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万古霉素交联细胞外基质支架在多功能抗菌骨感染治疗中的应用

Extracellular matrix scaffold crosslinked with vancomycin for multifunctional antibacterial bone infection therapy.

机构信息

Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, China; Department of Spine Surgery, The Central Hospital Affiliated to Shaoxing University, Shaoxing, China; Department of Spine Surgery, Shaoxing Central Hospital, China Medical University, Shaoxing, China; Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, China.

Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, China; Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, China.

出版信息

Biomaterials. 2021 Jan;268:120603. doi: 10.1016/j.biomaterials.2020.120603. Epub 2020 Dec 17.

DOI:10.1016/j.biomaterials.2020.120603
PMID:33378735
Abstract

The treatment of acute and chronic bone infections remains a major clinical challenge. The various factors released by the bacteria, acidic environment, and bacterial colonies in the bone grooves and implanted synthetic materials collectively promote the formation of biofilms. Dormant bacteria and biofilms cause infections that are difficult to cure and that can develop chronically. Therefore, a new antibacterial material was synthesized in the present study for multifunctional bone infection therapy and consists of specific demineralized extracellular cancellous bone (SDECM) crosslinked with vancomycin (Van) by means of electrostatic interactions and chemical bonds. It was verified in vitro that the new material (Van-SDECM) not only has pH-sensitive release and biofilm inhibition properties, but also maintains sustained bactericidal ability accompanied by the degradation of the scaffold, which does not affect its favorable osteogenic performance. The infectious bone defect in vivo model further confirms the comprehensive anti-infective and osteogenic ability of the Van-SDECM. Further, these favorable properties are due to the pH-sensitive sustained release sterilization and scaffold contact antibacterial properties, accompanied by osteoclast activity inhibition, osteogenesis promotion and immunoregulation effects. This study provides a new drug-scaffold composite preparation method based on a native-derived extracellular matrix scaffold.

摘要

急性和慢性骨感染的治疗仍然是一个主要的临床挑战。细菌释放的各种因子、酸性环境以及骨槽和植入的合成材料中的细菌菌落共同促进了生物膜的形成。休眠细菌和生物膜导致难以治愈且可能慢性发展的感染。因此,本研究合成了一种新的抗菌材料,用于多功能骨感染治疗,由通过静电相互作用和化学键交联万古霉素的特定脱矿细胞外松质骨(SDECM)组成。体外验证表明,新材料(Van-SDECM)不仅具有 pH 敏感释放和生物膜抑制特性,而且在支架降解的同时保持持续的杀菌能力,这不会影响其良好的成骨性能。体内感染性骨缺损模型进一步证实了 Van-SDECM 的综合抗感染和成骨能力。此外,这些有利特性是由于 pH 敏感的持续释放灭菌和支架接触抗菌特性,同时抑制破骨细胞活性、促进成骨和免疫调节作用。本研究提供了一种基于天然来源细胞外基质支架的新型药物-支架复合材料制备方法。

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