具有神经生长因子缓释功能的复孔聚外消旋丙交酯医用膜的制备与促进周围神经再生的实验研究

The post-injury regeneration of nerve fibers is critical for the repair of peripheral nerves. Biodegradable biofilms can be used as the conduit for nerve regeneration and prevent the adhesion of peripheral nerve to the surrounding tissues, which have received intensive studies in recent years. However, it is far from a complete understanding of how to combine molecular stimulators such as the nerve growth factor (NGF) with the biofilm to promote the nerve regeneration. This proposal is aimed at developing a porous, biodegradable poly-DL-lactic acid medical (PDLLA) film that can control the release of the combined NGF molecules. The raw PDLLA material is jointly developed by the Chinese Academy of Sciences. Both the conventional solvent casting and 3D bioprinting methods will be explored. Our in vitro studies will characterize the PDLLA film in terms of the structure, the preservation of biological activity of NGF, the controlled release of NGF, permeability, viscoelastic properties, biodegradability, biocompatibility, et al. The toxicity and degradability of PDLLA film and its ability to promote nerve healing will be systematically examined in the in vivo studies. The findings being achieved in this proposal will provide the theoretical basis and application foundation for the combination of bioactive compounds and the PDLLA film, thereby preparing the large-scale manufacture and clinical application of PDLLA-based medical products and, in the long term, providing a new clinical treatment for peripheral nerve injury.

周围神经损伤后神经纤维的再生是神经修复的关键。采用可降解生物膜作为神经周围屏障，提供神经生长管道、防止组织粘连是目前研究热点。但是如何在生物材料中复合神经生长因子从分子水平促神经再生仍是该领域研究的瓶颈。因此，本课题拟分别应用3D打印和溶液浇铸法制备具有复孔结构、可降解和具有神经生长因子（NGF）缓释功能的聚-DL-乳酸（PDLLA）医用膜。其中，通过搭建3D打印平台，探索制备结构均匀的PDLLA膜的工艺参数。通过体外试验对不同方法制备的医用膜的结构、NGF活性的体外保存、NGF释放速率、通透性、力学特性、降解性和生物相容性进行研究。并通过体内试验对该医用膜的毒理、病理、降解性及促进神经愈合的能力进行研究。从而为研究PDLLA与生物活性物质NGF结合提供理论依据及应用基础，并为PDLLA医用膜产品的批量制备和临床应用做前期准备工作，最终为临床治疗周围神经损伤提供新的治疗手段。

周围神经损伤后神经纤维的再生是神经修复的关键。采用可降解生物膜作为神经周围屏障，提供神经生长管道、防止组织粘连是目前研究热点。但是如何在生物材料中复合神经生长因子从分子水平促神经再生仍是该领域研究的瓶颈。本课题采用相分离技术，静电纺丝方法，制备负载促进周围神经再生的活性因子神经生长因子（NGF）及雷帕霉素（RAPA）的多孔PDLLA膜，之后对膜的性质、药物的释放进行检测，后进行细胞行为学、动物实验周围神经损伤再生水平检测等研究，为促进周围神经损伤修复提供了一种新的完整的实验思路。