骨髓炎清创术后感染性骨缺损重建及抑制局部感染复发是临床治疗面临的两大难题，赋予骨移植材料快速骨再生能力和长效抗菌活性是解决难题的关键。本项目拟以具有良好骨诱导能力的磷酸钙（CaP）纳米陶瓷为基底，通过多级抗菌结构设计，发挥纳米氧化锌（ZnO）和溶葡萄球菌酶（LST）优异抗菌能力，赋予CaP纳米陶瓷长效抗菌的功能。其技术核心为纳米ZnO在陶瓷中的原位负载，陶瓷表面空心管晶须构建和壳聚糖凝胶层的包覆以实现对LST的有效装载，进而构建具有时序控释LST（0~6周）和纳米ZnO（>6周）的多级抗菌结构。通过体内外生物实验，考察材料的抗菌能力和骨诱导活性，以及对感染性骨缺损的再生修复效果，探讨CaP纳米陶瓷在感染性成骨环境下诱导骨再生机理，并诠释LST和纳米ZnO时序释放及长效抗菌机制。通过本项目的实施，有望为临床突破感染性骨缺损的再生修复提供材料基础和设计思路。

Reconstructing infectious bone defects and suppressing local bone infection recurrence are two major clinical problems after osteomyelitis debridement. Rapid bone regeneration and long-term antibacterial capacity of bone grafts are key factors to solve these problems. Based on the excellent osteoinductivity of calcium phosphate (CaP) nanoceramics, this study intends to combine the excellent antibacterial effects of nano zinc oxide (ZnO) and lysostaphin (LST) through hierarchically antibacterial structure design, in order to endow CaP nanoceramics with long-acting antibacterial function. The hierarchically antibacterial structure with time-sequence controllable release of LST (0-6w) and nano ZnO (> 6w) is constructed by the in-situ loading of nano-ZnO into ceramic body, and the design of hollow-tube whiskers and chitosan gel layer to realize the effective loading of LST on the ceramic surface. The in vitro and in vivo biological experiments are performed to investigate the graft’s antibacterial activity, osteoinductivity and regenerative capacity of infectious bone defects. Meanwhile, the regenerative mechanism of osteoinductive CaP nanoceramics in infectious environment and the time-sequence antibacterial mechanism of nano-ZnO with LST are also explored. The implementation of this project holds promise in providing material basis and design idea for clinical breakthrough of the infectious bone defect regeneration.