Parameters for defining efficacy in fracture healing

PubMed Central

Shisha, Tamas

2010-01-01

Complications of the bone-healing process, especially in elderly, osteoporotic patients, are cause of important medical and economical burden. At the same time, there is no clinical study today to have shown the efficacy of a pharmacological treatment to enhance fracture repair. The author analyzes the potential criteria that could be used for the evaluation of treatment efficacy to enhance fracture healing in the frame of a clinical study. PMID:22461284

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.

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.

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

Fracture healing: mechanisms and interventions

PubMed Central

Einhorn, Thomas A.; Gerstenfeld, Louis C.

2015-01-01

Fractures are the most common large-organ, traumatic injuries to humans. The repair of bone fractures is a postnatal regenerative process that recapitulates many of the ontological events of embryonic skeletal development. Although fracture repair usually restores the damaged skeletal organ to its pre-injury cellular composition, structure and biomechanical function, about 10% of fractures will not heal normally. This article reviews the developmental progression of fracture healing at the tissue, cellular and molecular levels. Innate and adaptive immune processes are discussed as a component of the injury response, as are environmental factors, such as the extent of injury to the bone and surrounding tissue, fixation and the contribution of vascular tissues. We also present strategies for fracture treatment that have been tested in animal models and in clinical trials or case series. The biophysical and biological basis of the molecular actions of various therapeutic approaches, including recombinant human bone morphogenetic proteins and parathyroid hormone therapy, are also discussed. PMID:25266456

Biomechanical principles and mechanobiologic aspects of flexible and locked plating.

PubMed

Claes, Lutz

2011-02-01

The goal of minimally invasive surgery in extramedullary internal fixation has led to the development of flexible plates, bridging plates, and locked internal fixators. The change from conventional compression plates to these new implants, however, resulted in different biomechanics of fixation and different mechanobiologic processes for fracture healing. The aim of a flexible fixation is the stimulation of fracture healing by callus formation. Fracture healing follows mechanobiologic rules based mainly on interfragmentary strain, which is dependent on the stability of the fixation construct and the type of fracture. Knowledge of the mechanobiologic processes and the factors influencing the stability of fracture fixation are necessary for the surgeon to choose the correct technique for fracture fixation. Problems in the selection of the correct technique and limitations with the available implants as well as possible future developments are discussed.

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.

Fracture healing with alendronate treatment in the Brtl/+ mouse model of osteogenesis imperfecta

PubMed Central

Meganck, J.A.; Begun, D.L.; McElderry, J.D.; Swick, A.; Kozloff, K.M.; Goldstein, S.A.; Morris, M.D.; Marini, J.C.; Caird, M.S.

2014-01-01

Osteogenesis imperfecta (OI) is a heritable bone dysplasia characterized by increased skeletal fragility. Patients are often treated with bisphosphonates to attempt to reduce fracture risk. However, bisphosphonates reside in the skeleton for many years and long-term administration may impact bone material quality. Acutely, there is concern about risk of non-union of fractures that occur near the time of bisphosphonate administration. This study investigated the effect of alendronate, a potent aminobisphosphonate, on fracture healing. Using the Brtl/+ murine model of type IV OI, tibial fractures were generated in 8-week-old mice that were untreated, treated with alendronate before fracture, or treated before and after fracture. After 2, 3, or 5 weeks of healing, tibiae were assessed using microcomputed tomography (μCT), torsion testing, quantitative histomorphometry, and Raman microspectroscopy. There were no morphologic, biomechanical or histomorphometric differences in callus between untreated mice and mice that received alendronate before fracture. Alendronate treatment before fracture did not cause a significant increase in cartilage retention in fracture callus. Both Brtl/+ and WT mice that received alendronate before and after fracture had increases in the callus volume, bone volume fraction and torque at failure after 5 weeks of healing. Raman microspectroscopy results did not show any effects of alendronate in wild-type mice, but calluses from Brtl/+ mice treated with alendronate during healing had a decreased mineral-to-matrix ratio, decreased crystallinity and an increased carbonate-to-phosphate ratio. Treatment with alendronate altered the dynamics of healing by preventing callus volume decreases later in the healing process. Fracture healing in Brtl/+ untreated animals was not significantly different from animals in which alendronate was halted at the time of fracture. PMID:23774443

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

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.

The effect of both a thoracic trauma and a soft-tissue trauma on fracture healing in a rat model

PubMed Central

2011-01-01

Background and purpose There is some clinical evidence that fracture healing is impaired in multiply injured patients. Nothing is known, however, about the effects of various types of injuries and their contribution to a possible disturbance of the fracture-healing process. We investigated the effect of a thoracic trauma and an additional soft-tissue trauma on fracture healing in a rat tibia model. Methods 3 groups of rats were operated: group A with a simple fracture of the tibia and fibula, group B with a fracture and an additional thoracic trauma, and group C with a fracture, thoracic trauma, and an additional soft-tissue trauma. The fracture and the soft-tissue injury were produced by a special guillotine-like device and the thoracic trauma by a blast wave generator. After one day, the serum level of IL-6 was quantified, and at the end of the study (28 days) the mechanical properties and the callus volume of the healed tibia were determined. Results Increasing the severity of the injury caused IL-6 levels to more than double 1 day after injury. It halved the load to failure in mechanical tests and led to reduced callus volume after 28 days of healing. Interpretation Fracture healing is impaired when additional thoracic trauma and soft tissue trauma occurs. PMID:21463222

Identification of a progenitor cell population destined to form fracture fibrocartilage callus in Dickkopf-related protein 3-green fluorescent protein reporter mice.

PubMed

Mori, Yu; Adams, Douglas; Hagiwara, Yusuke; Yoshida, Ryu; Kamimura, Masayuki; Itoi, Eiji; Rowe, David W

2016-11-01

Fracture healing is a complex biological process involving the proliferation of mesenchymal progenitor cells, and chondrogenic, osteogenic, and angiogenic differentiation. The mechanisms underlying the proliferation and differentiation of mesenchymal progenitor cells remain unclear. Here, we demonstrate Dickkopf-related protein 3 (Dkk3) expression in periosteal cells using Dkk3-green fluorescent protein reporter mice. We found that proliferation of mesenchymal progenitor cells began in the periosteum, involving Dkk3-positive cell proliferation near the fracture site. In addition, Dkk3 was expressed in fibrocartilage cells together with smooth muscle α-actin and Col3.6 in the early phase of fracture healing as a cell marker of fibrocartilage cells. Dkk3 was not expressed in mature chondrogenic cells or osteogenic cells. Transient expression of Dkk3 disappeared in the late phase of fracture healing, except in the superficial periosteal area of fracture callus. The Dkk3 expression pattern differed in newly formed type IV collagen positive blood vessels and the related avascular tissue. This is the first report that shows Dkk3 expression in the periosteum at a resting state and in fibrocartilage cells during the fracture healing process, which was associated with smooth muscle α-actin and Col3.6 expression in mesenchymal progenitor cells. These fluorescent mesenchymal lineage cells may be useful for future studies to better understand fracture healing.

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.

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.

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.

Self-healing volcanoes: mechanical response of magma failure, sealing and healing on outgassing

NASA Astrophysics Data System (ADS)

Lamur, A.; Lavallée, Y.; Kendrick, J. E.; Wadsworth, F. B.; Vasseur, J.

2016-12-01

Cyclic patterns of eruptive activity and quiescent periods are commonly observed at silicic volcanoes (e.g. Santiaguito, Guatemala). Quiescence, characterised by outgassing and no magmatic emissions, can last from several minutes to several years. Eruptive activity is, by comparison, expressed as the extrusion of lava/ pyroclasts, lasting minutes to years, and the onset can be extremely sudden, especially during explosive eruptions. Previous studies have shown that the overpressure leading to explosive activity can be achieved through gas accumulation following the processes of pore collapse or fracture infill and healing, which act to obliterate permeable outgassing; subsequently, magma may fragment and erupt explosively once the pressure exceeds the tensile strength. Here, we build on these studies by systematically testing the effects of fracture opening and (mechanical) sealing as well as (physico-chemical) healing. The experimental data is used to model the kinetics of fracture healing and tensile strength recovery as well as to constrain the permeability of fractured media as a function of pressure in the system. We discuss how these fracture and healing processes may operate in the timescale of pressure build-up and outgassing observed at volcanoes, without a need to invoke the input of a new magma recharge in the upper conduit.

Cartilage to bone transformation during fracture healing is coordinated by the invading vasculature and induction of the core pluripotency genes.

PubMed

Hu, Diane P; Ferro, Federico; Yang, Frank; Taylor, Aaron J; Chang, Wenhan; Miclau, Theodore; Marcucio, Ralph S; Bahney, Chelsea S

2017-01-15

Fractures heal predominantly through the process of endochondral ossification. The classic model of endochondral ossification holds that chondrocytes mature to hypertrophy, undergo apoptosis and new bone forms by invading osteoprogenitors. However, recent data demonstrate that chondrocytes transdifferentiate to osteoblasts in the growth plate and during regeneration, yet the mechanism(s) regulating this process remain unknown. Here, we show a spatially-dependent phenotypic overlap between hypertrophic chondrocytes and osteoblasts at the chondro-osseous border in the fracture callus, in a region we define as the transition zone (TZ). Hypertrophic chondrocytes in the TZ activate expression of the pluripotency factors [Sox2, Oct4 (Pou5f1), Nanog], and conditional knock-out of Sox2 during fracture healing results in reduction of the fracture callus and a delay in conversion of cartilage to bone. The signal(s) triggering expression of the pluripotency genes are unknown, but we demonstrate that endothelial cell conditioned medium upregulates these genes in ex vivo fracture cultures, supporting histological evidence that transdifferentiation occurs adjacent to the vasculature. Elucidating the cellular and molecular mechanisms underlying fracture repair is important for understanding why some fractures fail to heal and for developing novel therapeutic interventions. © 2017. Published by The Company of Biologists Ltd.

Design of experiments confirms optimization of lithium administration parameters for enhanced fracture healing.

PubMed

Vachhani, Kathak; Pagotto, Andrea; Wang, Yufa; Whyne, Cari; Nam, Diane

2018-01-03

Fracture healing is a lengthy process which fails in 5-10% of cases. Lithium, a low-cost therapeutic used in psychiatric medicine, up-regulates the canonical Wingless pathway crucial for osteoblastic mineralization in fracture healing. A design-of-experiments (DOE) methodology was used to optimize lithium administration parameters (dose, onset time and treatment duration) to enhance healing in a rat femoral fracture model. In the previously completed first stage (screening), onset time was found to significantly impact healing, with later (day 7 vs. day 3 post-fracture) treatment yielding improved maximum yield torque. The greatest strength was found in healing femurs treated at day 7 post fracture, with a low lithium dose (20 mg/kg) for 2 weeks duration. This paper describes the findings of the second (optimization) and third (verification) stages of the DOE investigation. Closed traumatic diaphyseal femur fractures were induced in 3-month old rats. Healing was evaluated on day 28 post fracture by CT-based morphometry and torsional loading. In optimization, later onset times of day 10 and 14 did not perform as well as day 7 onset. As such, efficacy of the best regimen (20 mg/kg dose given at day 7 onset for 2 weeks duration) was reassessed in a distinct cohort of animals to complete the DOE verification. A significant 44% higher maximum yield torque (primary outcome) was seen with optimized lithium treatment vs. controls, which paralleled the 46% improvement seen in the screening stage. Successful completion of this robustly designed preclinical DOE study delineates the optimal lithium regimen for enhancing preclinical long-bone fracture healing. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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.

Lack of endogenous parathyroid hormone delays fracture healing by inhibiting vascular endothelial growth factor‑mediated angiogenesis.

PubMed

Ding, Qingfeng; Sun, Peng; Zhou, Hao; Wan, Bowen; Yin, Jian; Huang, Yao; Li, Qingqing; Yin, Guoyong; Fan, Jin

2018-07-01

Intermittent low‑dose injections of parathyroid hormone (PTH) have been reported to exert bone anabolic effects and to promote fracture healing. As an important proangiogenic cytokine, vascular endothelial growth factor (VEGF) is secreted by bone marrow mesenchymal stem cells (BMSCs) and osteoblasts, and serves a crucial regulatory role in the process of vascular development and regeneration. To investigate whether lack of endogenous PTH causes reduced angiogenic capacity and thereby delays the process of fracture healing by downregulating the VEGF signaling pathway, a PTH knockout (PTHKO) mouse fracture model was generated. Fracture healing was observed using X‑ray and micro‑computerized tomography. Bone anabolic and angiogenic markers were analyzed by immunohistochemistry and western blot analysis. The expression levels of VEGF and associated signaling pathways in murine BMSC‑derived osteoblasts were measured by quantitative polymerase chain reaction and western blot analysis. The expression levels of protein kinase A (PKA), phosphorylated‑serine/threonine protein kinase (pAKT), hypoxia‑inducible factor‑1α (HIF1α) and VEGF were significantly decreased in BMSC‑derived osteoblasts from PTHKO mice. In addition, positive platelet endothelial cell adhesion molecule staining was reduced in PTHKO mice, as determined by immunohistochemistry. The expression levels of HIF1α, VEGF, runt‑related transcription factor 2, osteocalcin and alkaline phosphatase were also decreased in PTHKO mice, and fracture healing was delayed. In conclusion, lack of endogenous PTH may reduce VEGF expression in BMSC‑derived osteoblasts by downregulating the activity of the PKA/pAKT/HIF1α/VEGF pathway, thus affecting endochondral bone formation by causing a reduction in angiogenesis and osteogenesis, ultimately leading to delayed fracture healing.

The interplay of transcriptional and post-transcriptional regulation of migration of mesenchymal stem cells during early stages of bone fracture healing.

PubMed

Dong, C-H; Deng, Y-S; Yang, X-J; Liu, J; Liu, R; Hou, F-Y; Li, S-S; Zhen, P

2017-12-01

Bone fractures are a medical condition where the continuity of the bone is broken due to a fall or accident. The fracture may also be the result of medical conditions such as osteoporosis, cancers of bone or osteogenesis imperfect. During the bone fracture healing process, the mesenchymal stem cells (undifferentiated connective tissue cells) are recruited from local and systemic sources. The modulation of mesenchymal cell migration to the fractured site is the desired goal. Still, there are many processes that are still required to be studied and analyzed. We aimed to consolidate and review the available information on this topic.

Nano-copper-bearing stainless steel promotes fracture healing by accelerating the callus evolution process.

PubMed

Wang, Lei; Li, Guoyuan; Ren, Ling; Kong, Xiangdong; Wang, Yugang; Han, Xiuguo; Jiang, Wenbo; Dai, Kerong; Yang, Ke; Hao, Yongqiang

2017-01-01

Treatment for fractures requires internal fixation devices, which are mainly produced from stainless steel or titanium alloy without biological functions. Therefore, we developed a novel nano-copper-bearing stainless steel with nano-sized copper-precipitation (317L-Cu SS). Based on previous studies, this work explores the effect of 317L-Cu SS on fracture healing; that is, proliferation, osteogenic differentiation, osteogenesis-related gene expression, and lysyl oxidase activity of human bone mesenchymal stem cells were detected in vitro. Sprague-Dawley rats were used to build an animal fracture model, and fracture healing and callus evolution were investigated by radiology (X-ray and micro-CT), histology (H&E, Masson, and safranin O/fast green staining), and histomorphometry. Further, the Cu 2+ content and Runx2 level in the callus were determined, and local mechanical test of the fracture was performed to assess the healing quality. Our results revealed that 317L-Cu SS did not affect the proliferation of human bone mesenchymal stem cells, but promoted osteogenic differentiation and the expression of osteogenesis-related genes. In addition, 317L-Cu SS upregulated the lysyl oxidase activity. The X-ray and micro-CT results showed that the callus evolution efficiency and fracture healing speed were superior for 317L-Cu SS. Histological staining displayed large amounts of fibrous tissues at 3 weeks, and cartilage and new bone at 6 weeks. Further, histomorphometric analysis indicated that the callus possessed higher osteogenic efficiency at 6 weeks, and a high Cu 2+ content and increased Runx2 expression were observed in the callus for 317L-Cu SS. Besides, the mechanical strength of the fracture site was much better than that of the control group. Overall, we conclude that 317L-Cu SS possesses the ability to increase Cu 2+ content and promote osteogenesis in the callus, which could accelerate the callus evolution process and bone formation to provide faster and better fracture healing.

Nano-copper-bearing stainless steel promotes fracture healing by accelerating the callus evolution process

PubMed Central

Kong, Xiangdong; Wang, Yugang; Han, Xiuguo; Jiang, Wenbo; Dai, Kerong; Yang, Ke; Hao, Yongqiang

2017-01-01

Treatment for fractures requires internal fixation devices, which are mainly produced from stainless steel or titanium alloy without biological functions. Therefore, we developed a novel nano-copper-bearing stainless steel with nano-sized copper-precipitation (317L-Cu SS). Based on previous studies, this work explores the effect of 317L-Cu SS on fracture healing; that is, proliferation, osteogenic differentiation, osteogenesis-related gene expression, and lysyl oxidase activity of human bone mesenchymal stem cells were detected in vitro. Sprague–Dawley rats were used to build an animal fracture model, and fracture healing and callus evolution were investigated by radiology (X-ray and micro-CT), histology (H&E, Masson, and safranin O/fast green staining), and histomorphometry. Further, the Cu2+ content and Runx2 level in the callus were determined, and local mechanical test of the fracture was performed to assess the healing quality. Our results revealed that 317L-Cu SS did not affect the proliferation of human bone mesenchymal stem cells, but promoted osteogenic differentiation and the expression of osteogenesis-related genes. In addition, 317L-Cu SS upregulated the lysyl oxidase activity. The X-ray and micro-CT results showed that the callus evolution efficiency and fracture healing speed were superior for 317L-Cu SS. Histological staining displayed large amounts of fibrous tissues at 3 weeks, and cartilage and new bone at 6 weeks. Further, histomorphometric analysis indicated that the callus possessed higher osteogenic efficiency at 6 weeks, and a high Cu2+ content and increased Runx2 expression were observed in the callus for 317L-Cu SS. Besides, the mechanical strength of the fracture site was much better than that of the control group. Overall, we conclude that 317L-Cu SS possesses the ability to increase Cu2+ content and promote osteogenesis in the callus, which could accelerate the callus evolution process and bone formation to provide faster and better fracture healing. PMID:29225463

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

Genetic factors responsible for long bone fractures non-union.

PubMed

Szczęsny, Grzegorz; Olszewski, Waldemar L; Zagozda, Małgorzata; Rutkowska, Joanna; Czapnik, Zanetta; Swoboda-Kopeć, Ewa; Górecki, Andrzej

2011-02-01

Approximately 10-15% of all fractures of long bones heal with delay, prolonged immobilization and repetitive operative interventions. Despite intense investigations, the pathomechanism of impaired healing of skeletal tissue remains unclear. An important role in the pathomechanism of mal-union of close fractures plays subclinically proceeding infections. The question arises whether colonization and proliferation of bacteria in the fracture gap could be related to the mutation of genes for factors regulating local antimicrobial response, such as pathogen recognizing receptors (PRR), cytokines and chemokines. We carried out studies in patients with delayed long bone fractures estimating the frequency of mutation of genes crucial for pathogen recognition (TLR2, TLR4 and CD14), and elimination (CRP, IL-6, IL-1ra), as well as wound healing (TGF-β). The molecular milieu regulating healing process (IGF-1, COLL1a, TGF-β, BMP-2, and PDGF) was validated by Western blot analysis of the gap tissue. Microbiological investigations showed the presence of viable bacterial strains in 34 out of 108 gaps in patients with non-healing fractures (31.5%) and in 20 out of 122 patients with uneventful healing (16.4%) (P < 0.05). The occurrence of mutated TLR4 1/W but not 2/W gene was significantly higher (P < 0.05) in the non-healing infected than sterile group. In the non-healing infected group 1/W mutated gene frequency was also higher than in healing infected. In the TGF-β codon 10 a significantly higher frequency of mutated homozygote T and heterozygote C/T in the non-healing infected versus non-healing sterile subgroup was observed (P < 0.05). Similar difference was observed in the non-healing infected versus healing infected subgroup (P < 0.05). The CRP (G1059C), IL1ra (genotype 2/2), IL-6 (G176C), CD14 (G-159T), TLR2 (G2259A) and TLR4/2 (Thr399Ile) polymorphisms did not play evident role in the delay of fracture healing. Individuals bearing the mutant TLR 4 gene 1/W (Asp299Gly) and TGF-β gene codon 10 mutant T and T/C allele may predispose to impaired pathogen recognition and elimination, leading to prolonged pathogen existence in the fracture gaps and healing delays.

Numerical Simulation of Callus Healing for Optimization of Fracture Fixation Stiffness

PubMed Central

Steiner, Malte; Claes, Lutz; Ignatius, Anita; Simon, Ulrich; Wehner, Tim

2014-01-01

The stiffness of fracture fixation devices together with musculoskeletal loading defines the mechanical environment within a long bone fracture, and can be quantified by the interfragmentary movement. In vivo results suggested that this can have acceleratory or inhibitory influences, depending on direction and magnitude of motion, indicating that some complications in fracture treatment could be avoided by optimizing the fixation stiffness. However, general statements are difficult to make due to the limited number of experimental findings. The aim of this study was therefore to numerically investigate healing outcomes under various combinations of shear and axial fixation stiffness, and to detect the optimal configuration. A calibrated and established numerical model was used to predict fracture healing for numerous combinations of axial and shear fixation stiffness under physiological, superimposed, axial compressive and translational shear loading in sheep. Characteristic maps of healing outcome versus fixation stiffness (axial and shear) were created. The results suggest that delayed healing of 3 mm transversal fracture gaps will occur for highly flexible or very rigid axial fixation, which was corroborated by in vivo findings. The optimal fixation stiffness for ovine long bone fractures was predicted to be 1000–2500 N/mm in the axial and >300 N/mm in the shear direction. In summary, an optimized, moderate axial stiffness together with certain shear stiffness enhances fracture healing processes. The negative influence of one improper stiffness can be compensated by adjustment of the stiffness in the other direction. PMID:24991809

Numerical simulation of callus healing for optimization of fracture fixation stiffness.

PubMed

Steiner, Malte; Claes, Lutz; Ignatius, Anita; Simon, Ulrich; Wehner, Tim

2014-01-01

The stiffness of fracture fixation devices together with musculoskeletal loading defines the mechanical environment within a long bone fracture, and can be quantified by the interfragmentary movement. In vivo results suggested that this can have acceleratory or inhibitory influences, depending on direction and magnitude of motion, indicating that some complications in fracture treatment could be avoided by optimizing the fixation stiffness. However, general statements are difficult to make due to the limited number of experimental findings. The aim of this study was therefore to numerically investigate healing outcomes under various combinations of shear and axial fixation stiffness, and to detect the optimal configuration. A calibrated and established numerical model was used to predict fracture healing for numerous combinations of axial and shear fixation stiffness under physiological, superimposed, axial compressive and translational shear loading in sheep. Characteristic maps of healing outcome versus fixation stiffness (axial and shear) were created. The results suggest that delayed healing of 3 mm transversal fracture gaps will occur for highly flexible or very rigid axial fixation, which was corroborated by in vivo findings. The optimal fixation stiffness for ovine long bone fractures was predicted to be 1000-2500 N/mm in the axial and >300 N/mm in the shear direction. In summary, an optimized, moderate axial stiffness together with certain shear stiffness enhances fracture healing processes. The negative influence of one improper stiffness can be compensated by adjustment of the stiffness in the other direction.

Do biodegradable magnesium alloy intramedullary interlocking nails prematurely lose fixation stability in the treatment of tibial fracture? A numerical simulation.

PubMed

Wang, Haosen; Hao, Zhixiu; Wen, Shizhu

2017-01-01

Intramedullary interlocking nailing is an effective technique used to treat long bone fractures. Recently, biodegradable metals have drawn increased attention as an intramedullary interlocking nailing material. In this study, numerical simulations were implemented to determine whether the degradation rate of magnesium alloy makes it a suitable material for manufacturing biodegradable intramedullary interlocking nails. Mechano-regulatory and bone-remodeling models were used to simulate the fracture healing process, and a surface corrosion model was used to simulate intramedullary rod degradation. The results showed that magnesium alloy intramedullary rods exhibited a satisfactory degradation rate; the fracture healed and callus enhancement was observed before complete dissolution of the intramedullary rod. Delayed magnesium degradation (using surface coating techniques) did not confer a significant advantage over the non-delayed degradation process; immediate degradation also achieved satisfactory healing outcomes. However, delayed degradation had no negative effect on callus enhancement, as it did not cause signs of stress shielding. To avoid risks of individual differences such as delayed union, delayed degradation is recommended. Although the magnesium intramedullary rod did not demonstrate rapid degradation, its ability to provide high fixation stiffness to achieve earlier load bearing was inferior to that of the conventional titanium alloy and stainless steel rods. Therefore, light physiological loads should be ensured during the early stages of healing to achieve bony healing; otherwise, with increased loading and degraded intramedullary rods, the fracture may ultimately fail to heal. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Formononetin promotes early fracture healing through stimulating angiogenesis by up-regulating VEGFR-2/Flk-1 in a rat fracture model.

PubMed

Huh, Jeong-Eun; Kwon, Na-Hyun; Baek, Young-Hyun; Lee, Jae-Dong; Choi, Do-Young; Jingushi, Seiya; Kim, Kang-il; Park, Dong-Suk

2009-11-01

Plant-derived phytoestrogens have bone protective effects, but the molecular mechanism behind these effects remains unclear. This study is aimed at fully characterizing the fracture healing process of formononetin, and investigating the mechanism underlying angiogenesis in calluses of a rat fracture model. Femoral fractures were produced in 2-month-old Sprague-Dawley rats. A 20 microg/kg or 200 microg/kg dose of formononetin was orally administrated once a day during the healing period of 21 days. The results showed that in the early stage of chondrogenesis (days 3), formononetin significantly increased the number of vessels, and expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2/flk-1) compared with control. However, the larger dose of formononetin had no significant difference on expression of VEGF and VEGFR-2/Flk-1 compared with that of the smaller dose of formononetin. After 7 days of administration, formononetin markedly induced differentiation of mesenchymal stem cells in the fracture site. After 14 days, gene expression of mesenchymal progenitors such as alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN) and collagen type I (Col I), indicating osteogenic differentiation, was markedly stimulated by formononetin compared with control. These results suggest that formononetin promotes early fracture healing through angiogenesis activation in the early stage of fracture repair, and osteogenesis acceleration in the later stages, and thus may be beneficial for fracture healing.

Do estrogen and alendronate improve metaphyseal fracture healing when applied as osteoporosis prophylaxis?

PubMed

Kolios, Leila; Hoerster, Ann Kristin; Sehmisch, Stephan; Malcherek, Marie Christin; Rack, Thomas; Tezval, Mohammed; Seidlova-Wuttke, Dana; Wuttke, Wolfgang; Stuermer, Klaus Michael; Stuermer, Ewa Klara

2010-01-01

Osteoporosis is accompanied by predominantly metaphyseal fractures with a delayed and qualitatively reduced healing process. This study addressed the question of whether fracture healing in the context of osteoporosis prophylaxis is improved with estrogen (E) or alendronate (ALN). Thirty-six ovariectomized and 12 sham-operated 12-week-old rats received soy-free (osteoporotic C, sham), E-, or ALN- supplemented diets. After 10 weeks, a metaphyseal tibia osteotomy and standardized T-plate fixation were performed. After a 5-week healing process, the fracture callus was evaluated qualitatively by biomechanical bending test and quantitatively in microradiographic sections. The time course of callus formation was examined using fluorochrome-labeled histological sections. Administration of E improved the biomechanical properties of callus (stiffness [N/mm]: sham: 110.2 + or - 76.07, C: 41.28 + or - 33.70, E: 85.72 + or - 47.24, ALN: 72.07 + or - 34.68). The resistance to microfracturing seen in E-treated animals was significantly enhanced and even superior to sham (yield load [N] sham: 27.44 + or - 9.72, C: 21.04 + or - 12.47, E: 42.85 + or - 13.74(Delta), ALN: 25.28 + or - 6.4(.)) (* P < 0.05 vs. sham group, (Delta) P < 0.05 vs. C group, (*) P < 0.05 vs. E group). Trabecular bone in particular was improved, indicating the presence of physiological endosteal bridging (Tr.Dn [%] sham: 10.53 + or - 18.9, C: 1.01 + or - 0.14, E: 24.13 + or - 34.09(Delta), ALN: 3.99 + or - 8.3(.)). ALN did not help bone healing, as shown by mechanical tests. Compared to the C group, statistically, ALN did not show worse properties. The induction of callus formation under ALN treatment was slightly delayed (Tt.Cl [mm(2)] sham: 3.68 + or - 0.66, C: 3.44 + or - 0.42, E: 3.69 + or - 0.58, ALN: 3.06 + or - 0.56). Osteoporotic metaphyseal fracture healing was qualitatively and quantitatively improved by E prophylaxis. The process of fracture healing occurred nearly physiologically (shamlike). Notably, ALN hardly improved metaphyseal callus properties when assessed as osteoporosis prophylaxis, but to a lesser extent than E.

Bioinformatics and Microarray Analysis of miRNAs in Aged Female Mice Model Implied New Molecular Mechanisms for Impaired Fracture Healing

PubMed Central

He, Bing; Zhang, Zong-Kang; Liu, Jin; He, Yi-Xin; Tang, Tao; Li, Jie; Guo, Bao-Sheng; Lu, Ai-Ping; Zhang, Bao-Ting; Zhang, Ge

2016-01-01

Impaired fracture healing in aged females is still a challenge in clinics. MicroRNAs (miRNAs) play important roles in fracture healing. This study aims to identify the miRNAs that potentially contribute to the impaired fracture healing in aged females. Transverse femoral shaft fractures were created in adult and aged female mice. At post-fracture 0-, 2- and 4-week, the fracture sites were scanned by micro computed tomography to confirm that the fracture healing was impaired in aged female mice and the fracture calluses were collected for miRNA microarray analysis. A total of 53 significantly differentially expressed miRNAs and 5438 miRNA-target gene interactions involved in bone fracture healing were identified. A novel scoring system was designed to analyze the miRNA contribution to impaired fracture healing (RCIFH). Using this method, 11 novel miRNAs were identified to impair fracture healing at 2- or 4-week post-fracture. Thereafter, function analysis of target genes was performed for miRNAs with high RCIFH values. The results showed that high RCIFH miRNAs in aged female mice might impair fracture healing not only by down-regulating angiogenesis-, chondrogenesis-, and osteogenesis-related pathways, but also by up-regulating osteoclastogenesis-related pathway, which implied the essential roles of these high RCIFH miRNAs in impaired fracture healing in aged females, and might promote the discovery of novel therapeutic strategies. PMID:27527150

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.

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

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

Outcome of limb fracture repair in rabbits: 139 cases (2007-2015).

PubMed

Sasai, Hiroshi; Fujita, Daisuke; Seto, Eiko; Denda, Yuki; Imai, Yutaro; Okamoto, Kanako; Okamura, Kensaku; Furuya, Masaru; Tani, Hiroyuki; Sasai, Kazumi

2018-02-15

OBJECTIVE To evaluate outcome of limb fracture repair in rabbits. DESIGN Retrospective case series. ANIMALS 139 client-owned rabbits with limb fractures treated between 2007 and 2015. PROCEDURES Medical records were reviewed for information on fracture location, fracture treatment, and time to fracture healing. RESULTS 25 rabbits had fractures involving the distal aspects of the limbs (ie, metacarpal or metatarsal bones, phalanges, and calcaneus or talus). Fractures were treated in 23 of these 25 rabbits (external coaptation, n = 17; external skeletal fixation, 4; and intramedullary pinning, 2) and healed in all 23, with a median healing time of 28 days (range, 20 to 45 days). One hundred ten rabbits had long bone fractures, and fractures were treated in 100 of the 110 (external skeletal fixation, n = 89; bone plating, 1; intramedullary pinning, 3; and external coaptation, 7). The percentage of fractures that healed was significantly lower for open (14/18) than for closed (26/26) tibial fractures and was significantly lower for femoral (19/26) and treated humeral (4/6) fractures than for radial (23/24) or closed tibial (26/26) fractures. Micro-CT was used to assess fracture realignment during external skeletal fixator application and to evaluate fracture healing. CONCLUSIONS AND CLINICAL RELEVANCE The prognosis for rabbits with limb fractures was good, with fractures healing in most rabbits following fracture repair (109/123). Micro-CT was useful in assessing fracture realignment and evaluating fracture healing.

In vivo effect of shock-waves on the healing of fractured bone.

PubMed

Augat, P; Claes, L; Suger, G

1995-10-01

In a controlled animal experiment we attempted to clarify the question of whether there is a stimulating effect of extracorporeal shock-waves on the repair process of fractured long bones. As a fracture model we used an osteotomy in the diaphysis of the ovine tibia and an external fixation device. Shock-wave treatment at two levels of intensity and with four different numbers of applied shocks was performed with an electromagnetic acoustic source. Healing of the osteotomized bone was evaluated by biomechanical and radiological investigations on the whole bone as well as on bone sections from areas of the fracture gap and the periosteal fracture callus. We found a non-significant tendency to deterioration of the fracture healing with increasing shock-wave intensities. The study of treatment parameters led neither to significantly different biomechanical outcomes nor to altered radiological results in comparison to the untreated control group. RELEVANCE:--While we cannot comment upon the effectiveness of extracorporeal shock-waves in the delayed treatment of fractures or pseudarthrosis, our results suggest that shock-waves have no beneficial effect in acute fracture repair.

Effects of foot posture on fifth metatarsal fracture healing: a finite element study.

PubMed

Brilakis, Emmanuel; Kaselouris, Evaggelos; Xypnitos, Frank; Provatidis, Christopher G; Efstathopoulos, Nicolas

2012-01-01

The goal of this study was to evaluate the effects of maintaining different foot postures during healing of proximal fifth metatarsal fractures for each of 3 common fracture types. A 3-dimensional (3D) finite element model of a human foot was developed and 3 loading situations were evaluated, including the following: (1) normal weightbearing, (2) standing with the affected foot in dorsiflexion at the ankle, and (3) standing with the affected foot in eversion. Three different stages of the fracture-healing process were studied, including: stage 1, wherein the material interposed between the fractured edges was the initial connective tissue; stage 2, wherein connective tissue had been replaced by soft callus; and stage 3, wherein soft callus was replaced by mature bone. Thus, 30 3D finite element models were analyzed that took into account fracture type, foot posture, and healing stage. Different foot postures did not statistically significantly affect the peak-developed strains on the fracture site. When the fractured foot was everted or dorsiflexed, it developed a slightly higher strain within the fracture than when it was in the normal weightbearing position. In Jones fractures, eversion of the foot caused further torsional strain and we believe that this position should be avoided during foot immobilization during the treatment of fifth metatarsal base fractures. Tuberosity avulsion fractures and Jones fractures seem to be biomechanically stable fractures, as compared with shaft fractures. Our understanding of the literature and experience indicate that current clinical observations and standard therapeutic options are in accordance with the results that we observed in this investigation, with the exception of Jones fractures. Copyright © 2012 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

A Case of Acromioclavicular Joint Dislocation Associated with Coracoid Process Fracture.

PubMed

Nakamura, Yosuke; Gotoh, Masafumi; Mitsui, Yasuhiro; Shirachi, Isao; Yoshikawa, Eiichiro; Uryu, Takuya; Murakami, Hidetaka; Okawa, Takahiro; Higuchi, Fujio; Shiba, Naoto

2015-01-01

Rupture of any two or more parts of the superior shoulder suspensory complex (SSSC) including the distal clavicle, acromion, coracoid process, glenoid cavity of the scapula, acromioclavicular ligament, and coracoclavicular ligament is associated with shoulder girdle instability and is an indication for surgery. Here we report a case of acromioclavicular joint dislocation associated with coracoid process fracture. A 48-year-old man sustained a hard blow to the left shoulder from a fall, and simple radiography detected a coracoid process fracture and acromioclavicular joint dislocation. The injury consisted of a rupture of two parts of the SSSC. For the coracoid process fracture, osteosynthesis was performed using hollow cancellous bone screws. For the acromioclavicular joint dislocation, hook plate fixation and the modified Neviaser's procedure were performed. The bone healed well 5 months after surgery, at which time the screws were removed. At 18 months after initial surgery, the coracoid process fracture had healed with a 10% rate of dislocation on radiography, and the patient currently has no problem performing daily activities, no range of motion limitations, and a Japanese Orthopaedic Association scale score of 93.

Prediction of fracture healing under axial loading, shear loading and bending is possible using distortional and dilatational strains as determining mechanical stimuli.

PubMed

Steiner, Malte; Claes, Lutz; Ignatius, Anita; Niemeyer, Frank; Simon, Ulrich; Wehner, Tim

2013-09-06

Numerical models of secondary fracture healing are based on mechanoregulatory algorithms that use distortional strain alone or in combination with either dilatational strain or fluid velocity as determining stimuli for tissue differentiation and development. Comparison of these algorithms has previously suggested that healing processes under torsional rotational loading can only be properly simulated by considering fluid velocity and deviatoric strain as the regulatory stimuli. We hypothesize that sufficient calibration on uncertain input parameters will enhance our existing model, which uses distortional and dilatational strains as determining stimuli, to properly simulate fracture healing under various loading conditions including also torsional rotation. Therefore, we minimized the difference between numerically simulated and experimentally measured courses of interfragmentary movements of two axial compressive cases and two shear load cases (torsional and translational) by varying several input parameter values within their predefined bounds. The calibrated model was then qualitatively evaluated on the ability to predict physiological changes of spatial and temporal tissue distributions, based on respective in vivo data. Finally, we corroborated the model on five additional axial compressive and one asymmetrical bending load case. We conclude that our model, using distortional and dilatational strains as determining stimuli, is able to simulate fracture-healing processes not only under axial compression and torsional rotation but also under translational shear and asymmetrical bending loading conditions.

Influence of mechanical rock properties and fracture healing rate on crustal fluid flow dynamics

NASA Astrophysics Data System (ADS)

Sachau, Till; Bons, Paul; Gomez-Rivas, Enrique; Koehn, Daniel; de Riese, Tamara

2016-04-01

Fluid flow in the Earth's crust is very slow over extended periods of time, during which it occurs within the connected pore space of rocks. If the fluid production rate exceeds a certain threshold, matrix permeability alone is insufficient to drain the fluid volume and fluid pressure builds up, thereby reducing the effective stress supported by the rock matrix. Hydraulic fractures form once the effective pressure exceeds the tensile strength of the rock matrix and act subsequently as highly effective fluid conduits. Once local fluid pressure is sufficiently low again, flow ceases and fractures begin to heal. Since fluid flow is controlled by the alternation of fracture permeability and matrix permeability, the flow rate in the system is strongly discontinuous and occurs in intermittent pulses. Resulting hydraulic fracture networks are largely self-organized: opening and subsequent healing of hydraulic fractures depends on the local fluid pressure and on the time-span between fluid pulses. We simulate this process with a computer model and describe the resulting dynamics statistically. Special interest is given to a) the spatially and temporally discontinuous formation and closure of fractures and fracture networks and b) the total flow rate over time. The computer model consists of a crustal-scale dual-porosity setup. Control parameters are the pressure- and time-dependent fracture healing rate, and the strength and the permeability of the intact rock. Statistical analysis involves determination of the multifractal properties and of the power spectral density of the temporal development of the total drainage rate and hydraulic fractures. References Bons, P. D. (2001). The formation of large quartz veins by rapid ascent of fluids in mobile hydrofractures. Tectonophysics, 336, 1-17. Miller, S. a., & Nur, A. (2000). Permeability as a toggle switch in fluid-controlled crustal processes. Earth and Planetary Science Letters, 183(1-2), 133-146. Sachau, T., Bons, P. D., & Gomez-Rivas, E. (2015). Transport efficiency and dynamics of hydraulic fracture networks. Frontiers in Physics, 3.

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

Guha, A.; Prasad, G.C.; Udupa, K.N.

Scintillography and autoradiography were used to study the healing of humeral fractures in rats injected with Sr/sup 85/. Among various agents studied for an influence on the rate of fracture healing, the total extract of the herb Cissus quadrangularis was tested. In both controls and animals receiving C. quadrangularis extract there was demineralization of the fractured bone at the site of fracture. In the treated group, there was a somewhat earlier rise in Sr/ sup 85/ uptake just after the first injection. Thereafter, uptake again became high, similar to the control samples from the 6th day onward. The maximum uptakemore » of control bone was found to be around the 19th day after fracturing, while in the treated group, maximum uptake was on 15th day. Though there was a minor difference in the period of maximum uptake between treated and control bone, the rate of uptake in the treated sample was markedly higher than that of the control sample. The fall of Sr/sup 85/ uptake in the treated bone was very rapid, whereas in the untreated animals it was more gradual. All these findings on the uptake of Sr/sup 85/ as measured by a G-M counter, corroborated x-ray pictures and gross autoradiography at different stages of fracture healing. The radiological and autoradiographic findings also clearly showed that the healing in the treated group was quicker than in the controls. Furthermore, the callus in the treated animals underwent remodeling processes much earlier than in the nontreated ones. It is concluded that if the uptake of Sr in the treated andimals is greater thand in the control samples at the site of fracture, healing activity is more pronounced. However, studies on patients have shown that the uptake of Sr/sup 85/ alone in the fractured region may not give an accurate picture of the healing processes. Thus, at the end of first week after fractures, accretion rate of Ca reached a peak and thereafter remained higher than normal throughout the period of healing. But when these results were compared with x-ray pictures, it was observed that the accretion rate in poorly uniting fractures did not diifer from that of normally healing fractures, so that in interpreting the rate of healing by the uptake of Sr/sup 85/, radiography is also required to make the correct assessment of the status of fracture healing. The Sr/sup 85/ uptake curves show that the uptake pattern can be divided into three definite phases. ln the first phase, which lasts for six days, there is and enormous amount of decalcification from the broken fragments of bone possibly due to increased vascularity of the region, and also to the increased accumulation of mucopolysaccharides locally. In the second phase, which lasts for another 8 to 12 days, rapid increase in the accretion of Ca as evidenced by increase in the uptake of Sr/sup 85/ noted. During the 2nd phase, histologic studies indicated that large amounts of collagen fibers appear, which possibly combine with all the available Ca salts there. The third phase shows a rapid fall of Sr/sup 85/ uptake, indicating that the callus formed in the second phase is rapidly being remodeled. (BBB)« less

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

Cast Care: Do's and Don'ts

MedlinePlus

... the healing process. Derby R, et al. General principles of acute fracture management. https://uptodate.com/contents/search. Accessed Jan. 25, 2018. Eiff MP, et al. General principles of fracture care. In: Fracture Management for Primary Care, Updated Edition. 3rd ed. Philadelphia, ...

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.

[Calcium and vitamin D in bone metabolism: Clinical importance for fracture treatment].

PubMed

Amling, M

2015-12-01

A balanced calcium homeostasis is of critical importance not only for bone remodeling, the physiological process of bone resorption and bone formation that constantly renews bone throughout life but also for normal fracture healing. Given that disturbances of calcium homeostasis are present in 50 % of the German population and that this might result in delayed fracture healing after correct surgical treatment, this paper focusses on calcium and vitamin D in the daily practice in orthopedics and trauma surgery. To ensure the required enteral calcium uptake the following three conditions are required: (1) sufficient calcium intake via the nutrition, (2) a 25-hydroxyvitamin D serum level > 30 µg/l and (3) the presence of sufficient gastric acidification. Given the endemic vitamin D deficiency in Germany as well as the constantly increasing number of people using proton pump inhibitors on a regular basis, it is necessary to closely connect trauma orthopedic surgery and osteological treatment. The first issue to be dealt with is to control and if needed normalize calcium homeostasis in order to allow a normal undisturbed fracture healing process after both conservative as well as operative treatment of fractures.

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.

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.

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.

Local administration of a hedgehog agonist accelerates fracture healing in a mouse model

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

Kashiwagi, Miki; Division of Clinical Biotechnology, The University of Tokyo Graduate School of Medicine, Bunkyo-ku, Tokyo, 113-0033; Hojo, Hironori

Bone fracture healing is processed through multiple biological stages including the transition from cartilaginous callus to bony callus formation. Because of its specific, temporal and indispensable functions demonstrated by mouse genetic studies, Hedgehog (Hh) signaling is one of the most potent signaling pathways involved in these processes, but the effect of Hh-signaling activation by small compounds on the repair process had not yet been addressed. Here we examined therapeutic effects of local and one shot-administration of the Hh agonist known as smoothened agonist (SAG) on bone fracture healing in a mouse model. A quantitative analysis with three-dimensional micro-computed tomography showedmore » that SAG administration increased the size of both the cartilaginous callus and bony callus at 14 days after the surgery. A histological analysis showed that SAG administration increased the number of cells expressing a proliferation marker and a chondrocyte marker in cartilaginous callus as well as the cells expressing an osteoblast marker in bony callus. These results indicate that the SAG administration resulted in an enhancement of callus formation during bone fracture healing, which is at least in part mediated by an increase in chondrocyte proliferation in cartilaginous callus and the promotion of bone formation in bony callus. Therapeutic strategies with a SAG-mediated protocol may thus be useful for the treatment of bone fractures. - Highlights: • Local administration of a Hh agonist accelerates callus formation. • The Hh agonist administration promotes chondrocyte proliferation in the soft callus. • The Hh agonist administration increases osteoblast formation in the hard callus.« less

Effect of autocontrol micromotion intramedullary interlocking nail on fracture healing: an experimental study.

PubMed

Xu, Wei-zhou; Guo, Xiao-dong; Zhao, Ju-cai; Wang, Yi-jin

2006-06-01

To investigate the effect of autocontrol micromotion locking nail (AMLN) on experimental fracture healing and its mechanism. 16 goats undergoing both sides of transverse osteotomy of the femoral shafts were fixed intramedullary with AMLN and Gross-Kempf (GK) nail, respectively. The follow-up time was 7, 14, 28 and 56 days. Roentgenographic, biomechanical, histological, scanning electromicroscopic and biochemical analyses were done. (1) The strength of anticompression, antiflexion and antitorsion in the fractural end in the AMLN-fixed group was higher than that of GK nail-fixed group; whereas, the rate of stress shelter in the fractured end decreased significantly (P<0.01). (2) The content of the total collagen, insoluble collagen, calcium and phosphate in the AMLN-fixed group was higher than that in the GK nail-fixed group (P<0.05). (3) Histological observation and quantitative analysis of calluses revealed that AMLN could promote the growth of bridge calluses and periosteum calluses. Hence the fracture healing and remolding process achieved early, which was much better than traditional GK nail fixation. (P<0.05). (4) 7-14 days postoperation, the calluses of AMLN-fixed group was flourish and camellarly arranged and the collagen fibril formed constantly in the absorption lacuna of bone trabecula. 28-56 days postoperation, the collagen fibril was flourish around the absorption lacuna and was parallel to the bone's longitudinal axis. Active bony absorption and formation were seen, so was remolding and rebuilding. Haversian system was intact and the bony structural net was very tenacious because of the deposition of calcium salt. None of the above findings was observed in the GK nail-fixed group. The design of AMLN accords well with the plastic fixation theory. As the geometry ametabolic system constituted by the intramedullary fixation instruments and the proximal and distal end of the fracture is very firm and stable, the disturbance to the physical stress distributed in the fractural end is light. The generation and conduct of the intermittent physical stress between the fractural parts could reach the balance between stress conduct and stress protection. The feature that the healing and remolding take place at the same time speeds up the fractural healing process.

Low-dose TNF augments fracture healing in normal and osteoporotic bone by up-regulating the innate immune response

PubMed Central

Chan, James K; Glass, Graeme E; Ersek, Adel; Freidin, Andrew; Williams, Garry A; Gowers, Kate; Espirito Santo, Ana I; Jeffery, Rosemary; Otto, William R; Poulsom, Richard; Feldmann, Marc; Rankin, Sara M; Horwood, Nicole J; Nanchahal, Jagdeep

2015-01-01

The mechanism by which trauma initiates healing remains unclear. Precise understanding of these events may define interventions for accelerating healing that could be translated to the clinical arena. We previously reported that addition of low-dose recombinant human TNF (rhTNF) at the fracture site augmented fracture repair in a murine tibial fracture model. Here, we show that local rhTNF treatment is only effective when administered within 24 h of injury, when neutrophils are the major inflammatory cell infiltrate. Systemic administration of anti-TNF impaired fracture healing. Addition of rhTNF enhanced neutrophil recruitment and promoted recruitment of monocytes through CCL2 production. Conversely, depletion of neutrophils or inhibition of the chemokine receptor CCR2 resulted in significantly impaired fracture healing. Fragility, or osteoporotic, fractures represent a major medical problem as they are associated with permanent disability and premature death. Using a murine model of fragility fractures, we found that local rhTNF treatment improved fracture healing during the early phase of repair. If translated clinically, this promotion of fracture healing would reduce the morbidity and mortality associated with delayed patient mobilization. PMID:25770819

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.

Locally applied simvastatin improves fracture healing at late period in osteoporotic rat

NASA Astrophysics Data System (ADS)

Tian, Faming; Zhang, Liu; Kang, Yuchuan; Zhang, Junshan; Ao, Jiao; Yang, Fang

effect of simvastatin locally applied from a bioactive polymer coating of implants on osteoporotic fracture healing at late period. Methods:Femur fracture model was established on normal or osteotoporotic mature female SD rats, intramedullary stabilization was achieved with uncoated titanium Kirschnerwires in normal rats(group A),with polymer-only coated vs. polymer plus simvastatin coated titanium Kirschner wires in osteoporotic rats(group B and C, respectively).Femurs were harvested after 12 weeks, and underwent radiographic and histologic analysis, as well as immunohistochemical evaluation for BMP-2 expression. Results:Radiographic results demonstrated progressed callus in the simvastatin-treated groups compared to the uncoated group.The histologic analysis revealed a significantly processed callus with irregular-shaped newly formed bone trabeculae in simvastatin-treated group. Immunohistochemical evaluation showed markedly higher expression levels of B:MP-2 in simvastatin-treated group.Conclusions: The present study revealed a improved fracture healing under local application of simvastatin in osteoporotic rat,which might partially from upregulation of the B:MP-2 expression at fractured site.

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

Delay in weight bearing in surgically treated tibial shaft fractures is associated with impaired healing: a cohort analysis of 166 tibial fractures.

PubMed

Houben, I B; Raaben, M; Van Basten Batenburg, M; Blokhuis, T J

2018-04-09

The relation between timing of weight bearing after a fracture and the healing outcome is yet to be established, thereby limiting the implementation of a possibly beneficial effect for our patients. The current study was undertaken to determine the effect of timing of weight bearing after a surgically treated tibial shaft fracture. Surgically treated diaphyseal tibial fractures were retrospectively studied between 2007 and 2015. The timing of initial weight bearing (IWB) was analysed as a predictor for impaired healing in a multivariate regression. Totally, 166 diaphyseal tibial fractures were included, 86 cases with impaired healing and 80 with normal healing. The mean age was 38.7 years (range 16-89). The mean time until IWB was significantly shorter in the normal fracture healing group (2.6 vs 7.4 weeks, p < 0.001). Correlation analysis yielded four possible confounders: infection requiring surgical intervention, fracture type, fasciotomy and open fractures. Logistic regression identified IWB as an independent predictor for impaired healing with an odds ratio of 1.13 per week delay (95% CI 1.03-1.25). Delay in initial weight bearing is independently associated with impaired fracture healing in surgically treated tibial shaft fractures. Unlike other factors such as fracture type or soft tissue condition, early resumption of weight bearing can be influenced by the treating physician and this factor therefore has a direct clinical relevance. This study indicates that early resumption of weight bearing should be the treatment goal in fracture fixation. 3b.

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

The effect of whole body vibration on fracture healing - a systematic review.

PubMed

Wang, J; Leung, K S; Chow, S K; Cheung, W H

2017-09-07

This systematic review examines the efficacy and safety of whole body vibration (WBV) on fracture healing. A systematic literature search was conducted with relevant keywords in PubMed and Embase, independently, by two reviewers. Original animal and clinical studies about WBV effects on fracture healing with available full-text and written in English were included. Information was extracted from the included studies for review. In total, 19 articles about pre-clinical studies were selected. Various vibration regimes are reported; of those, the frequencies of 35 Hz and 50 Hz show better results than others. Most of the studies show positive effects on fracture healing after vibration treatment and the responses to vibration are better in ovariectomised (OVX) animals than non-OVX ones. However, several studies provide insufficient evidence to support an improvement of fracture healing after vibration and one study even reports disruption of fracture healing after vibration. In three studies, vibration results in positive effects on angiogenesis at the fracture site and surrounding muscles during fracture healing. No serious complications or side effects of vibration are found in these studies. WBV is suggested to be beneficial in improving fracture healing in animals without safety problem reported. In order to apply vibration on fractured patients, more well-designed randomised controlled clinical trials are needed to examine its efficacy, regimes and safety.

Muscle-bone Interactions During Fracture Healing

DTIC Science & Technology

2015-03-01

stem cells (MSCs). The in- flammatory cells release cytokines such as TNF-α, IL-1, IL- 6, IL-11, and IL-18 to induce osteogenic differentiation of MSCs...Bone, Fracture, Mesenchymal Stem Cells , Paracrine Review Article Hylonome The authors have no conflict of interest. Corresponding author: Melissa...1992;(275):280-6. 16. Mills SJ, Cowin AJ, Kaur P. Pericytes, mesenchymal stem cells and the wound healing process. Cells 2013;2:621-34. 17. Kumar A

Low-dose TNF augments fracture healing in normal and osteoporotic bone by up-regulating the innate immune response.

PubMed

Chan, James K; Glass, Graeme E; Ersek, Adel; Freidin, Andrew; Williams, Garry A; Gowers, Kate; Espirito Santo, Ana I; Jeffery, Rosemary; Otto, William R; Poulsom, Richard; Feldmann, Marc; Rankin, Sara M; Horwood, Nicole J; Nanchahal, Jagdeep

2015-05-01

The mechanism by which trauma initiates healing remains unclear. Precise understanding of these events may define interventions for accelerating healing that could be translated to the clinical arena. We previously reported that addition of low-dose recombinant human TNF (rhTNF) at the fracture site augmented fracture repair in a murine tibial fracture model. Here, we show that local rhTNF treatment is only effective when administered within 24 h of injury, when neutrophils are the major inflammatory cell infiltrate. Systemic administration of anti-TNF impaired fracture healing. Addition of rhTNF enhanced neutrophil recruitment and promoted recruitment of monocytes through CCL2 production. Conversely, depletion of neutrophils or inhibition of the chemokine receptor CCR2 resulted in significantly impaired fracture healing. Fragility, or osteoporotic, fractures represent a major medical problem as they are associated with permanent disability and premature death. Using a murine model of fragility fractures, we found that local rhTNF treatment improved fracture healing during the early phase of repair. If translated clinically, this promotion of fracture healing would reduce the morbidity and mortality associated with delayed patient mobilization. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

Fracture healing in osteoporotic bone.

PubMed

Cheung, Wing Hoi; Miclau, Theodore; Chow, Simon Kwoon-Ho; Yang, Frank F; Alt, Volker

2016-06-01

As the world population rises, osteoporotic fracture is an emerging global threat to the well-being of elderly patients. The process of fracture healing by intramembranous ossification or/and endochondral ossification involve many well-orchestrated events including the signaling, recruitment and differentiation of mesenchymal stem cells (MSCs) during the early phase; formation of a hard callus and extracellular matrix, angiogenesis and revascularization during the mid-phase; and finally callus remodeling at the late phase of fracture healing. Through clinical and animal research, many of these factors are shown to be impaired in osteoporotic bone. Animal studies related to post-menopausal estrogen deficient osteoporosis (type I) have shown healing to be prolonged with decreased levels of MSCs and decreased levels of angiogenesis. Moreover, the expression of estrogen receptor (ER) was shown to be delayed in ovariectomy-induced osteoporotic fracture. This might be related to the observed difference in mechanical sensitivity between normal and osteoporotic bones, which requires further experiments to elucidate. In mice fracture models related to senile osteoporosis (type II), it was observed that chondrocyte and osteoblast differentiation were impaired; and that transplantation of juvenile bone marrow would result in enhanced callus formation. Other factors related to angiogenesis and vasculogenesis have also been noted to be impaired in aged models, affecting the degradation of cartilaginous matrixes and vascular invasion; the result is changes in matrix composition and growth factors concentrations that ultimately impairs healing during age-related osteoporosis. Most osteoporotic related fractures occur at metaphyseal sites clinically, and reports have indicated that differences exist between diaphyseal and metaphyseal fractures. An animal model that satisfies three main criteria (metaphyseal region, plate fixation, osteoporosis) is suggested for future research for more comprehensive understanding of the impairment in osteoporotic fractures. Therefore, a metaphyseal fracture or osteotomy that achieves complete discontinuity fixed with metal implants is suggested on ovariectomized aged rodent models. © 2016 Elsevier Ltd. All rights reserved.

Factors Associated With Development of Nonunion or Delayed Healing After an Open Long Bone Fracture: A Prospective Cohort Study of 736 Subjects.

PubMed

Westgeest, Joseph; Weber, Donald; Dulai, Sukhdeep K; Bergman, Joseph W; Buckley, Richard; Beaupre, Lauren A

2016-03-01

To determine factors associated with developing nonunion or delayed healing after open fracture. Prospective cohort between 2001 and 2009. Three level 1 Canadian trauma centers. Seven hundred thirty-six (791 fractures) subjects were enrolled. Six hundred eighty-nine (94%) subjects (739 fractures) provided adequate outcome data. Subjects were followed until fracture(s) healed; phone interviews and chart reviews were conducted 1 year after fracture. Patient, fracture, and injury information, and time to surgery and antibiotics were recorded during hospitalization. Nonunion defined as unplanned surgical intervention after definitive wound closure or incomplete radiographic healing at 1 year and delayed healing defined as 2 consecutive clinical assessments showing no radiographic progression or incomplete radiographic healing between 6 months and 1 year. There were 413 (52%) tibia/fibular, 285 (36%) upper extremity, and 93 (13%) femoral fractures. Nonunion developed in 124 (17%) and delayed healing in 63 (8%) fractures. The median time to surgery was not different for fractures that developed nonunion compared with those who did not (P = 0.36). Deep infection [Odd ratio (OR) 12.75; 95% confidence interval (CI) 6.07-26.8], grade 3A fractures (OR 2.49; 95% CI, 1.30-4.78), and smoking (OR 1.73; 95% CI, 1.09-2.76) were significantly associated with developing a nonunion. Delayed healing was also significantly associated with deep infection (OR 4.34; 95% CI, 1.22-15.48) and grade 3B/C fractures (OR 3.69; 95% CI, 1.44-9.44). Multivariate regression found no association between nonunion and time to surgery (P = 0.15) or antibiotics (P = 0.70). Deep infection and higher Gustilo grade fractures were associated with nonunion and delayed healing. Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

High revision rate but good healing capacity of atypical femoral fractures. A comparison with common shaft fractures.

PubMed

Schilcher, Jörg

2015-12-01

Healing of complete, atypical femoral fractures is thought to be impaired, but the evidence is weak and appears to be based on the delayed healing observed in patients with incomplete atypical fractures. Time until fracture healing is difficult to assess, therefore we compared the reoperation rates between women with complete atypical femoral fractures and common femoral shaft fractures. We searched the orthopaedic surgical registry in Östergötland County for patients with subtrochanteric and femoral shaft fractures (ICD-10 diagnosis codes S72.2, S72.3 and M84.3F) between January 1st 2007 and December 31st 2013. Out of 895 patients with surgically treated femoral shaft fractures, 511 were women 50 years of age or older. Among these we identified 24 women with atypical femoral shaft fractures, and 71 with common shaft fractures. Reoperations were performed in 6 and 5 patients, respectively, odds ratio 4.4 (95% CI 1.2 to 16.1). However, 5 reoperations in the atypical fracture group could not be ascribed to poor healing. In 3 patients the reoperation was due to a new fracture proximal to a standard intramedullary nail. In 2 patients the distal locking screws were removed due to callus formation that was deemed incomplete 5 months post-operatively. The one patient with poor healing showed faint callus formation at 5 months when the fracture was dynamised and callus remained sparse at 11 months. Among patients with common shaft fractures, 2 reoperations were performed to remove loose screws, 2 because of peri-implant fractures and 1 reoperation due to infection. Reoperation rates in patients with complete atypical femoral fractures are higher than in patients with common shaft fractures. The main reason for failure was peri-implant fragility fractures which might be prevented with the use of cephalomedullary nails at the index surgery. Fracture healing however, seems generally good. A watchful waiting approach is advocated in patients with fractures that appear to heal slowly. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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.

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.

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.

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.

Role of chemical and mechanical stimuli in mediating bone fracture healing.

PubMed

Zhang, Lihai; Richardson, Martin; Mendis, Priyan

2012-08-01

Bone is a remarkable living tissue that provides a framework for animal body support and motion. However, under excessive loads and deformations, bone is prone is to damage through fracture. Furthermore, once the bone is weakened by osteoporosis, bone fracture can occur even after only minimal trauma. Various techniques have been developed to treat bone fractures. Successful treatment outcomes depend on a fundamental understanding of the biochemical and biomechanical environments of the fracture site. Various cell types (e.g. mesenchymal stem cells, chondrocytes, osteoblasts and osteoclasts) within the fracture site tightly control the healing process by responding to the chemical and mechanical microenvironment. However, these mechanochemical regulatory mechanisms remain poorly understood at the system level owing to the large range of variables, such as age, sex and disease-associated material properties of the tissue. Computational modelling can play an important role in unravelling this complexity by combining mechanochemical interactions, revealing the dominant controlling processes and optimizing system behaviour, thereby enabling the development and evaluation of treatment strategies for individual patients. © 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.

Toughening and healing of composites by CNTs reinforced copolymer nylon micro-particles

NASA Astrophysics Data System (ADS)

Kostopoulos, V.; Kotrotsos, A.; Tsokanas, P.; Tsantzalis, S.

2018-02-01

In this work, nylon micro-particles, both undoped and doped with multiwall carbon nanotubes played the role of the self-healing agent into carbon fibre/epoxy composites (CFRPs). These micro-particles were blended with epoxy matrix and the resulting mixture was used for the composites fabrication. Three types of composites were manufactured; the reference CFRP and the modified CFRPs with undoped and doped nylon micro-particles. After manufacturing, these composites were tested under mode I and II fracture loading conditions and it was shown that the interlaminar fracture toughness characteristics of both nylon modified composites were significantly increased. After first fracture, healing process was activated for the tested nylon modified samples and revealed high fracture toughness characteristics recovery. Morphology examinations supported the results and elucidated the involved toughening and failure mechanisms. Finally, the in-plane mechanical and thermo-mechanical properties of all the composites were characterized for identifying possible knock-down effects due to the nylon modification of composites.

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

Fracture healing: a consensus report from the International Osteoporosis Foundation Fracture Working Group.

PubMed

Silverman, S L; Kupperman, E S; Bukata, S V

2016-07-01

We used the RAND UCLA appropriateness method to decide appropriateness of use of osteoporosis medication after incident fracture and potential for fracture healing and make suggestions for trial design for clinical and preclinical research. To develop appropriateness criteria to assist in the use and study of osteoporosis medications in patients with recent fracture and in the potential use of osteoporosis medications to enhance delayed fracture healing. To promote further research by suggesting preclinical and clinical trial design for studies where fracture healing is the endpoint. RAND/UCLA appropriateness method (RUAM). A panel of experts, both members and non-members of the International Osteoporosis Foundation Fracture Working Group, were identified consisting of geriatricians, rheumatologists, orthopedists, endocrinologists, and internists. This resulted in a round 1 panel of 15 panelists, round 2 panel of 15 members, and a round 3 panel of 14 members. Agreement on statements and scenarios using RUAM. Three rounds of voting by panelists took place. Agreement in a third round was reached for 111 statements and scenarios, measured by median panel ratings and the amount of dispersion of panel ratings, based on the interpercentile range. An expert panel validated a set of statements and scenarios about the use of osteoporosis medications after incident fracture and use of these medications to enhance delayed fracture healing and made recommendations for study designs to investigate the effect of osteoporosis medications on fracture healing. The result of this exercise is intended to assist in improving patient care by identifying the appropriateness of use of osteoporosis medications after fracture and in fracture healing and to make suggestions for further preclinical and clinical research.

Stimulating Fracture Healing in Ischemic Environments: Does Oxygen Direct Stem Cell Fate during Fracture Healing?

PubMed Central

Miclau, Katherine R.; Brazina, Sloane A.; Bahney, Chelsea S.; Hankenson, Kurt D.; Hunt, Thomas K.; Marcucio, Ralph S.; Miclau, Theodore

2017-01-01

Bone fractures represent an enormous societal and economic burden as one of the most prevalent causes of disability worldwide. Each year, nearly 15 million people are affected by fractures in the United States alone. Data indicate that the blood supply is critical for fracture healing; as data indicate that concomitant bone and vascular injury are major risk factors for non-union. However, the various role(s) that the vasculature plays remains speculative. Fracture stabilization dictates stem cell fate choices during repair. In stabilized fractures stem cells differentiate directly into osteoblasts and heal the injury by intramembranous ossification. In contrast, in non-stable fractures stem cells differentiate into chondrocytes and the bone heals through endochondral ossification, where a cartilage template transforms into bone as the chondrocytes transform into osteoblasts. One suggested role of the vasculature has been to participate in the stem cell fate decisions due to delivery of oxygen. In stable fractures, the blood vessels are thought to remain intact and promote osteogenesis, while in non-stable fractures, continual disruption of the vasculature creates hypoxia that favors formation of cartilage, which is avascular. However, recent data suggests that non-stable fractures are more vascularized than stable fractures, that oxygen does not appear associated with differentiation of stem cells into chondrocytes and osteoblasts, that cartilage is not hypoxic, and that oxygen, not sustained hypoxia, is required for angiogenesis. These unexpected results, which contrast other published studies, are indicative of the need to better understand the complex, spatio-temporal regulation of vascularization and oxygenation in fracture healing. This work has also revealed that oxygen, along with the promotion of angiogenesis, may be novel adjuvants that can stimulate healing in select patient populations. PMID:28523266

Can a fractured caprock self-heal?

NASA Astrophysics Data System (ADS)

Elkhoury, Jean E.; Detwiler, Russell L.; Ameli, Pasha

2015-05-01

The ability of geologic seals to prevent leakage of fluids injected into the deep subsurface is critical for mitigating risks associated with greenhouse-gas sequestration and natural-gas production. Fractures caused by tectonic or injection-induced stresses create potential leakage pathways that may be further enhanced by mineral dissolution. We present results from reactive-flow experiments in fractured caprock (dolomitic anhydrite), where additional dissolution occurs in the rock matrix adjacent to the fracture surfaces. Preferential dissolution of anhydrite left a compacted layer of dolomite in the fractures. At lower flow rate, rock-fluid reactions proceeded to near equilibrium within the fracture with preferential flow paths persisting over the 6-month duration of the experiment and a negligible change in permeability. At higher flow rate, permeability decreased by a dramatic two orders of magnitude. This laboratory-scale observation of self-healing argues against the likelihood of runaway permeability growth in fractured porous caprock composed of minerals with different solubilities and reaction kinetics. However, scaling arguments suggest that at larger length scales this self-healing process may be offset by the formation of dissolution channels. Our results have relevance beyond the greenhouse-gas sequestration problem. Chemical disequilibrium at waste injection sites and in hydrothermal reservoirs will lead to reactive flows that may also significantly alter formation permeability.

FLUOXETINE INHIBITS OSTEOBLAST DIFFERENTIATION & MINERALIZATION IN FRACTURE HEALING

PubMed Central

Bradaschia-Correa, Vivian; Josephson, Anne M; Mehta, Devan; Mizrahi, Matthew; Neibart, Shane S; Liu, Chao; Kennedy, Oran; Castillo, Alesha B; Egol, Kenneth A; Leucht, Philipp

2016-01-01

Chronic use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression has been linked to osteoporosis. In this study, we investigated the effect of chronic SSRI use on fracture healing in two murine models of bone regeneration. First, we performed a comprehensive analysis of endochondral bone healing in a femur fracture model. C57/BL6 mice treated with fluoxetine, the most commonly prescribed SSRI, developed a normal cartilaginous soft-callus at 14 days after fracture and demonstrated a significantly smaller and biomechanically weaker bony hard-callus at 28 days. In order to further dissect the mechanism that resulted in a smaller bony regenerate, we used an intramembranous model of bone healing and revealed that fluoxetine treatment resulted in a significantly smaller bony callus at 7 and 14 days postinjury. In order to test whether the smaller bony regenerate following fluoxetine treatment was caused by an inhibition of osteogenic differentiation and/or mineralization, we employed in vitro experiments, which established that fluoxetine treatment decreases osteogenic differentiation and mineralization and that this effect is serotonin-independent. Finally, in a translational approach, we tested whether cessation of the medication would result in restoration of the regenerative potential. However, histologic and µCT analysis revealed non-union formation in these animals with fibrous tissue interposition within the callus. In conclusion, fluoxetine exerts a direct, inhibitory effect on osteoblast differentiation and mineralization, shown in two disparate murine models of bone repair. Discontinuation of the drug did not result in restoration of the healing potential, but rather led to complete arrest of the repair process. Besides the well-established effect of SSRIs on bone homeostasis, our study provides strong evidence that fluoxetine use negatively impacts fracture healing. PMID:27869327

Do bisphosphonates inhibit direct fracture healing?: A laboratory investigation using an animal model.

PubMed

Savaridas, T; Wallace, R J; Salter, D M; Simpson, A H R W

2013-09-01

Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing. A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague-Dawley rats received daily subcutaneous injections of 1 µg/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology. The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm(-2) (sd 7.63) vs 24.65 Nmm(-2) (sd 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (sd 0.75) vs 4.6 mmAl (sd 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007). Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing.

An interface finite element model can be used to predict healing outcome of bone fractures.

PubMed

Alierta, J A; Pérez, M A; García-Aznar, J M

2014-01-01

After fractures, bone can experience different potential outcomes: successful bone consolidation, non-union and bone failure. Although, there are a lot of factors that influence fracture healing, experimental studies have shown that the interfragmentary movement (IFM) is one of the main regulators for the course of bone healing. In this sense, computational models may help to improve the development of mechanical-based treatments for bone fracture healing. Hence, based on this fact, we propose a combined repair-failure mechanistic computational model to describe bone fracture healing. Despite being a simple model, it is able to correctly estimate the time course evolution of the IFM compared to in vivo measurements under different mechanical conditions. Therefore, this mathematical approach is especially suitable for modeling the healing response of bone to fractures treated with different mechanical fixators, simulating realistic clinical conditions. This model will be a useful tool to identify factors and define targets for patient specific therapeutics interventions. © 2013 Published by Elsevier Ltd.

A Trigger Mechanism for Volcanic Low-Frequency Seismic Events on Montserrat

NASA Astrophysics Data System (ADS)

Neuberg, J. W.; Tuffen, H.; Jolly, A.; Green, D.

2003-12-01

Seismic observations of low-frequency earthquake swarms on Montserrat point to a non-destructive, repeatable source mechanism in a confined area inside or near the conduit. While the seismic wave propagation pattern of the subsequent resonance in and around the conduit is well studied, the trigger mechanism has remained elusive. In this contribution we suggest a trigger mechanism based on new field evidence for fracture and healing of magma in volcanic conduits, together with seismic observations from Montserrat and finite element modelling of magma deformation during conduit flow. As a seismic trigger we suggest a stick-slip motion of highly-viscous magma in the glass transition, that periodically generates networks of seismogenic shear fractures a few metres in length. These fractures are rapidly filled by fine-grained material [cataclasite] that is generated by friction processes on the fracture surfaces, such as corner abrasion, and is locally redeposited by gas flowing within the fracture system. Filled fractures are then swiftly healed as reloading leads to annealing and a return to cohesive viscous deformation. Such a fast healing process, probably on the order of tens of seconds, leads to a repeatable trigger mechanism. Due to a strong lateral viscosity gradient in the conduit, highly-viscous magma near the conduit walls, which can exhibit brittle behaviour, co-exists with low-viscosity, fluid magma in the conduit centre; such that brittle failure provides the seismic trigger mechanism while the fluid part can still act as a seismic resonator.

Healing of Horizontal Intra-alveolar Root Fractures after Endodontic Treatment with Mineral Trioxide Aggregate.

PubMed

Kim, Dohyun; Yue, Wonyoung; Yoon, Tai-Cheol; Park, Sung-Ho; Kim, Euiseong

2016-02-01

The purpose of this retrospective study was to evaluate the healing type and assess the outcome of horizontal intra-alveolar root fractures after endodontic treatment with mineral trioxide aggregate (MTA) as filling material. The clinical database of the Department of Conservative Dentistry at Yonsei University Dental Hospital, Seoul, Korea, was searched for patients with histories of intra-alveolar root fractures and endodontic treatments with MTA between October 2005 and September 2014. Radiographic healing at the fracture line was evaluated independently by 2 examiners and was classified into 4 types according to Andreasen and Hjørting-Hansen. Of the 22 root-fractured teeth that received endodontic treatment with MTA, 19 cases participated in the follow-up after a period of at least 3 months. Seventeen of the 19 teeth (89.5%) exhibited healing of the root fractures. For each healing type, 7 teeth (36.8%) showed healing with calcified tissue, 8 teeth (42.1%) showed interposition of connective tissue, 2 teeth (10.5%) showed interposition of connective tissue and bone, and 2 teeth (10.5%) showed interposition of granulation tissue without healing. Within the limitations of this study, intra-alveolar root fractures showed satisfactory healing outcomes after endodontic treatment with MTA. MTA could be considered to be suitable filling material for the endodontic treatment of horizontal intra-alveolar root fractures. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

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.

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

[Biomechanical analysis on healing process of sagittal fracture of the mandibular condyle after rigid fixation].

PubMed

Jing, Jie; Qu, Ai-li; Ding, Xiao-mei; Hei, Yu-na

2015-04-01

To analyze the biomechanical healing process on rigid fixation of sagittal fracture of the mandibular condyle (SFMC), and to provide guidelines for surgical treatment. Three-dimensional finite element model (3D-FEAM) of mandible and condyle was established. The right condyle was simulated as SFMC with 0.1 mm space across the condyle length ways. The 3D-FEAM of rigid fixation was established. The biomechanical factors such as stress distribution of condylar surface, displacement around fracture, stress on the plate and stress shielding were calculated during 0, 4, 8 and 12-week after rigid fixation. The maximum equivalent stress of normal condyle was located at the area of middle 1/3 of condylar neck. The maximum equivalent stress at 0-week after fixation was 23 times than that on normal condyle. They were located at the condylar stump and the plate near inferior punctual areas of fracture line. There were little stress on the other areas. The maximum equivalent stress at 4, 8 and 12-week was approximately 6 times than that on normal condyle. They were located at the areas same as the area at 0-week. There were little stress on the other areas at the condyle. The maximum total displacement and maximum total corner were increased 0.57-0.75 mm and 0.01-0.09° respectively during healing process. The maximum equivalent stress at 0-week on the condylar trump was 5-6 times compared with that at 4, 8, and 12-week. The maximum equivalent stress, maximum total displacement and maximum total corner on the fractured fragment were not changed significantly during healing process. The maximum equivalent stress at 0-week on the plate was 7-9 times compared with that at 4, 8, 12-week. The stress of the condyle and stress shielding of the plate may be the reasons of absorbing and rebuilding on the condyle in healing process of SFMC. The biomechanical parameters increase obviously at 4-week after fixation. Elastic intermaxillary traction is necessary to decrease total displacement and total corner of the condyle, and liquid diet is necessary to decrease equivalent stress within 4 weeks. Rehabilitation training should be used to recover TMJ functions after 4 weeks because the condyle and mandible have the ability to carry out normal functions.

A mechano-biological model of multi-tissue evolution in bone

NASA Astrophysics Data System (ADS)

Frame, Jamie; Rohan, Pierre-Yves; Corté, Laurent; Allena, Rachele

2017-12-01

Successfully simulating tissue evolution in bone is of significant importance in predicting various biological processes such as bone remodeling, fracture healing and osseointegration of implants. Each of these processes involves in different ways the permanent or transient formation of different tissue types, namely bone, cartilage and fibrous tissues. The tissue evolution in specific circumstances such as bone remodeling and fracturing healing is currently able to be modeled. Nevertheless, it remains challenging to predict which tissue types and organization can develop without any a priori assumptions. In particular, the role of mechano-biological coupling in this selective tissue evolution has not been clearly elucidated. In this work, a multi-tissue model has been created which simultaneously describes the evolution of bone, cartilage and fibrous tissues. The coupling of the biological and mechanical factors involved in tissue formation has been modeled by defining two different tissue states: an immature state corresponding to the early stages of tissue growth and representing cell clusters in a weakly neo-formed Extra Cellular Matrix (ECM), and a mature state corresponding to well-formed connective tissues. This has allowed for the cellular processes of migration, proliferation and apoptosis to be described simultaneously with the changing ECM properties through strain driven diffusion, growth, maturation and resorption terms. A series of finite element simulations were carried out on idealized cantilever bending geometries. Starting from a tissue composition replicating a mid-diaphysis section of a long bone, a steady-state tissue formation was reached over a statically loaded period of 10,000 h (60 weeks). The results demonstrated that bone formation occurred in regions which are optimally physiologically strained. In two additional 1000 h bending simulations both cartilaginous and fibrous tissues were shown to form under specific geometrical and loading cases and cartilage was shown to lead to the formation of bone in a beam replicating a fracture healing initial tissue distribution. This finding is encouraging in that it is corroborated by similar experimental observations of cartilage leading bone formation during the fracture healing process. The results of this work demonstrate that a multi-tissue mechano-biological model of tissue evolution has the potential for predictive analysis in the design and implementations of implants, describing fracture healing and bone remodeling processes.

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.

[Application of three-dimensional printing technology in treatment of internal or external ankle distal avulsed fracture].

PubMed

Shi, Weixiang; Luo, Xiaozhong; Wu, Gang; Ding, Yong; Zhou, Xin

2018-02-01

To explore the effectiveness and advantage of three-dimensional (3D) printing technology in treatment of internal or external ankle distal avulsed fracture. Between January 2015 and January 2017, 20 patients with distal avulsed fracture of internal or external ankle were treated with the 3D guidance of shape-blocking steel plate fixation (group A), and 18 patients were treated with traditional plaster external fixation (group B). There was no significant difference in gender, age, injury cause, disease duration, fracture side, and fracture type between 2 groups ( P >0.05). Recording the fracture healing rate, fracture healing time, the time of starting to ankle functional exercise, residual ankle pain, and evaluating ankle function recovery of both groups by the American Orthopaedic Foot and Ankle Society (AOFAS) score. All patients were followed up 8-24 months, with an average of 15.5 months. In group A: all incisions healed by first intention, the time of starting to ankle functional exercise was (14±3) days, fracture healing rate was 100%, and the fracture healing time was (10.15±2.00) weeks. At 6 months, the AOFAS score was 90.35±4.65. Among them, 13 patients were excellent and 7 patients were good. All patients had no post-operative incision infection, residual ankle pain, or dysfunction during the follow-up. In group B: the time of starting to ankle functional exercise was (40±10) days, the fracture healing rate was 94.44%, and the fracture healing time was (13.83±7.49) weeks. At 6 months, the AOFAS score was 79.28±34.28. Among them, 15 patients were good, 2 patients were medium, and 1 patient was poor. During the follow-up, 3 patients (16.67%) had pain of ankle joint with different degrees. There were significant differences in the postoperative fracture healing rate, fracture healing time, the time of starting to ankle functional exercise, and postoperative AOFAS score between 2 groups ( P <0.05). Application of 3D printing technology in treatment of internal or external ankle distal avulsed fracture is simple, safe, reliable, and effective. In particular, it is an ideal treatment for avulsed fracture.

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.

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.

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

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.

Knockdown of SVCT2 impairs in-vitro cell attachment, migration and wound healing in bone marrow stromal cells.

PubMed

Sangani, Rajnikumar; Pandya, Chirayu D; Bhattacharyya, Maryka H; Periyasamy-Thandavan, Sudharsan; Chutkan, Norman; Markand, Shanu; Hill, William D; Hamrick, Mark; Isales, Carlos; Fulzele, Sadanand

2014-03-01

Bone marrow stromal cell (BMSC) adhesion and migration are fundamental to a number of pathophysiologic processes, including fracture and wound healing. Vitamin C is beneficial for bone formation, fracture repair and wound healing. However, the role of the vitamin C transporter in BMSC adhesion, migration and wound healing is not known. In this study, we knocked-down the sodium-dependent vitamin C transporter, SVCT2, the only known transporter of vitamin C in BMSCs, and performed cell adhesion, migration, in-vitro scratch wound healing and F-actin re-arrangement studies. We also investigated the role of oxidative stress on the above processes. Our results demonstrate that both oxidative stress and down-regulation of SVCT2 decreased cell attachment and spreading. A trans-well cell migration assay showed that vitamin C helped in BMSC migration and that knockdown of SVCT2 decreased cell migration. In the in-vitro scratch wound healing studies, we established that oxidative stress dose-dependently impairs wound healing. Furthermore, the supplementation of vitamin C significantly rescued the BMSCs from oxidative stress and increased wound closing. The knockdown of SVCT2 in BMSCs strikingly decreased wound healing, and supplementing with vitamin C failed to rescue cells efficiently. The knockdown of SVCT2 and induction of oxidative stress in cells produced an alteration in cytoskeletal dynamics. Signaling studies showed that oxidative stress phosphorylated members of the MAP kinase family (p38) and that vitamin C inhibited their phosphorylation. Taken together, these results indicate that both the SVCT2 transporter and oxidative stress play a vital role in BMSC attachment, migration and cytoskeletal re-arrangement. BMSC-based cell therapy and modulation of SVCT2 could lead to a novel therapeutic approach that enhances bone remodeling, fracture repair and wound healing in chronic disease conditions. Published by Elsevier B.V.

Potential role of fibroblast growth factor in enhancement of fracture healing.

PubMed

Radomsky, M L; Thompson, A Y; Spiro, R C; Poser, J W

1998-10-01

Fibroblast growth factors are present in significant amounts in bone and several studies have suggested that they may be involved in normal fracture healing. It is well established that fibroblast growth factors have mitogenic and angiogenic activity on mesoderm and neuroectoderm derived cells. Of particular interest as a member of the fibroblast growth factor family, basic fibroblast growth factor stimulates mitogenesis, chemotaxis, differentiation, and angiogenesis. It also plays an important role in the development of vascular, nervous, and skeletal systems, promotes the maintenance and survival of certain tissues, and stimulates wound healing and tissue repair. Animal studies have shown that the direct injection of fibroblast growth factor into fresh fractures stimulates callus formation, which provides mechanical stability to the fracture, accelerates healing, and restores competence. The matrix used to present the fibroblast growth factor at the fracture site plays a critical role in the effectiveness of the treatment. The evaluation of injectable basic fibroblast growth factor in a sodium hyaluronate gel for its effectiveness in stimulating fracture healing is described. When applied directly into a freshly created fracture in the rabbit fibula, a single injection of the basic fibroblast growth factor and hyaluronan results in the stimulation of callus formation, increased bone formation, and earlier restoration of mechanical strength at the fracture site. The hyaluronan gel serves as a reservoir that sequesters the basic fibroblast growth factor at the injection site for the length of time necessary to create an environment conducive to fracture healing. It is concluded that basic fibroblast growth factor and sodium hyaluronate act synergistically to accelerate fracture healing and that the combination is suitable for clinical evaluation as a therapy in fracture treatment.

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.

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.

[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.

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.

Self-Healing of Unentangled Polymer Networks with Reversible Bonds

PubMed Central

Stukalin, Evgeny B.; Cai, Li-Heng; Kumar, N. Arun; Leibler, Ludwik; Rubinstein, Michael

2013-01-01

Self-healing polymeric materials are systems that after damage can revert to their original state with full or partial recovery of mechanical strength. Using scaling theory we study a simple model of autonomic self-healing of unentangled polymer networks. In this model one of the two end monomers of each polymer chain is fixed in space mimicking dangling chains attachment to a polymer network, while the sticky monomer at the other end of each chain can form pairwise reversible bond with the sticky end of another chain. We study the reaction kinetics of reversible bonds in this simple model and analyze the different stages in the self-repair process. The formation of bridges and the recovery of the material strength across the fractured interface during the healing period occur appreciably faster after shorter waiting time, during which the fractured surfaces are kept apart. We observe the slowest formation of bridges for self-adhesion after bringing into contact two bare surfaces with equilibrium (very low) density of open stickers in comparison with self-healing. The primary role of anomalous diffusion in material self-repair for short waiting times is established, while at long waiting times the recovery of bonds across fractured interface is due to hopping diffusion of stickers between different bonded partners. Acceleration in bridge formation for self-healing compared to self-adhesion is due to excess non-equilibrium concentration of open stickers. Full recovery of reversible bonds across fractured interface (formation of bridges) occurs after appreciably longer time than the equilibration time of the concentration of reversible bonds in the bulk. PMID:24347684

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.

Biomechanical assessment and clinical analysis of different intramedullary nailing systems for oblique fractures.

PubMed

Alierta, J A; Pérez, M A; Seral, B; García-Aznar, J M

2016-09-01

The aim of this study is to evaluate the fracture union or non-union for a specific patient that presented oblique fractures in tibia and fibula, using a mechanistic-based bone healing model. Normally, this kind of fractures can be treated through an intramedullary nail using two possible configurations that depends on the mechanical stabilisation: static and dynamic. Both cases are simulated under different fracture geometries in order to understand the effect of the mechanical stabilisation on the fracture healing outcome. The results of both simulations are in good agreement with previous clinical experience. From the results, it is demonstrated that the dynamization of the fracture improves healing in comparison with a static or rigid fixation of the fracture. This work shows the versatility and potential of a mechanistic-based bone healing model to predict the final outcome (union, non-union, delayed union) of realistic 3D fractures where even more than one bone is involved.

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.

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

Shear rheological characterization of gel healing response and construction of rheo-PIV system

NASA Astrophysics Data System (ADS)

Bawiskar, Abhishek D.

Thermo-reversible gels are solvent-filled 3D networks of polymer chains interconnected by physical (transient) crosslinks. On applying a high shear stress, the crosslinks are broken and these gels show a typical stress-strain behavior due to cohesive fracture of the gel. When heated above a critical temperature and cooled back to room temperature, all the crosslinks are re-formed. Interestingly, partial to full recovery of broken crosslinks is also observed by simply letting the gel stand at room temperature. In this study, the fracture and healing behavior of a model acrylic triblock copolymer gel has been characterized by shear rheometry. A mathematical model has also been proposed to better understand the mechanics at the molecular level and predict the healing time of a system. A rheo-PIV system was built as part of the project, to observe and confirm the bulk healing process in situ. Spontaneous self-healing behavior has immense potential in controlled drug delivery systems, coatings, food and various other applications.

External skeletal fixator intramedullary pin tie-in for the repair of tibiotarsal fractures in raptors: 37 cases (1995-2011).

PubMed

Bueno, Irene; Redig, Patrick T; Rendahl, Aaron K

2015-11-15

To evaluate the outcome of the application of an external skeletal fixator intramedullary pin tie-in (TIF) to tibiotarsal fractures in raptors. Retrospective case series. Thirty-four raptors with 37 tibiotarsal fractures. Medical records and radiographs for raptors with tibiotarsal fractures that were treated at The Raptor Center at the University of Minnesota between 1995 and 2011 were reviewed. Descriptive statistics were generated and univariate logistic regression analyses were used to assess whether age, sex, body weight, location and nature of the fracture, and type of surgical reduction were significantly associated with whether the fracture healed following surgical reduction and TIF application. 31 of 37 (84%) tibiotarsal fractures successfully healed following surgical reduction and TIF application. The mean healing time was 38 days (range, 15 to 70 days). None of the variables assessed were significantly associated with whether the tibiotarsal fracture healed. Twenty of the 34 (59%) raptors were eventually rehabilitated and released. Results indicated that most tibiotarsal fractures were successfully managed by surgical reduction and stabilization with a TIF. However, other comorbidities (eg, systemic infections and visual deficits) negatively affected the rehabilitation of raptors and sometimes resulted in euthanasia despite the fact that the tibiotarsal fracture had healed, and those comorbidities, along with the variables evaluated (eg, age, sex, and nature of the fracture), should be used as triage criteria and prognostic indicators.

Anti-osteoporosis therapy and fracture healing.

PubMed

Larsson, Sune; Fazzalari, Nicola L

2014-02-01

A number of medications are approved for treatment of osteoporosis. As mode of action usually is anti-catabolic/anti-resorptive or anabolic, it is of interest to know whether these drugs affect not only normal bone remodeling, but also fracture healing. The purpose of this paper is to give a short overview of the potential effect of various anti-osteoporotic medication on fracture healing. A narrative literature review was performed to describe the current knowledge. Anti-catabolic/anti-resorptive drugs: for bisphosphonates, the most common class of drugs in this group, experimental studies have shown a larger and stronger callus and delayed remodeling but no evidence of delayed healing. A human monoclonal antibody to RANKL is another anti-catabolic drug, with the only report to date showing enhanced healing in an animal model. Strontium ranelate is a drug where both anti-catabolic and a weak anabolic effect have been proposed, with experimental data ranging from no effect to significant increase in both callus volume and strength. Anabolic drugs: PTH has demonstrated accelerated healing of various experimental fractures and of distal radius and pelvic fractures in humans. While the exact mechanism is not fully understood, PTH results in increased recruitment and differentiation of chondrocytes and enhancement of endochondral ossification. A monoclonal antibody to block sclerostin is another potential anabolic pathway, where animal data have shown increase in bone mass and strength. The potential effect on fracture healing is yet to be studied. There are still large gaps in the understanding of the potential effect of anti-osteoporotic drugs on fracture healing, although based on present knowledge a recent or present fracture should not be considered as a contraindication to such treatment.

Radial and tibial fracture repair with external skeletal fixation. Effects of fracture type, reduction, and complications on healing.

PubMed

Johnson, A L; Kneller, S K; Weigel, R M

1989-01-01

Twenty-eight consecutive fractures of the canine radius and tibia were treated with external skeletal fixation as the primary method of stabilization. The time of fixation removal (T1) and the time to unsupported weight-bearing (T2) were correlated with: (1) bone involved; (2) communication of the fracture with the external environment; (3) severity of the fracture; (4) proximity of the fracture to the nutrient artery; (5) method of reduction; (6) diaphyseal displacement after reduction; and (7) gap between cortical fragments after reduction. The Kruskal-Wallis one-way analysis of variance was used to test the correlation with p less than .05 set as the criterion for significance. The median T1 was 10 weeks and the median T2 was 11 weeks. None of the variables correlated significantly with either of the healing times; however, there was a strong trend toward longer healing times associated with open fractures and shorter healing times associated with closed reduction. Periosteal and endosteal callus uniting the fragments were observed radiographically in comminuted fractures, with primary bone union observed in six fractures in which anatomic reduction was achieved. Complications observed in the treatment of these fractures included: bone lysis around pins (27 fractures), pin track drainage (27 fractures), pin track hemorrhage (1 fracture), periosteal reaction around pins (27 fractures), radiographic signs consistent with osteomyelitis (12 fractures), degenerative joint disease (2 dogs), and nonunion (1 fracture). Valgus or rotational malalignment resulted in 16 malunions of fractures. One external fixation device was replaced and four loose pins were removed before the fractures healed. One dog was treated with antibiotics during the postoperative period because clinical signs of osteomyelitis appeared.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

[Healing status of surgical incisions in human immunodeficiency virus-positive patients with fractures].

PubMed

Li, Xin; Zhang, Qiang; Zhao, Changsong; Sun, Sheng; Cai, Juan

2014-09-09

To observe the healing status of surgical incisions in human immunodeficiency virus (HIV)-positive patients with fractures and explore the factors related with poor wound healing, treatment and preventive measures. Retrospective analyses were performed for the clinical data of 61 HIV-positive patients with fractures. And the influencing factors, treatment and outcomes of poor wound healing were analyzed. Among them, the healing status was good (n = 50) and poor (n = 11). And the outcomes included redness (n = 10), oozing (n = 8), split (n = 3), infection (n = 2), hematoma (n = 1), fat liquefaction (n = 2) and delayed healing (n = 2). All healed well after treatment. There was no infection or death during the follow-up period. Compared with HIV-negative patients, it was not statistically significant in wound infection. However, poor healing rates were significantly different (P < 0.05). The risk factors included advanced age, low body mass index, low albumin, low hemoglobin, low total lymphocyte count, low CD4⁺ T lymphocyte count, high HIV infection clinical stage, long operative duration, emergency surgery and incision contamination. In HIV-positive patients with fractures, the healing of surgical incision is generally good. However few have poor wound healing due to multiple factors. If poor healing is identified early and handled timely and correctly, good healing ensues.

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.

Recombinant human parathyroid hormone (PTH 1-34) and low-intensity pulsed ultrasound have contrasting additive effects during fracture healing.

PubMed

Warden, Stuart J; Komatsu, David E; Rydberg, Johanna; Bond, Julie L; Hassett, Sean M

2009-03-01

Fracture healing is thought to be naturally optimized; however, recent evidence indicates that it may be manipulated to occur at a faster rate. This has implications for the duration of morbidity associated with bone injuries. Two interventions found to accelerate fracture healing processes are recombinant human parathyroid hormone [1-34] (PTH) and low-intensity pulsed ultrasound (LIPUS). This study aimed to investigate the individual and combined effects of PTH and LIPUS on fracture healing. Bilateral midshaft femur fractures were created in Sprague-Dawley rats, and the animals treated 7 days/week with PTH (10 microg/kg) or a vehicle solution. Each animal also had one fracture treated for 20 min/day with active-LIPUS (spatial-averaged, temporal-averaged intensity [I(SATA)]=100 mW/cm(2)) and the contralateral fracture treated with inactive-LIPUS (placebo). Femurs were harvested 35 days following injury to permit micro-computed tomography, mechanical property and histological assessments of the fracture calluses. There were no interactions between PTH and LIPUS indicating that their effects were additive rather than synergistic. These additive effects were contrasting with LIPUS primarily increasing total callus volume (TV) without influencing bone mineral content (BMC), and PTH having the opposite effect of increasing BMC without influencing TV. As a consequence of the effect of LIPUS on TV but not BMC, it decreased volumetric bone mineral density (vBMD) resulting in a less mature callus. The decreased maturity and persistence of cartilage at the fracture site when harvested offset any beneficial mechanical effects of the increased callus size with LIPUS. In contrast, the effect of PTH on callus BMC but not TV resulted in increased callus vBMD and a more mature callus. This resulted in PTH increasing fracture site mechanical strength and stiffness. These data suggest that PTH may have utility in the treatment of acute bone fractures, whereas LIPUS at an I(SATA) of 100 mW/cm(2) does not appear to be indicated in the management of closed, diaphyseal fractures.

The effects of extracorporeal shockwave on acute high-energy long bone fractures of the lower extremity.

PubMed

Wang, Ching-Jen; Liu, Hao-Chen; Fu, Te-Hu

2007-02-01

High-energy long bone fractures of the lower extremity are at risk of poor fracture healing and high rate of non-union. Extracorporeal shockwave was shown effective to heal non-union of long bone fracture. However, the effect of shockwave on acute fractures is unknown. The purpose of this study was to investigate the effects of shockwave on acute high-energy fractures of the lower extremity. Between January and October 2004, 56 patients with 59 acute high-energy fractures were enrolled in this study. Patients were randomly divided into two groups with 28 patients with 28 fractures in the study group and 28 patients with 31 fractures in the control group. Both groups showed similar age, gender, type of fracture and follow-up time. Patients in the study group received open reduction and internal fixation and shockwave treatment immediately after surgery on odd-numbered days of the week, whereas, patients in the control group received open reduction and internal fixation without shockwave treatment on even-numbered days of the week. Postoperative managements were similarly performed in both groups including crutch walking with non-weight bearing on the affected limb until fracture healing shown on radiographs. The evaluation parameters included clinical assessments of pain score and weight bearing status of the affected leg and serial radiographs at 3, 6 and 12 months. The primary end-point is the rate of non-union at 12 months, and the secondary end point is the rate of fracture healing at 3, 6 and 12 months. At 12 months, the rate of non-union was 11% for the study group versus 20% for the control group (P < 0.001). Significantly, better rate of fracture healing was noted in the study group than the control group at 3, 6 and 12 months (P < 0.001). Extracorporeal shockwave is effective on promoting fracture healing and decreasing the rate of non-union in acute high-energy fractures of the lower extremity.

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.

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.

Dkk1 haploinsufficiency requires expression of Bmp2 for bone anabolic activity

PubMed Central

Intini, Giuseppe; Nyman, Jeffry S.

2015-01-01

Bone fractures remain a serious health burden and prevention and enhanced healing of fractures has 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 (Bmp2c/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 Bmp2c/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. PMID:25603465

Treatment of proximal fifth metatarsal bone fractures in athletes.

PubMed

Japjec, M; Starešinić, M; Starjački, M; Žgaljardić, I; Štivičić, J; Šebečić, B

2015-11-01

Proximal fifth metatarsal (V MT) bone fractures are common injuries that are a major diagnostic and therapeutic challenge. Lawrence and Botte considered different treatment options and the possibility of recovery and divided these fractures into three different regions: tuberosity avulsion fractures (zone I), acute fractures of the metaphysis at the level of the intermetatarsal junction (zone II) and proximal diaphysis stress fracture (zone III). A total of 42 athletes with fracture of the V MT bone in zone II and III were treated in our institution during a 6-year period. All patients were offered surgical treatment, but nine patients refused surgery. Thus, the patients were divided into two groups: group 1 comprised 33 patients who underwent an intramedullary screw fixation operation under regional anaesthesia immediately after the fracture was diagnosed; group 2 contained the remaining nine patients who had refused surgery and received conservative therapy with non-weight-bearing short-leg casts or orthosis. Follow-up ranged from 6 to 24 months. All fractures healed in group 1: healing occurred within 8 weeks in 26 patients and was prolonged to 16 to 18 weeks in four patients. In group 2, fractures healed in four patients but did not heal in five patients even after 6 months. Four of the five patients in whom the fracture did not heal required subsequent osteosynthesis because they had constant problems that caused absence from sport. After the operation, their fractures healed in an average of 10 weeks. One patient decided not to undergo the operation due to the absence of subjective symptoms. Three patients in group 1 who started intensive training sustained a refracture and underwent re-operation in which osteosynthesis was performed with a stronger screw. The fractures then healed again. Treatment results were evaluated radiologically and clinically using the Modified Foot Score. Results in group 1 were significantly better than those in group 2 and there was an earlier return to full athletic activity. The authors concluded that intramedullary fixation of V MT zone II and III fractures with cannulated compression screws was associated with excellent functional results and early and complete recovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regenerative Medicine and Restoration of Joint Function

DTIC Science & Technology

2014-12-01

to resist fracture and excessive deformation under antici- pated mechanical loading conditions both during the early healing process and for longer...per sample type), the results sug- gest a correlation between percent fractured sinter neck area and mechanical properties with the lowest bending...joint replacement are used to treat a joint with an intra-articular fracture or destroyed by a combat injury. Generation of personalized, anatomically

The Role of Radiographs and Office Visits in the Follow-Up of Healed Intertrochanteric Hip Fractures: An Economic Analysis.

PubMed

Kempegowda, Harish; Richard, Raveesh; Borade, Amrut; Tawari, Akhil; Howenstein, Abby M; Kubiak, Erik N; Suk, Michael; Horwitz, Daniel S

2016-12-01

The purpose of this study was to evaluate the role and the necessity of radiographs and office visits obtained during follow-up of intertrochanteric hip injuries. Retrospective study. Two level I trauma centers. Four hundred sixty-five elderly patients who were surgically treated for an intertrochanteric fracture of the femur at 2 level I trauma centers between January 2009 and August 2014 were retrospectively identified from orthopaedic trauma databases. Analysis of all healed intertrochanteric hip fractures, including demographic characteristics, quality of reduction, time of healing, number of office visits, number of radiographs obtained, and each radiograph for fracture alignment, implant position or any pathological changes. The surgical fixation of 465 fractures included 155 short nails (33%), 232 long nails (50%), 69 sliding hip screw devices (15%), 7 trochanteric stabilizing plates (1.5%), and 2 proximal femur locking plates (0.5%). The average fracture healing time was 12.8 weeks and the average follow-up was 81.2 weeks. Radiographs of any patient obtained after the fracture had healed did not reveal any changes, including fracture alignment or implant position and hardware failure. In 9 patients, pathological changes, including arthritis (3), avascular necrosis (3), and ectopic ossification (3) were noted. The average number of elective office visits and radiographs obtained after the fracture had healed were 2.8 (range: 1-8) and 2.6 (range: 1-8), respectively. According to Medicare payments to the institution, these radiographs and office visits account for a direct cost of $360.81 and $192, respectively, per patient. The current study strongly suggests that there is a negligible role for radiographs and office visits during the follow-up of a well-healed hip fracture when there is documented evidence of radiographic and clinical healing with acceptable fracture alignment and implant position. Implementation of this simple measure will help in reducing the cost of care and inconvenience to elderly patients. Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Human immune cells' behavior and survival under bioenergetically restricted conditions in an in vitro fracture hematoma model

PubMed Central

Hoff, Paula; Maschmeyer, Patrick; Gaber, Timo; Schütze, Tabea; Raue, Tobias; Schmidt-Bleek, Katharina; Dziurla, René; Schellmann, Saskia; Lohanatha, Ferenz Leonard; Röhner, Eric; Ode, Andrea; Burmester, Gerd-Rüdiger; Duda, Georg N; Perka, Carsten; Buttgereit, Frank

2013-01-01

The initial inflammatory phase of bone fracture healing represents a critical step for the outcome of the healing process. However, both the mechanisms initiating this inflammatory phase and the function of immune cells present at the fracture site are poorly understood. In order to study the early events within a fracture hematoma, we established an in vitro fracture hematoma model: we cultured hematomas forming during an osteotomy (artificial bone fracture) of the femur during total hip arthroplasty (THA) in vitro under bioenergetically controlled conditions. This model allowed us to monitor immune cell populations, cell survival and cytokine expression during the early phase following a fracture. Moreover, this model enabled us to change the bioenergetical conditions in order to mimic the in vivo situation, which is assumed to be characterized by hypoxia and restricted amounts of nutrients. Using this model, we found that immune cells adapt to hypoxia via the expression of angiogenic factors, chemoattractants and pro-inflammatory molecules. In addition, combined restriction of oxygen and nutrient supply enhanced the selective survival of lymphocytes in comparison with that of myeloid derived cells (i.e., neutrophils). Of note, non-restricted bioenergetical conditions did not show any similar effects regarding cytokine expression and/or different survival rates of immune cell subsets. In conclusion, we found that the bioenergetical conditions are among the crucial factors inducing the initial inflammatory phase of fracture healing and are thus a critical step for influencing survival and function of immune cells in the early fracture hematoma. PMID:23396474

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.

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.

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

Complex tibial fracture outcomes following treatment with low-intensity pulsed ultrasound.

PubMed

Leung, Kwok-Sui; Lee, Wing-Sze; Tsui, Hon-For; Liu, Paul Po-Lung; Cheung, Wing-Hoi

2004-03-01

A clinical study was conducted to investigate the effect of low-intensity pulsed ultrasound (US) stimulation (LIPUS) on the healing of complex tibial fractures. Thirty complex tibial fractures were randomly assigned to the treatment with LIPUS (n = 16) or by a dummy machine (sham-exposed: n = 14). The fractures were immobilized by either internal or external fixations according to the clinical indications. LIPUS was given 20 min/day for 90 days. Fracture healing was monitored by clinical, radiological, densitometric and biochemical assessments. The LIPUS-treated group showed statistically significantly better healing, as demonstrated by all assessments. Complications were minimal in the LIPUS group. There were two cases of delayed union, with one in each group. There were two cases of infection in the control group. The delayed-union cases were subsequently treated by LIPUS and the infection cases were treated with standard protocol. Fracture healing in these patients was again treated by LIPUS.

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.

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.

Evaluating The Relation of Trace Fracture Inclination and Sound Pressure Level and Time-of-flight QUS Parameters Using Computational Simulation

NASA Astrophysics Data System (ADS)

Rosa, P. T.; Fontes-Pereira, A. J.; Matusin, D. P.; von Krüger, M. A.; Pereira, W. C. A.

Bone healing is a complex process that stars after the occurrence of a fracture to restore bone optimal conditions. The gold standards for bone status evaluation are the dual energy X-ray absorptiometry and the computerized tomography. Ultrasound-based technologies have some advantages as compared to X-ray technologies: nonionizing radiation, portability and lower cost among others. Quantitative ultrasound (QUS) has been proposed in literature as a new tool to follow up the fracture healing process. QUS relates the ultrasound propagation with the bone tissue condition (normal or pathological), so, a change in wave propagation may indicate a variation in tissue properties. The most used QUS parameters are time-of-flight (TOF) and sound pressure level (SPL) of the first arriving signal (FAS). In this work, the FAS is the well known lateral wave. The aim of this work is to evaluate the relation of the TOF and SPL of the FAS and fracture inclination trace in two stages of bone healing using computational simulations. Four fracture geometries were used: normal and oblique with 30, 45 and 60 degrees. The TOF average values were 63.23 μs, 63.14 μs, 63.03 μs 62.94 μs for normal, 30, 45 and 60 degrees respectively and average SPL values were -3.83 dB -4.32 dB, -4.78 dB, -6.19 dB for normal, 30, 45 and 60 degrees respectively. The results show an inverse pattern between the amplitude and time-of-flight. These values seem to be sensible to fracture inclination trace, and in future, can be used to characterize it.

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.

Impairment of wound healing after operative treatment of mandibular fractures, and the influence of dexamethasone.

PubMed

Snäll, Johanna; Kormi, Eeva; Lindqvist, Christian; Suominen, Anna Liisa; Mesimäki, Karri; Törnwall, Jyrki; Thorén, Hanna

2013-12-01

Our aim was to clarify the incidence of impaired wound healing after open reduction and ostheosynthesis of mandibular fractures, and to find out whether the use of dexamethasone during the operation increased the risk. Patients were drawn from a larger group of healthy adult dentate patients who had participated in a single-blind, randomised study, the aim of which was to clarify the benefits of operative dexamethasone after treatment of facial fractures. The present analysis comprised 41 patients who had had open reduction and fixation of mandibular fractures with titanium miniplates and monocortical screws through one or 2 intraoral approaches. The outcome variable was impaired healing of the wound. The primary predictive variable was the perioperative use of dexamethasone; other potential predictive variables were age, sex, smoking habit, type of fracture, delay in treatment, and duration of operation. Wound healing was impaired in 13/41 patients (32%) (13/53 of all fractures). The incidence among patients who were given dexamethasone and those who were not did not differ significantly. Only age over 25 was significantly associated with delayed healing (p=0.02). The use of dexamethasone 30 mg perioperatively did not significantly increase the risk of impaired wound healing in healthy patients with clinically uninfected mandibular fractures fixed with titanium miniplates through an intraoral approach. Older age is a significant predictor of impaired healing, which emphasises the importance of thorough anti-infective care in these patients during and after the operation. Copyright © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

The effects of different nutritional measurements on delayed wound healing after hip fracture in the elderly.

PubMed

Guo, Jiong Jiong; Yang, Huilin; Qian, Haixin; Huang, Lixin; Guo, Zhongxing; Tang, Tiansi

2010-03-01

It has been well recognized that malnutrition causes wounds to heal inadequately and incompletely. Malnutrition is often observed in the elderly, and it appears to be more severe in patients with hip fracture than in the general aging population. Few prospective studies give a detailed account of the identification and classification of nutritional status in the elderly. The objective of this study was to evaluate the effects of different nutritional measurements on wound healing status after hip fracture in the elderly. From September 2002 to December 2007, 207 hip fracture patients older than 60 y treated surgically were reviewed for preoperative nutritional status. There were 81 males and 126 females with an average age of 75.93 y (62-91 y); 131 cases with femoral neck fractures, 76 cases with intertrochanteric fractures. Parameters indicative of nutritional status (serum albumin, serum transferrin, serum pre-albumin, and total lymphocyte count levels) at the time of admission were assessed, along with anthropometric measurements, Rainey MacDonald nutritional index, and MNA tool. Suture removal was performed on postoperative day 14. Delayed wound healing complicated 46 (22.2%) of the 207 cases. The preoperative serum transferring total lymphocyte count levels, MNA total score, and Rainey MacDonald nutritional index were significantly lower for patients who subsequently had delayed wound healing. When all variables were subjected to multivariate analysis, only total lymphocyte count levels and MNA total score showed significant value in predicting which patients would have delayed wound healing. Through prophylactic antibiotics and adherence to strict aseptic precautions, on follow-up, wound healing was normal in all patients. Patients at risk for delayed wound healing problems after hip fracture can be identified using relatively inexpensive laboratory test such as TLC and MNA tool. The clinician must be aware of the risk values of both measurements. We believe this information is particularly important before planning procedures of hip fractures in the elderly. Copyright (c) 2010 Elsevier Inc. All rights reserved.

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

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.

A cohort study of 4,190 patients treated with low-intensity pulsed ultrasound (LIPUS): findings in the elderly versus all patients.

PubMed

Zura, Robert; Mehta, Samir; Della Rocca, Gregory J; Jones, John; Steen, R Grant

2015-03-01

Patient age is one of many potential risk factors for fracture nonunion. Our hypothesis is that older patients (≥ 60) with fracture risk factors treated with low-intensity pulsed ultrasound (LIPUS) have similar heal rate (HR) to the population as a whole. We evaluate the impact of age in conjunction with other risk factors on HR in LIPUS-treated patients with fresh fracture (≤ 90 days old). The Exogen Bone Healing System is a LIPUS device approved in 1994 to accelerate healing of fresh fracture. After approval, the FDA required a Post-Market Registry to assess performance. Patient data collected from October 1994 until October 1998 were individually reviewed and validated by a registered nurse. Four distinct data elements were required to report a patient: date fracture occurred; date treatment began; date treatment ended; and a dichotomous outcome of healed v. failed, by clinical and radiological criteria. Data were used to calculate two derived variables; days to treatment (DTT) and days on treatment (DOT). Every validated fresh fracture patient with DTT, DOT, and outcome is reported. The validated registry had 5,765 patients with fresh fracture; 73% (N = 4,190) are reported, while 13% of patients were lost to follow-up, 11% withdrew or were non-compliant, and 3% died or are missing outcome. Among treatment-compliant patients, HR was 96.2%. Logistic estimates of the odds ratio for healing are equivalent for patients age 30 to 79 years and all age cohorts had a HR > 94%. Open fracture, current smoking, diabetes, vascular insufficiency, osteoporosis, cancer, rheumatoid arthritis, and prescription NSAIDs all reduced HR, but older patients (≥ 60) had similar HRs to the population as a whole. DTT was significantly shorter for patients who healed (p < 0.0001). Comorbid conditions in conjunction with aging can reduce fracture HR. Patients with fracture who used LIPUS had a 96% HR, whereas the expected HR averages 93%. Time to treatment was significantly shorter among patients who healed (p < 0.0001), suggesting that it is beneficial to begin LIPUS treatment early. Older patients (≥ 60) with fracture risk factors treated with LIPUS exhibit similar heal rates to the population as a whole.

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.

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

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

A controlled trial of glutamine effects on bone healing.

PubMed

Polat, Onur; Kilicoglu, Sibel Serin; Erdemli, Esra

2007-01-01

Glutamine is considered a nonessential amino acid, but it may be conditionally essential in patients with catabolic conditions. For centuries, researchers have looked for ways to promote and accelerate fracture healing. This controlled animal study examines the effects of glutamine on fracture healing. The left tibias of 10 standardized albino rats were broken at the distal third to produce a closed fracture. L-glutamine/L-alanyl solution (2.0 mL/kg) was administered through the tail veins of half the rats for the first 7 d, and physiologic serum alone was given to the control group. On the 21st day, all rats were euthanized and their left legs removed; after histologic observation, the tibias were examined under light microscopy. In the glutamine-injected group, development of primary callus was quicker and more regular than in the control group. The control group produced insufficient fibrous callus, and the glutamine group attained formed cartilaginous callus. Glutamine was noted to have positive effects on healing of traumatically fractured bone through attainment of positive nitrogen balance. This effect was minimal in enhancing the quality of fracture healing under conditions of stress, but some effect was noted on the speed of healing. Further research is needed in this area.

Microdamage healing in asphalt and asphalt concrete, volume 3 : a micromechanics fracture and healing model for asphalt concrete.

DOT National Transportation Integrated Search

2001-06-01

Volume 3 documents the development of a micromechanics fracture and healing model for asphalt : concrete. This model can be used to calculate the density and growth of microcracks during repeated direct : tensile controlled-strain loading. The model ...

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.

The Effects of Targeted Deliveries of Lovastatin and Tocotrienol on Ossification-Related Gene Expressions in Fracture Healing in an Osteoporosis Rat Model

PubMed Central

Ibrahim, Nurul ‘Izzah; Mohamed, Norazlina; Soelaiman, Ima Nirwana; Shuid, Ahmad Nazrun

2015-01-01

Osteoporotic drugs are used to prevent fragility fractures, but their role in fracture healing still remains unknown. Thus, alternative agents with suitable mode of delivery are needed to promote fracture healing. This study was performed to investigate the effects of direct deliveries of lovastatin and tocotrienol to fracture sites on ossification-related gene expression in fracture healing in a postmenopausal osteoporosis model. Forty-eight Sprague Dawley female rats were divided into six groups. Group I comprised the sham-operated rats, while Groups II–VI were ovariectomized rats. After 8 weeks, the right tibiae of all rats were fractured and stabilized. Group I and Group II were given two single injections of lovastatin and tocotrienol carriers. Group III was given an estrogen preparation at 64.5 µg/kg daily via oral gavages. Group IV was injected with lovastatin particles (750 µg/kg), while Group V was injected with tocotrienol particles (60 mg/kg). Group VI received two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks, the gene expressions were measured. Group VI showed significantly higher gene expressions of osteocalcin, BMP-2, VEGF-α, and RUNX-2 compared to Group II. In conclusion, combined treatment of lovastatin and tocotrienol upregulated the expression of genes related to fracture healing. PMID:26501302

The Effects of Targeted Deliveries of Lovastatin and Tocotrienol on Ossification-Related Gene Expressions in Fracture Healing in an Osteoporosis Rat Model.

PubMed

Ibrahim, Nurul 'Izzah; Mohamed, Norazlina; Soelaiman, Ima Nirwana; Shuid, Ahmad Nazrun

2015-10-16

Osteoporotic drugs are used to prevent fragility fractures, but their role in fracture healing still remains unknown. Thus, alternative agents with suitable mode of delivery are needed to promote fracture healing. This study was performed to investigate the effects of direct deliveries of lovastatin and tocotrienol to fracture sites on ossification-related gene expression in fracture healing in a postmenopausal osteoporosis model. Forty-eight Sprague Dawley female rats were divided into six groups. Group I comprised the sham-operated rats, while Groups II-VI were ovariectomized rats. After 8 weeks, the right tibiae of all rats were fractured and stabilized. Group I and Group II were given two single injections of lovastatin and tocotrienol carriers. Group III was given an estrogen preparation at 64.5 µg/kg daily via oral gavages. Group IV was injected with lovastatin particles (750 µg/kg), while Group V was injected with tocotrienol particles (60 mg/kg). Group VI received two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks, the gene expressions were measured. Group VI showed significantly higher gene expressions of osteocalcin, BMP-2, VEGF-α, and RUNX-2 compared to Group II. In conclusion, combined treatment of lovastatin and tocotrienol upregulated the expression of genes related to fracture healing.

Mandibular body fracture repair with wire-reinforced interdental composite splint in small dogs.

PubMed

Guzu, Michel; Hennet, Philippe R

2017-11-01

To report the outcome of mandibular body fractures treated with a wire-reinforced interdental composite splint (WRICS) in small breed dogs. Retrospective case series. Client-owned small breed dogs (n = 24). Medical records (1998-2012) of small breed dogs (<10 kg) with mandibular body fractures treated by WRICS were reviewed for signalment, history, type of fracture, treatment, and clinical and radiological follow-up. The angle of the fracture line (ANG) was measured on dental radiographs. A mandibular injury severity score (MISS) and a dental injury score (DIS) were evaluated as potential prognostic factors. Fractures most commonly involved P4-M1 (56%), and healed in a mean time of 2.37 ± 0.7 months. Healing was slower (P = .012) if teeth were present in the fracture line and required extraction, hemisection, or root canal therapy prior to WRICS placement (2.39 ± 0.7 months) than if no dental treatment was required (1.46 ± 0.8 months). Contrary to the MISS, the DIS was associated with longer time to bone healing (P = .001; r = .63) and risk of complications (P = .004). Bone healing time was decreased (P = .003; r = .61) with increasing fracture angles. WRICS can be considered to treat mandibular body fractures in small breed dogs if the fracture is not severely comminuted, and if at least the canine and first molar tooth can be used for anchorage. More severe lesions, such as those with teeth in the fracture line and a shorter fracture surface, are associated with prolonged bone healing. © 2017 The American College of Veterinary Surgeons.

Targeted delivery of lovastatin and tocotrienol to fracture site promotes fracture healing in osteoporosis model: micro-computed tomography and biomechanical evaluation.

PubMed

Ibrahim, Nurul 'Izzah; Khamis, Mohd Fadhli; Mod Yunoh, Mohd Faridz; Abdullah, Shahrum; Mohamed, Norazlina; Shuid, Ahmad Nazrun

2014-01-01

Osteoporosis is becoming a major health problem that is associated with increased fracture risk. Previous studies have shown that osteoporosis could delay fracture healing. Although there are potential agents available to promote fracture healing of osteoporotic bone such as statins and tocotrienol, studies on direct delivery of these agents to the fracture site are limited. This study was designed to investigate the effects of two potential agents, lovastatin and tocotrienol using targeted drug delivery system on fracture healing of postmenopausal osteoporosis rats. The fracture healing was evaluated using micro CT and biomechanical parameters. Forty-eight Sprague-Dawley female rats were divided into 6 groups. The first group was sham-operated (SO), while the others were ovariectomized (OVx). After two months, the right tibiae of all rats were fractured at metaphysis region using pulsed ultrasound and were fixed with plates and screws. The SO and OVxC groups were given two single injections of lovastatin and tocotrienol carriers. The estrogen group (OVx+EST) was given daily oral gavages of Premarin (64.5 µg/kg). The Lovastatin treatment group (OVx+Lov) was given a single injection of 750 µg/kg lovastatin particles. The tocotrienol group (OVx+TT) was given a single injection of 60 mg/kg tocotrienol particles. The combination treatment group (OVx+Lov+TT) was given two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks of treatment, the fractured tibiae were dissected out for micro-CT and biomechanical assessments. The combined treatment group (OVx+Lov+TT) showed significantly higher callus volume and callus strength than the OVxC group (p<0.05). Both the OVx+Lov and OVx+TT groups showed significantly higher callus strength than the OVxC group (p<0.05), but not for callus volume. In conclusion, combined lovastatin and tocotrienol may promote better fracture healing of osteoporotic bone.

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

Association of Insulin-like Growth Factor-1, Bone Mass and Inflammation to Low-energy Distal Radius Fractures and Fracture Healing in Elderly Women Attending Emergency Care.

PubMed

Chisalita, Simona I; Chong, Lee Ti; Wajda, Maciej; Adolfsson, Lars; Woisetschläger, Mischa; Spångeus, Anna

2017-11-01

Elderly patients suffer fractures through low-energy mechanisms. The distal radius is the most frequent fracture localization. Insulin-like growth factor-1 (IGF1) plays an important role in the maintenance of bone mass and its levels decline with advancing age and in states of malnutrition. Our aim was to investigate the association of IGF1 levels, bone mass, nutritional status, and inflammation to low-energy distal radius fractures and also study if fracture healing is influenced by IGF1, nutritional status, and inflammation. Postmenopausal women, 55 years or older, with low-energy distal radius fractures occurring due to falling on slippery ground, indoors or outdoors, were recruited in the emergency department (ED) and followed 1 and 5 weeks after the initial trauma with biomarkers for nutritional status and inflammation. Fractures were diagnosed according to standard procedure by physical examination and X-ray. All patients were conservatively treated with plaster casts in the ED. Patients who needed interventions were excluded from our study. Fracture healing was evaluated from radiographs. Fracture healing assessment was made with a five-point scale where the radiological assessment included callus formation, fracture line, and stage of union. Blood samples were taken within 24 h after fracture and analyzed in the routine laboratory. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA). Thirty-eight Caucasian women, aged 70.5 ± 8.9 years (mean ± SD) old, were recruited. Nutritional status, as evaluated by albumin (40.3 ± 3.1 g/L), IGF1 (125.3 ± 39.9 μg/L), body mass index (26.9 ± 3.6 kg/m 2 ), arm diameter (28.9 ± 8.9 cm), and arm skinfold (2.5 ± 0.7 cm), was normal. A positive correlation was found between IGF1 at visit 1 and the lowest BMD for hip, spine, or radius (r = 0.39, P = 0.04). High sensitive C-reactive protein (hsCRP) and leukocytes were higher at the fracture event compared to 5 weeks later (P = 0.07 and P < 0.001, respectively). Fracture healing parameters (i.e. callus formation, fracture line, and stage of union) were positively correlated with the initial leukocyte count and to difference in thrombocyte count between visit 1 and 3. In elderly women with low-energy distal radius fractures, an association between IGF1 and lowest measures of BMD was found, indicating that low IGF1 could be an indirect risk factor for fractures. Fracture healing was associated with initial leukocytosis and a lower thrombocyte count, suggesting that inflammation and thrombocytes are important components in fracture healing. © 2017 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

Biomechanical Concepts for Fracture Fixation

PubMed Central

Bottlang, Michael; Schemitsch, Christine E.; Nauth, Aaron; Routt, Milton; Egol, Kenneth; Cook, Gillian E.; Schemitsch, Emil H.

2015-01-01

Application of the correct fixation construct is critical for fracture healing and long-term stability; however, it is a complex issue with numerous significant factors. This review describes a number of common fracture types, and evaluates their currently available fracture fixation constructs. In the setting of complex elbow instability, stable fixation or radial head replacement with an appropriately sized implant in conjunction with ligamentous repair is required to restore stability. For unstable sacral fractures, “standard” iliosacral screw fixation is not sufficient for fractures with vertical or multiplanar instabilities. Periprosthetic femur fractures, in particular Vancouver B1 fractures, have increased stability when using 90/90 fixation versus a single locking plate. Far Cortical Locking combines the concept of dynamization with locked plating in order to achieve superior healing of a distal femur fracture. Finally, there is no ideal construct for syndesmotic fracture stabilization; however, these fractures should be fixed using a device that allows for sufficient motion in the syndesmosis. In general, orthopaedic surgeons should select a fracture fixation construct that restores stability and promotes healing at the fracture site, while reducing the potential for fixation failure. PMID:26584263

Microdamage healing in asphalt and asphalt concrete, Volume 3 : a micromechanics fracture and healing model for asphalt concrete

DOT National Transportation Integrated Search

2001-06-01

Volume 3 documents the development of a micromechanics fracture and healing model for asphalt concrete. This model can be used to calculate the density and growth of microcracks during repeated direct tensile controlled-strain loading. The model is b...

Pathological fractures in children

PubMed Central

De Mattos, C. B. R.; Binitie, O.; Dormans, J. P.

2012-01-01

Pathological fractures in children can occur as a result of a variety of conditions, ranging from metabolic diseases and infection to tumours. Fractures through benign and malignant bone tumours should be recognised and managed appropriately by the treating orthopaedic surgeon. The most common benign bone tumours that cause pathological fractures in children are unicameral bone cysts, aneurysmal bone cysts, non-ossifying fibromas and fibrous dysplasia. Although pathological fractures through a primary bone malignancy are rare, these should be recognised quickly in order to achieve better outcomes. A thorough history, physical examination and review of plain radiographs are crucial to determine the cause and guide treatment. In most benign cases the fracture will heal and the lesion can be addressed at the time of the fracture, or after the fracture is healed. A step-wise and multidisciplinary approach is necessary in caring for paediatric patients with malignancies. Pathological fractures do not have to be treated by amputation; these fractures can heal and limb salvage can be performed when indicated. PMID:23610658

Chondromalacia of trochlear notch after healing of olecranon stress fracture: a case report.

PubMed

Lu, Cheng-Chang; Chen, Shen-Kai; Wang, Chih-Wei; Chou, Pei-Hsi

2006-05-01

Chondromalacia of the trochlear notch and stress fracture of olecranon are uncommon injuries in the throwing athletes. We report an 18-year-old high school pitcher who had persistent postero-lateral elbow pain after a healed olecranon stress fracture of the right elbow. Diagnostic arthroscopy revealed chondromalacia of the trochlear notch. After treatment with arthroscopic drilling and abrasion chondroplasty, he returned to competitive pitching 1 year later postsurgery. This rare association between chondromalacia and stress fracture of the olecranon has not been reported previously in the literatures. Chondromalacia of the trochlear notch should be included as a differential diagnosis in evaluating athletes with persistent elbow pain after healed olecranon stress fractures.

Development of novel self-healing and antibacterial dental composite containing calcium phosphate nanoparticles

PubMed Central

Wu, Junling; Weir, Michael D.; Melo, Mary Anne S.; Xu, Hockin H. K.

2015-01-01

Objectives Fracture and secondary caries are the primary reasons for dental restoration failure. The objective of this study was to develop a self-healing composite to heal cracks, while containing dimethylaminohexadecyl methacrylate (DMAHDM) for antibacterial function and nanoparticles of amorphous calcium phosphate (NACP) for remineralization. Methods Microcapsules were synthesized with poly(urea-formaldehyde) (PUF) shells containing triethylene glycol dimethacrylate (TEGDMA) and N,N-dihydroxyethyl-p-toluidine (DHEPT) as healing liquid. Composite contained 20 mass% of NACP and 35% glass fillers. In addition, composite contained 0%, 2.5%, 5%, 7.5%, or 10% of microcapsules. A single edge V-notched beam method measured fracture toughness (KIC) and self-healing efficiency. A dental plaque microcosm biofilm model was used to test the antibacterial properties. Results Incorporation of microcapsules up to 7.5% into the composite did not adversely affect the mechanical properties (p > 0.1). Successful self-healing was achieved, with KIC recovery of 65–81% (mean ± sd; n = 6) to regain the load-bearing capability after composite fracture. The self-healing DMAHDM-NACP composite displayed a strong antibacterial potency, inhibiting biofilm viability and lactic acid production, and reducing colony-forming units by 3–4 orders of magnitude, compared to control composite without DMAHDM. Conclusions A dental composite was developed with triple benefits of self-healing after fracture, antibacterial activity, and remineralization capability for the first time. Clinical significance The self-healing, antibacterial and remineralizing composite may be promising for tooth cavity restorations to combat bulk fracture and secondary caries. The method of using triple agents (self-healing microcapsules, DMAHDM, and NACP) may have wide applicability to other dental composites, adhesives, sealants and cements. PMID:25625674

Ketorolac administration does not delay early fracture healing in a juvenile rat model: a pilot study.

PubMed

Cappello, Teresa; Nuelle, Julia A V; Katsantonis, Nicolas; Nauer, Rachel K; Lauing, Kristen L; Jagodzinski, Jason E; Callaci, John J

2013-06-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective at controlling pain in children, especially in the treatment of fractures. Adult animal and adult clinical studies demonstrate conflicting evidence for the inhibitory relationship between NSAIDs and fracture healing. Published pediatric orthopaedic clinical studies do not demonstrate an inhibitory effect of ketorolac on bone healing. Little is known about the effects of any NSAID on bone formation in juvenile animals. This study investigates the effects of the NSAID ketorolac on fracture healing in a juvenile rat model. Unilateral surgically induced and stabilized tibial shaft fractures were created in 45 juvenile (3 to 4 wk old) male Sprague-Dawley rats. Either ketorolac (5 mg/kg; n=24) or saline (0.9% normal saline; n=21) was then administered to the rats 6 d/wk by intraperitoneal injections. Animals were then randomly assigned into time groups and euthanized at 7 days (n=8 ketorolac, n=7 saline), 14 days (n=8 ketorolac, n=7 saline), or 21 days (n=8 ketorolac, n=7 saline) postfracture. Biomechanical analysis was performed using a custom-designed 4-point bending loading apparatus. Statistics for tibial stiffness and strength data were performed using software package Systat 11. Specimens were also evaluated histologically using hematoxylin and eosin staining. Strength and stiffness of all fractured tibiae increased over time from day 7 to day 21 regardless of treatment type. No statistical difference was found between the fractured tibiae strength or stiffness in the ketorolac or control-treated specimens at the same time point. In addition, the quality of the fracture callus was similar in both groups at each of the time points. In this study of a juvenile rat model with a stabilized tibia fracture, fracture callus strength, stiffness, and histologic characteristics were not affected by the administration of ketorolac during the first 21 days of fracture healing. The absence of inhibitory effects of ketorolac on early juvenile rat fracture healing supports the clinical practice of utilizing NSAIDs for analgesia in children with long bone fractures.

Ketorolac Administration Does Not Delay Early Fracture Healing in a Juvenile Rat Model

PubMed Central

Cappello, Teresa; Nuelle, Julia A.V.; Katsantonis, Nicolas; Nauer, Rachel K.; Lauing, Kristen L.; Jagodzinski, Jason E.; Callaci, John J.

2014-01-01

Background Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective at controlling pain in children, especially in the treatment of fractures. Adult animal and adult clinical studies demonstrate conflicting evidence for the inhibitory relationship between NSAIDs and fracture healing. Published pediatric orthopaedic clinical studies do not demonstrate an inhibitory effect of ketorolac on bone healing. Little is known about the effects of any NSAID on bone formation in juvenile animals. This study investigates the effects of the NSAID ketorolac on fracture healing in a juvenile rat model. Methods Unilateral surgically induced and stabilized tibial shaft fractures were created in 45 juvenile (3 to 4wk old) male Sprague-Dawley rats. Either ketorolac (5 mg/kg; n=24) or saline (0.9% normal saline; n=21) was then administered to the rats 6 d/wk by intraperitoneal injections. Animals were then randomly assigned into time groups and euthanized at 7 days (n=8 ketorolac, n=7 saline), 14 days (n=8 ketorolac, n=7 saline), or 21 days (n=8 ketorolac, n=7 saline) postfracture. Biomechanical analysis was performed using a custom-designed 4-point bending loading apparatus. Statistics for tibial stiffness and strength data were performed using software package Systat 11. Specimens were also evaluated histologically using hematoxylin and eosin staining. Results Strength and stiffness of all fractured tibiae increased over time from day 7 to day 21 regardless of treatment type. No statistical difference was found between the fractured tibiae strength or stiffness in the ketorolac or control-treated specimens at the same time point. In addition, the quality of the fracture callus was similar in both groups at each of the time points. Conclusions In this study of a juvenile rat model with a stabilized tibia fracture, fracture callus strength, stiffness, and histologic characteristics were not affected by the administration of ketorolac during the first 21 days of fracture healing. Clinical Relevance The absence of inhibitory effects of ketorolac on early juvenile rat fracture healing supports the clinical practice of utilizing NSAIDs for analgesia in children with long bone fractures. PMID:23653032

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.

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.

Treatment of proximal ulna and olecranon fractures by dorsal plating.

PubMed

Kloen, Peter; Buijze, Geert A

2009-12-01

Anatomic reconstruction of proximal ulna and olecranon fractures allowing early mobilization and prevention of ulnohumeral arthritis. Comminuted olecranon or proximal ulna fractures (including Monteggia fractures), olecranon fractures extending distally from the coronoid process, nonunions of the proximal ulna, segmental fractures of the proximal ulna extending into the shaft, fractures of the proximal ulna associated with a coronoid fracture. Patients in poor general condition. Soft-tissue defects around the elbow preventing wound closure over the plate. Pediatric fractures with open growth plates where screws would cross the physis. Posterior approach to the elbow. Hinging the fracture site open by extension of the proximal fragment based on triceps insertion. Fracture involvement of the coronoid with a large displaced fracture fragment can generally be reduced through the fracture side. Reconstruction with temporary Kirschner wires. Fixation by placing a (precontoured) plate around the tip of the olecranon with a long intramedullary screw and orthogonal (uni)cortical screws in the shaft. Radial head pathology can be addressed - if needed - through the same incision. Internal fixation, resection or prosthetic replacement of the radial head is done based on injury pattern/stability. Functional rehabilitation using active assisted range of motion of the elbow may be started immediately out of splint. Posterior splint for 7-10 days to allow wound healing. Between 2003 and July 2008, 26 patients were treated with posterior plating of the proximal ulna and olecranon using this strategy. There were 23 acute fractures (of which one was referred for revision after suboptimal fixation a few days earlier), one nonunion that became traumatized, and two nascent malunions. A midline posterior approach allowed addressing both ulna and radial head pathology. The plate was contoured to wrap around the olecranon. All fractures healed. There were one postoperative infection, one transient ulnar neuropathy, one transient radial neuropathy, and one nonresolving ulnar/median neuropathy in a complex upper extremity injury. At follow-up after an average of 18 months, range of motion was on average 132 degrees /18 degrees of flexion/extension, and 75 degrees /70 degrees of pronation/supination. All fractures had healed at an average of 4.8 months. Ten patients had their hardware removed.

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.

A Novel Design Approach for Self-Crack-Healing Structural Ceramics with 3D Networks of Healing Activator.

PubMed

Osada, Toshio; Kamoda, Kiichi; Mitome, Masanori; Hara, Toru; Abe, Taichi; Tamagawa, Yuki; Nakao, Wataru; Ohmura, Takahito

2017-12-19

Self-crack-healing by oxidation of a pre-incorporated healing agent is an essential property of high-temperature structural ceramics for components with stringent safety requirements, such as turbine blades in aircraft engines. Here, we report a new approach for a self-healing design containing a 3D network of a healing activator, based on insight gained by clarifying the healing mechanism. We demonstrate that addition of a small amount of an activator, typically doped MnO localised on the fracture path, selected by appropriate thermodynamic calculation significantly accelerates healing by >6,000 times and significantly lowers the required reaction temperature. The activator on the fracture path exhibits rapid fracture-gap filling by generation of mobile supercooled melts, thus enabling efficient oxygen delivery to the healing agent. Furthermore, the activator promotes crystallisation of the melts and forms a mechanically strong healing oxide. We also clarified that the healing mechanism could be divided to the initial oxidation and additional two stages. Based on bone healing, we here named these stages as inflammation, repair, and remodelling stages, respectively. Our design strategy can be applied to develop new lightweight, self-healing ceramics suitable for use in high- or low-pressure turbine blades in aircraft engines.

A small interfering RNA targeting Lnk accelerates bone fracture healing with early neovascularization.

PubMed

Kawakami, Yohei; Ii, Masaaki; Matsumoto, Tomoyuki; Kawamoto, Atsuhiko; Kuroda, Ryosuke; Akimaru, Hiroshi; Mifune, Yutaka; Shoji, Taro; Fukui, Tomoaki; Asahi, Michio; Kurosaka, Masahiro; Asahara, Takayuki

2013-09-01

Lnk, an intracellular adapter protein, is expressed in hematopoietic cell lineages, which has recently been proved as an essential inhibitory signaling molecule for stem cell self-renewal in the stem cell factor-c-Kit signaling pathway with enhanced hematopoietic and osteogenic reconstitution in Lnk-deficient mice. Moreover, the therapeutic potential of hematopoietic stem/endothelial progenitor cells (EPCs) for fracture healing has been demonstrated with mechanistic insight into vasculogenesis/angiogenesis and osteogenesis enhancement in the fracture sites. We report here, Lnk siRNA-transfected endothelial commitment of c-kit+/Sca-1+/lineage- subpopulations of bone marrow cells have high EPC colony-forming capacity exhibiting endothelial markers, VE-Cad, VEGF and Ang-1. Lnk siRNA-transfected osteoblasts also show highly osteoblastic capacity. In vivo, locally transfected Lnk siRNA could successfully downregulate the expression of Lnk at the fracture site up to 1 week, and radiological and histological examination showed extremely accelerated fracture healing in Lnk siRNA-transfected mice. Moreover, Lnk siRNA-transfected mice exhibited sufficient therapeutic outcomes with intrinstic enhancement of angiogenesis and osteogenesis, specifically, the mice demonstrated better blood flow recovery in the sites of fracture. In our series of experiments, we clarified that a negatively regulated Lnk system contributed to a favorable circumstance for fracture healing by enhancing vasculogenesis/angiogenesis and osteogenesis. These findings suggest that downregulation of Lnk system may have the clinical potential for faster fracture healing, which contributes to the reduction of delayed unions or non-unions.

The effect of HIV on early wound healing in open fractures treated with internal and external fixation.

PubMed

Aird, J; Noor, S; Lavy, C; Rollinson, P

2011-05-01

There are 33 million people worldwide currently infected with human immunodeficiency virus (HIV). This complex disease affects many of the processes involved in wound and fracture healing, and there is little evidence available to guide the management of open fractures in these patients. Fears of acute and delayed infection often inhibit the use of fixation, which may be the most effective way of achieving union. This study compared fixation of open fractures in HIV-positive and -negative patients in South Africa, a country with very high rates of both HIV and high-energy trauma. A total of 133 patients (33 HIV-positive) with 135 open fractures fulfilled the inclusion criteria. This cohort is three times larger than in any similar previously published study. The results suggest that HIV is not a contraindication to internal or external fixation of open fractures in this population, as HIV is not a significant risk factor for acute wound/implant infection. However, subgroup analysis of grade I open fractures in patients with advanced HIV and a low CD4 count (< 350) showed an increased risk of infection; we suggest that grade I open fractures in patients with advanced HIV should be treated by early debridement followed by fixation at an appropriate time.

Delayed Expression of Circulating TGF-β1 and BMP-2 Levels in Human Nonunion Long Bone Fracture Healing.

PubMed

Hara, Yoshiaki; Ghazizadeh, Mohammad; Shimizu, Hajime; Matsumoto, Hisashi; Saito, Nobuyuki; Yagi, Takanori; Mashiko, Kazuki; Mashiko, Kunihiro; Kawai, Makoto; Yokota, Hiroyuki

2017-01-01

The healing process of bone fracture requires a well-controlled multistage and sequential order beginning immediately after the injury. However, complications leading to nonunion exist, creating serious problems and costs for patients. Transforming growth factor-beta 1 (TGF-β1) and bone morphogenic protein 2 (BMP-2) are two major growth factors involved in human bone fracture healing by promoting various stages of bone ossification. In this study, we aimed to determine the role of these factors during the fracture healing of human long bones and assess their impacts on nonunion condition. We performed a comprehensive analysis of plasma TGF-β1 and BMP-2 levels in blood samples from 10 patients with proved nonunion and 10 matched patients with normal union following a predetermined time schedule. The concentrations of TGF-β1 and BMP-2 were measured at each time point using a solid-phase ELISA. TGF-β1 and BMP-2 levels were detectable in all patients. For all patients, a maximal peak for TGF-β1 was found at 3-week. In normal union group, TGF-β1 showed a maximal peak at 2-week while nonunion group had a delayed maximal peak at 3-week. Plasma levels of BMP-2 for all patients and for normal union group reached a maximal peak at 1-week, but nonunion group showed a delayed maximal peak at 2-week. In general, plasma TGF-β1 or BMP-2 level was not significantly different between normal union and nonunion groups. The expression levels of TGF-β1 and BMP-2 appeared to be delayed in nonunion patients which could play an important role in developing an early marker of fracture union condition and facilitate improved patient's management.

Management of tibial fractures using a circular external fixator in two calves.

PubMed

Aithal, Hari Prasad; Kinjavdekar, Prakash; Amarpal; Pawde, Abhijit Motiram; Singh, Gaj Raj; Setia, Harish Chandra

2010-07-01

To report the repair of tibial diaphyseal fractures in 2 calves using a circular external skeletal fixator (CEF). Clinical report. Crossbred calves (n=2; age: 6 months; weight: 55 and 60 kg). Mid-diaphyseal tibial fractures were repaired by the use of a 4-ring CEF (made of aluminum rings with 2 mm K-wires) alone in 1 calf and in combination with hemicerclage wiring in 1 calf. Both calves had good weight bearing with moderate lameness postoperatively. Fracture healing occurred by day 60 in 1 calf and by day 30 in calf 2. The CEF was well maintained and tolerated by both calves through fracture healing. Joint mobility and limb usage improved gradually after CEF removal. CEF provided a stable fixation of tibial fractures and healing within 60 days and functional recovery within 90 days. CEF can be safely and successfully used for the management of selected tibial fractures in calves.

The effects of photobiomodulation and low-amplitude high-frequency vibration on bone healing process: a comparative study.

PubMed

Rajaei Jafarabadi, M; Rouhi, G; Kaka, G; Sadraie, S H; Arum, J

2016-12-01

This study aimed at investigating the effects of photobiomodulation (PBM) and low-amplitude high-frequency (LAHF) whole body mechanical vibration on bone fracture healing process when metallic plates are implanted in rats' femurs. Forty male rats weighing between 250 and 350 g, 12 weeks old, were employed in this study. A transverse critical size defect (CSD) was made in their right femurs that were fixed by stainless steel plates. After the surgery, the rats were divided equally into four groups: low-level laser therapy group (GaAlAs laser, 830 nm, 40 mW, 4 J/cm 2 , 0.35 cm beam diameter, LLLT), whole body vibration group (60 Hz, 0.1 mm amplitude, 1.5 g, WBV), a combination of laser and vibration group (LV), and the control group (C). Each group was divided into two subgroups based on sacrifice dates. The rats were sacrificed at intervals of 3 and 6 weeks after the surgery to extract their right femurs for radiography and biomechanical and histological analyses, and the results were analyzed using standard statistical methods. Radiographic analyses showed greater callus formation in the LLLT and WBV groups than in control group at both 3 (P < 0.05 and P < 0.001, respectively) and 6 weeks after surgery (P < 0.05 and P < 0.05, respectively). Histological evaluations showed a higher amount of new bone formation and better maturity in the LLLT and WBV groups than the control groups at 3 and 6 weeks after surgery. Biomechanical tests showed that the maximum force at fracture in the LLLT (P < 0.05 in 3 weeks and P < 0.05 in 6 weeks) and WBV (P < 0.001 in 3 weeks and P < 0.05 in 6 weeks) groups was greater than that in the control groups at both time intervals. But a combination of laser and vibration therapy, LV, did not show a positive interaction on bone fracture healing process. The biostimulation effects of PBM or LLLT and of low-amplitude high-frequency WBV both had a positive impact on bone healing process, for critical size defects in the presence of a stainless steel implant. But their combination, i.e., low-level laser therapy and low-amplitude high-frequency whole body vibration (LV), interestingly did not accelerate the fractured bone healing process.

Orthodontic movement of a horizontally fractured tooth: a case report.

PubMed

Erdemir, Ali; Ungor, Mete; Erdemir, Ebru Olgun

2005-06-01

Intra-alveolar root fractures are relatively uncommon, and sometimes may be healed without treatment. Diagnosis of intra-alveolar root fracture is frequently made by exclusion of clinical signs of other traumatic injury, and by radiographic examination with films taken at different tube angulations. This case report presents a horizontal root fractured tooth that was healed satisfactory without treatment and moved orthodontically after prolonged time from trauma.

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

Vitamin D in Foot and Ankle Fracture Healing: A Literature Review and Research Design.

PubMed

Bernhard, Andrew; Matuk, Jorge

2015-10-01

Vitamin D is a generic name for a group of essential vitamins, or secosteroids, important in calcium homeostasis and bone metabolism. Specifically, efficacy of vitamin D with regard to bone healing is in question. A literature review was performed, finding mostly large studies involving vitamin D effects on prevention of fractures and randomized animal model studies consisting of controlled fractures with vitamin D interventions. The prevention articles generally focus on at-risk populations, including menopausal women and osteoporotic patients, and also most often include calcium in the treatment group. Few studies look at vitamin D specifically. The animal model studies often focus more on vitamin D supplementation; however the results are still largely inconclusive. While recent case reports appear promising, the ambiguity of results on the topic of fracture healing suggests a need for more, higher level research. A novel study design is proposed to help determine the efficacy on vitamin D in fracture healing. Therapeutic, Level IV: Systematic Review. © 2015 The Author(s).

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.

Challenges experienced during rehabilitation after traumatic multiple rib fractures: a qualitative study.

PubMed

Claydon, Jacqueline; Maniatopoulos, Gregory; Robinson, Lisa; Fearon, Paul

2017-08-02

People with multiple rib fractures rarely receive rehabilitation aimed specifically at their chest wall injuries. This research explores patient perceptions of rehabilitation and recovery. A qualitative study exploring how a purposive sample of 15 people with traumatic multiple rib fractures at a Major Trauma Centre in the United Kingdom make sense of their recovery. Data collected during one-to-one interviews 4 to 9 months after injury. Transcripts analysed using Interpretative Phenomenological Analysis. Struggling with breathing and pain: Difficulties with breathing and pain were initially so severe ?it takes your breath away? and people felt scared they may not survive. These symptoms gradually improved but feeling "out of puff" often persisted. Life on hold: Healing was considered a natural process which people couldn't influence, creating frustration whilst waiting for injuries to heal. Many believed they would never fully recover and accepted limitations. Lucky to be alive: All participants expressed a sense of feeling lucky to be alive. The seriousness of injury prompted a change in attitude to make the most of life. Rib fractures can be painful, but also frightening. A rehabilitation intervention promoting pain management, normalises trauma and restores physical activity may improve recovery. Implications for Rehabilitation Patients identified challenges with rehabilitation throughout the entire recovery journey, and their rehabilitation needs evolved with time. People find it difficult to regain pre-injury fitness even after their fractures heal and pain subsides. A belief there is nothing that can be done to help rib fractures contributed to people lowering their expectations of achieving a full recovery and developing a sense of "making do". Rehabilitation and patient education after traumatic multiple rib fractures should focus on improving pain management, respiratory fitness and emotional well-being.

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

Risk of refracture through unicameral bone cysts of the proximal femur.

PubMed

Norman-Taylor, Fabian H; Hashemi-Nejad, Aresh; Gillingham, Bruce L; Stevens, David; Cole, William G

2002-01-01

The authors determined the results after traction or traction and hip spica treatment of the initial fractures through unicameral bone cysts of the proximal femur in 20 children. All of the eight displaced fractures healed, but with coxa vara and avascular necrosis in one, coxa vara in a second, and coxa breva in a third. Spontaneous healing of the cyst occurred in three of the eight children; satisfactory healing was achieved and maintained after intralesional corticosteroid injections in four of the eight children. In the remaining child with a displaced fracture, reactivation of the cyst and exercise-related pain, indicative of an incipient refracture, occurred 3 years after initial presentation. All of the 12 undisplaced fractures healed without deformity or avascular necrosis. Intralesional corticosteroids were used in all of the 12 children because none of them showed spontaneous healing of their cysts. Satisfactory radiographic healing was achieved 1 year after presentation in all of the 12 children. However, one or more refractures resulting from reactivation of the cyst occurred in 6 of the 12 children 2 to 5 years after initial presentation. The results of this study indicate that satisfactory radiographic healing needs to be achieved by the end of the first year and needs to be maintained thereafter to prevent refractures.

Root bark of Sambucus Williamsii Hance promotes rat femoral fracture healing by the BMP-2/Runx2 signaling pathway.

PubMed

Yang, Bingyou; Lin, Xiaoying; Tan, Jinyan; She, Xian; Liu, Yan; Kuang, Haixue

2016-09-15

Sambucus Williamsii Hance (SWH) is a plant from a family of Caprifoliaceae, which has a long medical history of use as an effective folk treatment for fracture bruises. To evaluate the effects of 50% ethanol extracts of root-bark of Sambucus Williamsii Hance(EE-rbSWH) on fracture healing of rats and explore its mechanism of actions related to the BMP-2 signaling pathway. EE-rbSWH was orally administered at the doses of 340 and 680mg/kg to adult Sprague-Dawley rats with operation of open femur fracture completely for 2, 4 and 8 weeks. And the rats of sham operation and Model groups were administered Vehicle (distilled water 0.8mL/200g/day). Firstly, the bone X-ray morphology and bone mineral density(BMD) of the fracture site were observed and measured after anesthesia the rats at weeks 2, 4, and 8 after surgery, then the serum levels of alkaline phosphatase(ALP) and osteocalcin (BGP) were measured; Secondly, the tissue morphology of the fracture site was observed after sacrificed the rats; Thirdly, the formation of mineralized nodules in bone marrow stromal cells(BMSC) were evaluated at week 2; Lastly, the genes levels of BMP-2 and Runx2 in the femur were detected at week 2 and 4, and the proteins expression of BMP-2 signaling pathway (BMP-2, BMPRIB, BMPRII and Runx2) in the femur also were detected at week 2. EE-rbSWH remarkably accelerated fracture healing by promoting bone formation at all the time points of fracture healing. Mainly by increasing the BMD level at the fracture site, the levels of serum ALP and BGP, and also the numbers increasing of calcified nodules in BMSC. The mechanism studies, EE-rbSWH can promote fracture healing by enhancing the expressions of BMP-2 and Runx2 mRNA, and also the proteins of BMP-2, BMPRIB, BMPRII and Runx2 at the fracture site of rats. Our results suggested that 50% ethanol extracts of root-bark of Sambucus Williamsii Hance can accelerate fracture healing by recruitment of osteoblasts at the fracture site and through up-regulation of the BMP-2 signaling pathway. Copyright © 2016. Published by Elsevier Ireland Ltd.

[Effect of axial stress stimulation on tibial and fibular open fractures healing after Taylor space stent fixation].

PubMed

Ge, Qihang; Wan, Chunyou; Liu, Yabei; Ji, Xu; Ma, Jihai; Cao, Haikun; Yong, Wei; Liu, Zhao; Zhang, Ningning

2017-08-01

To investigate the effect of axial stress stimulation on tibial and fibular open fractures healing after Taylor space stent fixation. The data of 45 cases with tibial and fibular open fractures treated by Taylor space stent fixation who meet the selection criteria between January 2015 and June 2016 were retrospectively analysed. The patients were divided into trial group (23 cases) and control group (22 cases) according to whether the axial stress stimulation was performed after operation. There was no significant difference in gender, age, affected side, cause of injury, type of fracture, and interval time from injury to operation between 2 groups ( P >0.05). The axial stress stimulation was performed in trial group after operation. The axial load sharing ratio was tested, and when the value was less than 10%, the external fixator was removed. The fracture healing time, full weight-bearing time, and external fixator removal time were recorded and compared. After 6 months of external fixator removal, the function of the limb was assessed by Johner-Wruhs criteria for evaluation of final effectiveness of treatment of tibial shaft fractures. There were 2 and 3 cases of needle foreign body reaction in trial group and control group, respectively, and healed after symptomatic anti allergic treatment. All the patients were followed up 8-12 months with an average of 10 months. All the fractures reached clinical healing, no complication such as delayed union, nonunion, or osteomyelitis occurred. The fracture healing time, full weight-bearing time, and external fixator removal time in trial group were significantly shorter than those in control group ( P <0.05). After 6 months of external fixator removal, the function of the limb was excellent in 13 cases, good in 6 cases, fair in 3 cases, and poor in 1 case in trial group, with an excellent and good rate of 82.6%; and was excellent in 5 cases, good in 10 cases, fair in 4 cases, and poor in 3 cases in control group, with an excellent and good rate of 68.2%, showing significant difference between 2 groups ( Z =-2.146, P =0.032). The axial stress stimulation of Taylor space stent fixation can promote the healing of tibial and fibular open fractures and promote local bone formation at fracture site.

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.

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.

Temporal variation of applied inter fragmentary displacement at a bone fracture in harmony with maturation of the fracture callus.

PubMed

Gardner, T N; Evans, M; Simpson, H

1998-09-01

The amplitude of inter fragmentary displacement in long bone fractures greatly influences the pattern and speed of healing. Unfortunately, the amplitude of natural cyclical displacement arising from patient activity is random because of the inherent flexibility of fixation devices under natural loading. Although fixators may be designed to control the amplitude of this displacement, the amplitudes most beneficial to healing have not been determined. Furthermore, the appropriate amplitude must vary during healing as the reparative tissue (callus) progresses histologically and stiffens during maturation. In this study on an experimental fracture, the amplitude of applied cyclical displacement is varied during healing to correspond with the inverse of the callus stiffness versus time curve. In vivo mechanical stiffness tests on the callus indicate that the end point of the fixation period is achieved more rapidly than with a constant level of applied displacement.

Histology of 8 atypical femoral fractures: remodeling but no healing.

PubMed

Schilcher, Jörg; Sandberg, Olof; Isaksson, Hanna; Aspenberg, Per

2014-06-01

The pathophysiology behind bisphosphonate-associated atypical femoral fractures remains unclear. Histological findings at the fracture site itself may provide clues. Between 2008 and 2013, we collected bone biopsies including the fracture line from 4 complete and 4 incomplete atypical femoral fractures. 7 female patients reported continuous bisphosphonate use for 10 years on average. 1 patient was a man who was not using bisphosphonates. Dual-energy X-ray absorptiometry of the hip and spine showed no osteoporosis in 6 cases. The bone biopsies were evaluated by micro-computed tomography, infrared spectroscopy, and qualitative histology. Incomplete fractures involved the whole cortical thickness and showed a continuous gap with a mean width of 180 µm. The gap contained amorphous material and was devoid of living cells. In contrast, the adjacent bone contained living cells, including active osteoclasts. The fracture surfaces sometimes consisted of woven bone, which may have formed in localized defects caused by surface fragmentation or resorption. Atypical femoral fractures show signs of attempted healing at the fracture site. The narrow width of the fracture gap and its necrotic contents are compatible with the idea that micromotion prevents healing because it leads to strains within the fracture gap that preclude cell survival.

Comparison of microCT and an inverse finite element approach for biomechanical analysis: Results in a MSC therapeutic system for fracture healing

PubMed Central

Weis, Jared A.; Granero-Moltó, Froilán; Myers, Timothy J.; Longobardi, Lara; Spagnoli, Anna; Miga, Michael I.

2013-01-01

An important concern in the study of fracture healing is the ability to assess mechanical integrity in response to candidate therapeutics in small-animal systems. In recent reports, it has been proposed that microCT image-derived densitometric parameters could be used as a surrogate for mechanical property assessment. Recently, we have proposed an inverse methodology that iteratively reconstructs the modulus of elasticity of the lumped soft callus/hard callus region by integrating both intrinsic mechanical property (from biomechanical testing) and geometrical information (from microCT) within an inverse finite element analysis (FEA) to define a callus quality measure. In this paper, data from a therapeutic system involving mesenchymal stem cells is analyzed within the context of comparing traditional microCT densitometric and mechanical property metrics. In addition, a novel multi-parameter regression microCT parameter is analyzed as well as our inverse FEA metric. The results demonstrate that the inverse FEA approach was the only metric to successfully detect both longitudinal and therapeutic responses. While the most promising microCT-based metrics were adequate at early healing states, they failed to track late-stage mechanical integrity. In addition, our analysis added insight to the role of MSCs by demonstrating accelerated healing and was the only metric to demonstrate therapeutic benefits at late-stage healing. In conclusion, the work presented here indicates that microCT densitometric parameters are an incomplete surrogate for mechanical integrity. Additionally, our inverse FEA approach is shown to be very sensitive and may provide a first-step towards normalizing the often challenging process of assessing mechanical integrity of healing fractures. PMID:22766379

Low Intensity Pulsed Ultrasound Enhanced Mesenchymal Stem Cell Recruitment through Stromal Derived Factor-1 Signaling in Fracture Healing

PubMed Central

Wei, Fang-Yuan; Leung, Kwok-Sui; Li, Gang; Qin, Jianghui; Chow, Simon Kwoon-Ho; Huang, Shuo; Sun, Ming-Hui; Qin, Ling; Cheung, Wing-Hoi

2014-01-01

Low intensity pulsed ultrasound (LIPUS) has been proven effective in promoting fracture healing but the underlying mechanisms are not fully depicted. We examined the effect of LIPUS on the recruitment of mesenchymal stem cells (MSCs) and the pivotal role of stromal cell-derived factor-1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) pathway in response to LIPUS stimulation, which are essential factors in bone fracture healing. For in vitro study, isolated rat MSCs were divided into control or LIPUS group. LIPUS treatment was given 20 minutes/day at 37°C for 3 days. Control group received sham LIPUS treatment. After treatment, intracellular CXCR4 mRNA, SDF-1 mRNA and secreted SDF-1 protein levels were quantified, and MSCs migration was evaluated with or without blocking SDF-1/CXCR4 pathway by AMD3100. For in vivo study, fractured 8-week-old young rats received intracardiac administration of MSCs were assigned to LIPUS treatment, LIPUS+AMD3100 treatment or vehicle control group. The migration of transplanted MSC to the fracture site was investigated by ex vivo fluorescent imaging. SDF-1 protein levels at fracture site and in serum were examined. Fracture healing parameters, including callus morphology, micro-architecture of the callus and biomechanical properties of the healing bone were investigated. The in vitro results showed that LIPUS upregulated SDF-1 and CXCR4 expressions in MSCs, and elevated SDF-1 protein level in the conditioned medium. MSCs migration was promoted by LIPUS and partially inhibited by AMD3100. In vivo study demonstrated that LIPUS promoted MSCs migration to the fracture site, which was associated with an increase of local and serum SDF-1 level, the changes in callus formation, and the improvement of callus microarchitecture and mechanical properties; whereas the blockade of SDF-1/CXCR4 signaling attenuated the LIPUS effects on the fractured bones. These results suggested SDF-1 mediated MSCs migration might be one of the crucial mechanisms through which LIPUS exerted influence on fracture healing. PMID:25181476

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.

Micro-Computed Tomography Assessment of Fracture Healing: Relationships among Callus Structure, Composition, and Mechanical Function

PubMed Central

Morgan, Elise F.; Mason, Zachary D.; Chien, Karen B.; Pfeiffer, Anthony J.; Barnes, George L.; Einhorn, Thomas A.; Gerstenfeld, Louis C.

2009-01-01

Non-invasive characterization of fracture callus structure and composition may facilitate development of surrogate measures of the regain of mechanical function. As such, quantitative computed tomography- (CT-) based analyses of fracture calluses could enable more reliable clinical assessments of bone healing. Although previous studies have used CT to quantify and predict fracture healing, it is unclear which of the many CT-derived metrics of callus structure and composition are the most predictive of callus mechanical properties. The goal of this study was to identify the changes in fracture callus structure and composition that occur over time and that are most closely related to the regain of mechanical function. Micro-computed tomography (μCT) imaging and torsion testing were performed on murine fracture calluses (n=188) at multiple post-fracture timepoints and under different experimental conditions that alter fracture healing. Total callus volume (TV), mineralized callus volume (BV), callus mineralized volume fraction (BV/TV), bone mineral content (BMC), tissue mineral density (TMD), standard deviation of mineral density (σTMD), effective polar moment of inertia (Jeff), torsional strength, and torsional rigidity were quantified. Multivariate statistical analyses, including multivariate analysis of variance, principal components analysis, and stepwise regression were used to identify differences in callus structure and composition among experimental groups and to determine which of the μCT outcome measures were the strongest predictors of mechanical properties. Although calluses varied greatly in the absolute and relative amounts of mineralized tissue (BV, BMC, and BV/TV), differences among timepoints were most strongly associated with changes in tissue mineral density. Torsional strength and rigidity were dependent on mineral density as well as the amount of mineralized tissue: TMD, BV, and σTMD explained 62% of the variation in torsional strength (p<0.001); and TMD, BMC, BV/TV, and σTMD explained 70% of the variation in torsional rigidity (p<0.001). These results indicate that fracture callus mechanical properties can be predicted by several μCT-derived measures of callus structure and composition. These findings form the basis for developing non-invasive assessments of fracture healing and for identifying biological and biomechanical mechanisms that lead to impaired or enhanced healing. PMID:19013264

Reaction processes and permeability changes during CO2-rich brine flow through fractured Portland cement

NASA Astrophysics Data System (ADS)

Abdoulghafour, H.; Luquot, L.; Gouze, P.

2012-12-01

So far, cement alteration was principally studied experimentally using batch reactor (with static or renewed fluid). All exhibit similar carbonation mechanisms. The acidic solution, formed by the dissolution of the CO2 into the pore water or directly surrounding the cement sample, diffuses into the cement and induces dissolution reactions of the cement hydrates in particular portlandite and CSH. The calcium released by the dissolution of these calcium bearing phases combining with carbonate ions of the fluid forms calcium carbonates. The cement pH, initially around 13, falls to values where carbonate ion is the most dominant element (pH ~ 9), then CaCO3 phases can precipitate. These studies mainly associate carbonation process with a reduction of porosity and permeability. Indeed an increase of volume (about 10%) is expected during the formation of calcite from portlandite (equation 2) assuming a stoichiometric reaction. Here we investigated the cement alteration mechanisms in the frame of a controlled continuous renewal of CO2-rich fluid in a fracture. This situation is that expected when seepage is activated by the mechanical failure of the cement material that initially seals two layers of distinctly different pressure: the storage reservoir and the aquifer above the caprock, for instance. We study the effect of flow rates from quasi-static flow to higher flow rates for well-connected fractures. In the quasi-static case we observed an extensive conversion of portlandite (Ca(OH)2) to calcite in the vicinity of the fracture similar to that observed in the published batch experiments. Eventually, the fracture was almost totally healed. The experiments with constant flow revealed a different behaviour triggered by the continuous renewing of the reactants and withdrawal of reaction products. We showed that calcite precipitation is more efficient for low flow rate. With intermediate flow rate, we measured that permeability increases slowly at the beginning of the experiment and then remains constant due to calcite precipitation in replacement of CSH and CH into fracture border. With higher flow rate, we measured a constant permeability which can be explained by the development of a highly hydrated Si-rich zone which maintains the initial fracture aperture during all over the experiment while noticeable mass is released from the sample. These preliminary results emphasize that more complex behaviours than that envisaged from batch experiments may take place in the vicinity of flowing fractures. We demonstrated that if only micro-cracks appear in the cement well, carbonation reaction may heal these micro-cracks and mitigate leakage whereas conductive fractures allowing high flow may represent a risk of perennial leakage because the net carbonation process, including the calcite precipitation and its subsequent re-dissolution, is sufficiently to heal the fracture. However, the precipitation of Si-rich amorphous phases may maintain the initial fracture aperture and limit the leakage rate. Keywords: leakage, cement alteration, flow rate, fracture, permeability changes, reaction processes.

The Pathobiology of Diabetes Mellitus in Bone Metabolism, Fracture Healing, and Complications.

PubMed

Forslund, Johan M; Archdeacon, Michael T

2015-10-01

Complications and inferior outcomes of fractures in the setting of diabetes mellitus (DM) are well documented. The incidence of DM is increasing rapidly, particularly in an aging and obese population. Thus, the combination of DM and fracture is becoming a serious health problem worldwide. As many fractures are relatively uncomplicated in the healthy patient population, a concerted effort to improve outcomes of fractures in patients with DM is warranted. In this article, we review relevant studies and examine the pathobiological mechanisms influencing fracture outcomes, including complications related to bone and soft-tissue healing, and infection.

Dipyrone has no effects on bone healing of tibial fractures in rats

PubMed Central

Gali, Julio Cesar; Sansanovicz, Dennis; Ventin, Fernando Carvalho; Paes, Rodrigo Henrique; Quevedo, Francisco Carlos; Caetano, Edie Benedito

2014-01-01

OBJECTIVE: To evaluate the effect of dipyrone on healing of tibial fractures in rats. METHODS: Fourty-two Wistar rats were used, with mean body weight of 280g. After being anesthetized, they were submitted to closed fracture of the tibia and fibula of the right posterior paw through manual force. The rats were randomly divided into three groups: the control group that received a daily intraperitoneal injection of saline solution; group D-40, that received saline injection containing 40mg/Kg dipyrone; and group D-80, that received saline injection containing 80mg/Kg dipyrone. After 28 days the rats were sacrificed and received a new label code that was known by only one researcher. The fractured limbs were then amputated and X-rayed. The tibias were disarticulated and subjected to mechanical, radiological and histological evaluation. For statistical analysis the Kruskal-Wallis test was used at a significance level of 5%. RESULTS: There wasn't any type of dipyrone effect on healing of rats tibial fractures in relation to the control group. CONCLUSION: Dipyrone may be used safely for pain control in the treatment of fractures, without any interference on bone healing. Level of Evidence II, Controlled Laboratory Study. PMID:25246852

Scar-free wound healing and regeneration following tail loss in the leopard gecko, Eublepharis macularius.

PubMed

Delorme, Stephanie Lynn; Lungu, Ilinca Mihaela; Vickaryous, Matthew Kenneth

2012-10-01

Many lizards are able to undergo scar-free wound healing and regeneration following loss of the tail. In most instances, lizard tail loss is facilitated by autotomy, an evolved mechanism that permits the tail to be self-detached at pre-existing fracture planes. However, it has also been reported that the tail can regenerate following surgical amputation outside the fracture plane. In this study, we used the leopard gecko, Eublepharis macularius, to investigate and compare wound healing and regeneration following autotomy at a fracture plane and amputation outside the fracture plane. Both forms of tail loss undergo a nearly identical sequence of events leading to scar-free wound healing and regeneration. Early wound healing is characterized by transient myofibroblasts and the formation of a highly proliferative wound epithelium immunoreactive for the wound keratin marker WE6. The new tail forms from what is commonly referred to as a blastema, a mass of proliferating mesenchymal-like cells. Blastema cells express the protease matrix metalloproteinase-9. Apoptosis (demonstrated by activated caspase 3 immunostaining) is largely restricted to isolated cells of the original and regenerating tail tissues, although cell death also occurs within dermal structures at the original-regenerated tissue interface and among clusters of newly formed myocytes. Furthermore, the autotomized tail is unique in demonstrating apoptosis among cells adjacent to the fracture planes. Unlike mammals, transforming growth factor-β3 is not involved in wound healing. We demonstrate that scar-free wound healing and regeneration are intrinsic properties of the tail, unrelated to the location or mode of tail detachment. Copyright © 2012 Wiley Periodicals, Inc.

Fractures of the distal tibia treated with polyaxial locking plating.

PubMed

Gao, Hong; Zhang, Chang-Qing; Luo, Cong-Feng; Zhou, Zu-Bin; Zeng, Bing-Fang

2009-03-01

We evaluated the healing rate, complications, and functional outcomes in 32 adult patients with very short metaphyseal fragments in fractures of the distal tibia treated with a polyaxial locking system. The average distance from the distal extent of the fracture to the tibial plafond was 11 mm. All fractures healed and the average time to union was 14 weeks. Six patients (19%) reported occasional local disturbance over the medial malleolus. There were two cases of postoperative superficial infections and evidence of delayed wound healing. Using the American Orthopaedic Foot and Ankle Society ankle score, the average functional score was 87.3 points (of 100 total possible points). Our results show the polyaxial locking plates, which offer more fixation versatility, may be a reasonable treatment option for distal tibia fractures with very short metaphyseal segments.

Fracture reduction and primary ankle arthrodesis: a reliable approach for severely comminuted tibial pilon fracture.

PubMed

Beaman, Douglas N; Gellman, Richard

2014-12-01

Posttraumatic arthritis and prolonged recovery are typical after a severely comminuted tibial pilon fracture, and ankle arthrodesis is a common salvage procedure. However, few reports discuss the option of immediate arthrodesis, which may be a potentially viable approach to accelerate overall recovery in patients with severe fracture patterns. (1) How long does it take the fracture to heal and the arthrodesis to fuse when primary ankle arthrodesis is a component of initial fracture management? (2) How do these patients fare clinically in terms of modified American Orthopaedic Foot and Ankle Society (AOFAS) scores and activity levels after this treatment? (3) Does primary ankle arthrodesis heal in an acceptable position when anterior ankle arthrodesis plates are used? During a 2-year period, we performed open fracture reduction and internal fixation in 63 patients. Eleven patients (12 ankles) with severely comminuted high-energy tibial pilon fractures were retrospectively reviewed after surgical treatment with primary ankle arthrodesis and fracture reduction. Average patient age was 58 years, and minimum followup was 6 months (average, 14 months; range, 6-22 months). Anatomically designed anterior ankle arthrodesis plates were used in 10 ankles. Ring external fixation was used in nine ankles with concomitant tibia fracture or in instances requiring additional fixation. Clinical evaluation included chart review, interview, the AOFAS ankle-hindfoot score, and radiographic evaluation. All of the ankle arthrodeses healed at an average of 4.4 months (range, 3-5 months). One patient had a nonunion at the metaphyseal fracture, which healed with revision surgery. The average AOFAS ankle-hindfoot score was 83 with 88% having an excellent or good result. Radiographic and clinical analysis confirmed a plantigrade foot without malalignment. No patients required revision surgery for malunion. Primary ankle arthrodesis combined with fracture reduction for the severely comminuted tibial pilon fracture reliably healed and restored acceptable function in this highly selective patient group. Ring external fixation may be a useful adjunct to internal fixation, and this concept should be further studied. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Dynamic Fixation of Humeral Shaft Fractures Using Active Locking Plates: A Prospective Observational Study.

PubMed

Madey, Steven M; Tsai, Stanley; Fitzpatrick, Daniel C; Earley, Kathleen; Lutsch, Michael; Bottlang, Michael

2017-01-01

Rigid locked plating constructs can suppress fracture healing by inhibiting interfragmentary motion required to stimulate natural bone healing by callus formation. Dynamic fixation with active locking plates reduces construct stiffness, enables controlled interfragmentary motion, and has been shown to induce faster and stronger bone healing in vivo compared to rigid locking plates. This prospective observational study represents the first clinical use of active locking plates. It documents our early clinical experience with active plates for stabilization of humeral shaft fractures to assess their durability and understand potential complications. Eleven consecutive patients with humeral shaft fractures (AO/OTA types 12 A-C) were prospectively enrolled at a level I and a level II trauma center. Fractures were stabilized by using active locking plates without supplemental bone graft or bone morphogenic proteins. The screw holes of active locking plates are elastically suspended in elastomer envelopes inside the plate, enabling up to 1.5 mm of controlled interfragmentary motion. Progression of fracture healing and integrity of implant fixation was assessed radiographically at 3, 6, 12, and 24 weeks post surgery. Patient-reported functional outcome measures were obtained at 6, 12, and 24 weeks post surgery. The primary endpoint of this study was plate durability in absence of plate bending or breakage, or failure of the elastically suspended locking hole mechanism. Secondary endpoints included fracture healing, complications requiring revision surgery, and functional outcome scores. The eleven patients had six simple AO/ OTA type 12A fractures, three wedge type 12B fractures, and two comminuted type 12C fracture, including one open fracture. All active locking plates endured the 6-month loading period without any signs of fatigue or failure. Ten of eleven fractures healed at 10.9 ± 5.2 weeks, as evident by bridging callus and pain-free function. One fracture required revision surgery 37 weeks post surgery due to late fixation failure at the screwbone interface in the presence of a atrophic delayed union. The average Disability of the Arm, Shoulder and Hand (DASH) score improved from 31 ± 22 at week 6 to 13 ± 15 by week 24, approaching that of the normal, healthy population (DASH = 10.1). By week 12, the difference between Constant shoulder scores, expressed as the difference between the affected and contralateral arm (8 ± 8), was considered excellent. By week 24, the SF-12 physical health score (44 ± 9) and mental health score (48 ± 11) approached the mean value of 50 that represents the norm for the general U.S. population. Absence of failure of the plate and locking holes suggests that dynamic fixation of humeral shaft fractures with active plates provides safe and effective fixation. Moreover, early callus bridging and excellent functional outcome scores suggest that dynamic fixation with active locking plates may promote increased fracture healing over standard locked plating.

Fracture healing in mice under controlled rigid and flexible conditions using an adjustable external fixator.

PubMed

Röntgen, Viktoria; Blakytny, Robert; Matthys, Romano; Landauer, Mario; Wehner, Tim; Göckelmann, Melanie; Jermendy, Philipp; Amling, Michael; Schinke, Thorsten; Claes, Lutz; Ignatius, Anita

2010-11-01

Mice are increasingly used to investigate mechanobiology in fracture healing. The need exists for standardized models allowing for adjustment of the mechanical conditions in the fracture gap. We introduced such a model using rigid and flexible external fixators with considerably different stiffness (axial stiffnesses of 18.1 and 0.82 N/mm, respectively). Both fixators were used to stabilize a 0.5 mm osteotomy gap in the femur of C57BL/6 mice (each n = 8). Three-point bending tests, µCT, and histomorphometry demonstrated a different healing pattern after 21 days. Both fixations induced callus formation with a mixture of intramembranous and enchondral ossification. Under flexible conditions, the bending stiffness of the callus was significantly reduced, and a larger but qualitatively inferior callus with a significantly lower fraction of bone but a higher fraction of cartilage and soft tissue was formed. Monitoring of the animal movement and the ground reaction forces demonstrated physiological loading with no significant differences between the groups, suggesting that the differences in healing were not based on a different loading behavior. In summary, flexible external fracture fixation of the mouse femur led to delayed fracture healing in comparison to a more rigid situation. © 2010 Orthopaedic Research Society.

Local delivery of HMGB1 in gelatin sponge scaffolds combined with mesenchymal stem cell sheets to accelerate fracture healing.

PubMed

Xue, Deting; Zhang, Wei; Chen, Erman; Gao, Xiang; Liu, Ling; Ye, Chenyi; Tan, Yanbin; Pan, Zhijun; Li, Hang

2017-06-27

Fracture nonunion and delayed union continue to pose challenges for orthopedic surgeons. In the present study, we combined HMGB1 gelatin sponges with MSC sheets to promote bone healing after surgical treatment of rat tibial fractures. The HMGB1 gelatin sponge scaffolds supported the expansion of mesenchymal stem cells (MSCs) and promoted the osteogenic differentiation of MSCs and MSC sheets. Lentiviral vectors were then used to overexpress HMGB1 in MSCs. The results indicated that HMGB1 promotes the osteogenic differentiation of MSCs through the STAT3 pathway. Both siRNA and a STAT3 inhibitor downregulated STAT3, further confirming that HMGB1 induces the osteogenic differentiation of MSCs partly via the STAT3 signal pathway. In a rat tibial osteotomy model, we demonstrated the ability of HMGB1 gelatin sponge scaffolds to increase bone formation. The addition of MSC sheets further enhanced fracture healing. These findings support the use of HMGB1-loaded gelatin sponge scaffolds combined with MSC sheets to enhance fracture healing after surgical intervention.

Local delivery of HMGB1 in gelatin sponge scaffolds combined with mesenchymal stem cell sheets to accelerate fracture healing

PubMed Central

Xue, Deting; Zhang, Wei; Chen, Erman; Gao, Xiang; Liu, Ling; Ye, Chenyi; Tan, Yanbin; Pan, Zhijun; Li, Hang

2017-01-01

Fracture nonunion and delayed union continue to pose challenges for orthopedic surgeons. In the present study, we combined HMGB1 gelatin sponges with MSC sheets to promote bone healing after surgical treatment of rat tibial fractures. The HMGB1 gelatin sponge scaffolds supported the expansion of mesenchymal stem cells (MSCs) and promoted the osteogenic differentiation of MSCs and MSC sheets. Lentiviral vectors were then used to overexpress HMGB1 in MSCs. The results indicated that HMGB1 promotes the osteogenic differentiation of MSCs through the STAT3 pathway. Both siRNA and a STAT3 inhibitor downregulated STAT3, further confirming that HMGB1 induces the osteogenic differentiation of MSCs partly via the STAT3 signal pathway. In a rat tibial osteotomy model, we demonstrated the ability of HMGB1 gelatin sponge scaffolds to increase bone formation. The addition of MSC sheets further enhanced fracture healing. These findings support the use of HMGB1-loaded gelatin sponge scaffolds combined with MSC sheets to enhance fracture healing after surgical intervention. PMID:28431400

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

[Clinical observation on the influence of earthquake crush injury on postoperative wound healing of extremity fractures].

PubMed

Chen, Fu-hong; Chen, Ze; Duan, Heng-qiong; Wan, Zhong-xian

2008-10-01

To observe the influence of earthquake crush injury on postoperative wound healing of extremity fractures. The study involved 85 patients with extremities fracture underwent internal fixation operation in 3 group, including 28 earthquake casualties with crush injuries in observation group, 27 earthquake casualties without crush injuries in control I group and 30 local patients during the same period in control II group. Urine routine, blood creatine kinase (CK) and wound conditions of patients in 3 groups were observed respectively. There was no significant difference in Urine routine and blood CK between 3 groups and was significant difference in wound conditions between observation group and each control group. Earthquake crush injuries can influence the postoperative wound healing of extremity fractures.

Toughening and healing of continuous fibre reinforced composites with bis-maleimide based pre-pregs

NASA Astrophysics Data System (ADS)

Kostopoulos, V.; Kotrotsos, A.; Tsantzalis, S.; Tsokanas, P.; Christopoulos, A. C.; Loutas, T.

2016-08-01

Unidirectional (UD) pre-pregs containing self-healing materials based on Diels-Alder reaction bis-maleimide (BMI) polymers were successfully incorporated on the mid-plane of UD carbon fibre reinforced polymers. The fracture toughness of these composites and the introduced healing capability were measured under mode I loading. The interlaminar fracture toughness was enhanced considerably, since the maximum load (P max) of the modified composite increased approximately 1.5 times and the mode I fracture energy (G IC) displayed a significant increase of almost 3.5 times when compared to the reference composites. Furthermore the modified composites displayed a healing efficiency (HE) value of about 30% for P max and 20% for G IC after the first healing, appearing to be an almost stable behaviour after the third healing cycle. The HE displayed a decrease of 20% and 15% for P max and G IC values, respectively, after the fifth healing cycle. During the tests, the monitored acoustic emission (AE) activity of the samples showed that there is no significant difference due to the presence of BMI polymer in terms of AE hits. Moreover, optical microscopy not only showed that the epoxy matrix at the interface is partly infiltrated by the BMI polymer, but it also revealed the presence of pulled out fibres at the fractured surface, indicating ductile behaviour.

Correlation between RUST assessments of fracture healing to structural and biomechanical properties.

PubMed

Cooke, Margaret E; Hussein, Amira I; Lybrand, Kyle E; Wulff, Alexander; Simmons, Erin; Choi, Jeffrey H; Litrenta, Jody; Ricci, William M; Nascone, Jason W; O'Toole, Robert V; Morgan, Elise F; Gerstenfeld, Louis C; Tornetta, Paul

2018-03-01

Radiographic Union Score for Tibia (RUST) and modified RUST (mRUST) are radiographic tools for quantitatively evaluating fracture healing using a cortical scoring system. This tool has high intra-class correlation coefficients (ICCs); however, little evidence has evaluated the scores against the physical properties of bone healing. Closed, stabilized fractures were made in the femora of C3H/HeJ male mice (8-12 week-old) of two dietary groups: A control and a phosphate restricted diet group. Micro-computed tomography (µCT) and torsion testing were carried out at post-operative days (POD) 14, 21, 35, and 42 (n = 10-16) per group time-point. Anteroposterior and lateral radiographic views were constructed from the µCT scans and scored by five raters. The raters also indicated if the fracture were healed. ICCs were 0.71 (mRUST) and 0.63 (RUST). Both RUST scores were positively correlated with callus bone mineral density (BMD) (r = 0.85 and 0.80, p < 0.001) and bone volume fraction (BV/TV) (r = 0.86 and 0.80, p < 0.001). Both RUST scores positively correlated with callus strength (r = 0.35 and 0.26, p < 0.012) and rigidity (r = 0.50 and 0.39, p < 0.001). Radiographically healed calluses had a mRUST ≥13 and a RUST ≥10 and had excellent relationship to structural and biomechanical metrics. Effect of delayed healing due to phosphate dietary restrictions was found at later time points with all mechanical properties (p < 0.011), however no differences found in the RUST scores (p > 0.318). Clinical relevance of this study is both RUST scores showed high correlation to physical properties of healing and generally distinguished healed vs. non-healed fractures. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:945-953, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Osthole Promotes Endochondral Ossification and Accelerates Fracture Healing in Mice.

PubMed

Zhang, Zhongrong; Leung, Wing Nang; Li, Gang; Lai, Yau Ming; Chan, Chun Wai

2016-12-01

Osthole has been found to restore bone mass in preclinical osteoporotic models. In the present study, we investigated the effects of osthole on bone fracture repair in mice. Adult C57BL/6 mice were subjected to transverse femoral fractures and administrated orally with 20 mg/kg osthole and vehicle solvent daily from week 1 post-operation. Fracture callus were analyzed by plain radiography, micro-computed tomography, histology, molecular imaging and immunohistochemistry and tartrate-resistant acid phosphatase staining. Results demonstrated that osthole treatment enhanced removal of cartilage and bony union during reparative stage without significant interfering on remodeling process. In vivo molecular imaging showed bone formation rate of the treatment group was almost twofold of control group at week 2 post-operation. Osthole augmented the expression of alkaline phosphatase and collagen type X in hypertrophic chondrocytes as well as expression of bone morphogenetic protein-2, osteocalcin and alkaline phosphatase in osteoblastic cells, indicating it promoted mineralization of hypertrophic cartilage and woven bone growth simultaneously during endochondral healing. In summary, osthole promotes endochondral ossification via upregulation of maturation osteogenic marker genes in chondrocytes and subsequently accelerates fracture repair and bony fusion.

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

[Treatment of proximal ulna and olecranon fractures by reconstruction plate combined with tension band wiring].

PubMed

Teng, Lin; Zhong, Gang; Xiao, Cong; Liu, Gang; Xiang, Zhou; Cen, Shiqiang; Huang, Fuguo

2011-01-01

OBJECTIVE To review the efficacy of reconstruction plate combined with tension band wiring for treating proximal ulna and olecranon fractures. Between November 2004 and September 2009, 10 patients with proximal ulna and olecranon fractures were treated by reconstruction plate combined with tension band wiring. There were 6 males and 4 females with an average age of 45.3 years (range, 21-75 years). Five fractures were caused by traffic accident, 2 by falling from height, 2 by tumbling, and 1 by a machine strangulation. The locations were the left side and the right side in 5 cases respectively. One case was open fracture (Gustilo II) and the other 9 were closed fractures. Olecranon fractures included 4 cases of traverse fractures and 6 cases of comminuted fractures, and proximal ulna fractures included 6 cases of comminuted fractures and 4 cases of oblique fractures. The combined fractures included 6 radial head fractures, 4 coronoid process fractures, 2 proximal humerus fractures, and 3 scapula fractures; other injury included 1 elbow dislocation and 1 shoulder dislocation. Two patients had secondary operation; the other 8 patients received the primary operations and the time from injury to operation varied from 7 days to 20 days, with an average of 11 days. One case had infection at the incision 1 week after operation, and recovered after 2 months of antibiotics and debridement; incisions healed by first intention in other 9 patients. All patients were followed up 12-64 months (mean, 40.5 months). The X-ray films showed that fracture healing was achieved at 10-24 weeks (mean, 12 weeks). There was no ulnar nerve symptom in all cases. Heterotopic ossification occurred in 1 case at 2 months and stiffness of the elbow in 1 case at 3 months after operation; they were both cured after symptomatic treatment. Proximal migration of Kirschner wires was found in 1 case at 6 months after operation, whose implants were taken out at 9 months after the first operation because fracture had healed. At last follow-up, the flexion and extension are of the elbow averaged 92.8 degrees (range, 23-130 degrees), and the arc of forearm rotation averaged 124.4 degrees (range, 42-175 degrees). According to the American Hospital for Special Surgery (HSS) evaluation method, the results were classified as excellent in 6 cases, good in 2, fair in 1, and poor in 1. Treating proximal ulna and olecranon fractures by reconstruction plate combined with tension band wiring allows patients to do postoperative exercise early and could effectively avoid complications.

Laboratory Evidence of Strength Recovery of Healed Faults

NASA Astrophysics Data System (ADS)

Masuda, K.

2015-12-01

Fault zones consist of a fault core and a surrounding damage zone. Fault zones are typically characterized by the presence of many healed surfaces, the strength of which is unknown. If a healed fault recovers its strength such that its cohesion is equal to or greater than that of the host rock, repeated cycles of fracture and healing may be one mechanism producing wide fault zones. I present laboratory evidence supporting the strength recovery of healed fault surface, obtained by AE monitoring, strain measurements and X-ray CT techniques. The loading experiment was performed with a specimen collected from an exhumed fault zone. Healed surfaces of the rock sample were interpreted to be parallel to slip surfaces. The specimen was a cylinder with 50 mm diameter and 100 mm long. The long axis of the specimen was inclined with respect to the orientation of the healed surfaces. The compression test used a constant loading rate under 50 MPa of confining pressure. Macroscopic failure occurred when the applied differential stress reached 439 MPa. The macro-fracture surface created during the experiment was very close to the preexisting plane. The AE hypocenters closely match the locations of the preexisting healed surface and the new fault plane. The experiment also revealed details of the initial stage of fault development. The new fault zone developed near, but not precisely on the preexisting healed fault plane. An area of heterogeneous structure where stress appears to have concentrated, was where the AEs began, and it was also where the fracture started. This means that the healed surface was not a weak surface and that healing strengthened the fault such that its cohesion was equal to or greater than that of the intact host rock. These results suggest that repeated cycles of fracture and healing may be the main mechanism creating wide fault zones with multiple fault cores and damage zones.

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

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.

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.

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.

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.

Effects of enviromental temperature and femoral fracture on wound healing in rats.

PubMed

Crowley, L V; Seifter, E; Kriss, P; Rettura, G; Nakao, K; Levenson, S M

1977-06-01

Femoral fracture, unilateral and bilateral, impaired the healing of dorsal skin incisions and formation of reparative granulation tissue in subcutaneously implanted polyvinyl alcohol sponges judged histologically and by breaking strengths and hydroxyproline contents, respectively, 1 week after injury in pair-fed rats kept at 22 degrees C. When rats were transferred to a room at 30 degrees C immediately after skin incision and sponge implants, with or without unilateral fracture, no differences in healing were observed between the two groups. Rats with skin incision, sponge implants, and either femoral fracture or sham-fracture excreted more urinary nitrogen than preoperatively when kept at 22 degrees. Counterpart groups transferred to a 30 degrees room right after operation excreted less urinary nitrogen than preoperatively, but because of lower food intakes postoperatively, the ratio of urinary nitrogen to food intake nitrogen was increased. With equivalent food intakes, pair-fed rats with fracture kept at 22 degrees postoperatively lost more weight and excreted more nitrogen than corresponding rats transfered to a 30 degrees room.

Complications of ankle fracture in patients with diabetes.

PubMed

Chaudhary, Saad B; Liporace, Frank A; Gandhi, Ankur; Donley, Brian G; Pinzur, Michael S; Lin, Sheldon S

2008-03-01

Ankle fractures in patients with diabetes mellitus have long been recognized as a challenge to practicing clinicians. Complications of impaired wound healing, infection, malunion, delayed union, nonunion, and Charcot arthropathy are prevalent in this patient population. Controversy exists as to whether diabetic ankle fractures are best treated noninvasively or by open reduction and internal fixation. Patients with diabetes are at significant risk for soft-tissue complications. In addition, diabetic ankle fractures heal, but significant delays in bone healing exist. Also, Charcot ankle arthropathy occurs more commonly in patients who were initially undiagnosed and had a delay in immobilization and in patients treated nonsurgically for displaced ankle fractures. Several techniques have been described to minimize complications associated with diabetic ankle fractures (eg, rigid external fixation, use of Kirschner wires or Steinmann pins to increase rigidity). Regardless of the specifics of treatment, adherence to the basic principles of preoperative planning, meticulous soft-tissue management, and attention to stable, rigid fixation with prolonged, protected immobilization are paramount in minimizing problems and yielding good functional outcomes.

Detecting the activation of a self-healing mechanism in concrete by acoustic emission and digital image correlation.

PubMed

Tsangouri, E; Aggelis, D G; Van Tittelboom, K; De Belie, N; Van Hemelrijck, D

2013-01-01

Autonomous crack healing in concrete is obtained when encapsulated healing agent is embedded into the material. Cracking damage in concrete elements ruptures the capsules and activates the healing process by healing agent release. Previously, the strength and stiffness recovery as well as the sealing efficiency after autonomous crack repair was well established. However, the mechanisms that trigger capsule breakage remain unknown. In parallel, the conditions under which the crack interacts with embedded capsules stay black-box. In this research, an experimental approach implementing an advanced optical and acoustic method sets up scopes to monitor and justify the crack formation and capsule breakage of concrete samples tested under three-point bending. Digital Image Correlation was used to visualize the crack opening. The optical information was the basis for an extensive and analytical study of the damage by Acoustic Emission analysis. The influence of embedding capsules on the concrete fracture process, the location of capsule damage, and the differentiation between emissions due to capsule rupture and crack formation are presented in this research. A profound observation of the capsules performance provides a clear view of the healing activation process.

Detecting the Activation of a Self-Healing Mechanism in Concrete by Acoustic Emission and Digital Image Correlation

PubMed Central

Tsangouri, E.; Aggelis, D. G.; Van Tittelboom, K.; De Belie, N.; Van Hemelrijck, D.

2013-01-01

Autonomous crack healing in concrete is obtained when encapsulated healing agent is embedded into the material. Cracking damage in concrete elements ruptures the capsules and activates the healing process by healing agent release. Previously, the strength and stiffness recovery as well as the sealing efficiency after autonomous crack repair was well established. However, the mechanisms that trigger capsule breakage remain unknown. In parallel, the conditions under which the crack interacts with embedded capsules stay black-box. In this research, an experimental approach implementing an advanced optical and acoustic method sets up scopes to monitor and justify the crack formation and capsule breakage of concrete samples tested under three-point bending. Digital Image Correlation was used to visualize the crack opening. The optical information was the basis for an extensive and analytical study of the damage by Acoustic Emission analysis. The influence of embedding capsules on the concrete fracture process, the location of capsule damage, and the differentiation between emissions due to capsule rupture and crack formation are presented in this research. A profound observation of the capsules performance provides a clear view of the healing activation process. PMID:24381518

Influence of 1800 MHz GSM-like electromagnetic radiation exposure on fracture healing.

PubMed

Aslan, Ahmet; Kırdemır, Vecihi; Kocak, Ahmet; Atay, Tolga; Baydar, Metin Lütfi; Özerdemoglu, Remzi Arif; Aydogan, Nevres Hürriyet

2014-02-01

In this study, we aimed to investigate whether 1800 MHz frequency electromagnetic radiation (EMR) has an effect on bone healing. A total of 30 Wistar albino rats were divided into two equal groups. Fractures were created in the right tibias of all rats; next, intramedullary fixations with K-wire were performed. A control group (Group I) was kept under the same experimental conditions except without EMR exposure. Rats in Group II were exposed to an 1800 MHz frequency EMR for 30 min a day for 5 days a week. Next, radiological, mechanical, and histological examinations were performed to evaluate tibial fracture healing. Radiological, histological and mechanical scores were not significantly different between groups (respectively, p = 0.114, p = 0.184 and p = 0.083), and all of these scores were lower than those of the controls. EMR at 1800 MHz frequency emitted from cellular phones has no effect on bone fracture healing. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

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.

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.

Cervical Fracture With Transient Tetraplegia in a Youth Football Player: Case Report and Review of the Literature

PubMed Central

Molinari, Robert; Molinari, William J

2010-01-01

Background/Objective: Serious cervical spinal injuries in organized youth football are rare. Cervical fracture with neurologic injury is rarely reported in organized youth football players with no pre-existing risk fractures for transient tetraplegia. Methods: Case report and literature review. Results: After being improperly tackled by an opponent of significantly larger body size, a player sustained a C7 posterior cervical fracture with transient tetraplegia. He was immobilized in a cervical collar and sent to a level 1 trauma center for evaluation. Initial examination showed bilateral paresthesia of the limbs with normal motor function (ASIA D). Initial radiographs of the cervical spine showed a displaced extension-compression fracture of the C7 spinous process. Magnetic resonance imaging of the cervical spine showed edema in the spinal cord in the region of the injury along with significant posterior injury. Imaging studies showed normal volumetric measurements of the spinal canal and no pre-existing risk factors for spinal stenosis or spinal cord injury. Radiographs showed that cervical fracture was healed at 9-month follow-up examination. At 1-year follow-up, the patient was asymptomatic. Radiographs showed healed fracture with no residual instability and full range of cervical spine motion on flexion–extension views. Conclusions: This case underscores the potential for serious cervical spinal injuries in organized youth sports when players are physically overmatched, and improper tackling technique is used. PMID:20486536

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.

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.

Individual risk factors for deep infection and compromised fracture healing after intramedullary nailing of tibial shaft fractures: a single centre experience of 480 patients.

PubMed

Metsemakers, W-J; Handojo, K; Reynders, P; Sermon, A; Vanderschot, P; Nijs, S

2015-04-01

Despite modern advances in the treatment of tibial shaft fractures, complications including nonunion, malunion, and infection remain relatively frequent. A better understanding of these injuries and its complications could lead to prevention rather than treatment strategies. A retrospective study was performed to identify risk factors for deep infection and compromised fracture healing after intramedullary nailing (IMN) of tibial shaft fractures. Between January 2000 and January 2012, 480 consecutive patients with 486 tibial shaft fractures were enrolled in the study. Statistical analysis was performed to determine predictors of deep infection and compromised fracture healing. Compromised fracture healing was subdivided in delayed union and nonunion. The following independent variables were selected for analysis: age, sex, smoking, obesity, diabetes, American Society of Anaesthesiologists (ASA) classification, polytrauma, fracture type, open fractures, Gustilo type, primary external fixation (EF), time to nailing (TTN) and reaming. As primary statistical evaluation we performed a univariate analysis, followed by a multiple logistic regression model. Univariate regression analysis revealed similar risk factors for delayed union and nonunion, including fracture type, open fractures and Gustilo type. Factors affecting the occurrence of deep infection in this model were primary EF, a prolonged TTN, open fractures and Gustilo type. Multiple logistic regression analysis revealed polytrauma as the single risk factor for nonunion. With respect to delayed union, no risk factors could be identified. In the same statistical model, deep infection was correlated with primary EF. The purpose of this study was to evaluate risk factors of poor outcome after IMN of tibial shaft fractures. The univariate regression analysis showed that the nature of complications after tibial shaft nailing could be multifactorial. This was not confirmed in a multiple logistic regression model, which only revealed polytrauma and primary EF as risk factors for nonunion and deep infection, respectively. Future strategies should focus on prevention in high-risk populations such as polytrauma patients treated with EF. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fundamental Solution For The Self-healing Fracture Pulse

NASA Astrophysics Data System (ADS)

Nielsen, S.; Madariaga, R.

We find the analytical solution for a fundamental fracture mode in the form of a self- similar, self-healing pulse. The existence of such a fracture mode was strongly sug- gested by recent numerical findings but, to our knwledge, no formal proof had been proposed up to date. We present a two dimensional, anti-plane solution for fixed rup- ture and healing velocities, that satisfies both wave equation and stress conditions; we argue that such a solution is plausible even in the absence of rate-weakening in the friction, as an alternative to the classic crack solution. In practice, the impulsive mode rather than the expanding crack mode is selected depending on details of fracture initiation, and is therafter self-maintained. We discuss stress concentration, fracture energy, rupture velocity and compare them to the case of a crack. The analytical study is complemented by various numerical examples and comparisons. On more general grounds, we argue that an infinity of marginally stable fracture modes may exist other than the crack solution or the impulseive fracture described here.

[Surgical treatment of tibial nonunion after wounding by high velocity missile and external fixators: a case report].

PubMed

Golubović, Ivan; Vukašinović, Zoran; Stojiljković, Predrag; Golubović, Zoran; Stojiljković, Danilo; Radovanović, Zoran; Ilić, Nenad; Najman, Stevo; Višnjić, Aleksandar; Arsić, Stojanka

2012-01-01

The missiles of modern firearms can cause severe fractures of the extremity. High velocity missile fractures of the tibia are characterized by massive tissue destruction and primary contamination with polymorphic bacteria. Treatment of these fractures is often complicated by delayed healing, poor position healing, nonhealing and bone tissue infection. We present the management of tibial nonunion after wounding by high velocity missile and primary treatment by external fixation in a 25-year-old patient. The patient was primarily treated with external fixation and reconstructive operations of the soft tissue without union of the fracture. Seven months after injury we placed a compression-distraction external fixator type Mitkovic and started with compression and distraction in the fracture focus after osteotomy of the fibula and autospongioplasty. We recorded satisfactory fracture healing and good functional outcome. Contamination and devitalization of the soft-tissue envelope increase the risk of infection and nonunion in fractures after wounding by high velocity missile. The use of the compression-distraction external fixator type Mitkovic may be an effective method in nonunions of the tibia after this kind of injury.

Unveiling the molecular mechanism of self-healing in a telechelic, supramolecular polymer network

PubMed Central

Yan, Tingzi; Schröter, Klaus; Herbst, Florian; Binder, Wolfgang H.; Thurn-Albrecht, Thomas

2016-01-01

Reversible polymeric networks can show self-healing properties due to their ability to reassemble after application of stress and fracture, but typically the relation between equilibrium molecular dynamics and self-healing kinetics has been difficult to disentangle. Here we present a well-characterized, self-assembled bulk network based on supramolecular assemblies, that allows a clear distinction between chain dynamics and network relaxation. Small angle x-ray scattering and rheological measurements provide evidence for a structurally well-defined, dense network of interconnected aggregates giving mechanical strength to the material. Different from a covalent network, the dynamic character of the supramolecular bonds enables macroscopic flow on a longer time scale and the establishment of an equilibrium structure. A combination of linear and nonlinear rheological measurements clearly identifies the terminal relaxation process as being responsible for the process of self-healing. PMID:27581380

Fractures of the Fifth Metatarsal

MedlinePlus

... overlooked when they occur with an ankle sprain. Jones fracture. Jones fractures occur in a small area of the ... therefore more prone to difficulties in healing. A Jones fracture can be either a stress fracture (a ...

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.

Fractures of the proximal fifth metatarsal: percutaneous bicortical fixation.

PubMed

Mahajan, Vivek; Chung, Hyun Wook; Suh, Jin Soo

2011-06-01

Displaced intraarticular zone I and displaced zone II fractures of the proximal fifth metatarsal bone are frequently complicated by delayed nonunion due to a vascular watershed. Many complications have been reported with the commonly used intramedullary screw fixation for these fractures. The optimal surgical procedure for these fractures has not been determined. All these observations led us to evaluate the effectiveness of percutaneous bicortical screw fixation for treating these fractures. Twenty-three fractures were operatively treated by bicortical screw fixation. All the fractures were evaluated both clinically and radiologically for the healing. All the patients were followed at 2 or 3 week intervals till fracture union. The patients were followed for an average of 22.5 months. Twenty-three fractures healed uneventfully following bicortical fixation, with a mean healing time of 6.3 weeks (range, 4 to 10 weeks). The average American Orthopaedic Foot & Ankle Society (AOFAS) score was 94 (range, 90 to 99). All the patients reported no pain at rest or during athletic activity. We removed the implant in all cases at a mean of 23.2 weeks (range, 18 to 32 weeks). There was no refracture in any of our cases. The current study shows the effectiveness of bicortical screw fixation for displaced intraarticular zone I fractures and displaced zone II fractures. We recommend it as one of the useful techniques for fixation of displaced zone I and II fractures.

Fracture healing in a magma: An experimental approach and implications for volcanic seismicity and degassing

NASA Astrophysics Data System (ADS)

Yoshimura, Shumpei; Nakamura, Michihiko

2010-09-01

The healing of magmatic fractures is considered essential to repetitive seismicity and the closure of degassing paths during emplacement of lavas. To estimate the healing time of magmatic fractures, we performed healing experiments on rhyolitic melts at 850°-1000°C and 1.6-3.2 MPa for 0.5-94 h. Two cylindrical obsidian cores were juxtaposed on surfaces prepared by cutting the cores both with and without polishing. These were annealed in an open-system cell. The contact interface became coherent and finally disappeared. The water content across the contact initially decreased toward the interface via diffusive dehydration, but later homogenized. This change was interpreted to reflect atomic-scale closure of the interface, probably by chemical bonding. We defined this closure interval as microscopic healing time and determined this by fitting the measured profiles with a diffusion model. The microscopic healing time was strongly dependent on temperature and roughness of the interface and was, for the nonpolished interfaces, 67-74, 4.0-4.9, and 0.36-0.38 h at 850°, 900°, and 950°C, respectively, whereas for the polished examples it was 1-3 and 0.5-0.6 h at 850° and 900°C, respectively. This microscopic healing time is consistent with the period of actual seismicity and is prolonged sufficiently to permit the formation of millimeter-thick bubble-free obsidian layers along fractures in vesicular lavas through bubble resorption due to diffusive degassing.

Effects of fracture and crack healing in sI methane and sII methane-ethane gas hydrate

NASA Astrophysics Data System (ADS)

Helgerud, M. B.; Waite, W. F.; Stern, L. A.; Kirby, S. H.

2005-12-01

Cracking within gas hydrate-bearing sediment can occur in the field at core-scales, due to unloading as material is brought to the surface during conventional coring, and at reservoir scales if the formation is fractured prior to production. Cracking can weaken hydrate-bearing sediment, but can also provide additional surface area for dissociation and permeability pathways for enhanced gas and fluid flow. In pulse-transmission wave speed measurements, we observe cracking in laboratory-formed pure sI methane and sII methane-ethane hydrates when samples are axially unloaded while being held under gas pressure to maintain hydrate stability. Cracking events are inferred from repeated, sharp decreases in shear wave speed occurring concurrently with abrupt increases in sample length. We also visually observe cracks in the solid samples after their recovery from the apparatus following each experiment. Following a cracking event, we observe evidence of rapid crack healing, or annealing expressed as nearly complete recovery of the shear wave speed within approximately 20 minutes. Gas hydrate recrystallization, grain growth, and annealing have also been observed in optical cell experiments and SEM imagery over a similar time frame. In a recovered hydrate-bearing core that is repressurized for storage or experimentation, rapid crack healing and recrystallization can partly restore lost mechanical strength and raise wave speeds. In a fractured portion of a hydrate-bearing reservoir, the rapid healing process can close permeable cracks and reduce the surface area available for dissociation.

Magma fracturing and degassing associated with obsidian formation: The explosive–effusive transition

USGS Publications Warehouse

Cabrera, Agustin; Weinberg, Roberto; Wright, Heather M.

2015-01-01

This paper explores the role of melt fracturing in degassing rhyolitic volcanic systems. The Monte Pilato-Rocche Rosse eruptions in Italy evolved from explosive to effusive in style, and H2O content in quenched glasses changed over time from relatively H2O-rich (~ 0.90 wt.%) to H2O-poor dense obsidian (~ 0.10–0.20 wt.%). In addition, healed fractures have been recorded in all different eruptive materials, from the glass of early-erupted tube pumice and rinds of breadcrusted obsidian pyroclasts, to the glass of late-erupted dense obsidian pyroclasts, and throughout the final effusive Rocche Rosse lava flow. These rocks show multiple fault sets, some with crenulated fault planes indicating resumption of viscous flow after faulting, complex obsidian breccias with evidence for post-brecciation folding and stretching, and centimetre- to metre-thick tuffisite preserved in pyroclasts and lava, representing collapsed foam due to fracturing of vesicle walls. These microstructural observations indicate that multiple fracturing and healing events occurred during both explosive and effusive eruptions. H2O content in glass decreases by as much as 0.14 wt.% towards healed fractures/faults and decreases in stretched obsidian breccias towards regions of intense brecciation. A drop in pressure and/or increase in temperature along fractures caused diffusive H2O migration through melt towards fracture surfaces. Repetitive and pervasive fracturing and healing thereby create conditions for diffusive H2O loss into fractures and subsequent escape through permeable paths. This type of progressive magma degassing provides a potential mechanism to explain the formation of dense obsidian and the evolution from explosive to effusive eruption style.

Application of biodegradable plates for treating pediatric mandibular fractures.

PubMed

An, Jingang; Jia, Pengcheng; Zhang, Yi; Gong, Xi; Han, Xiaodong; He, Yang

2015-05-01

We assessed the clinical results of a biodegradable plate system for the internal fixation of mandibular fractures in children, and observed the imaging features of fracture healing and bone changes around the biodegradable plates and screws during follow-up. We enrolled 39 patients (22 male, 17 female, average age 4 years 10 months) with different mandibular fractures. We used 2.0-mm resorbable plates to repair the fractures. Postoperative follow-up ranged from 6 months to 5 years; average follow-up was 1 year 2 months. The outcome measures identified and assessed included facial symmetry, mouth opening, occlusal relationship, infection, nonunion, malunion, and plate dehiscence. We fixed 42 fractures with 43 resorbable plates; the fracture site of one patient (aged 11 years 3 months) was fixed with two plates. Two patients developed small fistulas at the intraoral incision 2 months after surgery; the fistulas healed after 1 month without special treatment. In the other patients, the incision healed well, there was facial symmetry, mouth opening was >35 mm, and occlusion was good. Follow-up computed tomography examination data were available for 20 cases, and revealed different degrees of radiolucency indicating that osteolysis had occurred. Radiolucency was observed around the resorbable plates 1 month after the surgery. The extent and depth of the radiolucent region were obvious within 1 year of surgery. In the second year, there were obvious repairs, with the bony defect areas becoming shallower. After 2 years, the bony defect areas had almost disappeared. Biodegradable fixation devices are safe and efficient for treating pediatric mandibular fractures. Osteolysis commonly follows biodegradable fixation of pediatric mandibular fractures, and has no adverse effect on fracture healing. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

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.

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.

The role of the titanium functionally dynamic bridging plate for the treatment of the atrophic mandible fractures.

PubMed

Hachleitner, Johannes; Enzinger, Simon; Brandtner, Christian; Gaggl, Alexander

2014-07-01

The role of the titanium functionally dynamic bridging plate (TFDBP) in the fracture treatment of the severely atrophic mandible was assessed retrospectively. In 28 consecutive patients with fractures of a severely atrophic mandible fixation was carried out with TFDBPs. Twenty-one patients with 27 fractures were included in the study and then followed up for complications and the progress of fracture healing for 17 months postoperatively on average. There was only one case that required plate removal. All patients showed bone healing 3 months after surgery. The mental nerve sensation improved in 12 out of 23 fractures that had presented with nerve function disturbance. Every patient who had dentures prior to sustaining the fracture was able to return to denture wearing 3 weeks after surgery. No major complications occurred. A high proportion of bone healing with a low complication rate was observed with the use of TFDBPs in the treatment of severely atrophic mandible fractures. The TFDBP is an excellent alternative to conventional plating of the severely atrophic mandible. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Rickets or abuse? A histologic comparison of rickets and child abuse-related fractures.

PubMed

Kepron, Charis; Pollanen, Michael S

2015-03-01

The bone changes of vitamin D deficiency rickets have been invoked as an alternate explanation for child-abuse related fractures identified through medical imaging. The lack of modern histopathologic comparisons between these two entities limits the abilities of the forensic pathologist to address this differential diagnosis, both in their autopsy reports and on the witness stand. We report a comparison of the histologic appearance of the bones in a two year old child with vitamin D deficiency rickets with fractures occurring in three young children with child abuse. In the case of rickets, there was marked architectural disorganization of endochondral ossification at the costochondral junctions and growth plates of long bones. The child abuse-related fractures showed osteochondral callus at different stages of healing, either centered on a discrete fracture line or at metaphyses (e.g. classical metaphyseal lesions). In many instances, the healing fractures disrupted the line of endochondral ossification. In none of the child abuse-related fractures was there any similarity to the histologic appearance of rickets. The maturation disturbance in the growth plate that occurs in rickets is a distinctive entity that cannot be confused histologically with healing fractures, including the classical metaphyseal lesion.

Combining Through-Thickness Reinforcement and Self-Healing for Improved Damage Tolerance and Durability of Composites

NASA Technical Reports Server (NTRS)

O'Brien, T. Kevin; Czabaj, Michael W.; Hinkley, Jeffrey A.; Tsampas, Spiros; Greenhalgh, Emile S.; McCombe, Gregory; Bond, Ian P.; Trask, Richard

2013-01-01

A study was undertaken to develop a prototype method for adding through-thickness hollow glass tubes infused with uncured resin and hardener in a carbon Z-pin through-thickness reinforcement field embedded in a composite laminate. Two types of tube insertion techniques were attempted in an effort to ensure the glass tubes survived the panel manufacturing process. A self-healing resin was chosen with a very low viscosity, two component, liquid epoxy resin system designed to be mixed at a 2-to-1 ratio of epoxy to hardener. IM7/8552 carbon epoxy double cantilever beam (DCB) specimens were cut from the hybrid Z-pin and glass tube reinforced panels and tested. In-situ injection of resin and hardener directly into glass tubes, in a staggered pattern to allow for 2-to-1 ratio mixing, resulted in partial healing of the fracture plane, but only if the injection was performed while the specimen was held at maximum load after initial fracture. Hence, there is some potential for healing delamination via resin and hardener delivered through a network of through-thickness glass tubes, but only if the tubes are connected to a reservoir where additional material may be injected as needed.

Osteotomy models - the current status on pain scoring and management in small rodents.

PubMed

Lang, Annemarie; Schulz, Anja; Ellinghaus, Agnes; Schmidt-Bleek, Katharina

2016-12-01

Fracture healing is a complex regeneration process which produces new bone tissue without scar formation. However, fracture healing disorders occur in approximately 10% of human patients and cause severe pain and reduced quality of life. Recently, the development of more standardized, sophisticated and commercially available osteosynthesis techniques reflecting clinical approaches has increased the use of small rodents such as rats and mice in bone healing research dramatically. Nevertheless, there is no standard for pain assessment, especially in these species, and consequently limited information regarding the welfare aspects of osteotomy models. Moreover, the selection of analgesics is restricted for osteotomy models since non-steroidal anti-inflammatory drugs (NSAIDs) are known to affect the initial, inflammatory phase of bone healing. Therefore, opioids such as buprenorphine and tramadol are often used. However, dosage data in the literature are varied. Within this review, we clarify the background of osteotomy models, explain the current status and challenges of animal welfare assessment, and provide an example score sheet including model specific parameters. Furthermore, we summarize current refinement options and present a brief outlook on further 3R research. © The Author(s) 2016.

Quantifying mechanical properties in a murine fracture healing system using inverse modeling: preliminary work

NASA Astrophysics Data System (ADS)

Miga, Michael I.; Weis, Jared A.; Granero-Molto, Froilan; Spagnoli, Anna

2010-03-01

Understanding bone remodeling and mechanical property characteristics is important for assessing treatments to accelerate healing or in developing diagnostics to evaluate successful return to function. The murine system whereby mid-diaphaseal tibia fractures are imparted on the subject and fracture healing is assessed at different time points and under different therapeutic conditions is a particularly useful model to study. In this work, a novel inverse geometric nonlinear elasticity modeling framework is proposed that can reconstruct multiple mechanical properties from uniaxial testing data. To test this framework, the Lame' constants were reconstructed within the context of a murine cohort (n=6) where there were no differences in treatment post tibia fracture except that half of the mice were allowed to heal 4 days longer (10 day, and 14 day healing time point, respectively). The properties reconstructed were a shear modulus of G=511.2 +/- 295.6 kPa, and 833.3+/- 352.3 kPa for the 10 day, and 14 day time points respectively. The second Lame' constant reconstructed at λ=1002.9 +/-42.9 kPa, and 14893.7 +/- 863.3 kPa for the 10 day, and 14 day time points respectively. An unpaired Student t-test was used to test for statistically significant differences among the groups. While the shear modulus did not meet our criteria for significance, the second Lame' constant did at a value p<0.0001. Traditional metrics that are commonly used within the bone fracture healing research community were not found to be statistically significant.

Likelihood of surgery in isolated pediatric fifth metatarsal fractures.

PubMed

Mahan, Susan T; Hoellwarth, Jason S; Spencer, Samantha A; Kramer, Dennis E; Hedequist, Daniel J; Kasser, James R

2015-01-01

Fractures of the fifth metatarsal bone are common and surgery is uncommon. The "Jones" fracture is known to be in a watershed region that often leads to compromised healing, however, a "true Jones" fracture can be difficult to determine, and its impact on healing in pediatric patients is not well described. The purpose of this study was to retrospectively assess patterns of fifth metatarsal fracture that led to surgical fixation in an attempt to predict the likelihood for surgery in these injuries. A retrospective review was performed on patients aged 18 and under who were treated for an isolated fifth metatarsal fracture from 2003 through 2010 at our pediatric hospital. Patient demographics, treatment, and complications were noted. Radiographs were reviewed for location of fracture and fracture displacement. Patients and fracture characteristics were then compared. A total of 238 fractures were included and 15 were treated surgically. Most surgical indications were failure to heal in a timely manner or refracture and all patients underwent a trial of nonoperative treatment. Jones criteria for fracture location were predictive of needing surgery (P<0.01) but confusing in the clinic setting. Fractures that occurred between 20 and 40 mm (or 25% to 50% of overall metatarsal length) from the proximal tip went on to surgery in 18.8% (6/32) of the time, whereas those that occurred between <20 mm had surgery in 4.9% (9/184). This was a statistically significant correlation (P=0.0157). Although fractures of the fifth metatarsal are common, need for surgery in these fractures is not. However, a region of this bone is known to have trouble healing, and it can be difficult to identify these "at-risk" fractures in the clinical setting. We found simple ruler measurement from the proximal tip of the fifth metatarsal to the fracture to help determine this "at-risk" group and found a significant difference in those patients with a fracture of <20 mm compared with those 20 to 40 mm from the tip; this can help guide treatment and counsel patients. Level 3.

Studying the effect of photodynamic therapy (PDT) to enhance healing of femur fractures using polarimetric second-harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Golaraei, Ahmad; Raja, Vaishnavi; Akens, Margarete K.; Wilson, Brian C.; Barzda, Virginijus

2017-07-01

Linear polarization-in, polarization-out second-harmonic generation microscopy was used to study the effect of Photodynamic therapy treatment on enhancing the healing of femur fracture by investigating the ultrastructure of collagen as a major component of bone matrix.

Therapeutic Ultrasound Bypasses Canonical Syndecan-4 Signaling to Activate Rac1*S⃞

PubMed Central

Mahoney, Claire M.; Morgan, Mark R.; Harrison, Andrew; Humphries, Martin J.; Bass, Mark D.

2009-01-01

The application of pulsed, low intensity ultrasound is emerging as a potent therapy for the treatment of complex bone fractures and tissue damage. Ultrasonic stimuli accelerate fracture healing by up to 40% and enhance tendon and ligament healing by promoting cell proliferation, migration, and matrix synthesis through an unresolved mechanism. Ultrasound treatment also induces closure of nonunion fractures, at a success rate (85% of cases) similar to that of surgical intervention (68-96%) while avoiding the complications associated with surgery. The regulation of cell adhesion necessary for wound healing depends on cooperative engagement of the extracellular matrix receptors, integrin and syndecan, as exemplified by the wound healing defects observed in syndecan- and integrin-knock-out mice. This report distinguishes the influence of ultrasound on signals downstream of the prototypic fibronectin receptors, α5β1 integrin and syndecan-4, which cooperate to regulate Rac1 and RhoA. Ultrasonic stimulation fails to activate integrins or induce cell spreading on poor, electrostatic ligands. By contrast, ultrasound treatment overcomes the necessity of engagement or expression of syndecan-4 during the process of focal adhesion formation, which normally requires simultaneous engagement of both receptors. Ultrasound exerts an influence downstream of syndecan-4 and PKCα to specifically activate Rac1, itself a critical regulator of tissue repair, and to a lesser extent RhoA. The ability of ultrasound to bypass syndecan-4 signaling, which is known to facilitate efficient tissue repair, explains the reduction in healing times observed in ultrasound-treated patients. By substituting for one of the key axes of adhesion-dependent signaling, ultrasound therapy has considerable potential as a clinical technique. PMID:19147498

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).

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

The second fracture of the same clavicle: prevalence and fracture configurations.

PubMed

Asavamongkolkul, Apichat; Harnroongroj, Thos; Suteeraporn, Wuttipon; Sudjai, Narumol; Harnroongroj, Thossart

2012-12-01

To study second fracture at the same clavicle including prevalence, fracture configurations related to malunion types of the first fracture, and healing. Between 2008 and 2011, the authors reviewed medical records and radiographs of the clavicles of patients who sustained acute clavicular fractures from motorcycle accident. Second fracture at the same clavicle and prevalence were studied. Malunion of the first fracture of the same clavicle were typed and configurations of the second fracture at the same clavicles were described related to type of the malunion. There were 552 clavicular fractures. Four cases of which sustained a second fracture at the same clavicles. Malunion of the first clavicular fracture of the four cases were typed: type I, extension, type II, flexion, and type III, bayonet. There were one, two, and one case of second clavicular fractures of the type I, II, and III clavicular malunion. The configuration of second clavicular fracture of the type I malunion clavicle is located at lateral fragment, inferior displacement, and dorsal angulation with dorsal cortex conminution. The type II malunion clavicle is located at lateral fragment with minimal displacement. For the type III malunion clavicle, the second fracture is located at medial fragment with mild inferior displacement and inferior angulation. The four cases of the second fractures of the same clavicles healed within two months without complication. The prevalence of second fracture at the same clacicles was 7.2:1000. The three types of the first fracture malunion were extension, flexion, and bayonet. The configuration of the second fracture at the same clavicles depends on malunion types of the first clavicular fracture. They healed without complication.

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

Exposure to 100% Oxygen Abolishes the Impairment of Fracture Healing after Thoracic Trauma

PubMed Central

Kemmler, Julia; Bindl, Ronny; McCook, Oscar; Wagner, Florian; Gröger, Michael; Wagner, Katja; Scheuerle, Angelika; Radermacher, Peter; Ignatius, Anita

2015-01-01

In polytrauma patients a thoracic trauma is one of the most critical injuries and an important trigger of post-traumatic inflammation. About 50% of patients with thoracic trauma are additionally affected by bone fractures. The risk for fracture malunion is considerably increased in such patients, the pathomechanisms being poorly understood. Thoracic trauma causes regional alveolar hypoxia and, subsequently, hypoxemia, which in turn triggers local and systemic inflammation. Therefore, we aimed to unravel the role of oxygen in impaired bone regeneration after thoracic trauma. We hypothesized that short-term breathing of 100% oxygen in the early post-traumatic phase ameliorates inflammation and improves bone regeneration. Mice underwent a femur osteotomy alone or combined with blunt chest trauma 100% oxygen was administered immediately after trauma for two separate 3 hour intervals. Arterial blood gas tensions, microcirculatory perfusion and oxygenation were assessed at 3, 9 and 24 hours after injury. Inflammatory cytokines and markers of oxidative/nitrosative stress were measured in plasma, lung and fracture hematoma. Bone healing was assessed on day 7, 14 and 21. Thoracic trauma induced pulmonary and systemic inflammation and impaired bone healing. Short-term exposure to 100% oxygen in the acute post-traumatic phase significantly attenuated systemic and local inflammatory responses and improved fracture healing without provoking toxic side effects, suggesting that hyperoxia could induce anti-inflammatory and pro-regenerative effects after severe injury. These results suggest that breathing of 100% oxygen in the acute post-traumatic phase might reduce the risk of poorly healing fractures in severely injured patients. PMID:26147725

Deferoxamine restores callus size, mineralization, and mechanical strength in fracture healing after radiotherapy.

PubMed

Donneys, Alexis; Ahsan, Salman; Perosky, Joseph E; Deshpande, Sagar S; Tchanque-Fossuo, Catherine N; Levi, Benjamin; Kozloff, Ken M; Buchman, Steven R

2013-05-01

Therapeutic augmentation of fracture-site angiogenesis with deferoxamine has proven to increase vascularity, callus size, and mineralization in long-bone fracture models. The authors posit that the addition of deferoxamine would enhance pathologic fracture healing in the setting of radiotherapy in a model where nonunions are the most common outcome. Thirty-five Sprague-Dawley rats were divided into three groups. Fracture, irradiated fracture, and irradiated fracture plus deferoxamine. The irradiated fracture and irradiated fracture plus deferoxamine groups received a human equivalent dose of radiotherapy [7 Gy/day for 5 days, (35 Gy)] 2 weeks before mandibular osteotomy and external fixation. The irradiated fracture plus deferoxamine group received injections of deferoxamine into the fracture callus after surgery. After a 40-day healing period, mandibles were dissected, clinically assessed for bony union, imaged with micro-computed tomography, and tension tested to failure. Compared with irradiated fractures, metrics of callus size, mineralization, and strength in deferoxamine-treated mandibles were significantly increased. These metrics were restored to a level demonstrating no statistical difference from control fractures. In addition, the authors observed an increased rate of achieving bony unions in the irradiated fracture plus deferoxamine-treated group when compared with irradiated fracture (67 percent and 20 percent, respectively). The authors' data demonstrate nearly total restoration of callus size, mineralization, and biomechanical strength, and a threefold increase in the rate of union with the use of deferoxamine. The authors' results suggest that the administration of deferoxamine may have the potential for clinical translation as a new treatment paradigm for radiation-induced pathologic fractures.

Crack Extension and Possibility of Debonding in Encapsulation-Based Self-Healing Materials.

PubMed

Li, Wenting; Jiang, Zhengwu; Yang, Zhenghong

2017-05-27

The breakage of capsules upon crack propagation is crucial for achieving crack healing in encapsulation-based self-healing materials. A mesomechanical model was developed in this study to simulate the process of crack propagation in a matrix and the potential of debonding. The model used the extended finite element method (XFEM) combined with a cohesive zone model (CZM) in a two-dimensional (2D) configuration. The configuration consisted of an infinite matrix with an embedded crack and a capsule nearby, all subjected to a uniaxial remote tensile load. A parametric study was performed to investigate the effect of geometry, elastic parameters and fracture properties on the fracture response of the system. The results indicated that the effect of the capsule wall on the fracture behavior of the matrix is insignificant for t c / R c ≤ 0.05. The matrix strength influenced the ultimate crack length, while the Young's modulus ratio E c / E m only affected the rate of crack propagation. The potential for capsule breakage or debonding was dependent on the comparative strength between capsule and interface (S c /S int ), provided the crack could reach the capsule. The critical value of S c ,cr /S int,cr was obtained using this model for materials design.

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.

Basic principles of fracture treatment in children.

PubMed

Ömeroğlu, Hakan

2018-04-01

This review aims to summarize the basic treatment principles of fractures according to their types and general management principles of special conditions including physeal fractures, multiple fractures, open fractures, and pathologic fractures in children. Definition of the fracture is needed for better understanding the injury mechanism, planning a proper treatment strategy, and estimating the prognosis. As the healing process is less complicated, remodeling capacity is higher and non-union is rare, the fractures in children are commonly treated by non-surgical methods. Surgical treatment is preferred in children with multiple injuries, in open fractures, in some pathologic fractures, in fractures with coexisting vascular injuries, in fractures which have a history of failed initial conservative treatment and in fractures in which the conservative treatment has no/little value such as femur neck fractures, some physeal fractures, displaced extension and flexion type humerus supracondylar fractures, displaced humerus lateral condyle fractures, femur, tibia and forearm shaft fractures in older children and adolescents and unstable pelvis and acetabulum fractures. Most of the fractures in children can successfully be treated by non-surgical methods.

Effects of water-aging on self-healing dental composite containing microcapsules.

PubMed

Wu, Junling; Weir, Michael D; Melo, Mary Anne S; Strassler, Howard E; Xu, Hockin H K

2016-04-01

The objectives of this study were to develop a self-healing dental composite containing poly(urea-formaldehyde) (PUF) shells with triethylene glycol dimethacrylate (TEGDMA) and N,N-dihydroxyethyl-p-toluidine (DHEPT) as healing liquid, and to investigate the mechanical properties of the composite and its self-healing efficacy after water-aging for 6 months. PUF microspheres were synthesized encapsulating a TEGDMA-DHEPT healing liquid. Composite containing 30% of a resin matrix and 70% of glass fillers by mass was incorporated with 0%, 2.5%, 5%, 7.5% and 10% of microcapsules. A flexural test was used to measure flexural strength and elastic modulus. A single edge V-notched beam method was used to measure fracture toughness (KIC) and self-healing efficacy. Specimens were water-aged at 37 °C for 1 day to 6 months and then tested for self-healing. Fractured specimens were healed while being immersed in water to examine self-healing efficacy, in comparison with that in air. Incorporation of up to 7.5% of microcapsules into the resin composite achieved effective self-healing, without adverse effects on the virgin mechanical properties of the composite (p>0.1). An excellent self-healing efficacy of 64-77% recovery was obtained (mean±sd; n=6). Six months of water-aging did not decrease the self-healing efficacy compared to 1 day (p>0.1). Exposure to water did not decrease the healing efficacy, compared to that healed in air (p>0.1). A composite was developed with excellent self-healing efficacy even while being immersed in water. The self-healing efficacy did not decrease with increasing water-aging time for 6 months. The novel self-healing composite may be promising for dental applications to heal cracks, resist fracture, and increase the durability and longevity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of water-aging on self-healing dental composite containing microcapsules

PubMed Central

Wu, Junling; Weir, Michael D.; Melo, Mary Anne S.; Strassler, Howard E.; Xu, Hockin H. K.

2016-01-01

Objectives The objectives of this study were to develop a self-healing dental composite containing poly(urea-formaldehyde) (PUF) shells with triethylene glycol dimethacrylate (TEGDMA) and N,N-dihydroxyethyl-p-toluidine (DHEPT) as healing liquid, and to investigate the mechanical properties of the composite and its self-healing efficacy after water-aging for 6 months. Methods PUF microspheres were synthesized encapsulating a TEGDMA-DHEPT healing liquid. Composite containing 30% of a resin matrix and 70% of glass fillers by mass was incorporated with 0%, 2.5%, 5%, 7.5% and 10% of microcapsules. A flexural test was used to measure flexural strength and elastic modulus. A single edge V-notched beam method was used to measure fracture toughness (KIC) and self-healing efficacy. Specimens were water-aged at 37 °C for 1 d to 6 months and then tested for self-healing. Fractured specimens were healed while being immersed in water to examine self-healing efficacy, in comparison with that in air. Results Incorporation of up to 7.5% of microcapsules into the resin composite achieved effective self-healing, without adverse effects on the virgin mechanical properties of the composite (p > 0.1). An excellent self-healing efficacy of 64%–77% recovery was obtained (mean ± sd; n = 6). Six months of water-aging did not decrease the self-healing efficacy compared to 1 d (p > 0.1). Exposure to water did not decrease the healing efficacy, compared to that healed in air (p > 0.1). Conclusions A composite was developed with excellent self-healing efficacy even while being immersed in water. The self-healing efficacy did not decrease with increasing water-aging time for 6 months. Clinical significance The novel self-healing composite may be promising for dental applications to heal cracks, resist fracture, and increase the durability and longevity. PMID:26808158

Biomechanical concepts applicable to minimally invasive fracture repair in small animals.

PubMed

Chao, Peini; Lewis, Daniel D; Kowaleski, Michael P; Pozzi, Antonio

2012-09-01

Understanding the basic biomechanical principles of surgical stabilization of fractures is essential for developing an appropriate preoperative plan as well as making prudent intraoperative decisions. This article aims to provide basic biomechanical knowledge essential to the understanding of the complex interaction between the mechanics and biology of fracture healing. The type of healing and the outcome can be influenced by several mechanical factors, which depend on the interaction between bone and implant. The surgeon should understand the mechanical principles of fracture fixation and be able to choose the best type of fixation for each specific fracture. Copyright © 2012 Elsevier Inc. All rights reserved.

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

Analysis of bone healing in flail chest injury: do we need to fix both fractures per rib?

PubMed

Marasco, Silvana; Liew, Susan; Edwards, Elton; Varma, Dinesh; Summerhayes, Robyn

2014-09-01

Surgical rib fixation (SRF) for severe rib fracture injuries is generating increasing interest in the medical literature. It is well documented that poorly healed fractured ribs can lead to chronic pain, disability, and deformity. An unanswered question in SRF for flail chest injury is whether it is sufficient to fix one fracture per rib, on successive ribs, thus converting a flail chest injury into simple fractured ribs, or whether both ends of the floating segment of the chest wall should be fixed. This study aimed to analyze SRF in flail chest injury, assessing 3-month outcomes for nonfixed fractured rib ends in the flail segment. This is a retrospective review (2005-2013) of 60 consecutive patients who underwent SRF for flail chest injury admitted to the Alfred Hospital, Melbourne, Australia. Imaging by three-dimensional computed tomography (3D CT) of the chest at admission was compared with follow-up 3D CT at 3 months after injury. The 3-month CT scans were assessed for degree of healing and presence of residual deformity at the fracture fixation site. Follow-up CT was performed in 52 of the 60 patients. At 3 months after surgery, 86.5% of the patients had at least partial healing with good alignment and adequate fracture stabilization. Hardware failure was noted in five patients (9.6%) and occurred with the absorbable prostheses only. Six patients who had preoperative overlapping or displacement showed no improvement in deformity despite fixing the lateral fractures. Callus formation and bony bridging between adjacent ribs was often noted in the rib fractures not fixed (28 of 52 patients, 54%) This retrospective review of 3D CT chest at 3 months after rib fixation indicates that a philosophy of fixing only one fracture per rib in a flail segment does not avoid deformity and displacement, particularly in posterior rib fractures. Therapeutic study, level V; epidemiologic study, level V.

Transient gamma-secretase inhibition accelerates and enhances fracture repair likely via Notch signaling modulation

PubMed Central

Wang, Cuicui; Shen, Jie; Yukata, Kiminori; Inzana, Jason A.; O'Keefe, Regis J.; Awad, Hani A.; Hilton, Matthew J.

2014-01-01

Approximately 10% of skeletal fractures result in healing complications and non-union, while most fractures repair with appropriate stabilization and without pharmacologic intervention. It is the latter injuries that cannot be underestimated as the expenses associated with their treatment and subsequent lost productivity are predicted to increase to over $74 billion by 2015. During fracture repair, local mesenchymal stem/progenitor cells (MSCs) differentiate to form new cartilage and bone, reminiscent of events during skeletal development. We previously demonstrated that permanent loss of gamma-secretase activity and Notch signaling accelerates bone and cartilage formation from MSC progenitors during skeletal development, leading to pathologic acquisition of bone and depletion of bone marrow derived MSCs. Here, we investigated whether transient and systemic gamma-secretase and Notch inhibition is capable of accelerating and enhancing fracture repair by promoting controlled MSC differentiation near the fracture site. Our radiographic, microCT, histological, cell and molecular analyses reveal that single and intermittent gamma-secretase inhibitor (GSI) treatments significantly enhance cartilage and bone callus formation via the promotion of MSC differentiation, resulting in only a moderate reduction of local MSCs. Biomechanical testing further demonstrates that GSI treated fractures exhibit superior strength earlier in the healing process, with single dose GSI treated fractures exhibiting bone strength approaching that of un-fractured tibiae. These data further establish that transient inhibition of gamma-secretase activity and Notch signaling temporarily increases osteoclastogenesis and accelerates bone remodeling, which coupled with the effects on MSCs likely explains the accelerated and enhanced fracture repair. Therefore, we propose that the Notch pathway serves as an important therapeutic target during skeletal fracture repair. PMID:25527421

Application of 3D printed customized external fixator in fracture reduction.

PubMed

Qiao, Feng; Li, Dichen; Jin, Zhongmin; Gao, Yongchang; Zhou, Tao; He, Jinlong; Cheng, Li

2015-01-01

Long bone fracture is common in traumatic osteopathic patients. Good reduction is beneficial for bone healing, preventing the complications such as delayed union, nonunion, malunion, but is hard to achieve. Repeated attempts during the surgery would increase the operation time, cause new damage to the fracture site and excessive exposure to radiation. Robotic and navigation techniques can help improve the reduction accuracy, however, the high cost and complexity of operation have limited their clinical application. We combined 3D printing with computer-assisted reduction technique to develop a customised external fixator with the function of fracture reduction. The original CT data obtained by scanning the fracture was imported to computer for reconstructing and reducing the 3D image of the fracture, based on which the external fixator (named as Q-Fixator) was designed and then fabricated by 3D printing techniques. The fracture reduction and fixation was achieved by connecting the pins inserted in the bones with the customised Q-Fixator. Experiments were conducted on three fracture models to demonstrate the reduction results. Good reduction results were obtained on all three fractured bone models, with an average rotation of 1.21°(± 0.24), angulation of 1.84°(± 0.28), and lateral displacement of 2.22 mm(± 0.62). A novel customised external fixator for long bone fracture reduction was readily developed using 3D printing technique. The customised external fixator had the advantages of easy manipulation, accurate reduction, minimally invasion and experience-independence. Future application of the customised external fixator can be extended to include the fixation function with stress adjustment and potentially optimise the fracture healing process. Copyright © 2015 Elsevier Ltd. All rights reserved.

An animal model of co-existing sarcopenia and osteoporotic fracture in senescence accelerated mouse prone 8 (SAMP8).

PubMed

Zhang, Ning; Chow, Simon Kwoon Ho; Leung, Kwok Sui; Lee, Ho Hin; Cheung, Wing Hoi

2017-10-15

Sarcopenia and osteoporotic fracture are common aging-related musculoskeletal problems. Recent evidences report that osteoporotic fracture patients showed high prevalence of sarcopenia; however, current clinical practice basically does not consider sarcopenia in the treatment or rehabilitation of osteoporotic fracture. There is almost no report studying the relationship of the co-existing of sarcopenia and osteoporotic fracture healing. In this study, we validated aged senescence accelerated mouse prone 8 (SAMP8) and senescence accelerated mouse resistant 1 (SAMR1) as animal models of senile osteoporosis with/without sarcopenia. Bone mineral density (BMD) at the 5th lumbar and muscle testing of the two animal strains were measured to confirm the status of osteoporosis and sarcopenia, respectively. Closed fracture was created on the right femur of 8-month-old animals. Radiographs were taken weekly post-fracture. MicroCT and histology of the fractured femur were performed at week 2, 4 and 6 post-fracture, while mechanical test of both femora at week 4 and 6 post-fracture. Results showed that the callus of SAMR1 was significantly larger at week 2 but smaller at week 6 post-fracture than SAMP8. Mechanical properties were significantly better at week 4 post-fracture in SAMR1 than SAMP8, indicating osteoporotic fracture healing was delayed in sarcopenic SAMP8. This study validated an animal model of co-existing sarcopenia and osteoporotic fracture, where a delayed fracture healing might be resulted in the presence of sarcopenia. Copyright © 2017 Elsevier Inc. 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

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.

Success of long bone fracture healing in ancient Egypt: a paleoepidemiological study of the Giza Necropolis skeletons.

PubMed

Erfan Zaki, Moushira

2013-01-01

Complications may provide information regarding the management of fractures in ancient populations. The aim of this study was to determine the rates of long-bone fractures and the proportion of misalignments as indicators of failed treatment or no treatment at all in skeletons from the Giza Necropolis dating to the Old Kingdom period (2700-2190 BC). We visually examined for fractures 2287 long bones of 204 adult skeletons (112 male and 92 female) and took x-rays of fractured bones in standard AP and ML views, so that we can analyse misalignments. Fractures were found in 45 of the 2287 examined long bones (1.97 %). Most of the fractures healed with good alignment, most likely as a result of successful treatment, and only three fractures showed misalignment.

[Research on promotory effect of traditional Chinese medicine on fracture healing in cell and molecular level].

PubMed

Zhang, Kun; Niu, Liang-Chen; Yuan, Fu-Jie; Liu, Shen-Peng

2017-08-25

Traditional Chinese medicine is widely used in the treatment of fractures, osteoporosis, other bone related diseases for thousands of years. There are many animal experiments and clinical trials demonstrating that the traditional Chinese medicine such as epimedium, Drynaria and other traditional Chinese medicine can stimulate bone regeneration and inhibit bone resorption, accelerating the fracture healing. In recent years many cell experiments have shown that these herbal ingredients up-regulated the expression of intracellular osteogenic transcription factors and osteogenic related genes, and then induced osteoblastic differentiation and stimulated the proliferation of osteoblasts, bone nodule formation and matrix mineralization. Meanwhile these herbal ingredients up-regulated the expression of intracellular osteoclastic transcription factors and osteoclast related genes, inhibited osteoclast differentiation and bone resorption of osteoclasts. In addition, intracellular signaling pathways regulated these herbal ingredients by might be involved in the above effects. We can have a conclusion that the genes expression regulated by transcription factors in pre-osteoblast and pre-osteoclast and these signaling pathways are the major molecular mechanisms and research hotspots of traditional Chinese medicine in promoting fracture healing. Based on these molecular mechanisms to review, this review provides not only the foundation for the study of traditional Chinese medicine in promoting fracture healing, but also the basis for clinical treatment of fracture. Copyright© 2017 by the China Journal of Orthopaedics and Traumatology Press.

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.

Two case examples of pelvic fractures in medieval populations from central Europe.

PubMed

Hofmann, Maria Ines; Papageorgopoulou, Christina; Böni, Thomas; Rühli, Frank J

2010-01-01

Pelvic fractures are considered to be uncommon and difficult to treat, even in the modern medical literature. Serious and eventually life-threatening associated injuries may occur, requiring emergency abdominal, vascular or neurologic surgery. Pelvic fractures can also be managed non-operatively; however, a considerable dispute exists on the suitable management strategy. The treatment and healing of such injuries in the bioarchaeological record, is therefore of great interest for anthropological and medico-historical studies. Fractures of the pelvis are rarely reported in the anthropological literature either due to poor preservation of the innominate bone or lack of adequate examination. Here we present two cases of pelvic fractures observed on two adult male individuals from two European medieval sites. They differ in severity and in the pattern of healing. They are both adequately healed and probably had no acute life-threatening consequences, which gives us some insight into the medical knowledge and means of management of past populations.

Fracture healing: A review of clinical, imaging and laboratory diagnostic options.

PubMed

Cunningham, Brian P; Brazina, Sloane; Morshed, Saam; Miclau, Theodore

2017-06-01

A fundamental issue in clinical orthopaedics is the determination of when a fracture is united. However, there are no established "gold standards," nor standardized methods for assessing union, which has resulted in significant disagreement among orthopaedic surgeons in both clinical practice and research. A great deal of investigative work has been directed to addressing this problem, with a number of exciting new techniques described. This review provides a brief summary of the burden of nonunion fractures and addresses some of the challenges related to the assessment of fracture healing. The tools currently available to determine union are discussed, including various imaging modalities, biomechanical testing methods, and laboratory and clinical assessments. The evaluation of fracture healing in the setting of both patient care and clinical research is integral to the orthopaedic practice. Weighted integration of several available metrics must be considered to create a composite outcome measure of patient prognosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Internal fixators: a safe option for managing distal femur fractures?

PubMed Central

Batista, Bruno Bellaguarda; Salim, Rodrigo; Paccola, Cleber Antonio Jansen; Kfuri, Mauricio

2014-01-01

OBJECTIVE: Evaluate safety and reliability of internal fixator for the treatment of intra-articular and periarticular distal femur fractures. METHODS: Retrospective data evaluation of 28 patients with 29 fractures fixed with internal fixator was performed. There was a predominance of male patients (53.5%), with 52% of open wound fractures, 76% of AO33C type fractures, and a mean follow up of 21.3 months. Time of fracture healing, mechanical axis deviation, rate of infection and postoperative complications were registered. RESULTS: Healing rate was 93% in this sample, with an average time of 5.5 months. Twenty-seven percent of patients ended up with mechanical axis deviation, mostly resulting from poor primary intra-operative reduction. There were two cases of implant loosening; two implant breakage, and three patients presented stiff knee. No case of infection was observed. Healing rate in this study was comparable with current literature; there was a high degree of angular deviation, especially in the coronal plane. CONCLUSION: Internal fixators are a breakthrough in the treatment of knee fractures, but its use does not preclude application of principles of anatomical articular reduction and mechanical axis restoration. Level of Evidence II, Retrospective Study. PMID:25061424

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

Interfacial self-healing of nanocomposite hydrogels: Theory and experiment

NASA Astrophysics Data System (ADS)

Wang, Qiming; Gao, Zheming; Yu, Kunhao

2017-12-01

Polymers with dynamic bonds are able to self-heal their fractured interfaces and restore the mechanical strengths. It is largely elusive how to analytically model this self-healing behavior to construct the mechanistic relationship between the self-healing properties (e.g., healed interfacial strength and equilibrium healing time) and the material compositions and healing conditions. Here, we take a self-healable nanocomposite hydrogel as an example to illustrate an interfacial self-healing theory for hydrogels with dynamic bonds. In the theory, we consider the free polymer chains diffuse across the interface and reform crosslinks to bridge the interface. We analytically reveal that the healed strengths of nanocomposite hydrogels increase with the healing time in an error-function-like form. The equilibrium self-healing time of the full-strength recovery decreases with the temperature and increases with the nanoparticle concentration. We further analytically reveal that the healed interfacial strength decreases with increasing delaying time before the healing process. The theoretical results quantitatively match with our experiments on nanosilica hydrogels, and also agree well with other researchers' experiments on nanoclay hydrogels. We expect that this theory would open promising avenues for quantitative understanding of the self-healing mechanics of various polymers with dynamic bonds, and offer insights for designing high-performance self-healing polymers.

A new classification and treatment protocol for combined fractures of the femoral shaft with the proximal or distal femur with closed locked intramedullary nailing: clinical experience of 63 fractures.

PubMed

Lambiris, Elias; Giannikas, Dimitrios; Galanopoulos, George; Tyllianakis, Minos; Megas, Panagiotis

2003-03-01

The medical records and radiographs of 63 patients, who were admitted between 1989-1997, with a combined femur fracture, were reviewed. Associated injuries were present in 38 (60%) patients. The combined fractures were classified into four major types depending on their anatomical position: type I, femoral shaft fracture combined with hip neck fracture; type II, femoral shaft fracture combined with a trochanteric fracture; type III, femoral shaft fracture combined with a distal femur fracture; and type IV, femoral shaft fracture combined with a proximal or distal femur fracture. The fractures were treated with locked intramedullary nailing and additional free cancellous 6.5-mm screws as needed. Fifty-six fractures healed without further operations. Of the remaining 6 fractures, 2 were material failures, 1 malunion with 3-cm shortening and external rotation of the femoral diaphysis, 2 early infections of the surgical wound, and 1 pseudarthrosis of the femoral shaft. All fractures were healed between 16 and 32 weeks (average: 20 weeks).

Osteoblast-Specific Krm2 Overexpression and Lrp5 Deficiency Have Different Effects on Fracture Healing in Mice

PubMed Central

Liedert, Astrid; Röntgen, Viktoria; Schinke, Thorsten; Benisch, Peggy; Ebert, Regina; Jakob, Franz; Klein-Hitpass, Ludger; Lennerz, Jochen K.; Amling, Michael; Ignatius, Anita

2014-01-01

The canonical Wnt/β-catenin pathway plays a key role in the regulation of bone remodeling in mice and humans. Two transmembrane proteins that are involved in decreasing the activity of this pathway by binding to extracellular antagonists, such as Dickkopf 1 (Dkk1), are the low-density lipoprotein receptor related protein 5 (Lrp5) and Kremen 2 (Krm2). Lrp 5 deficiency (Lrp5−/−) as well as osteoblast-specific overexpression of Krm2 in mice (Col1a1-Krm2) result in severe osteoporosis occurring at young age. In this study, we analyzed the influence of Lrp5 deficiency and osteoblast-specific overexpression of Krm2 on fracture healing in mice using flexible and semi-rigid fracture fixation. We demonstrated that fracture healing was highly impaired in both mouse genotypes, but that impairment was more severe in Col1a1-Krm2 than in Lrp5−/− mice and particularly evident in mice in which the more flexible fixation was used. Bone formation was more reduced in Col1a1-Krm2 than in Lrp5−/− mice, whereas osteoclast number was similarly increased in both genotypes in comparison with wild-type mice. Using microarray analysis we identified reduced expression of genes mainly involved in osteogenesis that seemed to be responsible for the observed stronger impairment of healing in Col1a1-Krm2 mice. In line with these findings, we detected decreased expression of sphingomyelin phosphodiesterase 3 (Smpd3) and less active β-catenin in the calli of Col1a1-Krm2 mice. Since Krm2 seems to play a significant role in regulating bone formation during fracture healing, antagonizing KRM2 might be a therapeutic option to improve fracture healing under compromised conditions, such as osteoporosis. PMID:25061805

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

Fracture Toughness of Carbon Fiber Composites Containing Various Fiber Sizings and a Puncture Self-Healing Thermoplastic Matrix

NASA Technical Reports Server (NTRS)

Cano, Roberto J.; Grimsley, Brian W.; Ratcliffe, James G.; Gordon, Keith L.; Smith, Joseph G.; Siochi, Emilie J.

2015-01-01

Ongoing efforts at NASA Langley Research Center (LaRC) have resulted in the identification of several commercially available thermoplastic resin systems which self-heal after ballistic impact and through penetration. One of these resins, polybutylene graft copolymer (PBg), was selected as a matrix for processing with unsized carbon fibers to fabricate reinforced composites for further evaluation. During process development, data from thermo-physical analyses was utilized to determine a processing cycle to fabricate laminate panels, which were analyzed by photo microscopy and acid digestion. The process cycle was further optimized based on these results to fabricate panels for mechanical property characterization. The results of the processing development effort of this composite material, as well as the results of the mechanical property characterization, indicated that bonding between the fiber and PBg was not adequate. Therefore, three sizings were investigated in this work to assess their potential to improve fiber/matrix bonding compared to previously tested unsized IM7 fiber. Unidirectional prepreg was made at NASA LaRC from three sized carbon fibers and utilized to fabricate test coupons that were tested in double cantilever beam configurations to determine GIc fracture toughness.

Delayed union and nonunions: epidemiology, clinical issues, and financial aspects.

PubMed

Hak, David J; Fitzpatrick, Daniel; Bishop, Julius A; Marsh, J Lawrence; Tilp, Susanne; Schnettler, Reinhard; Simpson, Hamish; Alt, Volker

2014-06-01

Fracture healing is a critically important clinical event for fracture patients and for clinicians who take care of them. The clinical evaluation of fracture healing is based on both radiographic findings and clinical findings. Risk factors for delayed union and nonunion include patient dependent factors such as advanced age, medical comorbidities, smoking, non-steroidal anti-inflammatory use, various genetic disorders, metabolic disease and nutritional deficiency. Patient independent factors include fracture pattern, location, and displacement, severity of soft tissue injury, degree of bone loss, quality of surgical treatment and presence of infection. Established nonunions can be characterised in terms of biologic capacity, deformity, presence or absence of infection, and host status. Hypertrophic, oligotrophic and atrophic radiographic appearances allow the clinician to make inferences about the degree of fracture stability and the biologic viability of the fracture fragments while developing a treatment plan. Non-unions are difficult to treat and have a high financial impact. Indirect costs, such as productivity losses, are the key driver for the overall costs in fracture and non-union patients. Therefore, all strategies that help to reduce healing time with faster resumption of work and activities not only improve medical outcome for the patient, they also help reduce the financial burden in fracture and non-union patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

[APPLICATION OF BUTTERFLY SHAPED LOCKING COMPRESSION PLATE IN COMPLEX DISTAL RADIUS FRACTURES].

PubMed

Jiang, Zongyuan; Ma, Tao; Xia, Jiang; Hu, Caizhi; Xu, Lei

2014-06-01

To investigate the effectiveness of butterfly shaped locking compression plate for the treatment of complex distal radius fractures. Between June 2011 and January 2013, 20 cases of complex distal radius fractures were treated with butterfly shaped locking compression plate fixation. There were 11 males and 9 females with an average age of 54 years (range, 25-75 years). Injury was caused by falling in 10 cases, by traffic accident in 7 cases, and by falling from height in 3 cases. All of fractures were closed. According to AO classification system, there were 8 cases of type C1, 8 cases of type C2, and 4 cases of type C3. Of them, 9 cases had radial styloid process fracture, 4 cases had sigmoid notch fracture, and 7 cases had both radial styloid process fracture and sigmoid notch fracture. The mean interval between injury and operation was 5.2 days (range, 3-15 days). All incisions healed by first intention; no complications of infection and necrosis occurred. All cases were followed up 14 months on average (range, 10-22 months). All factures healed after 9.3 weeks on average (range, 6-11 weeks). No complications such as displacement of fracture, joint surface subsidence, shortening of the radius, and carpal tunnel syndrome were found during follow-up. At last follow-up, the mean palmar tilt angle was 10.2° (range, 7-15°), and the mean ulnar deviation angle was 21.8° (range, 17-24°). The mean range of motion of the wrist was 45.3° (range, 35-68°) in dorsal extension, 53.5° (range, 40-78°) in palmar flexion, 19.8° (range, 12-27°) in radial inclination, 26.6° (range, 18-31°) in ulnar inclination, 70.2° (range, 45-90°) in pronation, and 68.4° (range, 25-88°) in supination. According to the Dienst scoring system, the results were excellent in 8 cases, good in 10 cases, and fair in 2 cases, and the excellent and good rate was 90%. Treatment of complex distal radius fractures with butterfly shaped locking compression plate can reconstruct normal anatomic structures, especially for radial styloid process and sigmoid notch fractures, and it can get good functional recovery of the wrist and the distal radioulnar joint.

Radiation-induced alterations of fracture healing biomechanics

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

Pelker, R.R.; Friedlaender, G.E.; Panjabi, M.M.

1984-01-01

The effects of irradiation on the normal temporal progression of the physical properties of healing fractures were studied in a rat model. Fractures were surgically produced in the femur, stabilized with an intramedullary pin, and irradiated. One group of rats was exposed to 2,500 rads in divided doses over 2 weeks, beginning 3 days after fracture, and compared to a control group with fractures which were not irradiated. Animals were sacrificed at periodic intervals and the bones were tested to failure in torsion. The torque, stiffness, and energy increased and the angle decreased for the nonirradiated specimens in the expectedmore » fashion. This progression was deleteriously altered in the irradiated femurs.« less

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.

Intramedullary Mg2Ag nails augment callus formation during fracture healing in mice.

PubMed

Jähn, Katharina; Saito, Hiroaki; Taipaleenmäki, Hanna; Gasser, Andreas; Hort, Norbert; Feyerabend, Frank; Schlüter, Hartmut; Rueger, Johannes M; Lehmann, Wolfgang; Willumeit-Römer, Regine; Hesse, Eric

2016-05-01

Intramedullary stabilization is frequently used to treat long bone fractures. Implants usually remain unless complications arise. Since implant removal can become technically very challenging with the potential to cause further tissue damage, biodegradable materials are emerging as alternative options. Magnesium (Mg)-based biodegradable implants have a controllable degradation rate and good tissue compatibility, which makes them attractive for musculoskeletal research. Here we report for the first time the implantation of intramedullary nails made of an Mg alloy containing 2% silver (Mg2Ag) into intact and fractured femora of mice. Prior in vitro analyses revealed an inhibitory effect of Mg2Ag degradation products on osteoclast differentiation and function with no impair of osteoblast function. In vivo, Mg2Ag implants degraded under non-fracture and fracture conditions within 210days and 133days, respectively. During fracture repair, osteoblast function and subsequent bone formation were enhanced, while osteoclast activity and bone resorption were decreased, leading to an augmented callus formation. We observed a widening of the femoral shaft under steady state and regenerating conditions, which was at least in part due to an uncoupled bone remodeling. However, Mg2Ag implants did not cause any systemic adverse effects. These data suggest that Mg2Ag implants might be promising for intramedullary fixation of long bone fractures, a novel concept that has to be further investigated in future studies. Biodegradable implants are promising alternatives to standard steel or titanium implants to avoid implant removal after fracture healing. We therefore developed an intramedullary nail using a novel biodegradable magnesium-silver-alloy (Mg2Ag) and investigated the in vitro and in vivo effects of the implants on bone remodeling under steady state and fracture healing conditions in mice. Our results demonstrate that intramedullary Mg2Ag nails degrade in vivo over time without causing adverse effects. Importantly, radiographs, μCT and bone histomorphometry revealed a significant increase in callus size due to an augmented bone formation rate and a reduced bone resorption in fractures supported by Mg2Ag nails, thereby improving bone healing. Thus, intramedullary Mg2Ag nails are promising biomaterials for fracture healing to circumvent implant removal. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Determination of Radiographic Healing: An Assessment of Consistency Using RUST and Modified RUST in Metadiaphyseal Fractures.

PubMed

Litrenta, Jody; Tornetta, Paul; Mehta, Samir; Jones, Clifford; OʼToole, Robert V; Bhandari, Mohit; Kottmeier, Stephen; Ostrum, Robert; Egol, Kenneth; Ricci, William; Schemitsch, Emil; Horwitz, Daniel

2015-11-01

To determine the reliability of the Radiographic Union Scale for Tibia (RUST) score and a new modified RUST score in quantifying healing and to define a value for radiographic union in a large series of metadiaphyseal fractures treated with plates or intramedullary nails. Healing was evaluated using 2 methods: (1) evaluation of interrater agreement in a series of radiographs and (2) analysis of prospectively gathered data from 2 previous large multicenter trials to define thresholds for radiographic union. Part 1: 12 orthopedic trauma surgeons evaluated a series of radiographs of 27 distal femur fractures treated with either plate or retrograde nail fixation at various stages of healing in random order using a modified RUST score. For each radiographic set, the reviewer indicated if the fracture was radiographically healed. Part 2: The radiographic results of 2 multicenter randomized trials comparing plate versus nail fixation of 81 distal femur and 46 proximal tibia fractures were reviewed. Orthopaedic surgeons at 24 trauma centers scored radiographs at 3, 6, and 12 months postoperatively using the modified RUST score above. Additionally, investigators indicated if the fracture was healed or not healed. The intraclass correlation coefficient (ICC) with 95% confidence intervals was determined for each cortex, the standard and modified RUST score, and the assignment of union for part 1 data. The RUST and modified RUST that defined "union" were determined for both parts of the study. ICC: The modified RUST score demonstrated slightly higher ICCs than the standard RUST (0.68 vs. 0.63). Nails had substantial agreement, whereas plates had moderate agreement using both modified and standard RUST (0.74 and 0.67 vs. 0.59 and 0.53). The average standard and modified RUST at union among all fractures was 8.5 and 11.4. Nails had higher standard and modified RUST scores than plates at union. The ICC for union was 0.53 (nails: 0.58; plates: 0.51), which indicates moderate agreement. However, the majority of reviewers assigned union for a standard RUST of 9 and a modified RUST of 11, and >90% considered a score of 10 on the RUST and 13 on the modified RUST united. The ICC for the modified RUST is slightly higher than the standard RUST in metadiaphyseal fractures and had substantial agreement. The ICC for the assessment of union was moderate agreement; however, definite union would be 10 and 13 with over 90% of reviewers assigning union. These are the first data-driven estimates of radiographic union for these scores.

[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.

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.

[Miniplate internal fixation and autogenous iliac bone graft in surgical treatment of old metatarsal fractures].

PubMed

Pan, Hao; Yu, Guangrong; Xiong, Wen; Zhao, Zhiming; Ding, Fan; Zheng, Qiong; Kan, Wushen

2011-07-01

To summarize the experience of treating old metatarsal fractures with surgery methods of miniplate internal fixation and autogenous iliac bone. Between May 2009 and July 2010, 7 patients with old metatarsal fractures were treated surgically, including 5 multi-metatarsal fractures and 2 single metatarsal fractures. There were 5 males and 2 females aged from 25 to 43 years (mean, 33 years). The time from fracture to operation was 4-12 weeks. The X-ray films showed that a small amount of callus formed at both broken ends with shortening, angulation, or rotation displacement. The surgical treatments included open reduction, internal fixation by miniplate, and autogenous iliac bone graft (1.5-2.5 cm(3)). The external plaster fixation was used in all patients for 4 to 6 weeks postoperatively (mean, 5 weeks). All incisions healed by first intention. The 7 patients were followed up 8-18 months (mean, 13.5 months). The clinical fracture healing time was 6 to 12 weeks postoperatively (mean, 8.4 weeks). No pain of planta pedis occurred while standing and walking. The American Orthopaedic Foot and Ankle Society (AOFAS) mesopedes and propodium score was 75-96 (mean, 86.4). It has the advantages of reliable internal fixation, high fracture healing rate, less complications to treat old metatarsal fractures with surgery methods of miniplate internal fixation and autogenous iliac bone graft, so it is an effective treatment method.

Treatment of type II odontoid fracture with a novel technique

PubMed Central

Zhu, Ce; Wang, Lei; Liu, Hao; Song, Yueming; Liu, Limin; Li, Tao; Gong, Quan

2017-01-01

Abstract Surgical methods for type II odontoid fracture can be classified into 2 main groups: anterior or posterior approach. A more effective way to achieve bone fusion with the lowest possible surgical risk is needed. Therefore, the aim of our study was to describe and evaluate a novel technique, cable-dragged reduction/cantilever beam internal fixation for the treatment of type II odontoid fracture. This was a retrospective study enrolled 34 patients underwent posterior cable-dragged reduction/cantilever-beam internal fixation surgery. Medical records, rates of reduction, the location of the instrumentation and fracture healing during follow-up were analyzed. Once fracture healing was obtained, instrumentation was removed. Neck pain (scored using a visual analog scale [VAS]), neck stiffness, patient satisfaction, and neck disability index (NDI) were recorded before and after removing the instrumentation during follow-up. The mean duration of follow up was 22.8 ± 5.3 months. There was no iatrogenic damage to nerves or blood vessels. Radiographic evaluation showed complete reduction in the 20 patients with fracture displacement and satisfactory fracture healing in all 34 cases. Titanium cable breakage was observed in 4 patients after fracture healing. After removal of instrumentation, significant improvements were seen in neck-pain VAS score, neck stiffness, patient satisfaction, and NDI (all P < .01). Posterior cable-dragged reduction/cantilever-beam internal fixation was an optimal salvage maneuver to conventional surgical methods such as anterior screw fixation and C1–C2 screw-rod system. The operative difficulty and incidence of nerve and vascular injury were reduced. Its major disadvantage is the exposure and screw-setting at C3, which is left intact in traditional surgery, and it is suitable only for patients with intact C1 posterior arches. PMID:29095313

The value of magnetic resonance imaging in the diagnosis of penile fracture.

PubMed

Guler, Ibrahim; Ödev, Kemal; Kalkan, Havva; Simsek, Cihan; Keskin, Suat; Kilinç, Mehmet

2015-01-01

We studied the use of magnetic resonance imaging in the diagnosis of penile fracture. Between 1997 and 2012, fifteen patients (age range 17-48 years, mean age 37 years) with suspected penile fracture underwent MRI examinations. Ten patients were injured during sexual intercourse, whereas four patients were traumatized by non-physiological bending of the penis during self manupilation, one patient was traumatized falling from the bed. Investigations were performed with 1.5 T MR unit. With the patient in the supine position, the penis was taped against the abdominal wall and surface coil was placed on the penis. All patients were studied with axial, coronal, sagittal precontrast and postcontrast T1-weighted TSE(TR/TE:538/13 msn) and T2-weighted TSE(5290/110 msn) sequences. All patient underwent surgical exploration. The follow-up ranged from 3 months to 72 months. Clinically all patients showed normal healing process without complications. In 11 patients a shortening and thickening of tunica albuginea was observed. Three patients have post traumatic erectile disfunction. In all patient corpus cavernosum fractures were clearly depicted on a discontinuity of the low signal intensity of tunica albuginea. These findings were most evident on T1WI and also depicted on T2W sequences. Images obtained shortly after contrast medium administration showed considerable enhancement only in rupture site. Subcutaneous extratunical haematoma in all patients were also recognizable on T2 WI. MRI findings were confirmed at surgery. Magnetic resonance imaging is of great value for the diagnosis of penile fracture. Furthermore this method is well suited for visualising the post-operative healing process.

Carbon Dots as Fillers Inducing Healing/Self-Healing and Anticorrosion Properties in Polymers.

PubMed

Zhu, Cheng; Fu, Yijun; Liu, Changan; Liu, Yang; Hu, Lulu; Liu, Juan; Bello, Igor; Li, Hao; Liu, Naiyun; Guo, Sijie; Huang, Hui; Lifshitz, Yeshayahu; Lee, Shuit-Tong; Kang, Zhenhui

2017-08-01

Self-healing is the way by which nature repairs damage and prolongs the life of bio entities. A variety of practical applications require self-healing materials in general and self-healing polymers in particular. Different (complex) methods provide the rebonding of broken bonds, suppressing crack, or local damage propagation. Here, a simple, versatile, and cost-effective methodology is reported for initiating healing in bulk polymers and self-healing and anticorrosion properties in polymer coatings: introduction of carbon dots (CDs), 5 nm sized carbon nanocrystallites, into the polymer matrix forming a composite. The CDs are blended into polymethacrylate, polyurethane, and other common polymers. The healing/self-healing process is initiated by interfacial bonding (covalent, hydrogen, and van der Waals bonding) between the CDs and the polymer matrix and can be optimized by modifying the functional groups which terminate the CDs. The healing properties of the bulk polymer-CD composites are evaluated by comparing the tensile strength of pristine (bulk and coatings) composites to those of fractured composites that are healed and by following the self-healing of scratches intentionally introduced to polymer-CD composite coatings. The composite coatings not only possess self-healing properties but also have superior anticorrosion properties compared to those of the pure polymer coatings. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[APPLICATION OF COMPUTER-ASSISTED SURGICAL PLANNING IN SURGICAL TREATMENT OF ANKLE FRACTURES].

PubMed

Xia, Shengli; Wang, Xiuhui; Fu, Beigang; Lu, Yaogang; Wang, Minghui

2015-12-01

To explore the clinical value of computer-assisted surgical planning in the treatment of ankle fractures. Between January 2012 and January 2014, open reduction and internal fixation were performed on 42 patients with ankle fractures. There were 22 males and 20 females with an average age of 52 years (range, 19-72 years). The causes were spraining injury (20 cases), traffic accident injury (14 cases), and falling from height injury (8 cases). The time from injury to operation was 5 hours to 12 days (mean, 2.5 days). All fractures were closed trimalleolar fractures. According to Lauge-Hansen classification, 25 cases were rated as supination extorsion type IV, 13 as pronation extorsion type IV, and 4 as pronation abduction type III. The preoperative planning was made by virtual reduction and internal fixation using Superimage software. The mean operation time was 93.7 minutes (range, 76-120 minutes). Delayed wound healing occurred in 1 case, and secondary healing was obtained after treatment; primary healing of incision was achieved in the other patients. Postoperative X-ray films and CT images showed anatomic reduction of fracture and good position of internal fixation. All patients were followed up 14.6 months on average (range, 9-27 months). The range of motion of the affected ankle was close to the normal side at 6-8 weeks. The mean fracture healing time was 13.1 weeks (range, 11-17 weeks). Degenerative change of the ankle joint was observed in 3 cases (7.1%) with manifestation of mild narrowing of joint space on the X-ray films at last follow-up. According to Baird-Jackson score system, the results were excellent in 24 cases, good in 13 cases, and fair in 5 cases, with an excellent and good rate of 88%. Computer-assisted surgical planning for ankle fractures can help surgeons identify type of ankle fractures and improve surgical scheme for guiding fracture reduction and selecting and placing implants, so good effectiveness can be obtained.

A systematic review of current osteoporotic metaphyseal fracture animal models.

PubMed

Wong, R M Y; Choy, M H V; Li, M C M; Leung, K-S; K-H Chow, S; Cheung, W-H; Cheng, J C Y

2018-01-01

The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models. A literature search was performed on the Pubmed, Embase, and Web of Science databases, and relevant articles were selected. A total of 19 studies were included. Information on the animal, induction of osteoporosis, fracture technique, site and fixation, healing results, and utility of the model were extracted. Fracture techniques included drill hole defects (3 of 19), bone defects (3 of 19), partial osteotomy (1 of 19), and complete osteotomies (12 of 19). Drill hole models and incomplete osteotomy models are easy to perform and allow the study of therapeutic agents but do not represent the usual clinical setting. Additionally, biomaterials can be filled into drill hole defects for analysis. Complete osteotomy models are most commonly used and are best suited for the investigation of therapeutic drugs or noninvasive interventions. The metaphyseal defect models allow the study of biomaterials, which are associated with complex and comminuted osteoporotic fractures. For a clinically relevant model, we propose that an animal model should satisfy the following criteria to study osteoporotic fracture healing: 1) induction of osteoporosis, 2) complete osteotomy or defect at the metaphysis unilaterally, and 3) internal fixation. Cite this article : R. M. Y. Wong, M. H. V. Choy, M. C. M. Li, K-S. Leung, S. K-H. Chow, W-H. Cheung, J. C. Y. Cheng. A systematic review of current osteoporotic metaphyseal fracture animal models. Bone Joint Res 2018;7:6-11. DOI: 10.1302/2046-3758.71.BJR-2016-0334.R2. © 2018 Wong et al.

Treatment of type II and type III open tibia fractures in children.

PubMed

Bartlett, C S; Weiner, L S; Yang, E C

1997-07-01

To determine whether severe open tibial fractures in children behave like similar fractures in adults. A combined retrospective and prospective review evaluated treatment protocol for type II and type III open tibial fractures in children over a ten-year period from 1984 to 1993. Twenty-three fractures were studied in children aged 3.5 to 14.5 (18 boys and 5 girls). There were six type II, eight type IIIA, and nine type IIIB fractures. Type I fractures were not included. Seven fractures were comminuted with significant butterfly fragments or segmental patterns. Treatment consisted of adequate debridement of soft tissues, closure of dead space, and stabilization with external fixation. Bone debridement only included contaminated devitalized bone or devitalized bone without soft tissue coverage. Bone that could be covered despite periosteal stripping was preserved. Clinical and roentgenographic examinations were used to determine time to union. All fractures in this series healed between eight and twenty-six weeks. Wound coverage included two flaps, three skin grafts, and two delayed primary closures. No bone grafts were required. There were no deep infections, growth arrests, or malunions. Follow-up has ranged from six months to four years. Open tibia fractures in children differ from similar fractures in adults in the following ways: soft tissues have excellent healing capacity, devitalized bone that is not contaminated or exposed can be saved and will become incorporated, and external fixation can be maintained until the fracture has healed. Periosteum in young children can form bone even in the face of bone loss.

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.

Randomized prospective study of olecranon fracture fixation: cable pin system versus tension band wiring.

PubMed

Liu, Q-H; Fu, Z-G; Zhou, J-L; Lu, T; Liu, T; Shan, L; Liu, Y; Bai, L

2012-01-01

This prospective, randomized study compared the effectiveness of the cable pin system (CPS) versus tension band wiring (TBW) for olecranon fracture fixation. Patients with acute transverse or slight oblique olecranon fractures were randomly divided into two groups: one fixed by CPS and the other by TBW. Clinical outcome data were collected and analysed following a mean duration of 21 months. The mean ± SD fracture healing time was significantly shorter in the CPS group (n = 30; 9.73 ± 2.02 weeks) compared with the TBW group (n = 32; 11.13 ± 2.21 weeks). One patient in the CPS group and seven patients in the TBW group experienced postoperative complications; this difference was statistically significant. The mean ± SD Mayo Elbow Performance Score in the CPS group was significantly higher (88.67 ± 6.42) than that in the TBW group (80.78 ± 11.99). Logistic regression analysis showed an association between fixation method and fracture healing time, complications and elbow function. Internal fixation by CPS is an effective method for olecranon fracture and is associated with a shorter healing time, fewer complications and better function than TBW.

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

Gene identification and analysis of transcripts differentially regulated in fracture healing by EST sequencing in the domestic sheep.

PubMed

Hecht, Jochen; Kuhl, Heiner; Haas, Stefan A; Bauer, Sebastian; Poustka, Albert J; Lienau, Jasmin; Schell, Hanna; Stiege, Asita C; Seitz, Volkhard; Reinhardt, Richard; Duda, Georg N; Mundlos, Stefan; Robinson, Peter N

2006-07-05

The sheep is an important model animal for testing novel fracture treatments and other medical applications. Despite these medical uses and the well known economic and cultural importance of the sheep, relatively little research has been performed into sheep genetics, and DNA sequences are available for only a small number of sheep genes. In this work we have sequenced over 47 thousand expressed sequence tags (ESTs) from libraries developed from healing bone in a sheep model of fracture healing. These ESTs were clustered with the previously available 10 thousand sheep ESTs to a total of 19087 contigs with an average length of 603 nucleotides. We used the newly identified sequences to develop RT-PCR assays for 78 sheep genes and measured differential expression during the course of fracture healing between days 7 and 42 postfracture. All genes showed significant shifts at one or more time points. 23 of the genes were differentially expressed between postfracture days 7 and 10, which could reflect an important role for these genes for the initiation of osteogenesis. The sequences we have identified in this work are a valuable resource for future studies on musculoskeletal healing and regeneration using sheep and represent an important head-start for genomic sequencing projects for Ovis aries, with partial or complete sequences being made available for over 5,800 previously unsequenced sheep genes.

Structural properties of fracture haematoma: current status and future clinical implications.

PubMed

Wang, Xin; Friis, Thor; Glatt, Vaida; Crawford, Ross; Xiao, Yin

2017-10-01

Blood clots (haematomas) that form immediately following a bone fracture have been shown to be vital for the subsequent healing process. During the clotting process, a number of factors can influence the fibrin clot structure, such as fibrin polymerization, growth factor binding, cellular infiltration (including platelet retraction), protein concentrations and cytokines. The modulation of the fibrin clot structure within the fracture site has important clinical implications and could result in the development of multifunctional scaffolds that mimic the natural structure of a haematoma. Artificial haematoma structures such as these can be created from the patient's own blood and can therefore act as an ideal bone defect filling material for potential clinical application to accelerate bone regeneration. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

[Peripheral Factures of the Talus. Mid-Term Results].

PubMed

Peml, M; Kálal, P; Kopačka, P; Kloub, M

2016-01-01

PURPOSE OF THE STUDY Peripheral fractures of the talus (lateral talar process and posterior talar process) are rare injuries, easy to miss on examination due to their location and clinical manifestation. They account for 0.3% to 1.0% of all fractures of the talus. An incorrect or late treatment of talar process fractures can result in permanent pain, impingement syndrome, healing in malposition, pseudoarthrosis development and also, due to joint instability, in a potential development of severe subtalar arthritis. The aim of this retrospective study was to evaluate the results of surgical management of these fractures in our department. MATERIAL AND METHODS The study included 14 adult patients with fractures of the peripheral talar processes who met the criteria of the retrospective study and were treated in our department between 2008 and 2014. All patients underwent clinical examination with evaluation based on the AOFAS Ankle-Hindfoot score, VAS score and radiographic evidence of arthritis. Follow-up ranged from 24 to 95 months. The average age of the patients at the time of surgery was 34 years (range, 21-59 years); there was one woman and 13 men. All underwent pre-operative CT scanning. The surgical procedure included open reduction and internal fixation (ORIF) which, in indicated cases, was preceded by partial or total removal of the processes. RESULTS Of the 14 patients, seven were treated for fractures of the lateral talar process (LTP group) and seven for the posterior talar process (PTP group). All fractures healed completely. The median AOFAS score was 87 (72-100) points in the LTP group, and 84 (58-100) points in the PTP group. Excellent and good results on the AOFAS Ankle-Hindfoot scale were achieved in 10 (72%), satisfactory in two (14%) and poor in two (14%) patients. Of the LTP group, six patients (86%) showed the VAS score ≤ 3, and one (14%) had the VAS score = 4. In the PTP group, the VAS score ≤ 3 was reported by three (43%) and values of up to 5 by four (57%) patients. Arthritis in the talocrural and subtalar joints was evaluated as zero or grade 1 in 11 (79%) of all patients; of these 11 patients only two (14%) had a VAS score higher than 3. Only one patient had marginal wound necrosis; no deep wound infection was recorded. DISCUSSION The majority of fractures in our group were due to falls from a height or traffic accidents, which is in accordance with the literature data. In about 70% of these injuries, more parts of the leg are affected and, therefore, a thorough medical inspection is necessary. These mechanisms of injury most frequently produce type II LTP fracture (Hawkins classification). Four patients with a LTP fracture, who had the process partially removed, achieved good results on the AOFAS scale and the VAS score less than or equal to 3. As also published in the literature, the removal of small fragments has no crucial effect on ankle stability. CONSLUSIONS An adequate surgical treatment of displaced peripheral fractures of the talar processes provides good functional outcomes. In fractures with associated leg injuries or high-energy traumata, the prognosis is poorer. Fractures of talar processes often show symptoms and signs similar to those of more serious forms of dislocation of the talus and therefore a careful assessment of standard X-ray images taken for a "swollen ankle" is necessary. If the findings are not clear, CT examination is indicated. Key words: fracture, talus, processus lateralis tali, processus posterior tali.

[Comparison study on locking compress plate external fixator and standard external fixator for treatment of tibial open fractures].

PubMed

Wu, Gang; Luo, Xiaozhong; Tan, Lun; Lin, Xu; Wu, Chao; Guo, Yong; Zhong, Zewei

2013-11-01

To compare the clinical results of locking compress plate (LCP) as an external fixator and standard external fixator for treatment of tibial open fractures. Between May 2009 and June 2012, 59 patients with tibial open fractures were treated with LCP as an external fixator in 36 patients (group A), and with standard external fixator in 23 patients (group B). There was no significant difference in gender, age, cause of injury, affected side, type of fracture, location, and interval between injury and surgery between 2 groups (P > 0.05). The time of fracture healing and incision healing, the time of partial weight-bearing, the range of motion (ROM) of knee and ankle, and complications were compared between 2 groups. The incidence of pin-track infection in group A (0) was significantly lower than that in group B (21.7%) (P=0.007). No significant difference was found in the incidence of superficial infection and deep infection of incision, and the time of incision healing between 2 groups (P > 0.05). Deep vein thrombosis occurred in 5 cases of group A and 2 cases of group B, showing no significant difference (Chi(2)=0.036, P=0.085). All patients were followed up 15.2 months on average (range, 9-28 months) in group A, and 18.6 months on average (range, 9-47 months) in group B. The malunion rate and nonunion rate showed no significant difference between groups A and B (0 versus 13.0% and 0 versus 8.7%, P > 0.05); the delayed union rate of group A (2.8%) was significantly lower than that of group B (21.7%) (Chi(2)=5.573, P=0.018). Group A had shorter time of fracture healing, quicker partial weight-bearing, greater ROM of the knee and ankle than group B (P < 0.05). The LCP external fixator can obtain reliable fixation in treating tibial open fracture, and has good patients' compliance, so it is helpful to do functional exercise, improve fracture healing and function recovery, and reduce the complication incidence.

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.

Multiple Low Energy Long Bone Fractures in the Setting of Rothmund-Thomson Syndrome.

PubMed

Beckmann, Nicholas

2015-01-01

Rothmund-Thomson syndrome is a rare autosomal recessive genodermatosis characterized by a poikilodermatous rash starting in infancy as well as various skeletal anomalies, juvenile cataracts, and predisposition to certain cancers. Although Rothmund-Thomson syndrome is associated with diminished bone mineral density in addition to multiple skeletal abnormalities, there are few reports of the association with stress fractures or pathologic fractures in low energy trauma or delayed healing of fractures. Presented is a case of a young adult male with Rothmund-Thomson syndrome presenting with multiple episodes of long bone fractures caused by low energy trauma with one of the fractures exhibiting significantly delayed healing. The patient was also found to have an asymptomatic stress fracture of the lower extremity, another finding of Rothmund-Thomson syndrome rarely reported in the literature. A thorough review of the literature and comprehensive presentation of Rothmund-Thomson syndrome is provided in conjunction with our case.

[Cannulated lag screw combined with lateral supporting plate for treatment of Hoffa fracture of Letenneur type I and type III].

PubMed

Lin, Tao; Yang, Shuhua; Xiao, Baojun; Fu, Dehao

2013-09-01

To investigate the effectiveness of cannulated lag screws combined with lateral supporting plates in the treatment of Hoffa fracture of Letenneur type I and type III. Between May 2004 and April 2011, 11 patients with Hoffa fracture of Letenneur type I and type III were treated, including 6 males and 5 females with an average age of 36 years (range, 25-47 years). Factures were caused by traffic accident in 8 cases, by falling in 2 cases, and by the other in 1 case. Fracture involved the left knee in 7 patients and the right knee in 4 patients. According Letenneur's classification criteria, there were 7 type I fractures (6 lateral condyle fractures and 1 medial condyle fracture) and 4 type III fractures (3 lateral condyle fractures and 1 medial condyle fracture). Of 11 fractures, 9 were fresh fractures and 2 were old fractures. Two 6.5 mm cannulated lag screws combined with lateral supporting plates were used to fix fractures by anterolateral or anteromedial incision. All incisions achieved primary healing with no early complication. All patients were followed up 12-26 months (mean, 15 months). X-ray films showed bone healing with an average healing time of 15 weeks (range, 10-18 weeks). No loosening or breaking of internal fixator was observed; the removal time of internal fixation was 9-15 months (mean, 12 months). Accoding to Letenneur's functional assessment system, the results were excellent in 7 cases, good in 3 cases, and poor in 1 case at last follow-up. Cannulated lag screws combined with lateral supporting plates fixation is effective in treatment of Hoffa fracture of Letenneur type I and type III with a high union rate; anterolateral or anteromedial approach is the first choice for Hoffa fracture of type I and type III, especially for complicating by tibial plateau fracture or patella fracture.

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.

Anisotropy in Fracking: A Percolation Model for Observed Microseismicity

NASA Astrophysics Data System (ADS)

Norris, J. Quinn; Turcotte, Donald L.; Rundle, John B.

2015-01-01

Hydraulic fracturing (fracking), using high pressures and a low viscosity fluid, allow the extraction of large quantiles of oil and gas from very low permeability shale formations. The initial production of oil and gas at depth leads to high pressures and an extensive distribution of natural fractures which reduce the pressures. With time these fractures heal, sealing the remaining oil and gas in place. High volume fracking opens the healed fractures allowing the oil and gas to flow to horizontal production wells. We model the injection process using invasion percolation. We use a 2D square lattice of bonds to model the sealed natural fractures. The bonds are assigned random strengths and the fluid, injected at a point, opens the weakest bond adjacent to the growing cluster of opened bonds. Our model exhibits burst dynamics in which the clusters extend rapidly into regions with weak bonds. We associate these bursts with the microseismic activity generated by fracking injections. A principal object of this paper is to study the role of anisotropic stress distributions. Bonds in the y-direction are assigned higher random strengths than bonds in the x-direction. We illustrate the spatial distribution of clusters and the spatial distribution of bursts (small earthquakes) for several degrees of anisotropy. The results are compared with observed distributions of microseismicity in a fracking injection. Both our bursts and the observed microseismicity satisfy Gutenberg-Richter frequency-size statistics.

Healed Depressed Parasagittal Skull Fractures-A Feature of Archaic Australian Aboriginal Remains.

PubMed

Walshe, Keryn; Brophy, Brian; Cornish, Brian; Byard, Roger W

2016-11-01

The skeletal remains of eight Australian Aboriginals with healed depressed skull fractures were examined. Male:female ratio 5:3; age range 20-60 yrs. Burial dates by 14 C dating in three cases were 500 years BP (n = 2) and 1300 BP. There were 13 healed depressed skull fractures manifested by shallow indentations of cortical bone and thinning of diploe, with no significant disturbance of the inner skull tables. Nine (69%) were located within 35 mm of the sagittal suture/midline. These lesions represent another acquired feature that might be helpful in suggesting that a skull is from a tribal Aboriginal individual and may be particularly useful if the remains are represented by only fragments of calvarium. While obviously not a finding specific to this population, these healed injuries would be consistent with the possible results of certain types of conflict behavior reported in traditional Aboriginal groups that involved formalized inflicted blunt head trauma. © 2016 American Academy of Forensic Sciences.

Prostate-Specific Membrane Antigen Expression in Distal Radius Fracture.

PubMed

Hoberück, Sebastian; Michler, Enrico; Kaiser, Daniel; Röhnert, Anne; Zöphel, Klaus; Kotzerke, Jörg

2018-06-12

A 79-year old man with prostate cancer under active surveillance for 5 years was referred for a PSMA-PET/MRI for re-evaluation because of a rising prostate-specific antigen value. PET/MRI revealed a ribbonlike tracer accumulation in a healing fracture of the distal radius. This case illustrates that PSMA expression may occur in healing bone fractures in the distal radius. It can be assumed that benign causes of tracer accumulations in the upper extremities are missed in PET/CT due to elevated position of the arms during image acquisition.

Activation-deactivation of self-healing in supramolecular rubbers

NASA Astrophysics Data System (ADS)

Corte, Laurent; Maes, Florine; Montarnal, Damien; Cantournet, Sabine; Tournilhac, Francois; Leibler, Ludwik; Mines-Paristech Cnrs (Umr7633) Team; Espci-Paristech Cnrs (Umr7167) Team

2011-03-01

Self-healing materials have the ability to restore autonomously their structural integrity after damage. Such a remarkable property was obtained recently in supramolecular rubbers formed by a network of small molecules associated via hydrogen bonds. Here we explore this self-healing through an original tack experiment where two parts of supramolecular rubber are brought into contact and then separated. These experiments reveal that a strong self-healing ability is activated by damage even though the surfaces of a molded part are weakly self-adhesive. In our testing conditions, a five minute contact between crack faces is sufficient to recover most mechanical properties of the bulk while days are required to obtain such adhesion levels with melt-pressed surfaces. We show that the deactivation of this self-healing ability seems unexpectedly slow as compared to the predicted dynamics of supramolecular networks. Fracture faces stored apart at room temperature still self-heal after days but are fully deactivated within hours by annealing. Combining these results with microstructural observations gives us a deeper insight into the mechanisms involved in this self-healing process.

Intramedullary Stabilization of Periprosthetic Fractures of the Femur Taking Special Account of Bone Defects.

PubMed

Eingartner, Christoph; Volkmann, Rüdiger; Ochs, Uwe; Egetemeyr, Daniel; Weise, Kuno

2007-10-01

Healing of the periprosthetic fracture and area of defective bone by the bone healing mechanisms of intramedullary stabilization. Reconstruction of the correct length, axial alignment, and rotation of the fractured femoral shaft by anchoring a revision stem in the intact femoral diaphysis. Periprosthetic femoral shaft fracture in the region of the prosthetic stem combined with preexistent loosening and/or defect in the periprosthetic bone bed (Vancouver classification type B2 and B3). General contraindications, local infection. Lateral transmuscular approach to the femoral shaft. Longitudinal osteotomy of the proximal femur taking the geometry of the fracture into account. Opening of an anterior "bone shell". Removal of the loose prosthetic stem and cement. Debridement. Preparation of the femoral diaphysis and insertion of a distally anchored revision stem. Distal locking. Repositioning of the "bone shell", reduction of the fracture, and retention with cerclage wires. Bed rest for approximately 1 week, mobilization with 20 kg partial weight bearing for 12 weeks, gradual increase in weight bearing with radiologic checks on progress, removal of the distal locking bolts after 12-24 months at the earliest. 21 patients (13 women, eight men) aged between 43 and 86 years (mean age: 71.2 years) with periprosthetic fracture of the femur, additional loosening of the stem in eight cases (Vancouver B2) and additional bone loss in 13 cases (Vancouver B3). Postoperative complications: two fractures following another fall (repeat operations: one replacement, one plate), four revisions due to subsidence of the stem (three replacements involving change to a standard stem with healed proximal femur, one replacement with another interlocked revision stem). Bone healing occurred for all fractures after a mean 5.6 months (3-11 months). Follow- up examination after a mean 4.5 years: all patients were able to walk, average Harris Score 70.5 points (29- 95 points).

Intramedullary stabilization of periprosthetic fractures of the femur taking special account of bone defects.

PubMed

Eingartner, Christoph; Volkmann, Rüdiger; Ochs, Uwe; Egetemeyr, Daniel; Weise, Kuno

2006-10-01

Healing of the periprosthetic fracture and area of defective bone by the bone healing mechanisms of intramedullary stabilization. Reconstruction of the correct length, axial alignment, and rotation of the fractured femoral shaft by anchoring a revision stem in the intact femoral diaphysis. Periprosthetic femoral shaft fracture in the region of the prosthetic stem combined with preexistent loosening and/or defect in the periprosthetic bone bed (Vancouver classification type B2 and B3). General contraindications, local infection. Lateral transmuscular approach to the femoral shaft. Longitudinal osteotomy of the proximal femur taking the geometry of the fracture into account. Opening of an anterior "bone shell". Removal of the loose prosthetic stem and cement. Debridement. Preparation of the femoral diaphysis and insertion of a distally anchored revision stem. Distal locking. Repositioning of the "bone shell", reduction of the fracture, and retention with cerclage wires. Bed rest for approximately 1 week, mobilization with 20 kg partial weight bearing for 12 weeks, gradual increase in weight bearing with radiologic checks on progress, removal of the distal locking bolts after 12-24 months at the earliest. 21 patients (13 women, eight men) aged between 43 and 86 years (mean age: 71.2 years) with periprosthetic fracture of the femur, additional loosening of the stem in eight cases (Vancouver B2) and additional bone loss in 13 cases (Vancouver B3). Postoperative complications: two fractures following another fall (repeat operations: one replacement, one plate), four revisions due to subsidence of the stem (three replacements involving change to a standard stem with healed proximal femur, one replacement with another interlocked revision stem). Bone healing occurred for all fractures after a mean 5.6 months (3-11 months). Follow-up examination after a mean 4.5 years: all patients were able to walk, average Harris Score 70.5 points (29-95 points).

Experimental postseismic recovery of fractured rocks assisted by calcite sealing

NASA Astrophysics Data System (ADS)

Aben, F. M.; Doan, M.-L.; Gratier, J.-P.; Renard, F.

2017-07-01

Postseismic recovery within fault damage zones involves slow healing of coseismic fractures leading to permeability reduction and strength increase with time. To better understand this process, experiments were performed by long-term fluid percolation with calcite precipitation through predamaged quartz-monzonite samples subjected to upper crustal conditions of stress and temperature. This resulted in a P wave velocity recovery of 50% of its initial drop after 64 days. In contrast, the permeability remained more or less constant for the duration of the experiment. Microstructures, fluid chemistry, and X-ray microtomography demonstrate that incipient calcite sealing and asperity dissolution are responsible for the P wave velocity recovery. The permeability is unaffected because calcite precipitates outside of the main flow channels. The highly nonparallel evolution of strength recovery and permeability suggests that fluid conduits within fault damage zones can remain open fluid conduits after an earthquake for much longer durations than suggested by the seismic monitoring of fault healing.

In vitro simulation of pathological bone conditions to predict clinical outcome of bone tissue engineered materials

NASA Astrophysics Data System (ADS)

Nguyen, Duong Thuy Thi

According to the Centers for Disease Control, the geriatric population of ≥65 years of age will increase to 51.5 million in 2020; 40% of white women and 13% of white men will be at risk for fragility fractures or fractures sustained under normal stress and loading conditions due to bone disease, leading to hospitalization and surgical treatment. Fracture management strategies can be divided into pharmaceutical therapy, surgical intervention, and tissue regeneration for fracture prevention, fracture stabilization, and fracture site regeneration, respectively. However, these strategies fail to accommodate the pathological nature of fragility fractures, leading to unwanted side effects, implant failures, and non-unions. Compromised innate bone healing reactions of patients with bone diseases are exacerbated with protective bone therapy. Once these patients sustain a fracture, bone healing is a challenge, especially when fracture stabilization is unsuccessful. Traditional stabilizing screw and plate systems were designed with emphasis on bone mechanics rather than biology. Bone grafts are often used with fixation devices to provide skeletal continuity at the fracture gap. Current bone grafts include autologous bone tissue and donor bone tissue; however, the quality and quantity demanded by fragility fractures sustained by high-risk geriatric patients and patients with bone diseases are not met. Consequently, bone tissue engineering strategies are advancing towards functionalized bone substitutes to provide fracture reconstruction while effectively mediating bone healing in normal and diseased fracture environments. In order to target fragility fractures, fracture management strategies should be tailored to allow bone regeneration and fracture stabilization with bioactive bone substitutes designed for the pathological environment. The clinical outcome of these materials must be predictable within various disease environments. Initial development of a targeted treatment strategy should focus on simulating, in vitro, a physiological bone environment to predict clinical effectiveness of engineered bone and understand cellular responses due to the proposed agents and bioactive scaffolds. An in vitro test system can be the necessary catalyst to reduce implant failures and non-unions in fragility fractures.

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.

[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.

Analogous cellular contribution and healing mechanisms following digit amputation and phalangeal fracture in mice

PubMed Central

Dawson, Lindsay A.; Simkin, Jennifer; Sauque, Michelle; Pela, Maegan; Palkowski, Teresa

2016-01-01

Abstract Regeneration of amputated structures is severely limited in humans and mice, with complete regeneration restricted to the distal portion of the terminal phalanx (P3). Here, we investigate the dynamic tissue repair response of the second phalangeal element (P2) post amputation in the adult mouse, and show that the repair response of the amputated bone is similar to the proximal P2 bone fragment in fracture healing. The regeneration‐incompetent P2 amputation response is characterized by periosteal endochondral ossification resulting in the deposition of new trabecular bone, corresponding to a significant increase in bone volume; however, this response is not associated with bone lengthening. We show that cells of the periosteum respond to amputation and fracture by contributing both chondrocytes and osteoblasts to the endochondral ossification response. Based on our studies, we suggest that the amputation response represents an attempt at regeneration that ultimately fails due to the lack of a distal organizing influence that is present in fracture healing. PMID:27499878

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

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

Immediate versus delayed intramedullary nailing for open fractures of the tibial shaft: a multivariate analysis of factors affecting deep infection and fracture healing.

PubMed

Yokoyama, Kazuhiko; Itoman, Moritoshi; Uchino, Masataka; Fukushima, Kensuke; Nitta, Hiroshi; Kojima, Yoshiaki

2008-10-01

The purpose of this study was to evaluate contributing factors affecting deep infection and fracture healing of open tibia fractures treated with locked intramedullary nailing (IMN) by multivariate analysis. We examined 99 open tibial fractures (98 patients) treated with immediate or delayed locked IMN in static fashion from 1991 to 2002. Multivariate analyses following univariate analyses were derived to determine predictors of deep infection, nonunion, and healing time to union. The following predictive variables of deep infection were selected for analysis: age, sex, Gustilo type, fracture grade by AO type, fracture location, timing or method of IMN, reamed or unreamed nailing, debridement time (< or =6 h or >6 h), method of soft-tissue management, skin closure time (< or =1 week or >1 week), existence of polytrauma (ISS< 18 or ISS> or =18), existence of floating knee injury, and existence of superficial/pin site infection. The predictive variables of nonunion selected for analysis was the same as those for deep infection, with the addition of deep infection for exchange of pin site infection. The predictive variables of union time selected for analysis was the same as those for nonunion, excluding of location, debridement time, and existence of floating knee and superficial infection. Six (6.1%; type II Gustilo n=1, type IIIB Gustilo n=5) of the 99 open tibial fractures developed deep infections. Multivariate analysis revealed that timing or method of IMN, debridement time, method of soft-tissue management, and existence of superficial or pin site infection significantly correlated with the occurrence of deep infection (P< 0.0001). In the immediate nailing group alone, the deep infection rate in type IIIB + IIIC was significantly higher than those in type I + II and IIIA (P = 0.016). Nonunion occurred in 17 fractures (20.3%, 17/84). Multivariate analysis revealed that Gustilo type, skin closure time, and existence of deep infection significantly correlated with occurrence of nonunion (P < 0.05). Gustilo type and existence of deep infection were significantly correlated with healing time to union on multivariate analysis (r(2) = 0.263, P = 0.0001). Multivariate analyses for open tibial fractures treated with IMN showed that IMN after EF (especially in existence of pin site infection) was at high risk of deep infection, and that debridement within 6 h and appropriate soft-tissue managements were also important factor in preventing deep infections. These analyses postulated that both the Gustilo type and the existence of deep infection is related with fracture healing in open fractures treated with IMN. In addition, immediate IMN for type IIIB and IIIC is potentially risky, and canal reaming did not increase the risk of complication for open tibial fractures treated with IMN.

Postmenopausal women with osteopenia and a healed wrist fracture have reduced physical function and quality of life compared to a matched, healthy control group with no fracture

PubMed Central

2014-01-01

Background Fractures lead to reduced physical function and quality of life (QOL), but little is known about postmenopausal women with osteopenia and a healed wrist fracture. The purpose was to evaluate physical function in terms of quadriceps strength, dynamic balance, physical capacity and QOL in postmenopausal women with osteopenia and a healed wrist fracture compared to a matched, healthy control group with no previous fracture. Methods Eighteen postmenopausal women with osteopenia (patients) (mean age 59.1 years, range 54 – 65) and a healed wrist fracture were matched to 18 healthy control subjects on age (mean age 58.5 years, range 51 – 65), height, weight and body mass index (BMI). We measured quadriceps strength at 60°/sec and at 180°/sec with Biodex 6000, dynamic balance with the Four Square Step Test (FSST), physical capacity with the six-minute walk test (6MWT) followed by the Borg’s scale (BS), and QOL with the Short Form 36 (SF-36), bone mineral density (BMD) with dual x-ray absorptiometry (DXA) and physical activity level with the Physical Activity Scale for the Elderly. Results The patients had 17.6% lower quadriceps strength at 60°/sec (p = 0.025) at left limb and 18.5% at 180°/sec (p = 0.016) at right limb, and 21% lower at 180°/sec (p = 0.010) at left limb compared to the controls. Impaired performance for the patients was found with 2.4 seconds (p = 0.002) on the FSST, 74 metres (p < 0.001) on the 6MWT, and 1.4 points (p = 0.003) on the BS compared to the controls. The patients scored lower on the sub-scales on the SF-36 role limitations-physical (p = 0.014), bodily pain (p = 0.025) and vitality (p = 0.015) compared to the controls. Conclusions The patients with osteopenia and a healed wrist fracture scored significantly lower on quadriceps strength, dynamic balance, physical capacity and QOL compared to the matched controls. Greater focus should be put on this patient group in terms of rehabilitation and early prevention of subsequent fractures. PMID:25086601

Flow Through Cement Fracture Under Geological Carbon Sequestration Conditions: Critical Residence Time as a Unifying Parameter for Fracture Opening or Self-Sealing Behavior

NASA Astrophysics Data System (ADS)

Li, L.; Brunet, J. P. L.; Karpyn, Z.; Huerta, N. J.

2016-12-01

During geological carbon sequestration (GCS) large quantities of CO2 are injected in underground formations. Cement fractures represent preferential leakage pathways in abandoned wells upon exposure to CO2-rich fluid. Contrasting self- healing and fracture opening behavior have been observed while a unifying framework is still missing. The modelling of this process is challenging as it involves complex chemical, mechanical and transport interactions. We developed a process-based reactive transport model that explicitly simulates flow and multi-component reactive transport in fractured cement by reproducing experimental observations of sharp flow rate reduction during exposure to carbonated water. Mechanical interactions have not been included. The simulation shows a similar reaction network as in diffusion-controlled systems without flow. That is, CO2-rich water induced portlandite dissolution, releasing calcium that further reacted with carbonate to form calcite. This created localized changes in porosity and permeability inducing large differences in the long term response of the system through a complex positive feedback loop (e.g., a decrease in local permeability induces a decrease in flow that in turn amplifies the precipitation of calcite through a reduced acidic brine flow). The calibrated model was used to generate 250 numerical experiments of CO2-flooding in cement fractures with varying initial hydraulic apertures (b) and residence times (τ) defined as the ratio of fracture volume over flow rate. A long τ leads to slow replenishment of carbonated water, calcite precipitation, and self-sealing. The opposite occurs when τ is small with short fractures and fast flow rates. Simulation results indicate that a critical residence time τc - the minimum τ required for self-sealing -divides the conditions that trigger the diverging opening and self-sealing behavior. The τc value depends on the initial aperture size (see figure). Among the 250 simulated fracture cases, significant changes in effective permeability - self-healing or opening - typically occurs within hours to a day, thus providing a supporting argument for the extrapolation of short-term laboratory observations (hours to months) to long-term predictions at relevant GCS time scales (years to hundreds of years).

[Surgical treatment of midshaft clavicular fractures using intramedullary nail].

PubMed

Vlček, M; Niedoba, M; Jakubička, J; Pech, J; Kalvach, J

2018-01-01

The aim of our study was to assess treatment outcomes in fractures of the middle part of the clavicle using an intramedullary nail. We have evaluated a total of 58 patients with a clavicle bone fracture stabilized by the Hofer Clavicula Pin implant (HCP, Hofer GmbH & Co KG, Fürstenfeld, Germany). A static implant was used in 43 cases, and a dynamic implant was used in the remaining 15. The mean age of patients was 39.1 years (range 1871, SD 4.4), the male-to-female ratio being 43:15. The right collarbone was broken in 26 patients, the left one in 32. The average time between accident and surgery was 10.2 days (range 2-19, SD 4.4). The set included 24 two-, 14 three- and 20 four-fragment fractures of the clavicle midshaft. Open reduction was used in all the cases. The implant was introduced by the indirect method: first, insertion of the pin from the fracture antegrade into the lateral fragment took place, then it was inserted retrogradely into the medial fragment. The average patient follow-up was 7.1 months (range 623, SD 5.5). X-ray signs of healing were evident in all cases, with healing occurring at 8.4 weeks on average (range 620, SD 4.1). In one case (1.7%), however, healing did not occur - refracture was diagnosed 18 days following pin extraction with no clear mechanism of injury; two more refractures were caused by a new accident. The apex of the pin was broken in four cases (6.9%). In two cases (3.4%), angulation of the pin occurred; however, full fracture healing was satisfactorily achieved. Pin prominence was observed in a total of 23 cases (39.7%), requiring premature extraction of the implant due to perforation or irritation of skin and pain in 13 (22.4%) cases. 10 cases (17.2%) of prominence were asymptomatic. Six cases with skin perforation by the implant developed clinical signs of infection, wound healing was always achieved after extraction of the pin and application of antibiotics. A very good functional finding in the shoulder joint was observed in 57 patients (98.2%). The DASH score reached an average of 8.1 points (range 0.8-30.8, SD 4.4). Constant score was 93.1 (range 42.8-98.1, SD 3.2). Intramedullary stabilization of two-, three- and four-fragment fractures of the middle part of the clavicle using the Hofer Clavicula Pin provides very good stability during healing and leads to good healing of fractures. The complications of the method are soft tissue irritation or even skin perforation in the region of the lateral end of the implant. Preventive insertion of the pin closer to the bone may prevent such complications, but also result in difficult pin extraction.Key words: fractures - clavicle - osteosynthesis - intramedullary complications.

Adjustable patella grapple versus cannulated screw and cable technique for treatment of transverse patellar fractures.

PubMed

Yan, Ning; Yang, Anli; Liu, Xiaodong; Cai, Feng; Liu, Liang; Chang, Shimin

2014-03-01

Although the cannulated screw and cable (CSC) tension band technique is an effective method for fixation of transverse patellar fractures, it has shortcomings, such as extensive soft tissue damage, osseous substance damage, and complex manipulation. We conducted a retrospective comparison of the adjustable patella grapple (APG) technique and the CSC tension band technique. We retrospectively reviewed 78 patients with transverse patellar fractures (45 in the APG group and 33 in the CSC group). Follow-up was 18 months. Comparison criteria were operation time, fracture reduction, fracture healing time, the knee injury and osteoarthritis outcome score for knee function, and complications. The APG group showed shorter operation time and equal fracture reduction, fracture healing time, and knee function compared with the CSC group. Eleven patients in the APG group experienced skin irritation generated by implants. There was no complication in the CSC group. The APG technique should be considered as an alternative method for treatment of transverse patellar fractures.

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

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.

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

Fractured cement reactivity during CO2-rich brine leakage: Consequences on hydrodynamic and structural properties

NASA Astrophysics Data System (ADS)

abdelghafour, H.; Luquot, L.; Gouze, P.

2013-12-01

So far, cement alteration was principally studied experimentally using batch reactor (with static or renewed fluid). All exhibit similar carbonation mechanisms. The acidic solution, formed by the dissolution of the CO2 into the pore water or directly surrounding the cement sample, diffuses into the cement and induces dissolution reactions of the cement hydrates in particular portlandite and CSH. The calcium released by the dissolution of these calcium bearing phases combining with carbonate ions of the fluid forms calcium carbonates. The cement pH, initially around 13, falls to values where carbonate ion is the most dominant element (pH ~ 9), then CaCO3 phases can precipitate. These studies mainly associate carbonation process with a reduction of porosity and permeability. Indeed an increase of volume (about 10%) is expected during the formation of calcite from portlandite assuming a stoichiometric reaction. Here we investigated the cement alteration mechanisms in the frame of a controlled continuous renewal of CO2-rich fluid in a fracture. This situation is that expected when seepage is activated by the mechanical failure of the cement material that initially seals two layers of distinctly different pressure: the storage reservoir and the aquifer above the caprock, for instance. We study the effect of flow rates from quasi-static flow to higher flow rates for well-connected fractures. In the quasi-static case we observed an extensive conversion of portlandite (Ca(OH)2) to calcite in the vicinity of the fracture similar to that observed in the published batch experiments. Eventually, the fracture was almost totally healed. The experiments with constant flow revealed a different behavior triggered by the continuous renewing of the reactants and withdrawal of the reaction products. We showed that calcite precipitation is more efficient for low flow rate. With intermediate flow rate, we measured that permeability increases slowly at the beginning of the experiment and then remains constant due to calcite precipitation in replacement of CSH and CH into fracture border. With higher flow rate, we measured a constant permeability which can be explained by the development of a highly hydrated Si-rich zone which maintains the initial fracture aperture during all over the experiment while noticeable mass is released from the sample. These results emphasize that more complex behaviors than that envisaged from batch experiments may take place in the vicinity of flowing fractures. We demonstrated that if only micro-cracks appear in the cement well, carbonation reaction may heal these micro-cracks and mitigate leakage whereas conductive fractures allowing high flow may represent a risk of perennial leakage because the net carbonation process, including the calcite precipitation and its subsequent re-dissolution, is sufficiently to heal the fracture. However, the precipitation of Si-rich amorphous phases may maintain the initial fracture aperture and limit the leakage rate.

Noninvasive evaluation system of fractured bone based on speckle interferometry

NASA Astrophysics Data System (ADS)

Yamanada, Shinya; Murata, Shigeru; Tanaka, Yohsuke

2010-11-01

This paper presents a noninvasive evaluation system of fractured bone based on speckle interferometry using a modified evaluation index for higher performance, and the experiments are carried out to examine the feasibility in evaluating bone fracture healing and the influence of some system parameters on the performance. From experimental results, it is shown that the presence of fractured part of bone and the state of bone fracture healing are successfully estimated by observing fine speckle fringes on the object surface. The proposed evaluation index also can successfully express the difference between the cases with cut and without it. Since most system parameters are found not to affect the performance of the present technique, the present technique is expected to be applied to various patients that have considerable individual variability.

Unexpected timely fracture union in matrix metalloproteinase 9 deficient mice.

PubMed

Yuasa, Masato; Saito, Masanori; Molina, Cesar; Moore-Lotridge, Stephanie N; Benvenuti, Michael A; Mignemi, Nicholas A; Okawa, Atsushi; Yoshii, Toshitaka; Schwartz, Herbert S; Nyman, Jeffry S; Schoenecker, Jonathan G

2018-01-01

Immediately following a fracture, a fibrin laden hematoma is formed to prevent bleeding and infection. Subsequently, the organized removal of fibrin, via the protease plasmin, is essential to permit fracture repair through angiogenesis and ossification. Yet, when plasmin activity is lost, the depletion of fibrin alone is insufficient to fully restore fracture repair, suggesting the existence of additional plasmin targets important for fracture repair. Previously, activated matrix metalloproteinase 9 (MMP-9) was demonstrated to function in fracture repair by promoting angiogenesis. Given that MMP-9 is a defined plasmin target, it was hypothesized that pro-MMP-9, following plasmin activation, promotes fracture repair. This hypothesis was tested in a fixed murine femur fracture model with serial assessment of fracture healing. Contrary to previous findings, a complete loss of MMP-9 failed to affect fracture healing and union through 28 days post injury. Therefore, these results demonstrated that MMP-9 is dispensable for timely fracture union and cartilage transition to bone in fixed femur fractures. Pro-MMP-9 is therefore not a significant target of plasmin in fracture repair and future studies assessing additional plasmin targets associated with angiogenesis are warranted.

Evaluation of Two Miniplate Systems and Figure-of-eight Bandages for Stabilization of Experimentally Induced Ulnar and Radial Fractures in Pigeons ( Columba livia ).

PubMed

Bennert, Beatrice M; Kircher, Patrick R; Gutbrod, Andreas; Riechert, Juliane; Hatt, Jean-Michel

2016-06-01

Although plate fixation has advantages over other fixation methods for certain indications, it is rarely used in avian surgery, especially in birds that weigh less than 1000 g. Exceptionally small plating systems for these birds are required, which are relatively expensive and difficult to insert. To study avian fracture healing after repair using miniplates, we evaluated 2 steel miniplate systems in 27 pigeons ( Columba livia ) divided into 4 groups. In each pigeon, the left ulna and radius were transected and the ulna was repaired with a bone plate. In groups A and B, a 1.3-mm adaption plate was applied without and with a figure-of-eight bandage; in groups C and D, a 1.0-mm compression plate was applied without and with a bandage, respectively. Healing was evaluated with radiographs after 3, 14, and 28 days; flight tests were conducted after 14, 21, and 28 days; and the wing was macroscopically examined after euthanasia of birds on day 28. Fractures healed without bending or distortion of the plate in all 27 birds, and no significant differences in healing were found between treatment groups. At the end of the study, 23 pigeons (85.2%) showed good or very good flight ability. Results show the 1.3-mm adaption plate and the 1.0-mm compression plate meet the requirements for avian osteosynthesis and can be recommended for fracture repair of the ulna or other long bones in birds weighing less than 500 g. The application of a figure-of-eight bandage might be beneficial in fracture healing.

The value of magnetic resonance imaging in the diagnosis of penile fracture

PubMed Central

Guler, Ibrahim; Ödev, Kemal; Kalkan, Havva; Simsek, Cihan; Keskin, Suat; Kilinç, Mehmet

2015-01-01

Purpose We studied the use of magnetic resonance imaging in the diagnosis of penile fracture. Materials and Methods Between 1997 and 2012, fifteen patients (age range 17-48 years, mean age 37 years) with suspected penile fracture underwent MRI examinations. Ten patients were injured during sexual intercourse, whereas four patients were traumatized by non-physiological bending of the penis during self manupilation, one patient was traumatized falling from the bed. Investigations were performed with 1.5T MR unit. With the patient in the supine position, the penis was taped against the abdominal wall and surface coil was placed on the penis. All patients were studied with axial, coronal, sagittal precontrast and postcontrast T1-weighted TSE(TR/TE:538/13 msn) and T2-weighted TSE(5290/110 msn) sequences. All patient underwent surgical exploration. The follow-up ranged from 3 months to 72 months. Clinically all patients showed normal healing process without complications. In 11 patients a shortening and thickening of tunica albuginea was observed. Three patients have post traumatic erectil disfunction. Results In all patient corpus cavernosum fractures were clearly depicted on a discontinuity of the low signal intensity of tunica albuginea. These findings were most evident on T1WI and also depicted on T2W sequences. Images obtained shortly after contrast medium administration showed considerable enhancement only in rupture site. Subcutaneous extratunical haematoma in all patients were also recognizable on T2 WI. MRI findings were confirmed at surgery. Conclusions Magnetic resonance imaging is of great value for the diagnosis of penile fracture. Furthermore this method is well suited for visualising the post-operative healing process PMID:26005975

Transdifferentiation of myoblasts into osteoblasts - possible use for bone therapy.

PubMed

Lin, Daphne P L; Carnagarin, Revathy; Dharmarajan, Arun; Dass, Crispin R

2017-12-01

Transdifferentiation is defined as the conversion of one cell type to another and is an ever-expanding field with a growing number of cells found to be capable of such a process. To date, the fact remains that there are limited treatment options for fracture healing, osteoporosis and bone repair post-destruction by bone tumours. Hence, this review focuses on the transdifferentiation of myoblast to osteoblast as a means to further understand the transdifferentiation process and to investigate a potential therapeutic option if successful. The potent osteoinductive effects of the bone morphogenetic protein-2 are largely implicated in the transdifferentiation of myoblast to osteoblast. Bone morphogenetic protein-2-induced activation of the Smad1 protein ultimately results in JunB synthesis, the first transcriptional step in myoblast dedifferentiation. The upregulation of the activating protein-1 binding activity triggers the transcription of the runt-related transcription factor 2 gene, a transcription factor that plays a major role in osteoblast differentiation. This potential transdifferentiation treatment may be utilised for dental implants, fracture healing, osteoporosis and bone repair post-destruction by bone tumours. © 2017 Royal Pharmaceutical Society.

The use of resorbable plates in association with dental arch stabilization in the treatment of mandibular fractures in children.

PubMed

Li, Zhi; David, Ongodia; Li, Zu-Bing

2014-07-01

The purpose of this study was to investigate the effect of resorbable plate fixation in association with dental arch stabilization in the treatment of displaced mandibular fractures in children. Thirteen children (5 girls and 8 boys, age range 2 years 5 months to 12 years 2 months) with displaced mandibular fractures were included in this case series. Open reduction by intraoral approach was performed on these patients, and the fractures were fixed using resorbable plates and monocortical screws placed at the lower border of the mandible. At the same time, an arch bar or orthodontic wire splint was anchored using stainless steel wires or resin on the teeth to stabilize the whole mandibular dental arch. Postoperatively, follow-up was undertaken to evaluate the fracture healing, mandible movement, and mandible growth. Postoperatively, all patients achieved uneventful healing; premorbid occlusion restoration and wound healing were achieved, along with unimpaired function and normal growth and development of the mandible. Complications such as damage to tooth buds, infection, malunion, and nonunion were not encountered in these patients. Resorbable plates use in association with dental arch stabilization can provide good stabilization for mandibular fractures and is a promising approach for the treatment of displaced mandibular fractures in children. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

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.

Surgical and medical management for fractures of the second through fifth metacarpals in a red ruffed lemur (Varecia rubra).

PubMed

Cerveny, Shannon N S; Harper, Justin; Voges, Andra; Coke, Rob L

2013-03-01

A 21-yr-old female red ruffed lemur (Varecia rubra) was presented with swelling and disuse of the right manus. Severely displaced fractures of metacarpals II-V were diagnosed radiographically. The fractures were surgically stabilized with intramedullary Kirschner wires attached externally with an acrylic external fixator and a bone plate on the dorsal aspect of metacarpal III. The fractures of metacarpals II-V were predominantly healed on radiographs obtained 12 wk after surgery. However, diffuse disuse osteopenia and phalangeal contracture were present, with possible osteomyelitis. An exercise regimen of the affected hand was initiated due to the incomplete extension of the phalanges. After 4 wk of therapy, the extension of the phalanges had improved and the fractures appeared radiographically to be nearly completely healed. Although metacarpal fractures are common in nonhuman primates, they are reported infrequently in the literature.

Early Experience with Biodegradable Fixation of Pediatric Mandibular Fractures.

PubMed

Mazeed, Ahmed Salah; Shoeib, Mohammed Abdel-Raheem; Saied, Samia Mohammed Ahmed; Elsherbiny, Ahmed

2015-09-01

This clinical study aims to evaluate the stability and efficiency of biodegradable self-reinforced poly-l/dl-lactide (SR-PLDLA) plates and screws for fixation of pediatric mandibular fractures. The study included 12 patients (3-12 years old) with 14 mandibular fractures. They were treated by open reduction and internal fixation by SR-PLDLA plates and screws. Maxillomandibular fixation was maintained for 1 week postoperatively. Clinical follow-up was performed at 1 week, 6 weeks, 3 months, and 12 months postoperatively. Radiographs were done at 1 week, 3 months, and 12 months postoperatively to observe any displacement and fracture healing. All fractures healed both clinically and radiologically. No serious complications were reported in the patients. Normal occlusion was achieved in all cases. Biodegradable osteofixation of mandibular fractures offers a valuable clinical solution for pediatric patients getting the benefit of avoiding secondary surgery to remove plates, decreasing the hospital stay, further painful procedures, and psychological impact.

Steroid osteopathy

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

Conway, J.J.; Weiss, S.C.

1984-01-01

Patients receiving steroids or having disease processes which increase natural steroid production often demonstrate ''the classic x-ray changes'' of avascular necrosis of bone. Bone scintigraphy in these patients most frequently demonstrates an increased radionuclide localization. The literature suggests that the increased activity is related to healing of the avascular process. In a recent study of Legg-Calve-Perthes Disease (LCPD), 37 of the children had multiple studies and increased activity within the epiphysis during revascularization was extremely rare. Not only are the scintigraphic findings in steroid osteopathy dissimilar to that in healing LCPD, but the time interval for healing is much tomore » short for that of a vascular necrosis and no patients demonstrated an avascular phase on bone scintigraphy. Of 15 children with renal transplants on steroid therapy, 9 demonstrated x-ray and clinical findings of osteopathy. In 8 of 9 instances, bone scintigraphy showed increased localization of radionuclide in the affected bone. Improvement or a return to normal occurred in those patients in whom steroids were discontinued. The following is a proposed mechanism for steroid osteopathy. Steroids affect the osteoblastic and osteoclastic activity of bone and weaken its internal structure. Ordinary stress produces microtrabecular fractures. Fractures characteristically stimulate reactive hyperemia and increase bone metabolism. The result is increased bone radiopharmaceutical localization. The importance of recognizing this concept is that steroid osteopathy is preventable by reducing the administered steroid dose. As opposed to avascular necrosis, bone changes are reversible.« less

Self-Healing Efficiency of Cementitious Materials Containing Microcapsules Filled with Healing Adhesive: Mechanical Restoration and Healing Process Monitored by Water Absorption

PubMed Central

Li, Wenting; Jiang, Zhengwu; Yang, Zhenghong; Zhao, Nan; Yuan, Weizhong

2013-01-01

Autonomous crack healing of cementitious composite, a construction material that is susceptible to cracking, is of great significance to improve the serviceability and to prolong the longevity of concrete structures. In this study, the St-DVB microcapsules enclosing epoxy resins as the adhesive agent were embedded in cement paste to achieve self-healing capability. The self-healing efficiency was firstly assessed by mechanical restoration of the damaging specimens after being matured. The flexural and compressive configurations were both used to stimulate the localized and distributed cracks respectively. The effects of some factors, including the content of microcapsules, the curing conditions and the degree of damage on the healing efficiency were investigated. Water absorption was innovatively proposed to monitor and characterize the evolution of crack networks during the healing process. The healing cracks were observed by SEM-EDS following. The results demonstrated that the capsule-containing cement paste can achieve the various mechanical restorations depending on the curing condition and the degree of damage. But the voids generated by the surfactants compromised the strength. Though no noticeable improved stiffness obtained, the increasing fracture energy was seen particularly for the specimen acquiring 60% pre-damage. The sorptivity and amount of water decreased with cracks healing by the adhesive, which contributed to cut off and block ingress of water. The micrographs by SEM-EDS also validated that the cracks were bridged by the hardened epoxy as the dominated elements of C and O accounted for 95% by mass in the nearby cracks. PMID:24312328

Self-healing efficiency of cementitious materials containing microcapsules filled with healing adhesive: mechanical restoration and healing process monitored by water absorption.

PubMed

Li, Wenting; Jiang, Zhengwu; Yang, Zhenghong; Zhao, Nan; Yuan, Weizhong

2013-01-01

Autonomous crack healing of cementitious composite, a construction material that is susceptible to cracking, is of great significance to improve the serviceability and to prolong the longevity of concrete structures. In this study, the St-DVB microcapsules enclosing epoxy resins as the adhesive agent were embedded in cement paste to achieve self-healing capability. The self-healing efficiency was firstly assessed by mechanical restoration of the damaging specimens after being matured. The flexural and compressive configurations were both used to stimulate the localized and distributed cracks respectively. The effects of some factors, including the content of microcapsules, the curing conditions and the degree of damage on the healing efficiency were investigated. Water absorption was innovatively proposed to monitor and characterize the evolution of crack networks during the healing process. The healing cracks were observed by SEM-EDS following. The results demonstrated that the capsule-containing cement paste can achieve the various mechanical restorations depending on the curing condition and the degree of damage. But the voids generated by the surfactants compromised the strength. Though no noticeable improved stiffness obtained, the increasing fracture energy was seen particularly for the specimen acquiring 60% pre-damage. The sorptivity and amount of water decreased with cracks healing by the adhesive, which contributed to cut off and block ingress of water. The micrographs by SEM-EDS also validated that the cracks were bridged by the hardened epoxy as the dominated elements of C and O accounted for 95% by mass in the nearby cracks.

Open-wedge high tibial osteotomy: incidence of lateral cortex fractures and influence of fixation device on osteotomy healing.

PubMed

Dexel, Julian; Fritzsche, Hagen; Beyer, Franziska; Harman, Melinda K; Lützner, Jörg

2017-03-01

Open-wedge high tibial osteotomy (HTO) is an established treatment for young and middle-aged patients with medial compartment knee osteoarthritis and varus malalignment. Although not intended, a lateral cortex fracture might occur during this procedure. Different fixation devices are available to repair such fractures. This study was performed to evaluate osteotomy healing after fixation with two different locking plates. Sixty-nine medial open-wedge HTO without bone grafting were followed until osteotomy healing. In patients with an intact lateral hinge, no problems were noted with either locking plate. A fracture of the lateral cortex occurred in 21 patients (30.4 %). In ten patients, the fracture was not recognized during surgery but was visible on the radiographs at the 6-week follow-up. Lateral cortex fracture resulted in non-union with the need for surgical treatment in three out of eight (37.5 %) patients using the newly introduced locking plate (Position HTO Maxi Plate), while this did not occur with a well-established locking plate (TomoFix) (0 out of 13, p = 0.023). With regard to other adverse events, no differences between both implants were observed. In cases of lateral cortex fracture, fixation with a smaller locking plate resulted in a relevant number of non-unions. Therefore, it is recommended that bone grafting, another fixation system, or an additional lateral fixation should be used in cases with lateral cortex fracture. III.

Cyclic activity at silicic volcanoes: A response to dynamic permeability variations

NASA Astrophysics Data System (ADS)

Lamur, Anthony; Lavallée, Yan; Kendrick, Jackie; Eggertsson, Gudjon; Ashworth, James; Wall, Richard

2017-04-01

Silicic volcanoes exhibit cyclic eruptive activity characterised by effusive (dome growth) to quiescent periods punctuated by short explosive episodes. The latter, characterised by fast emissions of gas and ash into the atmosphere, results from stress release through fracturing and causes significant hazards to the surrounding environment. Understanding the formation, development and closure of fractures as well as their impact on the volcanic system is hence vital for better constraining current models. Here, we present the results of two sets of experiments designed to understand first, the development of permeability through fracturing and second, the timescale over which these fractures can persist in magmas. To characterise the influence of a macro-fracture, the permeability of intact volcanic rocks with a wide porosity range (1-41%) was measured at varying effective pressures (-0.001-30 MPa). We then fractured each sample using the Brazilian disc method to induce a tensile macro-fracture, before measuring the permeability under the same conditions. While our results for intact samples are consistent with previous studies, the results for fractured samples display a distinct permeability-porosity relationship. We show that low porosity samples (<18%) suffer a net increase in permeability of up to 4 orders of magnitude upon fracturing, compared to high porosity samples (>18%) that show a less than 1 order of magnitude increase. This suggests that a macro-fracture has the ability to efficiently localise the flow in low porosity rocks by becoming the prevailing structure in a previously micro-fracture-dominated porous network, whereas at higher porosities fluid flow remains controlled by pore connectivity, irrespective of the presence of a fracture. To assess the longevity of fractures in magmas we developed a novel experimental set-up, in which two glass rods were placed in contact for different timescales at high temperatures before being pulled apart to test the tensile strength recovery of the fracture. We show that fracture healing starts within timescales 50-100 times longer than the structural relaxation time of the melt and that that full healing can be achieved within only a few hours of contact (timescale decreasing with decreasing viscosities) at magmatic temperatures. These results are important for understanding the permeability decrease associated with annealing. We postulate that rapid permeability evolution due to fracturing or fracture healing may be the cause of observed cyclicity at silicic volcanoes, whereby "instantaneous" increases in permeability occur through the development of macro-fractures drives explosions. We propose that the timescale for this cyclicity is governed by the competition between stress build up through gas accumulation under a relatively impervious plug until failure and fracture healing through annealing or, as shown in other studies, mineral precipitation and sintering of particulate material in fractures.

THE FORMATION OF BONE CALLUS DURING RADIATION SICKNESS (in Russian)

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

Nazarishvill, G.P.; Vepkhvadze, R.Ya.; Vakhtangashvili, T.A.

1957-01-01

>Six dogs were irradiated with an x-ray dose of 408 r, and the skin bone was thee broken immediately after radiation. The healing process was followed by x rays in the control group of dogs in which a well-developed bone callus could be observed on the 50th day. No sign of the formation of a bone callus at the fracture site could be observed in any of the irradiated dogs. Even on the l02nd day after the fracture a wide slit could be seen on thee x-ray diagram at the point of fracture where the bones had not knit togethermore » in the irradiated dogs. (TTT)« less

[Multidisciplinary approach of hip fractures based on Hungarian data].

PubMed

Juhász, Krisztina; Turchányi, Béla; Mintál, Tibor; Somogyi, Péter

2016-09-01

Hip fractures are described by increased mortality, loss of quality of life, functional decline and burden of diseases. They show a growing number worldwide. The aim of the present study is to summarise the existing data on the incidence, mortality, complications and rehabilitation of hip fractures, which relevance is reported only by few studies. To reduce mortality and complications of hip fractures the authors emphasize the importance of primary treatment within 12 hours, appropriate selection of surgical methods corresponding to the fracture type after the assessment of femoral head viability, vitamin D supplementation, same conditions for primary treatment during everyday of the week, and an adequate acute treatment and rehabilitation for patient's general health status. In the future integrated processing of multidisciplinary results of hip fractures based on Hungarian data can support the development of efficient treatment and prevention strategies, which can be advantageous for the patient, families, health care system, and the society, too, by the reduction of costly complications of hip fracture healing and mortality. Orv. Hetil., 2016, 157(37), 1469-1475.

Pattern formation during healing of fluid-filled cracks: an analog experiment

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

F. Renard; D. K. Dysthe; J. G. Feder

2009-11-01

The formation and subsequent healing of cracks and crack networks may control such diverse phenomena as the strengthening of fault zones between earthquakes, fluid migrations in the Earth's crust, or the transport of radioactive materials in nuclear waste disposal. An intriguing pattern-forming process can develop during healing of fluid-filled cracks, where pockets of fluid remain permanently trapped in the solid as the crack tip is displaced driven by surface energy. Here, we present the results of analog experiments in which a liquid was injected into a colloidal inorganic gel to obtain penny-shaped cracks that were subsequently allowed to close andmore » heal under the driving effect of interfacial tension. Depending on the properties of the gel and the injected liquid, two modes of healing were obtained. In the first mode, the crack healed completely through a continuous process. The second mode of healing was discontinuous and was characterized by a 'zipper-like' closure of a front that moved along the crack perimeter, trapping fluid that may eventually form inclusions trapped in the solid. This instability occurred only when the velocity of the crack tip decreased to zero. Our experiments provide a cheap and simple analog to reveal how aligned arrays of fluid inclusions may be captured along preexisting fracture planes and how small amounts of fluids can be permanently trapped in solids, modifying irreversibly their material properties.« less

[Treatment of multi-segment fracture of complex femoral shaft with instrument-assisted reduction combined with intramedullary interlocking nail fixation].

PubMed

Fan, Ke-Jie; Chen, Ke; Ma, Wen-Long; Tian, Ke-Wei; Ye, Ye; Chen, Hong-Gan; Tang, Yan-Feng; Cai, Hong-Min

2018-05-25

To investigate the effect of minimally invasive mini-incision and instrumented reduction combined with interlocking intramedullary nailing in the treatment of patients with multi-segment fracture of complex femoral shaft. From January 2013 to January 2016, 32 patients with multiple fractures segments of femoral shaft were treated with instrumentation-assisted reduction combined with interlocking intramedullary nailing, including 22 males and 10 females with an average age of 45 years old ranging 17 to 68 years old. The time from injured to operation was 5 to 10 days with an average of 7 days. After admission, routine tibial tubercle or supracondylar bone traction was performed. The patient's general condition was evaluated, the operation time and intraoperative blood loss were recorded. According to Thorsen femoral fracture morphology evaluation criteria and Hohl knee function evaluation of postoperative efficacy, postoperative fracture healing, complications and postoperative recovery of limb function were observed. All patients were followed up for 6 to 24 months with an average of 12 months. The operative time ranged from 48 to 76 minutes with an average of 67 min. The intraoperative blood loss was 150 to 400 ml with an average of 220 ml. The surgical incisions all achieved grade A healing. The fractures reached the clinical standard of healing. The fracture healing time ranged from 4.2 to 10.8 months with an average of 5.7 months. There were no nonunion, incision infection and internal fixation fracture, failure and other complications. According to Thorsen femoral fracture morphology evaluation criteria, the result was excellent in 28 cases, good in 3 cases, fair in 1 case. According to Hohl knee function evaluation criteria, the result was excellent in 30 cases, good in 2 cases. Instrument-assisted reduction combined with interlocking intramedullary nail fixation is a safe and effective method for the treatment of complex femoral shaft fractures. It has advantages of small trauma, fixed fixation, quick recovery, early postoperative functional exercise. Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.

[EFFECTIVENESS OF SHARP TEETH HOOK PLATE FOR TREATMENT OF OLECRANON FRACTURES].

PubMed

Yin, Qudong; Gu, Sanjun; Liu, Jun; Wu, Yongwei; Lu, Yao; Ma, Yunhong; Sheng, Youyin

2016-09-08

To investigate the effectiveness of sharp teeth hook plate by cutting for the treatment of olecranon fractures by comparison with Kirschner wire tension belt and locking plate. Between January 2011 and April 2015, 32 cases of olecranon fractures were treated. Fracture was fixed with sharp teeth hook plate by cutting in 12 cases (trial group) and with Kirschner wire tension belt or locking plate in 20 cases (control group). There was no significant difference in gender, age, side and type of fracture, and time from injury to operation between 2 groups ( P >0.05). The healing time of fractures and complications were recorded. At 1 year after operation, the subjective function results were evaluated according to Disability of Arm, Shoulder, and Hand (DASH) score, and objective function results by Mayo Elbow Score (MEPS); visual analogue scale (VAS) was used for elbow joint pain, and range of motion of flexion and extension of elbow joint was measured. All incisions healed by first intention, with no vascular and nerve injuries. All patients were followed up 12-36 months with an average of 18 months. All fractures healed, and there was no significant difference in the healing time between 2 groups ( P >0.05). Loosening of Kirschner wire occurred in 2 cases of control group, but no loosening of internal fixation was observed in trial group after operation. There was no significant difference in the incidence of complications between 2 groups ( P >0.05). The DASH, MEPS, VAS score, and range of motion of flexion in trial group were superior to those in control group, showing significant differences ( P <0.05) at 1 year after operation. There was no significant difference in range of motion of extension between 2 groups ( P >0.05). Sharp teeth hook plate for treatment of olecranon fractures overcomes the shortcomings that Kirschner wire tension is easy to slide and locking plate has a compression effect on triceps tendon, so it has good effectiveness.

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.

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

Nonsteroidal anti-inflammatory drug-induced fracture nonunion: an inhibition of angiogenesis?

PubMed

Murnaghan, Mark; Li, Gang; Marsh, David R

2006-11-01

Approximately 5% to 10% of fractures may result in delayed union or nonunion. The results of research done over the past three decades have shown that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) has an inhibitory effect on fracture repair, but the exact mechanism of action remains to be elucidated. Cancer research has identified that NSAIDs impede cell proliferation by inhibiting angiogenesis. It is proposed that a similar mechanism occurs in the induction of NSAID-induced nonunions. This hypothesis was investigated in a randomized placebo-controlled trial of the NSAID rofecoxib with use of a murine femoral fracture model. Two hundred and forty mice were randomized to receive either the nonsteroidal anti-inflammatory drug rofecoxib (5 mg/kg orally) in a 0.5% methylcellulose solution (the NSAID group) or the 0.5% methylcellulose solution only (the control group). Two hundred and thirty-five of the 240 mice underwent surgery to induce an open transverse middiaphyseal femoral fracture, which was then treated with use of a custom-made external fixator. Five additional animals underwent sham surgery with no fracture induced. Outcomes measures included radiographic assessment, histologic analysis, biomechanical testing, and use of laser Doppler flowmetry to assess blood flow across the fracture gap. Radiography revealed similar healing patterns in both groups; however, at the later stages (day 32), the NSAID group had poorer healing. Histological analysis demonstrated that the control animals healed quicker (at days 24 and 32) and had more callus and less fibrous tissue (at days 8 and 32) than the NSAID animals did. Biomechanical testing found that the control animals were stronger at day 32. Both groups exhibited a similar pattern of blood flow; however, the NSAID group exhibited a lower median flow from day 4 onward (significant at days 4, 16, and 24). Positive correlations were demonstrated between both histological and radiographic assessments of healing and increasing blood flow. NSAID-treated animals exhibited lower blood flow and poorer healing by all parameters. Regression analysis, however, demonstrated that the negative effect of NSAIDs on fracture repair is independent of its inhibitory action on blood flow. Following the development of a novel method of analyzing functional vascularity across a fracture gap, we have demonstrated that the cyclooxygenase-2 (COX-2) inhibitor rofecoxib has a significant negative effect on blood flow across the fracture gap as well as an inhibiting effect on fracture repair. COX-2 inhibitors are marketed as having low side-effect profiles. We propose that these drugs should be used with caution in all patients following osseous trauma and, in particular, after injuries that may already predispose a fracture to a delayed union due to osseous, vascular, or patient-related factors.

Surface-enhanced Raman scattering study of the healing of radial fractures treated with or without Huo-Xue-Hua-Yu decoction therapy

NASA Astrophysics Data System (ADS)

Chen, Weiwei; Huang, Hao; Chen, Rong; Feng, Shangyuan; Yu, Yun; Lin, Duo; Lin, Jia

2014-11-01

This study aimed to assess, through surface-enhanced Raman scattering (SERS) spectroscopy, the incorporation of calcium hydroxyapatite (CHA ~960 cm-1) and other biochemical substances in the repair of complete radial fractures in rabbits treated with or without Huo-Xue-Hua-Yu decoction (HXHYD) therapy. A total of 18 rabbits with complete radial fractures were randomly divided into two groups; one group was treated with HXHYD therapy and the other without therapy acted as a control. The animals were sacrificed at 15, 30 and 45 d after surgery. Specimens were routinely prepared for SERS measurement and high quality SERS spectra from a mixture of bone tissues and silver nanoparticles were obtained. The mineral-to-matrix ratios from the control and treated groups were calculated. Results showed that both deposition content of CHA measured by SERS spectroscopy and the mineral-to-matrix ratio in the treated group were always greater than those of the control group during the experiment, demonstrating that HXHYD therapy is effective in improving fracture healing and that SERS spectroscopy might be a novel tool to assess fracture healing.

Stem cell- and scaffold-based tissue engineering approaches to osteochondral regenerative medicine

PubMed Central

Sundelacruz, Sarah; Kaplan, David L.

2009-01-01

In osteochondral tissue engineering, cell recruitment, proliferation, differentiation, and patterning are critical for forming biologically and structurally viable constructs for repair of damaged or diseased tissue. However, since constructs prepared ex vivo lack the multitude of cues present in the in vivo microenvironment, cells often need to be supplied with external biological and physical stimuli to coax them towards targeted tissue functions. To determine which stimuli to present to cells, bioengineering strategies can benefit significantly from endogenous examples of skeletogenesis. As an example of developmental skeletogenesis, the developing limb bud serves as an excellent model system in which to study how an osteochondral structures form from undifferentiated precursor cells. Alongside skeletal formation during embryogenesis, bone also possesses innate regenerative capacity, displaying remarkable ability to heal after damage. Bone fracture healing shares many features with bone development, driving the hypothesis that the regenerative process generally recapitulates development. Similarities and differences between the two modes of bone formation may offer insight into the special requirements for healing damaged or diseased bone. Thus, endogenous fracture healing, as an example of regenerative skeletogenesis, may also inform bioengineering strategies. In this review, we summarize the key cellular events involving stem and progenitor cells in developmental and regenerative skeletogenesis, and discuss in parallel the corresponding cell- and scaffold-based strategies that tissue engineers employ to recapitulate these events in vitro. PMID:19508851

Development of structural ceramics having large crack-healing ability and fracture toughness

NASA Astrophysics Data System (ADS)

Takahashi, Koji; Yokouchi, Masahiro; Lee, Sang-Kee; Ando, Kotoji

2004-02-01

Al2O3 reinforced by SiC whiskers (Al2O3/SiC-W) was hot pressed to investigate the crack-healing behavior. Semi-elliptical surface cracks of 50 to 450μm in surface length were introduced using a Vickers indenter. The specimens containing pre-cracks were crack-healed at temperatures between 1000°C and 1300°C for 1h in air, and their strengths were measured by three-point bending tests at room temperature and elevated temperatures between 400°C and 1300°C. The results show that Al2O3/SiC-W possesses considerable crack-healing ability. The surface cracks with length of 2c=100μm could be healed by crack-healing at 1200°C or 1300°C for 1h in air. The maximum crack size that can be healed for Al2O3/SiC-W is 2c=200μm. Fracture toughness of the material was also determined. As expected, the SiC whiskers made their Al2O3 tougher.

Minimally invasive fixation of type B and C interprosthetic femoral fractures.

PubMed

Ehlinger, M; Czekaj, J; Adam, P; Brinkert, D; Ducrot, G; Bonnomet, F

2013-09-01

Interprosthetic femoral fractures are rare and raise unresolved treatment issues such as the length of the fixation material that best prevents secondary fractures. Awareness of the advantages of locked-plate fixation via a minimally invasive approach remains limited, despite the potential of this method for improving success rates. Femur-spanning (from the trochanters to the condyles) locked-plate fixation via a minimally invasive approach provides high healing rates with no secondary fractures. From January 2004 to May 2011, all eight patients seen for interprosthetic fractures were treated with minimally invasive locked-plate fixation. Mean time since hip arthroplasty was 47.5 months and mean time since knee arthroplasty was 72.6 months. There were 12 standard primary prostheses and four revision prostheses; 11 prostheses were cemented and a single prosthesis showed femoral loosening. Classification about the hip prostheses was Vancouver B in one patient and Vancouver C in seven patients; about the knee prosthesis, the fracture was SoFCOT B in three patients and SOFCOT C in five patients, and a single fracture was SoFCOT D. Minimally invasive locking-plate fixation was performed in all eight patients, with installation on a traction table in seven patients. Healing was obtained in all eight patients, after a mean of 14 weeks (range, 12-16 weeks). One patient had malalignment with more than 5° of varus. There were no general or infectious complications. One patient died, 32 months after surgery. The mean Parker-Palmer mobility score decreased from 6.2 pre-operatively to 2.5 at last follow-up. Early construct failure after 3 weeks in one patient required surgical revision. There was no change in implant fixation at last follow-up. No secondary fractures were recorded. In patients with type B or C interprosthetic fractures, femur-spanning fixation not only avoids complications related to altered bone stock and presence of prosthetic material, but also decreases the risk of secondary fractures by eliminating stress riser zones. The minimally invasive option enhances healing by preserving the fracture haematoma. Thus, healing was obtained consistently in our patients, with no secondary fractures, although the construct failed in one patient. Level IV. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

The role of the lateral pterygoid muscle in the sagittal fracture of mandibular condyle (SFMC) healing process.

PubMed

Liu, Chng-Kui; Liu, Ping; Meng, Fan-Wen; Deng, Bang-Lian; Xue, Yang; Mao, Tian-Qiu; Hu, Kai-Jin

2012-06-01

The aim of this study was to examine the role of the lateral peterygoid muscle in the reconstruction of the shape of the condyle during healing of a sagittal fracture of the mandibular condyle. Twenty adult sheep were divided into 2 groups: all had a unilateral operation on the right side when the anterior and posterior attachments of the discs were cut, and an oblique vertical osteotomy was made from the lateral pole of the condyle to the medial side of the condylar neck. Ten sheep had the lateral pterygoid muscle cut, and the other 10 sheep did not. Sheep were killed at 4 weeks (n=2 from each group), 12 weeks (n=4), and 24 weeks (n=4) postoperatively. Computed tomograms (CT) were taken before and after operations. We dissected the joints, and recorded with the naked eye the shape, degree of erosion, and amount of calcification of the temporomandibular joint (TMJ). In the group in which the lateral peterygoid muscle had not been cut the joints showed overgrowth of new bone and more advanced ankylosis. Our results show that the lateral pterygoid muscle plays an important part in reconstructing the shape of the condyle during the healing of a sagittal fracture of the mandibular condyle, and combined with the dislocated and damaged disc is an important factor in the aetiology of traumatic ankylosis of the TMJ. Copyright © 2011. Published by Elsevier Ltd.

Fracture and healing in magmas: a dual role on permeability evolution

NASA Astrophysics Data System (ADS)

Lamur, Anthony; Lavallée, Yan; Wall, Richard; Ashworth, James; Kendrick, Jackie; Wadsworth, Fabian

2016-04-01

The development of a permeable network in silicic volcanic conduits controls outgassing and plays a major role on the subsequent eruptive behaviour. Efficient outgassing, at higher permeabilities, is achieved through the coalescence of pores and fractures. Whilst the relationship between permeability and increasing connected porosity is now relatively well constrained, the effects of fractures have, on the other hand, rarely been investigated. Here, we present the results of an experimental study focusing on the impacts of tensile fracturing and healing on permeability. Permeability measurements have been performed on over 60 disk-shaped samples (26 mm diameter, 13 mm thickness) with connected porosities ranging from 2 to 45%. Our results for unfractured samples display the same porosity-permeability trend as previous studies and permeabilities span from 10-15 at low porosities to over 5x10-12 m2 at higher porosities. These samples were then broken via Brazilian tests and the resultant permeability of the rocks were then measured across the fracture zone. Whilst high porosity samples reached permeabilities of about 5x10-10 m2 (2 orders of magnitude higher than intact samples), low porosity samples, on the other hand, reached permeabilities around 5x10-12 m2 (more than 3 orders of magnitude above intact samples). Our results show that fracturing favours the development of a permeable network that adheres to a different permeability-porosity relationship than previously presented, and that this effect is emphasized in magmas with low connected porosities. The effect of fracture healing by diffusion on permeability has been investigated through a series of experiments on borosilicate standard glass (NIST 717a). These experiments were conducted at 560oC (viscosity of 1010.33 Pa.s) on pairs of columns pressed and held in contact at constant load for times varying between 0.5s and 15000 s before being pulled apart at a strain rate of 10-3s-1. Using Maxwell's theory of viscoelasticity, we estimate the relaxation timescale for this viscosity at ˜2s. Results show that healing starts after a minimum contact time of 60 s, more than 1 order of magnitude slower than the time predicted by the theory of viscoelasticity. Furthermore, healing and strength recovery increase logarithmically from then. Strength recovery is estimated with respect to the tensile strength of this glass; 25 MPa when measured under the same conditions (560oC and strain rate of 10-3s-1). The time for full-healing can thus be estimated at ˜52000 s, or 2.5x104 times the relaxation timescale. We hereby propose that healing efficiency depends on the destruction of the contact area through atomic diffusive exchanges and bond creation during viscous sintering between the two parts of the sample. The combination of our two sets of experiments allows us to propose a model in which fractures can promote the development of a permeable network which may lead a volcano toward more effusive behaviour, or whereby healing can destroy permeability and allow pressure build-up that could lead to explosive eruption.

Optimisation of composite bone plates for ulnar transverse fractures.

PubMed

Chakladar, N D; Harper, L T; Parsons, A J

2016-04-01

Metallic bone plates are commonly used for arm bone fractures where conservative treatment (casts) cannot provide adequate support and compression at the fracture site. These plates, made of stainless steel or titanium alloys, tend to shield stress transfer at the fracture site and delay the bone healing rate. This study investigates the feasibility of adopting advanced composite materials to overcome stress shielding effects by optimising the geometry and mechanical properties of the plate to match more closely to the bone. An ulnar transverse fracture is characterised and finite element techniques are employed to investigate the feasibility of a composite-plated fractured bone construct over a stainless steel equivalent. Numerical models of intact and fractured bones are analysed and the mechanical behaviour is found to agree with experimental data. The mechanical properties are tailored to produce an optimised composite plate, offering a 25% reduction in length and a 70% reduction in mass. The optimised design may help to reduce stress shielding and increase bone healing rates. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Enchondromas of the hand: factors affecting recurrence, healing, motion, and malignant transformation.

PubMed

Sassoon, Adam A; Fitz-Gibbon, Patrick D; Harmsen, William S; Moran, Steven L

2012-06-01

Enchondromas represent the most common primary bone tumor in the hand. Despite their frequency, a standardized treatment protocol is lacking. This study examines the outcome of surgically treated enchondromas of the hand with regard to tumor location, graft choice, and presence or absence of fracture. We retrospectively reviewed 102 enchondromas in 80 patients, identified between 1991 and 2008, with a mean clinical follow-up of 38 months. We assessed the effects of age, tumor location, and graft choice on outcomes for all lesions. Patients presenting with Ollier disease, Maffucci syndrome, pathologic fractures, or recurrent disease were separated for additional analysis. Of the 102 lesions, 62 (61%) achieved complete radiographic healing in a median time of 6 months. Full range of motion was achieved following treatment of 68 lesions (67%) in a median time of 3 months. A total of 95 lesions (93%) remained recurrence free following surgery. One case of malignant transformation occurred in a patient with Maffucci syndrome. Tumor location and graft choice did not affect healing grade, time to healing, range of motion, or recurrence rate. Age at presentation greater than 30 was associated with more rapid healing. Monocentric, nonexpanding lesions were associated with improved postoperative range of motion. Patients with a diagnosis of multiple enchondromas had a higher rate of recurrence following surgery, and patients presenting with a recurrent lesion had a higher rate of complications. Following pathologic fracture, no differences in outcomes were observed when enchondromas were treated primarily or following fracture healing. Following surgical treatment of enchondromas in the hand, the majority of patients achieve complete bony healing and full range of motion, regardless of the graft material used. Malignant transformation is rare, and aggressive follow-up measures should be reserved for patients with a diagnosis of multiple enchondromas. Therapeutic IV. Copyright © 2012 American Society for Surgery of the Hand. All rights reserved.

[effectiveness of open reduction and internal fixation without opening joint capsule on tibial plateau fracture].

PubMed

Chen, Qi; Xu, Xiaofeng; Huang, Yonghui; Cao, Xingbing; Meng, Chen; Cao, Xueshu; Wei, Changbao

2014-12-01

To introduce the surgery method to reset and fix tibial plateau fracture without opening joint capsule, and evaluate the safety and effectiveness of this method. Between July 2011 and July 2013, 51 patients with tibial plateau fracture accorded with the inclusion criteria were included. All of 51 patients, 17 cases underwent open reduction and internal fixation without opening joint capsule in trial group, and 34 cases underwent traditional surgery method in control group. There was no significant difference in gender, age, cause of injury, time from injury to admission, side of injury, and types of fracture between 2 groups (P > 0.05). The operation time, intraoperative blood loss, incision length, incision healing, and fracture healing were compared between 2 groups. The tibial-femoral angle and collapse of joint surface were measured on X-ray film. At last follow-up, joint function was evaluated with Hospital for Special Surgery (HSS) knee function scale. The intraoperative blood loss in trial group was significantly less than that in control group (P < 0.05). The incision length in trial group was significantly shorter than that in control group (P < 0.05). Difference was not significant in operation time and the rate of incision healing between 2 groups (P > 0.05). The patients were followed up 12-30 months (mean, 20.4 months) in trial group and 12-31 months (mean, 18.2 months) in control group. X-ray films indicated that all cases in 2 groups obtained fracture healing; there was no significant difference in the fracture healing time between 2 groups (t=1.382, P=0.173). On X-ray films, difference was not significant in tibial-femoral angle and collapse of joint surface between 2 groups (P > 0.05). HSS score of the knee in trial group was significantly higher than that of control group (t=3.161, P=0.003). It can reduce the intraoperative blood loss and shorten the incision length to use open reduction and internal fixation without opening joint capsule for tibial plateau fracture. Traction of joint capsule is helpful in the reduction and good recovery of joint surface collapse. In addition, the surgery without opening joint capsule can avoid joint stiffness and obtain better joint function.

Treatment of open tibial fracture with bone defect caused by high velocity missiles: a case report.

PubMed

Golubović, Zoran; Vukajinović, Zoran; Stojiljković, Predrag; Golubović, Ivan; Visnjić, Aleksandar; Radovanović, Zoran; Najman, Stevo

2013-01-01

Tibia fracture caused by high velocity missiles is mostly comminuted and followed by bone defect which makes their healing process extremely difficult and prone to numerous complications. A 34-year-old male was wounded at close range by a semi-automatic gun missile. He was wounded in the distal area of the left tibia and suffered a massive defect of the bone and soft tissue. After the primary treatment of the wound, the fracture was stabilized with an external fixator type Mitkovic, with convergent orientation of the pins. The wound in the medial region of the tibia was closed with the secondary stitch, whereas the wound in the lateral area was closed with the skin transplant after Thiersch. Due to massive bone defect in the area of the rifle-missile wound six months after injury, a medical team placed a reconstructive external skeletal fixator type Mitkovic and performed corticotomy in the proximal metaphyseal area of the tibia. By the method of bone transport (distractive osteogenesis), the bone defect of the tibia was replaced. After the fracture healing seven months from the secondary surgery, the fixator was removed and the patient was referred to physical therapy. Surgical treatment of wounds, external fixation, performing necessary debridement, adequate antibiotic treatment and soft and bone tissue reconstruction are essential in achieving good results in patients with the open tibial fracture with bone defect caused by high velocity missiles. Reconstruction of bone defect can be successfully treated by reconstructive external fixator Mitkovic.

Effect of nicotine and tobacco administration method on the mechanical properties of healing bone following closed fracture.

PubMed

Hastrup, Sidsel Gaarn; Chen, Xinqian; Bechtold, Joan E; Kyle, Richard F; Rahbek, Ole; Keyler, Daniel E; Skoett, Martin; Soeballe, Kjeld

2010-09-01

We previously showed different effects of tobacco and nicotine on fracture healing, but due to pump reservoir limits, maximum exposure period was 4 weeks. To allow flexibility in pre- and post-fracture exposure periods, the objective of this study was to compare a new oral administration route for nicotine to the established pump method. Four groups were studied: (1) pump saline, (2) pump saline + oral tobacco, (3) pump saline/nicotine + oral tobacco, and (4) pump saline + oral nicotine/tobacco. Sprague-Dawley rats (n = 84) received a transverse femoral fracture stabilized with an intramedullary pin 1 week after initiating dosing. After 3 weeks, no difference was found in torsional strength or stiffness between oral nicotine/tobacco or pump nicotine + tobacco, while energy absorption with oral nicotine/tobacco was greater than pump nicotine + tobacco (p < 0.05). Compared to saline control, strength for oral nicotine/tobacco was higher than control (p < 0.05), and stiffnesses for pump nicotine + tobacco and oral nicotine/tobacco were higher than control (p < 0.05). No differences in energy were found for either nicotine-tobacco group compared to saline control. Mean serum cotinine (stable nicotine metabolite) was different between pump and oral nicotine at 1 and 4 weeks, but all groups were in the range of 1-2 pack/day smokers. In summary, relevant serum cotinine levels can be reached in rats with oral nicotine, and, in the presence of tobacco, nicotine can influence mechanical aspects of fracture healing, dependent on administration method. Caution should be exercised when comparing results of fracture healing studies using different methods of nicotine administration. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

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

A novel coupled system of non-local integro-differential equations modelling Young's modulus evolution, nutrients' supply and consumption during bone fracture healing

NASA Astrophysics Data System (ADS)

Lu, Yanfei; Lekszycki, Tomasz

2016-10-01

During fracture healing, a series of complex coupled biological and mechanical phenomena occurs. They include: (i) growth and remodelling of bone, whose Young's modulus varies in space and time; (ii) nutrients' diffusion and consumption by living cells. In this paper, we newly propose to model these evolution phenomena. The considered features include: (i) a new constitutive equation for growth simulation involving the number of sensor cells; (ii) an improved equation for nutrient concentration accounting for the switch between Michaelis-Menten kinetics and linear consumption regime; (iii) a new constitutive equation for Young's modulus evolution accounting for its dependence on nutrient concentration and variable number of active cells. The effectiveness of the model and its predictive capability are qualitatively verified by numerical simulations (using COMSOL) describing the healing of bone in the presence of damaged tissue between fractured parts.

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.

Image analysis software as a strategy to improve the radiographic determination of fracture healing.

PubMed

Duryea, Jeffrey; Evans, Christopher; Glatt, Vaida

2018-05-28

To develop and validate an unbiased, accurate, convenient and inexpensive means of determining when an osseous defect has healed and recovered sufficient strength to allow weight-bearing. A novel image processing software algorithm was created to analyze the radiographic images and produce a metric designed to reflect the bone strength. We used a rat femoral segmental defect model that provides a range of healing responses from complete union to non-union. Femora were examined by X-ray, micro-computed tomography (µCT) and mechanical testing. Accurate simulated radiographic images at different incident X-ray beam angles were produced from the µCT data files. The software-generated metric (SC) showed high levels of correlation with both the mechanical strength (τMech) and the polar moment of inertia (pMOI), with the mechanical testing data having the highest association. The optimization analysis yielded optimal oblique angles θB of 125° for τMech and 50° for pMOI. The Pearson's R values for the optimized model were 0.71 and 0.64 for τMech and pMOI, respectively. Further validation using true radiographs also demonstrated that the metric was accurate, and that the simulations were realistic. The preliminary findings suggest a very promising methodology to assess bone fracture healing using conventional radiography. With radiographs acquired at appropriate incident angles, it proved possible to calculate accurately the degree of healing and the mechanical strength of the bone. Further research is necessary to refine this approach and determine whether it translates to the human clinical setting.

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

Low Wound Complication Rates for the Lateral Extensile Approach for Calcaneal ORIF When the Lateral Calcaneal Artery Is Patent.

PubMed

Bibbo, Christopher; Ehrlich, David A; Nguyen, Hoang M L; Levin, L Scott; Kovach, Stephen J

2014-07-01

Historically, the lateral extensile approach for calcaneal fracture osteosynthesis has had relatively high rates of wound healing problems. The vascular territory (angiosome) of the lateral foot is now known to be dependent upon the lateral calcaneal branch of the peroneal artery (LCBP artery). We postulated that patency of the LCBP artery may have a profound positive impact on incisional wound healing for calcaneal open reduction and internal fixation (ORIF). Ninety consecutive calcaneal fractures that met operative criteria were preoperatively evaluated for the presence of a Doppler signal in the LCBP artery and were followed for the development of wound healing problems. Among these 90 fractures, 85 had a positive preoperative Doppler signal along the course of the LCBP artery (94%) and 5 had no Doppler signal (6%). All patients underwent ORIF via a lateral extensile approach. Overall, incisional wound healing problems occurred in 6 of 90 calcaneal incisions (6.5%). All 5 feet that exhibited an absent Doppler signal in the LCPB artery developed an incisional wound healing complication (5/6, approximately 83%): 2 large apical wounds and 3 major dehiscence/slough. However, among the 84 feet that possessed a positive preoperative Doppler signal in the LCBP artery, there was only 1 (1/84, approximately 1%) incisional wound healing problem (P < .0001, Fischer's exact test). Smokers with a positive Doppler signal in the LCBP artery did not develop a wound healing complication. This study suggests a strong link to low incisional wound healing complications for the lateral extensile approach to the calcaneus when a preoperative Doppler signal is present in the LCBP artery. We believe this simple examination should be routinely performed prior to calcaneal ORIF. Level III, comparative case series. © The Author(s) 2014.

Callus remodelling model

NASA Astrophysics Data System (ADS)

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

2018-01-01

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

[TREATMENT OF PRONATION EXTERNAL ROTATION ANKLE FRACTURE COMBINED WITH SEPARATION OF DISTAL TIBIOFIBULAR SYNDESMOSIS].

PubMed

Wu, Benwen; Ding, Zhenqi; Huang, Guofeng; Liu, Guojun; Cai, Zhemin; Ding, Luobin; Li, Xiang

2016-09-08

To evaluate the difference between using and not using syndesmotic screw to treat pronation external rotation (PER) ankle fracture combined with separation of distal tibiofibular syndesmosis. Between April 2011 and October 2014, 46 cases of PER ankle fracture combined with separation of distal tibiofibular syndesmosis were treated, and syndesmotic screw was used in 24 cases (fixation group) and syndesmotic screw was not used in 22 cases (non-fixation group). There was no significant difference in gender, age, weight, cause of injury, side, injury to operation time, and fracture type between 2 groups ( P >0.05). The time for full weight-bearing, fracture healing time, and complications were recorded after operation. Anteroposterior and lateral X-ray films were taken to measure the tibiofibular overlap (TBOL) and tibiofibular clear space (TBCS). Baird-Jackson score was used to evaluate functional recovery of the ankle. All incision healed by first intention without complications. The cases were followed up 13-18 months (mean, 15.2 months) in 2 groups. The time for full weight-bearing was 8-12 weeks (median, 11 weeks) in fixation group, which was significantly later than that in non-fixation group (range, 6-10 weeks; median, 8 weeks) ( Z =-5.049, P =0.000). X-ray examination showed reduction of separation of distal tibiofibular syndesmosis. All fractures healed. The fracture healing time was (13.83±1.37) weeks in fixation group, and was (13.91±1.31) weeks in non-fixation group, showing no significant difference ( t =-0.191, P =0.945). No separation of distal tibiofibular syndesmosis, delayed union, nonunion, loosening, or breakage of fixation devices was observed in 2 groups. There was no significant difference in TBOL, TBCS, Baird-Jackson score and the excellent and good rate between 2 groups ( P >0.05). If the medial, lateral, and posterior structures of the ankle could be repaired according to injury, no significant influence on functional outcome of ankle or radiologic findings could be detected whether syndesmotic fixation is given or not in treating PER ankle fracture (exclude Maisonneuve fracture) combined with separation of distal tibiofibular syndesmosis.

Art Dialogue Methods: Phronèsis and Its Potential for Restoring an Embodied Moral Authority in Local Communities

ERIC Educational Resources Information Center

Muijen, Heidi S. C. A.; Brohm, René

2018-01-01

We put forward Art-Dialogue-Methods (ADM) as an inquiry for practical wisdom within communities. It draws from a series of methodological traditions like artistic inquiry, participatory action research and narrative research. The practice of ADM could facilitate healing processes in fractured communities and organisations in today's world. ADM…

[One-stage operation for pelvis and acetabular fractures combined with Morel-Lavallée injury by internal fixation associated with vacuum sealing drainage].

PubMed

Wei, Dan; Wang, Yue; Yuan, Jiabin; Tang, Xiaoming; Zhang, Bin; Lu, Bing; Tan, Bo

2014-01-01

To investigate the methods and effectiveness of one-stage operation for pelvis and acetabular fractures combined with Morel-Lavallée injury by internal fixation associated with vacuum sealing drainage (VSD). Between June 2008 and October 2012, 15 cases of pelvis and acetabular fractures combined with Morel-Lavallée injury were treated. There were 5 males and 10 females, aged from 18 to 67 years (mean, 36.8 years). Fractures were caused by traffic accident in 11 cases and crashing injury of heavy object in 4 cases. The time from injury to hospitalization was 3 hours to 9 days (mean, 5.4 days). Morel-Lavallée injury located in the above posterior superior iliac spine in 4 cases, greater trochanter in 7 cases, and anterior proximal thigh in 4 cases. In 10 cases complicated by pelvic fracture, there were 1 case of anteroposterior compression type, 3 cases of lateral compression type, 5 cases of vertical shear type, and 1 case of compound injury type; in 5 cases complicated by acetabular fracture, there were 1 case of transverse fracture, 1 case of posterior wall and posterior column fracture, 1 case of transverse acetabulum plus posterior wall fracture, and 2 cases of both columns fracture. Open reduction and internal fixation were used to treat pelvic and acetabular fractures, and VSD to treat Morel-Lavallée injury. When the drainage volume was less than 20 mL/d, interrupted wound suture or free skin grafting was performed. The hospitalization time was 16-31 days (mean, 20.8 days). Thirteen cases were followed up 4-16 months (mean, 7.8 months). The healing time of Morel-Lavallée injury was 16-36 days after operation (mean, 21.3 days). All the wounds had primary healing, and no infection occurred. The X-ray films showed that all fractures healed, with a mean healing time of 13.6 weeks (range, 11-18 weeks). At 6.5 months after operation, according to Majeed function scoring system in 8 cases of pelvic fracture, the results were excellent in 5 cases, good in 2 cases, and fair in 1 case; according to Harris hip scoring in 4 cases of acetabular fracture, the results were excellent in 2 cases, good in 1 case, and fair in 1 case. To pelvis-acetabular fractures combined with Morel-Lavallée injury, internal fixation treatment for fracture and VSD for Morel-Lavallée injury not only can cure merge Morel-Lavallée injury effectively, but also can guarantee the operation timing and incision safty of the pelvis-acetabular fractures.

Multimodal noninvasive monitoring of soft tissue wound healing.

PubMed

Bodo, Michael; Settle, Timothy; Royal, Joseph; Lombardini, Eric; Sawyer, Evelyn; Rothwell, Stephen W

2013-12-01

Here we report results of non-invasive measurements of indirect markers of soft tissue healing of traumatic wounds in an observational swine study and describe the quantification of analog physiological signals. The primary purpose of the study was to measure bone healing of fractures with four different wound treatments. A second purpose was to quantify soft tissue wound healing by measuring the following indirect markers: (1) tissue oxygenation, (2) fluid content, and (3) blood flow, which were all measured by non-invasive modalities, measured with available devices. Tissue oxygenation was measured by near infrared spectroscopy; fluid content was measured by bipolar bio-impedance; and blood flow was measured by Doppler ultrasound. Immediately after comminuted femur fractures were produced in the right hind legs of thirty anesthetized female Yorkshire swine, one of four wound treatments was instilled into each wound. The four wound treatments were as follows: salmon fibrinogen/thrombin-n = 8; commercial bone filler matrix-n = 7; bovine collagen-n = 8; porcine fibrinogen/thrombin-n = 7. Fractures were stabilized with an external fixation device. Immediately following wound treatments, measurements were made of tissue oxygenation, fluid content and blood flow; these measurements were repeated weekly for 3 weeks after surgery. Analog signals of each modality were recorded on both the wounded (right) hind leg and the healthy (left) hind leg, for comparison purposes. Data were processed off-line. The mean values of 10-s periods were calculated for right-left leg comparison. ANOVA was applied for statistical analysis. Results of the bone healing studies are published separately (Rothwell et al. in J Spec Oper Med 13:7-18, 2013). For soft tissue wounds, healing did not differ significantly among the four wound treatments; however, regional oxygenation of wounds treated with salmon fibrinogen/thrombin showed slightly different time trends. Further studies are needed to establish standards for healthy wound healing and for detection of pathological alterations such as infection. Non-invasive measurement and quantification of indirect markers of soft tissue wound healing support the goals and principles of evidence-based medicine and show potential as easy to administer tools for clinicians and battlefield medical personnel to apply when procedures such as the PET scan are not available or affordable. The method we developed for storing analog physiological signals could be used for maintaining electronic health records, by incorporating vital signs such as ECG and EEG, etc.

Complications and functional recovery in treatment of femoral shaft fractures with unreamed intramedullary nailing.

PubMed

Sadic, Sahmir; Custovic, Svemir; Smajic, Nedim; Fazlic, Mirsad; Vujadinovic, Aleksandar; Hrustic, Asmir; Jasarevic, Mahir

2014-01-01

Fracture of the femoral shaft is a common fracture encountered in orthopedic practice. In the 1939, Küntscher introduced the concept of intramedullary nailing for stabilization of long bone fractures. Intramedullary nailing has revolutionized the treatment of fractures. The study included 37 male patients and 13 female patients, averaged 39 +/- 20.5 years (range, 16 to 76 years). There were 31 left femurs and 21 right femurs fractured. 46 fractures were the result of blunt trauma. Low energy trauma was the cause of fractures in six patients, of which five in elderly females. 49 fractures were closed. Healing time given in weeks was 19.36 +/- 6.1. The overall healing rate was 93.6%. There were three (6.25%) major complications nonunion. There were one (2%) delayed union, one (2%) rotational malunion and no infection. The shortening of 1 cm were in two patients. Antercurvatum of 10 degrees was found in one patient. There was no statistically significant reduction of a motion in the hip and knee (p < 0.05). There was statistically significant in the thigh (knee extensors) muscle weakness (p < 0.001). : Intramedullary nailing is the treatment of choice for femoral shaft fractures.

Role of Fas and Treg Cells in Fracture Healing as Characterized in the Fas-Deficient (lpr) Mouse Model of Lupus†

PubMed Central

Al-Sebaei, Maisa O; Daukss, Dana M; Belkina, Anna C; Kakar, Sanjeev; Wigner, Nathan A; Cusher, Daniel; Graves, Dana; Einhorn, Thomas; Morgan, Elise; Gerstenfeld, Louis C

2014-01-01

Previous studies showed that loss of tumor necrosis factor α (TNFα) signaling delayed fracture healing by delaying chondrocyte apoptosis and cartilage resorption. Mechanistic studies showed that TNFα induced Fas expression within chondrocytes; however, the degree to which chondrocyte apoptosis is mediated by TNFα alone or dependent on the induction of Fas is unclear. This question was addressed by assessing fracture healing in Fas-deficient B6.MRL/Faslpr/J mice. Loss of Fas delayed cartilage resorption but also lowered bone fraction in the calluses. The reduced bone fraction was related to elevated rates of coupled bone turnover in the B6.MRL/Faslpr/J calluses, as evidenced by higher osteoclast numbers and increased osteogenesis. Analysis of the apoptotic marker caspase 3 showed fewer positive chondrocytes and osteoclasts in calluses of B6.MRL/Faslpr/J mice. To determine if an active autoimmune state contributed to increased bone turnover, the levels of activated T cells and Treg cells were assessed. B6.MRL/Faslpr/J mice had elevated Treg cells in both spleens and bones of B6.MRL/Faslpr/J but decreased percentage of activated T cells in bone tissues. Fracture led to ∼30% to 60% systemic increase in Treg cells in both wild-type and B6.MRL/Faslpr/J bone tissues during the period of cartilage formation and resorption but either decreased (wild type) or left unchanged (B6.MRL/Faslpr/J) the numbers of activated T cells in bone. These results show that an active autoimmune state is inhibited during the period of cartilage resorption and suggest that iTreg cells play a functional role in this process. These data show that loss of Fas activity specifically in chondrocytes prolonged the life span of chondrocytes and that Fas synergized with TNFα signaling to mediate chondrocyte apoptosis. Conversely, loss of Fas systemically led to increased osteoclast numbers during later periods of fracture healing and increased osteogenesis. These findings suggest that retention of viable chondrocytes locally inhibits osteoclast activity or matrix proteolysis during cartilage resorption. © 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. PMID:24677136

Is obesity protective against wound healing complications in pilon surgery? Soft tissue envelope and pilon fractures in the obese.

PubMed

Graves, Matthew L; Porter, Scott E; Fagan, Bryan C; Brien, Glenn A; Lewis, Matthew W; Biggers, Marcus D; Woodall, James R; Russell, George V

2010-08-11

Open treatment of pilon fractures is associated with wound healing complications. A traumatized, limited soft tissue envelope contributes to wound healing complications. Obese patients have larger soft tissue envelopes around the ankle, theoretically providing a greater area for energy distribution and more accommodation to implants. This led us to test 2 hypotheses: (1) ankle dimensions in obese patients are larger than in lean patients, and (2) the increased soft tissue envelope volume translates into fewer wound complications. A consecutive series of 176 pilon fractures treated from March 2002 to December 2007 were retrospectively reviewed. Inclusion criteria were adults who received a preoperative computed tomography (CT) scan and were treated with a staged protocol including plating. Patients with body mass index (BMI) >30 were compared to those with BMI <30 for CT-derived ankle dimensions and wound complications. Comorbidities were evaluated for their role as potential confounders. Thirty-one fractures in obese patients were compared to 83 in lean patients. The average ratio of bone area to soft tissue area at the tibial plafond was 0.35 for the obese group and 0.38 for the lean group (P=.012). There were 8 major wound-healing complications. Four occurred in the obese group (incidence 13%), and 4 in the lean group (incidence 5%) (P=.252). Ankle dimensions in clinically obese patients are larger than in lean patients. Obesity does not appear to be protective of wound-healing complications, but rather there is a trend toward the opposite. Copyright 2010, SLACK Incorporated.

Mesenchymal stem cells expressing insulin-like growth factor-I (MSCIGF) promote fracture healing and restore new bone formation in Irs1 knockout mice: analyses of MSCIGF autocrine and paracrine regenerative effects.

PubMed

Granero-Moltó, Froilán; Myers, Timothy J; Weis, Jared A; Longobardi, Lara; Li, Tieshi; Yan, Yun; Case, Natasha; Rubin, Janet; Spagnoli, Anna

2011-10-01

Failures of fracture repair (nonunions) occur in 10% of all fractures. The use of mesenchymal stem cells (MSC) in tissue regeneration appears to be rationale, safe, and feasible. The contributions of MSC to the reparative process can occur through autocrine and paracrine effects. The primary objective of this study is to find a novel mean, by transplanting primary cultures of bone marrow-derived MSCs expressing insulin-like growth factor-I (MSC(IGF)), to promote these seed-and-soil actions of MSC to fully implement their regenerative abilities in fracture repair and nonunions. MSC(IGF) or traceable MSC(IGF)-Lac-Z were transplanted into wild-type or insulin-receptor-substrate knockout (Irs1(-/-)) mice with a stabilized tibia fracture. Healing was assessed using biomechanical testing, microcomputed tomography (μCT), and histological analyses. We found that systemically transplanted MSC(IGF) through autocrine and paracrine actions improved the fracture mechanical strength and increased new bone content while accelerating mineralization. We determined that IGF-I adapted the response of transplanted MSC(IGF) to promote their differentiation into osteoblasts. In vitro and in vivo studies showed that IGF-I-induced osteoglastogenesis in MSCs was dependent of an intact IRS1-PI3K signaling. Furthermore, using Irs1(-/-) mice as a nonunion fracture model through altered IGF signaling, we demonstrated that the autocrine effect of IGF-I on MSC restored the fracture new bone formation and promoted the occurrence of a well-organized callus that bridged the gap. A callus that was basically absent in Irs1(-/-) left untransplanted or transplanted with MSCs. We provided evidence of effects and mechanisms for transplanted MSC(IGF) in fracture repair and potentially to treat nonunions. Copyright © 2011 AlphaMed Press.

Minimally invasive treatment of clavicular fractures with cannulated screw.

PubMed

Sun, Jun-zhan; Zheng, Guo-hai; Zhao, Ke-yi

2014-05-01

To evaluate minimally invasive treatment of clavicular fractures with cannulated screw. Data of 65 patients who had undergone minimally invasive treatment with cannulated screws for clavicular fractures from April 2009 to October 2010 were retrospectively analyzed and compared with those of 65 patients with clavicular fractures who had been treated by the same surgeons with plates. In the study group, there were 41 males and 24 females, aged from 19-67 years (mean, 35.8 years). According to Craig's classification, there were 29 group 1 and 36 of group 2-II. Neer scores were used to evaluate shoulder function and radiographs to assess fracture union. The incision length was 4-5 cm in the cannulated screw group (CSG) and 10-11 cm in the reconstructive plate group (RPG). Radiographs showed bone union was achieved in both groups, the bone healing time being 13.2 ± 6.9 weeks in the CSG and 16.3 ± 8.7 weeks in the RPG. All patients were followed up for 6 to 20 months (average, 10.6 months). The average Neer score was 96.6 ± 3.4 in the CSG and 94.2 ± 5.8 in the RPG. In the CSG, screw loosening occurred in five, and fracture displacement in three. There was a significant difference in fracture healing time between two groups but not in Neer score. Minimally invasive treatment of clavicular fractures with cannulated screws has the advantages of minimal invasion, short bone healing time, good clinical outcomes, and being relatively inexpensive. © 2014 Chinese Orthopaedic Association and Wiley Publishing Asia Pty Ltd.

[Treatment of linguiform calcaneus fracture by close nail-pry reduction and internal fixation with hollow screws].

PubMed

Tu, Shu-Qiang; Huang, Ke-Di; Shuai, Yong-Ming; Xu, Nan-Yun; Yuan, Qiu-Wen; Guo, Jian

2012-06-01

To study the curative effects of close nail-pry reduction and internal fixation with hollow screws for treatment of linguiform calcaneus fracture. From May 2006 to October 2009,32 patients (35 feet) with linguiform calcaneus fracture were treated by close nail-pry reduction and internal fixation with hollow screws, including 23 males and 9 females ranging in age from 25 to 46 years, with a mean of 37.6 years. According to Paley classification, 3 cases were Paley II a, and 29 cases were Paley II b. All cases were close fractures. The time from injury to operation was 3 to 10 days after most swelling subsided. Böhler angle and Gissane angle were measured by X-ray before and after operation. The therapeutic effect was assessed according to ZHANG Tie-liang's foot score. All the patients were followed-up for 6 to 18 months, with a mean of 12 months. All fractures gained bone healing. The time of fracture healing averaged 12 months. The fractures healed completely and no infection occurred. According to ZHANG Tie-liang's foot scale, the postoperative function was excellent in 18 feet, good in 10 feet, moderate in 5 feet and poor in 2 feet. The Böhler angle and Gissane angle were significant improved after treatment (P < 0.01). The surgical method of close nail-pry reduction and internal fixation with hollow screws for treatment of linguiform calcaneus fracture can regain the foot function, with minimal injury, fewer complications, earlier recovery and lower costs.

[The randomized controlled trial of the treatment for clavicular fracture by rotatory manual reduction with forceps holder and retrograde percutaneous pinning transfixation].

PubMed

Bi, Hong-zheng; Yang, Mao-qing; Tan, Yuan-chao; Fu, Song

2008-07-01

To study the curative effect and safety of rotatory manual reduction with forceps holder and retrograde percutaneous pinning transfixation in treating clavicular fracture. All 201 cases of clavicular fractures were randomly divided into treatment group (101 cases) and control group (100 cases). The treatment group was treated by rotatory manual reduction with forceps holder and retrograde percutaneous pinning transfixation. The control group was treated by open reduction and internal fixation with Kirschner pin. All cases were followed up for 4 to 21 months (mean 10.6 months). SPSS was used to analyze clinic healing time of fracture and shoulder-joint function in both two groups. After operation, 101 cases of treatment group achieved union of fracture and the clinical healing time was 28 to 49 days (mean 34.5+/-2.7 days). In control group,there were 4 cases with nonunion of fracture,the other 96 cases were union,the clinical healing time was 36 to 92 days (mean 55.3+/-4.8 days). The excellent and good rate of shoulder-joint function was 100% in treatment group and 83% in control group. By t-test and chi2-test, there was significant difference between the two groups in curative effect (P<0.05). Rotatory manual reduction with forceps holder and retrograde pinning transfixation can be used in various kinds of clavicular shaft fracture, with many virtues such as easy operation, reliable fixation, short union time of fracture, good functional recovery of shoulder-joint and no incision scar affecting appearance.

Development of controlled drug delivery systems for bone fracture-targeted therapeutic delivery: A review.

PubMed

Wang, Yuchen; Newman, Maureen R; Benoit, Danielle S W

2018-06-01

Impaired fracture healing is a major clinical problem that can lead to patient disability, prolonged hospitalization, and significant financial burden. Although the majority of fractures heal using standard clinical practices, approximately 10% suffer from delayed unions or non-unions. A wide range of factors contribute to the risk for nonunions including internal factors, such as patient age, gender, and comorbidities, and external factors, such as the location and extent of injury. Current clinical approaches to treat nonunions include bone grafts and low-intensity pulsed ultrasound (LIPUS), which realizes clinical success only to select patients due to limitations including donor morbidities (grafts) and necessity of fracture reduction (LIPUS), respectively. To date, therapeutic approaches for bone regeneration rely heavily on protein-based growth factors such as INFUSE, an FDA-approved scaffold for delivery of bone morphogenetic protein 2 (BMP-2). Small molecule modulators and RNAi therapeutics are under development to circumvent challenges associated with traditional growth factors. While preclinical studies has shown promise, drug delivery has become a major hurdle stalling clinical translation. Therefore, this review overviews current therapies employed to stimulate fracture healing pre-clinically and clinically, including a focus on drug delivery systems for growth factors, parathyroid hormone (PTH), small molecules, and RNAi therapeutics, as well as recent advances and future promise of fracture-targeted drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

Stability of biodegradable implants in treatment of mandibular fractures.

PubMed

Yerit, Kaan C; Hainich, Sibylle; Turhani, Dritan; Klug, Clemens; Wittwer, Gert; Ockher, Michael; Ploder, Oliver; Undt, Gerhard; Baumann, Arnulf; Ewers, Rolf

2005-06-01

Biodegradable implants have not been used on a large scale for internal fixation of mandibular fractures because of presumed inferior mechanical properties. This prospective clinical trial was designed to elucidate the stability and biocompatibility of self-reinforced poly-L/D-lactide plates and screws used to stabilize a variety of mandible fractures by open reduction and internal fixation. Sixty-six consecutive patients (22 female, 44 male; mean age, 23.9 years) with a total of 89 fractures at various sites of the mandible were included in the study. Stability of plates and screws and bone healing were observed by clinical and radiographic assessment. Intermaxillary fixation was applied in eight patients with concomitant condylar fractures for 2 to 3 weeks. The self-reinforcement technique provided sufficient mechanical stability of the implants for primary healing of these high-load mandibular bone areas. Postoperative complications were transient and limited to wound dehiscence and localized wound infection (two patients). In some patients, hypesthesia (three patients) or slight pain (10 patients) was reported at the 1-year recall examination, but implant-related serious adverse tissue reactions were not observed during the follow-up (mean, 24.4 months; range 6.4 to 44.3 months). On the basis of these preliminary results, the authors conclude that biodegradable self-reinforced implants show efficient stability during initial bone healing and promise a high potential for successful use in osteofixation of mandibular fractures.

Vertebral Compression Fractures

MedlinePlus

... and monitored to avoid putting pressure on the ribs that can cause new fractures. Surgical Procedures • When there is severe incapacitating pain • When healing is delayed or when bone fragments ...

Loss of Gi G-Protein-Coupled Receptor Signaling in Osteoblasts Accelerates Bone Fracture Healing.

PubMed

Wang, Liping; Hsiao, Edward C; Lieu, Shirley; Scott, Mark; O'Carroll, Dylan; Urrutia, Ashley; Conklin, Bruce R; Colnot, Celine; Nissenson, Robert A

2015-10-01

G-protein-coupled receptors (GPCRs) are key regulators of skeletal homeostasis and are likely important in fracture healing. Because GPCRs can activate multiple signaling pathways simultaneously, we used targeted disruption of G(i) -GPCR or activation of G(s) -GPCR pathways to test how each pathway functions in the skeleton. We previously demonstrated that blockade of G(i) signaling by pertussis toxin (PTX) transgene expression in maturing osteoblastic cells enhanced cortical and trabecular bone formation and prevented age-related bone loss in female mice. In addition, activation of G(s) signaling by expressing the G(s) -coupled engineered receptor Rs1 in maturing osteoblastic cells induced massive trabecular bone formation but cortical bone loss. Here, we test our hypothesis that the G(i) and G(s) pathways also have distinct functions in fracture repair. We applied closed, nonstabilized tibial fractures to mice in which endogenous G(i) signaling was inhibited by PTX, or to mice with activated G(s) signaling mediated by Rs1. Blockade of endogenous G(i) resulted in a smaller callus but increased bone formation in both young and old mice. PTX treatment decreased expression of Dkk1 and increased Lef1 mRNAs during fracture healing, suggesting a role for endogenous G(i) signaling in maintaining Dkk1 expression and suppressing Wnt signaling. In contrast, adult mice with activated Gs signaling showed a slight increase in the initial callus size with increased callus bone formation. These results show that G(i) blockade and G(s) activation of the same osteoblastic lineage cell can induce different biological responses during fracture healing. Our findings also show that manipulating the GPCR/cAMP signaling pathway by selective timing of G(s) and G(i) -GPCR activation may be important for optimizing fracture repair. © 2015 American Society for Bone and Mineral Research.

Effects of low-dose microwave on healing of fractures with titanium alloy internal fixation: an experimental study in a rabbit model.

PubMed

Ye, Dongmei; Xu, Yiming; Zhang, Han; Fu, Tengfei; Jiang, Lan; Bai, Yuehong

2013-01-01

Microwave is a method for improving fracture repair. However, one of the contraindications for microwave treatment listed in the literature is surgically implanted metal plates in the treatment field. The reason is that the reflection of electromagnetic waves and the eddy current stimulated by microwave would increase the temperature of magnetic implants and cause heat damage in tissues. Comparing with traditional medical stainless steel, titanium alloy is a kind of medical implants with low magnetic permeability and electric conductivity. But the effects of microwave treatment on fracture with titanium alloy internal fixation in vivo were not reported. The aim of this article was to evaluate the security and effects of microwave on healing of a fracture with titanium alloy internal fixation. Titanium alloy internal fixation systems were implanted in New Zealand rabbits with a 3.0 mm bone defect in the middle of femur. We applied a 30-day microwave treatment (2,450MHz, 25W, 10 min per day) to the fracture 3 days after operation. Temperature changes of muscle tissues around implants were measured during the irradiation. Normalized radiographic density of the fracture gap was measured on the 10th day and 30th day of the microwave treatment. All of the animals were killed after 10 and 30 days microwave treatment with histologic and histomorphometric examinations performed on the harvested tissues. The temperatures did not increase significantly in animals with titanium alloy implants. The security of microwave treatment was also supported by histology of muscles, nerve and bone around the implants. Radiographic assessment, histologic and histomorphometric examinations revealed significant improvement in the healing bone. Our results suggest that, in the healing of fracture with titanium alloy internal fixation, a low dose of microwave treatment may be a promising method.

The microbiota of traumatic, open fracture wounds is associated with mechanism of injury.

PubMed

Bartow-McKenney, Casey; Hannigan, Geoffrey D; Horwinski, Joseph; Hesketh, Patrick; Horan, Annamarie D; Mehta, Samir; Grice, Elizabeth A

2018-05-26

Open fractures are characterized by disruption of the skin and soft tissue, which allows for microbial contamination and colonization. Preventing infection-related complications of open fractures and other acute wounds remains an evolving challenge due to an incomplete understanding of how microbial colonization and contamination influence healing and outcomes. Culture-independent molecular methods are now widely used to study human-associated microbial communities without introducing culture biases. Using such approaches, the objectives of this study were to 1) define the long-term temporal microbial community dynamics of open fracture wounds and 2) examine microbial community dynamics with respect to clinical and demographic factors. Fifty-two subjects with traumatic open fracture wounds (32 blunt and 20 penetrating injuries) were enrolled prospectively and sampled longitudinally from presentation to the emergency department and at each subsequent inpatient or outpatient encounter. Specimens were collected from both the wound center and adjacent skin. Culture-independent sequencing of the 16S ribosomal RNA gene was employed to identify and characterize microbiota. Upon presentation to the emergency department and time points immediately following, sample collection site (wound or adjacent skin) was the most defining feature discriminating microbial profiles. Microbial composition of adjacent skin and wound center converged over time. Mechanism of injury most strongly defined the microbiota after initial convergence. Further analysis controlling for race, gender, and age revealed that mechanism of injury remained a significant discriminating feature throughout the continuum of care. We conclude that the microbial communities associated with open fracture wounds are dynamic in nature until eventual convergence with the adjacent skin community during healing, with mechanism of injury as an important feature affecting both diversity and composition of the microbiota. A more complete understanding of the factors influencing microbial contamination and/or colonization in open fractures is a critical foundation for identifying markers indicative of outcome and deciphering their respective contributions to healing and/or complication. This article is protected by copyright. All rights reserved. © 2018 by the Wound Healing Society.

Effects of Low-Dose Microwave on Healing of Fractures with Titanium Alloy Internal Fixation: An Experimental Study in a Rabbit Model

PubMed Central

Zhang, Han; Fu, Tengfei; Jiang, Lan; Bai, Yuehong

2013-01-01

Background Microwave is a method for improving fracture repair. However, one of the contraindications for microwave treatment listed in the literature is surgically implanted metal plates in the treatment field. The reason is that the reflection of electromagnetic waves and the eddy current stimulated by microwave would increase the temperature of magnetic implants and cause heat damage in tissues. Comparing with traditional medical stainless steel, titanium alloy is a kind of medical implants with low magnetic permeability and electric conductivity. But the effects of microwave treatment on fracture with titanium alloy internal fixation in vivo were not reported. The aim of this article was to evaluate the security and effects of microwave on healing of a fracture with titanium alloy internal fixation. Methods Titanium alloy internal fixation systems were implanted in New Zealand rabbits with a 3.0 mm bone defect in the middle of femur. We applied a 30-day microwave treatment (2,450MHz, 25W, 10 min per day) to the fracture 3 days after operation. Temperature changes of muscle tissues around implants were measured during the irradiation. Normalized radiographic density of the fracture gap was measured on the 10th day and 30th day of the microwave treatment. All of the animals were killed after 10 and 30 days microwave treatment with histologic and histomorphometric examinations performed on the harvested tissues. Findings The temperatures did not increase significantly in animals with titanium alloy implants. The security of microwave treatment was also supported by histology of muscles, nerve and bone around the implants. Radiographic assessment, histologic and histomorphometric examinations revealed significant improvement in the healing bone. Conclusion Our results suggest that, in the healing of fracture with titanium alloy internal fixation, a low dose of microwave treatment may be a promising method. PMID:24086626

Groin injuries in sport: treatment strategies.

PubMed

Lynch, S A; Renström, P A

1999-08-01

Groin pain in athletes is a common problem that can result in significant amounts of missed playing time. Many of the problems are related to the musculoskeletal system, but care must be taken not to overlook other more serious and potentially life threatening medical cases of pelvis and groin pain. Stress fractures of the bones of the pelvis occur, particularly after a sudden increase in the intensity of training. Most of these stress fractures will heal with rest, but femoral neck stress fractures can potentially lead to more serious problems, and require closer evaluation and sometimes surgical treatment. Avulsion fractures of the apophyses occur through the relatively weaker growth plate in adolescents. Most of these will heal with a graduated physical therapy programme and do not need surgery. Osteitis pubis is characterised by sclerosis and bony changes about the pubic symphysis. This is a self-limiting disease that can take several months to resolve. Corticosteroid injection can sometimes hasten the rehabilitation process. Sports hernias can cause prolonged groin pain, and provide a difficult diagnostic dilemma. In athletes with prolonged groin pain, with increased pain during valsalva manoeuvres and tenderness along the posterior inguinal wall and external canal, an insidious sports hernia should be considered. In cases of true sports hernia, treatment is by surgical reinforcement of the inguinal wall. Nerve compression can occur to the nerves supplying the groin. In cases that do not respond to desensitisation measures, neurolysis can relieve the pain. Adductor strains are common problems in kicking sports such as soccer. The majority of these are incomplete muscle tendon tears that occur just adjacent to, the musculotendinous junction. Most of these will respond to a graduated stretching and strengthening programme, but these can sometimes take a long time to completely heal. Patience is the key to obtain complete healing, because a return to sports too early can lead to chronic pain, which becomes increasingly difficult to treat. Management of groin injuries can be challenging, and diagnosis can be difficult because of the degree of overlap of symptoms between the different problems. By careful history and clinical examination, with judicious use of special tests and good team work, a correct diagnosis can be obtained.

Experimental stimulation of bone healing with teriparatide: histomorphometric and microhardness analysis in a mouse model of closed fracture.

PubMed

Mognetti, Barbara; Marino, Silvia; Barberis, Alessandro; Martin, Anne-Sophie Bravo; Bala, Yohann; Di Carlo, Francesco; Boivin, Georges; Barbos, Michele Portigliatti

2011-08-01

Fracture consolidation is a crucial goal to achieve as early as possible, but pharmacological stimulation has been neglected so far. Teriparatide has been considered for this purpose for its anabolic properties. We set up a murine model of closed tibial fracture on which different doses of teriparatide were tested. Closed fracture treatment avoids any bias introduced by surgical manipulations. Teriparatide's effect on callus formation was monitored during the first 4 weeks from fracture. Callus evolution was determined by histomorphometric and microhardness assessment. Daily administration of 40 μg/kg of teriparatide accelerated callus mineralization from day 9 onward without significant increase of sizes, and at day 15 the microhardness properties of treated callus were similar to those of bone tissue. Teriparatide considerably improved callus consolidation in the very early phases of bone healing.

[CHANGES OF SEMAPHORIN 3A EXPRESSION IN HEALING OF TIBIA FRACTURE AFTER TRAUMATIC BRAIN INJURY].

PubMed

Li, Zhengzheng; Zhao, Junwei; Yi, Zhigang; Luo, Wei; Li, Kang; Wang, Yuliang; Wang, Jing; An, Liping; Ma, Jinglin

2016-10-08

To investigate the mechanism of Semaphorin 3A (Sema3A) in fracture healing after nerve injury by observing the expression of Sema3A in the tibia fracture healing after traumatic brain injury (TBI). A total of 192 Wistar female rats, 8-10 weeks old and weighing 220-250 g, were randomly divided into tibia fracture group (group A, n =48), TBI group (group B, n =48), TBI with tibia fracture group (group C, n =48), and control group (group D, n =48). The tibia fracture model was established at the right side of group A; TBI model was made in group B by the improved Feeney method; the TBI and tibia fracture model was made in group C; no treatment was given in group D. The tissue samples were respectively collected at 3, 5, 7, 14, 21, and 28 days after operation; HE staining, immunohistochemistry staining, and Western blot method were used for the location and quantitative detection of Sema3A in callus tissue. HE staining showed that no obvious changes were observed at each time point in groups B and D. At 3 and 5 days, there was no obvious callus growth at fracture site with inflammatory cells and fibrous tissue filling in groups A and C. At 7 and 14 days, fibrous tissue grew from periosteum to fracture site in groups A and C; the proliferation of chondrocytes in exterior periosteum gradually formed osteoid callus at fracture site in groups A and C. The chondrocyte had bigger size, looser arrangement, and more osteoid in group C than group A. Group B had disorder periosteum, slight subperiosteal bone hyperplasia, and no obvious change of bone trabecula in group B when compared with group D. At 21 and 28 days, cartilage callus was gradually replaced by new bone trabecula in groups A and C. Group C had loose arrange, disorder structure, and low density of bone trabecula, big callus area and few chondrocyte and osteoid when compared with group A; group B was similar to Group D. Immunohistochemistry staining showed that Sema3A expression in chondrocytes in group C was higher than that in group A, particularly at 7, 14, and 21 day. Sema3A was significantly higher in osteoblasts of new bone trabecula in group A than group C, especially at 14 and 21 days ( P <0.05). Western blot results showed that the Sema3A had the same expression trend during fracture healing in groups A and C. However, the expression of Sema3A protein was significantly higher in group C than group A ( P <0.05) and in group B than group D ( P <0.05) at 7, 14, 21, and 28 days. Abnormal expression of Sema3A may play a role in fracture healing after nerve injury by promoting the chondrocytes proliferation and reducing the distribution of sensory nerve fibers and osteoblast differentiation.

Femoral fracture repair using a locking plate technique in an adult captive polar bear (Ursus maritimus).

PubMed

Zimmerman, Dawn M; Dew, Terry; Douglass, Michael; Perez, Edward

2010-02-01

To report successful femoral fracture repair in a polar bear. Case report. Female polar bear (Ursus maritimus) 5 years and approximately 250 kg. A closed, complete, comminuted fracture of the distal midshaft femur was successfully reduced and stabilized using a compression plating technique with 2 specialized human femur plates offering axial, rotational, and bending support, and allowing the bone to share loads with the implant. Postoperative radiographs were obtained at 11.5 weeks, 11 months, and 24 months. Bone healing characterized by marked periosteal reaction was evident at 11 months with extensive remodeling evident at 24 months. No complications were noted. Distal mid shaft femoral fracture was reduced, stabilized, and healed in an adult polar bear with a locking plate technique using 2 plates. Previously, femoral fractures in polar bears were considered irreparable. Use of 2 plates applied with a locking plate technique can result in successful fracture repair despite large body weight and inability to restrict postoperative activity.

Early Experience with Biodegradable Fixation of Pediatric Mandibular Fractures

PubMed Central

Mazeed, Ahmed Salah; Shoeib, Mohammed Abdel-Raheem; Saied, Samia Mohammed Ahmed; Elsherbiny, Ahmed

2014-01-01

This clinical study aims to evaluate the stability and efficiency of biodegradable self-reinforced poly-l/dl-lactide (SR-PLDLA) plates and screws for fixation of pediatric mandibular fractures. The study included 12 patients (3–12 years old) with 14 mandibular fractures. They were treated by open reduction and internal fixation by SR-PLDLA plates and screws. Maxillomandibular fixation was maintained for 1 week postoperatively. Clinical follow-up was performed at 1 week, 6 weeks, 3 months, and 12 months postoperatively. Radiographs were done at 1 week, 3 months, and 12 months postoperatively to observe any displacement and fracture healing. All fractures healed both clinically and radiologically. No serious complications were reported in the patients. Normal occlusion was achieved in all cases. Biodegradable osteofixation of mandibular fractures offers a valuable clinical solution for pediatric patients getting the benefit of avoiding secondary surgery to remove plates, decreasing the hospital stay, further painful procedures, and psychological impact. PMID:26269728

[Fractures of the lower extremities in childhood : Part 2: lower leg and ankle fractures].

PubMed

Voth, M; Kremer, L; Marzi, I

2017-11-01

The treatment of pediatric patients in trauma surgery is a special situation in every aspect. For deciding on the correct treatment of fractures of the lower leg and ankle joint, various parameters, such as residual growth rate, skeletal age and height of the patient are decisive. The differences between fractures in children and adolescents are the open epiphyseal plate and the resulting residual growth. The bones of young children have a higher healing tendency and a greater potential for correction than in adolescents. Especially in the lower leg and the ankle joint, the potential for correction is decisive for the healing of fractures and for possible development of growth disorders. The limits of tolerance concerning axial malalignments and the expected spontaneous potential for correction must play an essential role for further treatment with conservative or operative therapy. This article deals with the special features of pediatric fractures of the lower leg and ankle joint.

Impaired fracture healing with high non-union rates remains irreversible after traumatic brain injury in leptin-deficient mice

PubMed Central

Graef, F.; Seemann, R.; Garbe, A.; Schmidt-Bleek, K.; Schaser, K-D.; Keller, J.; Duda, G.; Tsitsilonis, S.

2017-01-01

Patients with traumatic brain injury (TBI) and long-bone fractures can show increased callus formation. This effect has already been reproduced in wild-type (wt) mice. However, the mechanisms remain poorly understood. Leptin is significantly increased following TBI, while its role in bone healing remains unclear. The aim of this study was to evaluate fracture healing in leptin-deficient ob/ob mice and to measure any possible impact of TBI on callus formation. 138 female, 12 weeks old, ob/ob mice were divided into four groups: Control, fracture, TBI and combined trauma. Osteotomies were stabilized with an external fixator; TBI was induced with Controlled Cortical Impact Injury. Callus bridging was weekly evaluated with in vivo micro-CT. Biomechanical testing was performed ex vivo. Micro-CT showed high non-union rates after three and four weeks in the fracture and combined trauma group. No differences were observed in callus volume, density and biomechanical properties at any time point. This study shows that bony bridging is impaired in the present leptin-deficient trauma model. Furthermore, the phenomenon of increased callus formation after TBI could not be reproduced in ob/ob mice, as in wt mice. Our findings suggest that the increased callus formation after TBI may be dependent on leptin signaling. PMID:28574414

Temporal profile of inflammatory response to fracture and hemorrhagic shock: Proposal of a novel long-term survival murine multiple trauma model.

PubMed

Kleber, Christian; Becker, Christopher A; Malysch, Tom; Reinhold, Jens M; Tsitsilonis, Serafeim; Duda, Georg N; Schmidt-Bleek, Katharina; Schaser, Klaus D

2015-07-01

Hemorrhagic shock (hS) interacts with the posttraumatic immune response and fracture healing in multiple trauma. Due to the lack of a long-term survival multiple trauma animal models, no standardized analysis of fracture healing referring the impact of multiple trauma on fracture healing was performed. We propose a new long-term survival (21 days) murine multiple trauma model combining hS (microsurgical cannulation of carotid artery, withdrawl of blood and continuously blood pressure measurement), femoral (osteotomy/external fixation) and tibial fracture (3-point bending technique/antegrade nail). The posttraumatic immune response was measured via IL-6, sIL-6R ELISA. The hS was investigated via macrohemodynamics, blood gas analysis, wet-dry lung ration and histologic analysis of the shock organs. We proposed a new murine long-term survival (21 days) multiple trauma model mimicking clinical relevant injury patterns and previously published human posttraumatic immune response. Based on blood gas analysis and histologic analysis of shock organs we characterized and standardized our murine multiple trauma model. Furthermore, we revealed hemorrhagic shock as a causative factor that triggers sIL-6R formation underscoring the fundamental pathophysiologic role of the transsignaling mechanism in multiple trauma. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

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

Delayed wound healing after tooth extraction and self-reported kyphosis in Japanese men and women

PubMed Central

Taguchi, Akira; Kamimura, Mikio; Nakamura, Yukio; Sugino, Noriyuki; Ichinose, Akira; Maezumi, Hisayoshi; Fukuzawa, Takashi; Ashizawa, Ryouhei; Takahara, Kenji; Gushiken, Susumu; Mukaiyama, Keijiro; Ikegami, Shota; Uchiyama, Shigeharu; Kato, Hiroyuki

2016-01-01

It is unclear whether osteoporosis itself is a main risk factor for delayed wound healing after tooth extraction in humans. In this study, we evaluated the association between experience of delayed wound healing after last tooth extraction and self-reported kyphosis, with the possibility of having vertebral fractures, in Japanese patients. Among the 1,504 patients who responded to the structured questionnaire survey, 518 patients (134 men and 384 women) aged 55–97 years finally participated in this study. Patients who self-reported mild-moderate kyphosis were more likely to have problematic delayed wound healing after last tooth extraction than those who reported severe kyphosis (odds ratio [OR] 4.98; 95% confidence interval [CI], 1.86–13.38 and OR 2.30; 95% CI, 0.52–10.22, respectively) (p for trend = 0.005). Japanese patients with vertebral fractures may have a higher risk of having problematic delayed wound healing after tooth extraction. PMID:27848958

Delayed wound healing after tooth extraction and self-reported kyphosis in Japanese men and women.

PubMed

Taguchi, Akira; Kamimura, Mikio; Nakamura, Yukio; Sugino, Noriyuki; Ichinose, Akira; Maezumi, Hisayoshi; Fukuzawa, Takashi; Ashizawa, Ryouhei; Takahara, Kenji; Gushiken, Susumu; Mukaiyama, Keijiro; Ikegami, Shota; Uchiyama, Shigeharu; Kato, Hiroyuki

2016-11-16

It is unclear whether osteoporosis itself is a main risk factor for delayed wound healing after tooth extraction in humans. In this study, we evaluated the association between experience of delayed wound healing after last tooth extraction and self-reported kyphosis, with the possibility of having vertebral fractures, in Japanese patients. Among the 1,504 patients who responded to the structured questionnaire survey, 518 patients (134 men and 384 women) aged 55-97 years finally participated in this study. Patients who self-reported mild-moderate kyphosis were more likely to have problematic delayed wound healing after last tooth extraction than those who reported severe kyphosis (odds ratio [OR] 4.98; 95% confidence interval [CI], 1.86-13.38 and OR 2.30; 95% CI, 0.52-10.22, respectively) (p for trend = 0.005). Japanese patients with vertebral fractures may have a higher risk of having problematic delayed wound healing after tooth extraction.

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.

Aqueous extract of Peperomia pellucida (L.) HBK accelerates fracture healing in Wistar rats.

PubMed

Florence, Ngueguim Tsofack; Huguette, Sakouong Talle Suewellyne; Hubert, Donfack Jean; Raceline, Gounoue Kamkumo; Desire, Dzeufiet Djomeni Paul; Pierre, Kamtchouing; Theophile, Dimo

2017-04-04

Peperomia pellucida (L.) HBK is consumed as vegetable and used in Cameroonian traditional medicine for the management of diseases and for fracture healing. Therefore the aim of this study was to evaluate the effects of the aqueous whole plant extract of Peperomia pellucida on fracture healing in female Wistar rats. A drill hole injury was created by inserting a drill bit inthe diaphysis of the femur. The aqueous extract of the whole plant of Peperomia pellucida was administered orally at the doses of 100, 200 and 400 mg/kg to adult female Wistar rats. The vehicle (distilled water) was given to the control. Besides these rats, one group of rats without fracture received the extract (400 mg/kg). After 14 days of treatment, the rats were sacrificed under anesthesia and the effects of the extract were evaluated on body weight, the relative weights of organs (femurs, uteri and ovaries) and on hematology. Bone (calcium, phosphorus, alkaline phosphatase) and serum biochemical parameters (calcium, phosphorus, alkaline phosphatase) were also evaluated. Radiological and histological tests were carried out on the femurs. The mineral content of the plant extract was also investigated. The extract induced an increase in body weight at high dose and in WBCs count at low doses. Aqueous extract from Peperomia pellucida increased bone calcium at lowest dose but maintained this parameter at normal range at high dose in fractured rat. Alkaline phophatase and phosphorus concentrations reduced significantly (p < 0.01) at the dose of 400 mg/kg as compared to fractured rats. Moreover, radiological tests revealed a dose dependent formation of callus at the level of the fracture gap, confirmed by the formation of a highly dense and compact fibrocartilagenous callus. The mineral content of the plant extract revealed the presence of calcium, phosphorus, magnesium, sodium and potassium. The aqueous extract of P. pellucida accelerates bone healing due partly to the mineral content of the extract. These results confirm its traditional use in the treatment of bone fractures.

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

Time-Dependent Changes in T1 during Fracture Healing in Juvenile Rats: A Quantitative MR Approach

PubMed Central

Baron, Katharina; Neumayer, Bernhard; Amerstorfer, Eva; Scheurer, Eva; Diwoky, Clemens; Stollberger, Rudolf; Sprenger, Hanna; Weinberg, Annelie M.

2016-01-01

Quantitative magnetic resonance imaging (qMRI) offers several advantages in imaging and determination of soft tissue alterations when compared to qualitative imaging techniques. Although applications in brain and muscle tissues are well studied, its suitability to quantify relaxation times of intact and injured bone tissue, especially in children, is widely unknown. The objective observation of a fracture including its age determination can become of legal interest in cases of child abuse or maltreatment. Therefore, the aim of this study is the determination of time dependent changes in intact and corresponding injured bones in immature rats via qMRI, to provide the basis for an objective and radiation-free approach for fracture dating. Thirty-five MR scans of 7 Sprague-Dawley rats (male, 4 weeks old, 100 ± 5 g) were acquired on a 3T MRI scanner (TimTrio, Siemens AG, Erlangen, Germany) after the surgical infliction of an epiphyseal fracture in the tibia. The images were taken at days 1, 3, 7, 14, 28, 42 and 82 post-surgery. A proton density-weighted and a T1-weighted 3D FLASH sequence were acquired to calculate the longitudinal relaxation time T1 of the fractured region and the surrounding tissues. The calculation of T1 in intact and injured bone resulted in a quantitative observation of bone development in intact juvenile tibiae as well as the bone healing process in the injured tibiae. In both areas, T1 decreased over time. To evaluate the differences in T1 behaviour between the intact and injured bone, the relative T1 values (bone-fracture) were calculated, showing clear detectable alterations of T1 after fracture occurrence. These results indicate that qMRI has a high potential not only for clinically relevant applications to detect growth defects or developmental alterations in juvenile bones, but also for forensically relevant applications such as the dating of fractures in cases of child abuse or maltreatment. PMID:27832068

Experimental models for cancellous bone healing in the rat

PubMed Central

Bernhardsson, Magnus; Sandberg, Olof; Aspenberg, Per

2015-01-01

Background and purpose — Cancellous bone appears to heal by mechanisms different from shaft fracture healing. There is a paucity of animal models for fractures in cancellous bone, especially with mechanical evaluation. One proposed model consists of a screw in the proximal tibia of rodents, evaluated by pull-out testing. We evaluated this model in rats by comparing it to the healing of empty drill holes, in order to explain its relevance for fracture healing in cancellous bone. To determine the sensitivity to external influences, we also compared the response to drugs that influence bone healing. Methods — Mechanical fixation of the screws was measured by pull-out test and related to the density of the new bone formed around similar, but radiolucent, PMMA screws. The pull-out force was also related to the bone density in drill holes at various time points, as measured by microCT. Results — The initial bone formation was similar in drill holes and around the screw, and appeared to be reflected by the pull-out force. Both models responded similarly to alendronate or teriparatide (PTH). Later, the models became different as the bone that initially filled the drill hole was resorbed to restore the bone marrow cavity, whereas on the implant surface a thin layer of bone remained, making it change gradually from a trauma-related model to an implant fixation model. Interpretation — The similar initial bone formation in the different models suggests that pull-out testing in the screw model is relevant for assessment of metaphyseal bone healing. The subsequent remodeling would not be of clinical relevance in either model. PMID:26200395

Pulsed ultrasounds accelerate healing of rib fractures in an experimental animal model: an effective new thoracic therapy?

PubMed

Santana-Rodríguez, Norberto; Clavo, Bernardino; Fernández-Pérez, Leandro; Rivero, José C; Travieso, María M; Fiuza, María D; Villar, Jesús; García-Castellano, José M; Hernández-Pérez, Octavio; Déniz, Antonio

2011-05-01

Rib fractures are a frequent traumatic injury associated with a relatively high morbidity. Currently, the treatment of rib fractures is symptomatic. Since it has been reported that pulsed ultrasounds accelerates repair of limb fractures, we hypothesized that the application of pulsed ultrasounds will modify the course of healing in an animal model of rib fracture. We studied 136 male Sprague-Dawley rats. Animals were randomly assigned to different groups of doses (none, 50, 100, and 250 mW/cm(2) of intensity for 3 minutes per day) and durations (2, 10, 20, and 28 days) of treatment with pulsed ultrasounds. In every subgroup, we analyzed radiologic and histologic changes in the bone callus. In addition, we examined changes in gene expression of relevant genes involved in wound repair in both control and treated animals. Histologic and radiologic consolidation was significantly increased by pulsed ultrasound treatment when applied for more than 10 days. The application of 50 mW/cm(2) was the most effective dose. Only the 100 and 250 mW/cm(2) doses were able to significantly increase messenger RNA expression of insulin-like growth factor 1, suppressor of cytokine signaling-2 and -3, and vascular endothelial growth factor and decrease monocyte chemoattractant protein-1 and collagen type II-alpha 1. Our findings indicate that pulsed ultrasound accelerates the consolidation of rib fractures. This study is the first to show that pulsed ultrasound promotes the healing of rib fractures. From a translational point of view, this easy, cheap technique could serve as an effective new therapeutic modality in patients with rib fractures. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Complete Remodeling After Conservative Treatment of a Severely Angulated Odontoid Fracture in a Patient With Osteogenesis Imperfecta: A Case Report.

PubMed

Colo, Dino; Schlösser, Tom P C; Oostenbroek, Hubert J; Castelein, René M

2015-09-15

Case report. This is the first case report describing successful healing and remodeling of a traumatic odontoid fracture that was dislocated and severely angulated in a patient with osteogenesis imperfecta who was treated conservatively. Osteogenesis imperfecta (OI) is a rare genetic disorder resulting in a low bone mass and bone fragility, predisposing these patients to fractures that often occur at a young age. Although any bone in the body may be involved, odontoid fractures are uncommon in this population. Because of a very high fusion rate, conservative management is accepted as a safe and efficient treatment of fractures of the odontoid in children. Several authors, however, recommend surgical treatment of patients who have failure of conservative treatment and have severe angulation or displacement of the odontoid. A 5-year-old female, diagnosed with OI type I, presented with neck pain without any neurological deficits after falling out of a rocking chair backward, with her head landing first on the ground. Computed tomography confirmed a type III odontoid fracture without dislocation and she was initially treated with a rigid cervical orthosis. At 1 and 2 months of follow-up, progressive severe angulation of the odontoid was observed but conservative treatment was maintained as the space available for the spinal cord was sufficient and also considering the patient's history of OI. Eight months postinjury, she had no clinical symptoms and there was osseous healing of the fracture with remodeling of the odontoid to normal morphology. Even in patients with OI, severely angulated odontoid fractures might have the capacity for osseous healing and complete remodeling under conservative treatment. 5.

Increase of cortical bone after a cementless long stem in periprosthetic fractures.

PubMed

García-Rey, Eduardo; García-Cimbrelo, Eduardo; Cruz-Pardos, Ana; Madero, Rosário

2013-12-01

Healing and functional recovery have been reported using an extensively porous-coated stem in Vancouver B2 and B3 periprosthetic fractures; however, loss of cortical bone has been observed when using these stems in revision surgery for aseptic loosening. However, it is unclear whether this bone loss influences subsequent loosening. We analyze the healing fracture rate and whether the radiographic changes observed around and extensively porous-coated stem used for periprosthetic fractures affect function or loosening. We retrospectively reviewed 35 patients with periprosthetic fractures (20 Vancouver B2 and 15 Vancouver B3). Patients' mean age at surgery was 80 years (range, 51-86 years). No cortical struts were used in this series. We evaluated radiographs for signs of loosening or subsidence. The cortical index and the femoral cortical width were measured at different levels on the immediate pre- and postoperative radiographs and at different periods of followup. The minimum followup was 3 years (mean, 8.3 years; range, 3-17 years). All fractures had healed, and all stems were clinically and radiographically stable at the end of followup. Nineteen hips showed nonprogressive radiographic subsidence during the first 3 postoperative months without clinical consequences. The cortical index and the lateral and medial cortical thickness increased over time. Increase of femoral cortex thicknesses was greater in cases with moderate preoperative osteoporosis and in cases with stems less than 16 mm in thickness. Our data suggest an extensively porous-coated stem for Vancouver B2 and B3 periprosthetic fractures leads to a high rate of union and stable fixation. Cortical index and lateral cortex thickness increased in these patients with periprosthetic fractures. Patients with moderate osteoporosis and those using thin stems showed a major increase in femoral cortex thickness over time.

Ketorolac Administered in the Recovery Room for Acute Pain Management Does Not Affect Healing Rates of Femoral and Tibial Fractures.

PubMed

Donohue, David; Sanders, Drew; Serrano-Riera, Rafa; Jordan, Charles; Gaskins, Roger; Sanders, Roy; Sagi, H Claude

2016-09-01

To determine whether ketorolac administered in the immediate perioperative period affects the rate of nonunion in femoral and tibial shaft fractures. Retrospective comparative study. Single Institution, Academic Level 1 Trauma Center. Three hundred and thirteen skeletally mature patients with 137 femoral shaft (OTA 32) and 191 tibial shaft (OTA 42) fractures treated with intramedullary rod fixation. Eighty patients with 33 femoral shaft and 52 tibial shaft fractures were administered ketorolac within the first 24 hours after surgery (group 1-study group). Two-hundred thirty-three patients with 104 femoral shaft and 139 tibial shaft fractures were not (group 2-control group). Rate of reoperation for repair of a nonunion and time to union. Average time to union of the femur was 147 days for group 1 and 159 days for group 2 (P = 0.57). Average time to union of the tibia was 175 days for group 1 and 175 days for group 2 (P = 0.57). There were 3 femoral nonunions (9%) in group 1 and eleven femoral nonunions (11.6%) in group 2 (P = 1.00). There were 3 tibial nonunions (5.8%) in group 1 and 17 tibial nonunions (12.2%) in group 2 (P = 0.29). The average dose of ketorolac for patients who healed their fracture was 85 mg, whereas it was 50 mg for those who did not (P = 0.27). All patients with a nonunion in the study group were current smokers. Ketorolac administered in the first 24 hours after fracture repair for acute pain management does not seem to have a negative impact on time to healing or incidence of nonunion for femoral or tibial shaft fractures. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Flexible intramedullary nailing for the treatment of unicameral bone cysts in long bones.

PubMed

Roposch, A; Saraph, V; Linhart, W E

2000-10-01

Unicameral bone cyst is characterized by its tenacity and risk of recurrence. Pathological fracture is common and is often the presenting symptom. The objective of the present study was to evaluate the results of flexible intramedullary nailing for the treatment of a unicameral bone cyst with or without a pathological fracture. Flexible intramedullary nailing for the treatment of a unicameral bone cyst was performed in thirty-two patients. Thirty of these patients presented with a pathological fracture; twenty-four were managed immediately with intramedullary nailing, and the other six had been managed conservatively at other clinics before they were referred to our department. The remaining two cysts were detected incidentally. The cyst was located in the humerus in twenty-one patients, in the femur in nine, and in the radius in two. The mean age of the patients at the time of surgery was 9.8 years, and the mean duration of follow-up was 53.7 months. Radiographic evaluation was performed according to the criteria of Capanna et al., and the cyst was classified as completely healed, healed with residual radiolucency (osteolysis), recurred, or having no response. The healing period ranged from three to 105 months. Fourteen cysts healed completely, and sixteen healed with residual radiolucent areas visible on radiographs. There was recurrence of two cysts that had healed with residual radiolucency. All of the cysts in the present study responded to treatment. A change of nails was necessary in nine patients, as the nails had become too short after bone growth. No major complications were observed. Flexible intramedullary nailing provides early stability, which allows early mobilization and thus obviates the need for a plaster cast and decreases the prevalence of the most common complication: a pathological fracture. This method of treatment also allows for an early return to normal activity.

[Application of bone flap pedicled on retrograde branch of radial artery for treatment of old scaphoid bone fractures of type AO-B].

PubMed

Sun, Qing-peng

2015-05-01

To investigate application of the bone flap pedicled on the retrograde branch of radial artery for treatment of old scaphoid bone fractures of type AO-B. From October 2007 to October 2011,41 patients with old scaphoid bone fractures of type AO-B were treated by transplantation of the bone flap pedicled on the retrograde branch of radial artery including 26 males and 15 females with an average of (27.3±4.5) years old ranging from 16 to 43 years old. The courses before operation ranged from 6 to 22 months with an average of 11 months. All fractures belonged to the type B of AO classification, that is old wrist fracture of scaphoid bone. All patients' wrist function (pain, function, motion, grip strength) were evaluated by Cooney's modifiedwrist scoring system before and 6 months after operation,and the conditions of bone healing were observed during the follow-up time. Among them, 36 patients were followed up from 4 to 15 months with an average of 8.3 months. The wounds were healed well without other complications as infection appearing. X-rays or CT confirmed that all fractures were healed completely. The Cooney wrist score was improved from preoperative 53.61±13.97 to postoperative 81.81±8.71 (P<0.01). The operation of transplantation of the bone flap pedicled on the retrograde branch of radial artery is an effective method to treat old scaphoid bone fractures,which is scientific and has curative effects, and valuable for clinical application.

Cannabidiol, a Major Non-Psychotropic Cannabis Constituent Enhances Fracture Healing and Stimulates Lysyl Hydroxylase Activity in Osteoblasts.

PubMed

Kogan, Natalya M; Melamed, Eitan; Wasserman, Elad; Raphael, Bitya; Breuer, Aviva; Stok, Kathryn S; Sondergaard, Rachel; Escudero, Ana V Villarreal; Baraghithy, Saja; Attar-Namdar, Malka; Friedlander-Barenboim, Silvina; Mathavan, Neashan; Isaksson, Hanna; Mechoulam, Raphael; Müller, Ralph; Bajayo, Alon; Gabet, Yankel; Bab, Itai

2015-10-01

Cannabinoid ligands regulate bone mass, but skeletal effects of cannabis (marijuana and hashish) have not been reported. Bone fractures are highly prevalent, involving prolonged immobilization and discomfort. Here we report that the major non-psychoactive cannabis constituent, cannabidiol (CBD), enhances the biomechanical properties of healing rat mid-femoral fractures. The maximal load and work-to-failure, but not the stiffness, of femurs from rats given a mixture of CBD and Δ(9) -tetrahydrocannabinol (THC) for 8 weeks were markedly increased by CBD. This effect is not shared by THC (the psychoactive component of cannabis), but THC potentiates the CBD stimulated work-to-failure at 6 weeks postfracture followed by attenuation of the CBD effect at 8 weeks. Using micro-computed tomography (μCT), the fracture callus size was transiently reduced by either CBD or THC 4 weeks after fracture but reached control level after 6 and 8 weeks. The callus material density was unaffected by CBD and/or THC. By contrast, CBD stimulated mRNA expression of Plod1 in primary osteoblast cultures, encoding an enzyme that catalyzes lysine hydroxylation, which is in turn involved in collagen crosslinking and stabilization. Using Fourier transform infrared (FTIR) spectroscopy we confirmed the increase in collagen crosslink ratio by CBD, which is likely to contribute to the improved biomechanical properties of the fracture callus. Taken together, these data show that CBD leads to improvement in fracture healing and demonstrate the critical mechanical role of collagen crosslinking enzymes. © 2015 American Society for Bone and Mineral Research.

Transverse and Oblique Long Bone Fracture Evaluation by Low Order Ultrasonic Guided Waves: A Simulation Study

PubMed Central

Li, Ying; Liu, Dan; Xu, Kailiang; Le, Lawrence H.; Wang, Weiqi

2017-01-01

Ultrasonic guided waves have recently been used in fracture evaluation and fracture healing monitoring. An axial transmission technique has been used to quantify the impact of the gap breakage width and fracture angle on the amplitudes of low order guided wave modes S0 and A0 under a 100 kHz narrowband excitation. In our two dimensional finite-difference time-domain (2D-FDTD) simulation, the long bones are modeled as three layers with a soft tissue overlay and marrow underlay. The simulations of the transversely and obliquely fractured long bones show that the amplitudes of both S0 and A0 decrease as the gap breakage widens. Fixing the crack width, the increase of the fracture angle relative to the cross section perpendicular to the long axis enhances the amplitude of A0, while the amplitude of S0 shows a nonmonotonic trend with the decrease of the fracture angle. The amplitude ratio between the S0 and A0 modes is used to quantitatively evaluate the fracture width and angles. The study suggests that the low order guided wave modes S0 and A0 have potentials for transverse and oblique bone fracture evaluation and fracture healing monitoring. PMID:28182135

Transverse and Oblique Long Bone Fracture Evaluation by Low Order Ultrasonic Guided Waves: A Simulation Study.

PubMed

Li, Ying; Liu, Dan; Xu, Kailiang; Ta, Dean; Le, Lawrence H; Wang, Weiqi

2017-01-01

Ultrasonic guided waves have recently been used in fracture evaluation and fracture healing monitoring. An axial transmission technique has been used to quantify the impact of the gap breakage width and fracture angle on the amplitudes of low order guided wave modes S 0 and A 0 under a 100 kHz narrowband excitation. In our two dimensional finite-difference time-domain (2D-FDTD) simulation, the long bones are modeled as three layers with a soft tissue overlay and marrow underlay. The simulations of the transversely and obliquely fractured long bones show that the amplitudes of both S 0 and A 0 decrease as the gap breakage widens. Fixing the crack width, the increase of the fracture angle relative to the cross section perpendicular to the long axis enhances the amplitude of A 0, while the amplitude of S 0 shows a nonmonotonic trend with the decrease of the fracture angle. The amplitude ratio between the S 0 and A 0 modes is used to quantitatively evaluate the fracture width and angles. The study suggests that the low order guided wave modes S 0 and A 0 have potentials for transverse and oblique bone fracture evaluation and fracture healing monitoring.

Complications and Functional Recovery in Treatment of Femoral Shaft Fractures with Unreamed Intramedullary Nailing

PubMed Central

Sadic, Sahmir; Custovic, Svemir; Smajic, Nedim; Fazlic, Mirsad; Vujadinovic, Aleksandar; Hrustic, Asmir; Jasarevic, Mahir

2014-01-01

ABSTRACT Introduction: Fracture of the femoral shaft is a common fracture encountered in orthopedic practice. In the 1939, Küntscher introduced the concept of intramedullary nailing for stabilization of long bone fractures. Intramedullary nailing has revolutionized the treatment of fractures. Material and methods: The study included 37 male patients and 13 female patients, averaged 39±20,5 years (range, 16 to 76 years). Results and discussion: There were 31 left femurs and 21 right femurs fractured. 46 fractures were the result of blunt trauma. Low energy trauma was the cause of fractures in six patients, of which five in elderly females. 49 fractures were closed. Healing time given in weeks was 19,36 ± 6,1. The overall healing rate was 93,6%. There were three (6,25%) major complications nonunion. There were one (2%) delayed union, one (2%) rotational malunion and no infection. The shortening of 1 cm were in two patients. Antercurvatum of 10 degrees was found in one patient. There was no statistically significant reduction of a motion in the hip and knee (p<0.05). There was statistically significant in the thigh (knee extensors) muscle weakness (p<0.001). Conclusion: Intramedullary nailing is the treatment of choice for femoral shaft fractures. PMID:24783908

Treatment of Early Post-Op Wound Infection after Internal Fixation

DTIC Science & Technology

2017-10-01

the fracture stable while the bone heals. Approximately 10%-40% of severe fractures fixed with internal fixation develop a deep wound infection during...effect of treatment of post-op wound infection in bones after fracture fixation or joint fusion and either: (Group 1) operative debridement and PO

Thermo-mechanical process for treatment of welds

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

Malik, R K

1980-03-01

Benefits from thermo-mechanical processing (TMP) of austenitic stainless steel weldments, analogous to hot isostatic pressing (HIP) of castings, most likely result from compressive plastic deformation, enhanced diffusion, and/or increased dislocation density. TMP improves ultrasonic inspectability of austenitic stainless steel welds owing to: conversion of cast dendrites into equiaxed austenitic grains, reduction in size and number of stringers and inclusions, and reduction of delta ferrite content. TMP induces structural homogenization and healing of void-type defects and thus contributes to an increase in elongation, impact strength, and fracture toughness as well as a significant reduction in data scatter for these properties. Anmore » optimum temperature for TMP or HIP of welds is one which causes negligible grain growth and an acceptable reduction in yield strength, and permits healing of porosity.« less

Broken Toe

MedlinePlus

... fracture is severe — particularly if it involves your big toe — you may need a cast or even surgery to ensure proper healing. Most broken toes heal well, usually within four to six weeks. Sometimes, a broken toe may become infected ...

Autonomous self-healing structural composites with bio-inspired design

PubMed Central

D’Elia, Eleonora; Eslava, Salvador; Miranda, Miriam; Georgiou, Theoni K.; Saiz, Eduardo

2016-01-01

Strong and tough natural composites such as bone, silk or nacre are often built from stiff blocks bound together using thin interfacial soft layers that can also provide sacrificial bonds for self-repair. Here we show that it is possible exploit this design in order to create self-healing structural composites by using thin supramolecular polymer interfaces between ceramic blocks. We have built model brick-and-mortar structures with ceramic contents above 95 vol% that exhibit strengths of the order of MPa (three orders of magnitude higher than the interfacial polymer) and fracture energies that are two orders of magnitude higher than those of the glass bricks. More importantly, these properties can be fully recovered after fracture without using external stimuli or delivering healing agents. This approach demonstrates a very promising route towards the design of strong, ideal self-healing materials able to self-repair repeatedly without degradation or external stimuli. PMID:27146382

Autonomous self-healing structural composites with bio-inspired design.

PubMed

D'Elia, Eleonora; Eslava, Salvador; Miranda, Miriam; Georgiou, Theoni K; Saiz, Eduardo

2016-05-05

Strong and tough natural composites such as bone, silk or nacre are often built from stiff blocks bound together using thin interfacial soft layers that can also provide sacrificial bonds for self-repair. Here we show that it is possible exploit this design in order to create self-healing structural composites by using thin supramolecular polymer interfaces between ceramic blocks. We have built model brick-and-mortar structures with ceramic contents above 95 vol% that exhibit strengths of the order of MPa (three orders of magnitude higher than the interfacial polymer) and fracture energies that are two orders of magnitude higher than those of the glass bricks. More importantly, these properties can be fully recovered after fracture without using external stimuli or delivering healing agents. This approach demonstrates a very promising route towards the design of strong, ideal self-healing materials able to self-repair repeatedly without degradation or external stimuli.

Autonomous self-healing structural composites with bio-inspired design

NASA Astrophysics Data System (ADS)

D'Elia, Eleonora; Eslava, Salvador; Miranda, Miriam; Georgiou, Theoni K.; Saiz, Eduardo

2016-05-01

Strong and tough natural composites such as bone, silk or nacre are often built from stiff blocks bound together using thin interfacial soft layers that can also provide sacrificial bonds for self-repair. Here we show that it is possible exploit this design in order to create self-healing structural composites by using thin supramolecular polymer interfaces between ceramic blocks. We have built model brick-and-mortar structures with ceramic contents above 95 vol% that exhibit strengths of the order of MPa (three orders of magnitude higher than the interfacial polymer) and fracture energies that are two orders of magnitude higher than those of the glass bricks. More importantly, these properties can be fully recovered after fracture without using external stimuli or delivering healing agents. This approach demonstrates a very promising route towards the design of strong, ideal self-healing materials able to self-repair repeatedly without degradation or external stimuli.

Greenstick Fractures

MedlinePlus

... are the bones of adults. Even mild greenstick fractures are usually immobilized in a cast. In addition to holding the cracked pieces of the bone together so they can heal, a cast can help prevent the bone from ...

Defect nonunion of a metatarsal bone fracture in a cow: successful management with bone plating and autogenous cancellous bone graft.

PubMed

Raghunath, M; Singh, N; Singh, T; Gopinathan, A; Mohindroo, J; Atri, K

2013-01-01

A two-and-half-year-old cow was presented with a defect nonunion of the right metatarsal III/IV bone following a severely comminuted open fracture two months previously. The animal underwent open fixation using a 4.5 mm, broad, 10-hole, dynamic compression plate and autogenous cancellous bone graft collected from the contralateral iliac shaft. The animal started partial weight bearing after the third postoperative day and resumed complete weight bearing after the 10th day. Fracture healing was complete and the implants were removed after the 120th postoperative day. Stable fixation by means of a bone plate in conjunction with a cancellous bone graft facilitated complete healing and restoration of the bone column of the defect and the metatarsal fracture. The animal made a complete recovery.

Comparison of Tension-Band Wiring With the Cable Pin System in Patella Fractures: A Randomized Prospective Study.

PubMed

Tian, Qing-xian; Hai, Yong; Du, Xin-ru; Xu, Zi-yu; Lu, Tie; Shan, Lei; Liu, Yang; Zhou, Jun-lin

2015-12-01

To compare the outcome of tension-band wiring (TBW) with the cable pin system (CPS) for transverse fractures of the patella. Randomized prospective study. Academic Level I trauma center. From February 2008 to December 2011, 73 consecutive patients with transverse fractures of the patella were prospectively enrolled in this study. The patients were randomly divided into 2 groups: one group was treated using the CPS, and the other group was treated using the modified TBW. The clinical outcome assessment included analyses of the radiographic images, the modified Hospital for Special Surgery scoring system, and complications. The follow-up time ranged from 12 to 29 months. All fractures healed, with a union rate of 100%. The fracture healing time was significantly shorter in the CPS group (8.51 ± 2.59 weeks, n = 34) compared with the TBW group (11.79 ± 3.04 weeks, n = 39). Postoperative complications in the CPS and TBW groups were observed in 1 and 9 patients, respectively, a difference that was statistically significant. The mean Hospital for Special Surgery score for the CPS group (90.53 ± 5.19 points) was significantly higher than that for the TBW group (81.36 ± 12.71 points). The CPS is a viable option for transverse fractures of the patella and is associated with a shorter healing time, fewer complications, and better function than TBW. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Coupled external fixator and skin flap transposition for treatment of exposed and nonunion bone.

PubMed

Zhao, Yong-gang; Ding, Jing; Wang, Neng

2011-02-01

To discuss the effect of coupled external fixator and skin flap transposition on exposed and nonunion bones. The data of 12 cases of infected nonunion and exposed bone following open fracture treated in our hospital during the period of March 1998 to June 2008 were analysed. There were 10 male patients, 2 female patients, whose age were between 19-52 years and averaged 28 years. There were 10 tibial fractures and 2 femoral fractures. The course of diseases lasted for 12-39 months with the mean period of 19 months. All the cases were treated by the coupled external fixator and skin flap transposition. Primary healing were achieved in 10 cases and delayed healing in 2 cases in whom the tibia was exposed due to soft tissue defect and hence local flap transposition was performed. All the 12 cases had bony union within 6-12 months after operation with the average time of 8 months. They were followed up for 1-3 years and all fractures healed up with good function and no infection recurrence. The coupled external fixator and skin flap transposition therapy have shown optimal effects on treating infected, exposed and nonunion bones.

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.

[Comparison of clinical effect on locking plate for proximal humeral fracture with or without application of inferomedial screws].

PubMed

Guo, Xiu-wu; Fan, Jian; Yuan, Feng

2016-06-01

To compare clinical outcomes of locking plate for proximal humeral fracture whether application of inferomedial screws. From January 2012 to July 2013, 46 patients with proximal humeral fracture underwent locking plates were retrospectively analyzed. There were 25 males and 21 females aged from 29 to 80 years old with an average of 55.1 years old. Among them, 25 patients were treated with inferomedial screws (support group), including 13 males and 12 females aged from 38 to 80 years old with an average of (55.8 ± 11.8) years old; 8 cases were part two fracture,10 cases were part three fracture and 7 cases were part four fracture according to Neer classification. Twenty-one patients were treated without inferomedial screws (non-support group), including 12 males and 9 females aged from 29 to 79 years old with an average of (54.2 ± 14.8)years old; 6 cases were part two fracture, 9 cases were part three fracture and 6 cases were part four fracture according to Neer classification. Operative time, fracture healing time and complications were observed and compared, Neer scoring of shoulder joint were used to evaluate clinical effect. All patients were followed up from 12 to 41 months with an average of 15.6 months. Operative time and fracture healing time in support group was (1.6 ± 0.4) h and (3.0 ± 0.6) months, and (1.5 ± 0.4) h and (3.1 ± 0.6) months in non-support group, while there was no statistical difference in operative time and fracture healing time between two groups. There was significant differences in Neer score between support group (89.7± 4.9) and non-support group (83.1 ± 7.1). No complication occurred in support group,while 4 cases occurred complications in non-support group. Locking plate with inferomedial screws for proximal humeral fracture has advantages of stable fixation, less complications, quick recovery of function and satisfied clinical effect.

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.

Osteoblast-Specific Loss of IGF1R Signaling Results in Impaired Endochondral Bone Formation During Fracture Healing

PubMed Central

Wang, Tao; Wang, Yongmei; Menendez, Alicia; Fong, Chak; Babey, Muriel; Tahimic, Candice GT; Cheng, Zhiqiang; Li, Alfred; Chang, Wenhan; Bikle, Daniel D.

2017-01-01

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 IGF1Rflox/flox/2.3-kb α1(1)-collagen-Cre (KO) and IGF1Rflox/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. PMID:25801198

Delayed Union of a Jones Fracture in a Patient With Rothmund-Thomson Syndrome: A Case Report and Review of the Literature.

PubMed

Barisonek, Kirsten L; Protzman, Nicole M; Wobst, Garrett M; Brigido, Stephen A

2016-01-01

Rothmund-Thomson syndrome is a rare autosomal recessive genodermatosis, characterized by poikiloderma, small stature, juvenile cataracts, sparse hair, skeletal abnormalities, and a predisposition to osteogenic sarcomas and skin cancers. Although numerous skeletal abnormalities have been described in patients with Rothmund-Thomson syndrome, to our knowledge, only 1 study has shown evidence of delayed fracture healing in a patient with Rothmund-Thomson syndrome. We present the case of a 13-year-old female diagnosed with Rothmund-Thomson syndrome who demonstrated delayed union of her fifth metatarsal after a Jones fracture. She was treated conservatively for 6 weeks with non-weightbearing cast immobilization and was then transitioned to a controlled ankle motion walker for an additional 4 weeks. Two months later, however, she continued to experience pain, and, on radiographic examination, the fracture remained unchanged. Therefore, with her guardian's consent, the patient elected to undergo open reduction and internal fixation of the fifth metatarsal fracture. At 8 weeks postoperatively, the patient reported a subsidence of symptoms and had returned to normal activity. With our report, we hope to increase practitioner awareness that delayed bone healing could be a possibility in patients with Rothmund-Thomson syndrome and encourage consideration of routine imaging and supplementation with calcium and vitamin D. Additionally, the present findings suggest that patients with Rothmund-Thomson syndrome could benefit from early surgical intervention, given their poor bone healing capacity and high likelihood of nonunion. Although the association between impaired bone healing and Rothmund-Thomson syndrome is rational, additional studies are needed to determine the prevalence of chronic nonunion in this patient population. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Effect of strontium ranelate on fracture healing in rat tibia.

PubMed

Cebesoy, Oguz; Tutar, Ediz; Kose, Kamil Cagri; Baltaci, Yasemin; Bagci, Cahit

2007-12-01

Various anti-osteoporotic agents are available for clinical use. In contrast to other anti-osteoporotic drugs, strontium ranelate has anti-resorptive and bone-forming effects (dual action). Our objective in the present study is to investigate the efficacy of strontium ranelate (SR) on fracture healing in rat tibia. Forty-two male Wistar rats randomized into two groups (groups 1 and 2, n=21 for each). Left tibiae of all animals were broken in a closed manner using a manual three-point bending technique through mid-tibia following deep anesthesia with ketamine. The animals in group 1 were fed 25g/day specially produced food containing 450mg/kg SR starting from the first post-operative day. Group 2 were given 25g/day normal food. The animals were sacrificed on the 2nd, 3rd and 4th post-operative weeks (each week 7 animals were sacrificed from each group) and the broken tibiae were removed. The tibiae were examined first radiographically and second, histopathologically. Radiologically, callus maturity and bone union increased with time in both groups. But no significant differences were found regarding callus maturity and bone union in weekly comparisons (p=0.52, p=0.19, p=0.74). Histopathologically, it was seen that the fractures remarkably healed steadily in both groups on the 2nd, 3rd and 4th post-operative weeks. But no significant differences were found regarding the progression of fracture callus in weekly comparison (p=1.0, p=0.52, p=1.0). In the present study, we were unable to find any beneficial or harmful effects of strontium ranelate on fracture healing.

Functional role of Runx3 in the regulation of aggrecan expression during cartilage development.

PubMed

Wigner, Nathan A; Soung, Do Y; Einhorn, Thomas A; Drissi, Hicham; Gerstenfeld, Louis C

2013-11-01

Runx2 and Runx3 are known to be expressed in the growth plate during endochondral bone formation. Here we addressed the functional role of Runx3 as distinct from Runx2 by using two models of postnatal bone repair: fracture healing that proceeds by an endochondral process and marrow ablation that proceeds by only an intramembranous process. Both Runx2 and Runx3 mRNAs were differentially up regulated during fracture healing. In contrast, only Runx2 showed increased expression after marrow ablation. During fracture healing, Runx3 was expressed earlier than Runx2, was concurrent with the period of chondrogenesis, and coincident with maximal aggrecan expression a protein associated with proliferating and permanent cartilage. Immunohistological analysis showed Runx3 protein was also expressed by chondrocytes in vivo. In contrast, Runx2 was expressed later during chondrocyte hypertrophy, and primary bone formation. The functional activities of Runx3 during chondrocyte differentiation were assessed by examining its regulatory actions on aggrecan gene expression. Aggrecan mRNA levels and aggrecan promoter activity were enhanced in response to the over-expression of either Runx2 and Runx3 in ATDC5 chondrogenic cell line, while sh-RNA knocked down of each Runx protein showed that only Runx3 knock down specifically suppressed aggrecan mRNA expression and promoter activity. ChIP assay demonstrated that Runx3 interactions were selective to sites within the aggrecan promoter and were only observed during early periods of chondrogenesis before hypertrophy. Our studies suggest that Runx3 positively regulates aggrecan expression and suggest that its function is more limited to cartilage development than to bone. In aggregate these data further suggest that the various members of the Runx transcription factors are involved in the coordination of chondrocyte development, maturation, and hypertrophy during endochondral bone formation. Copyright © 2013 Wiley Periodicals, Inc.

[Comparative effectiveness of surgical and non-surgical treatment for pediatric mandibular condylar fractures].

PubMed

Hu, Min; Wang, Yanyi; Zhang, Lihai; Yao, Jun

2010-12-01

To compare the effectiveness of open reduction and conservative treatment for pediatric mandibular condylar fractures and to provide the evidence for the selection of clinical therapy. The clinical data were retrospectively analyzed from 25 patients with the mandibular condylar fractures between January 1988 and December 2006. Of them, 8 patients (11 fractures) were treated with surgical treatment (surgical group) and 17 patients (22 fractures) with non-surgical treatment (non-surgical group). In surgical group, there were 6 males (9 fractures) and 2 females (2 fractures) with an age range of 8-13 years; fracture was caused by tumbling in 7 cases and by traffic accident in 1 with an interval of 1-6 days between injury and hospitalization; and 5 cases were identified as unilateral condylar fractures (3 complicated by mental fractures) and 3 cases as bilateral condylar fractures complicated by mental fractures. In non-surgical group, there were 12 males (15 fractures) and 5 females (7 fractures) with an age range of 3-12 years; fracture was caused by falling from height in 4 cases, by tumbling in 10, and by traffic accident in 3 with an interval of 1-25 days between injury and hospitalization; and 12 cases were identified as unilateral condylar fractures (3 complicated by mental fractures) and 5 cases as bilateral condylar fractures (1 complicated by mental fracture). Incision healed by first intention in surgical group, and 25 cases were followed up 1-6 years with an average of 3.5 years. At 12 months after treatment, no temporomandibular joint pain, eating disorder, or limited mandibular movement occurred in 2 groups. No significant difference was observed in opening mouth extent, protrusive and lateral movements between 2 groups at 6 and 12 months (P > 0.05). During centric occlusion, mental point located at the midline with symmetric face figure. Two patients in surgical group and 3 in non-surgical group had slight snap when opening their mouths. Mandible deviation was observed in 3 patients of 2 groups, respectively when gaping. The X-ray films showed healing of fracture and condylar remodeling at 3-6 months. Mandibular ramus were symmetric in cephalometry. Good effectiveness can be obtained by surgical or non-surgical treatment in pediatric mandibular condylar fractures. Considering the pediatric mandibular condyle having powerful healing and reconstructing potency and avoiding secondary injury on the temporomandibular joint from surgery, non-surgical treatment should be first selected for the pediatric mandibular condylar fractures in patients under 7 years.

A Novel Low-Molecular-Weight Compound Enhances Ectopic Bone Formation and Fracture Repair

PubMed Central

Wong, Eugene; Sangadala, Sreedhara; Boden, Scott D.; Yoshioka, Katsuhito; Hutton, William C.; Oliver, Colleen; Titus, Louisa

2013-01-01

Background: Use of recombinant human bone morphogenetic protein-2 (rhBMP-2) is expensive and may cause local side effects. A small synthetic molecule, SVAK-12, has recently been shown in vitro to potentiate rhBMP-2-induced transdifferentiation of myoblasts into the osteoblastic phenotype. The aims of this study were to test the ability of SVAK-12 to enhance bone formation in a rodent ectopic model and to test whether a single percutaneous injection of SVAK-12 can accelerate callus formation in a rodent femoral fracture model. Methods: Collagen disks with rhBMP-2 alone or with rhBMP-2 and SVAK-12 were implanted in a standard athymic rat chest ectopic model, and radiographic analysis was performed at four weeks. In a second set of rats (Sprague-Dawley), SVAK-12 was percutaneously injected into the site of a closed femoral fracture. The fractures were analyzed radiographically and biomechanically (with torsional testing) five weeks after surgery. Results: In the ectopic model, there was dose-dependent enhancement of rhBMP-2 activity with use of SVAK-12 at doses of 100 to 500 μg. In the fracture model, the SVAK-12-treated group had significantly higher radiographic healing scores than the untreated group (p = 0.028). Biomechanical testing revealed that the fractured femora in the 200 to 250-μg SVAK-12 group were 43% stronger (p = 0.008) and 93% stiffer (p = 0.014) than those in the control group. In summary, at five weeks the femoral fracture group injected with SVAK-12 showed significantly improved radiographic and biomechanical evidence of healing compared with the controls. Conclusions: A single local dose of a low-molecular-weight compound, SVAK-12, enhanced bone-healing in the presence of low-dose exogenous rhBMP-2 (in the ectopic model) and endogenous rhBMPs (in the femoral fracture model). Clinical Relevance: This study demonstrates that rhBMP-2 responsiveness can be enhanced by a novel small molecule, SVAK-12. Local application of anabolic small molecules has the potential for potentiating and accelerating fracture-healing. Use of this small molecule to lower required doses of rhBMPs might both decrease their cost and improve their safety profile. PMID:23467869

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

Defining the Lower Limit of a "Critical Bone Defect" in Open Diaphyseal Tibial Fractures.

PubMed

Haines, Nikkole M; Lack, William D; Seymour, Rachel B; Bosse, Michael J

2016-05-01

To determine healing outcomes of open diaphyseal tibial shaft fractures treated with reamed intramedullary nailing (IMN) with a bone gap of 10-50 mm on ≥50% of the cortical circumference and to better define a "critical bone defect" based on healing outcome. Retrospective cohort study. Forty patients, age 18-65, with open diaphyseal tibial fractures with a bone gap of 10-50 mm on ≥50% of the circumference as measured on standard anteroposterior and lateral postoperative radiographs treated with IMN. IMN of an open diaphyseal tibial fracture with a bone gap. Level-1 trauma center. Healing outcomes, union or nonunion. Forty patients were analyzed. Twenty-one (52.5%) went on to nonunion and nineteen (47.5%) achieved union. Radiographic apparent bone gap (RABG) and infection were the only 2 covariates predicting nonunion outcome (P = 0.046 for infection). The RABG was determined by measuring the bone gap on each cortex and averaging over 4 cortices. Fractures achieving union had a RABG of 12 ± 1 mm versus 20 ± 2 mm in those going on to nonunion (P < 0.01). This remained significant when patients with infection were removed. Receiver operator characteristic analysis demonstrated that RABG was predictive of outcome (area under the curve of 0.79). A RABG of 25 mm was the statistically optimal threshold for prediction of healing outcome. Patients with open diaphyseal tibial fractures treated with IMN and a <25 mm RABG have a reasonable probability of achieving union without additional intervention, whereas those with larger gaps have a higher probability of nonunion. Research investigating interventions for RABGs should use a predictive threshold for defining a critical bone defect that is associated with greater than 50% risk of nonunion without supplementary treatment. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

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

Halovest treatment in traumatic cervical spine injury.

PubMed

Razak, M; Basir, T; Hyzan, Y; Johari, Z

1998-09-01

This is a cross-sectional study on the use of halovest appliance in the Orthopaedic and Traumatology Department, Kuala Lumpur Hospital from June 1993 to September 1996. Fifty-three patients with cervical spine injuries were treated by halovest stabilization. Majority of cases was caused by motor-vehicle accident; others were fall from height at construction sites, fall at home, hit by falling object and assault. The injuries were Jefferson fracture of C1, odontoid fractures, hangman fractures, open spinous process fracture and fracture body of C2, and fracture, and fracture-dislocation of the lower cervical spines. Majority of patients had hospital stay less than 30 days. The use of the halovest ranges from 4 to 16 weeks and the healing rate was 96%. Two patients of lower cervical spine injury had redislocation and one of them was operated. There was one case of non-union of type II odontoid fracture and treated by posterior fusion. Other complications encountered during halovest treatment were minor. They were pin-site infection, pin-loosening, clamp loosening and neck pain or neck stiffness. This method of treatment enables patient to ambulate early and reduces hospital stay. We found that halovest is easy to apply, safe and tolerable to most of the patients.

Simvastatin Prodrug Micelles Target Fracture and Improve Healing

PubMed Central

Dusad, Anand; Yuan, Hongjiang; Ren, Ke; Li, Fei; Fehringer, Edward V.; Purdue, P. Edward; Goldring, Steven R.; Daluiski, Aaron; Wang, Dong

2014-01-01

Simvastatin (SIM), a widely used anti-lipidaemic drug, has been identified as a bone anabolic agent. Its poor water solubility and the lack of distribution to the skeleton, however, have limited its application in the treatment of bone metabolic diseases. In this study, an amphiphilic macromolecular prodrug of SIM was designed and synthesized to overcome these limitations. The polyethylene glycol (PEG)-based prodrug can spontaneously self-assemble to form micelles. The use of SIM trimer as the prodrug’s hydrophobic segment allows easy encapsulation of additional free SIM. The in vitro studies showed that SIM/SIM-mPEG micelles were internalized by MC3T3 cells via lysosomal trafficking and consistently induced expression of both BMP2 and DKK1 mRNA, suggesting that the prodrug micelle retains the biological functions of SIM. After systemic administration, optical imaging suggests that the micelles would passively target to bone fracture sites associated with hematoma and inflammation. Furthermore, flow cytometry study revealed that SIM/SIM-mPEG micelles had preferred cellular uptake by inflammatory and resident cells within the fracture callus tissue. The treatment study using a mouse osteotomy model validated the micelles’ therapeutic efficacy in promoting bone fracture healing as demonstrated by micro-CT and histological analyses. Collectively, these data suggest that the macromolecular prodrug-based micelle formulation of SIM may have great potential for clinical management of impaired fracture healing. PMID:25542644

Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by Staphylococcus aureus and supports fracture healing

PubMed Central

Johnson, Christopher T.; Wroe, James A.; Agarwal, Rachit; Martin, Karen E.; Guldberg, Robert E.; Donlan, Rodney M.; Westblade, Lars F.; García, Andrés J.

2018-01-01

Orthopedic implant infections are a significant clinical problem, with current therapies limited to surgical debridement and systemic antibiotic regimens. Lysostaphin is a bacteriolytic enzyme with high antistaphylococcal activity. We engineered a lysostaphin-delivering injectable PEG hydrogel to treat Staphylococcus aureus infections in bone fractures. The injectable hydrogel formulation adheres to exposed tissue and fracture surfaces, ensuring efficient, local delivery of lysostaphin. Lysostaphin encapsulation within this synthetic hydrogel maintained enzyme stability and activity. Lysostaphin-delivering hydrogels exhibited enhanced antibiofilm activity compared with soluble lysostaphin. Lysostaphin-delivering hydrogels eradicated S. aureus infection and outperformed prophylactic antibiotic and soluble lysostaphin therapy in a murine model of femur fracture. Analysis of the local inflammatory response to infections treated with lysostaphin-delivering hydrogels revealed indistinguishable differences in cytokine secretion profiles compared with uninfected fractures, demonstrating clearance of bacteria and associated inflammation. Importantly, infected fractures treated with lysostaphin-delivering hydrogels fully healed by 5 wk with bone formation and mechanical properties equivalent to those of uninfected fractures, whereas fractures treated without the hydrogel carrier were equivalent to untreated infections. Finally, lysostaphin-delivering hydrogels eliminate methicillin-resistant S. aureus infections, supporting this therapy as an alternative to antibiotics. These results indicate that lysostaphin-delivering hydrogels effectively eliminate orthopedic S. aureus infections while simultaneously supporting fracture repair. PMID:29760099

Self-healing woven glass fabric/epoxy composites with the healant consisting of micro-encapsulated epoxy and latent curing agent

NASA Astrophysics Data System (ADS)

Yin, Tao; Zhou, Lin; Zhi Rong, Min; Qiu Zhang, Ming

2008-02-01

This paper reports a study of self-healing woven glass fabric reinforced epoxy composites. The healing agent was a two-component one synthesized in the authors' laboratory, which consisted of epoxy-loaded urea-formaldehyde microcapsules as the polymerizable binder and CuBr2(2-methylimidazole)4 (CuBr2(2-MeIm)4) as the latent hardener. Both the microcapsules and the matching catalyst were pre-embedded and pre-dissolved in the composites' matrix, respectively. When the microcapsules are split by propagating cracks, the uncured epoxy can be released into the damaged areas and then consolidated under the catalysis of CuBr2(2-MeIm)4 that was homogeneously distributed in the composites' matrix on a molecular scale. As a result, the cracked faces can be bonded together. The influence of the content of the self-healing agent on the composites' tensile properties, interlaminar fracture toughness and healing efficiency was evaluated. It was found that a healing efficiency over 70% relative to the fracture toughness of virgin composites was obtained in the case of 30 wt% epoxy-loaded microcapsules and 2 wt% latent hardener.

Fixation of osteochondral fractures in rabbit knees. A comparison of Kirschner wires, fibrin sealant, and polydioxanone pins.

PubMed

Plaga, B R; Royster, R M; Donigian, A M; Wright, G B; Caskey, P M

1992-03-01

We compared fibrin sealant, polydioxanone (PDS) pins and Kirschner wires in the fixation of osteochondral fractures in rabbit knees. Standardised osteochondral fractures of the right medial femoral condyle were made in 56 adult New Zealand white rabbits. There were equal groups of control knees, and those which had Kirschner-wire, fibrin-sealant or PDS-pin fixation. No external immobilisation was used. One animal from each group was killed at two, three and four weeks. The remaining rabbits were killed at six weeks. A fracture which healed with less than 1 mm of displacement was considered a success. There was successful healing in 29% of the control group, in all of the Kirschner-wire group, in 50% of the fibrin-sealant group, and in 86% of the PDS-pin group. The use of PDS pins appears to be a reliable alternative to the use of metal in the fixation of osteochondral fractures in rabbits.

Intra-articular fractures of the distal tibia

PubMed Central

Sitnik, Alexandre; Beletsky, Aleksander; Schelkun, Steven

2017-01-01

Results of the treatment of intra-articular fractures of the distal tibia have improved significantly during the last two decades. Recognition of the role of soft tissues has led to the development of a staged treatment strategy. At the first stage, joint-bridging external fixation and fibular fixation are performed. This leads to partial reduction of the distal tibial fracture and allows time for the healing of soft tissues and detailed surgical planning. Definitive open reduction and internal fixation of the tibial fracture is performed at a second stage, when the condition of the soft tissues is safe. The preferred surgical approach(es) is chosen based on the fracture morphology as determined from standard radiographic views and computed tomography. Meticulous atraumatic soft-tissue handling and the use of modern fixation techniques for the metaphyseal component such as minimally invasive plate osteosynthesis further facilitate healing. Cite this article: EFORT Open Rev 2017;2:352-361. DOI: 10.1302/2058-5241.2.150047 PMID:28932487

Development of a Novel Synthetic Drug for Osteoporosis and Fracture Healing

DTIC Science & Technology

2015-11-01

Four-point bending setup for mechanical testing. (C & D) X-ray images of the fractured tibiae. Of note, a stainless steel rod was inserted in the...respectively. Figure 15. Mechanical strength 4 weeks after fracture induction for experiment 1. (A) Force- displacement relationship for the hydrogel...University Purdue University Indianapolis, Indianapolis, IN 46202, USA Keywords: bone fracture , tibia, salubrinal, hydrogel, mechanical test Running

ELBOW AND WRIST INJURIES IN SPORTS

PubMed Central

Marmor, Leonard; Bechtol, Charles O.

1960-01-01

Any disabling injury of the elbow or wrist should be studied roentgenographically for evidence of fracture which may not be otherwise evident but which may cause permanent disability unless the joint is immobilized for healing. “Tennis elbow” may be treated with physical therapy and analgesic injection but may require splinting or tendon stripping. Elbow sprain can occur in the growing epiphysis but is rare in adults. A jarring fall on the hand may cause fracture or dislocation at the elbow. Full extension of the joint should be restored gradually by active exercise rather than passive or forcible stretching. Fracture at the head of the radius may cause joint hemorrhage with severe pain which can be relieved by aspiration. A displacing fracture at the head of the radius requires removal of the head to prevent arthritic changes. Myositis ossificans contraindicates operation until after it has cleared. Healing of wrist fractures may be facilitated by exercise of the shoulder and elbow while the wrist is still in a cast. Fractures of the navicular bone are difficult to detect even roentgenographically and splinting may have to be done on clinical evidence alone. PMID:14421374

Muscle: a source of progenitor cells for bone fracture healing.

PubMed

Henrotin, Yves

2011-12-22

Bone repair failure is a major complication of open fracture, leading to non-union of broken bone extremities and movement at the fracture site. This results in a serious disability for patients. The role played by the periosteum and bone marrow progenitors in bone repair is now well documented. In contrast, limited information is available on the role played by myogenic progenitor cells in bone repair. In a recent article published in BMC Musculoskeletal Disorders, Liu et al. compared the presence of myogenic progenitor (MyoD lineage cells) in closed and open fractures. They showed that myogenic progenitors are present in open, but not closed fractures, suggesting that muscle satellite cells may colonize the fracture site in the absence of intact periosteum. Interestingly, these progenitors sequentially expressed a chondrogenic and, thereafter, an osteoblastic phenotype, suggestive of a functional role in the repair process. This finding opens up new perspectives for the research of orthopedic surgical methods, which could maximize myogenic progenitor access and mobilization to augment bone repair. Please see related article: http://www.biomedcentral.com/1471-2474/12/288.

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

Olecranon stress fracture in a weight lifter: a case report

PubMed Central

Rao, P; Rao, S; Navadgi, B

2001-01-01

Stress fractures have been reported in the upper limb of sportspeople involved in upper limb dominated events. Olecranon stress fractures have been cited in baseball pitchers, javelin throwers, and gymnasts. The unusual case of a stress fracture of the olecranon in a young weight lifter is reported here. The minimally displaced stress fracture was treated with tension band and two Kirschner wires. The fracture healed in four months and the patient returned to light sports activity after six months. Key Words: weight lifter; olecranon; elbow; stress fracture PMID:11157469

Cracks dynamics under tensional stress - a DEM approach

NASA Astrophysics Data System (ADS)

Debski, Wojciech; Klejment, Piotr; Kosmala, Alicja; Foltyn, Natalia; Szpindler, Maciej

2017-04-01

Breaking and fragmentation of solid materials is an extremely complex process involving scales ranging from an atomic scale (breaking inter-atomic bounds) up to thousands of kilometers in case of catastrophic earthquakes (in energy scale it ranges from single eV up to 1024 J). Such a large scale span of breaking processes opens lot of questions like, for example, scaling of breaking processes, existence of factors controlling final size of broken area, existence of precursors, dynamics of fragmentation, to name a few. The classical approach to study breaking process at seismological scales, i.e., physical processes in earthquake foci, is essentially based on two factors: seismic data (mostly) and the continuum mechanics (including the linear fracture mechanics). Such approach has been gratefully successful in developing kinematic (first) and dynamic (recently) models of seismic rupture and explaining many of earthquake features observed all around the globe. However, such approach will sooner or latter face a limitation due to a limited information content of seismic data and inherit limitations of the fracture mechanics principles. A way of avoiding this expected limitation is turning an attention towards a well established in physics method of computational simulations - a powerful branch of contemporary physics. In this presentation we discuss preliminary results of analysis of fracturing dynamics under external tensional forces using the Discrete Element Method approach. We demonstrate that even under a very simplified tensional conditions, the fragmentation dynamics is a very complex process, including multi-fracturing, spontaneous fracture generation and healing, etc. We also emphasis a role of material heterogeneity on the fragmentation process.

Black bone disease in a healing fracture.

PubMed

Thiam, Desmond; Teo, Tse Yean; Malhotra, Rishi; Tan, Kong Bing; Chee, Yu Han

2016-01-28

Black bone disease refers to the hyperpigmentation of bone secondary to prolonged usage of minocycline. We present a report of a 34-year-old man who underwent femoral shaft fracture fixation complicated by deep infection requiring debridement. The implants were removed 10 months later after long-term treatment with minocycline and fracture union. A refracture of the femoral shaft occurred 2 days after implant removal and repeat fixation was required. Intraoperatively, abundant heavily pigmented and dark brown bone callus was noted over the old fracture site. There was no evidence of other bony pathology and the appearance was consistent with minocycline-associated pigmentation. As far as we are aware, this is the first case of black bone disease affecting callus within the interval period of bone healing. We also discuss the relevant literature on black bone disease to bring light on this rare entity that is an unwelcomed surprise to operating orthopaedic surgeons. 2016 BMJ Publishing Group Ltd.

Distal Radius Volar Rim Fracture Fixation Using DePuy-Synthes Volar Rim Plate

PubMed Central

Kachooei, Amir Reza; Tarabochia, Matthew; Jupiter, Jesse B.

2016-01-01

Background To assess the results of distal radius fractures with the involvement of the volar rim fixed with the DePuy-Synthes Volar Rim Plate. Case Description We searched for the patients with volar rim fracture and/or volar rim fractures as part of a complex fracture fixed with a volar rim plate. Ten patients met the inclusion criteria: three patients with type 23B3, six patients with type 23C, and one patient with very distal type 23A. The mean follow-up was 14 months (range: 2–26). Fractures healed in all patients. Of the three patients with isolated volar rim fractures (type 23B3), two patients had no detectable deficits in motion. These patients had an average Gartland and Werley score of 9 (range: 2–14). Of the other seven patients (six with type 23C and one with type 23A fracture), three patients healed with full range of motion and four had some deficits in range of motion. Two patients had excellent results, three had good results, and two had fair results using the Gartland and Werley categorical rating. One patient healed with a shortened radius and ulnar impingement requiring a second surgery for ulnar head resection arthroplasty. Literature Review Results after nonoperative treatment of volar rim fractures are not satisfactory and often require subsequent corrective osteotomy. Satisfactory outcomes are achieved when the fragments are well reduced and secured regardless of the device type. Clinical Relevance Volar rim plates give an adequate buttress of the volar radius distal to volar projection of the lunate facet and do not interfere with wrist mobility. Furthermore, the dorsal fragments can be fixed securely through the volar approach eliminating the need for a secondary posterior incision. However, patients should be informed of the potential problems and the need to remove the plate if symptoms develop. PMID:26855829

Outcomes, and factors affecting outcomes, following shoulder hemiarthroplasty for proximal humeral fracture repair.

PubMed

Liu, Jie; Li, Shao-Hua; Cai, Zheng-Dong; Lou, Lie-Ming; Wu, Xing; Zhu, Yu-Chang; Wu, Wei-Ping

2011-09-01

Hemiarthroplasty has been applied to treat proximal humeral fracture with variable outcomes. The purpose of this retrospective study was to assess factors affecting outcome in patients following hemiarthroplasty for proximal humeral fracture (PHF) repair. Patients with proximal humeral fractures treated over a 6-year period were included. Indications for hemiarthroplasty were severe three-part fractures associated with osteoporosis; four-part fractures with or without dislocation; splitting of the humeral head, or >45% collapse of the humeral head. Surgery outcome and postoperative complications were main outcome measures in this study. Thirty-three of 47 patients were included in the final analysis (mean age 64.3 years, range 43-82). Mean postoperative follow-up was 44.4 (range 36-57) months. Postoperative complications (shoulder dislocation, mild shoulder subluxation, heterotopic ossification) occurred in seven patients. Healing of the greater and lesser tubercles was abnormal or poor in 18 patients. These patients had significantly higher pain scores (4.0 ± 1.1 vs. 2.2 ± 1.1) and significantly lower capacities for active lifting (79.3 ± 9.6 vs. 121.7 ± 24.3), external rotation (20.7 ± 3.7 vs. 39.2 ± 10.3), and Neer scores (79.2 ± 5.7 vs. 90.6 ± 3.6) versus patients who exhibited complete healing (all P < 0.001). Patient age, type of surgical approach, and fracture type were not major influencers of outcome. In conclusion, the healing of the greater and lesser tubercles is the major determinant of outcome following hemiarthroplasty for PHF repair.

Comparing fracture healing disorders and long-term functional outcome of polytrauma patients and patients with an isolated displaced midshaft clavicle fracture.

PubMed

Ferree, Steven; Hietbrink, Falco; van der Meijden, Olivier A J; Verleisdonk, Egbert Jan M M; Leenen, Luke P H; Houwert, Roderick M

2017-01-01

Although clavicle fractures are a common injury in polytrauma patients, the functional outcome of displaced midshaft clavicle fractures (DMCFs) in this population is unknown. Our hypothesis was that there would be no differences in fracture healing disorders or functional outcome in polytrauma patients with a DMCF compared with patients with an isolated DMCF, regardless of the treatment modality. A retrospective cohort study of patients (treated at our level I trauma center) with a DMCF was performed and a follow-up questionnaire was administered. Polytrauma patients, defined as an Injury Severity Score ≥16, and those with an isolated clavicle fracture were compared. Fracture healing disorders (nonunion and delayed union) and delayed fixation rates were determined. Functional outcome was assessed by the Quick Disability of the Arm, Shoulder, and Hand questionnaire. A total of 152 patients were analyzed, 71 polytrauma patients and 81 patients with an isolated DMCF. Questionnaire response of 121 patients (80%) was available (mean, 53 months; standard deviation, 22 months). No differences were found between polytrauma patients and those with an isolated DMCF with regard to nonunion (7% vs. 5%, respectively), delayed union (4% vs. 4%), and delayed fixation rate (13% vs. 13%). Polytrauma patients had an overall worse functional outcome, regardless of initial nonoperative treatment or delayed operative fixation. Polytrauma patients had a similar nonunion and delayed fixation rate but had an overall worse functional outcome compared with patients with an isolated DMCF. For polytrauma patients, a wait and see approach can be advocated without the risk of decreased upper extremity function after delayed fixation. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

[EFFECTIVENESS COMPARISON OF PROXIMAL FEMORAL NAIL ANTI-ROTATION IN SUPINE "SCISSORS" POSITION AND IN LITHOTOMY POSITION TO TREAT FEMORAL INTERTROCHANTERIC FRACTURES OF OLD PATIENTS].

PubMed

Du, Shihao; Yin, Fei; Wei, Xuming; Song, Sheng; Gu, Sanjun; Sun, Zhenzhong; Rui, Yongjun

2016-02-01

To compare the effectiveness of proximal femoral nail anti-rotation (PFNA) between in the supine "scissors" position and in the lithotomy position for treating femoral intertrochanteric fractures of old patients. A retrospective study was performed on 58 patients with femoral intertrochanteric fractures treated with PFNA between January 2013 and January 2015. Fracture was treated with PFNA in the lithotomy position in 28 cases (group A) and in the supine "scissors" position in 30 cases (group B). There was no significant difference in gender, age, side, cause of injury, fracture type, and interval from injury to operation between 2 groups (P>0.05). The incision length, operation time, perspective times, intraoperative blood loss, complications, and fracture healing time were recorded; Harris hip score was used to access the effectiveness. The wound healed by first intention without infection, pressure sores, deep vein thrombosis of lower extremity, and other complications. There was no significant difference in incision length between 2 groups (t=1.313, P=0.212). Group B was significantly better than group A in operation time, perspective times, and intraoperative blood loss (P<0.05). All patients were followed up 10-31 months (mean, 15.3 months). Stretch injury at normal side and perineal discomfort occurred in 1 case and 5 cases of group A respectively, and no nonunion and other complications was observed in the other patients. There was no significant difference in fracture healing time and Harris hip score at last follow-up between 2 groups (P>0.05). PFNA in the supine "scissors" position has exact effectiveness and advantages of shorter operation time, less intraoperative blood loss, less perspective times, and fewer complications.

Effects of protein-rich supplementation and nandrolone in lean elderly women with femoral neck fractures.

PubMed

Tidermark, Jan; Ponzer, Sari; Carlsson, Pronoti; Söderqvist, Anita; Brismar, Kerstin; Tengstrand, Birgitta; Cederholm, Tommy

2004-08-01

To evaluate the effects of a protein-rich liquid supplementation, alone or in combination with the anabolic steroid nandrolone decanoate, on body composition, activities of daily living (ADL) status and the health-related quality of life (HRQoL) after a femoral neck fracture. Sixty women, aged 83 +/- 5 years (mean +/- SD), BMI < 24 kg/m2 (20.4 +/- 2 kg/m2 ) and capable of co-operating, with a femoral neck fracture treated with internal fixation, were randomised to open treatment during 6 months with a protein-rich liquid formula alone (PR, Fortimel, 200 ml/day, 20 g protein/day) or in combination with nandrolone decanoate (PR/N, Deca-Durabol 25 mg i.m./3 weeks) or to a control group (C). The patients were re-examined after 6 and 12 months regarding body weight (BW), lean body mass (LBM, DXA), ADL status according to Katz, HRQoL according to EQ 5-D and fracture healing. LBM decreased in the C (-1.2 +/- 2 kg) and PR groups (-1.2 +/- 1 kg) but remained the same in the PR/N group (0.3 +/- 1 kg) (P < 0.05 between groups). ADL remained at a high level in the two intervention groups but declined significantly in the C group (P < 0.005 between groups). The decline in HRQoL was least pronounced in the PR/N group at 6 months (P < 0.05 between groups). Patients with fracture healing complications lost more BW (P < 0.05) and LBM (P < 0.01) than patients with uneventful fracture healing. Protein-rich liquid supplementation in combination with nandrolone given for 6 months to lean elderly women after a femoral neck fracture may positively affect LBM, ADL and HRQoL. Copyright 2003 Elsevier Ltd.

Effects of Boric Acid on Fracture Healing: An Experimental Study.

PubMed

Gölge, Umut Hatay; Kaymaz, Burak; Arpaci, Rabia; Kömürcü, Erkam; Göksel, Ferdi; Güven, Mustafa; Güzel, Yunus; Cevizci, Sibel

2015-10-01

Boric acid (BA) has positive effects on bone tissue. In this study, the effects of BA on fracture healing were evaluated in an animal model. Standard closed femoral shaft fractures were created in 40 male Sprague-Dawley rats under general anesthesia. The rats were allocated into five groups (n = 8 each): group 1, control with no BA; groups 2 and 3, oral BA at doses of 4 and 8 mg/kg/day, respectively; group 4, local BA (8 mg/kg); and group 5, both oral and local BA (8 mg/kg/day orally and 8 mg/kg locally). After closed fracture creation, the fracture line was opened with a mini-incision, and BA was locally administered to the fracture area in groups 4 and 5. In groups 2, 3, and 5, BA was administered by gastric gavage daily until sacrifice. The rats were evaluated by clinical, radiological, and histological examinations. The control group (group 1) significantly differed from the local BA-exposed groups (groups 4 and 5) in the clinical evaluation. Front-rear and lateral radiographs revealed significant differences between the local BA-exposed groups and the control and other groups (p < 0.05). Clinical and radiological evaluations demonstrated adequate agreement between observers. The average histological scores significantly differed across groups (p = 0.007) and were significantly higher in groups 4 and 5 which were the local BA (8 mg/kg) and both oral and local BA (8 mg/kg/day orally and 8 mg/kg locally), respectively, compared to the controls. This study suggests that BA may be useful in fracture healing. Further research is required to demonstrate the most effective local dosage and possible use of BA-coated implants.

The effect of processing on autohesive strength development in thermoplastic resins and composites

NASA Technical Reports Server (NTRS)

Howes, Jeremy C.; Loos, Alfred C.; Hinkley, Jeffrey A.

1989-01-01

In the present investigation of processing effects on the autohesive bond strength of neat polysulfone resin and graphite-reinforced polysulfone-matrix composites measured resin bond strength development in precracked compact tension specimens 'healed' by heating over a contact period at a given temperature. The critical strain energy release rate of refractured composite specimens did not exhibit the strong time or temperature dependence of the neat resin tests; only 80-90 percent of the undamaged fracture energy is recoverable.

Biomechanics of far cortical locking.

PubMed

Bottlang, Michael; Feist, Florian

2011-02-01

The development of far cortical locking (FCL) was motivated by a conundrum: locked plating constructs provide inherently rigid stabilization, yet they should facilitate biologic fixation and secondary bone healing that relies on flexible fixation to stimulate callus formation. Recent studies have confirmed that the high stiffness of standard locked plating constructs can suppress interfragmentary motion to a level that is insufficient to reliably promote secondary fracture healing by callus formation. Furthermore, rigid locking screws cause an uneven stress distribution that may lead to stress fracture at the end screw and stress shielding under the plate. This review summarizes four key features of FCL constructs that have been shown to enhance fixation and healing of fractures: flexible fixation, load distribution, progressive stiffening, and parallel interfragmentary motion. Specifically, flexible fixation provided by FCL reduces the stiffness of a locked plating construct by 80% to 88% to actively promote callus proliferation similar to an external fixator. Load is evenly distributed between FCL screws to mitigate stress risers at the end screw. Progressive stiffening occurs by near cortex support of FCL screws and provides additional support under elevated loading. Finally, parallel interfragmentary motion by the S-shaped flexion of FCL screws promotes symmetric callus formation. In combination, these features of FCL constructs have been shown to induce more callus and to yield significantly stronger and more consistent healing compared with standard locked plating constructs. As such, FCL constructs function as true internal fixators by replicating the biomechanical behavior and biologic healing response of external fixators.

Biomechanics of Far Cortical Locking

PubMed Central

Bottlang, Michael; Feist, Florian

2011-01-01

The development of FCL was motivated by a conundrum: locked plating constructs provide inherently rigid stabilization, yet they should facilitate biological fixation and secondary bone healing that relies on flexible fixation to stimulate callus formation. Recent studies have confirmed that the high stiffness of standard locked plating constructs can suppress interfragmentary motion to a level that is insufficient to reliably promote secondary fracture healing by callus formation. Furthermore, rigid locking screws cause an uneven stress distribution that may lead to stress fracture at the end screw and stress shielding under the plate. This review summarizes four key features of FCL constructs that have shown to enhance fixation and fracture healing: Flexible fixation, load distribution, progressive stiffening, and parallel interfragmentary motion. Specifically, flexible fixation provided by FCL reduces the stiffness of a locked plating construct by 80–88% to actively promote callus proliferation similar to an external fixator. Load distribution is evenly shared between FCL screws to mitigate stress risers at the end screw. Progressive stiffening occurs by near cortex support of FCL screws and provides additional support under elevated loading. Finally, parallel interfragmentary motion by s-shaped flexion of FCL screws has shown to induce symmetric callus formation. In combination, these features of FCL constructs have shown to induce more callus and to yield significantly stronger and more consistent healing compared to standard locked plating constructs. As such, FCL constructs function as true internal fixators by replicating the biomechanical behavior and biological healing response of external fixators. PMID:21248556

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

Pulverized granite at the brittle-ductile transition: An example from the Kellyland fault zone, eastern Maine, U.S.A.

NASA Astrophysics Data System (ADS)

Sullivan, Walter A.; Peterman, Emily M.

2017-08-01

Granite from a 50-200-m-wide damage zone adjacent to the brittle-ductile Kellyland Fault Zone contains healed fracture networks that exhibit almost all of the characteristics of dynamically pulverized rocks. Fracture networks exhibit only weak preferred orientations, are mutually cross-cutting, separate jigsaw-like interlocking fragments, and are associated with recrystallized areas likely derived from pervasively comminuted material. Fracture networks in samples with primary igneous grain shapes further indicate pulverization. Minimum fracture densities in microcline are ∼100 mm/mm2. Larger fractures in microcline and quartz are sometimes marked by neoblasts, but most fractures are optically continuous with host grains and only visible in cathodoluminescence images. Fractures in plagioclase are crystallographically controlled and typically biotite filled. Petrologic observations and cross-cutting relationships between brittle structures and mylonitic rocks show that fracturing occurred at temperatures of 400 °C or more and pressures of 200 MPa. These constraints extend the known range of pulverization to much higher temperature and pressure conditions than previously thought possible. The mutually cross-cutting healed fractures also provide the first record of repeated damage in pulverized rocks. Furthermore, pulverization must have had a significant but transient effect on wall-rock porosity, and biotite-filled fracture networks in plagioclase form weak zones that could accommodate future strain localization.

[A clinical study on the relationship of the tail femur distance and the lag screw migration or cutting-out after the third generation of Gamma nail fixation of intertrochanteric fracture].

PubMed

Hou, Yu; Yao, Qi; Zhang, Gen'ai; Ding, Lixiang

2018-01-01

To confirm the association between tail femur distance (TFD) and lag screw migration or cutting-out in the treatment of intertrochanteric fracture with the third generation of Gamma nail (TGN). The clinical data of 124 cases of intertrochanteric fracture treated with TGN internal fixation and followed up more than 18 months between January 2012 and December 2015 were reviewed and analyzed. There were 52 males and 72 females, with an age of 46-93 years (mean, 78.5 years). According to AO/Association for the Study of Internal Fixation (AO/ASIF) classification, 43 cases were type 31-A1, 69 cases were type 31-A2, and 12 cases were type 31-A3. The time from injury to operation was 1-10 days (mean, 2.9 days). According to the fracture healing of the patients, the patients were divided into the healing group and failure group. The age, gender, height, bone mineral density (BMD), fracture AO/ASIF classification, the time from injury to operation, and the TFD value at 1 day after operation were recorded and compared. The risk factors for the migration or cutting-out of lag screw were analyzed by logistic regression. There were 111 cases in healing group, the healing time was 80-110 days (mean, 95.5 days). There were 13 cases in failure group, including 2 cases of lag screw cutting-out and 11 cases of significant migration. Except for the TFD value at 1 day after operation in failure group was significantly higher than that in the healing group( t =5.14, P =0.00), there was no significant difference in gender, age, height, BMD, fracture of AO/ASIF classification, and the time from injury to operation ( P >0.05) between 2 groups. logistic regression analysis showed that TFD value was a risk factor for the migration or cutting-out of lag screw (B=1.22, standardized coefficient=0.32, Wald χ 2 =14.66, P =0.00, OR=3.37). The patients with higher TFD value had higher risk of postoperative lag screw migration or cutting-out. This result indicates that the appropriate length of the lag screw is helpful to reduce TFD value and prevent postoperative lag screw migration or cutting-out.

Quantitative MR imaging in fracture dating--Initial results.

PubMed

Baron, Katharina; Neumayer, Bernhard; Widek, Thomas; Schick, Fritz; Scheicher, Sylvia; Hassler, Eva; Scheurer, Eva

2016-04-01

For exact age determinations of bone fractures in a forensic context (e.g. in cases of child abuse) improved knowledge of the time course of the healing process and use of non-invasive modern imaging technology is of high importance. To date, fracture dating is based on radiographic methods by determining the callus status and thereby relying on an expert's experience. As a novel approach, this study aims to investigate the applicability of magnetic resonance imaging (MRI) for bone fracture dating by systematically investigating time-resolved changes in quantitative MR characteristics after a fracture event. Prior to investigating fracture healing in children, adults were examined for this study in order to test the methodology for this application. Altogether, 31 MR examinations in 17 subjects (♀: 11 ♂: 6; median age 34 ± 15 y, scanned 1-5 times over a period of up to 200 days after the fracture event) were performed on a clinical 3T MR scanner (TimTrio, Siemens AG, Germany). All subjects were treated conservatively for a fracture in either a long bone or in the collar bone. Both, qualitative and quantitative MR measurements were performed in all subjects. MR sequences for a quantitative measurement of relaxation times T1 and T2 in the fracture gap and musculature were applied. Maps of quantitative MR parameters T1, T2, and magnetisation transfer ratio (MTR) were calculated and evaluated by investigating changes over time in the fractured area by defined ROIs. Additionally, muscle areas were examined as reference regions to validate this approach. Quantitative evaluation of 23 MR data sets (12 test subjects, ♀: 7 ♂: 5) showed an initial peak in T1 values in the fractured area (T1=1895 ± 607 ms), which decreased over time to a value of 1094 ± 182 ms (200 days after the fracture event). T2 values also peaked for early-stage fractures (T2=115 ± 80 ms) and decreased to 73 ± 33 ms within 21 days after the fracture event. After that time point, no significant changes could be detected for T2. MTR remained constant at 35.5 ± 8.0% over time. The study shows that the quantitative assessment of T1 and T2 behaviour over time in the fractured region enable the generation of a novel model allowing for an objective age determination of a fracture. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Serum from the Human Fracture Hematoma Contains a Potent Inducer of Neutrophil Chemotaxis.

PubMed

Bastian, Okan W; Mrozek, Mikolaj H; Raaben, Marco; Leenen, Luke P H; Koenderman, Leo; Blokhuis, Taco J

2018-06-01

A controlled local inflammatory response is essential for adequate fracture healing. However, the current literature suggests that local and systemic hyper-inflammatory conditions after major trauma induce increased influx of neutrophils into the fracture hematoma (FH) and impair bone regeneration. Inhibiting neutrophil chemotaxis towards the FH without compromising the hosts' defense may therefore be a target of future therapies that prevent impairment of fracture healing after major trauma. We investigated whether chemotaxis of neutrophils towards the FH could be studied in vitro. Moreover, we determined whether chemotaxis of neutrophils towards the FH was mediated by the CXCR1, CXCR2, FPR, and C5aR receptors. Human FHs were isolated during an open reduction internal fixation (ORIF) procedure within 3 days after trauma and spun down to obtain the fracture hematoma serum. Neutrophil migration towards the FH was studied using Ibidi™ Chemotaxis 3D μ-Slides and image analysis of individual neutrophil tracks was performed. Our study showed that the human FH induces significant neutrophil chemotaxis, which was not affected by blocking CXCR1 and CXCR2. In contrast, neutrophil chemotaxis towards the FH was significantly inhibited by chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS), which blocks FPR and C5aR. Blocking only C5aR with CHIPSΔ1F also significantly inhibited neutrophil chemotaxis towards the FH. Our finding that neutrophil chemotaxis towards the human FH can be blocked in vitro using CHIPS may aid the development of therapies that prevent impairment of fracture healing after major trauma.

Early experience with a novel nonmetallic cable in reconstructive hip surgery.

PubMed

Ting, Nicholas T; Wera, Glenn D; Levine, Brett R; Della Valle, Craig J

2010-09-01

Metallic wires and cables are commonly used in primary and revision THA for fixation of periprosthetic fractures and osteotomies of the greater trochanter. These systems provide secure fixation and high healing rates but fraying, third-body generation, accelerated wear of the bearing surface, and injury to the surgical team remain concerning. We determined the rate of cable failure, union, and complications associated with a novel, nonmetallic cerclage cable in periprosthetic fracture and osteotomy fixation during THA. We retrospectively reviewed 29 patients who had primary and revision THAs using nonmetallic cables. Indications for use included fixation of an extended trochanteric osteotomy, intraoperative fracture of the proximal femur, strut allograft fixation, and a Vancouver B1 periprosthetic fracture of the femur. All patients were evaluated clinically and radiographically immediately postoperatively, at 3 weeks, 6 weeks, 3 months, and then annually thereafter. The minimum followup was 13 months (mean, 21 months; range, 13-30 months). Two of the 29 patients (7%) developed a nonunion; all remaining osteotomies, fractures and allografts had healed at the time of most recent evaluation. Four patients (14%) dislocated postoperatively; two were treated successfully with closed reduction, while the other two required reoperation. We identified no evidence of breakage or other complications directly attributable to the cables. The nonmetallic periprosthetic cables used in this series provided adequate fixation to allow for both osteotomy and fracture healing. We did not observe any complications directly related to the cables. Level of Evidence Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Self-healing polymer cement composites for geothermal wellbore applications

NASA Astrophysics Data System (ADS)

Rod, K. A.; Fernandez, C.; Childers, I.; Koech, P.; Um, W.; Roosendaal, T.; Nguyen, M.; Huerta, N. J.; Chun, J.; Glezakou, V. A.

2017-12-01

Cement is vital for controlling leaks from wellbores employed in oil, gas, and geothermal operations by sealing the annulus between the wellbore casing and geologic formation. Wellbore cement failure due to physical and chemical stresses is common and can result in significant environmental consequences and ultimately significant financial costs due to remediation efforts. To date numerous alternative cement blends have been proposed for the oil and gas industry. Most of these possess poor mechanical properties, or are not designed to work in high temperature environments. This research investigates novel polymer-cement composites which could function at most geothermal temperatures. Thermal stability and mechanical strength of the polymer is attributed to the formation of a number of chemical interactions between the polymer and cement matrix including covalent bonds, hydrogen bonding, and van der Waals interactions. It has been demonstrated that the bonding between cement and casing is more predictable when polymer is added to cement and can even improve healing of adhesion break when subjected to stresses such as thermal shock. Fractures have also been healed, effectively reducing permeability with fractures up to 0.3-0.5mm apertures, which is two orders of magnitude larger than typical wellbore fractures. Additionally, tomography analysis was used to determine internal structure of the cement polymer composite and imaging reveals that polymers fill fractures in the cement and between the cement and casing. By plugging fractures that occur in wellbore cement, reducing permeability of fractures, both environmental safety and economics of subsurface operations will be improved for geothermal energy and oil and gas production.

Microcracks, micropores, and their petrologic interpretation for 72415 and 15418

NASA Technical Reports Server (NTRS)

Richter, D.; Simmons, G.; Siegfried, R.

1976-01-01

Lunar samples 72415 and 15418 have complex microstructures that indicate a series of fracturing and healing events. Both samples contain relatively few open microcracks but many sealed and healed microcracks. Dunite 72415 contains abundant healed cracks that formed tectonically, symplectic intergrowths spatially and probably genetically related to microcracks, and a cataclastic matrix that has been extensively sintered. Metamorphosed breccia 15418 contains many post-metamorphic healed cracks, large shock induced cracks that have been sealed with glass, and a few younger, thin, open shock induced cracks.

Finite element analysis to determine the stress distribution, displacement and safety factor on a microplate for the fractured jaw case

NASA Astrophysics Data System (ADS)

Pratama, Juan; Mahardika, Muslim

2018-03-01

Microplate is a connecting plate that can be used for jaw bone fixation. In the last two decades, microplate has been used so many times to help reconstruction of fractured jaw bone which is called mandibular bone or mandible bone. The plate is used to provide stable fixation of the fractured bone tissue during healing and reconstruction process. In this study Finite Element Analysis was used to predict the stress concentration and distribution on a microplate, displacement on the microplate and also to determine the safety factor of the microplate based on maximum allowable stress value, and finally to ascertain whether microplate is safe to use or not. The microplate was produced from punching process using titanium grade 1 (pure titanium) as material with a thickness of 500 µm. The results of the research indicated that the microplate was safe to use according to the maximum stress around the hole, displacement around the hole and also the safety factor of the microplate.

Management of a midroot and complicated crown fracture: a case report.

PubMed

Sheikh-Nezami, M; Mokhber, N; Shamsian, Kh; Saket, S

2009-05-01

This case report illustrates the management of a permanent right central maxillary incisor with midroot fracture and complicated crown fracture, which was treated by cervical pulpotomy and fixation of the fragments. After 4-month follow-up, radiography showed healing with interproximal bone and connective tissue at the fracture line at midroot. After 3 years, the tooth was still functional without any clinical sign and symptom.

Intramedullary nailing for the treatment of aseptic femoral shaft non-unions after plating failure: effectiveness and timing.

PubMed

Megas, Panagiotis; Syggelos, Spyros A; Kontakis, Georgios; Giannakopoulos, Andreas; Skouteris, Georgios; Lambiris, Elias; Panagiotopoulos, Elias

2009-07-01

This retrospective, multicentre study aimed to evaluate reamed intramedullary nailing (IMN) for the treatment of 30 cases of aseptic femoral shaft non-union after plating failure. Following nailing, 29 non-unions had healed by a mean 7.93 months. In one case a hypertrophic non-union required renailing after 8 months, using a nail of greater diameter, and united within five further months. Healing times were not related to whether the fracture was open or closed, the type non-union or the type of fracture. The delay from the initial plating to intramedullary nailing had a statistically significant effect on healing time and final outcome. This treatment is cost effective and should be implemented as soon as the non-union is diagnosed.

Occurrence and pattern of long bone fractures in growing dogs with normal and osteopenic bones.

PubMed

Kumar, K; Mogha, I V; Aithal, H P; Kinjavdekar, P; Singh, G R; Pawde, A M; Kushwaha, R B

2007-11-01

A retrospective study was undertaken to record the occurrence and pattern of long bone fractures, and the efficacy of Intramedullary (IM) Steinmann pin fixing in growing dogs. All the records of growing dogs during a 10-year-period were screened to record the cause of trauma, the age and sex of the animal, the bone involved, the type and location of the fracture, the status of fixation, alignment, maintenance of fixation and fracture healing. The results were analysed and comparisons were made between growing dogs with normal and osteopenic bones. Among the 310 cases of fractures recorded, the bones were osteopenic in 91 cases (29%). Minor trauma was the principal cause of fracture in dogs with osteopenia (25%), and indigenous breeds were most commonly affected (38%). Fractures in dogs with osteopenic bones were most commonly recorded in the age group of 2-4 months (53%), whereas fractures in normal dogs were almost equally distributed between 2 and 8 months of age. Male dogs were affected significantly more often in both groups. In osteopenic bones, most fractures were recorded in the femur (56%), and they were distributed equally along the length of the bone. Whereas in normal bones, fractures were almost equally distributed in radius/ulna, femur and tibia, and were more often recorded at the middle and distal third of long bones. Oblique fractures were most common in both groups; however, comminuted fractures were more frequent in normal bones, whereas incomplete fractures were more common in osteopenic bones. Ninety-nine fracture cases treated with IM pinning (66 normal, 33 osteopenic) were evaluated for the status of fracture reduction and healing. In a majority of the cases (61%) with osteopenic bones, the diameter of the pin was relatively smaller than the diameter of the medullary cavity (<70-75%), whereas in 68% of the cases in normal bones the pin diameter was optimum. The status of fracture fixing was satisfactory to good in significantly more osteonormal (59%) than osteopenic dogs (42%). Fracture healing, however, was satisfactory in significantly more cases with osteopenic than normal bones. The appearance of callus was relatively early and the amount of bridging callus was relatively large in greater number of osteopenic bone fractures. Mal-union and non-union were recorded more often in osteopenic cases than in normal cases. However, the incidence of bone shortening and osteomyelitis was significantly higher in normal bones than in osteopenic bones.

Treatment of open tibial shaft fracture with soft tissue and bone defect caused by aircraft bomb--case report.

PubMed

Golubović, Zoran; Vidić, Goran; Trenkić, Srbobran; Vukasinović, Zoran; Lesić, Aleksandar; Stojiljković, Predrag; Stevanović, Goran; Golubović, Ivan; Visnjić, Aleksandar; Najman, Stevo

2010-01-01

Aircraft bombs can cause severe orthopaedic injuries. Tibia shaft fractures caused by aircraft bombs are mostly comminuted and followed by bone defects, which makes the healing process extremely difficult and prone to numerous complications. The goal of this paper is to present the method of treatment and the end results of treatment of a serious open tibial fracture with soft and bone tissue defects resulting from aircraft bomb shrapnel wounds. A 26-year-old patient presented with a tibial fracture as the result of a cluster bomb shrapnel wound. He was treated applying the method of external bone fixation done two days after wounding, as well as of early coverage of the lower leg soft tissue defects done on the tenth day after the external fixation of the fracture. The external fixator was removed after five months, whereas the treatment was continued by means of functional plaster cast for another two months. The final functional result was good. Radical wound debridement, external bone fixation of the fracture, and early reconstruction of any soft tissue and bone defects are the main elements of the treatment of serious fractures.

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.

[Intramedullary nailing of the distal tibia illustrated with the Expert(TM) tibia nail].

PubMed

El Attal, R; Hansen, M; Rosenberger, R; Smekal, V; Rommens, P M; Blauth, M

2011-12-01

Restoration of axis, length, and rotation of the lower leg. Sufficient primary stability of the osteosynthesis for functional aftercare and to maintain joint mobility. Good bony healing in closed and open fractures. Closed and open fractures of the tibia and complete lower leg fractures distal to the isthmus (AO 42), extraarticular fractures of the distal tibia (AO 43 A1/A2/A3), segmental fractures of the tibia with a fracture in the distal tibia, and certain intraarticular fractures of the distal tibia without impression of the joint line with the use of additional implants (AO 43 C1) Patient in reduced general condition (e.g., bed ridden), flexion of the knee of less than 90°, patients with knee arthroplasty of the affected leg, infection in the area of the nail's insertion, infection of the tibial cavity, complex articular fractures of the proximal or distal tibia with joint depression. Closed reduction of the fracture preferably on a fracture table or using a distractor or an external fixation frame. If necessary, use pointed reduction clamps or sterile drapery. In some cases, additional implants like percutaneous small fragment screws, poller screws or k-wires are helpful. Open reduction is rarely necessary and must be avoided. Opening of the proximal tibia in line with the medullary canal. Canulated insertion of the Expert(TM) tibia nail (ETN; Synthes GmbH, Oberdorf, Switzerland) with reaming of the medullary canal. Control of axis, length, and rotation. Distal interlocking with the radiolucent drill and proximal interlocking with the targeting device. Immediate mobilization of ankle and knee joint. Mobilization with 20 kg weight-bearing with crutches. X-ray control 6 weeks postoperatively and increased weight-bearing depending on the fracture status. In cases with simple fractures, good bony contact, or transverse fracture pattern, full weight-bearing at the end of week 6 is targeted. Between July 2004 and May 2005, 180 patients were included in a multicenter study. The follow-up rate was 81% after 1 year. Of these, 91 fractures (50.6%) were located in the distal third of the tibia. In this segment, the rate of delayed union was 10.6%. Malalignment of > 5° was observed in 5.4%. A secondary malalignment after initial good reduction was detected in only 1.1% of all cases. The implant-specific risk for screw breakage was 3.2%. One patient sustained a deep infection. If additional fibula plating was performed an 8-fold higher risk for delayed bone healing was observed (95%CI: 2.9-21.2, p< 0.001). If the fracture of the fibula was at the same height as on the tibia, the risk for delayed healing was even 14-fold (95% CI: 3.4-62.5, p< 0.001). Biomechanically plating of the fibula does not increase stability in suprasyndesmal distal tibia-fibular fractures treated with an intramedullary nail. Using the ETN with its optimized locking options, fibula plating is not recommended, thus, avoiding soft tissue problems and potentially delayed bone healing.

Olefin metathesis for effective polymer healing via dynamic exchange of strong carbon-carbon bonds

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

Guan, Zhibin; Lu, Yixuan

A method of preparing a malleable and/or self-healing polymeric or composite material is provided. The method includes providing a polymeric or composite material comprising at least one alkene-containing polymer, combining the polymer with at least one homogeneous or heterogeneous transition metal olefin metathesis catalyst to form a polymeric or composite material, and performing an olefin metathesis reaction on the polymer so as to form reversible carbon-carbon double bonds in the polymer. Also provided is a method of healing a fractured surface of a polymeric material. The method includes bringing a fractured surface of a first polymeric material into contact withmore » a second polymeric material, and performing an olefin metathesis reaction in the presence of a transition metal olefin metathesis catalyst such that the first polymeric material forms reversible carbon-carbon double bonds with the second polymeric material. Compositions comprising malleable and/or self-healing polymeric or composite material are also provided.« less

Circummandibular Wiring of Symphysis Fracture in a Five-Year-Old Child

PubMed Central

Priya Vellore, Krishna; Gadipelly, Srinivas; Dutta, Brahmananda; Reddy, Vijay Bhaskar; Ram, Sri; Parsa, Arun

2013-01-01

The treatment of pediatric maxillofacial fractures is unique due to the psychological, physiological, developmental, and anatomical characteristics of children. Method. This case report describes the management of symphysis fracture of mandible in a 5-year-old boy. The fracture was treated by acrylic splint with circummandibular wiring. Results. The splint was removed after 3 weeks. The patient had no complaints, and radiograph revealed a healed fracture. Conclusion. The clinical outcome in the present case indicates the management of mandibular fractures in pediatric patients using acrylic splint with circummandibular wiring. PMID:23864964

Diabetic calcaneal fractures.

PubMed

Sagray, Bryan A; Stapleton, John J; Zgonis, Thomas

2013-01-01

Calcaneal fractures among the diabetic population are severe and complex injuries that warrant careful evaluation in an effort to carry out adequate conservative or surgical management. The complication rates associated with diabetic fracture management are increased and may include poor wound healing, deep infection, malunion, and Charcot neuroarthropathy, each of which can pose a risk for limb loss. The significant surgery-associated morbidity accompanying diabetic calcaneal fractures has led to improved methods of calcaneal fracture management. This article reviews the overall management of diabetic calcaneal fractures, complications, and outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by Staphylococcus aureus and supports fracture healing.

PubMed

Johnson, Christopher T; Wroe, James A; Agarwal, Rachit; Martin, Karen E; Guldberg, Robert E; Donlan, Rodney M; Westblade, Lars F; García, Andrés J

2018-05-29

Orthopedic implant infections are a significant clinical problem, with current therapies limited to surgical debridement and systemic antibiotic regimens. Lysostaphin is a bacteriolytic enzyme with high antistaphylococcal activity. We engineered a lysostaphin-delivering injectable PEG hydrogel to treat Staphylococcus aureus infections in bone fractures. The injectable hydrogel formulation adheres to exposed tissue and fracture surfaces, ensuring efficient, local delivery of lysostaphin. Lysostaphin encapsulation within this synthetic hydrogel maintained enzyme stability and activity. Lysostaphin-delivering hydrogels exhibited enhanced antibiofilm activity compared with soluble lysostaphin. Lysostaphin-delivering hydrogels eradicated S. aureus infection and outperformed prophylactic antibiotic and soluble lysostaphin therapy in a murine model of femur fracture. Analysis of the local inflammatory response to infections treated with lysostaphin-delivering hydrogels revealed indistinguishable differences in cytokine secretion profiles compared with uninfected fractures, demonstrating clearance of bacteria and associated inflammation. Importantly, infected fractures treated with lysostaphin-delivering hydrogels fully healed by 5 wk with bone formation and mechanical properties equivalent to those of uninfected fractures, whereas fractures treated without the hydrogel carrier were equivalent to untreated infections. Finally, lysostaphin-delivering hydrogels eliminate methicillin-resistant S. aureus infections, supporting this therapy as an alternative to antibiotics. These results indicate that lysostaphin-delivering hydrogels effectively eliminate orthopedic S. aureus infections while simultaneously supporting fracture repair. Copyright © 2018 the Author(s). Published by PNAS.

Flow and fracturing of viscoelastic media under diffusion-driven bubble growth: An analogue experiment for eruptive volcanic conduits

NASA Astrophysics Data System (ADS)

Taddeucci, J.; Spieler, O.; Ichihara, M.; Dingwell, D. B.; Scarlato, P.

2006-03-01

To visualize the behavior of erupting magma in volcanic conduits, we performed shock tube experiments on the ductile-brittle response of a viscoelastic medium to diffusion-driven bubble expansion. A sample of shear-thinning magma analogue is saturated by gas Ar under high pressure. On rapid decompression, Ar supersaturation causes bubbles to nucleate, grow, and coalesce in the sample, forcing it to expand, flow, and fracture. Experimental variables include saturation pressure and duration, and shape and lubrication of the flow path. Bubble growth in the experiments controls both flow and fracturing, and is consistent with physical models of magma vesiculation. Two types of fractures are observed: i) sharp fractures along the uppermost rim of the sample, and ii) fractures pervasively diffused throughout the sample. Rim fractures open when shear stress accumulates and strain rate is highest at the margin of the flow (a process already inferred from observations and models to occur in magma). Pervasive fractures originate when wall-friction retards expansion of the sample, causing pressure to build-up in the bubbles. When bubble pressure overcomes wall-friction and the tensile strength of the porous sample, fractures open with a range of morphologies. Both types of fracture open normally to flow direction, and both may heal as the flow proceeds. These experiments also illustrate how the development of pervasive fractures allows exsolving gas to escape from the sample before the generation of a permeable network via other processes, e.g., bubble coalescence. This is an observation that potentially impact the degassing of magma and the transition between explosive and effusive eruptions.

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.

Pulsed Electromagnetic Fields in the treatment of fresh scaphoid fractures. A multicenter, prospective, double blind, placebo controlled, randomized trial.

PubMed

Hannemann, Pascal; Göttgens, Kevin W A; van Wely, Bob J; Kolkman, Karel A; Werre, Andries J; Poeze, Martijn; Brink, Peter R G

2011-05-06

The scaphoid bone is the most commonly fractured of the carpal bones. In the Netherlands 90% of all carpal fractures is a fracture of the scaphoid bone. The scaphoid has an essential role in functionality of the wrist, acting as a pivot. Complications in healing can result in poor functional outcome. The scaphoid fracture is a troublesome fracture and failure of treatment can result in avascular necrosis (up to 40%), non-union (5-21%) and early osteo-arthritis (up to 32%) which may seriously impair wrist function. Impaired consolidation of scaphoid fractures results in longer immobilization and more days lost at work with significant psychosocial and financial consequences.Initially Pulsed Electromagnetic Fields was used in the treatment of tibial pseudoarthrosis and non-union. More recently there is evidence that physical forces can also be used in the treatment of fresh fractures, showing accelerated healing by 30% and 71% reduction in nonunion within 12 weeks after initiation of therapy. Until now no double blind randomized, placebo controlled trial has been conducted to investigate the effect of this treatment on the healing of fresh fractures of the scaphoid. This is a multi center, prospective, double blind, placebo controlled, randomized trial. Study population consists of all patients with unilateral acute scaphoid fracture. Pregnant women, patients having a life supporting implanted electronic device, patients with additional fractures of wrist, carpal or metacarpal bones and pre-existing impairment in wrist function are excluded. The scaphoid fracture is diagnosed by a combination of physical and radiographic examination (CT-scanning).Proven scaphoid fractures are treated with cast immobilization and a small Pulsed Electromagnetic Fields bone growth stimulating device placed on the cast. Half of the devices will be disabled at random in the factory.Study parameters are clinical consolidation, radiological consolidation evaluated by CT-scanning, functional status of the wrist, including assessment by means of the patient rated wrist evaluation (PRWE) questionnaire and quality of life using SF-36 health survey questionnaire.Primary endpoint is number of scaphoid unions at six weeks, secondary endpoints are time interval to clinical and radiological consolidation, number of non-unions, functional status at 52 weeks and non-adherence to the treatment protocol. Netherlands Trial Register (NTR): NTR2064. © 2011 Hannemann et al; licensee BioMed Central Ltd.

Pulsed Electromagnetic Fields in the treatment of fresh scaphoid fractures. A multicenter, prospective, double blind, placebo controlled, randomized trial

PubMed Central

2011-01-01

Background The scaphoid bone is the most commonly fractured of the carpal bones. In the Netherlands 90% of all carpal fractures is a fracture of the scaphoid bone. The scaphoid has an essential role in functionality of the wrist, acting as a pivot. Complications in healing can result in poor functional outcome. The scaphoid fracture is a troublesome fracture and failure of treatment can result in avascular necrosis (up to 40%), non-union (5-21%) and early osteo-arthritis (up to 32%) which may seriously impair wrist function. Impaired consolidation of scaphoid fractures results in longer immobilization and more days lost at work with significant psychosocial and financial consequences. Initially Pulsed Electromagnetic Fields was used in the treatment of tibial pseudoarthrosis and non-union. More recently there is evidence that physical forces can also be used in the treatment of fresh fractures, showing accelerated healing by 30% and 71% reduction in nonunion within 12 weeks after initiation of therapy. Until now no double blind randomized, placebo controlled trial has been conducted to investigate the effect of this treatment on the healing of fresh fractures of the scaphoid. Methods/Design This is a multi center, prospective, double blind, placebo controlled, randomized trial. Study population consists of all patients with unilateral acute scaphoid fracture. Pregnant women, patients having a life supporting implanted electronic device, patients with additional fractures of wrist, carpal or metacarpal bones and pre-existing impairment in wrist function are excluded. The scaphoid fracture is diagnosed by a combination of physical and radiographic examination (CT-scanning). Proven scaphoid fractures are treated with cast immobilization and a small Pulsed Electromagnetic Fields bone growth stimulating device placed on the cast. Half of the devices will be disabled at random in the factory. Study parameters are clinical consolidation, radiological consolidation evaluated by CT-scanning, functional status of the wrist, including assessment by means of the patient rated wrist evaluation (PRWE) questionnaire and quality of life using SF-36 health survey questionnaire. Primary endpoint is number of scaphoid unions at six weeks, secondary endpoints are time interval to clinical and radiological consolidation, number of non-unions, functional status at 52 weeks and non-adherence to the treatment protocol. Trial registration Netherlands Trial Register (NTR): NTR2064 PMID:21548951

Biologically inspired autonomous structural materials with controlled toughening and healing

NASA Astrophysics Data System (ADS)

Garcia, Michael E.; Sodano, Henry A.

2010-04-01

The field of structural health monitoring (SHM) has made significant contributions in the field of prognosis and damage detection in the past decade. The advantageous use of this technology has not been integrated into operational structures to prevent damage from propagating or to heal injured regions under real time loading conditions. Rather, current systems relay this information to a central processor or human operator, who then determines a course of action such as altering the mission or scheduling repair maintenance. Biological systems exhibit advanced sensory and healing traits that can be applied to the design of material systems. For instance, bone is the major structural component in vertebrates; however, unlike modern structural materials, bone has many properties that make it effective for arresting the propagation of cracks and subsequent healing of the fractured area. The foremost goal for the development of future adaptive structures is to mimic biological systems, similar to bone, such that the material system can detect damage and deploy defensive traits to impede damage from propagating, thus preventing catastrophic failure while in operation. After sensing and stalling the propagation of damage, the structure must then be repaired autonomously using self healing mechanisms motivated by biological systems. Here a novel autonomous system is developed using shape memory polymers (SMPs), that employs an optical fiber network as both a damage detection sensor and a network to deliver stimulus to the damage site initiating adaptation and healing. In the presence of damage the fiber optic fractures allowing a high power laser diode to deposit a controlled level of thermal energy at the fractured sight locally reducing the modulus and blunting the crack tip, which significantly slows the crack growth rate. By applying a pre-induced strain field and utilizing the shape memory recovery effect, thermal energy can be deployed to close the crack and return the system to its original operating state. The entire system will effectively detect, self toughen, and subsequently heal damage as biological materials such as bone does.

[Clinical application of continuous douche and vacuum sealing drainage in refractory tissue, bone and joint infections after debridement].

PubMed

Yang, Ping-lin; He, Xi-jing; Li, Hao-peng; Wang, Guo-yu; Zang, Quan-jin

2010-01-01

To explore effect and the application value of continuous douche and vacuum sealing drainage (VSD) in refractory tissue, and joint infections after complete debridement. As retrospective analysis of treatment time and restoration or recurrence, from Jan. 2006 to Dec. 2007, 61 cases of refractory tissue, bone and joint infections underwent continuous douche and VSD combined with the treatment of anti-inflammatory and rehabilitation training after debridement in our hospital. The 61 patients included 39 males and 22 females with age ranging from 10 to 58 years with an average of (35 +/- 12) years, among whom 61 identified to have ankle ulcers combined with infections,open fracture combined with infections, sacrococcygeal pressure ulcers combined with infections, infections after hip replacement, infections after open fracture, and infections after skin avulsion postoperation were 11, 15, 9, 3, 5 and 18 cases respectively. The course was from 2 weeks to 11 months with an average of 4 months. In all 61 patients,the mean healing time was 17, 36, 42, 24, 32, 29 and 28 days in ankle ulcers and infections, tibia and fibula open fracture and infections, femoral shaft fracture and infections, sacrococcygeal pressure ulcers and infections, infections after hip replacement, infections after open fracture, and infections after skin avulsion postoperation respectively. The replacement of VSD was 1, 2-4, 3-5, 1-3, 2-4, 2-3 and 1-3 times in each group respectively. There was no wound recurrence except for 2 cases with recurrent in 61 cases with external fixation nail hole semi-pathological fracture in 1 case of femoral shaft fracture and infection and 1 case of tibia and fibula fracture and infection after follow-up at least one year. Application of continuous douche and VSD can effectively decrease incidence of complications and promote the refractory tissue, bone and joint infections wound growth, healing and considerably shorten the healing time.

Novel Therapeutic Strategy for the Prevention of Bone Fractures

DTIC Science & Technology

2015-02-01

falls and fractures . Yet, the molecular mechanisms underlying age-related muscle wasting, and the ability of muscle to promote bone formation and... mechanical relationship between muscle and bone. On the other hand, a large portion of osteoporotic fractures do not occur in individuals with low bone... fracture healing, are unknown. We have focused our research on the role of myostatin (GDF-8) in muscle-bone interactions in order to develop more

Rib plating of acute and sub-acute non-union rib fractures in an adult with cystic fibrosis: a case report.

PubMed

Dean, Nathan C; Van Boerum, Don H; Liou, Theodore G

2014-10-01

Rib fractures associated with osteoporosis have been reported to occur ten times more frequently in adults with cystic fibrosis. Fractures cause chest pain, and interfere with cough and sputum clearance leading to worsened lung function and acute exacerbations which are the two main contributors to early mortality in cystic fibrosis. Usual treatment involves analgesics and time for healing; however considerable pain and disability result due to constant re-injury from chronic repetitive cough. Recently, surgical plating of rib fractures has become commonplace in treating acute, traumatic chest injuries. We describe here successful surgical plating in a White cystic fibrosis patient with multiple, non-traumatic rib fractures. A-37-year old White male with cystic fibrosis was readmitted to Intermountain Medical Center for a pulmonary exacerbation. He had developed localized rib pain while coughing 2 months earlier, with worsening just prior to hospital admission in conjunction with a "pop" in the same location while bending over. A chest computerized tomography scan at admission demonstrated an acute 5th rib fracture and chronic non-united 6th and 7th right rib fractures. An epidural catheter was placed both for analgesia and to make secretion clearance possible in preparation for the surgery performed 2 days later. Under general anesthesia, he had open reduction and internal fixation of the right 5th, 6th and 7th rib fractures with a Synthes Matrix rib set. After several days of increased oxygen requirements, fever, fluid retention, and borderline vital signs, he stabilized. Numerical pain rating scores from his ribs were lower post-operatively and he was able to tolerate chest physical therapy and vigorous coughing. In our case report, rib plating with bone grafting improved rib pain and allowed healing of the fractures and recovery, although the immediate post-op period required close attention and care. We believe repair may be of benefit in selected cystic fibrosis patients, such as our patient who had suffered multiple rib fractures that were healing poorly.

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

Efficacy of Dragon's blood cream on wound healing: A randomized, double-blind, placebo-controlled clinical trial

PubMed Central

Namjoyan, Foroogh; Kiashi, Fatemeh; Moosavi, Zahra Beigom; Saffari, Fatemeh; Makhmalzadeh, Behzad Sharif

2015-01-01

The blood-red sap of Dragon's blood has been used in folk medicine for fractures, wounds, inflammation, gastrointestinal disorders, rheumatism, blood circulation dysfunctions, and cancer. Existing in vitro and in vivo bioactivity of this herb on different mechanisms of healing shows strong potential of this sap in wound healing. This clinical trial study was designated to evaluate the wound healing effect of Dragon's blood on human wounds. Sixty patients, between the ages of 14–65 years, who were referred to remove their skin tag, were assigned to this double-blind, placebo-controlled, randomized clinical trial and received either Dragon's blood or a placebo cream. They were visited on the 3rd, 5th, 7th, 10th, 14th, and 20th day of the trial to check the process of healing and to measure the wound's surface. At the end of trial, there was a significant difference in the mean duration of wound healing between the two groups (p = 0.0001). The phenolic compounds and the alkaloid taspine, which exist in Dragon's-blood resin, are probably the main reasons for the wound healing property of this plant. Being natural accessible, safe, and affordable makes Dragon's blood cream, a good choice for addition to the wound healing armamentarium. Further studies on wounds with different causes and among larger populations are suggested to ensure the effectiveness and safety of Dragon's blood. PMID:26870678

Efficacy of Dragon's blood cream on wound healing: A randomized, double-blind, placebo-controlled clinical trial.

PubMed

Namjoyan, Foroogh; Kiashi, Fatemeh; Moosavi, Zahra Beigom; Saffari, Fatemeh; Makhmalzadeh, Behzad Sharif

2016-01-01

The blood-red sap of Dragon's blood has been used in folk medicine for fractures, wounds, inflammation, gastrointestinal disorders, rheumatism, blood circulation dysfunctions, and cancer. Existing in vitro and in vivo bioactivity of this herb on different mechanisms of healing shows strong potential of this sap in wound healing. This clinical trial study was designated to evaluate the wound healing effect of Dragon's blood on human wounds. Sixty patients, between the ages of 14-65 years, who were referred to remove their skin tag, were assigned to this double-blind, placebo-controlled, randomized clinical trial and received either Dragon's blood or a placebo cream. They were visited on the 3rd, 5th, 7th, 10th, 14th, and 20th day of the trial to check the process of healing and to measure the wound's surface. At the end of trial, there was a significant difference in the mean duration of wound healing between the two groups (p = 0.0001). The phenolic compounds and the alkaloid taspine, which exist in Dragon's-blood resin, are probably the main reasons for the wound healing property of this plant. Being natural accessible, safe, and affordable makes Dragon's blood cream, a good choice for addition to the wound healing armamentarium. Further studies on wounds with different causes and among larger populations are suggested to ensure the effectiveness and safety of Dragon's blood.

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.

Greenstick fracture of the mandible: a case report.

PubMed

Kalia, V; Singh, A P

2008-03-01

This case report is an insight in to pediatric traumatology whereby bilateral greenstick fracture of condyle is used as a means to discuss the incidence and anatomic considerations for the management of the same, highlighting the fact that dental surgeons require a unique understanding of the anatomy, growth considerations, healing pattern and operative management involving minimal manipulation while managing pediatric facial fractures.

The use of resorbable hardware for fixation of pediatric mandible fracture. Case report.

PubMed

Poore, Matthew C; Penna, Kevin J

2008-01-01

The diagnosis and management of mandible fractures in the pediatric patient population can pose multiple challenges to the oral and maxillofacial surgeon. Resorbable plates and screws for fixation in this population are both well tolerated and effective. They enable realignment and stable positioning of rapidly healing fracture segments, while obviating any potential impediments to long-term metal retention.

CaMKK2 Inhibition in Enhancing Bone Fracture Healing

DTIC Science & Technology

2016-05-01

active-duty military personnel as well as aging combat veterans. Fractures associated with osteoporosis and acute trauma result in significant medical...fractures, contributing to further medical costs and patient morbidity. Established therapies that treat osteoporosis such as bisphosphonates only reduce...permeable inhibitor STO-609 protects from ovariectomy-induced osteoporosis . Moreover, treatment of 32 week old male mice with STO-609 reverses age