β磷酸三钙-明胶复合人工骨材料缓释抗生素治疗复杂感染性骨缺损的实验研究

Osteomyelitis and infected bone defects remain a difficult infection to treat for orthopaedic surgeons regardless of the continuous advances in surgical techniques and anti-microbial agents. The controlled release of antibiotics from local delivery system is a promising method for eliminating infection. However, there are still no ideal products for the treatment of osteomyelitis and infected bone defects in clinics. Ideally, biomaterials for the local delivery of antibiotics should have comprehensive functions, such as the ability to provide controllable release rate of antibiotics, the provision of physicochemical characteristics necessary for osteoinduction, and the ability to serve as a scaffold with adequate strength which supports osteoconduction and osseous integration. The composite of ceramics and polymers is a good carrier for local delivery system. The ceramic phase in polymer composites is important for improving the mechanical properties of scaffolds. On the other hand, the addition of biodegradable polymers to calcium phosphate ceramics can allow for better manipulation and control in both the macro- and microstructure in shaping composite scaffolds to fit bone defects. Furthermore, biodegradable polymers can be used as binders for calcium phosphate ceramics to reduce the brittleness of the ceramics. Previous studies have proven that the gelatin/β-TCP hybrid scaffold is suitable for bone tissue engineering. And our studies showed that the composite scaffold can provide a local therapeutic drug levels over an extended duration and repair the infected bone defects. In this studies, the vancomycin and Tobramycin loaded gelatin/β-TCP hybrid scaffold was prepared to repair the infected bone defects in the experimental animal model of MRAS and Bacterium coli mixed infection.We aimed to find a new way for the treatment of osteomyelitis and infected bone defects.

骨髓炎、感染性骨缺损是骨科临床的难点，往往耗费大量人力、物力仍无法治愈，甚至需要截肢。抗生素局部缓释和骨组织工程技术的迅猛发展带来新希望，但至今临床上仍无理想产品。迫切需要开发一种具有定向、可控释放药物、能有效杀灭耐甲氧西林金葡菌（MRSA）、其它细菌以及无需二次取出并有传导成骨作用的人工骨材料。已有研究表明β磷酸三钙/明胶复合材料能有效促进骨缺损修复。我们的前期研究还发现其对万古霉素具有良好缓释性能，可以在体内持续释放万古霉素8周，并修复MRSA感染性骨缺损动物模型。但单纯载万古霉素复合人工骨材料对于因多种细菌混合感染所致的复杂感染性骨缺损并无治疗效果。本项目在前期研究的基础上，利用已制备的β磷酸三钙/明胶复合材料同时负载万古霉素、妥布霉素，并建立由MRSA和大肠杆菌混合感染所致的复杂感染性骨缺损动物模型，使其能够在局部持续释放两种抗生素，清除骨感染、修复骨缺损。为临床应用提供实验基础。