实现骨形态发生蛋白（BMP）长效缓释的关键是解决制备工艺复杂、蛋白活性保持、突释及不完全释放四大难题。解决途径是用BMP活性肽替代BMP或开发新的缓释材料、机制和技术。本课题拟用BMP-2活性肽替代BMP-2，并开发新的缓释机制和技术。通过模仿骨涎蛋白和骨桥蛋白与HA的结合机制，用多聚谷氨酸多肽序列修饰BMP-2活性肽，利用多聚谷氨酸多肽与纳米晶人工骨（nHAC）表面的HA组分的（002）晶面反应形成特异性生物结合，加强活性肽与nHAC载体的结合，提高载药量。通过前期开发的具有可注射性、生物降解性、生物相容性和骨传导性的温敏性壳聚糖/nHAC将活性肽注射入所需部位，实现局部释放、防止突释和保持蛋白活性的目的。通过多聚谷氨酸多肽的酶解实现BMP-2活性肽的缓释，重点研究活性肽与nHAC之间的作用机制和吸附机理，揭示新系统的降解规律、多肽降解与释放机制和生物活性变化规律及异位成骨诱导活性。

The key of the realization of long-term and slow-release delivery of bone-morphogenetic protein (BMP) is to resolve the problems of complexity of the preparation process, protection of activity of protein, burst effect, and incomplete release. There are two ways to resolve these problems, one is to replace BMP with BMP-derived peptide, and the other is to develop new slow-release materials, mechanism and technology. In this research, we will replace BMP-2 with BMP-2-derived peptide, and develop new slow-release mechanism and technology. Firstly, the BMP-2-derived peptide is modified with polyglutamate sequence, which can react with the (002) face of hydroxyapatite crystal on the surface of nano-hydroxyapatite/collagen (nHAC),and the peptide-binding efficiency and drug loading will be improved by the imitation of the combined mechanism of HA with bone sialoprotein and osteopontin. Secondly, the peptide will be injected to the areas needed using the former developed temperature-sensitive delivery system of chitosan/nHAC,which is injectable,biodegradable,biocompatible and osteoconductive. This procedure is designed for the following purposes: the local drug delivery, the prevention or reduction of burst and the protection of activity of protein. Thirdly，the polyglutamate sequence will be degraded by enzymolysis, and the BMP-2-derived peptide will be slow-released. This research will focus on the combined and adsorption mechanism of nHAC with BMP-2-derived peptide, and reveal the degradation rule of this new system, the biodegration and release mechanism of the BMP-2-derived peptide, the variation of biological activity, and the heterogenous ossification ability of this new system.