骨组织细胞与软骨细胞响应力电微环境的力学生物学研究

Bone and cartilage are main complex tissues of human body for load bearing and motion. Regeneration and repair of bone and cartilage play crucial roles in clinical treatment of bone trauma. Microenvironments (e.g. electrical and mechanical stimulation, mechanical properties and topology of extracellular matrix) have significant effect on remodeling of bone and cartilage. However, the influence of mechanical and electrical stimulation on cells of bone and cartilage tissues remains challenging, and interaction between the cell and extracellular matrix are needed to further studied. In this project, main researches are shown in three respects. First, cellular mechanobiology of cells of bone and cartilage tissue responding to electrical and mechanical stimulation are probed from different scales based on electrical active matrix material; Second, a detailed work is developed for the quantification of the molecular profile that reflect how two important mechanosensitive ion channel, including BK and TRPV4, regulate the response of chondrocytes to changes in matrix mechanical microenvironment; Third, microfluid model of porous matrix material is developed to probe the regulation of combined mechanical and electrical stimulation on bone growth. This project facilitates to further understanding of response mechanism of cells of bone and cartilage to mechanical and electrical microenvironment, and optimizing interaction between cell and matrix, providing a solid ground for further investigation of induced targeted cellular function and a theoretical support of regeneration and of bone and joint and the design of tissue engineering.

骨和软骨组织是人体重要的承载和运动器官。骨与软骨的再生和修复的研究对于临床上治疗骨损伤有着重要意义。骨与软骨的愈合和再生与所处微环境（如力、电、基质力学性质及拓扑结构等）紧密相关，但有关力电刺激影响骨组织细胞和软骨细胞生长的机理及刺激参数的优化、细胞与基质的相互作用等有待进一步研究。本项目基于二维电活性基底膜表面/三维电活性多孔基质材料，拟从不同维度开展骨组织细胞和软骨细胞对力电刺激响应的力学生物学研究；定量描述在力学微环境发生变化过程中，BK和TRPV4两类重要的力敏感离子通道协同调控软骨细胞感受基质微力学环境的分子机制；建立不同力电刺激下多孔基质材料内部微液流场模型，揭示力电耦合刺激对于骨组织生长的调控作用。项目将深入认识骨组织细胞和软骨细胞对力电微环境的响应机制，优化细胞-基质相互作用，为诱导相关细胞向预期功能发展提供参考，最终为骨与关节再生修复以及组织工程设计提供理论基础。

骨和软骨组织是人体重要的承载和运动器官。骨与软骨的再生和修复的研究对于临床上治疗骨损伤有着重要意义。骨与软骨的愈合和再生与所处微环境（如力、电、基质力学性质及拓扑结构等）紧密相关，但有关力电刺激影响骨组织细胞和软骨细胞生长的机理及刺激参数的优化、细胞与基质的相互作用等有待进一步研究。本项目构建了三维电活性多孔基质材料，设计研制了多通道电刺激器，为不同维度开展骨组织细胞和软骨细胞对力电刺激响应的力学生物学研究提供了技术支撑；定量描述了在力学微环境发生变化过程中，PIEZOs和TRPV4两类重要的力敏感离子通道协同调控软骨细胞感受基质微力学环境的分子机制；建立了不同力电刺激下多孔基质材料内部微液流场模型，揭示了力电耦合刺激对于骨组织生长的调控作用。项目将深入认识骨组织细胞和软骨细胞对力电微环境的响应机制，优化细胞-基质相互作用，为诱导相关细胞向预期功能发展提供参考，最终为骨与关节再生修复以及组织工程设计提供理论基础。