高强度、自修复纳米结构胶体凝胶的研发和组织工程应用

Colloidal gels are a novel class of hydrogels that allow for a facile “bottom-up” approach towards the design of biomaterials. Typically, colloidal gels are made of colloidal particles as building blocks for assembly into shape-specific and cohesive scaffolds of controllable micro-architecture and structural integrity. Due to the reversible interparticle attractions and the deformability of soft colloids, some colloidal gels have shown striking self-healing capability, which renders them with great potential to be used as tissue engineering scaffolds for regenerative medicine. However, current colloidal systems cannot achieve high mechanical strength in combination with self-healing capability, which limits their wide-spreading applications in biomedical fields. To address this issue, the current proposal hypothesize that by using hard core-soft shell structured, charged nanospheres as building blocks for electrostatic assembly of colloidal gels, a tough and self-healing particulate structure can be obtained. The mechanical strength of the hard core in combination with the deformability and surface charges of soft shell can result into close-packing and increasing volume fraction of the colloids, therefore leading to the formation of tough and self-healing gels. By using silica nanoparticles as the hard core, which can act as nucleation point for phase separation of gelatin nanospheres, core-shell particles can be synthesized for colloidal gels preparation. Moreover, the micro-architecture and mechanical properties of the colloidal gels will be characterized, and the interactions between them will be analyzed, which will provide proof for our hypothesis. Furthermore, by investigating the mechanisms of structure reinforcement and self-healing behavior of the colloidal gels, theoretical models can be established, which can be used for the design of similar biomaterials systems.

胶体凝胶是基于“自下而上”设计理念，以胶体颗粒为基本结构单元，通过颗粒间相互作用构建兼具可控微观组成和稳定宏观结构的新型水凝胶。借助可逆的颗粒间相互作用和柔性颗粒的高形变性，部分胶体凝胶表现出自修复能力，有望作为新型组织工程支架用于再生医学。然而，现有的胶体凝胶体系难以兼顾高机械强度和自修复能力，限制了该新型材料在生物医学领域的推广。为此，本项目创新性的提出以具有刚性核-柔性壳结构的带电纳米球为基本单元，通过静电自组装形成胶体凝胶。高强度的刚性核和高形变性、表面带电的柔性壳的有机结合，可促进胶体密堆积，增加体积分数，从而实现高强度、自修复凝胶的构建。拟以二氧化硅纳米颗粒为核，并作为制备明胶微球的成核点，控制壳层的生长，得到复合微球。拟考察凝胶的微观结构和宏观强度，阐明凝胶强度增加和自修复行为的机理，建立理论模型，为这类新型生物材料的设计开发奠定基础。

胶体凝胶是基于“自下而上”方式，以胶体颗粒为基本结构单元的新型水凝胶。通过引入可逆的颗粒间相互作用，胶体凝胶可以被赋予剪切变稀和自修复能力，这种特殊力学特性有望使其作为新型组织工程支架用于再生医学。然而，由于凝胶网络是基于非共价键交联，因此胶体凝胶体系普遍难以兼顾机械强度和自修复能力，这大大限制了该新材料的广泛应用。. 本项目针对自修复水凝胶材料大多难以兼顾高力学强度和自修复性能的难题，提出基于刚性无机纳米颗粒和柔性微凝胶纳米颗粒，构建具有高力学增强和优异自修复性能的复合胶体凝胶新材料，并将其作为可注射填充材料用于硬组织的修复和再生。基于带相反电荷的明胶和二氧化硅纳米颗粒，我们通过pH调控二元胶体的自组装过程，从而避免两相体系共混时常见的相分离发生，实现均匀分布的二元胶体网络体系。与已有的聚合物一元胶体凝胶相比，该复合材料组成和精准的网络控制和设计显著提高了胶体凝胶的力学性能。该复合胶体凝胶体系能承受较大的压缩和拉伸载荷，这在已有自修复水凝胶体系鲜有报道。更重要的是，该复合胶体凝胶展现了优异的自修复效应，能在反复剪切破坏过程中快速自修复。因此，该新凝胶材料具有在生物医学领域广阔的应用价值，包括再生医学和3D生物打印等。本项目有助于深入理解胶体凝胶体系的微观结构和力学性质关系，突破了胶体凝胶难以兼顾高强度和自修复双重特性的难题，发现凝是胶网络微观结构对自修复行为影响的新现象，为胶体凝胶的设计开发提供新的理论支持。相关工作在材料科学领域的重要期刊《Advanced Materials》和《Small》上发表，在水凝胶生物材料领域建立了国际影响力。