Biomechanical model to simulate tissue differentiation and bone regeneration: Application to fracture healing

2002 ◽  
Vol 40 (1) ◽  
pp. 14-21 ◽  
Author(s):  
D. Lacroix ◽  
P. J. Prendergast ◽  
G. Li ◽  
D. Marsh
Keyword(s):  
Fracture Healing ◽  
Bone Regeneration ◽  
Biomechanical Model ◽  
Tissue Differentiation

FRACTURE HEALING SIMULATION REGULATED BY FORCE AND OXYGEN

2019 ◽  
Vol 19 (07) ◽  
pp. 1940029
Author(s):  
MONAN WANG ◽  
XINYU WANG ◽  
QIYOU YANG
Keyword(s):  
Simulation Model ◽  
Fracture Healing ◽  
Control Method ◽  
Mechanical Stability ◽  
Healing Process ◽  
Tissue Differentiation ◽  
Simulation Program ◽  
Spatial And Temporal Variation ◽  
Oxygen Levels ◽  
Axial Stability

According to the mechanical conditions of fracture fixation and the oxygen levels in the tissues, a simulation model of fracture healing process was built to describe the relationship among mechanical stability, oxygen levels in tissues and tissue differentiation during the second fracture healing. Different from the previous simulation model, in this paper, we took the three-dimensional model as the research object, solved the mechanical stimulation by finite element method, established the partial differential equation to solve the spatial and temporal variation of the oxygen in tissues. The process of tissue differentiation was described by fuzzy control method. The initial stage of fracture healing, intramembranous ossification, chondrogenesis, cartilage calcification and endochondral ossification during the fracture healing process were simulated, and the properties of tissue materials were continuously updated to complete the iterative process. The simulation program of fracture healing process was independently developed in Eclipse environment, and the simulation results were compared with experimental data and those of other fracture healing simulation models to verify the simulation program in this paper. Finally, the processes of transverse fracture healing in rats with different axial stability under normoxic, hypoxic and hyperoxic conditions was simulated, and the effects of different tissue oxygen levels and interosseous stabilities on fracture healing were analyzed. It is concluded by simulation that the delayed healing or non-union of bone will occur when in state of tissue hypoxia or interosseous instability, normal healing will occur when in state of tissue normoxia, and the healing will be accelerated when in state of tissue hyperoxia.

Dynamic protein corona influences immune-modulating osteogenesis in magnetic nanoparticle (MNP)-infiltrated bone regeneration scaffoldsin vivo

Nanoscale ◽  
2019 ◽  
Vol 11 (14) ◽  
pp. 6817-6827 ◽  
Author(s):  
Yue Zhu ◽  
Peipei Jiang ◽  
Bin Luo ◽  
Fang Lan ◽  
Jing He ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Regeneration ◽  
Inflammatory Reaction ◽  
Magnetic Nanoparticle ◽  
Protein Corona ◽  
Underlying Mechanism

An inflammatory reaction initiates fracture healing and directly influences the osteoinductive effect of the magnetic hydroxyapatite (MHA) scaffold, but the underlying mechanism is yet to be elucidated.

scholarly journals A novel MRI compatible mouse fracture model to characterize and monitor bone regeneration and tissue composition

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Nina Schmitz ◽  
Melanie Timmen ◽  
Katharina Kostka ◽  
Verena Hoerr ◽  
Christian Schwarz ◽  
...  
Keyword(s):  
Fracture Healing ◽  
Bone Regeneration ◽  
Cell Attachment ◽  
Healing Process ◽  
Living Organism ◽  
Fracture Site ◽  
Tissue Composition ◽  
Metal Implants ◽  
Callus Tissues

Abstract Over the last years, murine in vivo magnetic resonance imaging (MRI) contributed to a new understanding of tissue composition, regeneration and diseases. Due to artefacts generated by the currently used metal implants, MRI is limited in fracture healing research so far. In this study, we investigated a novel MRI-compatible, ceramic intramedullary fracture implant during bone regeneration in mice. Three-point-bending revealed a higher stiffness of the ceramic material compared to the metal implants. Electron microscopy displayed a rough surface of the ceramic implant that was comparable to standard metal devices and allowed cell attachment and growth of osteoblastic cells. MicroCT-imaging illustrated the development of the callus around the fracture site indicating a regular progressing healing process when using the novel implant. In MRI, different callus tissues and the implant could clearly be distinguished from each other without any artefacts. Monitoring fracture healing using MRI-compatible implants will improve our knowledge of callus tissue regeneration by 3D insights longitudinal in the same living organism, which might also help to reduce the consumption of animals for future fracture healing studies, significantly. Finally, this study may be translated into clinical application to improve our knowledge about human bone regeneration.

scholarly journals Anabolic Therapies in Osteoporosis and Bone Regeneration

2018 ◽  
Vol 20 (1) ◽  
pp. 83 ◽  
Author(s):  
Gabriele Russow ◽  
Denise Jahn ◽  
Jessika Appelt ◽  
Sven Märdian ◽  
Serafeim Tsitsilonis ◽  
...  
Keyword(s):  
Bone Formation ◽  
Fracture Healing ◽  
Bone Regeneration ◽  
Treatment Options ◽  
Therapeutic Approaches ◽  
Delayed Fracture ◽  
Stimulate Bone Formation ◽  
Intrinsic Factors ◽  
Delayed Fracture Healing ◽  
Extrinsic And Intrinsic Factors

Osteoporosis represents the most common bone disease worldwide and results in a significantly increased fracture risk. Extrinsic and intrinsic factors implicated in the development of osteoporosis are also associated with delayed fracture healing and impaired bone regeneration. Based on a steadily increasing life expectancy in modern societies, the global implications of osteoporosis and impaired bone healing are substantial. Research in the last decades has revealed several molecular pathways that stimulate bone formation and could be targeted to treat both osteoporosis and impaired fracture healing. The identification and development of therapeutic approaches modulating bone formation, rather than bone resorption, fulfils an essential clinical need, as treatment options for reversing bone loss and promoting bone regeneration are limited. This review focuses on currently available and future approaches that may have the potential to achieve these aims.

scholarly journals Protein kinase G1 regulates bone regeneration and rescues diabetic fracture healing

JCI Insight ◽  
2020 ◽  
Vol 5 (9) ◽  
Author(s):  
Nadine Schall ◽  
Julian J. Garcia ◽  
Hema Kalyanaraman ◽  
Shyamsundar Pal China ◽  
Jenna J. Lee ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Fracture Healing ◽  
Bone Regeneration

scholarly journals HSPB7 Protected the Osteogenic Differentiation of Mesenchymal Stem Cells From TNF-α Through Chaperone-mediated Autophagy/beta-catenin Pathway

2021 ◽  
Author(s):  
Kai Hang ◽  
Li Ying ◽  
Jinwu Bai ◽  
Yibo Wang ◽  
Zhihui Kuang ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Fracture Healing ◽  
Bone Regeneration ◽  
Protein Family ◽  
Family Network ◽  
Tnf Α ◽  
Chaperone Mediated Autophagy ◽  
Small Member

Abstract Background Managing healing of impaired bone fracture has long been a subject of concern. Prolonged or uncontrolled inflammation exerts detrimental effects on bone healing. Tumor necrosis factor (TNF)-α is a critical inflammatory factor, whose absence impairs normal bone formation. However, TNF-α exposure for longer duration inhibits bone regeneration. In this study, we aim to find a new therapeutic target for the impaired osteogenesis induced by long exposure of TNF-α.MethodsIn vitro, mRNA microarray analysis was used to identify differentially expressed genes. Cell proliferation assay was used to assess the proliferation of cells. qPCR and Western blotting analysis were applied to detect the expression of target genes and proteins respectively. ALP staining and Alizarin Red staining (ARS) were used to evaluate ALP activity and mineral deposition respectively. Co-immunoprecipitation was used to detect the interaction of proteins. In vivo, a murie tibial fracture model was established, histological evaluation and radiographic analysis was used to confirm bone regeneration in fracture healing. statistical significance between two groups was determined by Student’s t test, one-way ANOVA or Bonferroni’s post-hoc test according to the distribution of the tested population.ResultsIn this study, we show that heat shock protein family B (small) member 7 (HSPB7) mitigates negative impact of long-term TNF-α exposure on bone formation by binding heat shock protein family H (small) member 1 (HSPH1). HSPH1, in turn, inhibits the ATPase of heat shock cognate A8 (HSCA8), one of the key components involved in chaperone-mediated autophagy (CMA). Deletion of genes encoding for either HSCA8 or lysosome-associated membrane protein 2A (LAMP2A), another component of CMA, failed to reverse the osteogenic differentiation of hBMSCs induced by TNF-α by deleting HSPH1. Moreover, LAMP2A overexpression reverse the impaired osteogenesis induced by TNF-α, and this effect was attenuated by DKK1, a specific Wnt/β-catenin signaling pathway inhibitors. Thus, a heat shock protein family network composed by HAPB7, HSPH1 and HSCA8 rescued the impairment of bone healing by TNF-α through the CMA/β-catenin pathway, making it a potential therapeutic agent for bone regeneration in cases of prolonged or severe inflammation in the clinical settings. ConclusionsTaken together, these findings indicate that a heat shock protein family network including HSPB7, HSPH1 and HSCA8 protects the impaired osteogenesis induced by TNF-α via the CMA/β-catenin pathway. And in vivo, HSPB7 overexpression lentiviral particles effectively protects the impaired fracture healing induced by TNF-α in a mouse tibia fracture healing model.

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