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多功能复合支架响应微环境并指导成骨作用,用于修复感染性骨缺损。

A multifunctional composite scaffold responds to microenvironment and guides osteogenesis for the repair of infected bone defects.

机构信息

Medical 3D Printing Center, Orthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Biology and Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215000, China.

出版信息

J Nanobiotechnology. 2024 Sep 19;22(1):577. doi: 10.1186/s12951-024-02823-8.

Abstract

Treating bone defect concomitant with microbial infection poses a formidable clinical challenge. Addressing this dilemma necessitates the implementation of biomaterials exhibiting dual capabilities in anti-bacteria and bone regeneration. Of particular significance is the altered microenvironment observed in infected bones, characterized by acidity, inflammation, and an abundance of reactive oxygen species (ROS). These conditions, while challenging, present an opportunity for therapeutic intervention in the context of contaminated bone defects. In this study, we developed an oriented composite scaffold containing copper-coated manganese dioxide (MnO) nanoparticles loaded with parathyroid hormone (PMPC/Gelatin). The characteristics of these scaffolds were meticulously evaluated and confirmed the high sensitivity to H, responsive drug release and ROS elimination. In vitro antibacterial analysis underscored the remarkable ability of PMPC/Gelatin scaffolds to substantially suppressed bacterial proliferation and colony formation. Furthermore, this nontoxic material demonstrated efficacy in mitigating ROS levels, thereby fostering osteogenic differentiation of bone marrow mesenchymal stem cells and enhancing angiogenic ability. Subsequently, the infected models of bone defects in rat skulls were established to investigate the effects of composite scaffolds on anti-bacteria and bone formation in vivo. The PMPC/Gelatin treatment exhibited excellent antibacterial activity, coupled with enhanced vascularization and osteogenesis at the defect sites. These compelling findings affirm that the PMPC/Gelatin composite scaffold represents a promising avenue for anti-bacteria and bone regeneration.

摘要

治疗伴有微生物感染的骨缺损是一个巨大的临床挑战。解决这个难题需要使用具有抗菌和骨再生双重功能的生物材料。特别重要的是感染骨中观察到的改变的微环境,其特征为酸性、炎症和大量的活性氧物种 (ROS)。这些条件虽然具有挑战性,但为污染性骨缺损的治疗干预提供了机会。在这项研究中,我们开发了一种含有载有甲状旁腺激素的铜涂层二氧化锰 (MnO) 纳米粒子的定向复合支架 (PMPC/Gelatin)。这些支架的特性经过精心评估并证实了对 H 的高灵敏度、响应性药物释放和 ROS 消除。体外抗菌分析强调了 PMPC/Gelatin 支架显著抑制细菌增殖和菌落形成的能力。此外,这种无毒材料在减轻 ROS 水平方面表现出疗效,从而促进骨髓间充质干细胞的成骨分化并增强血管生成能力。随后,在大鼠颅骨的骨缺损感染模型中研究了复合支架对体内抗菌和骨形成的影响。PMPC/Gelatin 处理表现出优异的抗菌活性,同时在缺陷部位增强了血管生成和成骨作用。这些有力的发现证实了 PMPC/Gelatin 复合支架是一种有前途的抗菌和骨再生途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59b3/11411996/e7a94c64d5e9/12951_2024_2823_Figa_HTML.jpg

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