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水凝胶递送抗菌酶治疗骨折伤口感染,或能替代抗生素

发布日期:2018-06-13来源:热心肠日报发布人:梦缘徽州

原标题:水凝胶递送溶葡球菌酶清除金黄色葡萄球菌引起的感染并促进骨折愈合

① 开发可注射的聚乙二醇水凝胶,用于递送溶葡球菌酶,以治疗骨折中的感染;

② 水凝胶可粘附于暴露组织及断裂面,促进溶葡球菌酶的高效局部递送,封装于水凝胶中的溶葡球菌酶维持了酶活性及稳定性;

③ 通过水凝胶递送的溶葡球菌酶在股骨骨折小鼠模型中清除感染,效果比预防性抗生素及可溶性溶葡球菌酶更好;

④ 通过水凝胶递送的溶葡球菌酶可使骨折感染在5周内痊愈,并促进骨形成;

⑤ 还能够清除耐甲氧西林的金黄色葡萄球菌感染,或可代替抗生素。

Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by and supports fracture healing

DOI: 10.1073/pnas.1801013115

Abstract:
Orthopedic implant infections are a significant clinical problem, with current therapies limited to surgical debridement and systemic antibiotic regimens. Lysostaphin is a bacteriolytic enzyme with high antistaphylococcal activity. We engineered a lysostaphin-delivering injectable PEG hydrogel to treat infections in bone fractures. The injectable hydrogel formulation adheres to exposed tissue and fracture surfaces, ensuring efficient, local delivery of lysostaphin. Lysostaphin encapsulation within this synthetic hydrogel maintained enzyme stability and activity. Lysostaphin-delivering hydrogels exhibited enhanced antibiofilm activity compared with soluble lysostaphin. Lysostaphin-delivering hydrogels eradicated infection and outperformed prophylactic antibiotic and soluble lysostaphin therapy in a murine model of femur fracture. Analysis of the local inflammatory response to infections treated with lysostaphin-delivering hydrogels revealed indistinguishable differences in cytokine secretion profiles compared with uninfected fractures, demonstrating clearance of bacteria and associated inflammation. Importantly, infected fractures treated with lysostaphin-delivering hydrogels fully healed by 5 wk with bone formation and mechanical properties equivalent to those of uninfected fractures, whereas fractures treated without the hydrogel carrier were equivalent to untreated infections. Finally, lysostaphin-delivering hydrogels eliminate methicillin-resistant infections, supporting this therapy as an alternative to antibiotics. These results indicate that lysostaphin-delivering hydrogels effectively eliminate orthopedic infections while simultaneously supporting fracture repair.

First Authors:
Christopher T Johnson

Correspondence:
Andrés J García

All Authors:
Christopher T Johnson,James A Wroe,Rachit Agarwal,Karen E Martin,Robert E Guldberg,Rodney M Donlan,Lars F Westblade,Andrés J García

5/14/18Article