基于数学几何材料梯度建模数值模拟与细胞打印的关节软骨生长调控机理研究

Articular cartilage is a special tissue with no blood vessel, no lymphoid tissue, no eneurosis, and relies on the dispersion mechanism for nutrition. The chondrocytes that being surrounded in the extracellular matrix are terminally differentiated cell, with lower mitosis, results in the limitation of self-healing when injuried.Even a tiny injury can cause prominent pain, swell and sysfunction, and retrogression in the end.It has been a tough nut to the orthopedics department, orthopedic surgery and sport medicine to repair the articular cartilage injury. 3D bio-printing tissue engineering method based on additive manufacturing has brought new hope for the repair of cartilage injury. Systematic study on the scaffold geometrical gradient modelling, scaffold materials gradient configuration, seed cells, growth factors and scaffold dynamic cultivation is insufficient. This proosal plan to study on the optimization desigh of cartilage scaffold with bio-CATE, modelling of materials and cell growth, explore the optimal environment and mechanism through numerical modelling, cell controlled packaging technique(3D bro-printing) and orthogonal test on numerical controlled cultivation of scaffolds. Build a platform for cartilage scaffold design, forming, cultivation and analysis.

关节软骨是一种无血管、无淋巴组织、无神经支配依靠弥散机制营养的特殊组织，而被包绕在细胞外基质中的软骨细胞是一种终末分化细胞，有丝分裂低下，导致软骨损伤自身愈合能力有限，即使比较小的软骨损伤也可能产生比较显著的症状如疼痛、肿胀、功能障碍，最终发生关节的退行性变。如何有效地修复关节软骨一直是骨科、矫形外科及运动医学界一个非常棘手的问题。基于增材制造的生物3D打印组织工程方法为软骨损伤修复带来希望。但是，将支架几何梯度构型、支架材料梯度配置、种子细胞、生长因子和支架动态培养环境因素等系统研究尚很缺乏。本项目拟采用Bio-CATE（计算机辅助组织工程仿生）方法对软骨支架几何结构的优化设计、材料与细胞生长环境建模，通过数值模拟和细胞受控组装技术（生物三维打印）以及数控动态培养进行正交试验，探索促进软骨增殖修复的最优环境和内在机理。建立一个软骨支架设计、成形、培养和分析实验的平台。

本项目采用多种方法对软骨支架几何结构的优化设计、材料与细胞生长环境建模，通过数值模拟和细胞受控组装技术（生物三维打印）以及数控动态培养进行正交试验。.几何结构的优化设计，包括进行层状结构设计，梯度设计。配置优化生物墨水，并进行两批次动物实验。其中第一批次动物实验结果已经获得，第二批次已接近尾声。申请发明专利12项，已经获得授权4项。申请军口发明专利4项，已经授权3项。发表论文13篇。其中英文论文9篇。为软骨损伤修复带来新的希望。