具有多尺度孔结构纤维素基超分子水凝胶的制备及其细胞粘附性能研究

Hydrogels based on self-assembled molecules demonstrate precise control on micro- and nano- structures, excellent biocompatibility and similarities to native extracellular matrix (ECM). They are collectively an important class of biomaterial that have extensive uses in cell culture and three-dimensional tissue engineering. However, to archive outstanding performance on mechanical strength, permeability, cell adhesion and communications for self-assembled hydrogel still remains major challenge. In this research proposal, we demonstrate the design of a new class of hierarchical porous hydrogel scaffolds based on supramolecular polymer modified renewable nanofibrillar cellulose (NFC) by combining Pickering high internal phase emulsion (HIPE) method with 3D printing reverse templating technique. We will study the morphology and stimuli-responsive properties of the supramolecular polymer grafted NFC, and investigate the effect of the responsive quadruple hydrogen bonding from supramolecular polymers on the mechanical strength of hydrogel. The inherent relation between the hierarchical porous structures and cell adhesion, protein adsorption and nutrient diffusion in hydrogel will be also extensively explored. We believe this approach will represent a robust and versatile platform to fabricate a range of high performance hierarchical porous hydrogel scaffolds for tissue engineering.

自组装水凝胶具有精确的微纳结构、优异的生物相容性及类细胞外基质特性，是诱导细胞生长及三维组织培养的首选基材，在新材料及生物医学领域具有重要应用前景。但自组装水凝胶要同时满足良好的机械强度、通透性及细胞粘附等性能要求目前仍然极具挑战性。本项目拟通过刺激响应性超分子聚合物接枝纤维素纳米纤丝，结合Pickering高内相乳液方法及3D打印反相模板技术，制备具有多尺度孔结构的纳米纤维素基超分子水凝胶，以实现优异的细胞外基质功能模拟。掌握纳米纤维素表面接枝超分子聚合物方法，探索超分子聚合物对水凝胶力学强度调控的作用机制，揭示水凝胶的多尺度孔结构与细胞粘附、蛋白吸附以及营养有效输送的内在联系与规律，为高性能多孔水凝胶的研究和应用提供新途径和理论基础。

自组装水凝胶具有精确的微纳结构、优异的生物相容性及类细胞外基质特性，是诱导细胞 生长及三维组织培养的首选基材，在新材料及生物医学领域具有重要应用前景。但自组装水凝胶要同时满足良好的机械强度、通透性及细胞粘附等性能要求目前仍然极具挑战性。本研究课题旨在通过刺激响应性超分子聚合物接枝纤维素纳米纤丝，结合高内相乳液模板，制备具有多尺度孔结构的纳米纤维素基超分子水凝胶，并揭示水凝胶结构、理化性质与细胞粘附以及营养有效输送的内在联系与规律。在2017-2019年项目执行期间，项目组以UPy四重氢键官能团改性纳米纤维素、GelMA等为乳液稳定剂，获得了高内相乳液模板，并成功构建了多孔复合水凝胶支架材料，发现水凝胶的孔结构及力学强度可通过稳定剂浓度进行精确调控，凝胶内部相互连通的多孔结构有利水分子及营养物质快速交换，促进细胞的三维粘附生长。同时，项目组设计了包含UPy官能团以及温敏疏水链段的超分子共聚物，调控溶胶-凝胶转变特性，构建了具有优异自愈合以及可注射性的超分子水凝胶体系，包裹的干细胞存活率可达90%以上。研究成果拓展了超分子水凝胶功能化设计与制备策略，对推动功能水凝胶的生物医学应用具有重要科学意义。