硅掺杂纳米结构羟基磷灰石生物陶瓷负载万古霉素调控慢性骨髓炎的治疗及机理研究

Chronic osteomyelitis usually happens after bone tissue infection. It greatly hinders the repair and regeneration of bone tissue and leads to low cure rate and high disability rate, which becomes a big challenge in trauma and reparative surgery. Design of new biomaterials with antibacterial properties and the abilities to rapidly induce the osteogenesis would be the key to achieve infected bone repair in chronic osteomyelitis. In present project, the silicon element with functions of stimulating osteogenesis will be doped into the osteoinductive nano-structured hydroxyapatite bioceramics with optimal surface topography from our previous studies. And we further develop the nano structure of materials to enable its high effective loading and controlled release of vancomycin. By in vitro and in vivo experiments, we evaluated the synergistic effect of this novel materials in terms of osteogenic and antibacterial activity, as well as its association with icaA/icaD/icaR signaling path ways. Further, the prepared materials was applied to heal MRSA chronic osteomyelitis in rabbit tibia and the treatment effect was systematically evaluated, which revealed the coordinately regulatory pattern of silicon substitution and controlled release of vancomycin on bone tissue repair. The present study may provide an ideal new bone graft material for repairing bone defects in the state of chronic osteomyelitis and a new strategy to design the new bioactive bone repair materials for specific diseases.

慢性骨髓炎是骨组织感染后病程的延续，其迁延顽固、治愈率低、致残率高，极大地阻碍了骨组织的修复与再生，是创伤修复外科面临的一大挑战。设计具有长效抗菌与快速诱导成骨特性的新型骨修复材料，是实现慢性骨髓炎条件下骨重塑的关键。本项目在前期工作中制备出的具有良好成骨诱导活性的纳米结构羟基磷灰石生物陶瓷材料的基础上，掺杂硅元素以进一步协同增强其促成骨功能，同时使该材料具备对万古霉素的高效负载与长效缓释功能。通过体内外实验验证该材料的协同促成骨活性、抗菌活性，以及与菌膜形成特异性基因icaA/icaD/icaR等的关联；并进一步将该材料用于耐甲氧西林金黄色葡萄球菌感染的兔胫骨慢性骨髓炎模型的治疗，系统评价治疗效果，揭示通过纳米结构缓释万古霉素与硅元素掺杂协同调控体内骨修复性能的规律。本研究有望为治疗慢性骨髓炎提供较为理想的新型植骨材料，同时为特定疾病状态下骨修复材料的研发提供新的策略。

慢性骨髓炎是骨组织感染后病程的延续，其迁延顽固、治愈率低、致残率高，极大地阻碍了骨组织的修复与再生，是创伤修复外科面临的一大挑战。设计具有长效抗菌与快速诱导成骨特性的新型骨修复材料，是实现慢性骨髓炎条件下骨重塑的关键。本项目在前期工作中制备出的具有良好成骨诱导活性的纳米结构羟基磷灰石生物陶瓷材料的基础上，掺杂硅元素以进一步协同增强其促成骨功能，同时使该材料具备对万古霉素的高效负载与长效缓释功能。通过体内外实验验证该材料的协同促成骨活性、抗菌活性，以及万古霉素与L-Homocarnosine（L-高肌肽）、omega-3 fatty acids（Ω-3脂肪酸）均具有良好的协同效应，能有效减轻金黄色葡萄球菌引发的大鼠骨髓炎模型。并进一步将该材料用于耐甲氧西林金黄色葡萄球菌感染的大鼠股骨慢性骨髓炎模型的治疗，系统评价治疗效果，揭示通过纳米结构缓释万古霉素与硅元素掺杂协同调控体内骨修复性能的规律。本研究有望为治疗慢性骨髓炎提供较为理想的新型植骨材料，同时为特定疾病状态下骨修复材料的研发提供新的策略。