仿生ECM聚谷氨酸/透明质酸水凝胶的可控梯度层状构筑及软骨修复研究

Tissue engineering provides a new and crucial strategy for cartilage repair. Hydrogels are considered ideal scaffolds for its biomimetic three-dimensional microenvironment of extracellular matrix (ECM). In this project, multiple network hydrogels will be prepared based on biocompatible γ-polyglutamic acid and hyaluronic acid using multiple methods, which are click chemistry and dynamic chemical crosslinking and ultra-violet lithography (UV lithography) technique. With excellent mechanical and self-healing properties, these biomimetic hydrogel scaffolds are expected to achieve good treatment for cartilage which has limited self-repair potential. Moreover, to mimic cartilage tissue, we demonstrate a synthetic strategy that exploits ultra-violet lithography (UV lithography) technique to achieve reversible immobilization of bioactive factors with good spatial and temporal control within the biomimetic triplicated network hydrogels scaffolds. In these tailored gradient photopatterning systems, functional structures of the layer of articular cartilage adapted to its biological mechanisms are optimised to promote cartilage tissue repair and reconstruction efficiently. This research developes intelligent dynamic self-healing hydrogels systems with gradient structures, providing biomimetic natural extracellular matrix microenvironment and function of articular cartilage in response to the cellular and molecular signals. This will reveal the interaction relationships between cells and materials in physiological conditions, and provide experimental and theoretical data for foundation research and clinical application of new articular cartilage materials.

利用软骨组织工程的策略实现关节软骨修复是目前发展的重要方向。水凝胶因仿似细胞外基质（ECM）的3D微环境，成为软骨修复和再生的较为理想的支架材料。本项目采用生物相容性优良的γ-聚谷氨酸和透明质酸为基材，从仿生角度出发，结合点击化学、动态化学键交联和紫外光刻技术构建多重网络高强度水凝胶支架材料，不仅可解决水凝胶机械强度弱的问题，并且具有自愈合功能，可望弥补关节软骨自修复能力有限的天然缺陷；项目同时采用三维图案化技术实现生物活性因子在水凝胶支架中的时间和空间的精准调控，对关节软骨材料层区进行功能化设计及其生物适配机制研究，最大效率的促进软骨组织的新生和重建。本研究的开展，从细胞和分子水平上设计了动态智能化自愈合水凝胶梯度层状体系，实现结构和功能上的最高仿生，可望获得生理条件下细胞-材料之间相互作用规律，并为新型关节软骨材料的研发和临床应用提供实验数据和理论指导。

利用软骨组织工程的策略实现关节软骨修复是目前发展的重要方向。水凝胶因仿似细胞外基质（ECM）的3D微环境，成为软骨修复和再生的较为理想的支架材料。本项目采用生物相容性优良的γ-聚谷氨酸和透明质酸为基材，从仿生角度出发，结合点击化学、动态化学键交联构建多重网络高强度水凝胶支架材料，不仅可解决水凝胶机械强度弱的问题，并且具有自愈合功能，能够弥补关节软骨自修复能力弱的缺陷；项目同时采用光掩模和3D打印技术实现梯度层状结构在水凝胶支架中的精准调控，对关节软骨材料层区进行功能化设计及其生物适配机制研究，最大效率的促进软骨组织的新生和重建。本研究从细胞和分子水平上设计了动态智能化自愈合水凝胶梯度层状体系，实现结构和功能上的最高仿生，获得了一系列细胞-材料之间相互作用规律，为新型关节软骨材料的研发和临床应用提供实验数据和理论指导。