基于3D打印皮克林高内相乳液构建形状记忆多级孔复合生物支架

Tissue engineering has been considered as a very vital approach based on employing the tissue-engineered porous bioscaffold to repair the damaged tissues. And the porous bioscaffold is a key material for successfully implementing the tissue engineering technology. However, the construction and application of the porous bioscaffold still remain the following challenges. The porous scaffold generally possesses the relatively simple pore structure, which lowers the bionic function of the scaffold. Moreover, the scaffold shape is difficult to match with the irregular shape of the damaged tissue, which leads to the difficulty in performing the scaffold implant surgery. In this research proposal, for achieving excellent bionic function, matching defective tissue shape, and meeting the minimally invasive implant, a new series of hierarchical porous organic/inorganic composite bioscaffolds with shape memory property will be facilely and effectively fabricated by combining the 3D printing technique and Pickering high internal phase emulsion (HIPE) template method. The formation conditions and properties of Pickering HIPEs will be investigated. The key technologies for 3D printing of HIPEs will be studied. The effects of the preparation factors on the structures and properties of the bioscaffolds will be systematically explored. The shape memory controllability of the bioscaffolds will be evaluated. The inherent relation between the hierarchically porous structures and the cell adhesion, proliferation, migration, differentiation in bioscaffolds will be also extensively explored. This research provides new thought and theoretical guidance for the facile and effective construction of the hierarchical porous bioscaffolds with shape memory property for tissue engineering application.

组织工程是一种基于仿生理念利用组织化多孔生物支架来修复损伤或缺失组织的重要方法。多孔生物支架是组织工程技术得以实施的一个关键材料，然而其构建及应用面临如下挑战：支架孔洞结构较为单一，不利于发挥仿生功能；支架形状难与不规则的缺损组织匹配，植入手术难度大。为此，本项目结合3D打印技术与皮克林高内相乳液模板法，便捷、温和、有效地构建形状记忆多级孔有机/无机复合生物支架，以实现优异仿生功能，匹配缺损组织形状，并满足微创植入。考察影响皮克林高内相乳液形成及性能的主要因素，掌握3D打印乳液的关键技术，探索制备条件对支架结构、性能的影响，评价支架形状记忆可控性，揭示支架多尺度孔结构与细胞粘附、增殖、迁移及分化的内在联系与规律，为形状记忆多级孔复合生物支架的构建研究及其组织工程应用提供新思路和理论基础。

组织工程是一种基于仿生理念采用组织化多孔生物支架来修复组织结构与功能非常重要的方法，其中多孔生物支架是该方法得以实施的一个关键材料。但多孔生物支架构建及应用中面临着支架孔洞结构单一，形状难与缺损组织匹配，植入难度大的问题。本项目通过3D打印技术结合皮克林乳液模板法，制备了个性化的多级孔形状记忆有机/无机复合生物支架，研究了制备条件对支架结构与性能的影响，探讨了支架形状记忆调控性，并考察了支架结构与细胞生长的内在联系。项目组在项目执行期间，以聚乳酸改性的生物无机纳米粒子、疏水性增稠剂、热致形状记忆可降解聚酯为基材，获得了油包水型粘稠状皮克林乳液，研究发现乳液具有良好的稳定性、明显的剪切变稀行为及快速的粘度回复能力，赋予支架良好的可3D打印性。将制备的粘稠乳液作为墨水，通过3D打印，再经溶剂蒸发，成功个性化制备了兼具毫米级大孔与微米级微孔共存的多级孔生物支架，同时研究发现生物支架的孔结构与生物活性、形状记忆、药物释放等性能可通过纳米粒子含量进行精确调控；生物支架的热致形状记忆回复转变温度可控在37到50℃间，通过加入能量转换剂还可实现支架非接触刺激引发的形状记忆行为，赋予支架在微创植入中良好的应用前景；生物支架相互连通的多孔结构有利于营养物质的输送，促进了细胞的粘附、生长、增殖及分化。本项目研究结果为形状记忆多级孔复合生物支架的构建、表征研究及微创植入型组织工程应用等方面提供了实验和理论基础。