less mineralized bone was formed in the Test group than in the Control group. The present study suggests that the use of titanium granules in fresh extraction sockets was conducive to new bone formation. The graft of titanium granules seems, however, to delay the early phase of the healing process. Copyright © 2012 Wiley Periodicals, Inc.

Periotest values of implants placed in sockets augmented with calcium phosphosilicate putty graft: a comparative analysis against implants placed in naturally healed sockets.

PubMed

Mahesh, Lanka; Narayan, Tv; Kostakis, Georgios; Shukla, Sagrika

2014-03-01

To measure implant stability using periotest values of implants placed in sockets augmented with calcium phospho-silicate putty (CPS Putty) as compared with implant stability in naturally healed sockets. Twenty two sockets were implanted with CPS Putty immediately after extraction. The sockets were re-entered after a healing period at 5 to 6 months (average 5.3 months) for implant placement. Periotest values were recorded during implant insertion to assess primary stability. These were compared with the Periotest values of 26 implants placed in 22 patients, with naturally healed sockets. Periotest values were significantly lower in the grafted group, indicating better implant stability in sites grafted with CPS putty. Implant stability seems to be significantly higher in sockets augmented using CPS putty when compared to nongrafted sites. This suggests that socket grafting with CPS putty may enhance the quality of available bone for implantation.

Osseointegration of Plateau Root Form Implants: Unique Healing Pathway Leading to Haversian-Like Long-Term Morphology.

PubMed

Coelho, Paulo G; Suzuki, Marcelo; Marin, Charles; Granato, Rodrigo; Gil, Luis F; Tovar, Nick; Jimbo, Ryo; Neiva, Rodrigo; Bonfante, Estevam A

2015-01-01

Endosteal dental implants have been utilized as anchors for dental and orthopedic rehabilitations for decades with one of the highest treatment success rates in medicine. Such success is due to the phenomenon of osseointegration where after the implant surgical placement, bone healing results into an intimate contact between bone and implant surface. While osseointegration is an established phenomenon, the route which osseointegration occurs around endosteal implants is related to various implant design factors including surgical instrumentation and implant macro, micro, and nanometer scale geometry. In an implant system where void spaces (healing chambers) are present between the implant and bone immediately after placement, its inherent bone healing pathway results in unique opportunities to accelerate the osseointegration phenomenon at the short-term and its maintenance on the long-term through a haversian-like bone morphology and mechanical properties.

The use of autologous blood-derived growth factors in bone regeneration

PubMed Central

Civinini, Roberto; Macera, Armando; Nistri, Lorenzo; Redl, Birgit; Innocenti, Massimo

2011-01-01

Platelet-rich plasma (PRP) is defined as a portion of the plasma fraction of autologous blood having platelet concentrations above baseline. When activated the platelets release growth factors that play an essential role in bone healing such as Platelet-derived Growth Factor, Transforming Growth Factor-β, Vascular Endothelial Growth Factor and others. Multiple basic science and in vivo animal studies agree that PRP has a role in the stimulation of the healing cascade in ligament, tendon, muscle cartilage and in bone regeneration in the last years PRP had a widespread diffusion in the treatment of soft tissue and bone healing. The purpose of this review is to describe the biological properties of platelets and its factors, the methods used for producing PRP, to provide a background on the underlying basic science and an overview of evidence based medicine on clinical application of PRP in bone healing. PMID:22461800

Short-term muscle atrophy caused by botulinum toxin-A local injection impairs fracture healing in the rat femur.

PubMed

Hao, Yongqiang; Ma, Yongcheng; Wang, Xuepeng; Jin, Fangchun; Ge, Shengfang

2012-04-01

Damaged bone is sensitive to mechanical stimulation throughout the remodeling phase of bone healing. Muscle damage and muscular atrophy associated with open fractures and subsequent fixation are not beneficial to maintaining optimum conditions for mechanical stability. The aim of this study was to investigate whether local muscle atrophy and dysfunction affect fracture healing in a rat femur fracture model. We combined the rat model of a short period atrophy of the quadriceps with femur fracture. Forty-four-month-old male Wistar rats were adopted for this study. Two units of botulinum toxin-A (BXTA) were administered locally into the right side of the quadriceps of each rat, while the same dose of saline was injected into the contralateral quadriceps. After BXTA had been fully absorbed by the quadriceps, osteotomy was performed in both femurs with intramedullary fixation. Gross observation and weighing of muscle tissue, X-ray analysis, callus histology, and bone biomechanical testing were performed at different time points up to 8 weeks post-surgery. Local injection of BXTA led to a significant decrease in the volume and weight of the quadriceps compared to the control side. At the eighth week, the left side femurs of the saline-injected quadriceps almost reached bony union, and fibrous calluses were completely calcified into woven bone. However, a gap was still visible in the BXTA-treated side on X-ray images. As showed by bone histology, there were no mature osseous calluses or woven bone on the BXTA-treated side, but a resorption pattern was evident. Biomechanical testing indicated that the femurs of the BXTA-treated side exhibited inferior mechanical properties compared with the control side. The inferior outcome following BXTA injection, compared with saline injection, in terms of callus resistance may be the consequence of unexpected load and mechanical unsteadiness caused by muscle atrophy and dysfunction. Copyright © 2011 Orthopaedic Research Society.

Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis

PubMed Central

Locatelli, Vittorio; Bianchi, Vittorio E.

2014-01-01

Background. Growth hormone (GH) and insulin-like growth factor (IGF-1) are fundamental in skeletal growth during puberty and bone health throughout life. GH increases tissue formation by acting directly and indirectly on target cells; IGF-1 is a critical mediator of bone growth. Clinical studies reporting the use of GH and IGF-1 in osteoporosis and fracture healing are outlined. Methods. A Pubmed search revealed 39 clinical studies reporting the effects of GH and IGF-1 administration on bone metabolism in osteopenic and osteoporotic human subjects and on bone healing in operated patients with normal GH secretion. Eighteen clinical studies considered the effect with GH treatment, fourteen studies reported the clinical effects with IGF-1 administration, and seven related to the GH/IGF-1 effect on bone healing. Results. Both GH and IGF-1 administration significantly increased bone resorption and bone formation in the most studies. GH/IGF-1 administration in patients with hip or tibial fractures resulted in increased bone healing, rapid clinical improvements. Some conflicting results were evidenced. Conclusions. GH and IGF-1 therapy has a significant anabolic effect. GH administration for the treatment of osteoporosis and bone fractures may greatly improve clinical outcome. GH interacts with sex steroids in the anabolic process. GH resistance process is considered. PMID:25147565

Serum leptin, bone mineral density and the healing of long bone fractures in men with spinal cord injury.

PubMed

Wang, Lei; Liu, Linjuan; Pan, Zhanpeng; Zeng, Yanjun

2015-11-16

Previously reported fracture rates in patients with spinal cord injury range from 1% to 20%. However, the exact role of spinal cord injury in bone metabolism has not yet been clarified. In order to investigate the effects of serum leptin and bone mineral density on the healing of long bone fractures in men with spinal cord injury, 15 male SCI patients and 15 matched controls were involved in our study. The outcome indicated that at 4 and 8 weeks after bone fracture, callus production in patients with spinal cord injury was lower than that in controls. Besides, bone mineral density was significantly reduced at 2, 4 and 8 weeks. In addition, it was found that at each time point, patients with spinal cord injury had significantly higher serum leptin levels than controls and no association was found between serum leptin level and bone mineral density of lumbar vertebrae. Moreover, bone mineral density was positively correlated with bone formation in both of the groups. These findings suggest that in early phases i.e. week 4 and 8, fracture healing was impaired in patients with spinal cord injury and that various factors participated in the complicated healing process, such as hormonal and mechanical factors.

Modeling the effects of inflammation in bone fracture healing

NASA Astrophysics Data System (ADS)

Kojouharov, H. V.; Trejo, I.; Chen-Charpentier, B. M.

2017-10-01

A new mathematical model is presented to study the early inflammatory effects in bone healing. It consists of a system of nonlinear ordinary differential equations that represents the interactions among macrophages, mesenchymal stem cells, and osteoblasts. A qualitative analysis of the model is performed to determine the equilibria and their corresponding stability properties. A set of numerical simulations is performed to support the theoretical results. The model is also used to numerically monitor the evolution of a broken bone for different types of fractures and to explore possible treatments to accelerate bone healing by administrating anti-inflammatory drugs.

Forces associated with launch into space do not impact bone fracture healing.

PubMed

Childress, Paul; Brinker, Alexander; Gong, Cynthia-May S; Harris, Jonathan; Olivos, David J; Rytlewski, Jeffrey D; Scofield, David C; Choi, Sungshin Y; Shirazi-Fard, Yasaman; McKinley, Todd O; Chu, Tien-Min G; Conley, Carolynn L; Chakraborty, Nabarun; Hammamieh, Rasha; Kacena, Melissa A

2018-02-01

Segmental bone defects (SBDs) secondary to trauma invariably result in a prolonged recovery with an extended period of limited weight bearing on the affected limb. Soldiers sustaining blast injuries and civilians sustaining high energy trauma typify such a clinical scenario. These patients frequently sustain composite injuries with SBDs in concert with extensive soft tissue damage. For soft tissue injury resolution and skeletal reconstruction a patient may experience limited weight bearing for upwards of 6 months. Many small animal investigations have evaluated interventions for SBDs. While providing foundational information regarding the treatment of bone defects, these models do not simulate limited weight bearing conditions after injury. For example, mice ambulate immediately following anesthetic recovery, and in most cases are normally ambulating within 1-3 days post-surgery. Thus, investigations that combine disuse with bone healing may better test novel bone healing strategies. To remove weight bearing, we have designed a SBD rodent healing study in microgravity (µG) on the International Space Station (ISS) for the Rodent Research-4 (RR-4) Mission, which launched February 19, 2017 on SpaceX CRS-10 (Commercial Resupply Services). In preparation for this mission, we conducted an end-to-end mission simulation consisting of surgical infliction of SBD followed by launch simulation and hindlimb unloading (HLU) studies. In brief, a 2 mm defect was created in the femur of 10 week-old C57BL6/J male mice (n = 9-10/group). Three days after surgery, 6 groups of mice were treated as follows: 1) Vivarium Control (maintained continuously in standard cages); 2) Launch Negative Control (placed in the same spaceflight-like hardware as the Launch Positive Control group but were not subjected to launch simulation conditions); 3) Launch Positive Control (placed in spaceflight-like hardware and also subjected to vibration followed by centrifugation); 4) Launch Positive Experimental (identical to Launch Positive Control group, but placed in qualified spaceflight hardware); 5) Hindlimb Unloaded (HLU, were subjected to HLU immediately after launch simulation tests to simulate unloading in spaceflight); and 6) HLU Control (single housed in identical HLU cages but not suspended). Mice were euthanized 28 days after launch simulation and bone healing was examined via micro-Computed Tomography (µCT). These studies demonstrated that the mice post-surgery can tolerate launch conditions. Additionally, forces and vibrations associated with launch did not impact bone healing (p = .3). However, HLU resulted in a 52.5% reduction in total callus volume compared to HLU Controls (p = .0003). Taken together, these findings suggest that mice having a femoral SBD surgery tolerated the vibration and hypergravity associated with launch, and that launch simulation itself did not impact bone healing, but that the prolonged lack of weight bearing associated with HLU did impair bone healing. Based on these findings, we proceeded with testing the efficacy of FDA approved and novel SBD therapies using the unique spaceflight environment as a novel unloading model on SpaceX CRS-10. Copyright © 2017 The Committee on Space Research (COSPAR). All rights reserved.

Investigation of Peri-Implant Bone Healing Using Autologous Plasma Rich in Growth Factors in the Canine Mandible After 12 Weeks: A Pilot Study

PubMed Central

Birang, Reza; Tavakoli, Mohammad; Shahabouei, Mohammad; Torabi, Alireza; Dargahi, Ali; Soolari, Ahmad

2011-01-01

Introduction: Faster reconstruction of patients’ masticatory systems is the aim of modern dentistry. A number of studies have indicated that application of growth factors to the surface of a dental implant leads to accelerated and enhanced osseointegration. The objective of the present study was to investigate the effect of plasma rich in growth factors on peri-implant bone healing. Materials and Methods: For the purpose of this study, two healthy, mixed-breed canines were selected, and the premolars were extracted from both sides of the mandible. Three months after premolar removal, 12 implants, each 5 mm in diameter and 10 mm in length, were placed in osteotomy sites on both sides of the mandible. Prior to placement, plasma rich in growth factors was applied to the surfaces of six implants, while the other six were used without plasma rich in growth factors. The implants were removed after 12 weeks along with the bone surrounding the sites using a trephine bur. One mesiodistal section containing the surrounding bone from each implant block, 50 µm in diameter, was prepared for histologic and histomorphometric investigation with an optical microscope. Results: The sites with implants treated with plasma rich in growth factors showed more bone-to-implant contact compared to control sites. Also, higher values for bone trabecular thickness and bone maturity were recorded for the PRGF-treated sites than for the control sites. Conclusion: Application of plasma rich in growth factors to the surface of an implant may enhance the bone healing process as well as bone-to-implant contact, thereby helping to achieve faster osseointegration. PMID:22145011

Beta-Catenin Signaling Plays a Disparate Role in Different Phases of Fracture Repair: Implications for Therapy to Improve Bone Healing

PubMed Central

Chen, Yan; Whetstone, Heather C; Lin, Alvin C; Nadesan, Puviindran; Wei, Qingxia; Poon, Raymond; Alman, Benjamin A

2007-01-01

Background Delayed fracture healing causes substantial disability and usually requires additional surgical treatments. Pharmacologic management to improve fracture repair would substantially improve patient outcome. The signaling pathways regulating bone healing are beginning to be unraveled, and they provide clues into pharmacologic management. The β-catenin signaling pathway, which activates T cell factor (TCF)-dependent transcription, has emerged as a key regulator in embryonic skeletogenesis, positively regulating osteoblasts. However, its role in bone repair is unknown. The goal of this study was to explore the role of β-catenin signaling in bone repair. Methods and Findings Western blot analysis showed significant up-regulation of β-catenin during the bone healing process. Using a β-Gal activity assay to observe activation during healing of tibia fractures in a transgenic mouse model expressing a TCF reporter, we found that β-catenin-mediated, TCF-dependent transcription was activated in both bone and cartilage formation during fracture repair. Using reverse transcription-PCR, we observed that several WNT ligands were expressed during fracture repair. Treatment with DKK1 (an antagonist of WNT/β-catenin pathway) inhibited β-catenin signaling and the healing process, suggesting that WNT ligands regulate β-catenin. Healing was significantly repressed in mice conditionally expressing either null or stabilized β-catenin alleles induced by an adenovirus expressing Cre recombinase. Fracture repair was also inhibited in mice expressing osteoblast-specific β-catenin null alleles. In stark contrast, there was dramatically enhanced bone healing in mice expressing an activated form of β-catenin, whose expression was restricted to osteoblasts. Treating mice with lithium activated β-catenin in the healing fracture, but healing was enhanced only when treatment was started subsequent to the fracture. Conclusions These results demonstrate that β-catenin functions differently at different stages of fracture repair. In early stages, precise regulation of β-catenin is required for pluripotent mesenchymal cells to differentiate to either osteoblasts or chondrocytes. Once these undifferentiated cells have become committed to the osteoblast lineage, β-catenin positively regulates osteoblasts. This is a different function for β-catenin than has previously been reported during development. Activation of β-catenin by lithium treatment has potential to improve fracture healing, but only when utilized in later phases of repair, after mesenchymal cells have become committed to the osteoblast lineage. PMID:17676991

Beta-catenin signaling plays a disparate role in different phases of fracture repair: implications for therapy to improve bone healing.

PubMed

Chen, Yan; Whetstone, Heather C; Lin, Alvin C; Nadesan, Puviindran; Wei, Qingxia; Poon, Raymond; Alman, Benjamin A

2007-07-31

Delayed fracture healing causes substantial disability and usually requires additional surgical treatments. Pharmacologic management to improve fracture repair would substantially improve patient outcome. The signaling pathways regulating bone healing are beginning to be unraveled, and they provide clues into pharmacologic management. The beta-catenin signaling pathway, which activates T cell factor (TCF)-dependent transcription, has emerged as a key regulator in embryonic skeletogenesis, positively regulating osteoblasts. However, its role in bone repair is unknown. The goal of this study was to explore the role of beta-catenin signaling in bone repair. Western blot analysis showed significant up-regulation of beta-catenin during the bone healing process. Using a beta-Gal activity assay to observe activation during healing of tibia fractures in a transgenic mouse model expressing a TCF reporter, we found that beta-catenin-mediated, TCF-dependent transcription was activated in both bone and cartilage formation during fracture repair. Using reverse transcription-PCR, we observed that several WNT ligands were expressed during fracture repair. Treatment with DKK1 (an antagonist of WNT/beta-catenin pathway) inhibited beta-catenin signaling and the healing process, suggesting that WNT ligands regulate beta-catenin. Healing was significantly repressed in mice conditionally expressing either null or stabilized beta-catenin alleles induced by an adenovirus expressing Cre recombinase. Fracture repair was also inhibited in mice expressing osteoblast-specific beta-catenin null alleles. In stark contrast, there was dramatically enhanced bone healing in mice expressing an activated form of beta-catenin, whose expression was restricted to osteoblasts. Treating mice with lithium activated beta-catenin in the healing fracture, but healing was enhanced only when treatment was started subsequent to the fracture. These results demonstrate that beta-catenin functions differently at different stages of fracture repair. In early stages, precise regulation of beta-catenin is required for pluripotent mesenchymal cells to differentiate to either osteoblasts or chondrocytes. Once these undifferentiated cells have become committed to the osteoblast lineage, beta-catenin positively regulates osteoblasts. This is a different function for beta-catenin than has previously been reported during development. Activation of beta-catenin by lithium treatment has potential to improve fracture healing, but only when utilized in later phases of repair, after mesenchymal cells have become committed to the osteoblast lineage.

Harnessing and Modulating Inflammation in Strategies for Bone Regeneration

PubMed Central

Mountziaris, Paschalia M.; Spicer, Patrick P.; Kasper, F. Kurtis

2011-01-01

Inflammation is an immediate response that plays a critical role in healing after fracture or injury to bone. However, in certain clinical contexts, such as in inflammatory diseases or in response to the implantation of a biomedical device, the inflammatory response may become chronic and result in destructive catabolic effects on the bone tissue. Since our previous review 3 years ago, which identified inflammatory signals critical for bone regeneration and described the inhibitory effects of anti-inflammatory agents on bone healing, a multitude of studies have been published exploring various aspects of this emerging field. In this review, we distinguish between regenerative and damaging inflammatory processes in bone, update our discussion of the effects of anti-inflammatory agents on bone healing, summarize recent in vitro and in vivo studies demonstrating how inflammation can be modulated to stimulate bone regeneration, and identify key future directions in the field. PMID:21615330

[Analysis of the results of bone healing in femurs lengthened by the gradual distraction method in children and adolescents].

PubMed

Jochymek, J; Skvaril, J; Ondrus, S

2009-10-01

Treatment of leg length inequality via lengthening of the shorter extremity is an infrequent orthopedic procedure due to the requirement of special distraction devices and possible serious complications. Essential qualitative changes in operative technique development are associated with the name of G. A. Ilizarov, who paved the way for the autoregenerate gradual distraction method in the 1950s. In the years 1990 through 2007 a total of 67 patients underwent femur lengthening via gradual distraction using various types of external fixators at the Department of Pediatric Surgery, Orthopedics, and Traumatology, Faculty Hospital in Brno. The quality of bone healing was monitored and a number of parameters followed and statistically evaluated using regularly scheduled X-ray examinations. In 13 cases we had to remove the external fixator following the distraction phase, perform an osteosynthesis via a splint and fill the distraction gap via spongioplasty. The bone healing was satisfactory in the remaining 54 patients and the lengthened bone required no other fixation method. The analysis showed statistically significant deceleration in bone healing following distraction in female patients over 12 years of age, and in boys over 14 years of age. Lack of periosteal callus five weeks after surgery always signified serious problems in further healing. Severe complications were recorded in 11 cases during the distraction phase, and in 12 cases after the removal of the distraction apparatus. Our results fully correspond with the data and experience of others cited authors. In addition our study showed deceleration in bone healing in girls over 12 years and in boys over 14 years of age and serious problem in healing when is lack of periostal callus five weeks after surgery. The aim of this report was to present the results of our study of distraction gap bone healing using the gradual lengthening approach. Key words: leg lengthening, gradual distraction, external fixation, leg discrepancy, complication.

Healing in the new millennium: bone stimulators: an overview of where we've been and where we may be heading.

PubMed

Cook, Jeremy J; Summers, N Jake; Cook, Emily A

2015-01-01

Electromagnetic fields and their uses in bone healing have been fairly well studied, with most results showing improvement in healing of both bone and cartilage. Most supportive data are found in relation to the spine, femur, and tibia, but there is increasing evidence for its use in the foot and ankle for treatment of nonunions and as an adjunctive device in arthrodeses, particularly in high-risk populations. There are varying data and a significant variety of quality in the current research and publications concerning the use of electrical bone stimulation in the treatment of the foot and ankle. Thus, there is a definite need for further investigation and high-quality study designs to determine the most effective treatment modalities and pathologies best used with bone stimulation. Bone stimulation should be viewed as an adjunctive procedure in which the surgeon optimizes the high-risk patient both medically or surgically whenever possible. But when used appropriately, bone stimulation has the potential to influence outcomes and aid in bone healing when complications arise and in high-risk populations. Copyright © 2015 Elsevier Inc. All rights reserved.

A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients

PubMed Central

Hoff, Paula; Gaber, Timo; Strehl, Cindy; Jakstadt, Manuela; Hoff, Holger; Schmidt-Bleek, Katharina; Lang, Annemarie; Röhner, Eric; Huscher, Dörte; Matziolis, Georg; Burmester, Gerd-Rüdiger; Schmidmaier, Gerhard; Perka, Carsten; Duda, Georg N.; Buttgereit, Frank

2017-01-01

Immunologically restricted patients such as those with autoimmune diseases or malignancies often suffer from delayed or insufficient fracture healing. In human fracture hematomas and the surrounding bone marrow obtained from immunologically restricted patients, we analyzed the initial inflammatory phase on cellular and humoral level via flow cytometry and multiplex suspension array. Compared with controls, we demonstrated higher numbers of immune cells like monocytes/macrophages, natural killer T (NKT) cells, and activated T helper cells within the fracture hematomas and/or the surrounding bone marrow. Also, several pro-inflammatory cytokines such as Interleukin (IL)-6 and Tumor necrosis factor α (TNFα), chemokines (e.g., Eotaxin and RANTES), pro-angiogenic factors (e.g., IL-8 and Macrophage migration inhibitory factor: MIF), and regulatory cytokines (e.g., IL-10) were found at higher levels within the fracture hematomas and/or the surrounding bone marrow of immunologically restricted patients when compared to controls. We conclude here that the inflammatory activity on cellular and humoral levels at fracture sites of immunologically restricted patients considerably exceeds that of control patients. The initial inflammatory phase profoundly differs between these patient groups and is probably one of the reasons for prolonged or insufficient fracture healing often occurring within immunologically restricted patients. PMID:28282868

Reduced COX-2 expression in aged mice is associated with impaired fracture healing.

PubMed

Naik, Amish A; Xie, Chao; Zuscik, Michael J; Kingsley, Paul; Schwarz, Edward M; Awad, Hani; Guldberg, Robert; Drissi, Hicham; Puzas, J Edward; Boyce, Brendan; Zhang, Xinping; O'Keefe, Regis J

2009-02-01

The cellular and molecular events responsible for reduced fracture healing with aging are unknown. Cyclooxygenase 2 (COX-2), the inducible regulator of prostaglandin E(2) (PGE(2)) synthesis, is critical for normal bone repair. A femoral fracture repair model was used in mice at either 7-9 or 52-56 wk of age, and healing was evaluated by imaging, histology, and gene expression studies. Aging was associated with a decreased rate of chondrogenesis, decreased bone formation, reduced callus vascularization, delayed remodeling, and altered expression of genes involved in repair and remodeling. COX-2 expression in young mice peaked at 5 days, coinciding with the transition of mesenchymal progenitors to cartilage and the onset of expression of early cartilage markers. In situ hybridization and immunohistochemistry showed that COX-2 is expressed primarily in early cartilage precursors that co-express col-2. COX-2 expression was reduced by 75% and 65% in fractures from aged mice compared with young mice on days 5 and 7, respectively. Local administration of an EP4 agonist to the fracture repair site in aged mice enhanced the rate of chondrogenesis and bone formation to levels observed in young mice, suggesting that the expression of COX-2 during the early inflammatory phase of repair regulates critical subsequent events including chondrogenesis, bone formation, and remodeling. The findings suggest that COX-2/EP4 agonists may compensate for deficient molecular signals that result in the reduced fracture healing associated with aging.

In vivo impact testing on a lengthened femur with external fixation: a future option for the non-invasive monitoring of fracture healing?

PubMed

Mattei, Lorenza; Di Puccio, Francesca; Marchetti, Stefano

2018-05-01

Non-invasive methods for assessing fracture healing are crucial for biomedical engineers. An approach based on mechanical vibrations was tried out in the 1990s, but was soon abandoned due to insufficiently advanced technologies. The same approach is re-proposed in the present study in order to monitor the healing process of a lengthened femur with an external fixator. The pins screwed into the bone were exploited for the impact testing (IT) to excite the bone and capture its response. Transmission through the soft tissues was thus prevented, and the quality of the signals was improved. Impact tests were performed every three to four weeks for five months. Unfortunately, after seven weeks, some pins were removed due to infection, and thus, the system was modified. Two different configurations were considered: before and after pin removal. An additional configuration was examined in the last two sessions, when the fixator body was removed, while four pins were left in the femur. The evolution of the frequency response function and of the resonant frequencies of the system were analysed for the duration of the monitoring period. The IT results were compared to the indications provided by X-ray images. During the evolution of the callus from the soft phase to the woven bone, the resonant frequencies of the system were found to increase by approximately 2-3% per week. The largest increase (approx. 22%) was observed for the first resonant frequency. After formation of the woven bone, the vibratory response remained almost the same, suggesting that the healing assessment could be related to the relative variation in the resonant frequencies. The results presented support the application of the IT approach for fracture healing assessment. © 2018 The Author(s).

Bone graft

MedlinePlus

... dry. Follow instructions about showering. DO NOT smoke. Smoking slows or prevents bone healing. If you smoke, the graft is more likely to fail. Be aware that nicotine patches slow healing just like smoking does.

Characterization and evaluation of graphene oxide scaffold for periodontal wound healing of class II furcation defects in dog

PubMed Central

Kawamoto, Kohei; Miyaji, Hirofumi; Nishida, Erika; Miyata, Saori; Kato, Akihito; Tateyama, Akito; Furihata, Tomokazu; Shitomi, Kanako; Iwanaga, Toshihiko; Sugaya, Tsutomu

2018-01-01

Introduction The 3-dimensional scaffold plays a key role in volume and quality of repair tissue in periodontal tissue engineering therapy. We fabricated a novel 3D collagen scaffold containing carbon-based 2-dimensional layered material, named graphene oxide (GO). The aim of this study was to characterize and assess GO scaffold for periodontal tissue healing of class II furcation defects in dog. Materials and methods GO scaffolds were prepared by coating the surface of a 3D collagen sponge scaffold with GO dispersion. Scaffolds were characterized using cytotoxicity and tissue reactivity tests. In addition, GO scaffold was implanted into dog class II furcation defects and periodontal healing was investigated at 4 weeks postsurgery. Results GO scaffold exhibited low cytotoxicity and enhanced cellular ingrowth behavior and rat bone forming ability. In addition, GO scaffold stimulated healing of dog class II furcation defects. Periodontal attachment formation, including alveolar bone, periodontal ligament-like tissue, and cementum-like tissue, was significantly increased by GO scaffold implantation, compared with untreated scaffold. Conclusion The results suggest that GO scaffold is biocompatible and possesses excellent bone and periodontal tissue formation ability. Therefore, GO scaffold would be beneficial for periodontal tissue engineering therapy. PMID:29713167

Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone implantation.

PubMed

Sebecić, B; Nikolić, V; Sikirić, P; Seiwerth, S; Sosa, T; Patrlj, L; Grabarević, Z; Rucman, R; Petek, M; Konjevoda, P; Jadrijević, S; Perović, D; Slaj, M

1999-03-01

Gastrectomy often results in increased likelihood of osteoporosis, metabolic aberration, and risk of fracture, and there is a need for a gastric peptide with osteogenic activity. A novel stomach pentadecapeptide, BPC-157, improves wound and fracture healing in rats in addition to having an angiogenic effect. Therefore, in the present study, using a segmental osteoperiosteal bone defect (0.8 cm, in the middle of the left radius) that remained incompletely healed in all control rabbits for 6 weeks (assessed in 2 week intervals), pentadecapeptide BPC-157 was further studied (either percutaneously given locally [10 microg/kg body weight] into the bone defect, or applied intramuscularly [intermittently, at postoperative days 7, 9, 14, and 16 at 10 microg/kg body weight] or continuously [once per day, postoperative days 7-21 at 10 microg or 10 ng/kg body weight]). For comparison, rabbits percutaneously received locally autologous bone marrow (2 mL, postoperative day 7). As standard treatment, immediately after its formation, the bone defect was filled with an autologous cortical graft. Saline-treated (2 mL intramuscularly [i.m.] and 2 mL locally into the bone defect), injured animals were used as controls. Pentadecapeptide BPC-157 significantly improved the healing of segmental bone defects. For instance, upon radiographic assessment, the callus surface, microphotodensitometry, quantitative histomorphometry (10 microg/kg body weight i.m. for 14 days), or quantitative histomorphometry (10 ng/kg body weight i.m. for 14 days) the effect of pentadecapeptide BPC-157 was shown to correspond to improvement after local application of bone marrow or autologous cortical graft. Moreover, a comparison of the number of animals with unhealed defects (all controls) or healed defects (complete bony continuity across the defect site) showed that besides pentadecapeptide intramuscular application for 14 days (i.e., local application of bone marrow or autologous cortical graft), also following other pentadecapeptide BPC-157 regimens (local application, or intermittent intramuscular administration), the number of animals with healed defect was increased. Hopefully, in the light of the suggested stomach significance for bone homeostasis, the possible relevance of this pentadecapeptide BPC-157 effect (local or intramuscular effectiveness, lack of unwanted effects) could be a basis for methods of choice in the future management of healing impairment in humans, and requires further investigation.

Local strategies to prevent and treat osteoporosis.

PubMed

Torstrick, F Brennan; Guldberg, Robert E

2014-03-01

Despite advances in systemic osteoporosis therapeutic outcomes, management of fragility fractures and implant fixation in osteoporotic bone remain difficult clinical challenges. Low initial bone density and a prolonged healing response can lead to fracture nonunion and aseptic implant loosening. Local treatment strategies could be used to prevent fracture, accelerate healing, and increase implant fixation by locally stimulating anabolic pathways or inhibiting catabolic pathways. Local strategies under investigation include direct drug release from injectable materials or implant surface coatings. Common locally delivered drugs include bisphosphonates, parathyroid hormone, and bone morphogenetic proteins, yet additional compounds targeting novel pathways in bone biology are also being actively explored. Mechanical stimulation via low intensity pulsed ultrasound, alone or in combination with drug therapy, may also prove effective to promote local bone healing and implant fixation within osteoporotic bone.

Icariin Promotes Tendon-Bone Healing during Repair of Rotator Cuff Tears: A Biomechanical and Histological Study.

PubMed

Ye, Chenyi; Zhang, Wei; Wang, Shengdong; Jiang, Shuai; Yu, Yuanbin; Chen, Erman; Xue, Deting; Chen, Jianzhong; He, Rongxin

2016-10-25

To investigate whether the systematic administration of icariin (ICA) promotes tendon-bone healing after rotator cuff reconstruction in vivo, a total of 64 male Sprague Dawley rats were used in a rotator cuff injury model and underwent rotator cuff reconstruction (bone tunnel suture fixation). Rats from the ICA group ( n = 32) were gavage-fed daily with ICA at 0.125 mg/g, while rats in the control group ( n = 32) received saline only. Micro-computed tomography, biomechanical tests, serum ELISA (calcium; Ca, alkaline phosphatase; AP, osteocalcin; OCN) and histological examinations (Safranin O and Fast Green staining, type I, II and III collagen (Col1, Col2, and Col3), CD31, and vascular endothelial growth factor (VEGF)) were analyzed two and four weeks after surgery. In the ICA group, the serum levels of AP and OCN were higher than in the control group. More Col1-, Col2-, CD31-, and VEGF-positive cells, together with a greater degree of osteogenesis, were detected in the ICA group compared with the control group. During mechanical testing, the ICA group showed a significantly higher ultimate failure load than the control group at both two and four weeks. Our results indicate that the systematic administration of ICA could promote angiogenesis and tendon-bone healing after rotator cuff reconstruction, with superior mechanical strength compared with the controls. Treatment for rotator cuff injury using systematically-administered ICA could be a promising strategy.

Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair

PubMed Central

Reumann, Marie K.; Strachna, Olga; Yagerman, Sarah; Torrecilla, Daniel; Kim, Jihye; Doty, Steven B.; Lukashova, Lyudmila; Boskey, Adele L.; Mayer-Kuckuk, Philipp

2011-01-01

Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1−/− mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1−/− mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1−/− callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair. PMID:21726677

Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair.

PubMed

Reumann, Marie K; Strachna, Olga; Yagerman, Sarah; Torrecilla, Daniel; Kim, Jihye; Doty, Stephen B; Lukashova, Lyudmila; Boskey, Adele L; Mayer-Kuckuk, Philipp

2011-10-01

Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1(-/-) mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1(-/-) mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1(-/-) callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparison of surface modified zirconia implants with commercially available zirconium and titanium implants: a histological study in pigs.

PubMed

Gredes, Tomasz; Kubasiewicz-Ross, Pawel; Gedrange, Tomasz; Dominiak, Marzena; Kunert-Keil, Christiane

2014-08-01

New biomaterials and their various surface modifications should undergo in vitro and in vivo evaluation before clinical trials. The objective of our in vivo study was to evaluate the biocompatibility of newly created zirconium implant surfaces after implantation in the lower jaw of pigs and compare the osseointegration of these dental implants with commercially available zirconium and titanium implants. After a healing period of 12 weeks, a histological analysis of the soft and hard tissues and a histomorphometric analysis of the bone-implant contact (BIC) were performed. The implant surfaces showed an intimate connection to the adjacent bone for all tested implants. The 3 newly created zirconium implant surfaces achieved a BIC of 45% on average in comparison with a BIC of 56% from the reference zirconium implants and 35% from titanium implants. Furthermore, the new zirconium implants had a better attachment to gingival and bone tissues in the range of implant necks as compared with the reference implants. The results suggest that the new implants comparably osseointegrate within the healing period, and they have a good in vivo biocompatibility.

EFFECT OF USE OF BONE-MARROW CENTRIFUGATE ON MUSCLE INJURY TREATMENT: EXPERIMENTAL STUDY ON RABBITS

PubMed Central

Vieira, Daniel Ferreira Fernandes; Guarniero, Roberto; Vaz, Carlos Eduardo Sanches; de Santana, Paulo José

2015-01-01

Objective: The objective of this study was to evaluate the effect of bone-marrow centrifugate on the healing of muscle injuries in rabbits. Methods: This experimental study involved use of fifteen adult male New Zealand White rabbits. Each animal received a transverse lesion in the middle of the right tibialis anterior muscle, to which an absorbable collagen sponge, soaked in a centrifugate of bone marrow aspirate from the ipsilateral iliac bone, was added. The left hind limb was used as a control and underwent the same injury, but in this case only the absorbable collagen sponge. Thirty days later, the animals were sacrificed to study the muscle healing. These muscle areas were subjected to histological analysis with histomorphometry, with the aim of measuring the number of muscle cells per square micrometer undergoing regeneration and the proportion of resultant fibrosis. Results: The centrifugation method used in this study resulted in an average concentration of nucleated cells greater than the number of these cells in original aspirates, without causing significant cell destruction. Addition of the bone marrow centrifugate did not result in any significant increase in the number of muscle cells undergoing regeneration, in relation to the control group. There was also no significant difference in the proportion of resultant fibrosis, compared with the control group. Conclusion: Administration of the bone marrow centrifugate used in this study did not favor healing of muscle injuries in rabbits. PMID:27047832

Micro-CT Sections and Histological Sections of Mouse Skull Defects Implanted with Cartilage Grown in a Rotating Bioreactor

NASA Astrophysics Data System (ADS)

Duke, P. J.; Montufar-Solis, D.; Nguyen, H. C.; Cody, D. D.

2008-06-01

Using cartilage to replace/repair bone is advantageous as no scaffolding is required to form the implant which disappears as bone is formed during the endochondral process. Previously, we demonstrated that cartilage spheroids, grown in a rotating bioreactor, (Synthecon, Inc.) and implanted into a 2 mm skull defect, contributed to healing of the defect. In this report, skulls with or without implants were subjected to microCT scans, and sections from these scans were compared to histological sections of the defect region of demineralized skulls from the same experiment. The area of the defect staining for bone in histological sections of demineralized skulls was the same region shown as mineralized in CT sections. Defects without implants were shown in serial CT sections and histological sections, to be incompletely healed. This study demonstrates that microCT scans are an important corollary to histological studies evaluating the use of implants in healing of bony defects. Supported in part by NIH/NIDCR Training Grant T35 DE07252 and by Cancer Center Support Grant (CA-16672).

Can platelet-rich plasma (PRP) improve bone healing? A comparison between the theory and experimental outcomes.

PubMed

Malhotra, Angad; Pelletier, Matthew H; Yu, Yan; Walsh, William R

2013-02-01

The increased concentration of platelets within platelet-rich plasma (PRP) provides a vehicle to deliver supra-physiologic concentrations of growth factors to an injury site, possibly accelerating or otherwise improving connective tissue regeneration. This potential benefit has led to the application of PRP in several applications; however, inconsistent results have limited widespread adoption in bone healing. This review provides a core understanding of the bone healing mechanisms, and corresponds this to the factors present in PRP. In addition, the current state of the art of PRP preparation, the key aspects that may influence its effectiveness, and treatment outcomes as they relate specifically to bone defect healing are presented. Although PRP does have a sound scientific basis, its use for bone healing appears only beneficial when used in combination with osteoconductive scaffolds; however, neither allograft nor autograft appear to be appropriate carriers. Aggressive processing techniques and very high concentrations of PRP may not improve healing outcomes. Moreover, many other variables exist in PRP preparation and use that influence its efficacy; the effect of these variables should be understood when considering PRP use. This review includes the essentials of what has been established, what is currently missing in the literature, and recommendations for future directions.

Marginal Bone Remodeling around healing Abutment vs Final Abutment Placement at Second Stage Implant Surgery: A 12-month Randomized Clinical Trial.

PubMed

Nader, Nabih; Aboulhosn, Maissa; Berberi, Antoine; Manal, Cordahi; Younes, Ronald

2016-01-01

The periimplant bone level has been used as one of the criteria to assess the success of dental implants. It has been documented that the bone supporting two-piece implants undergoes resorption first following the second-stage surgery and later on further to abutment connection and delivery of the final prosthesis. The aim of this multicentric randomized clinical trial was to evaluate the crestal bone resorption around internal connection dental implants using a new surgical protocol that aims to respect the biological distance, relying on the benefit of a friction fit connection abutment (test group) compared with implants receiving conventional healing abutments at second-stage surgery (control group). A total of partially edentulous patients were consecutively treated at two private clinics, with two adjacent two-stage implants. Three months after the first surgery, one of the implants was randomly allocated to the control group and was uncovered using a healing abutment, while the other implant received a standard final abutment and was seated and tightened to 30 Ncm. At each step of the prosthetic try-in, the abutment in the test group was removed and then retightened to 30 Ncm. Horizontal bone changes were assessed using periapical radiographs immediately after implant placement and at 3 (second-stage surgery), 6, 9 and 12 months follow-up examinations. At 12 months follow-up, no implant failure was reported in both groups. In the control group, the mean periimplant bone resorption was 0.249 ± 0.362 at M3, 0.773 ± 0.413 at M6, 0.904 ± 0.36 at M9 and 1.047 ± 0.395 at M12. The test group revealed a statistically significant lower marginal bone loss of 20.88% at M3 (0.197 ± 0.262), 22.25% at M6 (0.601 ± 0.386), 24.23% at M9 (0.685 ± 0.341) and 19.2% at M9 (0.846 ± 0.454). The results revealed that bone loss increased over time, with the greatest change in bone loss occurring between 3 and 6 months. Alveolar bone loss was significantly greater in the control condition than the test condition. The results of this prospective study demonstrated the benefit of placing a prosthetic component with a stable connection at second-stage surgery, in terms of reduced marginal bone remodeling when compared with conventional procedure. The use of a stable connection in a healing component during try-in stages prior to final restoration placement leads to less periimplant marginal bone loss.

Milk thistle: a future potential anti-osteoporotic and fracture healing agent.

PubMed

Mohd Fozi, Nur Farhana; Mazlan, Mazliadiyana; Shuid, Ahmad Nazrun; Isa Naina, Mohamed

2013-12-01

Osteoporosis is a progressive disease of the skeleton characterised by bone fragility due to a reduction in bone mass and possibly to alteration in bone architecture that lead to a propensity to fracture with minimum trauma. Most osteoporotic fractures occur at locations rich in trabecular or cancellous bone and usually related to post menopausal women. Recently, silymarin received attention due to its alternative beneficial effect on bone formation. It is a mixture of flavonoids with powerful antioxidant properties. This review focuses on the use of milk thistle or silymarin for the treatment of osteoporosis that may be related to fracture bone. Silymarin shows potent antioxidant herb that may modulate multiple genes in favour of helping to build bone and prevent bone loss. In the mouse fracture healing model, silymarin supplementation improved tibial healing with elevated BMD and serum levels of ALP and osteocalcin. Silymarin also demonstrated clear estrogenic antiosteoporotic effects in bone structure. Silymarin appears to play a crucial role to prevent bone loss and might regulate osteogenesis and may be beneficial for fracture healing. If silymarin is considered for the use of post menopausal women, it may be used for the treatment of osteoporosis. It would be of great benefit to postmenopausal women to develop an oestrogen antagonist that is as potent and efficacious as oestrogen in preventing bone loss without the major side effect associated with HRT.

Effectiveness of methods for detaching orthodontic implants likely to fracture upon rotational torque – an animal study

PubMed Central

Nakagaki, Susumu; Yasuda, Yoshitaka; Handa, Keisuke; Koike, Toshiyuki; Saito, Takashi; Mizoguchi, Itaru

2016-01-01

Abstract Orthodontic implants may fracture at the cortical bone level upon rotational torque. The impacted fragment can be detached by a range of methods, which are all more or less time‐consuming and injurious to the cortical bone. The aim of this study was to compare three different methods for detaching an orthodontic implant impacted in cortical bone. Health Sciences University of Hokkaido animal ethics committee approved the study protocol. Orthodontic titanium‐alloy (Ti‐6Al‐4 V) implants were placed bilaterally on the buccal side of the mandible of beagle dogs. Subsequently, the implants were detached using either a low‐speed handpiece with a round bur, alternatively by use of a low‐power or a high‐power ultrasonic instrument. In the first experiment, 56 orthodontic implants were placed into the dissected mandible from 7 animals. The methods for detachment were compared with respect to time interval, as well as associated undesirable bone loss as appraised by use of cone‐beam computed tomography. In experiment two, 2x2 implants were placed bilaterally in the mandible of 8 animals and subsequently detached by manual rotational torque, and the described three methods for detachment. The implant socket was investigated histologically as a function of removal method immediately after removal, and after 1, 3 and 8 weeks and contrasted with the healing of the socket of the implant that was detached by manual rotational torque. Statistical significance was appraised by the use of non‐parametric Kruskal‐Wallis one‐way analysis of variance. The method using the low‐power ultrasonic required significantly longer removal time versus the two other methods, i.e. high‐power ultrasonic and low‐speed handpiece with a round bur (p < 0.02). The amount of undesirable bone loss was substantially larger with low‐speed handpiece with a round bur compared to the two ultrasonic methods (p < 0.05). Bone formation after 3 weeks of healing was more complete following the use of low or high‐power ultrasonic instrument in comparison with a low‐speed handpiece rotary instrument method. Orthodontic implants likely to fracture upon rotational torque or impacted fractured fragments should be detached preferably with an ultrasonic instrument, because of less associated bone loss and more rapid bone healing compared to the use of a low‐speed handpiece rotary instrument. PMID:29744149

Mechanistic, Mathematical Model to Predict the Dynamics of Tissue Genesis in Bone Defects via Mechanical Feedback and Mediation of Biochemical Factors

PubMed Central

Moore, Shannon R.; Saidel, Gerald M.; Knothe, Ulf; Knothe Tate, Melissa L.

2014-01-01

The link between mechanics and biology in the generation and the adaptation of bone has been well studied in context of skeletal development and fracture healing. Yet, the prediction of tissue genesis within - and the spatiotemporal healing of - postnatal defects, necessitates a quantitative evaluation of mechano-biological interactions using experimental and clinical parameters. To address this current gap in knowledge, this study aims to develop a mechanistic mathematical model of tissue genesis using bone morphogenetic protein (BMP) to represent of a class of factors that may coordinate bone healing. Specifically, we developed a mechanistic, mathematical model to predict the dynamics of tissue genesis by periosteal progenitor cells within a long bone defect surrounded by periosteum and stabilized via an intramedullary nail. The emergent material properties and mechanical environment associated with nascent tissue genesis influence the strain stimulus sensed by progenitor cells within the periosteum. Using a mechanical finite element model, periosteal surface strains are predicted as a function of emergent, nascent tissue properties. Strains are then input to a mechanistic mathematical model, where mechanical regulation of BMP-2 production mediates rates of cellular proliferation, differentiation and tissue production, to predict healing outcomes. A parametric approach enables the spatial and temporal prediction of endochondral tissue regeneration, assessed as areas of cartilage and mineralized bone, as functions of radial distance from the periosteum and time. Comparing model results to histological outcomes from two previous studies of periosteum-mediated bone regeneration in a common ovine model, it was shown that mechanistic models incorporating mechanical feedback successfully predict patterns (spatial) and trends (temporal) of bone tissue regeneration. The novel model framework presented here integrates a mechanistic feedback system based on the mechanosensitivity of periosteal progenitor cells, which allows for modeling and prediction of tissue regeneration on multiple length and time scales. Through combination of computational, physical and engineering science approaches, the model platform provides a means to test new hypotheses in silico and to elucidate conditions conducive to endogenous tissue genesis. Next generation models will serve to unravel intrinsic differences in bone genesis by endochondral and intramembranous mechanisms. PMID:24967742

Risk Factors for Injury and Cigarette Smoking and Temporal Trends in Demographic and Lifestyle Characteristics Among U.S. Army Ordinance School Students

DTIC Science & Technology

2008-07-01

took 166 ± 92 days or had a 24% slower healing time to clinical union , compared with nonsmokers at 134 ± 71 days. Possible attributes of the delayed ...1993). Are smokers a risk group for delayed healing of tibial shaft fractures . Annales Chirurgiae et Gynaeacologiae, 82:254-262. 47. Mazess R...experience stress fractures , compared with Caucasians(29), possibly because Blacks having a higher bone density(30,31).Other studies performed

Periodontal healing in one-wall intra-bony defects in dogs following implantation of autogenous bone or a coral-derived biomaterial.

PubMed

Kim, Chang-Sung; Choi, Seong-Ho; Cho, Kyoo-Sung; Chai, Jung-Kiu; Wikesjö, Ulf M E; Kim, Chong-Kwan

2005-06-01

Autogenous bone grafts and bone biomaterials are being used as part of protocols aiming at reconstruction of periodontal defects. There is a limited biologic information on the effect of such materials on periodontal healing, in particular aberrant healing events that may prevent their general use. The objective of this study was, using histological techniques, to evaluate periodontal healing with focus on root resorption and ankylosis following implantation of autogenous bone and a coral-derived biomaterial into intra-bony defects in dogs. One-wall intra-bony periodontal defects were surgically created at the distal aspect of the second and the mesial aspect of the fourth mandibular premolars in either right or left jaw quadrants in four Beagle dogs. Each animal received particulated autogenous bone and the resorbable calcium carbonate biomaterial into discrete one-wall intra-bony defects. The mucoperiosteal flaps were positioned and sutured to their pre-surgery position. The animals were euthanized 8 weeks post-surgery when block sections of the defect sites were collected and prepared for qualitative histological analysis. There were no significant differences in periodontal healing between sites receiving autograft bone and the coral-derived biomaterial. A well-organized periodontal ligament bridging new bone and cementum regeneration was observed extending coronal to a notch prepared to delineate the apical extent of the defect. Osteoid and bone with enclosed osteocytes were formed onto the surface of both autograft and coral particles. Although small resorption pits were evident in most teeth, importantly none of the biomaterials provoked marked root resorption. Ankylosis was not observed. Particulated autogenous bone and the coral-derived biomaterial may be implanted into periodontal defects without significant healing aberrations such as root resorption and ankylosis. The histopathological evaluation suggests that the autogenous bone graft has a limited osteogenic potential as demonstrated in this study model.

Hydroxyapatite paste Ostim, without elevation of full-thickness flaps, improves alveolar healing stimulating BMP- and VEGF-mediated signal pathways: an experimental study in humans.

PubMed

Canuto, R A; Pol, R; Martinasso, G; Muzio, G; Gallesio, G; Mozzati, M

2013-08-01

Tooth extraction is considered as the starting point of jaw atrophy via osteoclast activity stimulation. The maintenance of dental alveolar bone depends on surgery procedure and use of materials to maintain prior space favoring bone regeneration. Among substitutes used in dentistry to fill bone defects, Ostim-Pastes (Ostim) is a nanocrystalline paste tested for treatment of severe clinical conditions. This research first investigated the effect of Ostim on alveolar healing, comparing in the same healthy subjects, an Ostim-filled socket with a not-filled one. Moreover, it also proposed a new surgical protocol for the post-extractive socket treatment using the graft materials without elevation of full-thickness flaps. Fourteen patients were enrolled to bilateral maxillary or mandibular extraction that was performed without elevation of full-thickness flaps. In each patient, one socket was filled using Ostim, and the other one was allowed to undergo natural healing. No suture was carried out. Clinical and biologic parameters were screened at 1, 7, and 14 days. Obtained results evidenced that nanocrystalline hydroxyapatite supports bone regeneration, increasing the synthesis of pro-osteogenic factors as bone morphogenetics protein (BMP)-4, BMP-7, alkaline phosphatase, and osteocalcin. Moreover, filling post-extractive socket with nanocrystalline hydroxyapatite paste leads to a complete epithelialization already at 7 days after extraction, despite the fact that the teeth were extracted without elevation of full-thickness flaps . The improved epithelialization is mediated by increased vascular endothelial growth factor (VEGF) expression. No significant change was observed in inflammatory parameters, with exception of an early and transient IL-1β induction, that could trigger and improve alveolar healing. Clinical and biomolecular observations of this explorative study evidenced that nanocrystalline hydroxyapatite improves alveolar socket healing, increasing angiogenesis, epithelialization, and osteogenesis, also in absence of elevation of full-thickness flaps. © 2011 John Wiley & Sons A/S.

PTH 1-34 Ameliorates the Osteopenia and Delayed Healing of Stabilized Tibia Fracture in Mice with Achondroplasia Resulting from Gain-Of-Function Mutation of FGFR3

PubMed Central

Chen, Hangang; Sun, Xianding; Yin, Liangjun; Chen, Shuai; Zhu, Ying; Huang, Junlan; Jiang, Wanling; Chen, Bo; Zhang, Ruobin; Chen, Lin; Nie, Mao; Xie, Yangli; Deng, Zhongliang

2017-01-01

Bone fracture healing is processed through multiple stages including the cartilaginous callus formation and its transition to bony callus. FGFR3 negatively regulates chondrogenesis and enhances osteogenesis during skeleton development. We previously found in mice carrying gain-of-function mutation of FGFR3 that FGFR3 delays the healing of un-stabilized fracture that heals mainly through endochondral ossification. Since fracture is regularly treated in clinics with rigid fixation, and stabilized fracture is healed largely through intramembranous ossification, we asked whether FGFR3, a key regulator of osteogenesis, also affect the regeneration of stabilized fracture. We found that gain-of-function mutation of FGFR3 inhibits the initiation of chondrogenesis and the subsequent bone formation. We further studied whether PTH1-34 can improve the osteopenia and delayed healing of the stabilized tibia fracture in mice with achondroplasia. Fracture healing was evaluated by radiography, micro-CT, biomechanical tests, histology, and real-time polymerase chain reaction (RT-PCR) analysis. We found that PTH 1-34 can alleviate the decreased bone mass and compromised architecture in ACH mice. Histological analysis revealed that administration of PTH1-34 increased the size of both the total callus and cartilaginous callus at 14 days after the surgery in ACH mice. RT-PCR data suggested that systemic PTH1-34 accelerated the initiation of chondrogenesis and chondrocyte maturation (earlier and higher levels of expression of chondrogenesis related markers) and enhanced the osteogenic differentiation in the fracture callus in ACH mice. These results indicate that the PTH1-34 administration resulted in an enhanced callus formation during bone fracture healing in ACH mice, which is at least in part mediated by an increase of cartilaginous callus at early stage and the promotion of bone formation in bony callus. In summary, in this study we revealed that FGFR3 delays the regeneration of stabilized fracture by inhibiting both the chondrogenesis and osteogenesis, and PTH1-34 treatment can improve the dysregulated bone metabolism and delayed bone injury healing resulting from gain-of-function mutation of FGFR3. PMID:29104492

The effect of mesenchymal stem cell sheets on structural allograft healing of critical-sized femoral defects in mice

PubMed Central

Long, Teng; Zhu, Zhenan; Awad, Hani A.; Schwarz, Edward M.; Hilton, Matthew J.; Dong, Yufeng

2014-01-01

Structural bone allografts are widely used in the clinic to treat critical sized bone defects, despite lacking the osteoinductive characteristics of live autografts. To address this, we generated revitalized structural allografts wrapped with mesenchymal stem/progenitor cell (MSC) sheets, which were produced by expanding primary syngenic bone marrow derived cells on temperature-responsive plates, as a tissue engineered periosteum. In vitro assays demonstrated maintenance of the MSC phenotype in the sheets, suggesting that short-term culturing of MSC sheets is not detrimental. To test their efficacy in vivo, allografts wrapped with MSC sheets were transplanted into 4-mm murine femoral defects and compared to allografts with direct seeding of MSCs and allografts without cells. Evaluations consisted of x-ray plain radiography, 3D microCT, histology, and biomechanical testing at 4- and 6-weeks post-surgery. Our findings demonstrate that MSC sheets induce prolonged cartilage formation at the graft-host junction and enhanced bone callus formation, as well as graft-host osteointegration. Moreover, a large periosteal callus was observed spanning the allografts with MSC sheets, which partially mimics live autograft healing. Finally, biomechanical testing showed a significant increase in the structural and functional properties of MSC sheet grafted femurs. Taken together, MSC sheets exhibit enhanced osteogenicity during critical sized bone defect repair, demonstrating the feasibility of this tissue engineering solution for massive allograft healing. PMID:24393269

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

Is a synthetic augmentation in medial open wedge high tibial osteotomies superior to no augmentation in terms of bone-healing?

PubMed

Ferner, Felix; Dickschas, Joerg; Ostertag, Helmut; Poske, Ulrich; Schwitulla, Judith; Harrer, Joerg; Strecker, Wolf

2016-01-01

Medial open-wedge high tibial osteotomy (MOWHTO) is an established method to treat unicompartimental osteoarthritis of the knee joint. However, augmentation of the created tibial gap after osteotomy is controversially discussed. We performed a prospective investigation of 49 consecutive cases of MOWHTO at our department. Patients were divided into two groups: group A consisted of 19 patients while group B consisted of 30 patients. In group A, the augmentation of the opening gap after osteotomy was filled with a synthetic bone graft, whereas group B received no augmentation. As an indicator for bone healing we investigated the non-union rate in our study population and compared the non-union-rate between the two groups. The non-union rate was 28% in group A (five of 19 patients had to undergo revision) which received synthetic augmentation, while it was 3.3% in group B (one of 30 patients had to undergo revision) which received no augmentation. The difference between the groups was statistically significant (p-value 0.027). With regard to bone healing after MOWHTO, synthetic augmentation was not superior to no augmentation in terms of non-union rates after surgery. In fact, we registered a significantly higher rate of non-union after augmentation with synthetic bone graft. III. Copyright © 2015 Elsevier B.V. All rights reserved.

Ovariectomy-induced osteopenia influences the middle and late periods of bone healing in a mouse femoral osteotomy model.

PubMed

Pang, Jian; Ye, Meina; Cao, Yuelong; Zheng, Yuxin; Guo, Hailing; Zhao, Yongfang; Zhan, Hongsheng; Shi, Yinyu

2014-10-09

Objective It is known that bone healing was delayed in the presence of osteoporosis in humans. However, due to the complexities of the healing of osteoporotic fractures, animal models may be more appropriate to study the effects of osteoporosis in more details and to test drugs on the fracture repair process. The purpose of this study was to investigate the influence of ovariectomy-induced osteopenia in bone healing in an open femoral osteotomy model, and to test the feasibility of this model for evaluating the healing process under osteopenic conditions. Methods In assessing the effects of osteopenia on fracture healing, ovariectomized mouse models were employed. A mid-shaft femur osteotomy model was also established 3 weeks after ovariectomy as an osteopenic fracture group (OVX group). Femurs were then harvested at 2 weeks and 6 weeks after fracture for X-ray radiography, micro-computed tomography (micro-CT), histology and biomechanical analysis. A sham-operated group (Sham group) was used for comparison. Results The OVX mice had significantly lower BVF, vBMD and TMD in the fracture calluses at 6 weeks (P < 0.05), and similar trend was observed in 2 weeks. Additionally, larger calluses in OVX animals were observed via micro-CT and X-ray, but these did not result in better healing outcomes as determined by biomechanical test at 6 weeks. Histological images of the healing fractures in the OVX mice found forward of broken end resorption and delay of hard callus remodeling. The impaired biomechanical measurements in the OVX group (P < 0.05) were consistent with micro-CT measurements and radiographic scoring, which also indicated delay in fracture healing of the OVX group. Conclusions This study provided evidences that ovariectomy-induced osteopenia impair the middle and late bone healing process once more. These data also supported the validity of the mouse femoral osteotomy model in evaluating the process of bone healing under osteopenic conditions.

Maxillary post-traumatic outcome correction literature review and our experience. Part I: maxillary bone non-unions-"poor bone positioning".

PubMed

D'Agostino, A; Toffanetti, G; Scala, R; Trevisiol, L; Ferrari, F

2004-04-01

Still today, there is no classification of non-unions in maxillofacial traumatology. There is a broad spectrum of definitions that simultaneously describe the pathological conditions and functional implications determined by the anatomical location of the fractures and the time factor. In this article the authors describe a literature review about bone non-union classification. Weber, in 1973, introduced the term "pseudo-arthrosis" to describe an altered process of bone healing characterised by the presence of fibrous tissue interposed between the fracture segments, that was lined with cartilaginous tissue and joined by a capsule; Spiessl, in 1988, used the term "non-union" to define any alteration of the bone healing process after a time period of more than 6 months from the initial traumatic event; Rosen, in 1990, proposed a new classification of the modes of altered bone healing in fractures, distinguishing 5 categories: delayed consolidation, non-union, non-union vascular, non union avascular, pseudoarthrosis. The authors also talk about "poor bone positioning". This factor describes the incorrect anatomical position of the bone fragments despite perfectly normal healing according to Gruss. In this article they also discuss about the treatment of non-unions and the treatment of occlusal alterations caused by poor post-traumatic bone positioning.

Clinical assessment of bone quality of human extraction sockets after conversion with growth factors.

PubMed

Ntounis, Athanasios; Geurs, Nico; Vassilopoulos, Philip; Reddy, Michael

2015-01-01

The study was conducted to evaluate the effect of mineralized freeze-dried bone allograft (FDBA), alone or in combination with growth factors in extraction sockets, on subjective assessment of bone quality during implant placement. Forty-one patients whose treatment plan involved extraction of anterior or premolar teeth were randomized into four groups: Group 1, collagen plug (control); Group 2, FDBA/β-tricalcium phosphate (β-TCP)/collagen plug; Group 3, FDBA/β-TCP/platelet-rich plasma (PRP)/collagen plug; Group 4, FDBA/β-TCP/recombinant human platelet-derived growth factor BB (rhPDGF-BB)/collagen plug. After 8 weeks of healing, implants were placed. The clinicians assessed bone quality according to the Misch classification. A benchtop calibration exercise test was conducted to evaluate agreement and accuracy of operators in recognizing different bone qualities. Differences were analyzed using one-way analysis of variance (ANOVA) or chi-square tests for continuous and categorical data. Pairwise comparisons were tested using least squares means (LS means). Spearman correlation coefficients were used to evaluate the relationship of bone growth with potential confounders. P < .05 was considered statistically significant. A simple (not weighted) kappa statistic was used to assess the agreement between raters. To assess accuracy in identifying bone quality, a chi-square test was used to compare the percent correct for each rater. The benchtop calibration exercise test demonstrated agreement among clinicians (0.75 and 0.92 between raters 1 and 2 and raters 1 and 3, respectively). Raters were more likely to identify the correct bone quality (P > .05). Inclusion of bone grafting is associated with a shift from D4 quality to D3 quality bone. Inclusion of PRP in bone grafting eliminates the incidence of D4 bone, establishing D3 and D2 quality bone as prevalent (56% vs. 42%, respectively). Inclusion of rhPDGF-BB and β-TCP in combination with the bone grafting has the same effect, although D2 quality is less prevalent. When compared to sockets grafted with FDBA/β-TCP/collagen plug alone, the sockets with growth factors demonstrated fewer residual bone graft particles. (1) Inclusion of bone grafting enhanced bone quality as assessed during implant placement. (2) Overall inclusion of PRP and rhPDGF-BB enhanced subjective bone quality, eliminating incidence of D4 quality in human extraction sockets. (3) The use of PRP or rhPDGF-BB may enhance healing within extraction sockets and decrease the healing time prior to dental implant placement.

Evaluation of osteoblastic activity in extraction sockets treated with platelet-rich fibrin

PubMed Central

Tumer, Celal; Ugur, Omer; Vatankulu, Betul

2015-01-01

Objective: The aim of this study was to determine whether the use of platelet rich fibrin (PRF) improved the healing of extraction sockets. Study Design: A total of 20 patients with bilateral soft tissue impacted mandibular third molars were included in this study. The left and right third molars were extracted during the same session. Subsequently, the PRF membrane was randomly administered to one of the extraction sockets, whereas the contra lateral sockets were left without treatment. On postoperative 30. and 90. days, panoramic images and bone scintigrams were taken to evaluate the bone healing between PRF-treated and non-PRF-treated sockets. Also, periodontal evaluation was performed in the same control sessions. Dependent group t test for paired samples was used for statistical analysis. Results: The average increase in technetium-99m methylene diphosphonate uptake as an indication of enhanced bone healing did not differ significantly between PRF-treated and non-PRF-treated sockets 30 and 90 days post operatively. Radio opacity that can show the bone healing on panoramic images were measured by Image J programmer and they did not differ significantly. Also periodontal values did not differ significantly. Conclusions: PRF might not lead to enhanced bone healing in impacted mandibular third molar extraction sockets 30 and 90 days after surgery. It is thought that PRF has the potential characteristics of an autologous fibrin matrix and can accelerate the healing. To better understand the effects of PRF on healing, further research is warranted with larger sample sizes. Key words:PRF, scintigraphy, healing, extraction sockets. PMID:25475771

A study of 23 unicameral bone cysts of the calcaneus: open chip allogeneic bone graft versus percutaneous injection of bone powder with autogenous bone marrow.

PubMed

Park, Il-Hyung; Micic, Ivan Dragoljub; Jeon, In-Ho

2008-02-01

The treatment of unicameral bone cyst varies from percutaneous needle biopsy, aspiration and local injection of steroid, autologous bone marrow, or demineralized bone matrix to curettage and open bone-grafting. The purpose of this study was to compare the results of open chip allogeneic bone graft versus percutaneous injection of demineralized bone powder with autogenous bone marrow in management of calcaneal cysts. Twenty-three calcaneal unicameral cysts in 20 patients were treated. Lyophilized irradiated chip allogeneic bone (CAB) and autogenous bone marrow were used for treatment of 13 cysts in 11 patients, and 10 cysts in 9 patients were treated with percutaneous injection of irradiated allogeneic demineralized bone powder (DBP) and autogenous bone marrow. There were 11 males and 9 female patients with mean age of 17 years. The patients were followed for an average of 49.4 months. Complete healing was achieved in 9 cysts treated with chip allogeneic bone and in 5 cysts treated with powdered bone. Four cysts treated with CAB and 3 cysts treated with DBP healed with a defect. Two cysts treated with powdered bone and autogenous bone marrow were classified as persistent. No infections or pathological fractures were observed during the followup period. Percutaneous injection of a mixture of allogeneic bone powder with autogenous bone marrow is a minimal invasive method and could be an effective alternative in the treatment of unicameral calcaneal bone cysts. The postoperative morbidity was low, the hospital stay was brief, and patient's comfort for unrestricted activity was enhanced.

Strontium-Doped Calcium Phosphate and Hydroxyapatite Granules Promote Different Inflammatory and Bone Remodelling Responses in Normal and Ovariectomised Rats

PubMed Central

Xia, Wei; Emanuelsson, Lena; Norlindh, Birgitta; Omar, Omar; Thomsen, Peter

2013-01-01

The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-α (TNF-α), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone. PMID:24376855

Sequential healing of open extraction sockets. An experimental study in monkeys.

PubMed

Scala, Alessandro; Lang, Niklaus P; Schweikert, Michael T; de Oliveira, José Américo; Rangel-Garcia, Idelmo; Botticelli, Daniele

2014-03-01

To describe the sequential healing of open extraction sockets at which no attempts to obtain a primary closure of the coronal access to the alveolus have been made. The third mandibular premolar was extracted bilaterally in 12 monkeys, and no sutures were applied to close the wound. The healing after 4, 10, 20, 30, 90 and 180 days was morphometrically studied. After 4 days of healing, a blood clot mainly occupied the extraction sockets, with the presence of an inflammatory cells' infiltrate. A void was confined in the central zones of the coronal and middle regions, in continuity with the entrance of the alveoli. At 10 days, the alveolus was occupied by a provisional matrix, with new bone formation lining the socket bony walls. At 20 days, the amount of woven bone was sensibly increasing. At 30 days, the alveolar socket was mainly occupied by mineralized immature bone at different stages of healing. At 90 and 180 days, the amount of mineralized bone decreased and substituted by trabecular bone and bone marrow. Bundle bone decreased from 95.5% at 4 days to 7.6% at 180 days, of the whole length of the inner alveolar surface. Modeling processes start from the lateral and apical walls of the alveolus, leading to the closure of the socket with newly formed bone within a month from extraction. Remodeling processes will follow the previous stages, resulting in trabecular and bone marrow formation and in a corticalization of the socket access. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

The biomechanical behavior on the interface of tumor arthrosis/allograft prosthetic composite by finite element analysis

NASA Astrophysics Data System (ADS)

Chen, H. Z.; Jiang, W.; Zou, W.; Luo, J. M.; Chen, J. Y.; Tu, C. Q.; Xing, B. B.; Gu, Z. W.; Zhang, X. D.

2008-11-01

The biomechanical behavior of the uniting interface between the allograft bone and the autogenetic bone plays an important role in the treatment of the proximal femur massive defects with artificial tumor arthrosis/allograft prosthetic composite (TAAPC). According to the CT data of a patient, a 3D medical treatment model of TAAPC was established. Under the loads of 1.5 and 2.5 times standard body weight (70 kg), the mechanical behavior of the treatment model was analyzed by finite element analysis (FEA) for three typical healing periods. The results show that there are significant differences in the stress values and distribution in different healing periods. With healing of osteotomy, the hardness of the tissue of the uniting interface increases, the stress in uniting area was increased greatly and the stress concentration decreased. After cured the stress almost reached the level of normal bone. In the initial stage of healing, the healing training is not encouraged because there is an obvious risk of fracture of prosthesis and bone cement. In addition, porous hydroxyapatite (HA) ceramic used as bone tissue scaffold for this case, not only facilitates the generation of new bone, but also can avoid this risk caused by the non-uniting interface.

Dissolution behavior and early bone apposition of calcium phosphate-coated machined implants

PubMed Central

Hwang, Ji-Wan; Lee, Eun-Ung; Lee, Jung-Seok; Jung, Ui-Won; Lee, In-Seop

2013-01-01

Purpose Calcium phosphate (CaP)-coated implants promote osseointegration and survival rate. The aim of this study was to (1) analyze the dissolution behavior of the residual CaP particles of removed implants and (2) evaluate bone apposition of CaP-coated machined surface implants at the early healing phase. Methods Mandibular premolars were extracted from five dogs. After eight weeks, the implants were placed according to drilling protocols: a nonmobile implant (NI) group and rotational implant (RI) group. For CaP dissolution behavior analysis, 8 implants were removed after 0, 1, 2, and 4 weeks. The surface morphology and deposition of the coatings were observed. For bone apposition analysis, block sections were obtained after 1-, 2-, and 4-week healing periods and the specimens were analyzed. Results Calcium and phosphorus were detected in the implants that were removed immediately after insertion, and the other implants were composed mainly of titanium. There were no notable differences between the NI and RI groups in terms of the healing process. The bone-to-implant contact and bone density in the RI group showed a remarkable increase after 2 weeks of healing. Conclusions It can be speculated that the CaP coating dissolves early in the healing phase and chemically induces early bone formation regardless of the primary stability. PMID:24455442

Histomorphometric evaluation of a calcium-phosphosilicate putty bone substitute in extraction sockets.

PubMed

Kotsakis, Georgios A; Joachim, Frederic P C; Saroff, Stephen A; Mahesh, Lanka; Prasad, Hari; Rohrer, Michael D

2014-01-01

The objective of this study was to evaluate bone regeneration in 24 sockets grafted with a calcium phosphosilicate putty alloplastic bone substitute. A core was obtained from 17 sockets prior to implant placement for histomorphometry at 5 to 6 months postextraction. Radiographic analysis during the same postextraction healing period showed radiopaque tissue in all sockets. Histomorphometric analysis revealed a mean vital bone content of 31.76% (± 14.20%) and residual graft content of 11.47% (± 8.99%) after a mean healing period of 5.7 months. The high percentage of vital bone in the healed sites in combination with its timely absorption rate suggest that calcium phosphosilicate putty can be a reliable choice for osseous regeneration in extraction sockets.

Biomechanical assessment of composite versus metallic intramedullary nailing system in femoral shaft fractures: A finite element study.

PubMed

Samiezadeh, Saeid; Tavakkoli Avval, Pouria; Fawaz, Zouheir; Bougherara, Habiba

2014-08-01

Intramedullary nails are the primary choice for treating long bone fractures. However, complications following nail surgery including non-union, delayed union, and fracture of the bone or the implant still exist. Reducing nail stiffness while still maintaining sufficient stability seems to be the ideal solution to overcome the abovementioned complications. In this study, a new hybrid concept for nails made of carbon fibers/flax/epoxy was developed in order to reduce stress shielding. The mechanical performance of this new implant in terms of fracture stability and load sharing was assessed using a comprehensive non-linear FE model. This model considers several mechanical factors in nine fracture configurations at immediately post-operative, and in the healed bone stages. Post-operative results showed that the hybrid composite nail increases the average normal force at the fracture site by 319.23N (P<0.05), and the mean stress in the vicinity of fracture by 2.11MPa (P<0.05) at 45% gait cycle, while only 0.33mm and 0.39mm (P<0.05) increases in the fracture opening and the fragments' shear movement were observed. The healed bone results revealed that implantation of the titanium nail caused 20.2% reduction in bone stiffness, while the composite nail lowered the stiffness by 11.8% as compared to an intact femur. Our results suggest that the composite nail can provide a preferred mechanical environment for healing, particularly in transverse shaft fractures. This may help bioengineers better understand the biomechanics of fracture healing, and aid in the design of effective implants. Copyright © 2014. Published by Elsevier Ltd.

Studies on focal alveolar bone healing with technetium (Tc)-99m labeled methylene diphosphonate and gold-collimated cadmium telluride probe

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

Tsuchimochi, M.; Hosain, F.; Engelke, W.

1991-01-01

The benefit of using a collimator for a miniaturized cadmium telluride probe was evaluated by monitoring the bone-healing processes for 13 weeks after the induction of small iatrogenic alveolar bone lesions in one side of the mandible in beagles. Technetium (Tc)-99m labeled methylene diphosphonate (200 to 300 MBq, 5.1 to 8.1 mCi, in a solution of 0.5 to 1 ml, intravenously) was used as a bone-seeking radiopharmaceutical. The radioactivity over the bone lesion (L) and the contralateral normal site (C) in the mandible were measured between 1.5 and 2 hours after injection of the tracer, and the activity ratio L/Cmore » served as an index of relative bone uptake. A study of six dogs revealed that the healing response to a hemispheric bone defect of 2 mm diameter in the cortical bone could not be detected by an uncollimated probe, and in a repeated study in two dogs the use of a gold collimator (5 mm in diameter, 5 mm in length) did not increase the L/C ratio significantly. A second study in six dogs with 5 mm lesions showed that although systematic trends in the time courses of the L/C ratio obtained both with and without the collimator could be demonstrated, the L/C ratio of collimated versus uncollimated measurements was significantly (p less than 0.005) increased. In three of the latter six dogs, abscesses developed after 9 weeks, leading to a second increase (p less than 0.05) of the L/C ratio with collimation compared with the noninflammation group; without collimation no significant (p greater than 0.15) difference between the two groups could be demonstrated.« less

Novel bone substitute material in alveolar bone healing following tooth extraction: an experimental study in sheep.

PubMed

Liu, Jinyi; Schmidlin, Patrick R; Philipp, Alexander; Hild, Nora; Tawse-Smith, Andrew; Duncan, Warwick

2016-07-01

Electrospun cotton wool-like nanocomposite (ECWN) is a novel synthetic bone substitute that incorporates amorphous calcium phosphate nanoparticles into a biodegradable synthetic copolymer poly(lactide-co-glycolide). The objectives of this study were to develop a tooth extraction socket model in sheep for bone graft research and to compare ECWN and bovine-derived xenograft (BX) in this model. Sixteen cross-bred female sheep were used. Bilateral mandibular premolars were extracted atraumatically. Second and third premolar sockets were filled (Latin-square allocation) with BX, ECWN or left unfilled. Resorbable collagen membranes were placed over BX and selected ECWN grafted sockets. Eight sheep per time period were sacrificed after 8 and 16 weeks. Resin-embedded undemineralised sections were analysed for descriptive histology and histomorphometric analyses. At 8 weeks, there were with no distinct differences in healing among the different sites. At 16 weeks, osseous healing followed a fine trabecular pattern in ECWN sites. Non-grafted sites showed thick trabeculae separated by large areas of fibrovascular connective tissue. In BX grafted sites, xenograft particles were surrounded by newly formed bone or fibrovascular connective tissue. There were no statistically significant differences in bone formation across the four groups. However, ECWN sites had significantly less residual graft material than BX sites at 16 weeks (P = 0.048). This first description of a tooth extraction socket model in sheep supports the utility of this model for bone graft research. The results of this study suggested that the novel material ECWN did not impede bone ingrowth into sockets and showed evidence of material resorption. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of bone healing in femurs lengthened via the gradual distraction method.

PubMed

Jochymek, Jiri; Gal, Petr

2007-06-01

Treatment of leg length inequality via lengthening of the shorter extremity is an infrequent orthopedic procedure due to the requirement of special distraction devices and possible serious complications. Essential qualitative changes in operative technique development are associated with the name of G. A. Ilizarov, who paved the way for the autoregenerate gradual distraction method in the 1950s. In the years 1990 through 2006 a total of 57 patients underwent femur lengthening via gradual distraction using various types of external fixators at the Department of Pediatric Surgery, Orthopedics, and Traumatology, Faculty Hospital in Brno. The quality of bone healing was monitored and a number of parameters followed and statistically evaluated using regularly scheduled X-ray examinations. In 11 cases we had to remove the external fixator following the distraction phase, perform an osteosynthesis via a splint and fill the distraction gap via spongioplasty. The bone healing was satisfactory in the remaining 46 patients and the lengthened bone required no other fixation method. The analysis showed statistically significant deceleration in bone healing following distraction in female patients over 12 years of age, and in boys over 14 years of age. Lack of periosteal callus five weeks after surgery always signified serious problems in further healing. Severe complications were recorded in 11 cases during the distraction phase, and in 9 cases after the removal of the distraction apparatus. The aim of this report was to present the results of our study of distraction gap bone healing using the gradual lengthening approach.

Alveolar bone regeneration for immediate implant placement using an injectable bone substitute: an experimental study in dogs.

PubMed

Boix, Damien; Gauthier, Olivier; Guicheux, Jérôme; Pilet, Paul; Weiss, Pierre; Grimandi, Gaël; Daculsi, Guy

2004-05-01

The aim of the present study was to assess the efficacy of a ready-to-use injectable bone substitute for bone regeneration around dental implants placed into fresh extraction sockets. Third and fourth mandibular premolars were extracted from three beagle dogs and the interradicular septa were surgically reduced to induce a mesial bone defect. Thereafter, titanium implants were immediately placed. On the left side of the jaw, mesial bone defects were filled with an injectable bone substitute (IBS), obtained by combining a polymer and biphasic calcium phosphate ceramic granules. The right defects were left unfilled as controls. After 3 months of healing, specimens were prepared for histological and histomorphometric evaluations. No post-surgical complications were observed during the healing period. In all experimental conditions, histological observations revealed a lamellar bone formation in contact with the implant. Histomorphometric analysis showed that IBS triggers a significant (P<0.05) increase in terms of the number of threads in contact with bone, bone-to-implant contact, and peri-implant bone density of approximately 8.6%, 11.0%, and 14.7%, respectively. In addition, no significant difference was observed when number of threads, bone-to-implant contact, and bone density in the filled defects were compared to the no-defect sites. It is concluded that an injectable bone substitute composed of a polymeric carrier and calcium phosphate significantly increases bone regeneration around immediately placed implants.

Evaluation of osteoblastic activity in extraction sockets treated with platelet-rich fibrin.

PubMed

Baslarli, Ozgur; Tumer, Celal; Ugur, Omer; Vatankulu, Betul

2015-01-01

The aim of this study was to determine whether the use of platelet rich fibrin (PRF) improved the healing of extraction sockets. A total of 20 patients with bilateral soft tissue impacted mandibular third molars were included in this study. The left and right third molars were extracted during the same session. Subsequently, the PRF membrane was randomly administered to one of the extraction sockets, whereas the contralateral sockets were left without treatment. On postoperative 30. and 90. days, panoramic images and bone scintigrams were taken to evaluate the bone healing between PRF-treated and non-PRF-treated sockets. Also, periodontal evaluation was performed in the same control sessions. Dependent group t test for paired samples was used for statistical analysis. The average increase in technetium-99m methylene diphosphonate uptake as an indication of enhanced bone healing did not differ significantly between PRF-treated and non-PRF-treated sockets 30 and 90 days postoperatively. Radio-opacity that can show the bone healing on panoramic images were measured by Image J programme and they did not differ significantly. Also periodontal values did not differ significantly. PRF might not lead to enhanced bone healing in impacted mandibular third molar extraction sockets 30 and 90 days after surgery. It is thought that PRF has the potential characteristics of an autologous fibrin matrix and can accelerate the healing. To better understand the effects of PRF on healing, further research is warranted with larger sample sizes.

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.

Effect of PDGF-BB and beta-tricalcium phosphate (β-TCP) on bone formation around dental implants: a pilot study in sheep.

PubMed

Choo, Tina; Marino, Victor; Bartold, P Mark

2013-02-01

The aim of this investigation was to examine the effect of a combination of purified recombinant human platelet-derived growth factor (rhPDGF-BB) mixed with a synthetic beta-tricalcium phosphate (β-TCP) on bone healing around dental implants with critical size circumferential defects. Three critical size circumferential defects were prepared in the ilium of six sheep. Three dental implants were placed into the centre of each defect and the 3.25 mm circumferential gap was filled with (a) blood clot alone; (b) β-TCP; (c) rhPDGF-BB (0.3 mg/ml) with β-TCP. All the defects in each group were covered with a Bio-Gide(®) resorbable barrier membrane. The sheep were sacrificed at 2 and 4 weeks and histological and histomorphometric analyses were performed to determine the percentage of new mineralized bone formation and residual β-TCP graft particles in the defects. Defects filled with rhPDGF-BB/β-TCP showed the highest rate of bone formation after 2 and 4 weeks with limited degradation of the β-TCP particles over 4 weeks. Defects filled with β-TCP showed the least bone fill after 2 and 4 weeks, and faster degradation of the β-TCP particles over 4 weeks compared with defects filled with rhPDGF-BB/β-TCP. Percentage of new mineralized bone was comparable in defects to blood clot alone and β-TCP after 4 weeks of healing, but there was a collapse in the defect area in defects with blood clot alone. In comparison, the space was maintained when β-TCP was used in defects at 4 weeks. Defects which had β-TCP alone showed an inhibition in bone healing at 2 and 4 weeks; however, the combination of rhPDGF-BB with β-TCP enhanced bone regeneration in these peri-implant bone defects at the same time intervals. © 2011 John Wiley & Sons A/S.

Finite element analysis of a bone healing model: 1-year follow-up after internal fixation surgery for femoral fracture.

PubMed

Jiang-Jun, Zhou; Min, Zhao; Ya-Bo, Yan; Wei, Lei; Ren-Fa, Lv; Zhi-Yu, Zhu; Rong-Jian, Chen; Wei-Tao, Yu; Cheng-Fei, Du

2014-03-01

Finite element analysis was used to compare preoperative and postoperative stress distribution of a bone healing model of femur fracture, to identify whether broken ends of fractured bone would break or not after fixation dislodgement one year after intramedullary nailing. Method s: Using fast, personalized imaging, bone healing models of femur fracture were constructed based on data from multi-slice spiral computed tomography using Mimics, Geomagic Studio, and Abaqus software packages. The intramedullary pin was removed by Boolean operations before fixation was dislodged. Loads were applied on each model to simulate a person standing on one leg. The von Mises stress distribution, maximum stress, and its location was observed. Results : According to 10 kinds of display groups based on material assignment, the nodes of maximum and minimum von Mises stress were the same before and after dislodgement, and all nodes of maximum von Mises stress were outside the fracture line. The maximum von Mises stress node was situated at the bottom quarter of the femur. The von Mises stress distribution was identical before and after surgery. Conclusion : Fast, personalized model establishment can simulate fixation dislodgement before operation, and personalized finite element analysis was performed to successfully predict whether nail dislodgement would disrupt femur fracture or not.

Topical combined application of dexamethasone, vitamin C, and β-sodium glycerophosphate for healing the extraction socket in rabbits.

PubMed

Chen, J; He, Y; Shan, C; Pan, Q; Li, M; Xia, D

2015-10-01

An osteogenic inducer (OI) consisting of dexamethasone, vitamin C, and β-sodium glycerophosphate has the capacity to induce bone formation in vitro. The aim of this study was to assess the efficacy of the application of this OI on extraction socket healing. The bilateral first mandibular premolars were extracted from 75 New Zealand rabbits. Gelatin sponges carrying OI were implanted into the sockets. Sockets undergoing implantation of gelatin sponges alone were also evaluated, as well as non-implantation sockets. Specimens from each group were evaluated radiographically, histologically, and histomorphometrically using haematoxylin-eosin staining. Results showed earlier new bone formation and higher bone quality and quantity in the OI group compared to the other groups, and the differences were significant at 2, 4, 8, and 12 weeks postoperative. The OI significantly reduced the absorption of alveolar bone in terms of height; however, changes in the width were not significantly different between the three groups (P>0.05). The OI was shown to have a positive effect on healing of the tooth extraction sockets, was inexpensive, and was convenient to use during the operational procedure; therefore this could represent a promising implant material for human clinical application. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Present status and future potential of enhancing bone healing using nanotechnology.

PubMed

Stylios, George; Wan, Taoyu; Giannoudis, Peter

2007-03-01

An overview of the current state of tissue engineering material systems used in bone healing is presented. A variety of fabrication processes have been developed that have resulted in porous implant substrates that can address unresolved clinical problems. The merits of these biomaterial systems are evaluated in the context of the mechanical properties and biomedical performances most suitable for bone healing. An optimal scaffold for bone tissue engineering applications should be biocompatible and act as a 3D template for in vitro and in vivo bone growth; in addition, its degradation products should be non-toxic and easily excreted by the body. To achieve these features, scaffolds must consist of an interconnected porous network of micro- and nanoscale to allow extensive body fluid transport through the pores, which will trigger bone ingrowth, cell migration, tissue ingrowth, and eventually vascularization.

Effect of Electromagnetic Wave on Bone Healing in Fixed and Unfixed Conditions.

PubMed

Onger, Mehmet Emin; Göçer, Hasan; Çirakli, Alper; Büyükceran, Ismail; Kiliç, Mesut; Kaplan, Süleyman

2016-09-01

Mobile phones have come into daily life and are now one of the most frequently used devices for communication. The aim of this study was to evaluate possible effect of electromagnetic wave (EMW) with and without fixation material on bone healing.Forty male rats were exposed to fracture on tibia bone and were randomly divided into 4 groups as E(+)K(+), E(+)K(-), E(-)K(+), and E(-)K(-) where E(+) means EMW exposure and K(+) means Kirschner wire fixation. At the end of study tibia samples were taken from all the groups for the quantitative evaluation of regeneration.Significant difference was found between Group E(+)K(+) and E(-)K(+) in terms of both new bone and capillary volume.Electromagnetic wave may be harmful for bone healing with fixation whereas it has no same effect on bone regeneration without fixation.

Biomechanics of bone-fracture fixation by stiffness-graded plates in comparison with stainless-steel plates

PubMed Central

Ganesh, VK; Ramakrishna, K; Ghista, Dhanjoo N

2005-01-01

Background In the internal fixation of fractured bone by means of bone-plates fastened to the bone on its tensile surface, an on-going concern has been the excessive stress-shielding of the bone by the excessively-stiff stainless-steel plate. The compressive stress-shielding at the fracture-interface immediately after fracture-fixation delays callus formation and bone healing. Likewise, the tensile stress-shielding of the layer of the bone underneath the plate can cause osteoporosis and decrease in tensile strength of this layer. Method In order to address this problem, we propose to use stiffness-graded plates. Accordingly, we have computed (by finite-element analysis) the stress distribution in the fractured bone fixed by composite plates, whose stiffness is graded both longitudinally and transversely. Results It can be seen that the stiffness-graded composite-plates cause less stress-shielding (as an example: at 50% of the healing stage, stress at the fracture interface is compressive in nature i.e. 0.002 GPa for stainless steel plate whereas stiffness graded plates provides tensile stress of 0.002 GPa. This means that stiffness graded plate is allowing the 50% healed bone to participate in loadings). Stiffness-graded plates are more flexible, and hence permit more bending of the fractured bone. This results in higher compressive stresses induced at the fractured faces accelerate bone-healing. On the other hand, away from the fracture interface the reduced stiffness and elastic modulus of the plate causes the neutral axis of the composite structure to be lowered into the bone resulting in the higher tensile stress in the bone-layer underneath the plate, wherein is conducive to the bone preserving its tensile strength. Conclusion Stiffness graded plates (with in-built variable stiffness) are deemed to offer less stress-shielding to the bone, providing higher compressive stress at the fractured interface (to induce accelerated healing) as well as higher tensile stress in the intact portion of the bone (to prevent bone remodeling and osteoporosis). PMID:16045807

Nanotechnology and bone healing.

PubMed

Harvey, Edward J; Henderson, Janet E; Vengallatore, Srikar T

2010-03-01

Nanotechnology and its attendant techniques have yet to make a significant impact on the science of bone healing. However, the potential benefits are immediately obvious with the result that hundreds of researchers and firms are performing the basic research needed to mature this nascent, yet soon to be fruitful niche. Together with genomics and proteomics, and combined with tissue engineering, this is the new face of orthopaedic technology. The concepts that orthopaedic surgeons recognize are fabrication processes that have resulted in porous implant substrates as bone defect augmentation and medication-carrier devices. However, there are dozens of applications in orthopaedic traumatology and bone healing for nanometer-sized entities, structures, surfaces, and devices with characteristic lengths ranging from 10s of nanometers to a few micrometers. Examples include scaffolds, delivery mechanisms, controlled modification of surface topography and composition, and biomicroelectromechanical systems. We review the basic science, clinical implications, and early applications of the nanotechnology revolution and emphasize the rich possibilities that exist at the crossover region between micro- and nanotechnology for developing new treatments for bone healing.

Role of FGFs/FGFRs in skeletal development and bone regeneration.

PubMed

Du, Xiaolan; Xie, Yangli; Xian, Cory J; Chen, Lin

2012-12-01

Fibroblast growth factor (FGF)/FGF (FGFR) signaling is an important pathway involved in skeletal development. Missense mutations in FGFs and FGFRs were found clinically to cause multiple congenital skeleton diseases including chondrodysplasia, craniosynostosis, syndromes with dysregulated phosphate metabolism. FGFs/FGFRs also have crucial roles in bone fracture repair and bone regeneration. Understanding the molecular mechanisms for the role of FGFs/FGFRs in the regulation of skeletal development, genetic skeletal diseases, and fracture healing will ultimately lead to better treatment of skeleton diseases caused by mutations of FGFs/FGFRs and fracture. This review summarizes the major findings on the role of FGF signaling in skeletal development, genetic skeletal diseases and bone healing, and discusses issues that remain to be resolved in applying FGF signaling-related measures to promote bone healing. This review has also provided a perspective view on future work for exploring the roles and action mechanisms of FGF signaling in skeletal development, genetic skeletal diseases, and fracture healing. Copyright © 2012 Wiley Periodicals, Inc.

Boon and Bane of Inflammation in Bone Tissue Regeneration and Its Link with Angiogenesis.

PubMed

Schmidt-Bleek, Katharina; Kwee, Brian J; Mooney, David J; Duda, Georg N

2015-08-01

Delayed healing or nonhealing of bone is an important clinical concern. Although bone, one of the two tissues with scar-free healing capacity, heals in most cases, healing is delayed in more than 10% of clinical cases. Treatment of such delayed healing condition is often painful, risky, time consuming, and expensive. Tissue healing is a multistage regenerative process involving complex and well-orchestrated steps, which are initiated in response to injury. At best, these steps lead to scar-free tissue formation. At the onset of healing, during the inflammatory phase, stationary and attracted macrophages and other immune cells at the fracture site release cytokines in response to injury. This initial reaction to injury is followed by the recruitment, proliferation, and differentiation of mesenchymal stromal cells, synthesis of extracellular matrix proteins, angiogenesis, and finally tissue remodeling. Failure to heal is often associated with poor revascularization. Since blood vessels mediate the transport of circulating cells, oxygen, nutrients, and waste products, they appear essential for successful healing. The strategy of endogenous regeneration in a tissue such as bone is interesting to analyze since it may represent a blueprint of successful tissue formation. This review highlights the interdependency of the time cascades of inflammation, angiogenesis, and tissue regeneration. A better understanding of these inter-relations is mandatory to early identify patients at risk as well as to overcome critical clinical conditions that limit healing. Instead of purely tolerating the inflammatory phase, modulations of inflammation (immunomodulation) might represent a valid therapeutic strategy to enhance angiogenesis and foster later phases of tissue regeneration.

Selection of animal models for pre-clinical strategies in evaluating the fracture healing, bone graft substitutes and bone tissue regeneration and engineering.

PubMed

Bigham-Sadegh, Amin; Oryan, Ahmad

2015-06-01

In vitro assays can be useful in determining biological mechanism and optimizing scaffold parameters, however translation of the in vitro results to clinics is generally hard. Animal experimentation is a better approximation than in vitro tests, and usage of animal models is often essential in extrapolating the experimental results and translating the information in a human clinical setting. In addition, usage of animal models to study fracture healing is useful to answer questions related to the most effective method to treat humans. There are several factors that should be considered when selecting an animal model. These include availability of the animal, cost, ease of handling and care, size of the animal, acceptability to society, resistance to surgery, infection and disease, biological properties analogous to humans, bone structure and composition, as well as bone modeling and remodeling characteristics. Animal experiments on bone healing have been conducted on small and large animals, including mice, rats, rabbits, dogs, pigs, goats and sheep. This review also describes the molecular events during various steps of fracture healing and explains different means of fracture healing evaluation including biomechanical, histopathological and radiological assessments.

Comparison of autogenous cancellous bone grafting and extracorporeal shock wave therapy on osteotomy healing in the tibial tuberosity advancement procedure in dogs. Radiographic densitometric evaluation.

PubMed

Barnes, K; Lanz, O; Werre, S; Clapp, K; Gilley, R

2015-01-01

To compare optical values in the osteotomy gap created after a tibial tuberosity advancement (TTA) treated with autogenous cancellous bone graft, extracorporeal shock wave therapy, a combination of autogenous cancellous bone graft and extracorporeal shock wave therapy, and absence of both autogenous cancellous bone graft and extracorporeal shock wave therapy using densitometry. Dogs that were presented for surgical repair of a cranial cruciate ligament rupture were randomly assigned to one of four groups: TTA with autogenous cancellous bone graft (TTA-G), TTA with autogenous cancellous bone graft and extracorporeal shock wave therapy (TTA-GS), TTA with extracorporeal shock wave therapy (TTA-S), and TTA with no additional therapy (TTA-O). Mediolateral radiographs at zero, four and eight weeks after surgery were evaluated to compare healing of the osteotomy gap via densitometry. An analysis of variance was used to compare the densitometric values between groups. At four weeks after surgery, a significant difference in osteotomy gap density was noted between TTA-GS (8.4 millimetres of aluminium equivalent [mmAleq]) and TTA-S (6.1 mmAleq), and between TTA-GS (8.4 mmAleq) and TTA-O (6.4 mmAleq). There were no significant differences noted between any groups at the eight week re-evaluation. There were no significant differences in the osteotomy gap density at eight weeks after surgery regardless of the treatment modality used. The combination of autogenous cancellous bone graft and extracorporeal shock wave therapy may lead to increased radiographic density of the osteotomy gap in the first four weeks after surgery. Densitometry using an aluminium step wedge is a feasible method for comparison of bone density after TTA in dogs.

Smoking and Bone Healing - A Risky Surgical Combination

MedlinePlus

... Risky Surgical Combination A A A | Print | Share Smoking and Bone Healing – A Risky Surgical Combination Imagine ... saying that they'd prefer patients to quit smoking. There hasn't been a great deal of ...

Local delivery of parathyroid hormone-related protein-derived peptides coated onto a hydroxyapatite-based implant enhances bone regeneration in old and diabetic rats.

PubMed

Ardura, Juan A; Portal-Núñez, Sergio; Lozano, Daniel; Gutiérrez-Rojas, Irene; Sánchez-Salcedo, Sandra; López-Herradón, Ana; Mulero, Francisca; Villanueva-Peñacarrillo, María L; Vallet-Regí, María; Esbrit, Pedro

2016-08-01

Diabetes mellitus (DM) and aging are associated with bone fragility and increased fracture risk. Both (1-37) N- and (107-111) C-terminal parathyroid hormone-related protein (PTHrP) exhibit osteogenic properties. We here aimed to evaluate and compare the efficacy of either PTHrP (1-37) or PTHrP (107-111) loaded into gelatin-glutaraldehyde-coated hydroxyapatite (HA-Gel) foams to improve bone repair of a transcortical tibial defect in aging rats with or without DM, induced by streptozotocin injection at birth. Diabetic old rats showed bone structural deterioration compared to their age-matched controls. Histological and μ-computerized tomography studies showed incomplete bone repair at 4 weeks after implantation of unloaded Ha-Gel foams in the transcortical tibial defects, mainly in old rats with DM. However, enhanced defect healing, as shown by an increase of bone volume/tissue volume and trabecular and cortical thickness and decreased trabecular separation, occurred in the presence of either PTHrP peptide in the implants in old rats with or without DM. This was accompanied by newly formed bone tissue around the osteointegrated HA-Gel implant and increased gene expression of osteocalcin and vascular endothelial growth factor (bone formation and angiogenic markers, respectively), and decreased expression of Sost gene, a negative regulator of bone formation, in the healing bone area. Our findings suggest that local delivery of PTHrP (1-37) or PTHrP (107-111) from a degradable implant is an attractive strategy to improve bone regeneration in aged and diabetic subjects. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2060-2070, 2016. © 2016 Wiley Periodicals, Inc.

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.

Anti-DKK1 antibody promotes bone fracture healing through activation of β-catenin signaling

PubMed Central

Jin, Hongting; Wang, Baoli; Li, Jia; Xie, Wanqing; Mao, Qiang; Li, Shan; Dong, Fuqiang; Sun, Yan; Ke, Hua-Zhu; Babij, Philip; Tong, Peijian; Chen, Di

2015-01-01

In this study we investigated if Wnt/β-catenin signaling in mesenchymal progenitor cells plays a role in bone fracture repair and if DKK1-Ab promotes fracture healing through activation of β-catenin signaling. Unilateral open transverse tibial fractures were created in CD1 mice and in β-cateninPrx1ER conditional knockout (KO) and Cre-negative control mice (C57BL/6 background). Bone fracture callus tissues were collected and analyzed by radiography, micro-CT (μCT), histology, biomechanical testing and gene expression analysis. The results demonstrated that treatment with DKK1-Ab promoted bone callus formation and increased mechanical strength during the fracture healing processinCD1 mice. DKK1-Ab enhanced fracture repair by activation of endochondral ossification. The normal rate of bone repair was delayed when the β-catenin gene was conditionally deleted in mesenchymal progenitor cells during the early stages of fracture healing. DKK1-Ab appeared to act through β-catenin signaling to enhance bone repair since the beneficial effect of DKK1-Ab was abrogated in β-cateninPrx1ER conditional KO mice. Further understanding of the signaling mechanism of DKK1-Ab in bone formation and bone regeneration may facilitate the clinical translation of this anabolic agent into therapeutic intervention. PMID:25263522

Boron containing poly-(lactide-co-glycolide) (PLGA) scaffolds for bone tissue engineering.

PubMed

Doğan, Ayşegül; Demirci, Selami; Bayir, Yasin; Halici, Zekai; Karakus, Emre; Aydin, Ali; Cadirci, Elif; Albayrak, Abdulmecit; Demirci, Elif; Karaman, Adem; Ayan, Arif Kursat; Gundogdu, Cemal; Sahin, Fikrettin

2014-11-01

Scaffold-based bone defect reconstructions still face many challenges due to their inadequate osteoinductive and osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calcium mineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highly warranted for the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics. The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Sclerostin antibody treatment improves fracture outcomes in a Type I diabetic mouse model

DOE PAGES

Yee, Cristal S.; Xie, LiQin; Hatsell, Sarah; ...

2015-05-04

Type 1 diabetes mellitus (T1DM) patients have osteopenia and impaired fracture healing due to decreased osteoblast activity. Further, no adequate treatments are currently available that can restore impaired healing in T1DM; hence a significant need exists to investigate new therapeutics for treatment of orthopedic complications. Sclerostin (SOST), a WNT antagonist, negatively regulates bone formation, and SostAb is a potent bone anabolic agent. To determine whether SOST antibody (SostAb) treatment improves fracture healing in streptozotocin (STZ) induced T1DM mice, we administered SostAb twice weekly for up to 21 days post-fracture, and examined bone quality and callus outcomes at 21 days andmore » 42 days post-fracture (11 and 14 weeks of age, respectively). Here we show that SostAb treatment improves bone parameters; these improvements persist after cessation of antibody treatment. Markers of osteoblast differentiation such as Runx2, collagen I, osteocalcin, and DMP1 were reduced, while an abundant number of SP7/osterix-positive early osteoblasts were observed on the bone surface of STZ calluses. These results suggest that STZ calluses have poor osteogenesis resulting from failure of osteoblasts to fully differentiate and produce mineralized matrix, which produces a less mineralized callus. SostAb treatment enhanced fracture healing in both normal and STZ groups, and in STZ + SostAb mice, also reversed the lower mineralization seen in STZ calluses. Micro-CT analysis of calluses revealed improved bone parameters with SostAb treatment, and the mineralized bone was comparable to Controls. Additionally, we found sclerostin levels to be elevated in STZ mice and β-catenin activity to be reduced. Consistent with its function as a WNT antagonist, SostAb treatment enhanced β-catenin activity, but also increased the levels of SOST in the callus and in circulation. Lastly, our results indicate that SostAb treatment rescues the impaired osteogenesis seen in the STZ induced T1DM fracture model by facilitating osteoblast differentiation and mineralization of bone.« less

Improved autologous cortical bone harvest and viability with 2Flute otologic burs.

PubMed

Roth, Adam A; Tang, Pei-Ciao; Ye, Michael J; Mohammad, Khalid S; Nelson, Rick F

2018-01-01

To determine if 2Flute (Stryker Corporation, Kalamazoo, MI) otologic burs improve the size, cellular content, and bone healing of autologous cortical bone grafts harvested during canal wall reconstruction (CWR) tympanomastoidectomy with mastoid obliteration. Institutional review board-approved prospective cohort study. Human autologous cortical bone chips were harvested using various burs (4 and 6 mm diameter; multiflute, and 2Flute [Stryker Corporation]) from patients undergoing CWR tympanomastoidectomy for the treatment of chronic otitis media with cholesteatoma. Bone chip size, cell counts, cellular gene expression, and new bone formation were quantified. Bone chips were significantly larger when harvested with 2Flute (Stryker Corporation) bur compared to multiflute burs at both 6 mm diameter (113 ± 14 μm 2 vs. 66 ± 8 μm 2 ; P < 0.05) and 4 mm diameter (70 ± 8 μm 2 vs. 50 ± 3 μm 2 ; P < 0.05). After 2 weeks in culture, cell numbers were significantly higher when harvested with 2Flute (Stryker Corporation) bur compared to multiflute burs at both 6 mm diameter (48.7 ± 3 vs. 31.8 ± 3 cells/μg bone; P < 0.05) and 4 mm diameter (27.6 ± 1.2 vs. 8.8 ± 1.2 cells/μg bone; P < 0.05). Bone-derived cells express osteoblast markers (alkaline phosphatase, osteocalcin). Cultured cells are able to form new bone in culture, and bone formation is facilitated by the presence of bone chips. Use of 2Flute (Stryker Corporation) otologic burs for human autologous cortical bone harvest results in more viable bone fragments, with larger bone chips and more osteoblasts. Future studies are needed to determine if this leads to improved bone healing. NA. Laryngoscope, 128:E41-E46, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Healing of donor site in bone-tendon-bone ACL reconstruction accelerated with plasma rich in growth factors: a randomized clinical trial.

PubMed

Seijas, Roberto; Rius, Marta; Ares, Oscar; García-Balletbó, Montserrat; Serra, Iván; Cugat, Ramón

2015-04-01

To determine whether the use of plasma rich in growth factors accelerates healing of the donor site in bone-tendon-bone anterior cruciate ligament (ACL) reconstruction (patellar graft). The use of the patellar graft presents post-operative problems such as anterior knee pain, which limits its use and leads to preference being taken for alternative grafts. A double-blind, randomized, clinical trial was performed comparing two groups of patients who underwent ACL reconstruction using patellar tendon graft and comparing the use of plasma rich in growth factors at the donor site after graft harvest in terms of local regeneration by ultrasound assessment. The plasma rich in growth factors group shows earlier donor site regeneration in comparison with the control group (2 months earlier), with significant differences in the first 4 months of the follow-up. The application of plasma rich in growth factors shows accelerated tissue regeneration processes with respect to the control group. This fact, together with the previously published with similar conclusions, can create a knowledge basis in order to set out new recovery guidelines following ACL reconstruction. Therapeutic study, Level I.

Bone regeneration by implantation of adipose-derived stromal cells expressing BMP-2

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

Li Huiwu; Health and Science Center, SIBS CAS and SSMU, 225 South Chongqing Road, Shanghai 200025; Dai Kerong

2007-05-18

In this study, we reported that the adipose-derived stromal cells (ADSCs) genetically modified by bone morphogenetic protein 2 (BMP-2) healed critical-sized canine ulnar bone defects. First, the osteogenic and adipogenic differentiation potential of the ADSCs derived from canine adipose tissue were demonstrated. And then the cells were modified by the BMP-2 gene and the expression and bone-induction ability of BMP-2 were identified. Finally, the cells modified by BMP-2 gene were applied to a {beta}-tricalcium phosphate (TCP) carrier and implanted into ulnar bone defects in the canine model. After 16 weeks, radiographic, histological, and histomorphometry analysis showed that ADSCs modified bymore » BMP-2 gene produced a significant increase of newly formed bone area and healed or partly healed all of the bone defects. We conclude that ADSCs modified by the BMP-2 gene can enhance the repair of critical-sized bone defects in large animals.« less

Octacalcium phosphate collagen composite facilitates bone regeneration of large mandibular bone defect in humans.

PubMed

Kawai, Tadashi; Suzuki, Osamu; Matsui, Keiko; Tanuma, Yuji; Takahashi, Tetsu; Kamakura, Shinji

2017-05-01

Recently it was reported that the implantation of octacalcium phosphate (OCP) and collagen composite (OCP-collagen) was effective at promoting bone healing in small bone defects after cystectomy in humans. In addition, OCP-collagen promoted bone regeneration in a critical-sized bone defect of a rodent or canine model. In this study, OCP-collagen was implanted into a human mandibular bone defect with a longer axis of approximately 40 mm, which was diagnosed as a residual cyst with apical periodontitis. The amount of OCP-collagen implanted was about five times greater than the amounts implanted in previous clinical cases. Postoperative wound healing was satisfactory and no infection or allergic reactions occurred. The OCP-collagen-treated lesion was gradually filled with radio-opaque figures, and the alveolar region occupied the whole of the bone defect 12 months after implantation. This study suggests that OCP-collagen could be a useful bone substitute material for repairing large bone defects in humans that might not heal spontaneously. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Bone regenerative medicine: classic options, novel strategies, and future directions

PubMed Central

2014-01-01

This review analyzes the literature of bone grafts and introduces tissue engineering as a strategy in this field of orthopedic surgery. We evaluated articles concerning bone grafts; analyzed characteristics, advantages, and limitations of the grafts; and provided explanations about bone-tissue engineering technologies. Many bone grafting materials are available to enhance bone healing and regeneration, from bone autografts to graft substitutes; they can be used alone or in combination. Autografts are the gold standard for this purpose, since they provide osteogenic cells, osteoinductive growth factors, and an osteoconductive scaffold, all essential for new bone growth. Autografts carry the limitations of morbidity at the harvesting site and limited availability. Allografts and xenografts carry the risk of disease transmission and rejection. Tissue engineering is a new and developing option that had been introduced to reduce limitations of bone grafts and improve the healing processes of the bone fractures and defects. The combined use of scaffolds, healing promoting factors, together with gene therapy, and, more recently, three-dimensional printing of tissue-engineered constructs may open new insights in the near future. PMID:24628910

Efficacy of Platelet-Rich Fibrin After Mandibular Third Molar Extraction: A Systematic Review and Meta-Analysis.

PubMed

Al-Hamed, Faez Saleh; Tawfik, Mohamed Abdel-Monem; Abdelfadil, Ehab; Al-Saleh, Mohammed A Q

2017-06-01

To assess the effect of platelet-rich fibrin (PRF) on the healing process of the alveolar socket after surgical extraction of the mandibular third molars. PubMed, the Cochrane Central Register of Controlled Trials, Scopus, and relevant journals were searched using a combination of specific keywords ("platelet-rich fibrin," "oral surgery," and "third molar"). The final search was conducted on November 2, 2015. Randomized controlled clinical trials, as well as controlled clinical trials, aimed at comparing the effect of PRF versus natural healing after extraction of mandibular third molars were included. Five randomized controlled trials and one controlled clinical trial were included. There were 335 extractions (168 with PRF and 167 controls) in 183 participants. Considerable heterogeneity in study characteristics, outcome variables, and estimated scales was observed. Positive results were generally recorded for pain, trismus, swelling, periodontal pocket depth, soft tissue healing, and incidence of localized osteitis, but not in all studies. However, no meta-analysis could be conducted for such variables because of the different measurement scales used. The qualitative and meta-analysis results showed no significant improvement in bone healing with PRF-treated sockets compared with the naturally healing sockets. Within the limitations of the available evidence, PRF seems to have no beneficial role in bone healing after extraction of the mandibular third molars. Future standardized randomized controlled clinical trials are required to estimate the effect of PRF on socket regeneration. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Acceleration of hard and soft tissue healing in the oral cavity by a single transmucosal injection of fluvastatin-impregnated poly (lactic-co-glycolic acid) microspheres. An in vitro and rodent in vivo study.

PubMed

Yasunami, Noriyuki; Ayukawa, Yasunori; Furuhashi, Akihiro; Atsuta, Ikiru; Rakhmatia, Yunia Dwi; Moriyama, Yasuko; Masuzaki, Tomohiro; Koyano, Kiyoshi

2015-12-23

Antihyperlipidemic drug statins reportedly promote both bone formation and soft tissue healing. We examined the effect of sustained-release, fluvastatin-impregnated poly(lactic-co-glycolic acid) (PLGA) microspheres on the promotion of bone and gingival healing at an extraction socket in vivo, and the effect of fluvastatin on epithelial cells and fibroblasts in vitro. The maxillary right first molar was extracted in rats, then one of the following was immediately injected, as a single dose, into the gingivobuccal fold: control (no administration), PLGA microspheres without a statin (active control), or PLGA microspheres containing 20 or 40 μg kg(-1) of fluvastatin. At days 1, 3, 7, 14, and 28 after injection, bone and soft tissue healing were histologically evaluated. Cell proliferation was measured under the effect of fluvastatin at dosages of 0, 0.01, 0.1, 1.0, 10, and 50 μM. Cell migration and morphology were observed at dosages of 0 and 0.1 μM. Following tooth extraction, the statin significantly enhanced bone volume and density, connective tissue volume, and epithelial wound healing. In the in vitro study, it promoted significant proliferation and migration of epithelial cells and fibroblasts. A single dose of topically administered fluvastatin-impregnated PLGA microspheres promoted bone and soft tissue healing at the extraction site.

Vibration acceleration promotes bone formation in rodent models

PubMed Central

Uchida, Ryohei; Nakata, Ken; Kawano, Fuminori; Yonetani, Yasukazu; Ogasawara, Issei; Nakai, Naoya; Mae, Tatsuo; Matsuo, Tomohiko; Tachibana, Yuta; Yokoi, Hiroyuki; Yoshikawa, Hideki

2017-01-01

All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal) accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF) mouse model and a rib fracture healing (RFH) rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups) were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups) were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model) or nine days (RFH model). All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT). In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model) had significantly greater wet weight and were significantly larger (macroscopically and radiographically) than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV) in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group), but BV in the centrifuge acceleration group had no significant difference compared those in control-CA group. Union rate and BV in the low-magnitude group of RFH model were also significantly higher than those in the other groups (Union rate: 60% v.s. 0% in the high-magnitude group and 10% in the control-VA group, BV: 0.69±0.30mm3 v.s. 0.15±0.09mm3 in high-magnitude group and 0.22±0.17mm3 in control-VA group). BV/TV in the low-magnitude group of RFH model was significantly higher than that in control-VA group (59.4±14.9% v.s. 35.8±13.5%). On the other hand, radiographic union rate (10% in centrifuge acceleration group v.s. 20% in control-CA group) and micro-CT parameters in RFH model were not significantly different between two groups in the constant acceleration studies. Radiographic images of non-union rib fractures showed cartilage at the fracture site and poor new bone formation, whereas union samples showed only new bone. In conclusion, low-magnitude vibration acceleration promoted bone formation at the trunk in both BMP-induced ectopic bone formation and rib fracture healing models. However, the micro-CT parameters were not similar between two models, which suggested that there might be difference in the mechanism of effect by vibration between two models. PMID:28264058

Vibration acceleration promotes bone formation in rodent models.

PubMed

Uchida, Ryohei; Nakata, Ken; Kawano, Fuminori; Yonetani, Yasukazu; Ogasawara, Issei; Nakai, Naoya; Mae, Tatsuo; Matsuo, Tomohiko; Tachibana, Yuta; Yokoi, Hiroyuki; Yoshikawa, Hideki

2017-01-01

All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal) accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF) mouse model and a rib fracture healing (RFH) rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups) were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups) were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model) or nine days (RFH model). All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT). In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model) had significantly greater wet weight and were significantly larger (macroscopically and radiographically) than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV) in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group), but BV in the centrifuge acceleration group had no significant difference compared those in control-CA group. Union rate and BV in the low-magnitude group of RFH model were also significantly higher than those in the other groups (Union rate: 60% v.s. 0% in the high-magnitude group and 10% in the control-VA group, BV: 0.69±0.30mm3 v.s. 0.15±0.09mm3 in high-magnitude group and 0.22±0.17mm3 in control-VA group). BV/TV in the low-magnitude group of RFH model was significantly higher than that in control-VA group (59.4±14.9% v.s. 35.8±13.5%). On the other hand, radiographic union rate (10% in centrifuge acceleration group v.s. 20% in control-CA group) and micro-CT parameters in RFH model were not significantly different between two groups in the constant acceleration studies. Radiographic images of non-union rib fractures showed cartilage at the fracture site and poor new bone formation, whereas union samples showed only new bone. In conclusion, low-magnitude vibration acceleration promoted bone formation at the trunk in both BMP-induced ectopic bone formation and rib fracture healing models. However, the micro-CT parameters were not similar between two models, which suggested that there might be difference in the mechanism of effect by vibration between two models.

Effects of local vibration and pulsed electromagnetic field on bone fracture: A comparative study.

PubMed

Bilgin, Hakkı Murat; Çelik, Ferhat; Gem, Mehmet; Akpolat, Veysi; Yıldız, İsmail; Ekinci, Aysun; Özerdem, Mehmet Siraç; Tunik, Selçuk

2017-07-01

The effectiveness of various therapeutic methods on bone fracture has been demonstrated in several studies. In the present study, we tried to evaluate the effect of local low-magnitude, high-frequency vibration (LMHFV) on rat tibia fracture in comparison with pulsed electromagnetic fields (PEMF) during the healing process. Mid-diaphysis tibiae fractures were induced in 30 Sprague-Dawley rats. The rats were assigned into groups such as control (CONT), LMHFV (15 min/day, 7 days/week), and PEMF (3.5 h/day, 7 days/week) for a three-week treatment. Nothing was applied to control group. Radiographs, serum osteocalcin levels, and stereological bone analyses of the three groups were compared. The X-rays of tibiae were taken 21 days after the end of the healing process. PEMF and LMHFV groups had more callus formation when compared to CONT group; however, the difference was not statistically significant (P = 0.375). Serum osteocalcin levels were elevated in the experimental groups compared to CONT (P ≤ 0.001). Stereological tests also showed higher osteogenic results in experimental groups, especially in LMHFV group. The results of the present study suggest that application of direct local LMHFV on fracture has promoted bone formation, showing great potential in improving fracture outcome. Bioelectromagnetics. 38:339-348, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Staphylococcal enterotoxin C2 promotes osteogenesis of mesenchymal stem cells and accelerates fracture healing

PubMed Central

Wu, T.; Wang, B.; Sun, Y.; Liu, Y.; Li, G.

2018-01-01

Objectives As one of the heat-stable enterotoxins, Staphylococcal enterotoxin C2 (SEC2) is synthesized by Staphylococcus aureus, which has been proved to inhibit the growth of tumour cells, and is used as an antitumour agent in cancer immunotherapy. Although SEC2 has been reported to promote osteogenic differentiation of human mesenchymal stem cells (MSCs), the in vivo function of SCE2 in animal model remains elusive. The aim of this study was to further elucidate the in vivo effect of SCE2 on fracture healing. Materials and Methods Rat MSCs were used to test the effects of SEC2 on their proliferation and osteogenic differentiation potentials. A rat femoral fracture model was used to examine the effect of local administration of SEC2 on fracture healing using radiographic analyses, micro-CT analyses, biomechanical testing, and histological analyses. Results While SEC2 was found to have no effect on rat MSCs proliferation, it promoted the osteoblast differentiation of rat MSCs. In the rat femoral fracture model, the local administration of SEC2 accelerated fracture healing by increasing fracture callus volumes, bone volume over total volume (BV/TV), and biomechanical recovery. The SEC2 treatment group has superior histological appearance compared with the control group. Conclusion These data suggest that local administration of SEC2 may be a novel therapeutic approach to enhancing bone repair such as fracture healing. Cite this article: T. Wu, J. Zhang, B. Wang, Y. Sun, Y. Liu, G. Li. Staphylococcal enterotoxin C2 promotes osteogenesis of mesenchymal stem cells and accelerates fracture healing. Bone Joint Res 2018;7:179–186. DOI: 10.1302/2046-3758.72.BJR-2017-0229.R1. PMID:29682284

Clinical application of bone morphogenetic proteins for bone healing: a systematic review.

PubMed

Krishnakumar, Gopal Shankar; Roffi, Alice; Reale, Davide; Kon, Elizaveta; Filardo, Giuseppe

2017-06-01

This paper documents the existing evidence on bone morphogenetic proteins (BMPs) use for the treatment of bone fractures, non-union, and osteonecrosis, through a review of the clinical literature, underlying potential and limitations in terms of cost effectiveness and risk of complications. A systematic review was performed on the PubMed database using the following string: (bone morphogenetic proteins OR BMPs) and (bone repair OR bone regeneration) including papers from 2000 to 2016. The search focused on clinical trials dealing with BMPs application to favor bone regeneration in bone fractures, non-union, and osteonecrosis, in English language, with level of evidence I, II, III, and IV. Relevant data (type of study, number of patients, BMPs delivery material, dose, site, follow-up, outcome, and adverse events) were extracted and analyzed. Forty-four articles met the inclusion criteria: 10 randomized controlled trials (RCTs), 7 comparative studies, 18 case series, and 9 case reports. rhBMP-2 was documented mainly for the treatment of fractures, and rhBMP-7 mainly for non-unions and osteonecrosis. Mixed results were found among RCTs and comparative papers: 11 reported positive results for BMPs augmentation, 3 obtained no significant effects, and 2 showed negative results. The only study comparing the two BMPs showed a better outcome with rhBMP-2 for non-union treatment. Clinical evidence on BMPs use for the treatment of fractures, non-union, and osteonecrosis is still controversial, with the few available reports being mainly of low quality. While positive findings have been described in many studies, mixed results are still present in the literature in terms of efficacy and adverse events. The difficulties in drawing clear conclusions are also due to the studies heterogeneity, mainly in terms of different BMPs applied, with different concomitant treatments for each bone pathology. Therefore, further research with well-designed studies is needed in order to understand the real potential of this biological approach to favour bone healing.

Review of techniques for monitoring the healing fracture of bones for implementation in an internally fixated pelvis.

PubMed

Wong, Lydia Chwang Yuh; Chiu, Wing Kong; Russ, Matthias; Liew, Susan

2012-03-01

Sacral fractures from high-impact trauma often cause instability in the pelvic ring structure. Treatment is by internal fixation which clamps the fractured edges together to promote healing. Healing could take up to 12 weeks whereby patients are bedridden to avoid hindrances to the fracture from movement or weight bearing activities. Immobility can lead to muscle degradation and longer periods of rehabilitation. The ability to determine the time at which the fracture is stable enough to allow partial weight-bearing is important to reduce hospitalisation time. This review looks into different techniques used for monitoring the fracture healing of bones which could lead to possible methods for in situ and non-invasive assessment of healing fracture in a fixated pelvis. Traditional techniques being used include radiology and CT scans but were found to be unreliable at times and very subjective in addition to being non in situ. Strain gauges have proven to be very effective for accurate assessment of fracture healing as well as stability for long bones with external fixators but may not be suitable for an internally fixated pelvis. Ultrasound provides in situ monitoring of stiffness recovery but only assesses local fracture sites close to the skin surface and has only been tested on long bones. Vibration analysis can detect non-uniform healing due to its assessment of the overall structure but may suffer from low signal-to-noise ratio due to damping. Impedance techniques have been used to assess properties of non-long bones but recent studies have only been conducted on non-biological materials and more research needs to be done before it can be applicable for monitoring healing in the fixated pelvis. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

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.

SDF-1 promotes endochondral bone repair during fracture healing at the traumatic brain injury condition.

PubMed

Liu, Xiaoqi; Zhou, Changlong; Li, Yanjing; Ji, Ye; Xu, Gongping; Wang, Xintao; Yan, Jinglong

2013-01-01

The objective of this study was to investigate the role of stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, on bone healing and whether SDF-1 contributes to accelerating bone repair in traumatic brain injury (TBI)/fracture model. Real-time polymerase chain reaction and immunohistochemical analysis were used to detect the expression of SDF-1 during the repair of femoral bone in TBI/fracture model. The TBI/fracture model was treated with anti-SDF-1 neutralizing antibody or AMD3100, an antagonist for CXCR4, and evaluated by histomorphometry. In vitro and in vivo migration assays were used to evaluate the functional effect of SDF-1 on primary mesenchymal stem cells. The expression of SDF1 and CXCR4 messenger RNA was increased during the bone healing in TBI/fracture model but was less increased in fracture only model. High expression of SDF-1 protein was observed in the surrounding tissue of the damaged bone. Treated with anti-SDF-1 antibody or AMD3100 could inhibit new bone formation. SDF-1 increased mesenchymal stem cell chemotaxis in vitro in a dose-dependent manner. The in vivo migration study demonstrated that mesenchymal stem cells recruited by SDF-1 participate in endochondral bone repair. The SDF-1/CXCR4 axis plays a crucial role in the accelerating fracture healing under the condition of TBI and contributes to endochondral bone repair.

Bone healing in 2016

PubMed Central

Buza, John A.; Einhorn, Thomas

2016-01-01

Summary Delayed fracture healing and nonunion occurs in up to 5–10% of all fractures, and can present a challenging clinical scenario for the treating physician. Methods for the enhancement of skeletal repair may benefit patients that are at risk of, or have experienced, delayed healing or nonunion. These methods can be categorized into either physical stimulation therapies or biological therapies. Physical stimulation therapies include electrical stimulation, low-intensity pulsed ultrasonography, or extracorporeal shock wave therapy. Biological therapies can be further classified into local or systemic therapy based on the method of delivery. Local methods include autologous bone marrow, autologous bone graft, fibroblast growth factor-2, platelet-rich plasma, platelet-derived growth factor, and bone morphogenetic proteins. Systemic therapies include parathyroid hormone and bisphosphonates. This article reviews the current applications and supporting evidence for the use of these therapies in the enhancement of fracture healing. PMID:27920804

Laser for bone healing after oral surgery: systematic review.

PubMed

Noba, Claudio; Mello-Moura, Anna Carolina Volpi; Gimenez, Thais; Tedesco, Tamara Kerber; Moura-Netto, Cacio

2018-04-01

The purpose of this study is to perform a systematic review on the use of lasers in oral surgery for bone healing. Selection of articles was carried out by two evaluators in Pubmed and Web of Science databases for published articles and OpenGray for gray literature. Search strategy was developed based on the PICO Question "Does the use of lasers after oral surgery improve bone healing?". Eligibility criteria were: being on laser; evaluate bone healing; involve oral surgery; do not be about implant, periodontics, orthodontics, osteonecrosis or radiotherapy, nor revisions, clinical cases, etc. Data were collected from each article in a structured spreadsheet and a descriptive analysis was performed. Risk assessment of bias of the articles was carried out through the tool elaborated by the Cochrane collaboration. A total of 827 potentially relevant references were identified. No articles were found in OpenGray. Eleven articles met the eligibility criteria and were included in the systematic review. Most of studies were in vivo and in jaw, being conducted with low-power lasers which were applied immediately after the surgical procedure of extraction. Neoformation and bone density were the outcomes of choice and there was a tendency of increase in bone density, neoformation, regeneration, mineralization, or bone condensation when laser was applied. Regarding the bias risk assessment, studies were not clear in reporting most of the parameters. Low-power laser therapy seems to reduce time of bone healing in oral surgery, although there are no defined protocols and the level of evidence is still considered weak.

Selective effect of hydroxyapatite nanoparticles on osteoporotic and healthy bone formation correlates with intracellular calcium homeostasis regulation.

PubMed

Zhao, Rui; Xie, Pengfei; Zhang, Kun; Tang, Zhurong; Chen, Xuening; Zhu, Xiangdong; Fan, Yujiang; Yang, Xiao; Zhang, Xingdong

2017-09-01

Adequate bone substitutes osseointegration has been difficult to achieve in osteoporosis. Hydroxyapatite of the osteoporotic bone, secreted by pathologic osteoblasts, had a smaller crystal size and lower crystallinity than that of the normal. To date, little is known regarding the interaction of synthetic hydroxyapatite nanoparticles (HANPs) with osteoblasts born in bone rarefaction. The present study investigated the biological effects of HANPs on osteoblastic cells derived from osteoporotic rat bone (OVX-OB), in comparison with the healthy ones (SHM-OB). A selective effect of different concentrations of HANPs on the two cell lines was observed that the osteoporotic osteoblasts had a higher tolerance. Reductions in cell proliferation, ALP activity, collagen secretion and osteoblastic gene expressions were found in the SHM-OB when administered with HANPs concentration higher than 25µg/ml. In contrast, those of the OVX-OB suffered no depression but benefited from 25 to 250µg/ml HANPs in a dose-dependent manner. We demonstrated that the different effects of HANPs on osteoblasts were associated with the intracellular calcium influx into the endoplasmic reticulum. The in vivo bone defect model further confirmed that, with a critical HANPs concentration administration, the osteoporotic rats had more and mechanically matured new bone formation than the non-treated ones, whilst the sham rats healed no better than the natural healing control. Collectively, the observed epigenetic regulation of osteoblastic cell function by HANPs has significant implication on defining design parameters for a potential therapeutic use of nanomaterials. In this study, we investigated the biological effects of hydroxyapatite nanoparticles (HANPs) on osteoporotic rat bone and the derived osteoblast. Our findings revealed a previously unrecognized phenomenon that the osteoporotic individuals could benefit from higher concentrations of HANPs, as compared with the healthy individuals. The in vivo bone defect model confirmed that, with a critical HANPs concentration administration, the osteoporotic rats had more mechanically matured new bone formation than the non-treated ones, whilst the sham rats healed no better than the natural healing control. The selective effect of HANPs might be associated with the intracellular calcium influx into the endoplasmic reticulum. Collectively, the observed epigenetic regulation by HANPs has significant implication on defining design parameters for a potential therapeutic use of nanomaterials in a pathological condition. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Immunohistochemical response in rats of beta-tricalcium phosphate (TCP) with or without BMP-2 in the production of collagen matrix critical defects.

PubMed

Luvizuto, Eloá Rodrigues; de Oliveira, Júlio César Silva; Gomes-Ferreira, Pedro Henrique Silva; Pereira, Cassiano Costa Silva; Faverani, Leonardo Perez; Antoniali, Cristina; Okamoto, Roberta

2017-04-01

This study aimed to assess the biological response of BMP-2 (bone morphogenetic protein-2) in supplementation with β-tricalcium phosphate (TCP) as a carrier in the bone healing of surgical defects in rats' calvaria. A critical-size defect (5mm in diameter) was filled with β-TCP alone or added with that plus 5mg of BMP-2 at 5, 15, and 30 postoperative days. Histomorphometric and immunohistochemical (osteocalcin, collagen type I, and metalloproteinase-9) analysis was performed to assess the features of bone healing. Histological behavior and collagen type I labeling showed increased formation of the collagen matrix, leading to a higher percentage of newly formed bone and biomaterial for tissue and more total mineralization of pure TCP when compared to the other groups. The supplementation with BMP-2 promoted faster TCP remodeling; however, there was no statistically significant difference for the bone formed in both groups (P>0.05). Collagen-matrix formation and new bone formation reached maximum levels when the defects were filled with pure TCP, even exceeding the levels from BMP-2 supplementation. Copyright © 2017 Elsevier GmbH. All rights reserved.

High-Frequency, Low-Intensity Pulsed Ultrasound Enhances Alveolar Bone Healing of Extraction Sockets in Rats: A Pilot Study.

PubMed

Kang, Kyung Lhi; Kim, Eun-Cheol; Park, Joon Bong; Heo, Jung Sun; Choi, Yumi

2016-02-01

Most studies of the beneficial effects of low-intensity pulsed ultrasound (LIPUS) on bone healing have used frequencies between 1.0 and 1.5 MHz. However, after consideration of ultrasound wave characteristics and depth of target tissue, higher-frequency LIPUS may have been more effective on superficially positioned alveolar bone. We investigated this hypothesis by applying LIPUS (frequency, 3.0 MHz; intensity, 30 mW/cm(2)) on shaved right cheeks over alveolar bones of tooth extraction sockets in rats for 10 min/d for 2 wk after tooth extraction; the control group (left cheek of the same rats) did not receive LIPUS treatment. Compared with the control group, the LIPUS group manifested more new bone growth inside the sockets on histomorphometric analysis (maximal difference = 2.5-fold on the seventh day after extraction) and higher expressions of osteogenesis-related mRNAs and proteins than the control group did. These findings indicate that 3.0-MHz LIPUS could enhance alveolar bone formation and calcification in rats. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

A Comparative Histological Study of Bone Healing in Rat Calvarial Defect Using the Erbium-Doped Yttrium Aluminum Garnet Laser and Rotary Instruments

NASA Astrophysics Data System (ADS)

Jung, Mi-Kyung; Kim, Su-Gwan; Oh, Ji-Su; Jin, Seung-Chan; Lee, Sook-Young; Jang, Eun-Sook; Piao, Zheng-Gang; Lim, Sung-Chul; Jeong, Mi-Ae

2012-01-01

Erbium-doped yttrium aluminum garnet (Er:YAG) lasers have been used in dentistry for cutting bone and removal of caries. The purpose of this study was to evaluate the bone healing in a skull defect prepared in rats using various instruments including Er:YAG laser. The 7 mm calvarial defects were created in 45 rats and 45 rats were divided into three groups (n = 15): a high-speed rotation engine with carbide round bur (2-mm diameter), a low-speed rotation engine with carbide round bur (2-mm diameter), and an Er:YAG laser. Specimens obtained after 3 days or 4 or 8 weeks were submitted for histological analysis. Three days after surgery, no bone formation had occurred in any of the groups. Four weeks after surgery, 90 ±8.16% new bone formation was observed in the high-speed group, and 8 weeks after surgery, 100 ±0% new bone formation was observed in the low- and high-speed groups. There were significant differences among the periods after surgery, but no significant differences were observed among final results with in different device groups.

Promoting Endochondral Bone Repair Using Human Osteoarthritic Articular Chondrocytes.

PubMed

Bahney, Chelsea S; Jacobs, Linsey; Tamai, Robert; Hu, Diane; Luan, Tammy F; Wang, Miqi; Reddy, Sanjay; Park, Michelle; Limburg, Sonja; Kim, Hubert T; Marcucio, Ralph; Kuo, Alfred C

2016-03-01

Current tissue engineering strategies to heal critical-size bone defects through direct bone formation are limited by incomplete integration of grafts with host bone and incomplete graft vascularization. An alternative strategy for bone regeneration is the use of cartilage grafts that form bone through endochondral ossification. Endochondral cartilages stimulate angiogenesis and are remodeled into bone, but are found in very small quantities in growth plates and healing fractures. We sought to develop engineered endochondral cartilage grafts using osteoarthritic (OA) articular chondrocytes as a cell source. Such chondrocytes often undergo hypertrophy, which is a characteristic of endochondral cartilages. We compared the ability of unmodified human OA (hOA) cartilage and cartilage grafts formed in vitro from hOA chondrocytes to undergo endochondral ossification in mice. Scaffold-free engineered chondrocyte grafts were generated by pelleting chondrocytes, followed by culture with transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein 4. Samples derived from either primary or passaged chondrocytes were implanted subcutaneously into immunocompromised mice. Grafts derived from passaged chondrocytes from three patients were implanted into critical-size tibial defects in mice. Bone formation was assessed with histology after 4 weeks of implantation. The composition of tibial repair tissue was quantified with histomorphometry. Engineered cartilage grafts generated from passaged OA chondrocytes underwent endochondral ossification after implantation either subcutaneously or in bone. Cartilage grafts integrated with host bone at 15 out of 16 junctions. Grafts variably remodeled into woven bone, with the proportion of bony repair tissue in tibial defects ranging from 22% to 85% (average 48%). Bony repair tissue bridged the tibial defects in half of the animals. In contrast, unmodified OA cartilage and engineered grafts formed from primary chondrocytes did not undergo endochondral ossification in vivo. hOA chondrocytes can adopt an endochondral phenotype after passaging and TGF-β superfamily treatment. Engineered endochondral cartilage grafts can integrate with host bone, undergo ossification, and heal critical-size long-bone defects in a mouse model. However, additional methods to further enhance ossification of these grafts are required before the clinical translation of this approach.

An ultrasound wearable system for the monitoring and acceleration of fracture healing in long bones.

PubMed

Protopappas, Vasilios C; Baga, Dina A; Fotiadis, Dimitrios I; Likas, Aristidis C; Papachristos, Athanasios A; Malizos, Konstantinos N

2005-09-01

An ultrasound wearable system for remote monitoring and acceleration of the healing process in fractured long bones is presented. The so-called USBone system consists of a pair of ultrasound transducers, implanted into the fracture region, a wearable device and a centralized unit. The wearable device is responsible to carry out ultrasound measurements using the axial-transmission technique and initiate therapy sessions of low-intensity pulsed ultrasound. The acquired measurements and other data are wirelessly transferred from the patient-site to the centralized unit, which is located in a clinical setting. The evaluation of the system on an animal tibial osteotomy model is also presented. A dataset was constructed for monitoring purposes consisting of serial ultrasound measurements, follow-up radiographs, quantitative computed tomography-based densitometry and biomechanical data. The animal study demonstrated the ability of the system to collect ultrasound measurements in an effective and reliable fashion and participating orthopaedic surgeons accepted the system for future clinical application. Analysis of the acquired measurements showed that the pattern of evolution of the ultrasound velocity through healing bones over the postoperative period monitors a dynamic healing process. Furthermore, the ultrasound velocity of radiographically healed bones returns to 80% of the intact bone value, whereas the correlation coefficient of the velocity with the material and mechanical properties of the healing bone ranges from 0.699 to 0.814. The USBone system constitutes the first telemedicine system for the out-hospital management of patients sustained open fractures and treated with external fixation devices.

Tissue regeneration in dentistry: Can salamanders provide insight?

PubMed

Sader, F; Denis, J-F; Roy, S

2018-05-01

The ability to regenerate damaged tissues would be of tremendous benefit for medicine and dentistry. Unfortunately, humans are unable to regenerate tissues such as teeth and fingers or to repair injured spinal cord. With an aging population, health problems are more prominent and dentistry is no exception as loss of bone tissue in the orofacial sphere from periodontal disease is on the rise. Humans can repair oral soft tissues exceptionally well; however, hard tissues, such as bone and teeth, are devoid of the ability to repair well or at all. Fortunately, Mother Nature has solved nearly every problem that we would like to solve for our own benefit and tissue regeneration is no exception. By studying animals that can regenerate, like Axolotls (Mexican salamander), we hope to find ways to stimulate regeneration in humans. We will discuss the role of the transforming growth factor beta cytokines as they are central to wound healing in humans and regeneration in Axolotls. We will also compare wound healing in humans (skin and oral mucosa) to Axolotl skin wound healing and limb regeneration. Finally, we will address the problem of bone regeneration and present results in salamanders which indicate that in order to regenerate bone you need to recruit non-bone cells. Fundamental research, such as the work being performed in animals that can regenerate, offers insight to help understand why some treatments are successful while others fail when it comes to specific tissues such as bones. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A randomized controlled clinical trial comparing small buccal dehiscence defects around dental implants treated with guided bone regeneration or left for spontaneous healing.

PubMed

Jung, Ronald E; Herzog, Milan; Wolleb, Karin; Ramel, Christian F; Thoma, Daniel S; Hämmerle, Christoph H F

2017-03-01

The aim of the present randomized controlled clinical study was to test whether small bony dehiscence defects (≤5 mm) left to heal spontaneously result in the same clinical and radiological outcome as defects treated with guided bone regeneration (GBR). Twenty-two patients who received at least one implant with a small bony dehiscence defect were enrolled in the study. If the defect height was ≤5 mm, the site was randomly assigned to either the spontaneous healing (SH) group or the GBR group. In the SH group, the defect was left without any treatment. In the GBR group, the defects around the implants were grafted with deproteinized bovine bone mineral (DBBM) and covered with a native collagen membrane. Clinical and radiographic measurements were performed 6 months after implant placement with a reentry surgery and at the time of crown insertion and the subsequent follow-up appointments at 3, 6, 12 and 18 months after loading. For statistical analyses, the mixed linear model was applied for the clinical and radiographic measurements observed around the implants. Simple comparisons of the location of the measurements in the two independent groups are performed with the Mann-Whitney U-test. In addition, the mixed model assumptions were checked. The implant and crown survival rate 18 months after loading was 100%, revealing no serious biologic or prosthetic complication. The mean changes of the buccal vertical bone height between implant placement and reentry surgery after 6 months revealed a small bone loss of -0.17 ± 1.79 mm (minimum -4 mm and maximum 2.5 mm) for the SH group and a bone gain of 1.79 ± 2.24 mm (minimum of -2.5 mm and maximum of 5 mm) for the GBR group, respectively (P = 0.017). Radiographic measurements demonstrated a slight bone loss of -0.39 ± 0.49 mm for the SH group and a stable bone level of 0.02 ± 0.48 mm for GBR group after 18 months. All peri-implant soft tissue parameters revealed healthy tissues with no difference between the two groups. Small bony dehiscence defects left for spontaneous healing demonstrated high implant survival rates with healthy and stable soft tissues. However, they revealed more vertical bone loss at the buccal aspect 6 months after implant insertion and also more marginal bone loss between crown insertion and 18 months after loading compared to sites treated with GBR. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Bone and gallium scanning in the pre-op evaluation of the infected dysvascular foot

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

Stewart, C.; Sakimura, I.; Dillon, A.

1984-01-01

The purpose of this study is to determine the value of bone and gallium scans in predicting healing levels in the dysvascular foot with an infection requiring amputation. Healing requires amputation at a level both free of infection and with adequate blood flow. Forty-one such patients had bone and gallium scans and Doppler studies prior to amputation at a level selected by the surgeon. Eight patients required multiple surgeries before healing was obtained. Bone and soft tissue infections were determined from scans and healing levels predicted (SPHL) as the most distal amputation level free from infection: toectomy, Reye's, transmetatarsal, calcanectomy,more » Syme's, below knee. Doppler healing levels (DPHL) were predicted using a standard ischemic index. Doppler alone predicted the final healing level (FHL) in 41% with 59% needing more proximal amputation. Scans alone predicted FHL in 64% with 26% needing more proximal amputation. Ten percent were distal to the SPHL and all healed. These scans showed infection at transition sites between amputation levels, and the more proximal level had been predicted. Using the more proximal of the DPHL and SPHL the FHL was predicted in 78% with another 12% having more proximal amputation for nursing reasons. In 10% amputation was performed between DPHL and SPHL or at the more distal level. In no case was successful surgery performed distal to the more distal SPHL or DPHL. Bone and gallium scans used with Doppler studies are useful in optimizing the choice of amputation level in the infected, dysvascular foot.« less

Osteoimmune Mechanisms of Segmental Bone Fracture Healing and Therapy

DTIC Science & Technology

2016-09-01

to civilians. Despite efforts involving allografts , surgery and fixators, intramedullary nailing and invasive plate fixing to heal segmental...efforts are focused on: tissue engineering approaches aimed at developing osteoconductive scaffolds, better quality synthetic bone grafts, and use of

Juvenile Swine Surgical Alveolar Cleft Model to Test Novel Autologous Stem Cell Therapies

PubMed Central

Caballero, Montserrat; Morse, Justin C.; Halevi, Alexandra E.; Emodi, Omri; Pharaon, Michael R.; Wood, Jeyhan S.

2015-01-01

Reconstruction of craniofacial congenital bone defects has historically relied on autologous bone grafts. Engineered bone using mesenchymal stem cells from the umbilical cord on electrospun nanomicrofiber scaffolds offers an alternative to current treatments. This preclinical study presents the development of a juvenile swine model with a surgically created maxillary cleft defect for future testing of tissue-engineered implants for bone generation. Five-week-old pigs (n=6) underwent surgically created maxillary (alveolar) defects to determine critical-sized defect and the quality of treatment outcomes with rib, iliac crest cancellous bone, and tissue-engineered scaffolds. Pigs were sacrificed at 1 month. Computed tomography scans were obtained at days 0 and 30, at the time of euthanasia. Histological evaluation was performed on newly formed bone within the surgical defect. A 1 cm surgically created defect healed with no treatment, the 2 cm defect did not heal. A subsequently created 1.7 cm defect, physiologically similar to a congenitally occurring alveolar cleft in humans, from the central incisor to the canine, similarly did not heal. Rib graft treatment did not incorporate into adjacent normal bone; cancellous bone and the tissue-engineered graft healed the critical-sized defect. This work establishes a juvenile swine alveolar cleft model with critical-sized defect approaching 1.7 cm. Both cancellous bone and tissue engineered graft generated bridging bone formation in the surgically created alveolar cleft defect. PMID:25837453

Concise review: Insights from normal bone remodeling and stem cell-based therapies for bone repair.

PubMed

Khosla, Sundeep; Westendorf, Jennifer J; Mödder, Ulrike I

2010-12-01

There is growing interest in the use of mesenchymal stem cells for bone repair. As a major reason for normal bone remodeling is the removal of fatigue microcracks, advances in our understanding of this process may inform approaches to enhance fracture healing. Increasing evidence now indicates that physiological bone remodeling occurs in close proximity to blood vessels and that these vessels carry perivascular stem cells that differentiate into osteoblasts. Similarly, fracture healing is critically dependent on the ingrowth of blood vessels not only for a nutrient supply but also for the influx of osteoblasts. A number of animal and human studies have now shown the potential benefit of bone marrow-derived mesenchymal stem cells in enhancing bone repair. However, as in other tissues, the question of whether these cells improve fracture healing directly by differentiating into osteoblasts or indirectly by secreting paracrine factors that recruit blood vessels and the accompanying perivascular stem cells remains a major unresolved issue. Moreover, CD34+ cells, which are enriched for endothelial/hematopoietic cells, have also shown efficacy in various bone repair models, at least in part due to the induction of angiogenesis and recruitment of host progenitor cells. Thus, mesenchymal and nonmesenchymal stem/progenitor cells are attractive options for bone repair. It is possible that they contribute directly to bone repair, but it is also likely that they express paracrine factors in the appropriate amounts and combinations that promote and sustain the healing process.

Nano-crystalline diamond-coated titanium dental implants - a histomorphometric study in adult domestic pigs.

PubMed

Metzler, Philipp; von Wilmowsky, Cornelius; Stadlinger, Bernd; Zemann, Wolfgang; Schlegel, Karl Andreas; Rosiwal, Stephan; Rupprecht, Stephan

2013-09-01

Promising biomaterial characteristics of diamond-coatings in biomedicine have been described in the literature. However, there is a lack of knowledge about implant osseointegration of this surface modification compared to the currently used sandblasted acid-etched Ti-Al6-V4 implants. The aim of this study was to investigate the osseointegration of microwave plasma-chemical-vapour deposition (MWP-CVD) diamond-coated Ti-Al6-V4 dental implants after healing periods of 2 and 5 months. Twenty-four MWP-CVD diamond-coated and 24 un-coated dental titanium-alloy implants (Ankylos(®)) were placed in the frontal skull of eight adult domestic pigs. To evaluate the effects of the nano-structured surfaces on bone formation, a histomorphometric analysis was performed after 2 and 5 months of implant healing. Histomorphometry analysed the bone-to-implant contact (BIC). No significant difference in BIC for the diamond-coated implants in comparison to reference implants could be observed for both healing periods. Scanning electron microscopy revealed an adequate interface between the bone and the diamond surface. No delamination or particle-dissociation due to shearing forces could be detected. In this study, diamond-coated dental titanium-alloy implants and sandblasted acid-etched implants showed a comparable degree of osseointegration. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Single-staged vs. two-staged implant placement using bone ring technique in vertically deficient alveolar ridges - Part 1: histomorphometric and micro-CT analysis.

PubMed

Nakahara, Ken; Haga-Tsujimura, Maiko; Sawada, Kosaku; Kobayashi, Eizaburo; Mottini, Matthias; Schaller, Benoit; Saulacic, Nikola

2016-11-01

Simultaneous implant placement with bone grafting shortens the overall treatment period, but might lead to the peri-implant bone loss or even implant failure. The aim of this study was to compare the single-staged to two-staged implant placement using the bone ring technique. Four standardized alveolar bone defects were made in the mandibles of nine dogs. Dental implants (Straumann BL ® , Basel, Switzerland) were inserted simultaneously with bone ring technique in test group and after 6 months of healing period in control group. Animals of both groups were euthanized at 3 and 6 months of osseointegration period. The harvested samples were analyzed by means of histology and micro-CT. The amount of residual bone decreased while the amount of new bone increased up to 9 months of healing period. All morphometric parameters remained stable between 3 and 6 months of osseointegration period within groups. Per a given time point, median area of residual bone graft was higher in test group and area of new bone in control group. The volume of bone ring was greater in test than in control group, reaching the significance at 6 months of osseointegration period (P = 0.002). In the present type of bone defect, single-staged implant placement may be potentially useful to shorten an overall treatment period. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The effect of mesenchymal stem cell sheets on structural allograft healing of critical sized femoral defects in mice.

PubMed

Long, Teng; Zhu, Zhenan; Awad, Hani A; Schwarz, Edward M; Hilton, Matthew J; Dong, Yufeng

2014-03-01

Structural bone allografts are widely used in the clinic to treat critical sized bone defects, despite lacking the osteoinductive characteristics of live autografts. To address this, we generated revitalized structural allografts wrapped with mesenchymal stem/progenitor cell (MSC) sheets, which were produced by expanding primary syngenic bone marrow derived cells on temperature-responsive plates, as a tissue-engineered periosteum. In vitro assays demonstrated maintenance of the MSC phenotype in the sheets, suggesting that short-term culturing of MSC sheets is not detrimental. To test their efficacy in vivo, allografts wrapped with MSC sheets were transplanted into 4-mm murine femoral defects and compared to allografts with direct seeding of MSCs and allografts without cells. Evaluations consisted of X-ray plain radiography, 3D microCT, histology, and biomechanical testing at 4- and 6-weeks post-surgery. Our findings demonstrate that MSC sheets induce prolonged cartilage formation at the graft-host junction and enhanced bone callus formation, as well as graft-host osteointegration. Moreover, a large periosteal callus was observed spanning the allografts with MSC sheets, which partially mimics live autograft healing. Finally, biomechanical testing showed a significant increase in the structural and functional properties of MSC sheet grafted femurs. Taken together, MSC sheets exhibit enhanced osteogenicity during critical sized bone defect repair, demonstrating the feasibility of this tissue engineering solution for massive allograft healing. Copyright © 2013 Elsevier Ltd. All rights reserved.

Socket Preservation using Enzyme-treated Equine Bone Granules and an Equine Collagen Matrix: A Case Report with Histological and Histomorphometrical Assessment.

PubMed

Leonida, Alessandro; Todeschini, Giovanni; Lomartire, Giovanni; Cinci, Lorenzo; Pieri, Laura

2016-11-01

To histologically assess the effectiveness of a socket-preservation technique using enzyme-treated equine bone granules as a bone-graft material in combination with an equine collagen matrix as a scaffold for soft-tissue regeneration. Enzyme-treated equine bone granules and equine collagen matrix recently have been developed to help overcome alveolar bone deficiencies that develop in the wake of edentulism. The patient had one mandibular molar extracted and the socket grafted with equine bone granules. The graft was covered with the equine collagen matrix, placed in a double layer. No flap was prepared, and the gingival margins were stabilized with a single stitch, leaving the matrix partially exposed and the site to heal by secondary intention. The adjacent molar was extracted 1 month later, and that socket was left to heal by secondary intention without any further treatment. Three months after each surgery, an implant was placed and a biopsy was collected. The two biopsies underwent histological processing and qualitative evaluation. Histomorphometric analysis was also performed to calculate the percentage of newly formed bone (NFB) in the two cores. Healing at both sites was uneventful, and no inflammation or other adverse reactions were observed in the samples. Soft-tissue healing by secondary intention appeared to occur faster at the grafted site. The corresponding core showed a marked separation between soft and hard tissue that was not observed in the core from the nongrafted site, where soft-tissue hypertrophy could be observed. Newly formed bone at the grafted and nongrafted sites was not significantly different (27.2 ± 7.1 and 29.4 ± 6.2% respectively, p = 0.45). The surgical technique employed in this case appeared to facilitate postextraction soft-tissue healing by second intention and simplify soft-tissue management. Using a collagen-based matrix to cover a postextraction grafted site may facilitate second intention soft-tissue healing and proper soft-tissue growth.

Microcracks induce osteoblast alignment and maturation on hydroxyapatite scaffolds

NASA Astrophysics Data System (ADS)

Shu, Yutian

Physiological bone tissue is a mineral/collagen composite with a hierarchical structure. The features in bone, such as mineral crystals, fibers, and pores can range from the nanometer to the centimeter in size. Currently available bone tissue scaffolds primarily address the chemical composition, pore size, and pore size distribution. While these design parameters are extensively investigated for mimicking bone function and inducing bone regeneration, little is known about microcracks, which is a prevalent feature found in fractured bone in vivo and associated with fracture healing and repair. Since the purpose of bone tissue engineering scaffold is to enhance bone regeneration, the coincidence of microcracks and bone densification should not be neglected but rather be considered as a potential parameter in bone tissue engineering scaffold design. The purpose of this study is to test the hypothesis that microcracks enhance bone healing. In vitro studies were designed to investigate the osteoblast (bone forming cells) response to microcracks in dense (94%) hydroxyapatite substrates. Microcracks were introduced using a well-established Vickers indentation technique. The results of our study showed that microcracks induced osteoblast alignment, enhanced osteoblast attachment and more rapid maturation. These findings may provide insight into fracture healing mechanism(s) as well as improve the design of bone tissue engineering orthopedic scaffolds for more rapid bone regeneration.

A Porous Hydroxyapatite/Gelatin Nanocomposite Scaffold for Bone Tissue Repair: In Vitro and In Vivo Evaluation.

PubMed

Azami, Mahmoud; Tavakol, Shima; Samadikuchaksaraei, Ali; Hashjin, Mehran Solati; Baheiraei, Nafiseh; Kamali, Mehdi; Nourani, Mohammad Reza

2012-01-01

In this study, a nano-structured scaffold was designed for bone repair using hydroxapatite and gelatin as its main components. The scaffold was prepared via layer solvent casting combined with freeze-drying and lamination techniques and characterized by the commonly used bulk techniques. The biocompatibility and osteoconductivity of this scaffold and its capacity to promote bone healing were also evaluated. Osteoblast-like cells were seeded on these scaffolds and their proliferation rate, intracellular alkaline phosphatase (ALP) activity and ability to form mineralized bone nodules were compared with those osteoblasts grown on cell culture plastic surfaces. Also, the scaffolds were implanted in a critical bone defect created on rat calvarium. Engineering analyses show that the scaffold posses a three dimensional interconnected homogenous porous structure with a porosity of about 82% and pore sizes ranging from 300 to 500 μm. Mechanical indices are in the range of spongy bones. The results obtained from biological assessment show that this scaffold does not negatively affect osteoblasts proliferation rate and improves osteoblasts function as shown by increasing the ALP activity and calcium deposition and formation of mineralized bone nodules. In addition, the scaffold promoted healing of critical size calvarial bone defect in rats. It could be concluded that this scaffold fulfills all the main requirements to be considered as a bone substitute.

A comparison of treating Unicameral bone cyst using steroids and percutaneous autologous bone marrow aspiration injection.

PubMed

Akram, Muhammad; Farooqi, Faheem Mubashir; Shahzad, Muhammad Latif; Awais, Syed Muhammad

2015-11-01

To compare the results of percutaneous autologous bone aspiration injection and steroids injections in the treatment of unicameral bone cyst. The prospective study was conducted at Mayo Hospital, Lahore, from January 2008 to March 2014, and comprised patients diagnosed radiologically as a case of unicameral bone cyst. The patients were divided into two groups, with group 1 being treated with bone marrow aspiration injection, while group 2 was given steroids injection. Aspiration of bone marrow was done from tibial tuberosity. The 30 patients in the study were divided into two groups of 15(50%) each. In group 1, 8(53.34%) patients and in group 2, 3 (20%) patients achieved healing after the first injection (p<0.05), while overall success rates were 13(86.67%) in group 1, and 11(73.33%) in group 2 (p> 0.05). The mean number of procedures required in group 1 was 1.57± 0.495 (range: 01-3) and for 2.19 ± 1.076 (range: 1-5) in group 2 (p<0.05), and mean interval-to-healing was 14.3 months ± 8.705 (range: 7-36) for group 1 and 12.5 months ± 7.88 (range: 4-32) for group 2 (p> 0.05). Bone marrow aspiration injection was better than steroids in treating unicameral bone cyst.

Role of Cbl-PI3K Interaction during Skeletal Remodeling in a Murine Model of Bone Repair.

PubMed

Scanlon, Vanessa; Soung, Do Yu; Adapala, Naga Suresh; Morgan, Elise; Hansen, Marc F; Drissi, Hicham; Sanjay, Archana

2015-01-01

Mice in which Cbl is unable to bind PI3K (YF mice) display increased bone volume due to enhanced bone formation and repressed bone resorption during normal bone homeostasis. We investigated the effects of disrupted Cbl-PI3K interaction on fracture healing to determine whether this interaction has an effect on bone repair. Mid-diaphyseal femoral fractures induced in wild type (WT) and YF mice were temporally evaluated via micro-computed tomography scans, biomechanical testing, histological and histomorphometric analyses. Imaging analyses revealed no change in soft callus formation, increased bony callus formation, and delayed callus remodeling in YF mice compared to WT mice. Histomorphometric analyses showed significantly increased osteoblast surface per bone surface and osteoclast numbers in the calluses of YF fractured mice, as well as increased incorporation of dynamic bone labels. Furthermore, using laser capture micro-dissection of the fracture callus we found that cells lacking Cbl-PI3K interaction have higher expression of Osterix, TRAP, and Cathepsin K. We also found increased expression of genes involved in propagating PI3K signaling in cells isolated from the YF fracture callus, suggesting that the lack of Cbl-PI3K interaction perhaps results in enhanced PI3K signaling, leading to increased bone formation, but delayed remodeling in the healing femora.

Autonomic healing of acrylic bone cement.

PubMed

Gladman, A Sydney; Celestine, Asha-Dee N; Sottos, Nancy R; White, Scott R

2015-01-28

Self-healing in orthopedic bone cement is demonstrated with a novel thermoplastic solvent-bonding approach. Low toxicity solvent-filled microcapsules, embedded in a commercial acrylic bone cement matrix, enable recovery of up to 80% of the virgin fracture toughness of the cement at room and body temperature conditions without external stimuli or human intervention. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A theoretical analysis and finite element simulation of fixator-bone system stiffness on healing progression.

PubMed

Li, Jianfeng; Zhao, Xia; Hu, Xiaojie; Tao, Chunjing; Ji, Run

2018-03-01

The unilateral external fixator has become a quick and easy application for fracture stabilization of the extremities; the main value for evaluation of mechanical stability of the external fixator is stiffness. The stiffness property of the external fixator affects the local biomechanical environment of fractured bone. In this study, a theoretical model with changing Young's modulus of the callus is established by using the Castigliano's theory, investigating compression stiffness, torsional stiffness and bending stiffness of the fixator-bone system during the healing process. The effects of pin deviation angle on three stiffness methods are also investigated. In addition, finite element simulation is discussed regarding the stress distribution between the fixator and bone. The results reveal the three stiffness evaluation methods are similar for the fixator-bone system. Finite element simulation shows that with increased healing time, the transmission of the load between the fixator and bone are different. In addition, the finite element analyses verify the conclusions obtained from the theoretical model. This work helps orthopedic doctors to monitor the progression of fracture healing and determine the appropriate time for removal of a fixation device and provide important theoretical methodology.

Biological Evaluation of Implant Drill Made from Zirconium Dioxide.

PubMed

Akiba, Yosuke; Eguchi, Kaori; Akiba, Nami; Uoshima, Katsumi

2017-04-01

Zirconia is a good candidate material in the dental field. In this study, we evaluated biological responses against a zirconia drill using a bone cavity healing model. Zirconia drills, stainless steel drills, and the drilled bone surface were observed by scanning electron microscopy (SEM), before and after cavity preparation. For the bone cavity healing model, the upper first and second molars of Wistar rats were extracted. After 4 weeks, cavities were prepared with zirconia drills on the left side. As a control, a stainless steel drill was used on the right side. At 3, 7, and 14 days after surgery, micro-CT images were taken. Samples were prepared for histological staining. SEM images revealed that zirconia drills maintained sharpness even after 30 drilling procedures. The bone surface was smoother with the zirconia drill. Micro-CT images showed faster and earlier bone healing in the zirconia drill cavity. On H-E staining, at 7 days, the zirconia drill defect had a smaller blank lacunae area. At 14 days, the zirconia drill defect was filled with newly formed bone. The zirconia drill induces less damage during cavity preparation and is advantageous for bone healing. (197 words). © 2016 The Authors Clinical Implant Dentistry and Related Research Published by Wiley Periodicals, Inc.

Surface modification of biomedical and dental implants and the processes of inflammation, wound healing and bone formation.

PubMed

Stanford, Clark M

2010-01-25

Bone adaptation or integration of an implant is characterized by a series of biological reactions that start with bone turnover at the interface (a process of localized necrosis), followed by rapid repair. The wound healing response is guided by a complex activation of macrophages leading to tissue turnover and new osteoblast differentiation on the implant surface. The complex role of implant surface topography and impact on healing response plays a role in biological criteria that can guide the design and development of future tissue-implant surface interfaces.

A histological study of stainless steel and titanium screws in bone.

PubMed

Millar, B G; Frame, J W; Browne, R M

1990-04-01

This study compared histologically the tissue response of stainless steel and titanium screws when inserted into the calvaria of eight beagle dogs for periods of 1, 4, 12, and 24 weeks. There was minimal fibrous reaction around both screw types with excellent long-term bone healing. After 24 weeks there was no discernable difference in the tissue reaction between the two types of screw.

Soft Tissue Alterations in Esthetic Postextraction Sites: A 3-Dimensional Analysis.

PubMed

Chappuis, V; Engel, O; Shahim, K; Reyes, M; Katsaros, C; Buser, D

2015-09-01

Dimensional alterations of the facial soft and bone tissues following tooth extraction in the esthetic zone play an essential role to achieve successful outcomes in implant therapy. This prospective study is the first to investigate the interplay between the soft tissue dimensions and the underlying bone anatomy during an 8-wk healing period. The analysis is based on sequential 3-dimensional digital surface model superimpositions of the soft and bone tissues using digital impressions and cone beam computed tomography during an 8-wk healing period. Soft tissue thickness in thin and thick bone phenotypes at extraction was similar, averaging 0.7 mm and 0.8 mm, respectively. Interestingly, thin bone phenotypes revealed a 7-fold increase in soft tissue thickness after an 8-wk healing period, whereas in thick bone phenotypes, the soft tissue dimensions remained unchanged. The observed spontaneous soft tissue thickening in thin bone phenotypes resulted in a vertical soft tissue loss of only 1.6 mm, which concealed the underlying vertical bone resorption of 7.5 mm. Because of spontaneous soft tissue thickening, no significant differences were detected in the total tissue loss between thin and thick bone phenotypes at 2, 4, 6, and 8 wk. More than 51% of these dimensional alterations occurred within 2 wk of healing. Even though the observed spontaneous soft tissue thickening in thin bone phenotypes following tooth extraction conceals the pronounced underlying bone resorption pattern by masking the true bone deficiency, spontaneous soft tissue thickening offers advantages for subsequent bone regeneration and implant therapies in sites with high esthetic demand (Clinicaltrials.gov NCT02403700). © International & American Associations for Dental Research.

Healing at the Interface Between Autologous Block Bone Grafts and Recipient Sites Using n-Butyl-2-Cyanoacrylate Adhesive as Fixation: Histomorphometric Study in Rabbits.

PubMed

De Santis, Enzo; Silva, Erick Ricardo; Martins, Evandro Neto Carneiro; Favero, Riccardo; Botticelli, Daniele; Xavier, Samuel Porfirio

2017-12-01

The aim of the present split-mouth (split-plot) study was to describe the sequential healing in the interface between autologous bone grafts and recipient parent bone, fixed using an n-butyl-2-cyanoacrylate adhesive with or without an additional titanium fixation screw. Bone grafts were collected from the calvaria and fixed to the lateral aspect of the mandible in 24 rabbits. The cortical layers of the recipient sites were perforated, and the grafts were randomly fixed using an n-butyl-2-cyanocrylate adhesive, either alone or in conjunction with a 1.5 mm × 6.0 mm titanium fixation screw. The animals were sacrificed after 3, 7, 20, and 40 days, and histomorphometric evaluations of the interface between graft and parent bone were performed. Only 2 of 6 grafts in each group were partially incorporated to the parent bone after 40 days of healing. The remaining grafts were separated from the parent bone by adhesive and connective tissue. It was concluded that the use of n-butyl-2-cyanoacrylate as fixation of an autologous bone graft to the lateral aspect of the mandible was able to maintain the fixation over time but did not incorporate the graft to the recipient sites. Use of fixation screws did not improve the healing.

Systemic Delivery of Free Chitosan Accelerates Femur Fracture Healing in Rats.

PubMed

Shao, Peng; Wei, Yongzhong; Dass, Crispin R; Zhang, Guoying; Wu, Zhisheng

2018-01-01

Chitosan-containing compounds have been shown to be suitable for bone replacement, but few studies demonstrate the impact of the chitosan as a free drug on the fracture.In this study, we aimed to evaluate possible effects of free chitosan on fracture healing. Thirty adult male Sprague-Dawley rats with a mean body weight of 205 g (range from 200g to 210g) were randomly and equally divided into two groups. Standardized femur fractures were created in all rats. Treatments were administered intraperitoneally twice weekly at 1 mg chitosan per injection and the controls were administered physiological saline. The site of the fracture was compared with the control group at 1, 2 and 4 weeks after surgery (n=5 in each group). The weight, activity and reaction of the rats were observed at all the timepoints. Anterior-posterior radiographs and micro-CT scans of all fractures were taken after surgery, and the parameters included: the volume of callus that was calculated using the Perkins volume formula, BV/TV, BV, BMD of cortical bone, cortical thickness, and cortical number at the fracture sites. After sacrifice, fractured femurs from rats were dissected and carefully cleaned of muscle around the fracture callus to preserve callus integrity. Sections were stained with haematoxylin and eosin for histological evaluation of healing. Radiological (X-ray and micro-CT) evaluation showed that fracture healing of the experimental group was better than control group at the second week and fourth week. Histological evaluation revealed fracture healing of the experimental group was better than control group at the same time. There was no statistically significant difference in fracture healing between the two groups at the first week. Systemic delivery of free chitosan can accelerate the bone healing process in rat femur fracture at the early-middle stage. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase: Acceleration of fracture healing via inducible nitric oxide synthase.

PubMed

Rajfer, R A; Kilic, A; Neviaser, A S; Schulte, L M; Hlaing, S M; Landeros, J; Ferrini, M G; Ebramzadeh, E; Park, S-H

2017-02-01

We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days. Unilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression nail. Rats were treated daily either with vehicle, tadalafil or COMB-4. Biomechanical testing of the healed fracture was performed on day 42. The volume, mineral content and bone density of the callus were measured by quantitative CT on days 14 and 42. Expression of iNOS was measured by immunohistochemistry. When compared with the control group, the COMB-4 group exhibited 46% higher maximum strength ( t -test, p = 0.029) and 92% higher stiffness ( t -test, p = 0.023), but no significant changes were observed in the tadalafil group. At days 14 and 42, there was no significant difference between the three groups with respect to callus volume, mineral content and bone density. Expression of iNOS at day 14 was significantly higher in the COMB-4 group which, as expected, had returned to baseline levels at day 42. This study demonstrates an enhancement in fracture healing by an oral natural product known to augment iNOS expression. Cite this article: R. A. Rajfer, A. Kilic, A. S. Neviaser, L. M. Schulte, S. M. Hlaing, J. Landeros, M. G. Ferrini, E. Ebramzadeh, S-H. Park. Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase: Acceleration of fracture healing via inducible nitric oxide synthase. Bone Joint Res 2017:6:-97. DOI: 10.1302/2046-3758.62.BJR-2016-0164.R2. © 2017 Park et al.

Multiple roles of tumor necrosis factor-alpha in fracture healing.

PubMed

Karnes, Jonathan M; Daffner, Scott D; Watkins, Colleen M

2015-09-01

This review presents a summary of basic science evidence examining the influence of tumor necrosis factor-alpha (TNF-α) on secondary fracture healing. Multiple studies suggest that TNF-α, in combination with the host reservoir of peri-fracture mesenchymal stem cells, is a main determinant in the success of bone healing. Disease states associated with poor bone healing commonly have inappropriate TNF-α responses, which likely contributes to the higher incidence of delayed and nonunions in these patient populations. Appreciation of TNF-α in fracture healing may lead to new therapies to augment recovery and reduce the incidence of complications. Copyright © 2015 Elsevier Inc. All rights reserved.

Continuous decompression of unicameral bone cyst with cannulated screws: a comparative study.

PubMed

Brecelj, Janez; Suhodolcan, Lovro

2007-09-01

We determined the role of mechanical decompression in the resolution of unicameral bone cyst. A total of 69 children with unicameral bone cysts were treated either by (i) open curettage and bone grafting, (ii) steroid injection or (iii) cannulated screw insertion. During a mean follow-up of 69 months (range, 12-58), the cysts were evaluated by radiological criteria. The healing rates in the three groups were 25, 12 and 29% after the first treatment, and a further 50, 19 and 65% after the second. The study has demonstrated the advantages of the decompression technique for unicameral bone cysts over other treatment modalities studied.

Mixing implants of differing metallic composition in the treatment of upper-extremity fractures.

PubMed

Acevedo, Daniel; Loy, Bo Nasmyth; Loy, Bo Nasymuth; Lee, Brian; Omid, Reza; Itamura, John

2013-09-01

Mixing implants with differing metallic compositions has been avoided for fear of galvanic corrosion and subsequent failure of the implants and of bone healing. The purpose of this study was to evaluate upper-extremity fractures treated with open reduction and internal fixation with metallic implants that differed in metallic composition placed on the same bone. The authors studied the effects of using both stainless steel and titanium implants on fracture healing, implant failure, and other complications associated with this method of fixation. Their hypothesis was that combining these metals on the same bone would not cause clinically significant nonunions or undo clinical effects from galvanic corrosion. A retrospective review was performed of 17 patients with upper-extremity fractures fixed with metal implants of differing metallic compositions. The primary endpoint was fracture union. Eight clavicles, 2 proximal humeri, 3 distal humeri, 3 olecranons, and 1 glenoid fracture with an average follow-up 10 months were reviewed. All fractures healed. One patient experienced screw backout, which did not affect healing. This study implies that mixing implants with differing metallic compositions on the same bone for the treatment of fractures does not adversely affect bone healing. No evidence existed of corrosion or an increase in complications with this method of treatment. Contrary to prior belief, small modular hand stainless steel plates can be used to assist in reduction of smaller fracture fragments in combination with anatomic titanium plates to obtain anatomic reduction of the fracture without adversely affecting healing. Copyright 2013, SLACK Incorporated.

The effect of diabetes on bone formation following application of the GBR principle with the use of titanium domes.

PubMed

Lee, Sang-Bok; Retzepi, Maria; Petrie, Aviva; Hakimi, Ahmad-Reza; Schwarz, Frank; Donos, Nikolaos

2013-01-01

The aim of the study was to evaluate the effect of experimental diabetes and metabolic control on de novo bone formation following the GBR principle under titanium dome with a hydrophobic or hydrophilic surface. Three groups of equal number of randomly allocated Wistar strain rats were created: (a) uncontrolled, streptozotocin-induced diabetes (D); (b) insulin-controlled diabetes (CD); (c) healthy (H). Each group was then further divided into two groups according to either 7 or 42 days of healing period, which received either a hydrophobic (SLA: A) or a hydrophilic (SLActive: B) dome. The undecalcified sections were evaluated by qualitative and quantitative histological analysis and the differences between means for the groups (D, CD, and H) and the type of domes (SLA and SLActive) at each of two observational periods (i.e. 7 and 42 days) were assessed by performing a two-way analysis of variance (ANOVA). In all experimental groups, significant de novo bone formation under the domes was observed at 42 days of healing. There was a tendency of increased new total bone (TB) formation in H and CD groups compared to D group at 42 days of healing. Also, the SLActive titanium surface showed a trend of promoting superior TB formation at the early observational period among the experimental groups, however these differences did not reach statistical significance. In regards to the bone-to-implant contact (BIC%) under the both dome treatments (SLA and SLActive), there was no statistically significant difference among the H, CD, and D groups at both 7 and 42 days. Despite of the presence of uncontrolled diabetes, substantial de novo bone formation can be achieved in titanium domes with a hydrophobic and a hydrophilic surface. The use of SLActive titanium surface may present a tendency to promote new bone formation in healthy and diabetic conditions at 7 days of healing, however the obtained data do not allow any robust conclusions. © 2012 John Wiley & Sons A/S.

A randomized and controlled clinical trial of two different compositions of deproteinized bovine bone and autogenous bone used for lateral ridge augmentation.

PubMed

Mordenfeld, Arne; Johansson, Carina B; Albrektsson, Tomas; Hallman, Mats

2014-03-01

The aim of the study was to radiologically and histologically evaluate the graft healing and volumetric changes after lateral augmentation with two different compositions of deproteinized bovine bone (DPBB) and autogenous bone (AB). Thirteen patients with a mean age of 59.6 ± 12.1 years (six men and seven women) were included in this randomized and controlled trial, designed as a split-mouth study. Ten edentulous and four partially edentulous jaws with an alveolar ridge width of ≤4 mm were laterally augmented with a graft composition of 60 : 40 (DPBB/AB) on one side and 90 : 10 (DPBB/AB) on the contralateral side. Cone beam computed tomography (CB/CT) was obtained immediately postoperatively and after a healing period of 7.5 months. Width changes were measured on CB/CT scans. After a mean healing period of 8.1 months (range, 7.9-8.3), biopsies were retrieved perpendicular to the crest from each graft by means of a trephine bur. Histomorphometry was performed, and the following variables were recorded: Ingrowth of new bone (percentage of total graft width), percentage of DPBB, bone and soft tissue, and percentage of DPBB particles in contact with bone. The mean gained width of the alveolar crest after 7.5 months was significantly more for the 60 : 40 mixture compared with the 90 : 10 mixture, 3.5 (±1.3) mm and 2.9 (±1.3) mm, respectively. There was a significant difference in graft width reduction between 60 : 40 and 90 : 10 after 7.5 months, 37 (±19.9)% and 46.9 (±23.5)%, respectively. New bone ingrowth had occurred in 82.1 (±23.3)% and 82.3 (±26.6)% of the graft, respectively. There were no statistical differences between fractions of different tissues between the 90 : 10 and 60 : 40 compositions. However, there were significantly more soft tissue and less new bone formation closer to the periosteum compared with the graft portion closer to the residual bone in both 60 : 40 and 90 : 10 compositions. There was significantly less graft width reduction with a mixture of 60 : 40 (DPBB/AB) compared with a mixture of 90 : 10 composition, but the results from the histomorphometry showed no statistical differences comparing the groups. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Whole body vibration during fracture healing intensifies the effects of estradiol and raloxifene in estrogen-deficient rats.

PubMed

Stuermer, Ewa K; Komrakova, Marina; Sehmisch, Stephan; Tezval, Mohammad; Dullin, Christian; Schaefer, Nadine; Hallecker, Jan; Stuermer, Klaus M

2014-07-01

Current osteoporosis therapies aim to delay bone destruction and have additional anabolic effects. While they have demonstrated some positive effects on bone healing, more progress is needed in this area. This study used the well-known osteoporotic agents estrogen (E) and raloxifene (R) in conjunction with biomechanical whole body vibration (WBV) at a frequency of 70 Hz twice daily for six weeks to stimulate bone healing. Eighty-four 3-month old female Sprague-Dawley rats (12 per group) were bilaterally ovariectomized to develop osteopenia within eight weeks. Osteotomy of the metaphyseal tibiae was performed and fracture healing was then studied using mechanical tests, histomorphometry, computed tomography (μCT), and gene analysis. We found that E and R improved the structure of osteopenic bones as did WBV alone, although significant levels for WBV were seldom reached. Combination treatments significantly enhanced stiffness (R+WBV; p<0.05), endosteal bone (R+WBV; p<0.01), and trabecular density (E+WBV; p<0.05, R+WBV; p<0.05). In addition, the expression of osteoclast-specific Trap was significantly reduced after treatment with E, R, or their combination with WBV (p<0.01). The effects were additive and not inhibitory, leading us to conclude that the combined applications of WBV with E or R may improve the healing of osteopenic bones. The therapies studied are all currently approved for human use, suggesting ready applicability to clinical practice. To better understand the effects of WBV on osteopenic bones, the ideal vibration regime will require further study. Copyright © 2014 Elsevier Inc. All rights reserved.

Combined application of latissimus dorsi myocutaneous flap and iliac bone flap in the treatment of chronic osteomyelitis of the lower extremity.

PubMed

Ju, Jihui; Li, Lei; Zhou, Rong; Hou, Ruixing

2018-05-18

To evaluate the clinical efficacy and safety of latissimus dorsi myocutaneous flap (stage I) combined with iliac bone flap (stage II) in the treatment of chronic osteomyelitis of the lower extremity. Clinical data of 18 patients undergoing latissimus dorsi myocutaneous flap in combination with iliac bone flap grafting were retrospectively analyzed. Among them, 2 patients developed chronic osteomyelitis of the lower segment of the femur, 4 were diagnosed with chronic osteomyelitis of the tibial plateau, and 12 with chronic osteomyelitis of the lower segment of the tibia. All the latissimus dorsi myocutaneous flaps survived in 18 patients. After the corresponding surgery, primary wound healing was achieved in 11 patients, and delayed wound healing was obtained in 7 cases. All wounds were completely healed with postoperative 2 months. Following the iliac bone flap grafting, primary would healing was accomplished in all cases. All dorsal window chambers survived. The bone defects were properly restored within 4-12 postoperative months. Functional training was performed after removal of the internal and external fixators. Postoperative follow-up was endured from 6 months to 10 years. All patients were satisfied with the bone healing and flap texture without the incidence of osteomyelitis and sinus tract. No contraction was observed in the grafting area of 2 patients receiving latissimus dorsi myocutaneous flap grafting. Residual linear scars were noted in the dorsal and iliac donor sites. Combined usage of stage I latissimus dorsi myocutaneous flap and stage II iliac bone flap grafting is an efficacious and safe surgical technique in clinical practice.

Three-dimensional analysis of bone remodeling following ridge augmentation of compromised extraction sockets in periodontitis patients: A randomized controlled study.

PubMed

Aimetti, Mario; Manavella, Valeria; Corano, Lisa; Ercoli, Elena; Bignardi, Cristina; Romano, Federica

2018-02-01

The aim of this study was to analyze linear and volumetric hard tissue changes in severely resorbed alveolar sockets after ridge augmentation procedure and to compare them with spontaneous healing using three-dimensional cone beam computed tomography (CBCT). Thirty patients (mean age 53.2 ± 6.3 years) requiring tooth extraction for advanced periodontitis were randomly allocated to test and control groups. The test sites were grafted using a collagenated bovine-derived bone (DBBM-C) covered with a collagen membrane, while control sites had spontaneous healing. Both groups healed by secondary intention. Linear and volumetric measurements were taken on superimposed CBCT images obtained after tooth extraction and 12 months later. Greater horizontal shrinkage, localized mainly in the crestal zone, was observed in the control group (4.92 ± 2.45 mm) compared to the test group (2.60 ± 1.24 mm). While both groups presented a rebuilding of the buccal wall, it was most pronounced in the grafted sockets (2.50 ± 2.12 mm vs. 0.51 ± 1.02 mm). A significant difference was also registered in the percentage of volume loss between grafted and non-grafted sites (9.14% vs. 35.16%, p-value <.0001). Alveolar sockets with extensive buccal bone deficiencies undergo significant three-dimensional volumetric alterations following natural healing. The immediate application of a slow-resorbing xenograft with a covering collagen membrane seems to be effective in improving alveolar ridge shape and dimensions, thus potentially reducing the need for adjunctive regenerative procedures at the time of implant placement. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The influence of alendronate on the healing of extraction sockets of ovariectomized rats assessed by in vivo micro-computed tomography.

PubMed

Jee, Jeong-Hyun; Lee, Wan; Lee, Byung Do

2010-08-01

Many dental patients take bisphosphonates to reduce the risk of hip and vertebral fractures. In vivo micro-computed tomography (micro-CT) was used to examine the longitudinal inhibitory effect of alendronate on the healing of extraction sockets in ovariectomized rats. Twenty 5-week-old Sprague-Dawley rats were assigned randomly to 1 of 3 groups: sham-operated (n = 5), and 2 ovariectomized (OVX) groups: saline treated (0.1 mL/100 g/d, n = 7) and alendronate treated (1 mg/kg/d, n = 8). Before micro-CT scanning, the left maxillary first molars of the rats were extracted. In vivo micro-CT (spatial resolution 50 x 50 mum) of the jaw was performed at baseline and at 2-week intervals for 6 weeks. Alveolar-bone radiographic densities and dimensions were analyzed with repeated measures analysis of variance. The bony healing patterns of the extraction sockets were also evaluated in each group. The radiographic socket densities of the sham-treated and OVX-alendronate groups significantly increased during the first 4 weeks after extraction (P < .05). At 2 weeks, the radiographic densities of the sockets in the OVX-saline group increased, but the increase was significantly lower than for the other groups at 4 weeks (P < .05). Newly formed bone was identified in the extraction sockets in all groups 2 to 6 weeks after extraction. There was a significant loss of alveolar ridge height at the second week postextraction compared with baseline, and at the fourth week compared with the second week (P < .05) except in the alendronate group. Alendronate appears to promote the healing of extraction sockets in estrogen-deficient rats and helps resist the loss of alveolar bone adjacent to extraction sockets. Copyright 2010 Mosby, Inc. All rights reserved.

Modulation of early functional recovery of Achilles tendon to bone unit after transection by BPC 157 and methylprednisolone.

PubMed

Krivic, A; Majerovic, M; Jelic, I; Seiwerth, S; Sikiric, P

2008-05-01

In the presented study we compared the effect of stable peptide BPC 157 and methylprednisolone on early functional recovery after Achilles tendon to bone transection in a rat model before collagen healing started. Surgical transection of the right Achilles tendon to bone area was performed in seventy two Wistar Albino male rats. Healing Achilles tendon edges were harvested at days 1-4 following the transection. Using Achilles functional index (AFI), myeloperoxidase activity, histological inflammatory cell influx and vascular index early functional recovery was evaluated. Agents (stable peptide BPC 157 10 microg methylprednisolone 5 mg, normal saline 5 ml) were given alone (/kg b.w., intraperitoneally, once daily, first 30 min after surgery, last 24 h before analysis). Control group received normal saline 5 ml/kg. BPC 157 improved functional recovery (AFI values increased at all time points, p <0.05) by anti-inflammatory (decreased myeloperoxidase (MPO) activity and histological inflammatory cell influx, p <0.05) and increased new blood vessel formation (increased vascular index, p <0.05). Methyprednisolone decreased MPO activity and histological inflammatory cell influx, (p <0.05) but also decreased new blood vessel formation and did not affect early functional recovery. Stable peptide BPC 157 with combined anti-inflammatory action and induction of early new blood vessel formation facilitates early functional recovery in Achilles tendon to bone healing.

Anterior Cruciate Ligament Reconstruction in a Rabbit Model Using Silk-Collagen Scaffold and Comparison with Autograft

PubMed Central

Bi, Fanggang; Shi, Zhongli; Liu, An; Guo, Peng; Yan, Shigui

2015-01-01

The objective of the present study was to perform an in vivo assessment of a novel silk-collagen scaffold for anterior cruciate ligament (ACL) reconstruction. First, a silk-collagen scaffold was fabricated by combining sericin-extracted knitted silk fibroin mesh and type I collagen to mimic the components of the ligament. Scaffolds were electron-beam sterilized and rolled up to replace the ACL in 20 rabbits in the scaffold group, and autologous semitendinosus tendons were used to reconstruct the ACL in the autograft control group. At 4 and 16 weeks after surgery, grafts were retrieved and analyzed for neoligament regeneration and tendon-bone healing. To evaluate neoligament regeneration, H&E and immunohistochemical staining was performed, and to assess tendon-bone healing, micro-CT, biomechanical test, H&E and Russell-Movat pentachrome staining were performed. Cell infiltration increased over time in the scaffold group, and abundant fibroblast-like cells were found in the core of the scaffold graft at 16 weeks postoperatively. Tenascin-C was strongly positive in newly regenerated tissue at 4 and 16 weeks postoperatively in the scaffold group, similar to observations in the autograft group. Compared with the autograft group, tendon-bone healing was better in the scaffold group with trabecular bone growth into the scaffold. The results indicate that the silk-collagen scaffold has considerable potential for clinical application. PMID:25938408

Damping Factor as a Diagnostic Parameter for Assessment of Osseointegration during the Dental Implant Healing Process: An Experimental Study in Rabbits.

PubMed

Feng, Sheng-Wei; Ho, Kuo-Ning; Chan, Ya-Hui; Chang, Kai-Jung; Lai, Wei-Yi; Huang, Haw-Ming

2016-12-01

The purpose of this study was to evaluate the possibility of using damping factor (DF) analysis to provide additional information on osseointegration of dental implants during the healing period. A total of 30 dental implants were installed in the bilateral femoral condyles of 15 rabbits. A DF analyzer detected with an impulse-forced vibration method and a commercialized dental implant stability analyzer based on resonance frequency (RF) analysis were used to measure the implant stability immediately after implant placement and 1, 2, 4, and 8 weeks post-surgically. Results of DF and RF analyses at different time points were compared with the corresponding osseointegration performance of dental implants via micro-computed tomography (micro-CT), histological and histomorphometrical analysis. The DF values revealed a decrease with time and reached 0.062 ± 0.007 at 8 weeks after implantation, which is almost 50% lower than the initial value. Moreover, highly significant correlations between DF values and bone volume densities (R 2  = 0.9797) and percentages of bone-to-implant contact measured at trabecular bone area (R 2  = 0.9773) were also observed. These results suggested that DF analysis combined with RF analysis results in a more sensitive assessment of changes in the dental implant/bone complex during the healing period than RF analysis alone.

Long-term Observation of Regenerated Periodontium Induced by FGF-2 in the Beagle Dog 2-Wall Periodontal Defect Model

PubMed Central

Anzai, Jun; Nagayasu-Tanaka, Toshie; Terashima, Akio; Asano, Taiji; Yamada, Satoru; Nozaki, Takenori; Kitamura, Masahiro; Murakami, Shinya

2016-01-01

The long-term stability and qualitative characteristics of periodontium regenerated by FGF-2 treatment were compared with normal physiological healing tissue controls in a Beagle dog 2-wall periodontal defect model 13 months after treatment by assessing tissue histology and three-dimensional microstructure using micro-computed tomography (μCT). After FGF-2 (0.3%) or vehicle treatment at the defect sites, serial changes in the bone mineral content (BMC) were observed using periodic X-ray imaging. Tissues were harvested at 13 months, evaluated histomorphometrically, and the cortical bone volume and trabecular bone structure of the newly formed bone were analyzed using μCT. FGF-2 significantly increased the BMC of the defect area at 2 months compared with that of the control group, and this difference was unchanged through 13 months. The cortical bone volume was significantly increased by FGF-2, but there was no difference between the groups in trabecular bone structure. Bone maturation was occurring in both groups because of the lower cortical volume and denser trabecular bone than what is found in intact bone. FGF-2 also increased the area of newly formed bone as assessed histomorphometrically, but the ratios of trabecular bone in the defect area were similar between the control and FGF-2 groups. These results suggest that FGF-2 stimulates neogenesis of alveolar bone that is of similar quality to that of the control group. The lengths of the regenerated periodontal ligament and cementum, measured as the distance from the defect bottom to the apical end of the gingival epithelium, and height and area of the newly formed bone in the FGF-2 group were larger than those in the control group. The present study demonstrated that, within the limitation of artificial periodontal defect model, the periodontal tissue regenerated by FGF-2 was maintained for 13 months after treatment and was qualitatively equivalent to that generated through the physiological healing process. PMID:27391131

Rotator Cuff Repair with a Tendon-Fibrocartilage-Bone Composite Bridging Patch

PubMed Central

Ji, Xiaoxi; Chen, Qingshan; Thoreson, Andrew R.; Qu, Jin; An, Kai-Nan; Amadio, Peter C.; Steinmann, Scott P.; Zhao, Chunfeng

2015-01-01

Background To compare the mechanical performance of a rotator cuff repaired with a novel tendon-fibrocartilage-bone composite bridging patch vs the traditional Mason-Allen repair in an in vitro canine model. Methods Twenty shoulders and 10 bridging patches from patellar tendon were harvested. The patches were trimmed and sliced into 2 layers. An infraspinatus tendon tear was created in each shoulder. Modified Mason-Allen sutures were used to repair the infraspinatus tendon to the greater tuberosity, with or without the bridging patch (bridging patch group and controls, respectively). Shoulders were loaded to failure under displacement control at a rate of 0.5mm/sec. Findings The ultimate tensile load was significantly higher in the bridging patch group than control (mean [SD], 365.46 [36.45] vs 272.79 [48.88] N; P<.001). Stiffness at the greater tuberosity repair site and the patch-infraspinatus tendon repair site was significantly higher than the control repair site (93.96 [27.72] vs 42.62 [17.48] N/mm P<.001; 65.94 [24.51] vs 42.62 [17.48] N/mm P=.02, respectively). Interpretation The tendon-fibrocartilage-bone composite bridging patch achieved higher ultimate tensile load and stiffness at the patch–greater tuberosity repair site compared with traditional repair in a canine model. This composite tissue transforms the traditional tendon-to-bone healing interface (with dissimilar tissues) into a pair of bone-to-bone and tendon-to-tendon interfaces, which may improve healing quality and reduce retear rate. PMID:26190097

Rotator cuff repair with a tendon-fibrocartilage-bone composite bridging patch.

PubMed

Ji, Xiaoxi; Chen, Qingshan; Thoreson, Andrew R; Qu, Jin; An, Kai-Nan; Amadio, Peter C; Steinmann, Scott P; Zhao, Chunfeng

2015-11-01

To compare the mechanical performance of a rotator cuff repaired with a novel tendon-fibrocartilage-bone composite bridging patch vs the traditional Mason-Allen repair in an in vitro canine model. Twenty shoulders and 10 bridging patches from patellar tendon were harvested. The patches were trimmed and sliced into 2 layers. An infraspinatus tendon tear was created in each shoulder. Modified Mason-Allen sutures were used to repair the infraspinatus tendon to the greater tuberosity, with or without the bridging patch (bridging patch group and controls, respectively). Shoulders were loaded to failure under displacement control at a rate of 0.5mm/s. The ultimate tensile load was significantly higher in the bridging patch group than control (mean [SD], 365.46 [36.45] vs 272.79 [48.88] N; P<.001). Stiffness at the greater tuberosity repair site and the patch-infraspinatus tendon repair site was significantly higher than the control repair site (93.96 [27.72] vs 42.62 [17.48] N/mm P<.001; 65.94 [24.51] vs 42.62 [17.48] N/mm P=.02, respectively). The tendon-fibrocartilage-bone composite bridging patch achieved higher ultimate tensile load and stiffness at the patch-greater tuberosity repair site compared with traditional repair in a canine model. This composite tissue transforms the traditional tendon-to-bone healing interface (with dissimilar tissues) into a pair of bone-to-bone and tendon-to-tendon interfaces, which may improve healing quality and reduce retear rate. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of an injectable rhGDF-5/PLGA construct for minimally invasive periodontal regenerative procedures: a histological study in the dog.

PubMed

Kwon, David H; Bennett, William; Herberg, Samuel; Bastone, Patrizia; Pippig, Susanne; Rodriguez, Nancy A; Susin, Cristiano; Wikesjö, Ulf M E

2010-04-01

To evaluate the injectability, biocompatibility, safety, and periodontal wound healing/regeneration following application of a novel bioresorbable recombinant human growth/differentiation factor-5 (rhGDF-5)/poly(lactic-co-glycolic acid) (PLGA) construct. Periodontal pockets (3 x 6 mm, width x depth) were surgically created over the buccal roots of the second and fourth mandibular pre-molars in eight adult Hound Labrador mongrel dogs. Surgeries including injection of the rhGDF-5/PLGA construct into the pockets were sequenced that four animals provided 2-/4-week and four animals 6-/8-week observations of sites receiving rhGDF-5/PLGA or serving as sham-surgery control. The rhGDF-5/PLGA construct was easy to prepare and apply. Approximately 0.2 ml (93 microg rhGDF-5)/tooth was used. Clinical and radiographic healing was exemplary without adverse events. Healing was characterized by a non-specific connective tissue attachment, acellular/cellular cementum, periodontal ligament (PDL), bone regeneration, and a junctional epithelium. PLGA fragments were observed in 4/7, 2/8, and 1/8 sites at 2, 4, and 6 weeks, respectively. Associated inflammatory reactions exhibited no limiting effect on periodontal wound healing/regeneration. Root resorption/ankylosis was not observed. Bone formation showed apparent increased maturity (lamellar bone) at 6 weeks in sites receiving rhGDF-5/PLGA compared with the control. Both protocols exhibited significant increases in PDL, cementum, and bone regeneration over time, without significant differences between treatments. In time, PDL and cementum regeneration was twofold greater for the control at 4 weeks (p=0.04) while increased bone formation was observed at sites receiving rhGDF-5/PLGA (p<0.01). In conclusion, the rhGDF-5/PLGA construct appears to be a safe technology for injectable, ease-of-use application of rhGDF-5-stimulated periodontal wound healing/regeneration. Additional work to optimize the polymer carrier and rhGDF-5 release kinetics/dose might be required before evaluating the efficacy of this technology in clinical settings using minimally invasive approaches.

Laser vs bur for bone cutting in impacted mandibular third molar surgery: A randomized controlled trial.

PubMed

Passi, Deepak; Pal, Uma Shankar; Mohammad, Shadab; Singh, Rakesh Kumar; Mehrotra, Divya; Singh, Geeta; Kumar, Manoj; Chellappa, Arul A L; Gupta, Chandan

2013-01-01

The aim of this study was to assess the feasibility of Er: YAG laser in bone cutting for removal of impacted lower third molar teeth and compare its outcomes with that of surgical bur. The study comprised 40 subjects requiring removal of impacted mandibular third molar, randomly categorized into two equal groups of 20 each, who had their impacted third molar removed either using Er: YAG laser or surgical bur as per their group, using standard methodology of extraction of impacted teeth. Clinical parameters like pain, bleeding, time taken for bone cutting, postoperative swelling, trismus, wound healing and complications were compared for both groups. Clinical parameters like pain, bleeding and swelling were lower in laser group than bur group, although the difference was statistically not significant. However, postoperative swelling showed significant difference in the two groups. Laser group required almost double the time taken for bone cutting with bur. Trismus persisted for a longer period in laser group. Wound healing and complications were assessed clinically and there was no significant difference in both the groups. Based on the results of our study, the possibility of bone cutting using lasers is pursued, the osteotomy is easily performed and the technique is better suited to minimally invasive surgical procedures. The use of Er: YAG laser may be considered as an alternative tool to surgical bur, specially in anxious patients.

Enhanced Bone Formation in Segmental Defects with BMP2 in a Biologically Relevant Molecular Context

DTIC Science & Technology

2016-10-16

gun shots . These do not heal on their own once a ‘critical size’ segment of bone is missing. One strategy to induce healing is to use bone-inducing...accelerate BMP2-induced bone formation by presenting the growth factor in a more biologically relevant context. This is based on our observation...that manganese increases the binding of BMP2 to COMP. The next steps are to validate these observations using BMP2:COMP on HA/PLG scaffolds in-vitro

[Mechanobiology and bone metabolism: Clinical relevance for fracture treatment].

PubMed

Haffner-Luntzer, M; Liedert, A; Ignatius, A

2015-12-01

Mechanical stimuli are known to significantly influence bone metabolism and fracture healing. Various studies have demonstrated the involvement of complex molecular mechanotransduction pathways, such as the Wnt/beta-catenin, bone morphogenetic protein (BMP) and estrogen receptor signaling pathways in mechanotransduction. Mechanotransduction is influenced by aging and the comorbidities of the patient. Pharmacological modulation of signal transduction influences bone formation and the mechanosensitivity of skeletal tissue. The combination of pharmacological and biomechanical therapies may be useful for the treatment of fractures with impaired healing.

Smooth muscle cells healing atherosclerotic plaque disruptions are of local, not blood, origin in apolipoprotein E knockout mice.

PubMed

Bentzon, Jacob F; Sondergaard, Claus S; Kassem, Moustapha; Falk, Erling

2007-10-30

Signs of preceding episodes of plaque rupture and smooth muscle cell (SMC)-mediated healing are common in atherosclerotic plaques, but the source of the healing SMCs is unknown. Recent studies suggest that activated platelets adhering to sites of injury recruit neointimal SMCs from circulating bone marrow-derived progenitor cells. Here, we analyzed the contribution of this mechanism to plaque healing after spontaneous and mechanical plaque disruption in apolipoprotein E knockout (apoE-/-) mice. To determine the origin of SMCs after spontaneous plaque disruption, irradiated 18-month-old apoE-/- mice were reconstituted with bone marrow cells from enhanced green fluorescent protein (eGFP) transgenic apoE-/- mice and examined when they died up to 9 months later. Plaque hemorrhage, indicating previous plaque disruption, was widely present, but no bone marrow-derived eGFP+ SMCs were detected. To examine the origin of healing SMCs in a model that recapitulates more features of human plaque rupture and healing, we developed a mechanical technique that produced consistent plaque disruption, superimposed thrombosis, and SMC-mediated plaque healing in apoE-/- mice. Mechanical plaque disruption was produced in irradiated apoE-/- mice reconstituted with eGFP+ apoE-/- bone marrow cells and in carotid bifurcations cross-grafted between apoE-/- and eGFP+ apoE-/- mice. Apart from few non-graft-derived SMCs near the anastomosis site in 1 transplanted carotid bifurcation, no SMCs originating from outside the local arterial segment were detected in healed plaques. Healing SMCs after atherosclerotic plaque disruption are derived entirely from the local arterial wall and not circulating progenitor cells in apoE-/- mice.

Periodontal and endodontic pathology delays extraction socket healing in a canine model

PubMed Central

2017-01-01

Purpose The aim of the present exploratory study was to evaluate extraction socket healing at sites with a history of periodontal and endodontic pathology. Methods The mandibular 4th premolar teeth in 5 adult beagle dogs served as experimental units. Periodontal and endodontic lesions were induced in 1 premolar site in each animal using wire ligatures and pulpal exposure over 3 months (diseased sites). The contralateral premolar sites served as healthy controls. The mandibular 4th premolar teeth were then extracted with minimal trauma, followed by careful wound debridement. The animals were sacrificed at days 1, 7, 30, 60, and 90 post-extraction for analysis, and the healing patterns at the healthy and diseased extraction sites were compared using radiography, scanning electron microscopy, histology, and histometry. Results During the first 7 days of healing, a significant presence of inflammatory granulation tissue was noted at the diseased sites (day 1), along with a slightly accelerated rate of fibrin clot resolution on day 7. On day 30, the diseased extraction sites showed a greater percentage of persistent fibrous connective tissue, and an absence of bone marrow formation. In contrast, healthy sites showed initial signs of bone marrow formation on day 30, and subsequently a significantly greater proportion of mature bone marrow formation on both days 60 and 90. Radiographs exhibited sclerotic changes adjoining apical endodontic lesions, with scanning electron microscopy showing collapsed Volkmann canals protruding from these regions in the diseased sites. Furthermore, periodontal ligament fibers exhibited a parallel orientation to the alveolar walls of the diseased sites, in contrast to a perpendicular arrangement in the healthy sites. Conclusions Within the limitations of this study, it appears that a history of periodontal and endodontic pathology may critically affect bone formation and maturation, leading to delayed and compromised extraction socket healing. PMID:28680710

Micromotion-induced strain fields influence early stages of repair at bone-implant interfaces

PubMed Central

Wazen, Rima M.; Currey, Jennifer A.; Guo, Hongqiang; Brunski, John B.; Helms, Jill A.; Nanci, Antonio

2013-01-01

Implant loading can create micromotion at the bone-implant interface. The interfacial strain associated with implant micromotion could contribute to regulating the tissue healing response. Excessive micromotion can lead to fibrous encapsulation and implant loosening. Our objective was to characterize the influence of interfacial strain on bone regeneration around implants in mouse tibiae. A micromotion system was used to create strain under conditions of (1) no initial contact between implant and bone, and (2) a direct bone-implant contact. Pin- and screw-shaped implants were subjected to displacements of 150 μm or 300 μm, 60 cycles/day, for 7 days. Pin-shaped implants placed in 5 animals were subjected to 3 sessions of 150 μm displacement per day, with 60 cycles per session. Control implants in both types of interfaces were stabilized throughout the healing period. Experimental strain analyses, microtomography, image-based displacement mapping, and finite element simulations were used to characterize interfacial strain fields. Calcified tissue sections were prepared and stained with Goldner to evaluate tissue reaction in higher and lower strain regions. In stable implants, bone formation occurred consistently around the implants. In implants subjected to micromotion, bone regeneration was disrupted in areas of high strain concentrations (e.g. > 30%), whereas lower strain values were permissive of bone formation. Increasing implant displacement or number of cycles per day also changed the strain distribution and disturbed bone healing. These results indicate that not only implant micromotion but also the associated interfacial strain field contributes to regulating the interfacial mechanobiology at healing bone-implant interfaces. PMID:23337705

Clinical evaluation of an allogeneic bone matrix containing viable osteogenic cells in patients undergoing one- and two-level posterolateral lumbar arthrodesis with decompressive laminectomy.

PubMed

Musante, David B; Firtha, Michael E; Atkinson, Brent L; Hahn, Rebekah; Ryaby, James T; Linovitz, Raymond J

2016-05-27

Trinity Evolution® cellular bone allograft (TE) possesses the osteogenic, osteoinductive, and osteoconductive elements essential for bone healing. The purpose of this study is to evaluate the radiographic and clinical outcomes when TE is used as a graft extender in combination with locally derived bone in one- and two-level instrumented lumbar posterolateral arthrodeses. In this retrospective evaluation, a consecutive series of subject charts that had posterolateral arthrodesis with TE and a 12-month radiographic follow-up were evaluated. All subjects were diagnosed with degenerative disc disease, radiculopathy, stenosis, and decreased disc height. At 2 weeks and at 3 and 12 months, plain radiographs were performed and the subject's back and leg pain (VAS) was recorded. An evaluation of fusion status was performed at 12 months. The population consisted of 43 subjects and 47 arthrodeses. At 12 months, a fusion rate of 90.7 % of subjects and 89.4 % of surgical levels was observed. High-risk subjects (e.g., diabetes, tobacco use, etc.) had fusion rates comparable to normal patients. Compared with the preoperative leg or back pain level, the postoperative pain levels were significantly (p < 0.0001) improved at every time point. There were no adverse events attributable to TE. Fusion rates using TE were higher than or comparable to fusion rates with autologous iliac crest bone graft that have been reported in the recent literature for posterolateral fusion procedures, and TE fusion rates were not adversely affected by several high-risk patient factors. The positive results provide confidence that TE can safely replace autologous iliac crest bone graft when used as a bone graft extender in combination with locally derived bone in the setting of posterolateral lumbar arthrodesis in patients with or without risk factors for compromised bone healing. Because of the retrospective nature of this study, the trial was not registered.

Unicameral bone cysts: a comparison of injection of steroid and grafting with autologous bone marrow.

PubMed

Cho, H S; Oh, J H; Kim, H-S; Kang, H G; Lee, S H

2007-02-01

Open surgery is rarely justified for the initial treatment of a unicameral bone cyst, but there is some debate concerning the relative effectiveness of closed methods. This study compared the results of steroid injection with those of autologous bone marrow grafting for the treatment of unicameral bone cysts. Between 1990 and 2001, 30 patients were treated by steroid injection and 28 by grafting with autologous bone marrow. The overall success rates were 86.7% and 92.0%, respectively (p>0.05). The success rate after the initial procedure was 23.3% in the steroid group and 52.0% in those receiving autologous bone marrow (p<0.05), and the respective cumulative success rates after second injections were 63.3% and 80.0% (p>0.05). The mean number of procedures required was 2.19 (1 to 5) and 1.57 (1 to 3) (p<0.05), the mean interval to healing was 12.5 months (4 to 32) and 14.3 months (7 to 36) (p>0.05), and the rate of recurrence after the initial procedure was 41.7% and 13.3% in the steroid and in the autologous bone marrow groups, respectively (p<0.05). Although the overall rates of success of both methods were similar, the steroid group had higher recurrence after a single procedure and required more injections to achieve healing.

Bone compositional study during healing of subcritical calvarial defects in rats by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Ahmed, Rafay; Wing Lun Law, Alan; Cheung, Tsz Wing; Lau, Condon

2017-07-01

Subcritical calvarial defects are important to study bone regeneration during healing. In this study 1mm calvarial defects were created using trephine in the parietal bones of Sprague-Dawley rats (n=7) that served as in vivo defects. Subjects were sacrificed after 7 days and the additional defects were created on the harvested skull with the same method to serve as control defects. Raman spectroscopy is established to investigate mineral/matrix ratio, carbonate/phosphate ratio and crystallinity of three different surfaces; in vivo defects, control defects and normal surface. Results show 21% and 23% decrease in mineral/matrix after 7 days of healing from surface to in vivo and control to in vivo defects, respectively. Carbonate to phosphate ratio was found to be increased by 39% while crystallinity decreased by 26% in both surface to in vivo and control to in vivo defects. This model allows to study the regenerated bone without mechanically perturbing healing surface.

The effect of strontium ranelate on the healing of a fractured ulna with bone gap in rabbit.

PubMed

Ibrahim, Mohd Rafiq Mohd; Singh, Simmrat; Merican, Azhar Mahmood; Raghavendran, Hanumantha Rao Balaji; Murali, Malliga Raman; Naveen, Sangeetha Vasudevaraj; Kamarul, Tunku

2016-06-16

Fracture healing in bone gap is one of the major challenges encountered in Orthopedic Surgery. At present, the treatment includes bone graft, employing either internal or external fixation which has a significant impact on the patient, family and even society. New drugs are emerging in the markets such as anabolic bone-forming agents including teriparatide and strontium ranelate to stimulate bone growth. Based on the mechanism of their actions, we embarked on a study on the healing of a fractured ulna with bone gap in a rabbit model. We segregated ten rabbits into two groups: five rabbits in the test group and five rabbits in the control group. We created a 5 mm bone gap in the ulna bone, removing the periosteum as well. Rabbits in the test group received 450 mg/kg of strontium ranelate via oral administration, daily, for six weeks. The x-rays, CT scans and blood tests were performed every two weeks. At the end of six weeks, the rabbits were sacrificed, and the radius and ulna bones harvested for histopathological examination. Based on the x-rays and CT scans, fracture healing or bone formation was observed to be faster in the control group. From the x-ray findings, 80 % of the fracture united and by CT scan, 60 % of the fracture united in the control group at the end of the six-week study. None of the fractures united in the test group. However, the histopathology report showed that a callus of different stages was being formed in both groups, consisting of 80 % of bone. The serum levels of osteocalcin and alkaline phosphatase initially remained similar up to three weeks and changed slightly at the end of six weeks. We conclude that the strontium effect begins slowly, and while it may not interfere with bone cell proliferation it may interfere in the mineralization and delay the acute stage of fracture healing. We recommend that a larger sample size and a longer duration of the study period be implemented to confirm our finding.

A Comparison of More and Less Aggressive Bone Debridement Protocols for the Treatment of Open Supracondylar Femur Fractures

PubMed Central

Ricci, William M.; Collinge, Cory; Streubel, Philipp N.; McAndrew, Christopher M.; Gardner, Michael J.

2014-01-01

Objectives This study compared results of aggressive and nonaggressive debridement protocols for the treatment of high energy open supracondylar femur fractures after the primary procedure, with respect to the requirement for secondary bone grafting procedures, and deep infection. Design Retrospective review Setting Level I and Level II Trauma Centers Patients/Participants Twenty-nine consecutive patients with high grade open (Gustilo Types II and III) supracondylar femur fractures (OTA/AO 33A and C) treated with debridement and locked plating. Intervention Surgeons at two different Level I trauma centers had different debridement protocols for open supracondylar femur fractures. One center used a More Aggressive (MA)protocol in their patients (n=17) that included removal of all devitalized bone and placement of antibiotic cement spacers to fill large segmental defects. The other center used a Less Aggressive (LA) protocol in their patients (n=12) that included debridement of grossly contaminated bone with retention of other bone fragments and no use of antibiotic cement spacers. All other aspects of the treatment protocol at the two centers were similar: definitive fixation with locked plates in all cases; IV antibiotics were used until definitive wound closure; and weight bearing was advanced upon clinical and radiographic evidence of fracture healing. Main Outcome Measurements Healing after the primary procedure, requirement for secondary bone grafting procedures, and the presence of deep infection. Results Demographics were similar between included patients at each center with regard to: age; gender; rate of open fractures; open fracture classification; mechanism; and smoking (p>.05). Patients at the MA center were more often diabetic (p<.05).Cement spacers to fill segmental defects were used more often after MA debridement (35% vs 0%, p<0.006) and more patients had a plan for staged bone grafting after MA debridement (71% vs 8%, p<0.006). Healing after the index fixation procedure occurred more often after LA debridement (92% vs 35%, p<0.003). There was no difference in infection rate between the two protocols: 25% with the LA protocol; and 18% with the MA protocol, (p=0.63). All patients in both groups eventually healed and were without evidence of infection at an average of 1.8 years of follow-up. Conclusion The degree to which bone should be debrided after a high energy, high grade, open supracondylar femur fracture is a matter of surgeon judgment and falls along a continuous spectrum. Based on the results of the current study, the theoretic tradeoff between infection risk and osseous healing potential, seems to favor a less aggressive approach towards bone debridement in the initial treatment. PMID:23760177

A comparison of more and less aggressive bone debridement protocols for the treatment of open supracondylar femur fractures.

PubMed

Ricci, William M; Collinge, Cory; Streubel, Philipp N; McAndrew, Christopher M; Gardner, Michael J

2013-12-01

This study compared results of aggressive and nonaggressive debridement protocols for the treatment of high-energy, open supracondylar femur fractures after the primary procedure, with respect to the requirement for secondary bone grafting procedures, and deep infection. Retrospective review. Level I and level II trauma centers. Twenty-nine consecutive patients with high-grade, open (Gustilo types II and III) supracondylar femur fractures (OTA/AO 33A and C) treated with debridement and locked plating. Surgeons at 2 different level I trauma centers had different debridement protocols for open supracondylar femur fractures. One center used a more aggressive (MA) protocol in their patients (n = 17) that included removal of all devitalized bone and placement of antibiotic cement spacers to fill large segmental defects. The other center used a less aggressive (LA) protocol in their patients (n = 12) that included debridement of grossly contaminated bone with retention of other bone fragments and no use of antibiotic cement spacers. All other aspects of the treatment protocol at the 2 centers were similar: definitive fixation with locked plates in all cases, IV antibiotics were used until definitive wound closure, and weight bearing was advanced upon clinical and radiographic evidence of fracture healing. Healing after the primary procedure, requirement for secondary bone grafting procedures, and the presence of deep infection. Demographics were similar between included patients at each center with regard to age, gender, rate of open fractures, open fracture classification, mechanism, and smoking (P > 0.05). Patients at the MA center were more often diabetic (P < 0.05). Cement spacers to fill segmental defects were used more often after MA debridement (35% vs. 0%, P < 0.006), and more patients had a plan for staged bone grafting after MA debridement (71% vs. 8%, P < 0.006). Healing after the index fixation procedure occurred more often after LA debridement (92% vs. 35%, P < 0.003). There was no difference in infection rate between the 2 protocols: 25% with the LA protocol and 18% with the MA protocol (P = 0.63). All patients in both groups eventually healed and were without evidence of infection at an average of 1.8 years of follow-up. The degree to which bone should be debrided after a high-energy, high-grade, open supracondylar femur fracture is a matter of surgeon judgment and falls along a continuous spectrum. Based on the results of the current study, the theoretic trade-off between infection risk and osseous healing potential seems to favor an LA approach toward bone debridement in the initial treatment. Therapeutic level III.

Healing of the bone with anti-fracture drugs.

PubMed

Vannucci, Letizia; Brandi, Maria Luisa

2016-12-01

Fracture healing is a complex physiological process. As impaired fracture healing is more frequent in osteoporotic subjects, anti-osteoporotic drugs could have some impact on this process. Areas covered: We reviewed the current literature to evaluate the effects of these drugs on fracture healing and their potential role in supporting this process, especially when impaired. A PubMed/Medline search was undertaken combining the terms 'fracture healing', 'anti-resorptive drugs', 'anabolic agents', 'anti-osteoporotic drugs'. Expert opinion: As clinical evidence on the role of anti-osteoporotic drugs in the process of fracture healing consists mainly of case reports or studies with a relatively small number of patients, large randomized clinical trials are needed in order to extend to the human setting the promising results on these agents as inductors or co-adjuvants of bone healing derived from animal studies.

Use of a platelet-rich fibrin membrane to repair traumatic tympanic membrane perforations: a comparative study.

PubMed

Gür, Özer Erdem; Ensari, Nuray; Öztürk, Mehmet Türker; Boztepe, Osman Fatih; Gün, Taylan; Selçuk, Ömer Tarık; Renda, Levent

2016-10-01

(1) To evaluate the effects of a platelet-rich fibrin (PRF) membrane in the repair of traumatic tympanic membrane (TM) perforations; and (2) to compare the use of a PRF membrane with the paper patch technique with regard to recovery rates, healing time, and correction of the mean air-bone gap. A randomized, prospective analysis was performed for 60 patients who were treated for traumatic TM perforations using one of the two methods. Closure rate, speed of healing, and hearing gain were compared between the PRF (Group 1) and paper patch (Group 2) groups. Closure was obtained in 28 (93%) perforations in Group 1 and 25 (83%) perforations in Group 2 (p > 0.05). On day 10, full closure of the TM was observed in 24 (80%) patients in Group 1 and 16 (53%) patients in Group 2 (p < 0.05). The improvement in the mean air-bone gap was 14.1 dB in Group 1 and 12.4 dB in Group 2 on post-operative day 45 (p < 0.05). In comparison with the paper patch method, PRF, a new method, provided more rapid healing with more successful audiological results, and with no requirement for a second procedure.

Open tibial fractures grade IIIC treated successfully with external fixation, negative-pressure wound therapy and recombinant human bone morphogenetic protein 7.

PubMed

Babiak, Ireneusz

2014-10-01

The aim of the therapy in open tibial fractures grade III was to cover the bone with soft tissue and achieve healed fracture without persistent infection. Open tibial fractures grade IIIC with massive soft tissue damage require combined orthopaedic, vascular and plastic-reconstructive procedures. Negative-pressure wound therapy (NPWT), used in two consecutive cases with open fracture grade IIIC of the tibia diaphysis, healed extensive soft tissue defect with exposure of the bone. NPWT eventually allowed for wound closure by split skin graft within 21-25 days. Ilizarov external fixator combined with application of recombinant human bone morphogenetic protein-7 at the site of delayed union enhanced definitive bone healing within 16-18 months. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Osteoblast-Specific Loss of IGF1R Signaling Results in Impaired Endochondral Bone Formation During Fracture Healing.

PubMed

Wang, Tao; Wang, Yongmei; Menendez, Alicia; Fong, Chak; Babey, Muriel; Tahimic, Candice G T; Cheng, Zhiqiang; Li, Alfred; Chang, Wenhan; Bikle, Daniel D

2015-09-01

Insulin-like growth factors (IGFs) are important local regulators during fracture healing. Although IGF1 deficiency is known to increase the risk of delayed union or non-union fractures in the elderly population, the underlying mechanisms that contribute to this defect remains unclear. In this study, IGF1 signaling during fracture healing was investigated in an osteoblast-specific IGF1 receptor (IGF1R) conditional knockout (KO) mouse model. A closed tibial fracture was induced in IGF1R(flox/flox) /2.3-kb α1(1)-collagen-Cre (KO) and IGF1R(flox/flox) (control) mice aged 12 weeks. Fracture callus samples and nonfractured tibial diaphysis were collected and analyzed by μCT, histology, immunohistochemistry, histomorphometry, and gene expression analysis at 10, 15, 21, and 28 days after fracture. A smaller size callus, lower bone volume accompanied by a defect in mineralization, bone microarchitectural abnormalities, and a higher cartilage volume were observed in the callus of these KO mice. The levels of osteoblast differentiation markers (osteocalcin, alkaline phosphatase, collagen 1α1) were significantly reduced, but the early osteoblast transcription factor runx2, as well as chondrocyte differentiation markers (collagen 2α1 and collagen 10α1) were significantly increased in the KO callus. Moreover, increased numbers of osteoclasts and impaired angiogenesis were observed during the first 15 days of fracture repair, but decreased numbers of osteoclasts were found in the later stages of fracture repair in the KO mice. Although baseline nonfractured tibias of KO mice had decreased trabecular and cortical bone compared to control mice, subsequent studies with mice expressing the 2.3-kb α1(1)-collagen-Cre ERT2 construct and given tamoxifen at the time of fracture and so starting with comparable bone levels showed similar impairment in fracture repair at least initially. Our data indicate that not only is the IGF1R in osteoblasts involved in osteoblast differentiation during fracture repair, but it plays an important role in coordinating chondrocyte, osteoclast, and endothelial responses that all contribute to the endochondral bone formation required for normal fracture repair. © 2015 American Society for Bone and Mineral Research.

Treatment of unicameral bone cysts in pediatric patients with an injectable regenerative graft: a preliminary report.

PubMed

Gentile, John V; Weinert, Carl R; Schlechter, John A

2013-01-01

Multiple treatment modalities exist for unicameral bone cysts (UBC), including steroid injection, autologous bone marrow injection, mechanical decompression, intramedullary fixation, curettage, and bone grafting. All have their own potential limitations such as high recurrence rates, cyst persistence, need for multiple procedures, and prolonged immobilization. A minimally invasive regimen consisting of curettage, decompression, and injection of a calcium sulfate-calcium phosphate (CaSO4-CaPO4) composite has been utilized at our institution in an attempt to obtain optimal results for the treatment of UBCs in the pediatric population. We retrospectively evaluated 16 patients with pathologically confirmed UBC who were treated with curettage, decompression, and injection of a calcium sulfate-calcium phosphate composite between April 2006 and August 2010 at a single institution. The average age of the patients at time of surgical intervention was 9.4 years of age (range, 3 to 16 y). Average follow-up was 16 months (range, 6 to 36 mo). Radiographic healing, clinical outcomes, and complications were evaluated. Final follow-up radiographs demonstrated healing in 93.7% (15 of 16) of patients after a single procedure. Complete healing was observed in 14 of 16 patients and partially healed with a defect in 1 of 16 patients. One patient had a persistent cyst but did not wish to receive further treatment. All patients returned to full activities including sports on average at 3.1 months (range, 1 to 6 mo) and were asymptomatic on most recent follow-up. No postoperative complications, including refracture, were observed. Curettage, decompression, and injection of a calcium sulfate-calcium phosphate composite for UBC in the pediatric population demonstrates encouraging results with low recurrence rates and complications compared with conventional methods. Case series, Level of Evidence IV.

Bone Regeneration after Treatment with Covering Materials Composed of Flax Fibers and Biodegradable Plastics: A Histological Study in Rats

PubMed Central

Gedrange, Tomasz

2016-01-01

The aim of this study was to examine the osteogenic potential of new flax covering materials. Bone defects were created on the skull of forty rats. Materials of pure PLA and PCL and their composites with flax fibers, genetically modified producing PHB (PLA-transgen, PCL-transgen) and unmodified (PLA-wt, PCL-wt), were inserted. The skulls were harvested after four weeks and subjected to histological examination. The percentage of bone regeneration by using PLA was less pronounced than after usage of pure PCL in comparison with controls. After treatment with PCL-transgen, a large amount of new formed bone could be found. In contrast, PCL-wt decreased significantly the bone regeneration, compared to the other tested groups. The bone covers made of pure PLA had substantially less influence on bone regeneration and the bone healing proceeded with a lot of connective tissue, whereas PLA-transgen and PLA-wt showed nearly comparable amount of new formed bone. Regarding the histological data, the hypothesis could be proposed that PCL and its composites have contributed to a higher quantity of the regenerated bone, compared to PLA. The histological studies showed comparable bone regeneration processes after treatment with tested covering materials, as well as in the untreated bone lesions. PMID:27597965

Bone Regeneration after Treatment with Covering Materials Composed of Flax Fibers and Biodegradable Plastics: A Histological Study in Rats.

PubMed

Gredes, Tomasz; Kunath, Franziska; Gedrange, Tomasz; Kunert-Keil, Christiane

2016-01-01

The aim of this study was to examine the osteogenic potential of new flax covering materials. Bone defects were created on the skull of forty rats. Materials of pure PLA and PCL and their composites with flax fibers, genetically modified producing PHB (PLA-transgen, PCL-transgen) and unmodified (PLA-wt, PCL-wt), were inserted. The skulls were harvested after four weeks and subjected to histological examination. The percentage of bone regeneration by using PLA was less pronounced than after usage of pure PCL in comparison with controls. After treatment with PCL-transgen, a large amount of new formed bone could be found. In contrast, PCL-wt decreased significantly the bone regeneration, compared to the other tested groups. The bone covers made of pure PLA had substantially less influence on bone regeneration and the bone healing proceeded with a lot of connective tissue, whereas PLA-transgen and PLA-wt showed nearly comparable amount of new formed bone. Regarding the histological data, the hypothesis could be proposed that PCL and its composites have contributed to a higher quantity of the regenerated bone, compared to PLA. The histological studies showed comparable bone regeneration processes after treatment with tested covering materials, as well as in the untreated bone lesions.

Current Options for Determining Fracture Union

PubMed Central

2014-01-01

Determining whether a bone fracture is healed is one of the most important and fundamental clinical determinations made in orthopaedics. However, there are currently no standardized methods of assessing fracture union, which in turn has created significant disagreement among orthopaedic surgeons in both clinical and research settings. An extensive amount of research has been dedicated to finding novel and reliable ways of determining healing with some promising results. Recent advancements in imaging techniques and introduction of new radiographic scores have helped decrease the amount of disagreement on this topic among physicians. The knowledge gained from biomechanical studies of bone healing has helped us refine our tools and create more efficient and practical research instruments. Additionally, a deeper understanding of the molecular pathways involved in the bone healing process has led to emergence of serologic markers as possible candidates in assessment of fracture union. In addition to our current physician centered methods, patient-centered approaches assessing quality of life and function are gaining popularity in assessment of fracture union. Despite these advances, assessment of union remains an imperfect practice in the clinical setting. Therefore, clinicians need to draw on multiple modalities that directly and indirectly measure or correlate with bone healing when counseling patients. PMID:26556422

Fracture bone healing and biodegradation of AZ31 implant in rats.

PubMed

Iglesias, C; Bodelón, O G; Montoya, R; Clemente, C; Garcia-Alonso, M C; Rubio, J C; Escudero, M L

2015-04-17

The ideal temporary implant should offer enough mechanical support to allow healing of the fracture and then biodegrade and be resorbed by metabolic mechanisms without causing any toxic effect. The aim of this research has been to simultaneously study in situ bone healing and the biodegradation of AZ31 Mg alloy as an osteosynthesis material. The in vivo study was carried out in AZ31 implants with and without Mg-fluoride coating inserted in un-fractured and fractured femurs of Wistar rats for long experimentation time, from 1 to 13 months, by means of computed tomography, histological and histomorphometric analysis. Tomography analysis showed the bone healing and biodegradation of AZ31 implants. The fracture is healed in 100% of the animals, and AZ31 maintains its mechanical integrity throughout the healing process. Biodegradation was monitored, quantifying the evolution of gas over time by 3D composition of tomography images. In all the studied groups, gas pockets disappear with time as a result of the diffusion process through soft tissues. Histomorphometric studies reveal that after 13 months the 46.32% of AZ31 alloy has been resorbed. The resorption of the coated and uncoated AZ31 implants inserted in fractured femurs after 1, 9 and 13 months does not have statistically significant differences. There is a balance between the biodegradation of AZ31 and bone healing which allows the use of AZ31 to be proposed as an osteosynthesis material.

Pressure Bearing Device Affects Extraction Socket Remodeling of Maxillary Anterior Tooth. A Prospective Clinical Trial.

PubMed

Jiang, Xi; Zhang, Yu; Chen, Bo; Lin, Ye

2017-04-01

Extraction socket remodeling and ridge preservation strategies have been extensively explored. To evaluate the efficacy of applying a micro-titanium stent as a pressure bearing device on extraction socket remodeling of maxillary anterior tooth. Twenty-four patients with a extraction socket of maxillary incisor were treated with spontaneous healing (control group) or by applying a micro-titanium stent as a facial pressure bearing device over the facial bone wall (test group). Two virtual models obtained from cone beam computed tomography data before extraction and 4 months after healing were 3-dimenionally superimposed. Facial bone wall resorption, extraction socket remodeling features and ridge width preservation rate were determined and compared between the groups. Thin facial bone wall resulted in marked resorption in both groups. The greatest palatal shifting distance of facial bone located at the coronal level in the control group, but middle level in the test group. Compared with the original extraction socket, 87.61 ± 5.88% ridge width was preserved in the test group and 55.09 ± 14.46% in the control group. Due to the facial pressure bearing property, the rigid micro-titanium stent might preserve the ridge width and alter the resorption features of extraction socket. © 2016 Wiley Periodicals, Inc.

Comparison of Piezosurgery and Conventional Rotary Instruments for Removal of Impacted Mandibular Third Molars: A Randomized Controlled Clinical and Radiographic Trial

PubMed Central

Shokry, Mohamed; Aboelsaad, Nayer

2016-01-01

The purpose of this study was to test the effect of the surgical removal of impacted mandibular third molars using piezosurgery versus the conventional surgical technique on postoperative sequelae and bone healing. Material and Methods. This study was carried out as a randomized controlled clinical trial: split mouth design. Twenty patients with bilateral mandibular third molar mesioangular impaction class II position B indicated for surgical extraction were treated randomly using either the piezosurgery or the conventional bur technique on each site. Duration of the procedure, postoperative edema, trismus, pain, healing, and bone density and quantity were evaluated up to 6 months postoperatively. Results. Test and control sites were compared using paired t-test. There was statistical significance in reduction of pain and swelling in test sites, where the time of the procedure was statistically increased in test site. For bone quantity and quality, statistical difference was found where test site showed better results. Conclusion. Piezosurgery technique improves quality of patient's life in form of decrease of postoperative pain, trismus, and swelling. Furthermore, it enhances bone quality within the extraction socket and bone quantity along the distal aspect of the mandibular second molar. PMID:27597866

Osteosynthesis of partial rib osteotomy in a miniature pig model using human standard-sized magnesium plate/screw systems: Effect of cyclic deformation on implant integrity and bone healing.

PubMed

Schaller, Benoit; Saulacic, Nikola; Beck, Stefan; Imwinkelried, Thomas; Liu, Edwin Wei Yang; Nakahara, Ken; Hofstetter, Willy; Iizuka, Tateyuki

2017-06-01

Magnesium alloys are candidates for resorbable material in bone fixation. However, the degradation and performance of osteosynthesis plate/screw systems in vivo, under cyclic deformation, is unknown. We evaluated the outcomes of human standard-sized magnesium plate/screw systems with or without plasma-electrolytic surface modifications in a miniature pig rib model. Of a total of 14 minipigs, six were implanted with coated magnesium WE43 six-hole plates/screws, six received magnesium uncoated plates/screws, and two received titanium osteosynthesis systems. The performance of the plate/screw fixation system on partially osteotomized 7th ribs was compared with that on intact 9th ribs. Radiological examinations were performed in vivo at 1, 4 and 8 weeks and after euthanasia at 12 and 24 weeks. After euthanasia the bone blocks were analyzed by computed tomography (CT), microfocus computed tomography (micro-CT), histology and histomorphometry. Follow-up post-surgery showed no trouble with wound healing. In vivo radiological examinations showed higher amounts of gas formation above the uncoated magnesium plates fixed on the partially osteotomized and intact ribs. CT scans showed no broken plates or implant displacement. The micro-CT examination demonstrated better surrounding bone properties around the coated than the uncoated magnesium implants 12 weeks after surgery. No negative influence of magnesium degradation on bone healing was observed with histological examinations. Plastic deformation during surgery and cyclic deformation did not affect the integrity of the used magnesium plates. This study showed promising results for the further development of coated magnesium plate/screw systems for bone fixation. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference

PubMed Central

Yao, Wei; Evan Lay, Yu-An; Kot, Alexander; Liu, Ruiwu; Zhang, Hongliang; Chen, Haiyan; Lam, Kit; Lane, Nancy E.

2017-01-01

Mesenchymal stem cell (MSC) transplantation has been tested in animal and clinical fracture studies. We have developed a bone-seeking compound, LLP2A-Alendronate (LLP2A-Ale) that augments MSC homing to bone. The purpose of this study was to determine whether treatment with LLP2A-Ale or a combination of LLP2A-Ale and MSCs would accelerate bone healing in a mouse closed fracture model and if the effects are sex dependent. A right mid-femur fracture was induced in two-month-old osterix-mCherry (Osx-mCherry) male and female reporter mice. The mice were subsequently treated with placebo, LLP2A-Ale (500 µg/kg, IV), MSCs derived from wild-type female Osx-mCherry adipose tissue (ADSC, 3 × 105, IV) or ADSC + LLP2A-Ale. In phosphate buffered saline-treated mice, females had higher systemic and surface-based bone formation than males. However, male mice formed a larger callus and had higher volumetric bone mineral density and bone strength than females. LLP2A-Ale treatment increased exogenous MSC homing to the fracture gaps, enhanced incorporation of these cells into callus formation, and stimulated endochondral bone formation. Additionally, higher engraftment of exogenous MSCs in fracture gaps seemed to contribute to overall fracture healing and improved bone strength. These effects were sex-independent. There was a sex-difference in the rate of fracture healing. ADSC and LLP2A-Ale combination treatment was superior to on callus formation, which was independent of sex. Increased mobilization of exogenous MSCs to fracture sites accelerated endochondral bone formation and enhanced bone tissue regeneration. PMID:27334693

Nerve growth factor and associated nerve sprouting contribute to local mechanical hyperalgesia in a rat model of bone injury.

PubMed

Yasui, M; Shiraishi, Y; Ozaki, N; Hayashi, K; Hori, K; Ichiyanagi, M; Sugiura, Y

2012-08-01

To clarify the mechanism of tenderness after bone injury, we investigated changes in the withdrawal threshold to mechanical stimuli, nerve distribution and nerve growth factor (NGF)-expression in a rat model of bone injury without immobilization for bone injury healing. Rats were divided into three groups as follows: (1) rats incised in the skin and periosteum, followed by drilling a hole in the tibia [bone lesion group (BLG)]; (2) those incised in the skin and periosteum without bone drilling [periosteum lesion group (PLG)]; and (3) those incised in the skin [skin lesion group (SLG)]. Mechanical hyperalgesia continued for 28 days at a lesion in the BLG, 21 days in PLG and 5 days in SLG after treatments, respectively. Endochondral ossification was observed on days 5-28 in BLG and on days 5-21 in PLG. Nerve growth appeared in deep connective tissue (DCT) at day 28 in BLG. Nerve fibres increased in both cutaneous tissue and DCT at day 7 in PLG, but they were not found at day 28. Mechanical hyperalgesia accompanied with endochondral ossification and nerve fibres increasing at the lesion in both BLG and PLG. NGF was expressed in bone-regenerating cells during the bone injury healing. Anti-NGF and trk inhibitor K252a inhibited hyperalgesia in the different time course. This study shows that localized tenderness coincides with the bone healing and involves NGF expression and nerve sprouting after bone injury. The findings present underlying mechanisms and provide pathophysiological relevance of local tenderness to determination of bone fracture and its healing. © 2011 European Federation of International Association for the Study of Pain Chapters.

Biological Perspectives of Delayed Fracture Healing

PubMed Central

Hankenson, KD; Zmmerman, G; Marcucio, R

2015-01-01

Fracture healing is a complex biological process that requires interaction among a series of different cell types. Maintaining the appropriate temporal progression and spatial pattern is essential to achieve robust healing. We can temporally assess the biological phases via gene expression, protein analysis, histologically, or non-invasively using biomarkers as well as imaging techniques. However, determining what leads to normal verses abnormal healing is more challenging. Since the ultimate outcome of the process of fracture healing is to restore the original functions of bone, assessment of fracture healing should include not only monitoring the restoration of structure and mechanical function, but also an evaluation of the restoration of normal bone biology. Currently very few non-invasive measures of the biology of healing exist; however, recent studies that have correlated non-invasive measures with fracture healing outcome in humans have shown that serum TGFbeta1 levels appear to be an indicator of healing vs non-healing. In the future, developing additional serum measures to assess biological healing will improve the reliability and permit us to assess stages of fracture healing. Additionally, new functional imaging technologies could prove useful for better understanding both normal fracture healing and predicting dysfunctional healing in human patients. PMID:24857030

Enhanced Healing of Segmental Bone Defects by Modulation of the Mechanical Environment

DTIC Science & Technology

2013-10-01

Employment opportunities received based upon experience/ training supported by this award Partly based upon her research during the completion of...School, Coventry CV4 7AL, United Kingdom References 1. Stevenson S. Enhancement of fracture healing with autogenous and allogeneic bone grafts. Clin

Low-level laser therapy induces an upregulation of collagen gene expression during the initial process of bone healing: a microarray analysis

NASA Astrophysics Data System (ADS)

Tim, Carla Roberta; Bossini, Paulo Sérgio; Kido, Hueliton Wilian; Malavazi, Iran; von Zeska Kress, Marcia Regina; Carazzolle, Marcelo Falsarella; Rennó, Ana Cláudia; Parizotto, Nivaldo Antonio

2016-08-01

This study investigates the histological modifications produced by low level laser therapy (LLLT) on the first day of bone repair, as well as evaluates the LLLT effects on collagen expression on the site of a fracture. Twenty Wistar rats were distributed into a control group (CG) and a laser group (LG). Laser irradiation of Ga-Al-As laser 830 nm, 30 mW, 94 s, 2.8 J was performed in five sessions. Animals were euthanized on day 5 postsurgery. Histopathological analysis showed that LLLT was able to increase deposition of granulation tissue and newly formed bone at the site of the injury. In addition, picrosirius analysis showed that collagen fiber organization in the LG was enhanced compared to CG. Microarray analysis demonstrated that LLLT produced an upregulation type I collagen (COL-I). Immunohistochemical analysis revealed that the subjects that were treated presented a higher immunoexpression of COL-I. Our findings indicated that LLLT improves bone healing by producing a significant increase in the expression of collagen genes.

Skeletal Complications in Neurofibromatosis Type 1: The Role of Neurofibromin Haploinsufficiency in Defective Skeletal Remodeling and Bone Healing in NF1

DTIC Science & Technology

2007-01-01

including scoliosis and pseudoarthrosis, which are compounded by osteoporosis and poor bone healing. Corrective orthopaedic intervention often fails...3 - Introduction: A large proportion of patients with Neurofibromatosis Type 1 display skeletal abnormalities including scoliosis and...abnormalities including alterations in bone size and shape, the presence of scoliosis , and a tendency to develop pseudoarthrosis. These skeletal

Monitoring of bone healing by piezoelectric-EMI method

NASA Astrophysics Data System (ADS)

Mazlina, M. H.; Sarpinah, Bibi; Tawie, Rudy; Daho, Claira Dalislone; Annuar, Ishak

2016-02-01

Smart Piezoelectric devices which have excellent piezoelectric properties have been employed for various sensor and actuators applications. The work presented here is an attempt to demonstrate the feasibility of bone healing monitoring by using piezoelectric-electromechanical impedance (EMI) method that have several advantages such as low cost, portable, light weight and simplicity in measurement. A Piezoelectric sensor (PZT) has been widely used in damage detection of various structures including concrete, pipes and bones due to their unique sensing and actuating properties. The EMI technique has emerged as a universal Structural Health Monitoring (SHM) tool suitable for almost all engineering materials and structures. The method used for this proposed study consists of put healing agent in the host structure in particular cracks bone to be monitored by PZT-needle sensor which is embedded to the host structure. The measurements were taken in the frequency range between 0.04 to 100 kHz at 1 kHz interval using AD5933 evaluation board. The signals retrieved from the AD5933 evaluation board, were quantify and analyse to obtain Root Mean Square Deviation (RMSD) percentage value. Measurements were taken every hour for 12 hours. The result from the study shows the feasibility of the piezoelectric-EMI method to effectively detect changes during bone-cracks healing process until the cracks bone is fully recovered.

Effects of Platelet-Poor Plasma, Platelet-Rich Plasma, and Platelet-Rich Fibrin on Healing of Extraction Sockets with Buccal Dehiscence in Dogs

PubMed Central

Hatakeyama, Ichiro; Takahashi, Yukinobu; Omura, Ken

2014-01-01

Alveolar bone resorption generally occurs during healing after tooth extraction. This study aimed to evaluate the effects of platelet-poor plasma (PPP), platelet-rich plasma (PRP), and platelet-rich fibrin (PRF) on healing in a ridge-augmentation model of the canine socket with dehiscence of the buccal wall. The third mandibular premolars of 12 beagle dogs were extracted and a 3 mm buccal dehiscence from the alveolar crest to the buccal wall of the extraction socket was created. These sockets were then divided into four groups on the basis of the material used to fill the sockets: PPP, PRP, PRF, and control (no graft material) groups. Results were evaluated at 4 and 8 weeks after surgery. The ultrastructural morphology and constructs of each blood product were studied by a scanning electron microscope (SEM) or calculating concentrations of platelets, fibrinogen, platelet-derived growth factor, and transforming growth factor-β. A total of five microcomputed tomography images of specimens were selected for measurement, and the area occupied by the newly formed bone as well as the horizontal bone width were measured. Moreover, decalcified tissue specimens from each defect were analyzed histologically. The median area of new bone at 4 and 8 weeks and median horizontal bone width at 8 weeks were the highest in the PPP group. However, bone maturation in the PRF and the PRP groups was more progressed than that in the PPP and control groups. By SEM findings, the PRF group showed a more highly condensed fibrin fiber network that was regularly arranged when compared with the PPP and PRP groups. The growth factors released from platelets in PRP indicated higher concentrations than that in PRF. Under more severe conditions for bone formation, as in this experiment, the growth factors released from platelets had a negative effect on bone formation. This study showed that PPP is an effective material for the preservation of sockets with buccal dehiscence. PMID:24098948

Effects of platelet-poor plasma, platelet-rich plasma, and platelet-rich fibrin on healing of extraction sockets with buccal dehiscence in dogs.

PubMed

Hatakeyama, Ichiro; Marukawa, Eriko; Takahashi, Yukinobu; Omura, Ken

2014-02-01

Alveolar bone resorption generally occurs during healing after tooth extraction. This study aimed to evaluate the effects of platelet-poor plasma (PPP), platelet-rich plasma (PRP), and platelet-rich fibrin (PRF) on healing in a ridge-augmentation model of the canine socket with dehiscence of the buccal wall. The third mandibular premolars of 12 beagle dogs were extracted and a 3 mm buccal dehiscence from the alveolar crest to the buccal wall of the extraction socket was created. These sockets were then divided into four groups on the basis of the material used to fill the sockets: PPP, PRP, PRF, and control (no graft material) groups. Results were evaluated at 4 and 8 weeks after surgery. The ultrastructural morphology and constructs of each blood product were studied by a scanning electron microscope (SEM) or calculating concentrations of platelets, fibrinogen, platelet-derived growth factor, and transforming growth factor-β. A total of five microcomputed tomography images of specimens were selected for measurement, and the area occupied by the newly formed bone as well as the horizontal bone width were measured. Moreover, decalcified tissue specimens from each defect were analyzed histologically. The median area of new bone at 4 and 8 weeks and median horizontal bone width at 8 weeks were the highest in the PPP group. However, bone maturation in the PRF and the PRP groups was more progressed than that in the PPP and control groups. By SEM findings, the PRF group showed a more highly condensed fibrin fiber network that was regularly arranged when compared with the PPP and PRP groups. The growth factors released from platelets in PRP indicated higher concentrations than that in PRF. Under more severe conditions for bone formation, as in this experiment, the growth factors released from platelets had a negative effect on bone formation. This study showed that PPP is an effective material for the preservation of sockets with buccal dehiscence.

Autologous bone graft versus demineralized bone matrix in internal fixation of ununited long bones.

PubMed

Pieske, Oliver; Wittmann, Alexandra; Zaspel, Johannes; Löffler, Thomas; Rubenbauer, Bianka; Trentzsch, Heiko; Piltz, Stefan

2009-12-15

Non-unions are severe complications in orthopaedic trauma care and occur in 10% of all fractures. The golden standard for the treatment of ununited fractures includes open reduction and internal fixation (ORIF) as well as augmentation with autologous-bone-grafting. However, there is morbidity associated with the bone-graft donor site and some patients offer limited quantity or quality of autologous-bone graft material. Since allogene bone-grafts are introduced on the market, this comparative study aims to evaluate healing characteristics of ununited bones treated with ORIF combined with either iliac-crest-autologous-bone-grafting (ICABG) or demineralized-bone-matrix (DBM). From 2000 to 2006 out of sixty-two consecutive patients with non-unions presenting at our Level I Trauma Center, twenty patients had ununited diaphyseal fractures of long bones and were treated by ORIF combined either by ICABG- (n = 10) or DBM-augmentation (n = 10). At the time of index-operation, patients of the DBM-group had a higher level of comorbidity (ASA-value: p = 0.014). Mean duration of follow-up was 56.6 months (ICABG-group) and 41.2 months (DBM-group). All patients were clinically and radiographically assessed and adverse effects related to bone grafting were documented. The results showed that two non-unions augmented with ICABG failed osseous healing (20%) whereas all non-unions grafted by DBM showed successful consolidation during the first year after the index operation (p = 0.146). No early complications were documented in both groups but two patients of the ICABG-group suffered long-term problems at the donor site (20%) (p = 0.146). Pain intensity were comparable in both groups (p = 0.326). However, patients treated with DBM were more satisfied with the surgical procedure (p = 0.031). With the use of DBM, the costs for augmentation of the non-union-site are more expensive compared to ICABG (calculated difference: 160 euro/case). Nevertheless, this study demonstrated that the application of DBM compared to ICABG led to an advanced outcome in the treatment of non-unions and simultaneously to a decreased quantity of adverse effects. Therefore we conclude that DBM should be offered as an alternative to ICABG, in particular to patients with elevated comorbidity and those with limited availability or reduced quality of autologous-bone graft material.

Repair of Segmental Bone Defect Using Totally Vitalized Tissue Engineered Bone Graft by a Combined Perfusion Seeding and Culture System

PubMed Central

Feng, Ya-Fei; Li, Xiang; Hu, Yun-Yu; Wang, Zhen; Ma, Zhen-Sheng; Lei, Wei

2014-01-01

Background The basic strategy to construct tissue engineered bone graft (TEBG) is to combine osteoblastic cells with three dimensional (3D) scaffold. Based on this strategy, we proposed the “Totally Vitalized TEBG” (TV-TEBG) which was characterized by abundant and homogenously distributed cells with enhanced cell proliferation and differentiation and further investigated its biological performance in repairing segmental bone defect. Methods In this study, we constructed the TV-TEBG with the combination of customized flow perfusion seeding/culture system and β-tricalcium phosphate (β-TCP) scaffold fabricated by Rapid Prototyping (RP) technique. We systemically compared three kinds of TEBG constructed by perfusion seeding and perfusion culture (PSPC) method, static seeding and perfusion culture (SSPC) method, and static seeding and static culture (SSSC) method for their in vitro performance and bone defect healing efficacy with a rabbit model. Results Our study has demonstrated that TEBG constructed by PSPC method exhibited better biological properties with higher daily D-glucose consumption, increased cell proliferation and differentiation, and better cell distribution, indicating the successful construction of TV-TEBG. After implanted into rabbit radius defects for 12 weeks, PSPC group exerted higher X-ray score close to autograft, much greater mechanical property evidenced by the biomechanical testing and significantly higher new bone formation as shown by histological analysis compared with the other two groups, and eventually obtained favorable healing efficacy of the segmental bone defect that was the closest to autograft transplantation. Conclusion This study demonstrated the feasibility of TV-TEBG construction with combination of perfusion seeding, perfusion culture and RP technique which exerted excellent biological properties. The application of TV-TEBG may become a preferred candidate for segmental bone defect repair in orthopedic and maxillofacial fields. PMID:24728277

Histological and molecular-biological analyses of poly(3-hydroxybutyrate) (PHB) patches for enhancement of bone regeneration.

PubMed

Gredes, Tomasz; Gedrange, Tomasz; Hinüber, Claudia; Gelinsky, Michael; Kunert-Keil, Christiane

2015-05-01

Tissue engineered cell-seeded constructs with poly(3)hydroxybutyrate (PHB) induced ectopic bone formation after implantation into the back muscle of rats. The objective of our in vivo study was to evaluate the osteogenic potential of pure PHB patches in surgically created cranial defects. For this, PHB patches were analyzed after implantation in surgically created defects on the cranium of adult male rats. After healing periods of 4, 8 and 12 weeks, the bone tissue specimens containing PHB patches were processed and analyzed histologically as well as molecular-biologically. After 4 weeks, the PHB patches were completely embedded in connective tissue. Eight weeks after PHB insertion, bone regeneration proceeding from bearing bone was found in 50% of all treated animals, whereas all PHB treated cavities showed both bone formation and embedding of the patches in bone 12 weeks after surgery. Furthermore, all slices showed pronounced development of blood vessels. Histomorphometric analysis presented a regenerated bone mean value between 46.4 ± 16.1% and 54.2 ± 19.3% after 4-12 weeks of healing. Caveolin-1 staining in capillary-like structures showed a 1.16-1.38 fold increased expression in PHB treated defects compared to controls. Real-time RT-PCR analyses showed significantly lower expressions of Alpl, Col1a1 and VEGFA in cranium defects after treatment with PHB patches compared to untreated bony defects of the same cranium. Within the limits of the presented animal investigation, it could conclude that the tested PHB patches featured a good biocompatibility and an osteoconductive character. Copyright © 2014 Elsevier GmbH. All rights reserved.

Distinctive Tooth-Extraction Socket Healing: Bisphosphonate Versus Parathyroid Hormone Therapy

PubMed Central

Kuroshima, Shinichiro; Mecano, Rodan B.; Tanoue, Ryuichiro; Koi, Kiyono; Yamashita, Junro

2014-01-01

Background Patients with osteoporosis who receive tooth extractions are typically on either oral bisphosphonate or parathyroid hormone (PTH) therapy. Currently, the consequence of these therapies on hard- and soft-tissue healing in the oral cavity is not clearly defined. The aim of this study is to determine the differences in the therapeutic effect on tooth-extraction wound healing between bisphosphonate and PTH therapies. Methods Maxillary second molars were extracted in Sprague Dawley rats (n = 30), and either bisphosphonate (zoledronate [Zol]), PTH, or saline (vehicle control [VC]) was administered for 10 days (n = 10 per group). Hard-tissue healing was evaluated by microcomputed tomography and histomorphometric analyses. Collagen, blood vessels, inflammatory cell infiltration, and cathepsin K expression were assessed in soft tissue using immunohistochemistry, quantitative polymerase chain reaction, and immunoblotting. Results Both therapies significantly increased bone fill and suppressed vertical bone loss. However, considerably more devital bone was observed in the sockets of rats on Zol versus VC. Although Zol increased the numbers of blood vessels, the total blood vessel area in soft tissue was significantly smaller than in VC. PTH therapy increased osteoblastic bone formation and suppressed osteoclasts. PTH therapy promoted soft-tissue maturation by suppressing inflammation and stimulating collagen deposition. Conclusion Zoledronate therapy deters whereas PTH therapy promotes hard- and soft-tissue healing in the oral cavity, and both therapies prevent vertical bone loss. PMID:23688101

Flow velocity-driven differentiation of human mesenchymal stromal cells in silk fibroin scaffolds: A combined experimental and computational approach.

PubMed

Vetsch, Jolanda Rita; Betts, Duncan Colin; Müller, Ralph; Hofmann, Sandra

2017-01-01

Mechanical loading plays a major role in bone remodeling and fracture healing. Mimicking the concept of mechanical loading of bone has been widely studied in bone tissue engineering by perfusion cultures. Nevertheless, there is still debate regarding the in-vitro mechanical stimulation regime. This study aims at investigating the effect of two different flow rates (vlow = 0.001m/s and vhigh = 0.061m/s) on the growth of mineralized tissue produced by human mesenchymal stromal cells cultured on 3-D silk fibroin scaffolds. The flow rates applied were chosen to mimic the mechanical environment during early fracture healing or during bone remodeling, respectively. Scaffolds cultured under static conditions served as a control. Time-lapsed micro-computed tomography showed that mineralized extracellular matrix formation was completely inhibited at vlow compared to vhigh and the static group. Biochemical assays and histology confirmed these results and showed enhanced osteogenic differentiation at vhigh whereas the amount of DNA was increased at vlow. The biological response at vlow might correspond to the early stage of fracture healing, where cell proliferation and matrix production is prominent. Visual mapping of shear stresses, simulated by computational fluid dynamics, to 3-D micro-computed tomography data revealed that shear stresses up to 0.39mPa induced a higher DNA amount and shear stresses between 0.55mPa and 24mPa induced osteogenic differentiation. This study demonstrates the feasibility to drive cell behavior of human mesenchymal stromal cells by the flow velocity applied in agreement with mechanical loading mimicking early fracture healing (vlow) or bone remodeling (vhigh). These results can be used in the future to tightly control the behavior of human mesenchymal stromal cells towards proliferation or differentiation. Additionally, the combination of experiment and simulation presented is a strong tool to link biological responses to mechanical stimulation and can be applied to various in-vitro cultures to improve the understanding of the cause-effect relationship of mechanical loading.

A single topical dose of erythropoietin applied on a collagen carrier enhances calvarial bone healing in pigs

PubMed Central

2014-01-01

Background and purpose The osteogenic potency of erythropoietin (EPO) has been documented. However, its efficacy in a large-animal model has not yet been investigated; nor has a clinically safe dosage. The purpose of this study was to overcome such limitations of previous studies and thereby pave the way for possible clinical application. Our hypothesis was that EPO increases calvarial bone healing compared to a saline control in the same subject. Methods We used a porcine calvarial defect model. In each of 18 pigs, 6 cylindrical defects (diameter: 1 cm; height: 1 cm) were drilled, allowing 3 pairwise comparisons. Treatment consisted of either 900 IU/mL EPO or an equal volume of saline in combination with either autograft, a collagen carrier, or a polycaprolactone (PCL) scaffold. After an observation time of 5 weeks, the primary outcome (bone volume fraction (BV/TV)) was assessed with high-resolution quantitative computed tomography. Secondary outcome measures were histomorphometry and blood samples. Results The median BV/TV ratio of the EPO-treated collagen group was 1.06 (CI: 1.02–1.11) relative to the saline-treated collagen group. Histomorphometry showed a similar median effect size, but it did not reach statistical significance. Autograft treatment had excellent healing potential and was able to completely regenerate the bone defect independently of EPO treatment. Bony ingrowth into the PCL scaffold was sparse, both with and without EPO. Neither a substantial systemic effect nor adverse events were observed. The number of blood vessels was similar in EPO-treated defects and saline-treated defects. Interpretation Topical administration of EPO on a collagen carrier moderately increased bone healing. The dosing regime was safe, and could have possible application in the clinical setting. However, in order to increase the clinical relevance, a more potent but still clinically safe dose should be investigated. PMID:24564750

Limb reconstruction with vascularized fibular grafts after bone tumor resection.

PubMed

Brown, K L

1991-01-01

Limb-salvage operations are being used with increasing frequency for patients with malignant bone tumors. For children, when a biologic reconstruction is desired, the choice is often between conventional and vascularized fibular grafts. An experimental study was performed in dogs to compare the two types of fibular grafts for bridging segmental defects in the radius and ulna. Twenty-six adult dogs were divided into two groups and studied at intervals of two, three, four, six, and 12 months after transplantation. The conventional grafts healed by creeping substitution i.e., they were first partially resorbed before new bone was laid down. In contrast, the vascularized fibulae maintained their normal structure and hypertrophied by subperiosteal new bone formation. The conventional fibulae eventually hypertrophied but much later than the vascularized grafts. The vascularized grafts were stronger at four and six months. Between six and 12 months, both grafts remodeled to resemble the size and shape of the forearm bones they were replacing. These experimental results have influenced the treatment of patients. Vascularized fibular grafts are ideal for diaphyseal defects greater than 10 cm long, especially in very young children, a poorly vascularized bed, or when bone healing is delayed by chemotherapeutic agents. To maximize hypertrophy, an external fixator is used to immobilize the graft rather than a plate, which acts as a stress shield.

Designer bFGF-incorporated d-form self-assembly peptide nanofiber scaffolds to promote bone repair.

PubMed

He, Bin; Ou, Yunsheng; Chen, Shuo; Zhao, Weikang; Zhou, Ao; Zhao, Jinqiu; Li, Hong; Jiang, Dianming; Zhu, Yong

2017-05-01

d-Form and l-form peptide nanofiber scaffolds can spontaneously form stable β-sheet secondary structures and nanofiber hydrogel scaffolds, and hold some promise in hemostasis and wound healing. We report here on the synthetic self-assembling peptide d-RADA16 and l-RADA16 are both found to produce stable β-sheet secondary structure and nanofiber hydrogel scaffolds based on circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM) and rheology analysis etc. d-RADA16 hydrogel and l-RADA16 hydrogel can enhance obvious bone repair in femoral condyle defects of the Sprague-Dawley (SD) rat model compared to PBS treatment. Based on micro-computed tomography (CT), it was revealed that d-RADA16 hydrogel and l-RADA16 hydrogel were capable to obtain the extensive bone healing. Histological evaluation also found that these two hydrogels facilitate the presence of more mature bone tissue within the femoral condyle defects. Additionally, d-RADA16 hydrogel showed some potential in storing and releasing basic-fibroblast growth factor (bFGF) which was able to further promote bone regeneration based on micro-CT analysis. These results indicate that d-form peptide nanofiber hydrogel have some special capacity for bone repair. Copyright © 2016 Elsevier B.V. All rights reserved.

[Bone fracture and the healing mechanisms. The role of BMP signaling in fracture healing].

PubMed

Imai, Yuuki; Takaoka, Kunio

2009-05-01

When bone tissue, which plays a central role in locomotive organs, is broken by trauma and decreased in its own function of support, it is lead to be remarkable decline in the activity of daily life (ADL). Recently, in a clinical situation, various treatments have been tried for prophylaxis of fractures, and these treatments have been rewarded with good results. However, fractures would be occurred in a certain amount and there would be serious problems in ADL if the treatment fails to repair fractures. Furthermore, fractures could spontaneously heal in several weeks, it can be achieved in early rehabilitation and improvement of ADL, if we can accelerate fracture healing. Bone morphogenetic proteins, which were advocated by Dr. Urist, would be expected to be a key to establish much better society especially for the old.

Efficacy of platelet-rich plasma in arthroscopic repair of full-thickness rotator cuff tears: a meta-analysis.

PubMed

Cai, You-zhi; Zhang, Chi; Lin, Xiang-jin

2015-12-01

The use of platelet-rich plasma (PRP) is an innovative clinical therapy, especially in arthroscopic rotator cuff repair. The purpose of this study was to compare the clinical improvement and tendon-to-bone healing with and without PRP therapy in arthroscopic rotator cuff repair. A systematic search was done in the major medical databases to evaluate the studies using PRP therapy (PRP+) or with no PRP (PRP-) for the treatment of patients with rotator cuff tears. We reviewed clinical scores such as the Constant score, the American Shoulder and Elbow Surgeons score, the University of California at Los Angeles (UCLA) Shoulder Rating Scale, the Simple Shoulder Test, and the failure-to-heal rate by magnetic resonance imaging between PRP+ and PRP- groups. Five studies included in this review were used for a meta-analysis based on data availability. There were no statistically significant differences between PRP+ and PRP- groups for overall outcome scores (P > .05). However, the PRP+ group exhibited better healing rates postoperatively than the PRP- group (P = .03) in small/moderate full-thickness tears. The use of PRP therapy in full-thickness rotator cuff repairs showed no statistically significant difference compared with no PRP therapy in clinical outcome scores, but the failure-to-heal rate was significantly decreased when PRP was used for treatment of small-to-moderately sized tears. PRP therapy may improve tendon-to-bone healing in patients with small or moderate rotator cuff tears. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Sodium hyaluronate accelerates the healing process in tooth sockets of rats.

PubMed

Mendes, Renato M; Silva, Gerluza A B; Lima, Miguel F; Calliari, Marcelo V; Almeida, Alvair P; Alves, José B; Ferreira, Anderson J

2008-12-01

In this study we evaluated the effects of sodium hyaluronate (HY) in the healing process of tooth sockets of rats. Immediately after the extraction of the upper first molars of male Holtzman rats, right sockets were treated with 1% HY gel (approximately 0.1 ml), while left sockets were used as control (blood clot). The animals were sacrificed at 2, 7, and 21 days after tooth extraction and upper maxillaries processed for histological and morphometric analysis of the apical and medium thirds of the sockets. Carbopol, an inert gel, was used to evaluate the mechanical effect of gel injection into sockets. Expression of bone morphogenetic protein-2 (BMP-2) and osteopontin (OPN) was determined by immunohistochemistry at 1, 2, 3, 4, 5, and 7 days after tooth extraction. Histological analysis showed that HY treatment induced earlier trabecular bone deposition resulting in a bone matrix more organized at 7 and 21 days after tooth extraction. Also, HY elicited significant increase in the amount of bone trabeculaes at 7 and 21 days after tooth extraction (percentage of trabecular bone area at 7 days: 13.21+/-4.66% vs. 2.58+/-1.36% in the apical third of control sockets) and in the vessels counting at 7 days. Conversely, the number of cell nuclei was decreased in HY-treated sockets. Additionally, expression of BMP-2 and OPN was enhanced in HY-treated sockets compared with control sockets. These findings suggest that HY accelerates the healing process in tooth sockets of rats stimulating the expression of osteogenic proteins.

Intermittent parathyroid hormone administration improves periodontal healing in rats.

PubMed

Vasconcelos, Daniel Fernando Pereira; Marques, Marcelo Rocha; Benatti, Bruno Braga; Barros, Silvana Pereira; Nociti, Francisco Humberto; Novaes, Pedro Duarte

2014-05-01

Intermittent administration of parathyroid hormone (PTH) promotes new bone formation in patients with osteoporosis and bone fractures. It was shown previously that PTH also reduces periodontitis-related bone loss. The aim of this study is to evaluate the effect of treatment with PTH on periodontal healing in rats. Fenestration defects were created at the buccal surface of the distal root of the mandibular first molars, and both periodontal ligament (PDL) and cementum were removed. Animals were then assigned to two groups (eight animals per group): group 1: control, placebo administration; and group 2: test, human PTH (hPTH) 1-34 administration at a concentration of 40 μg/kg. For both groups, the animals were injected every 2 days, and the animals were sacrificed at 14 and 21 days after surgery. Specimens were harvested and processed for routine decalcified histologic sections. The following parameters were assessed: 1) remaining bone defect extension (RBDE); 2) newly formed bone density (NFBD); 3) total callus area (TCA); 4) osteoclast number (ON) in the callus region; and 5) newly formed dental cementum-like tissue (NFC). Birefringence of root PDL reattachment was also evaluated. Birefringence analysis showed root PDL reattachment for both groups 21 days after treatment. Intermittent hPTH 1-34 administration decreased RBDE (P <0.01) and increased NFBD (P <0.01), TCA (P <0.01), area of NFC (P <0.01), and ON in the callus region (P <0.01). Within the limits of the present study, intermittent administration of hPTH 1-34 led to an enhanced periodontal healing process compared with non-treated animals.

Effect of hyperbaric oxygen therapy combined with autologous platelet concentrate applied in rabbit fibula fraction healing

PubMed Central

Neves, Paulo César Fagundes; de Campos Vieira Abib, Simone; Neves, Rogério Fagundes; Pircchio, Oronzo; Saad, Karen Ruggeri; Saad, Paulo Fernandes; Simões, Ricardo Santos; Moreira, Marcia Bento; de Souza Laurino, Cristiano Frota

2013-01-01

OBJECTIVES: The purpose is to study the effects of hyperbaric oxygen therapy and autologous platelet concentrates in healing the fibula bone of rabbits after induced fractures. METHODS: A total of 128 male New Zealand albino rabbits, between 6–8 months old, were subjected to a total osteotomy of the proximal portion of the right fibula. After surgery, the animals were divided into four groups (n = 32 each): control group, in which animals were subjected to osteotomy; autologous platelet concentrate group, in which animals were subjected to osteotomy and autologous platelet concentrate applied at the fracture site; hyperbaric oxygen group, in which animals were subjected to osteotomy and 9 consecutive daily hyperbaric oxygen therapy sessions; and autologous platelet concentrate and hyperbaric oxygen group, in which animals were subjected to osteotomy, autologous platelet concentrate applied at the fracture site, and 9 consecutive daily hyperbaric oxygen therapy sessions. Each group was divided into 4 subgroups according to a pre-determined euthanasia time points: 2, 4, 6, and 8 weeks postoperative. After euthanasia at a specific time point, the fibula containing the osseous callus was prepared histologically and stained with hematoxylin and eosin or picrosirius red. RESULTS: Autologous platelet concentrates and hyperbaric oxygen therapy, applied together or separately, increased the rate of bone healing compared with the control group. CONCLUSION: Hyperbaric oxygen therapy and autologous platelet concentrate combined increased the rate of bone healing in this experimental model. PMID:24141841

Use of Bioresorbable Hydrogels and Genetic Engineering to Accomplish Rapid Stabilization and Healing in Segmental Long Bone Defects

DTIC Science & Technology

2013-04-29

transduction of human mesenchymal stem cells (MSCs), BMP2 was not detectable by Western blotting, whereas high levels of the protein were produced by A549 (human... mesenchymal stem cells , generating high levels of BMP2. When Ad5BMP2 or Ad5F35BMP2 were compared in vitro for their ability to induce BMP2 synthesis...in human mesenchymal stem cells and in vivo for their ability to stimulate formation of heterotopic bone, mineralized bone was radiologically

Size Does Matter: An Integrative In Vivo-In Silico Approach for the Treatment of Critical Size Bone Defects

PubMed Central

Carlier, Aurélie; van Gastel, Nick; Geris, Liesbet; Carmeliet, Geert; Van Oosterwyck, Hans

2014-01-01

Although bone has a unique restorative capacity, i.e., it has the potential to heal scarlessly, the conditions for spontaneous bone healing are not always present, leading to a delayed union or a non-union. In this work, we use an integrative in vivo - in silico approach to investigate the occurrence of non-unions, as well as to design possible treatment strategies thereof. The gap size of the domain geometry of a previously published mathematical model was enlarged in order to study the complex interplay of blood vessel formation, oxygen supply, growth factors and cell proliferation on the final healing outcome in large bone defects. The multiscale oxygen model was not only able to capture the essential aspects of in vivo non-unions, it also assisted in understanding the underlying mechanisms of action, i.e., the delayed vascularization of the central callus region resulted in harsh hypoxic conditions, cell death and finally disrupted bone healing. Inspired by the importance of a timely vascularization, as well as by the limited biological potential of the fracture hematoma, the influence of the host environment on the bone healing process in critical size defects was explored further. Moreover, dependent on the host environment, several treatment strategies were designed and tested for effectiveness. A qualitative correspondence between the predicted outcomes of certain treatment strategies and experimental observations was obtained, clearly illustrating the model's potential. In conclusion, the results of this study demonstrate that due to the complex non-linear dynamics of blood vessel formation, oxygen supply, growth factor production and cell proliferation and the interactions thereof with the host environment, an integrative in silico-in vivo approach is a crucial tool to further unravel the occurrence and treatments of challenging critical sized bone defects. PMID:25375821

Marginal and apical bone stability after staged sinus floor augmentation using bone condensing implants with variable-thread design: a two-dimensional analysis.

PubMed

Younes, F; Eghbali, A; De Troyer, S; De Bruyckere, T; Cleymaet, R; Cosyn, J

2016-09-01

Studies on the vertical stability of augmented bone after sinus lifting differ substantially. In addition, long healing periods are usually advocated prior to implant installation. The purpose of this case series study was to evaluate the changes in bone height after sinus lifting with a bovine-derived xenograft and to evaluate the clinical outcome of bone condensing implants installed after a short healing period. Patients treated during the years 2010-2013 were re-examined using peri-apical radiographs to evaluate the changes in augmented bone height (BH) and marginal bone loss (BL). Fifty-seven of 70 eligible subjects (28 male and 29 female, mean age 56 years) attended for reassessment. Data were available for 53 sinus lifts and 105 implants installed after a mean healing period of 4.6±1.5 months. Implant survival was 99% after a mean time in function of 19±9 months. Baseline BH, BH at implant placement, and final BH were on average 3.87±1.74mm, 13.75±2.12mm, and 13.11±2.12mm, respectively (P<0.001). Mean BL was 0.51±0.65mm. Only limited resorption is to be expected after sinus lifting in the short term. A bone condensing implant can be used in the early healing phase with successful outcomes in terms of implant survival and bone adaptation. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Multiscale mechanobiology of de novo bone generation, remodeling and adaptation of autograft in a common ovine femur model.

PubMed

Knothe Tate, Melissa L; Dolejs, Scott; McBride, Sarah H; Matthew Miller, R; Knothe, Ulf R

2011-08-01

The link between mechanics and biology in the generation and the adaptation of bone has been studied for more than a century in the context of skeletal development and fracture healing. However, the interplay between mechanics and biology in de novo generation of bone in postnatal defects as well as healing of morcellized bone graft or massive cortical bone autografts is less well understood. To address this, here we integrate insights from our previously published studies describing the mechanobiology on both de novo bone generation and graft healing in a common ovine femoral defect model. Studying these effects in a common experimental model provides a unique opportunity to elucidate factors conducive to harnessing the regenerative power of the periosteum, and ultimately, to provide mechanistic insights into the multiscale mechanobiology of bone generation, remodeling and adaptation. Taken together, the studies indicate that, as long as adequate, directional transport of cells and molecules can be insured (e.g. with periosteum in situ or a delivery device), biological factors intrinsic to the periosteum suffice to bridge critical sized bone defects, even in the absence of a patent blood supply. Furthermore, mechanical stimuli are crucial for the success of periosteal bone generation and bone graft healing. Interestingly, areas of highest periosteal strain around defects correlate with greatest amounts albeit not greatest mineralization of newly generated bone. This may indicate a role for convection enhanced transport of cells and molecules in modulation of tissue generation by pluripotent cells that ingress into the defect center, away from the periosteum and toward the surface of the intramedullary nail that fills the medullary cavity. These insights bring us much closer to understanding the mechanobiological environment and stimuli that stimulate the proliferation and differentiation of periosteum-derived progenitor cells and ultimately drive the generation of new bone tissue. Furthermore, these insights provide a foundation to create virtual predictive computational models of bone mechanophysiology, to develop cell seeding protocols for scale up and manufacture of engineered tissues, to optimize surgical procedures, and to develop post-surgical therapies with the ultimate goal of achieving the best possible healing outcomes for treatment and/or reconstruction of postnatal bone defects. Copyright © 2011 Elsevier Ltd. All rights reserved.

Periosteal BMP2 activity drives bone graft healing.

PubMed

Chappuis, Vivianne; Gamer, Laura; Cox, Karen; Lowery, Jonathan W; Bosshardt, Dieter D; Rosen, Vicki

2012-10-01

Bone graft incorporation depends on the orchestrated activation of numerous growth factors and cytokines in both the host and the graft. Prominent in this signaling cascade is BMP2. Although BMP2 is dispensable for bone formation, it is required for the initiation of bone repair; thus understanding the cellular mechanisms underlying bone regeneration driven by BMP2 is essential for improving bone graft therapies. In the present study, we assessed the role of Bmp2 in bone graft incorporation using mice in which Bmp2 has been removed from the limb prior to skeletal formation (Bmp2(cKO)). When autograft transplantations were performed in Bmp2cKO mice, callus formation and bone healing were absent. Transplantation of either a vital wild type (WT) bone graft into a Bmp2(cKO) host or a vital Bmp2(cKO) graft into a WT host also resulted in the inhibition of bone graft incorporation. Histological analyses of these transplants show that in the absence of BMP2, periosteal progenitors remain quiescent and healing is not initiated. When we analyzed the expression of Sox9, a marker of chondrogenesis, on the graft surface, we found it significantly reduced when BMP2 was absent in either the graft itself or the host, suggesting that local BMP2 levels drive periosteal cell condensation and subsequent callus cell differentiation. The lack of integrated healing in the absence of BMP2 was not due to the inability of periosteal cells to respond to BMP2. Healing was achieved when grafts were pre-soaked in rhBMP2 protein, indicating that periosteal progenitors remain responsive in the absence of BMP2. In contrast to the requirement for BMP2 in periosteal progenitor activation in vital bone grafts, we found that bone matrix-derived BMP2 does not significantly enhance bone graft incorporation. Taken together, our data show that BMP2 signaling is not essential for the maintenance of periosteal progenitors, but is required for the activation of these progenitors and their subsequent differentiation along the osteo-chondrogenic pathway. These results indicate that BMP2 will be among the signaling molecules whose presence will determine success or failure of new bone graft strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

Dilemma in pediatric mandible fractures: resorbable or metallic plates?

PubMed

Taylan Filinte, Gaye; Akan, İsmail Mithat; Ayçiçek Çardak, Gülçin Nujen; Özkaya Mutlu, Özay; Aköz, Tayfun

2015-12-01

The aim of this study was to compare the efficiency of resorbable and metallic plates in open reduction and internal fixation of mandible fractures in children. Thirty-one patients (mean age, 8.05 years; range 20 months-14 years) were operated on various fractures of the mandible (26 [60.4%] symphysis- parasymphysis, 12 [27.9%] condylar-subcondylar fractures, 5 [11.6%] angulus and ramus fractures). Twelve patients were treated with resorbable plates and 19 patients with metallic plates. Mean follow-up time was 41 months (11-74 months) in the metallic hardware group and was 22 months (8-35 months) in the resorbable plate group. Both groups were investigated for primary bone healing, complications, number of operations, and mandibular growth. The results were discussed below. Both groups demonstrated primary bone healing. Minor complications were similar in both groups. The metallic group involved secondary operations for plate removal. Mandibular growth was satisfactory in both groups. Resorbable plates cost more than the metallic ones; however, when the secondary operations are included in the total cost, resorbable plates were favourable. As mandibular growth and complication parameters are similar in both groups, resorbable plates are favored due to avoidance of potential odontogenic injury, elimination of long-term foreign body retention and provision of adequate stability for rapid bone healing. However, learning curve and concerns for decreased stability against heavy forces of mastication accompanied with the resorbable plates when compared to the metallic ones should be kept in mind.

A Comparative 68Ga-Citrate and 68Ga-Chloride PET/CT Imaging of Staphylococcus aureus Osteomyelitis in the Rat Tibia

PubMed Central

Lankinen, Petteri; Noponen, Tommi; Autio, Anu; Luoto, Pauliina; Löyttyniemi, Eliisa; Hakanen, Antti J.

2018-01-01

There may be some differences in the in vivo behavior of 68Ga-chloride and 68Ga-citrate leading to different accumulation profiles. This study compared 68Ga-citrate and 68Ga-chloride PET/CT imaging under standardized experimental models. Methods. Diffuse Staphylococcus aureus tibial osteomyelitis and uncomplicated bone healing rat models were used (n = 32). Two weeks after surgery, PET/CT imaging was performed on consecutive days using 68Ga-citrate or 68Ga-chloride, and tissue accumulation was confirmed by ex vivo analysis. In addition, peripheral quantitative computed tomography and conventional radiography were performed. Osteomyelitis was verified by microbiological analysis and specimens were also processed for histomorphometry. Results. In PET/CT imaging, the SUVmax of 68Ga-chloride and 68Ga-citrate in the osteomyelitic tibias (3.6 ± 1.4 and 4.7 ± 1.5, resp.) were significantly higher (P = 0.0019 and P = 0.0020, resp.) than in the uncomplicated bone healing (2.7 ± 0.44 and 2.5 ± 0.49, resp.). In osteomyelitic tibias, the SUVmax of 68Ga-citrate was significantly higher than the uptake of 68Ga-chloride (P = 0.0017). In animals with uncomplicated bone healing, no difference in the SUVmax of 68Ga-chloride or 68Ga-citrate was seen in the operated tibias. Conclusions. This study further corroborates the use of 68Ga-citrate for PET imaging of osteomyelitis. PMID:29681785

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.

T and B cells participate in bone repair by infiltrating the fracture callus in a two-wave fashion.

PubMed

Könnecke, Ireen; Serra, Alessandro; El Khassawna, Thaqif; Schlundt, Claudia; Schell, Hanna; Hauser, Anja; Ellinghaus, Agnes; Volk, Hans-Dieter; Radbruch, Andreas; Duda, Georg N; Schmidt-Bleek, Katharina

2014-07-01

Fracture healing is a regenerative process in which bone is restored without scar tissue formation. The healing cascade initiates with a cycle of inflammation, cell migration, proliferation and differentiation. Immune cells invade the fracture site immediately upon bone damage and contribute to the initial phase of the healing process by recruiting accessory cells to the injury site. However, little is known about the role of the immune system in the later stages of fracture repair, in particular, whether lymphocytes participate in soft and hard callus formation. In order to answer this question, we analyzed femoral fracture healing in mice by confocal microscopy. Surprisingly, after the initial inflammatory phase, when soft callus developed, T and B cells withdrew from the fracture site and were detectable predominantly at the femoral neck and knee. Thereafter lymphocytes massively infiltrated the callus region (around day 14 after injury), during callus mineralization. Interestingly, lymphocytes were not found within cartilaginous areas of the callus but only nearby the newly forming bone. During healing B cell numbers seemed to exceed those of T cells and B cells progressively underwent effector maturation. Both, osteoblasts and osteoclasts were found to have direct cell-cell contact with lymphocytes, strongly suggesting a regulatory role of the immune cells specifically in the later stages of fracture healing. Copyright © 2014 Elsevier Inc. All rights reserved.

Platelet-Rich Plasma in the Animal Long-Bone Model: An Analysis of Basic Science Evidence.

PubMed

Gianakos, Arianna; Zambrana, Lester; Savage-Elliott, Ian; Lane, Joseph M; Kennedy, John G

2015-12-01

Platelet-rich plasma (PRP) has been suggested as an adjunct to aid in long-bone healing. The purpose of this study was to systematically review the basic science in vivo evidence for the use of PRP in the treatment of bone pathology. The PubMed/MEDLINE and EMBASE databases were screened using the following search criteria: "(Platelet-rich plasma OR PRP OR autologous conditioned plasma OR ACP) AND (bone OR osteocytes OR osteogenesis OR nonunion OR delayed union)." Studies were included if they fulfilled the following criteria: (1) studied the effect of PRP or a similar concentrated platelet product, defined as a blood product with platelet concentration elevated to higher than baseline; (2) established a control with which to compare PRP; (3) were published in a peer-reviewed journal; and (4) looked specifically at animal long-bone models. All review articles and clinical studies, including randomized controlled trials and case series, were excluded from the review. Studies examining the effects of PRP on bones of animals with confounding pathology were excluded. In studies that contained additional treatment variables, only the portion of the experiment that compared PRP directly with the control were evaluated. Data were then extracted with a standardized table. The search yielded 29 articles for inclusion. Seventy-two percent of the studies reported platelet concentrations. Eighty-nine percent of studies reported significant improvement in earlier bone healing on histologic/histomorphometric assessment. One hundred percent showed significant increase in bone formation on radiographs in the PRP group. Eighty percent of studies reported a significant increase in bone area on microcomputed tomography. One hundred percent of studies showed a higher torsional stiffness for the PRP-treated defects. In the in vivo studies evaluated, PRP confers several beneficial effects on animal long-bone models. Proof of concept for PRP as a biologic adjunct in long-bone models has been determined. Copyright 2015, SLACK Incorporated.

Bone Regeneration Using Bone Morphogenetic Proteins and Various Biomaterial Carriers

PubMed Central

Sheikh, Zeeshan; Javaid, Mohammad Ahmad; Hamdan, Nader; Hashmi, Raheel

2015-01-01

Trauma and disease frequently result in fractures or critical sized bone defects and their management at times necessitates bone grafting. The process of bone healing or regeneration involves intricate network of molecules including bone morphogenetic proteins (BMPs). BMPs belong to a larger superfamily of proteins and are very promising and intensively studied for in the enhancement of bone healing. More than 20 types of BMPs have been identified but only a subset of BMPs can induce de novo bone formation. Many research groups have shown that BMPs can induce differentiation of mesenchymal stem cells and stem cells into osteogenic cells which are capable of producing bone. This review introduces BMPs and discusses current advances in preclinical and clinical application of utilizing various biomaterial carriers for local delivery of BMPs to enhance bone regeneration. PMID:28788032

Regenerate Healing Outcomes in Unilateral Mandibular Distraction Osteogenesis Using Quantitative Histomorphometry

PubMed Central

Schwarz, Daniel A.; Arman, Krikor G.; Kakwan, Mehreen S.; Jamali, Ameen M.; Elmeligy, Ayman A.; Buchman, Steven R.

2015-01-01

Background The authors’ goal was to ascertain regenerate bone-healing metrics using quantitative histomorphometry at a single consolidation period. Methods Rats underwent either mandibular distraction osteogenesis (n=7) or partially reduced fractures (n=7); their contralateral mandibles were used as controls (n=11). External fixators were secured and unilateral osteotomies performed, followed by either mandibular distraction osteogenesis (4 days’ latency, then 0.3 mm every 12 hours for 8 days; 5.1 mm) or partially reduced fractures (fixed immediately postoperatively; 2.1 mm); both groups underwent 4 weeks of consolidation. After tissue processing, bone volume/tissue volume ratio, osteoid volume/tissue volume ratio, and osteocyte count per high-power field were analyzed by means of quantitative histomorphometry. Results Contralateral mandibles had statistically greater bone volume/tissue volume ratio and osteocyte count per high-power field compared with both mandibular distraction osteogenesis and partially reduced fractures by almost 50 percent, whereas osteoid volume/tissue volume ratio was statistically greater in both mandibular distraction osteogenesis specimens and partially reduced fractures compared with contralateral mandibles. No statistical difference in bone volume/tissue volume ratio, osteoid volume/tissue volume ratio, or osteocyte count per high-power field was found between mandibular distraction osteogenesis specimens and partially reduced fractures. Conclusions The authors’ findings demonstrate significantly decreased bone quantity and maturity in mandibular distraction osteogenesis specimens and partially reduced fractures compared with contralateral mandibles using the clinically analogous protocols. If these results are extrapolated clinically, treatment strategies may require modification to ensure reliable, predictable, and improved outcomes. PMID:20463629

Effect of microthreads on coronal bone healing of narrow-diameter implants with reverse-tapered design in beagle dogs.

PubMed

Chang, Yun-Young; Kim, Su-Hwan; Park, Keun-Oh; Yun, Jeong-Ho

2017-12-01

The objective of this study was to investigate the effect of microthreads on the coronal bone healing of narrow-diameter implants with reverse-tapered design. A total of 52 implants were classified into two groups according to presence or absence of coronal microthreads, the reverse-tapered narrow-diameter implant (RTN) group, and the reverse-tapered narrow-diameter implant with microthreads (RTNM) group. The implants were installed in split-mouth design in the edentulous mandible of six dogs. Three animals were sacrificed at 4 weeks and three at 8 weeks. Resonance frequency analysis, bone measurement using microcomputed tomography (micro-CT), removal torque test, and histometric analysis were performed. No significant differences in implant stability quotient value were observed between the groups at baseline, 4 weeks, or 8 weeks. Bone measurement using micro-CT showed that bone-implant contact volume (BICV) and bone-implant contact volume ratio (BICVR) in the coronal part of RTNM were statistically higher than those in RTN at 4 and 8 weeks. Histometric analysis showed statistically higher bone-implant contact length (BICL) in the coronal part of RTNM than in RTN at 4 weeks; however, bone-implant contact ratio (BICR) was not significantly different between the groups. At 8 weeks, the BICL and BICR did not differ significantly between the groups. Removal torque test showed no significant differences between the groups at 4 and 8 weeks. The microthreads might facilitate more coronal bone-implant contact due to increased surface areas at an early healing phase; however, they did not significantly affect coronal bone healing at 8 weeks. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Apatite-coated Silk Fibroin Scaffolds to Healing Mandibular Border Defects in Canines

PubMed Central

Zhao, Jun; Zhang, Zhiyuan; Wang, Shaoyi; Sun, Xiaojuan; Zhang, Xiuli; Chen, Jake; Kaplan, David L.; Jiang, Xinquan

2010-01-01

Tissue engineering has become a new approach for repairing bony defects. Highly porous osteoconductive scaffolds perform the important role for the success of bone regeneration. By biomimetic strategy, apatite-coated porous biomaterial based on silk fibroin scaffolds (SS) might provide an enhanced osteogenic environment for bone-related outcomes. To assess the effects of apatite-coated silk fibroin (mSS) biomaterials for bone healing as a tissue engineered bony scaffold, we explored a tissue engineered bony graft using mSS seeded with osteogenically induced autologous bone marrow stromal cells (bMSCs) to repair inferior mandibular border defects in a canine model. The results were compared with those treated with bMSCs/SS constructs, mSS alone, SS alone, autologous mandibular grafts and untreated blank defects. According to radiographic and histological examination, new bone formation was observed from 4 weeks post-operation, and the defect site was completely repaired after 12 months for the bMSCs/mSS group. In the bMSCs/SS group, new bone formation was observed with more residual silk scaffold remaining at the center of the defect compared with the bMSCs/mSS group. The engineered bone with bMSCs/mSS achieved satisfactory bone mineral densities (BMD) at 12 months post-operation close to those of normal mandible (p>0.05). The quantities of newly formed bone area for the bMSCs/mSS group was higher than the bMSCs/SS group (p<0.01), but no significant differences were found when compared with the autograft group (p>0.05). In contrast, bony defects remained in the center with undegraded silk fibroin scaffold and fibrous connective tissue, and new bone only formed at the periphery in the groups treated with mSS or SS alone. The results suggested apatite-coated silk fibroin scaffolds combined with bMSCs could be successfully used to repair mandibular critical size border defects and the premineralization of these porous silk fibroin protein scaffolds provided an increased osteoconductive environment for bMSCs to regenerate sufficient new bone tissue. PMID:19505603

Novel Therapy for Bone Regeneration in Large Segmental Defects

DTIC Science & Technology

2017-12-01

HC, Giannoudis PV. Fat embolism and IM nailing. Injury. 2006;37(Suppl 4):S1–2. 38. Wenda K, Ritter G, Degreif J, Rudigier J. Pathogenesis of pul...morphogenetic protein (BMP), thrombopoietin (TPO), therapy, fracture healing, bone regeneration, minipig, pig 16. SECURITY CLASSIFICATION OF: 17... fracture healing, bone regeneration, minipig, pig 3. OVERALL PROJECT SUMMARY: Project start date 30/09/2013 Project end date 29/09/2017 (with 1 year NCE

Composite Bone and Soft Tissue Loss Treated with Distraction Histiogenesis

DTIC Science & Technology

2010-01-01

their frames removed had healed docking sites, and the fourth whose frame remained in place had a healing fracture without evidence of delayed union ...interventions (3–8). The goals of limb salvage surgery in this setting are to restore length and alignment, regenerate bone loss, obtain fracture union ...angulation to manage composite bone and soft tissue loss associated with combat-related type IIIB open tibia fractures . Four patients underwent placement

Carbon Nanoparticle Enhance Photoacoustic Imaging and Therapy for Bone Tissue Engineering

NASA Astrophysics Data System (ADS)

Talukdar, Yahfi

Healing critical sized bone defects has been a challenge that led to innovations in tissue engineering scaffolds and biomechanical stimulations that enhance tissue regeneration. Carbon nanocomposite scaffolds have gained interest due to their enhanced mechanical properties. However, these scaffolds are only osteoconductive and not osteoinductive. Stimulating regeneration of bone tissue, osteoinductivity, has therefore been a subject of intense research. We propose the use of carbon nanoparticle enhanced photoacoustic (PA) stimulation to promote and enhance tissue regeneration in bone tissue-engineering scaffolds. In this study we test the feasibility of using carbon nanoparticles and PA for in vivo tissue engineering applications. To this end, we investigate 1) the effect of carbon nanoparticles, such as graphene oxide nanoplatelets (GONP), graphene oxide nano ribbons (GONR) and graphene nano onions (GNO), in vitro on mesenchymal stem cells (MSC), which are crucial for bone regeneration; 2) the use of PA imaging to detect and monitor tissue engineering scaffolds in vivo; and 3) we demonstrate the potential of carbon nanoparticle enhanced PA stimulation to promote tissue regeneration and healing in an in vivo rat fracture model. The results from these studies demonstrate that carbon nanoparticles such as GNOP, GONR and GNO do not affect viability or differentiation of MSCs and could potentially be used in vivo for tissue engineering applications. Furthermore, PA imaging can be used to detect and longitudinally monitor subcutaneously implanted carbon nanotubes incorporated polymeric nanocomposites in vivo. Oxygen saturation data from PA imaging could also be used as an indicator for tissue regeneration within the scaffolds. Lastly, we demonstrate that daily stimulation with carbon nanoparticle enhanced PA increases bone fracture healing. Rats stimulated for 10 minutes daily for two weeks showed 3 times higher new cortical bone BV/TV and 1.8 times bone mineral density, compared to non-stimulated controls. The results taken together indicate that carbon nanoparticle enhanced PA stimulation serves as an anabolic stimulus for bone regeneration. The results suggest opportunities towards the development of implant device combination therapies for bone loss due to disease or trauma.

Analysis of the osseointegrative force of a hyperhydrophilic and nanostructured surface refinement for TPS surfaces in a gap healing model with the Göttingen minipig.

PubMed

Seidling, Roland; Lehmann, Lars J; Lingner, Manuel; Mauermann, Eckhard; Obertacke, Udo; Schwarz, Markus L R

2016-10-17

A lot of advantages can result in a high wettability as well as a nanostructure at a titanium surface on bone implants. Thus, the aim of this study was to evaluate the osseointegrative potential of a titan plasma-sprayed (TPS) surface refinement by acid-etching with chromosulfuric acid. This results in a hyperhydrophilic surface with a nanostructure and an extreme high wetting rate. In total, 72 dumbbell shape titan implants were inserted in the spongy bone of the femora of 18 Göttingen minipigs in a conservative gap model. Thirty-six titan implants were coated with a standard TPS surface and 36 with the hyperhydrophilic chromosulfuric acid (CSA) surface. After a healing period of 4, 8, and 12 weeks, the animals were killed. The chronological healing process was histomorphometrically analyzed. The de novo bone formation, represented by the bone area (BA), is increased by approximately 1.5 times after 12 weeks with little additional benefit by use of the CSA surface. The bone-to-implant contact (BIC), which represents osseoconductive forces, shows results with a highly increased osteoid production in the CSA implants beginning at 8 and 12 weeks compared to TPS. This culminates in a 17-fold increase in BIC after a healing period of 12 weeks. After 4 weeks, significantly more osteoid was seen in the gap as de novo formation in the CSA group (p = 0.0062). Osteoid was also found more frequently after 12 weeks at the CSA-treated surface (p = 0.0355). The site of implantation, intertrochanteric or intercondylar, may influence on the de novo bone formation in the gap. There is a benefit by the CSA surface treatment of the TPS layer for osseointegration over an observation time up to 12 weeks. Significant differences were able to be shown in two direct comparisons between the CSA and the TPS surface for osteoid formation in the gap model. Further trials may reveal the benefit of the CSA treatment of the TPS layer involving mechanical tests if possible.

Healing improvement after rotator cuff repair using gelatin-grafted poly(L-lactide) electrospun fibrous membranes.

PubMed

Zhao, Song; Xie, Xiaoxing; Pan, Guoqing; Shen, Peng; Zhao, Jinzhong; Cui, Wenguo

2015-01-01

Rotator cuff tears (RCTs) are a common cause of shoulder pain and disability in middle and older age. Despite improvements in the understanding of this disease process and advances in surgical treatment, rotator cuff (RC) repair failure rates remain high. Insufficient healing capacity is likely the main factor for failure of reconstruction. We fabricated implantable biodegradable gelatin-grafted poly(L-lactide) (PLLA) fibrous membranes using electrospinning technology and evaluated them using in vitro cell proliferation assays. Then, we established chronic rat RCT models and randomly assigned rats into one of three groups. In group 1 (n = 48), the detached supraspinatus tendon was repaired to its anatomic footprint (transosseous repair). In groups 2 and 3, the rats underwent transosseous repair and were implanted with either pure PLLA membranes (n = 48) or gelatin-PLLA membranes (n = 48) to augment the repairs. The animals were killed at 2, 4, and 8 wk postoperatively, which was followed by histomorphometric and biomechanical evaluation. Histologic observations revealed that gelatin-PLLA membranes have excellent biocompatibility and biodegradability. At 2, 4, and 8 wk postoperatively, the gelatin-PLLA membranes significantly increased the area of glycosaminoglycan staining at the tendon-bone interface compared with the control group (P < 0.05) and significantly improved collagen organization, as measured by birefringence under polarized light at the healing enthesis compared with the control and PLLA groups (P < 0.05). Biomechanical testing revealed that the gelatin-PLLA group had a greater ultimate load to failure and stiffness than the control group at 4 and 8 wk (P < 0.05). The gelatin-PLLA membranes had the highest stress of the healing enthesis. Local application of gelatin-PLLA fibrous membranes to the healing tendon-bone interface after RC repair in a rat chronic RCT model was found to strengthen the healing enthesis, increase the area of fibrocartilage, and improve collagen organization compared with repair alone. Augmentation with gelatin-grafted PLLA may enhance healing after RC repair and might eventually lead to improvement of clinical surgical outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase

PubMed Central

Rajfer, R. A.; Kilic, A.; Neviaser, A. S.; Schulte, L. M.; Hlaing, S. M.; Landeros, J.; Ferrini, M. G.; Ebramzadeh, E.

2017-01-01

Objectives We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days. Materials and Methods Unilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression nail. Rats were treated daily either with vehicle, tadalafil or COMB-4. Biomechanical testing of the healed fracture was performed on day 42. The volume, mineral content and bone density of the callus were measured by quantitative CT on days 14 and 42. Expression of iNOS was measured by immunohistochemistry. Results When compared with the control group, the COMB-4 group exhibited 46% higher maximum strength (t-test, p = 0.029) and 92% higher stiffness (t-test, p = 0.023), but no significant changes were observed in the tadalafil group. At days 14 and 42, there was no significant difference between the three groups with respect to callus volume, mineral content and bone density. Expression of iNOS at day 14 was significantly higher in the COMB-4 group which, as expected, had returned to baseline levels at day 42. Conclusion This study demonstrates an enhancement in fracture healing by an oral natural product known to augment iNOS expression. Cite this article: R. A. Rajfer, A. Kilic, A. S. Neviaser, L. M. Schulte, S. M. Hlaing, J. Landeros, M. G. Ferrini, E. Ebramzadeh, S-H. Park. Enhancement of fracture healing in the rat, modulated by compounds that stimulate inducible nitric oxide synthase: Acceleration of fracture healing via inducible nitric oxide synthase. Bone Joint Res 2017:6:–97. DOI: 10.1302/2046-3758.62.BJR-2016-0164.R2. PMID:28188129

Tendon and Ligament Regeneration and Repair: Clinical Relevance and Developmental Paradigm

PubMed Central

Tuan, Rocky S.

2014-01-01

Tendon and ligament (T/L) are dense connective tissues connecting bone to muscle and bone to bone, respectively. Similar to other musculoskeletal tissues, T/L arise from the somitic mesoderm, but they are derived from a recently discovered somitic compartment, the syndetome. The adjacent sclerotome and myotome provide inductive signals to the interposing syndetome, thereby upregulating the expression of the transcription factor Scleraxis, which in turn leads to further tenogenic and ligamentogenic differentiation. These advances in the understanding of T/L development have been sought to provide a knowledge base for improving the healing of T/L injuries, a common clinical challenge due to the intrinsically poor natural healing response. Specifically, the three most common tendon injuries involve tearing of the rotator cuff of the shoulder, the flexor tendon of the hand, and the Achilles tendon. At present, injuries to these tissues are treated by surgical repair and/or conservative approaches, including biophysical modalities such as physical rehabilitation and cryotherapy. Unfortunately, the healing tissue forms fibrovascular scar and possesses inferior mechanical and biochemical properties as compared to native T/L. Therefore, tissue engineers have sought to improve upon the natural healing response by augmenting the injured tissue with cells, scaffolds, bioactive agents, and mechanical stimulation. These strategies show promise, both in vitro and in vivo, for improving T/L healing. However, several challenges remain in restoring full T/L function following injury, including uncertainties over the optimal combination of these biological agents as well how to best deliver tissue engineered elements to the injury site. A greater understanding of the molecular mechanisms involved in T/L development and natural healing, coupled with the capability of producing complex biomaterials to deliver multiple growth factors with high spatiotemporal resolution and specificity, will allow tissue engineers to more closely recapitulate T/L morphogenesis, thereby offering future patients the prospect of T/L regeneration, as opposed to simple tissue repair. PMID:24078497

Improved Healing of Large, Osseous, Segmental Defects by Reverse Dynamization: Evaluation in a Sheep Model

DTIC Science & Technology

2015-10-01

IFM ) through the separated bone cortices (fracture gap). In research funded by a CDMRP Idea Development Award, we used a rat segmental defect...491, 2011. [3] V. Glatt, M . Miller, a Ivkovic, F. Liu, N. Parry, D. Griffin, M . Vrahas, and C. Evans, “Improved healing of large segmental defects...2012. [4] M . Mehta, S . Checa, J. Lienau, D. Hutmacher, and G. N. Duda, “In vivo tracking of segmental bone defect healing reveals that callus

[Early application of the antibiotic-laden bone cement (ALBC) combined with the external fixation support in treating the open fractures of lower limbs complicated with bone defect].

PubMed

Xiao, Jian; Mao, Zhao-Guang; Zhu, Hui-Hua; Guo, Liang

2017-03-25

To discuss the curative effect of the early application of the antibiotic-laden bone cement (ALBC) combined with the external fixation support in treating the open fractures of lower limbs complicated with bone defect. From December 2013 to January 2015, 36 cases of lower limb open comminuted fractures complicated with bone defects were treated by the vancomycin ALBC combined with the external fixation support, including 26 males and 10 females with an average age of 38.0 years old ranging from 19 to 65 years old. The included cases were all open fractures of lower limbs complicated with bone defects with different degree of soft tissue injuries. Among them, 25 cases were tibial fractures, 11 cases were femoral fractures. The radiographs indicated a presence of bone defects, which ranged from 3.0 to 6.1 cm with an average of 4.0 cm. The Gustilo classification of open fractures:24 cases were type IIIA, 12 cases were typr IIIB. The percentage of wound infection, bone grafting time, fracture healing time and postoperative joint function of lower limb were observed. The function of injured limbs was evaluated at 1 month after the clinical healing of fracture based on Paley evaluation criterion. All cases were followed up for 3 to 24 months with an average of (6.0±3.0) months. The wound surface was healed well, neither bone infections nor unhealed bone defects were presented. The reoperation of bone grafting was done at 6 weeks after the patients received an early treatment with ALBC, some of them were postponed to 8 weeks till the approximate healing of fractures, the treatment course lasted for 4 to 8 months with an average of(5.5±1.5) months. According to Paley and other grading evaluations of bone and function, there were 27 cases as excellent, 5 cases as good, 3 cases as ordinary. The ALBC combined with external fixation support was an effective method for early treatment to treat the traumatic lower limb open fractures complicated with bone defects. This method was typified with the advantages such as easy operation, short operation time, overwhelming superiority in controlling infection and provision of good bone grafting bed, a good bone healing can be realized by the use of membrane induction technology for bone grafting.

Tendon healing in a bone tunnel. Part II: Histologic analysis after biodegradable interference fit fixation in a model of anterior cruciate ligament reconstruction in sheep.

PubMed

Weiler, Andreas; Hoffmann, Reinhard F G; Bail, Hermann J; Rehm, Oliver; Südkamp, Norbert P

2002-02-01

Tendon-to-bone healing of soft-tissue grafts has been described to progress by the development of a fibrous interzone that undergoes a maturation process leading to the development of an indirect type of ligament insertion. Previous studies used extra-articular models or fixation far away from the joint line; thus, no data are available investigating tendon-to-bone healing of a soft-tissue graft fixed anatomically. Therefore, we studied the tendon-to-bone healing of the anatomic soft-tissue graft interference fit fixation in a model of anterior cruciate ligament (ACL) reconstruction in sheep. Animal study. Thirty-five mature sheep underwent ACL reconstruction with an autologous Achilles tendon split graft. Grafts were directly fixed with biodegradable poly-(D,L-lactide) interference screws. Animals were euthanized after 6, 9, 12, 24, and 52 weeks and histologic evaluations were performed. Undecalcified specimens were evaluated under normal and polarized light. Additionally, animals received a polychrome sequential labeling (tetracycline, xylenol orange, and calcein green) to determine bone growth per time under fluorescent light. Intratunnel histologic findings at 6 weeks showed a tendon-bone junction with only a partial fibrous interzone between the graft tissue and the surrounding bone. A mature intratunnel tendon-bone junction with a zone of fibrocartilage was found at 9 to 12 weeks. At the tunnel entrance site a wide regular ligamentous insertion site was seen in all specimens after 24 weeks. This insertion showed regular patterns such as the direct type of insertion of a normal ligament with a dense basophilic transition zone consisting of mineralized cartilage. A fibrous interzone between the graft tissue and the bone tunnel was only partially developed, which is in contrast to all previous studies in which nonanatomic fixation was used. Thus, it is reasonable to assume that the tendon-to-bone healing in the present study may progress partially by direct-contact healing without the development of a fibrous interzone. To our knowledge, this is the first report describing the development of a direct type of ligament insertion after ACL replacement with a soft-tissue graft. This is in contrast to previous studies reporting the development of an indirect type of insertion when using nonanatomic fixation far away from the joint line. Thus, histologic data strongly indicate that anatomic interference fit fixation is beneficial for tendon-to-bone incorporation by leading to the development of a direct type of ligament insertion.

Effects of platelet-rich fibrin on healing of intra-bony defects treated with anorganic bovine bone mineral.

PubMed

Sezgin, Yasemin; Uraz, Ahu; Taner, I Levent; Çulhaoğlu, Rana

2017-01-26

Anorganic bovine bone mineral (ABBM) is extensively used in the treatment of intra-bony defects. Platelet-rich fibrin (PRF) is a new-generation platelet concentrate with a simplified technique. Although certain studies have reported the use of PRF in the treatment of intra-bony defects, to date, none of them have evaluated its additive effects with ABBM. Therefore, a randomised, split-mouth clinical trial was conducted to compare healing of intra-bony defects treated with an ABBM-PRF combination with healing of those treated with ABBM alone. By using a split-mouth design, 15 paired intra-bony defects were randomly treated with either ABBM alone (control group) or ABBM-PRF combination (test group). Following clinical parameters and radiographical measurements were recorded at baseline and 6 months after treatment: plaque index (PI), gingival index (GI), probing depth (PD), gingival recession (GR), clinical attachment level (CAL), vertical bone loss, depth of defect and defect angle. Preoperative clinical and radiographical measurements were similar for the test and control groups. Statistically significant reductions in GI, PD, CAL, vertical bone loss, depth of intra-bony defect and widening of defect angle were detected after treatment in both groups. With respect to inter-group analysis, gain in CAL was significantly greater in the test group than in the control group, whereas no inter-group differences were observed in any other parameter. The results of this study indicate that both therapies are effective in the treatment of intra-bony defects.

Predictive value of ridge dimensions on autologous bone graft resorption in staged maxillary sinus augmentation surgery using Cone-Beam CT.

PubMed

Klijn, R J; van den Beucken, J J J P; Bronkhorst, E M; Berge, S J; Meijer, G J; Jansen, J A

2012-04-01

No studies are available that provide predictive parameters regarding the expected amount of resorption after maxillary sinus augmentation surgery using autologous bone grafts. Therefore, the aim of this study was to determine parameters influencing the outcome of the bone graft resorption process. In 20 patients, three-dimensional analysis of alveolar ridge dimensions and bone graft volume change in the atrophic posterior maxilla was performed by Cone-Beam Computerized Tomography imaging. Ridge dimensions were assessed before maxillary sinus augmentation surgery. Bone graft volumes were compared after maxillary sinus floor augmentation surgery and a graft healing interval of several months. To analyze the relation between bone volume changes with the independent variables, patients' gender, age, alveolar crest height and width, and graft healing time interval, a multi-level extension of linear regression was applied. A residual bone height of 6.0 mm (SD = 3.6 mm) and 6.2 mm (SD = 3.6 mm) was found at the left and right sides, respectively. Moreover, alveolar bone widths of 6.5 mm (SD = 2.2 mm) and 7.0 mm (SD = 2.3 mm) at the premolars, and 8.8 mm (SD = 2.2 mm) and 8.9 mm (SD = 2.5 mm) at the molars regions were found at the left and right site, respectively. Bone graft volume decreased by 25.0% (SD = 21.0%) after 4.7 months (SD = 2.7, median = 4.0 months) of healing time. The variables "age" (P = 0.009) and mean alveolar crest "bone height" (P = 0.043), showed a significant influence on bone graft resorption. A decrease of 1.0% (SE = 0.3%) of bone graft resorption was found for each year the patient grew older, and an increase in bone graft resorption of 1.8% (SE = 0.8%) was found for each mm of original bone height before sinus floor augmentation. Graft resorption occurs when using autologous bone grafts for maxillary sinus augmentation. Alveolar crest bone height and patient age have a significant effect on graft resorption, with increased resorption for higher alveolar crest bone height and decreased resorption for older patients. Consequently, patient characteristics that affect the process of bone graft resorption should be given full consideration, when performing sinus augmentation surgery. © 2011 John Wiley & Sons A/S.

Preparation of porous PLA/DBM composite biomaterials and experimental research of repair rabbit radius segmental bone defect.

PubMed

Zhang, Yumin; Wang, Jianru; Wang, Jue; Niu, Xiaojun; Liu, Jianchun; Gao, Lan; Zhai, Xiaoyan; Chu, Kaibo

2015-12-01

Bone substitutes are used in wide range of orthopaedic application. An ideal bone substitute should exhibit superior osteoinductive and osteoconductive properties. Neither bio-derived materials nor synthetic materials can meet the needs of an ideal bone substitute. Preparation of composite materials is a promising way to improve properties of biomaterial. In this study, the porous poly lactic acid (PLA)/demineralized bone matrix (DBM) composite biomaterials prepared by supercritical CO2 technique were implanted to repair rabbit radius segmental bone defect. By comparing with PLA and bone autograft, the X-ray result and histological analysis showed the repair effect of PLA/DBM porous composite materials is significantly better than that of the PLA group and the blank control group, and is similar to autologous bone. The PLA/DBM can promote the healing of bone defects and can be used as a kind of ideal alternative materials to repair bone defects.

Nonsurgical Clinical Management of Periapical Lesions Using Calcium Hydroxide-Iodoform-Silicon-Oil Paste

PubMed Central

Al Khasawnah, Qusai; Hassan, Fathi; Malhan, Deeksha; Engelhardt, Markus; Daghma, Diaa Eldin S.; Obidat, Dima; Lips, Katrin S.; Heiss, Christian

2018-01-01

Background The study aim is to avoid tooth extraction by nonsurgical treatment of periapical lesion. It assesses healing progress in response to calcium hydroxide-iodoform-silicon oil paste (CHISP). Numeric Pain Rating Scale was used to validate the approach. Furthermore, CHISP was used to treat cystic lesions secondary to posttraumatic avulsion of permanent teeth. Materials and Methods Over 200 patients with radicular cysts were treated with CHISP through the root canal. Radiographs were used to verify lesion size and position, ensure correct delivery to the site, and monitor the progress of bone healing in the lesion area. Ten males and 10 females were randomly selected for statistical assessment. Results No severe pain, complications, or failure in cyst healing was reported. Complete healing was achieved in an average of 75 days. Furthermore, healing of radicular cyst secondary to posttraumatic tooth avulsion was successful. Conclusion CHISP indicated an antiseptic effect, which enhanced and shortened healing time of periapical lesions. The less invasive procedure avoids tooth extraction and reduces bone resorption. Cyst management with CHISP can remedy failed root canal treatments. The results show a bone regenerative capacity of CHISP suggested in first rapid phase and a second slow phase. PMID:29619378

Ethanol extract of Peperomia pellucida (Piperaceae) promotes fracture healing by an anabolic effect on osteoblasts.

PubMed

Ngueguim, Florence Tsofack; Khan, Mohd Parvez; Donfack, Jean Hubert; Tewari, Deepshikha; Dimo, Theophile; Kamtchouing, Pierre; Maurya, Rakesh; Chattopadhyay, Naibedya

2013-06-21

The whole plant or some part of Peperomia pellucida (L.) HBK is used in some parts of Cameroon as a treatment for fracture healing. To evaluate the effect of ethanolic extracts of Peperomia pellucida (L.), a Cameroonian medicinal plant on bone regeneration following bone and marrow injury, and determine the mode of action. Ethanol extract of Peperomia pellucida was administered at 100 and 200mg/kg doses orally to adult female Sprague-Dawley rats having a drill hole injury (0.8mm) in the femur diaphysis. Vehicle (gum-acacia in distilled water) was given to the control group. After 12 days of treatment, animals were euthanized and femur bones collected. Confocal microscopy of calcein labeling at the drill hole site was performed to evaluate bone regeneration. 3-D microarchitecture of drill hole site was analyzed by micorocomputed tomography. Osteogenic effects of the extract were evaluated by assessing mineralized nodule formation of bone marrow stromal cells and expression of osteogenic genes (mRNA level of type-1 collagen, bone morphogenetic protein-2 and osteocalcin genes) in the femur. Ethanol extract from Peperomia Pellucida (L.) dose-dependently induced bone regeneration at the fracture site. At 200mg/kg dose, the extract significantly increased mineral deposition compared to controls. The extract also improved microarchitecture of the regenerating bone evident from increased bone volume fraction, trabecular thickness, trabecular number, and decreased trabecular separation and structure model index. In addition, the extract increased the formation of mineralized nodules from the bone marrow stromal cells. Furthermore, the extract induced the expression of osteogenic genes in the femur including type 1 collagen, osteocalcin and BMP-2, compared to control. Ethanolic extract of P. pellucid (L.) accelerates fracture repair in rats via stimulatory effects on osteoblast differentiation and mineralization, thereby justifying its traditional use. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Embryonic stem cell therapy improves bone quality in a model of impaired fracture healing in the mouse; tracked temporally using in vivo micro-CT.

PubMed

Taiani, J T; Buie, H R; Campbell, G M; Manske, S L; Krawetz, R J; Rancourt, D E; Boyd, S K; Matyas, J R

2014-07-01

In the current study, we used an estrogen-deficient mouse model of osteoporosis to test the efficacy of a cell-generated bone tissue construct for bone augmentation of an impaired healing fracture. A reduction in new bone formation at the defect site was observed in ovariectomized fractures compared to the control group using repeated measures in vivo micro-computed tomography (μCT) imaging over 4 weeks. A significant increase in the bone mineral density (BMD), trabecular bone volume ratio, and trabecular number, thickness and connectivity were associated with fracture repair in the control group, whereas the fractured bones of the ovariectomized mice exhibited a loss in all of these parameters (p<0.001). In a separate group, ovariectomized fractures were treated with murine embryonic stem (ES) cell-derived osteoblasts loaded in a three-dimensional collagen I gel and recovery of the bone at the defect site was observed. A significant increase in the trabecular bone volume ratio (p<0.001) and trabecular number (p<0.01) was observed by 4 weeks in the fractures treated with cell-loaded collagen matrix compared to those treated with collagen I alone. The stem cell-derived osteoblasts were identified at the fracture site at 4 weeks post-implantation through in situ hybridization histochemistry. Although this cell tracking method was effective, the formation of an ectopic cellular nodule adjacent to the knee joints of two mice suggested that alternative in vivo cell tracking methods should be employed in order to definitively assess migration of the implanted cells. To our knowledge, this study is the first of its kind to examine the efficacy of stem cell therapy for fracture repair in an osteoporosis-related fracture model in vivo. The findings presented provide novel insight into the use of stem cell therapies for bone injuries. Copyright © 2014 Elsevier Inc. All rights reserved.

Potential osteogenic activity of ethanolic extract and oxoflavidin isolated from Pholidota articulata Lindley.

PubMed

Sharma, Chetan; Dixit, Manisha; Singh, Rohit; Agrawal, Manali; Mansoori, Mohd Nizam; Kureel, Jyoti; Singh, Divya; Narender, Tadigoppula; Arya, Kamal Ram

2015-07-21

Pholidota articulata Lindley (PA) locally known as Hadjojen (bone jointer) belongs to family Orchidaceae is used for healing fractures in folklore tradition of Kumaon region of Uttarakhand, Himalaya, India. Bone is a dynamic organ and is constantly being remodeled in order to facilitate growth and repair. This process requires the involvement of bone forming osteoblast and bone resorbing osteoclast cells, which function in generating and mineralizing bone, giving strength and rigidity to the skeletal system. Present study was aimed to determine the therapeutic potential of ethanolic extract of PA and its isolated compound oxoflavidin, by characterizing their fracture healing properties. Ovariectomized (Ovx) estrogen deficient adult female Balb/c mice were used for in vivo evaluation of osteogenic or bone healing potential of ethanolic extract of PA. Further, its isolated compounds were tested for their osteogenic efficacy using alkaline phosphatase assay and mineralization assay in vitro in mice calvarial osteoblasts. The ethanolic extract of PA exhibited significant restoration of trabecular micro-architecture in both femoral and tibial bones. Additionally, treatment with PA extract led to better bone quality and devoid of any uterine estrogenicity in ovariectomized estrogen deficient mice. One of the isolated compound, oxoflavidin enhanced ALP activity (a marker of osteoblast differentiation), mineral nodule formation and mRNA levels of osteogenic markers like BMP-2, Type 1 Collagen, RUNX-2 and osteocalcin. These results warrant that ethanolic extract of PA and it's pure compound oxoflavidin have fracture healing properties. The extract and oxoflavidin exhibit a strong threapeutical potential for the treatment and management of postmenopausal osteoporosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dkk1 haploinsufficiency requires expression of Bmp2 for bone anabolic activity.

PubMed

Intini, Giuseppe; Nyman, Jeffry S

2015-06-01

Bone fractures remain a serious health burden and prevention and enhanced healing of fractures have been obtained by augmenting either BMP or Wnt signaling. However, whether BMP and Wnt signaling are both required or are self-sufficient for anabolic and fracture healing activities has never been fully elucidated. Mice haploinsufficient for Dkk1 (Dkk1(+/-)) exhibit a high bone mass phenotype due to an up-regulation of canonical Wnt signaling while mice lacking Bmp2 expression in the limbs (Bmp2(c/c);Prx1::cre) succumb to spontaneous fracture and are unable to initiate fracture healing; combined, these mice offer an opportunity to examine the requirement for activated BMP signaling on the anabolic and fracture healing activity of Wnts. When Dkk1(+/-) mice were crossed with Bmp2(c/c);Prx1::cre mice, the offspring bearing both genetic alterations were unable to increase bone mass and heal fractures, indicating that increased canonical Wnt signaling is unable to exploit its activity in absence of Bmp2. Thus, our data suggest that BMP signaling is required for Wnt-mediated anabolic activity and that therapies aimed at preventing fractures and fostering fracture repair may need to target both pathways for maximal efficacy. Copyright © 2015 Elsevier Inc. All rights reserved.