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一种多功能含钴植入物,通过巨噬细胞介导的免疫调节治疗生物膜感染并促进感染性骨缺损中的骨整合。

A Multifunctional Cobalt-Containing Implant for Treating Biofilm Infections and Promoting Osteointegration in Infected Bone Defects Through Macrophage-Mediated Immunomodulation.

作者信息

Yan Nongyang, Zhou Hao, Jin Penghe, Li Tengfei, Liu Qi, Ning Hao, Ma Zhixin, Feng Linfei, Jin Tao, Deng Youwen, Wu Zhengwei

机构信息

Institute of Advanced Technology, University of Science and Technology of China, No. 5089 Wangjiang West Road, Hefei, Anhui, 230031, China.

Department of Spine Surgery, The Third Xiangya Hospital, Central South University, No. 138 Tongzi Road, Changsha, Hunan, 410013, China.

出版信息

Adv Sci (Weinh). 2025 Jan;12(3):e2409200. doi: 10.1002/advs.202409200. Epub 2024 Nov 26.

Abstract

Treating bone infections and ensuring bone recovery is one of the major global problems facing modern orthopedics. Prolonged antibiotic use may increase the risk of antimicrobial resistance, and inflammation caused by biofilms can obstruct tissue healing, making bone infection treatment even more challenging. The optimal treatment strategy combines immune response modification to promote osteogenesis with effective bacterial infection removal that does not require long-term antibiotic use. A one-step plasma immersion ion implantation approach is used to create titanium alloy implants incorporating cobalt. According to experimental findings, cobalt-containing titanium implants exhibit improved antibacterial activity by efficiently disrupting biofilm formations and reducing Methicillin-resistant Staphylococcus aureus adherence by over 80%. Additionally, the implants exhibit superior anti-inflammatory and osseointegration properties. RNA sequencing analysis reveals the potential mechanism of Co in regulating the polarization of macrophages toward the anti-inflammatory M2 phenotype, which is crucial for creating an immune environment conducive to bone healing. Concurrently, these implants promote osteogenic differentiation while suppressing osteoclast activity, further supporting bone repair. Overall, without exogenous recombinant proteins or antibiotics, the implants effectively eradicate infections and expedite bone repair, offering a novel therapeutic strategy for complex skeletal diseases with clinical promise.

摘要

治疗骨感染并确保骨修复是现代骨科面临的主要全球性问题之一。长期使用抗生素可能会增加抗菌耐药性的风险,生物膜引起的炎症会阻碍组织愈合,使骨感染治疗更具挑战性。最佳治疗策略是将促进成骨的免疫反应调节与有效清除细菌感染相结合,且无需长期使用抗生素。采用一步式等离子体浸没离子注入方法来制造含钴的钛合金植入物。根据实验结果,含钴钛植入物通过有效破坏生物膜形成和将耐甲氧西林金黄色葡萄球菌的黏附减少80%以上,表现出改善的抗菌活性。此外,这些植入物还具有卓越的抗炎和骨整合特性。RNA测序分析揭示了钴调节巨噬细胞向抗炎M2表型极化的潜在机制,这对于创造有利于骨愈合的免疫环境至关重要。同时,这些植入物促进成骨分化,同时抑制破骨细胞活性,进一步支持骨修复。总体而言,在没有外源性重组蛋白或抗生素的情况下,这些植入物能有效根除感染并加速骨修复,为具有临床前景的复杂骨骼疾病提供了一种新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc26/11744729/ab0de1a598cd/ADVS-12-2409200-g002.jpg

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