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用具有抗菌活性的骨相容性微球再生感染性骨缺损。

Regenerating infected bone defects with osteocompatible microspheres possessing antibacterial activity.

机构信息

State Key Laboratory of Organic-Inorganic Composites; Beijing Laboratory of Biomedical Materials; Beijing University of Chemical Technology, Beijing 100029, P.R. China.

出版信息

Biomater Sci. 2018 Dec 18;7(1):272-286. doi: 10.1039/c8bm00903a.

DOI:10.1039/c8bm00903a
PMID:30467569
Abstract

Treatment of infected bone defects still remains a formidable clinical challenge, and the design of bone implants with both anti-bacterial activity and -osteogenesis effects is nowadays regarded as a powerful strategy for infection control and bone healing. In the present study, bioresorbable porous-structured microspheres were fabricated from an amphiphilic block copolymer composed of poly(l-lactide) and poly(ethyl glycol) blocks. After being surface coated with mussel-inspired polydopamine, the microspheres were loaded with nanosilver via the reduction of silver nitrate and apatite via biomineralization in sequence. At optimized loading amounts, the nanosilver-loaded microspheres showed no unfavorable effects on the proliferation and differentiation of bone marrow mesenchymal stem cells despite preserving strong antibacterial activity in in vitro evaluations. For the critical-sized defects (φ = 8 mm) in the rat cranium that was pre-infected with Staphylococcus aureus, the filling of the dual-purpose microspheres demonstrated an effective way to kill bacteria in vivo, and in the meantime, it promoted new bone formation efficiently alongside the degradation of microspheres. Thus, the results suggested that bioresorbable microspheres with both osteoconductive and antibacterial activities were a good choice for treating infected bone defects.

摘要

治疗感染性骨缺损仍然是一个巨大的临床挑战,设计具有抗菌活性和骨生成作用的骨植入物被认为是控制感染和促进骨愈合的有效策略。在本研究中,采用聚(L-乳酸)和聚乙二醇嵌段组成的两亲性嵌段共聚物制备了可生物降解的多孔结构微球。在经过贻贝类聚多巴胺表面涂层处理后,通过硝酸银还原和生物矿化依次将纳米银和磷灰石负载到微球上。在优化的载药量下,尽管纳米银负载的微球在体外评价中仍保持着较强的抗菌活性,但对骨髓间充质干细胞的增殖和分化没有不利影响。对于预先感染金黄色葡萄球菌的大鼠颅骨临界尺寸(φ=8mm)缺损,双用途微球的填充证明了一种在体内有效杀死细菌的方法,同时,随着微球的降解,它也能有效地促进新骨形成。因此,研究结果表明,具有骨传导和抗菌活性的可生物降解微球是治疗感染性骨缺损的一种较好选择。

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