骨关节系统软组织力学失稳损伤及修复的机制

In bone-joint system, soft tissue degeneration has been characterized by high incidence, high morbidity and increasing occurrence in younger populations. It is hypothesized that mechanical imbalance is the key initiating factor of soft tissue degeneration, which showed repeated inflammation and angiogenesis during progression. However, the exact mechanism of soft tissue degeneration and corresponding remediation technology has not yet been identified. Therefore, by using mechanical imbalance model, we aim to explore the effect and mechano-biological mechanism of mechanical imbalance on tissue inflammation and angiogenesis, which may lead to establish its mechanism on tissue degeneration. We also target to verify the hypothesis whether mechanical imbalance cause inflammation and create hypoxic environment, which may lead to induce angiogenesis, aggravate inflammation and finally cause tissue degeneration. Based on this hypothesis, biomimetic scaffold will be designed for implantation to discover the influence and mechanism when force is involved in tissue degeneration remediation. This research will not only provide new method to explore the mechanism of mechanical imbalance induced soft tissue degeneration, but would also contribute to theoretical basis for optimal design of remediation scaffold and choice of adjuvant therapy in bone-joint system.

骨关节系统软组织退行性病变（简称为退变）发生率高、极易致残，且呈年轻化趋势。尽管，已有研究提出力学失稳可能是骨关节软组织退变发生的关键始动因素，并发现其退变的过程伴随着反复炎症和血管新生。但有关其退变发生的机制至今仍不清楚，难以提出有效的修复方案。为此，本课题拟通过构建力学失稳模型，探讨力学失稳对骨关节系统软组织炎症反应和血管新生的影响及机制，进而阐明其在骨关节系统软组织退变中的作用及力生物学机制；并验证本项目提出的“力学失稳将导致骨关节系统软组织炎症介质大量产生、造成低氧环境；继而，在炎症介质和低氧协同下，力学失稳将诱导血管新生，加重炎症反应，最终导致其退变”假说。基于此，优化设计仿生支架，探索支架植入和力学介入对力学失稳性退变组织修复的影响及其机制。本研究不仅能为阐明骨关节系统软组织的力学失稳性退变机制提供新的研究思路，还将为新型软组织修复支架的优化设计和辅助治疗手段选择提供理论依据。

骨关节系统软组织退行性病变（简称为退变）发生率高、极易致残，且呈年轻化趋势。尽管，已有研究提出力学失稳可能是骨关节软组织退变发生的关键始动因素，并发现其退变的过程伴随着反复炎症和血管新生。但有关其退变发生的机制至今仍不清楚，难以提出有效的修复方案。因此，本项目将力学失稳与骨关节系统软组织退变联系起来，建立了力学失稳损伤的动物模型和细胞力学加载模型，明确了力学失稳和关节系统软组织损伤退变二者间的关系；结合力学失稳损伤动物模型和细胞力学加载模型，从胞外基质结构稳定调节器（LOX）入手，探讨了其在骨关节系统软组织力学失稳损伤及修复中的作用及机制，提出了对抗其损伤的技术与思路；从力学载荷与生物材料表面拓扑结构（/化学因子）协同的角度，探讨了其组织替代物促进肌腱修复的作用及机制；同时，探讨了力学介入在促进软骨损伤修复中的作用；此外，从力学与干细胞命运调控角度，探讨了力学载荷（适度运动）在骨骼肌干细胞干性维持及骨骼肌功能维持中的作用及机制，提出其预防的策略和思路。本项目全面揭示了力学失稳环境下骨关节系统软组织损伤及修复的机制，发展和丰富了组织力学失稳诱导骨关节系统损伤、修复及预防的理论与技术。