基于“活性玻璃/明胶”多糖修饰的因子时序缓释支架构建及其促血管化和骨再生机制研究

骨诱导活性不足和血管化程度低是临床骨修复材料普遍存在的问题，生长因子负载是调控其活性的有效手段。然而根据骨组织的结构特点和修复过程的需要，设计制备能维持生长因子活性和时序释放、有效促进细胞快速响应、利于血管/骨组织新生和营养传输的材料是当前骨修复领域面临的重大挑战。为此，本项目拟基于“介孔活性玻璃（MBG）/明胶（GelMA）”构建多糖修饰的双因子时序缓释体系。利用MBG/GelMA的基体差异实现VEGF的早期表达和BMP-2的持续释放；利用材料表面类肝素多糖26SCS的修饰提高因子的体内活性并优化其释放行为；利用微纳结构-微流道设计，加速成骨相关细胞响应和组织新生。深入探索材料的可控制备与生长因子的优化装载，及其共同调控细胞行为和体内骨缺损修复的作用机制。重点解决生长因子载体的设计制备与材料介导的骨再生机制的探究两大科学问题。该项目的实施有望为骨引导再生材料的开发和性能研究提供新方法。

Low osteoinductivity and poor vascularization are the common problems of current bone substitutes. Incorporating growth factors with bone substitutes is considered as an efficient strategy to accelerate tissues regeneration. However, development of bone substitutes that can controlled-release growth factors with preserved bioactivity and stimulate angiogenesis/osteogenesis remains a significant challenge. Herein, this study aims to develop a spatiotemporal release system based on 2-N,6-O-sulfated chitosan (26SCS) modified mesoporous bioactive glass (MBG)/gelatin methacryloyl-based hydrogels (GelMA) scaffold. Combining the mesoporous texture of MBG with permeability property of GelMA, this scaffold can provide an initial release of VEGF with long-term BMP-2 delivery. Through the 26SCS modification, an enhanced protein bioactivity, desirable VEGF concentration gradient and better BMP-2 release kinetics of the scaffold could be achieved. For better cell penetration and tissue ingrowth, a customized hierarchically microchannel structure is further developed. On the basis of these, we will systematically explore the characteristics and underlying mechanism of bone regeneration guided by 26SCS modified MBG/GelMA-based growth factor delivery system, and illuminate the key factors in growth factor immobilization and bone healing. The concepts propose in this study might provide new thoughts on development of future orthopedic biomaterials.