Lysostaphin and BMP-2 co-delivery reduces S. aureus infection and regenerates critical-sized segmental bone defects
Lysostaphin and BMP-2 co-delivery reduces S. aureus infection and regenerates critical-sized segmental bone defects
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DOI：
10.1126/sciadv.aaw1228
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发表时间：
2019-05-01
期刊：
影响因子：
13.6
通讯作者：
Garcia, Andres J.
中科院分区：
文献类型：
--
作者：
Johnson, Christopher T.;Sok, Mary Caitlin P.;Garcia, Andres J.
金黄色葡萄球菌是骨科手术中与细菌感染相关的最常见病原体。感染通常会导致植入失败和随后的移除，从而推动了双功能材料的发展，这些材料既促进修复又防止感染导致的失败。溶葡萄球菌酶是一种抗葡萄球菌酶，导致细菌裂解和生物膜减少。溶葡萄球菌酶的使用受到缺乏有效递送方法以向感染部位提供持续的高剂量酶的限制。我们设计了一种装载BMP-2的溶葡萄球菌酶水凝胶，同时防止S。金黄色葡萄球菌感染和修复小鼠桡骨中的不愈合节段性骨缺损。溶葡萄球菌酶水凝胶根除了S。金黄色葡萄球菌感染，并导致机械活性骨。细胞因子和免疫细胞分析表明，溶葡萄球菌酶递送水凝胶将局部炎症环境恢复到无菌损伤的环境。这些结果表明，BMP-2加载溶葡萄球菌酶递送水凝胶疗法有效地消除了S。金黄色葡萄球菌感染，同时再生功能性骨，导致缺损愈合。
Staphylococcus aureus is the most common pathogen associated with bacterial infections in orthopedic procedures. Infections often lead to implant failure and subsequent removal, motivating the development of bifunctional materials that both promote repair and prevent failure due to infection. Lysostaphin is an anti-staphylococcal enzyme resulting in bacterial lysis and biofilm reduction. Lysostaphin use is limited by the lack of effective delivery methods to provide sustained, high doses of enzyme to infection sites. We engineered a BMP-2-loaded lysostaphin-delivering hydrogel that simultaneously prevents S. aureus infection and repairs nonhealing segmental bone defects in the murine radius. Lysostaphin-delivering hydrogels eradicated S. aureus infection and resulted in mechanically competent bone. Cytokine and immune cell profiling demonstrated that lysostaphin-delivering hydrogels restored the local inflammatory environment to that of a sterile injury. These results show that BMP-2-loaded lysostaphin-delivering hydrogel therapy effectively eliminates S. aureus infection while simultaneously regenerating functional bone resulting in defect healing.