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具有级联放大治疗能力的多功能生物HJ酶工程聚醚醚酮植入物用于治疗难治性植入相关感染

Multi-Functional Bio-HJzyme Engineered Polyetheretherketone Implant with Cascade-Amplification Therapeutic Capabilities Toward Intractable Implant-Associated Infections.

作者信息

Gong Jing, Lai Shuangquan, Zhang Shuting, Liang Kunneng, Deng Yi

机构信息

State Key Laboratory of Oral Diseases, School of Chemical Engineering, National Center for Stomatology & National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, China.

Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.

出版信息

Small. 2025 Feb;21(7):e2409437. doi: 10.1002/smll.202409437. Epub 2024 Dec 31.

DOI:10.1002/smll.202409437
PMID:39737662
Abstract

Intractable implant-associated infections (IAIs) are the primary cause of prosthetic implant failure, particularly in the context of diabetes mellitus. There is an urgent need to design and construct versatile engineered implants integrated with cascade amplification therapeutic modality to significantly improve the treatment of diabetic IAIs. To address this issue, a multi-functional MXene/AgPO@glucose oxidase bio-heterojunction enzyme (M/A@GOx bio-HJzyme) coating is developed, which is decorated with an inert sulfonated polyetheretherketone implant (SP-M/A@G) via hydrothermal treatment and layered deposition. The decorated bio-HJzyme coating promoted cellular adhesion and proliferation of osteoblast cells on the implant. Simultaneously, upon 808 nm near-infrared (NIR) light irradiation, the decorated coating not only induces localized hyperthermia and reactive oxygen species (ROS) generation but also initiates Fenton-like and laccase-mimicking reactions and depletes glutathione (GSH) within the diabetes infection microenvironment. The cascade amplification therapeutic effects of phototherapy and biocatalytic therapy confer the engineered implants with robust cyclic antibacterial properties. Furthermore, in vivo, assessment demonstrated that the multi-functional bio-HJzyme can effectively eradicate infectious pathogens located on the implant and peri-implant tissues and promote the regeneration of diabetic infectious skin. Collectively, this study provides a revolutionary approach for constructing multi-functional implants with cascade amplification therapeutic capabilities for intractable diabetic IAIs.

摘要

难治性植入物相关感染(IAIs)是假体植入失败的主要原因,尤其是在糖尿病背景下。迫切需要设计和构建集成级联放大治疗模式的多功能工程植入物,以显著改善糖尿病IAIs的治疗。为了解决这个问题,开发了一种多功能的MXene/AgPO@葡萄糖氧化酶生物异质结酶(M/A@GOx生物杂化酶)涂层,通过水热处理和分层沉积将其装饰在惰性磺化聚醚醚酮植入物(SP-M/A@G)上。装饰后的生物杂化酶涂层促进了植入物上成骨细胞的细胞粘附和增殖。同时,在808nm近红外(NIR)光照射下,装饰后的涂层不仅诱导局部热疗和活性氧(ROS)生成,还引发类芬顿反应和模拟漆酶反应,并耗尽糖尿病感染微环境中的谷胱甘肽(GSH)。光疗和生物催化疗法的级联放大治疗效果赋予工程植入物强大的循环抗菌性能。此外,体内评估表明,多功能生物杂化酶可以有效根除位于植入物和植入物周围组织上的感染病原体,并促进糖尿病感染皮肤的再生。总的来说,这项研究为构建具有级联放大治疗能力的多功能植入物以治疗难治性糖尿病IAIs提供了一种革命性的方法。

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