空间异质性仿生半月板支架促半月板缺损原位再生研究

无细胞支架技术是实现半月板损伤原位再生的潜在策略之一，如何构建无细胞支架又是其核心内容。假设无细胞支架技术存在两个关键节点：早期迁移内源性干细胞于损伤原位以及后期诱导干细胞增殖、分化与成熟。构建无细胞半月板支架需结合其空间异质性特点，并精准把控无细胞支架构建两个关键节点，合理选择生物活性刺激以及局部微环境刺激。基于课题组前期无细胞半月板支架研究及不足，提出构建空间异质性仿生半月板支架再生半月板损伤假说。通过对无细胞支架构建关键节点逐一击破，设计兼备空间异质性生物活性刺激以及适宜微环境诱导条件的无细胞半月板支架。首先制备两种空间异质性生物墨水，联合3D打印技术实现半月板内侧以及外侧空间生物活性刺激以及微环境的异质性仿生；最后通过动物体内半月板损伤再生模型评价其空间异质性再生效应，并进一步验证无细胞支架构建两个关键节点假设。项目实施将为空间异质性仿生半月板支架再生及其潜在临床应用提供理论基础。

The cell-free scaffold approach is one of the potential strategies for achieving the meniscus injury in situ regeneration, and how to fabricate the cell-free scaffold is the most significant parts of it. It is assumed that there are two key nodes in cell-free scaffold approach: the early migration of endogenous stem cells to the injury site and the later induction of stem cells proliferation, differentiation and maturation. The cell-free meniscus scaffold construction should combine with its spatial heterogeneity, accurately regulate the two key nodes of cell-free meniscus scaffolds construction, and rationally select the bioactive stimulus and local micro-environmental stimulus. Based on the previous studies and their shortage in terms of cell-free meniscus scaffolds in our research group, we proposed a hypothesis that constructing a spatially heterogeneous biomimetic meniscus scaffold to regenerate meniscus injury. This project will build one by one according to the two key nodes of the cell-free meniscus scaffold construction. We designed the cell-free meniscus scaffold with spatial heterogeneity in both bioactive stimulus and suitable micro-environmental induction conditions. Firstly, we produce two kinds of bio-inks with spatial heterogeneity, then achieve the heterogeneous biomimetic of both the bioactive stimulus and micro-environmental induction conditions in the inner and outer space of meniscus combined with 3D printing technology. Lastly, the meniscal defect regeneration model will be applied to assess the spatial heterogeneous regeneration effect, and further verify the hypothesis of the two key nodes in the cell-free scaffold construction. The implementation of this project will provide a theoretical foundation for the biomimetic meniscus scaffold with spatial heterogeneity and its potential clinical application.