载P物质的胶原/聚乳酸己内酯电纺膜用于心脏瓣膜快速再生的实验研究

瓣膜置换是心脏瓣膜疾病的最终治疗手段，而理想的瓣膜替代物缺乏一直是困扰心脏外科医生的难题。最新文献及我们的前期研究表明：通过计算机模拟设计及3D打印方法制备出心脏瓣膜内核后直接皮下移植，依靠自体细胞迁移覆盖内核表面，从而再生出瓣膜组织，是一种较为理想的瓣膜再生方法。然而上述方法依然存在不足：由于内核表面光滑，细胞无附着点，因此瓣膜再生慢，耗时长，力学性能不足。针对这一问题，本课题首次提出：在瓣膜内核的外表面包裹一层疏松多孔的材料作为细胞粘附的支架，并在上述材料中添加促进细胞迁移及分泌胞外基质的P物质，从而促使瓣膜快速再生的设想。为证实这一假设，本项目首先制备出载P物质的明胶/聚乳酸己内酯电纺膜, 并将其包裹在3D打印的瓣膜内核表面，皮下移植使其快速再生出瓣膜组织，最终进行大动物自体瓣膜置换并评价其功能。该项目的成功将为临床提供快速再生的自体瓣膜，解决瓣膜移植物缺乏的难题。

Most heart valve diseases eventually need valve replacement. Currently, the valve prostheses used in valve replacement surgery have different degrees of disadvantages. Hence, engineering an ideal valve substitute is necessary. By computational aided design and 3D printing technique, we have previously made a heart valve core, and subcutaneously transplanted the “core” into rabbit. Gradually, the core will be covered by cells, which help form a newly generated tissue i.e. regenerated heart valve. This individualized, non-immunogenic subcutaneous generated valve, however, has an obvious disadvantage –the valve regenerates slowly (>2 months) for the nude core can not provide cells a scaffold for adherence. In this study, we hypothesize that a porous material loaded with substance P(SP) recruiting cells can accelerate valve regeneration. So here, firstly we need to fabricate collagen/poly(L-Lactide-co-caprolactone)[PLCL] electrospun membrane loaded with SP, and then cover the film fully along the surface of 3D printed valve core, and eventually, subcutaneously transplant into big animal to verify its fast valve regeneration capability. Autologous valve replacement will be applied to assess valve function as well. The success of this study will provide patients an autologous regenerated valve within a short time.