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用于抗菌治疗和保护糖尿病患者骨整合的葡萄糖预载 PEEK 骨科植入物。

Glucose-primed PEEK orthopedic implants for antibacterial therapy and safeguarding diabetic osseointegration.

机构信息

School of Chemical Engineering, College of Biomedical Engineering, West China Hospital of Stomatology, Sichuan University, Chengdu, 610065, China.

School of Chemical Engineering, College of Biomedical Engineering, West China Hospital of Stomatology, Sichuan University, Chengdu, 610065, China; State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China.

出版信息

Biomaterials. 2023 Dec;303:122355. doi: 10.1016/j.biomaterials.2023.122355. Epub 2023 Nov 4.

Abstract

Diabetic infectious microenvironment (DIME) frequently leads to a critical failure of osseointegration by virtue of its main peculiarities including typical hyperglycemia and pathogenic infection around implants. To address the plaguing issue, we devise a glucose-primed orthopedic implant composed of polyetheretherketone (PEEK), Cu-chelated metal-polyphenol network (hauberk coating) and glucose oxidase (GOx) for boosting diabetic osseointegration. Upon DIME, GOx on implants sostenuto consumes glucose to generate HO, and Cu liberated from hauberk coating catalyzes the HO to highly germicidal •OH, which massacres pathogenic bacteria through photo-augmented chemodynamic therapy. Intriguingly, the catalytic efficiency of the coating gets greatly improved with the turnover number (TON) of 0.284 s. Moreover, the engineered implants exhibit satisfactory cytocompatibility and facilitate osteogenicity due to the presence of Cu and osteopromotive polydopamine coating. RNA-seq analysis reveals that the implants enable to combat infections and suppress pro-inflammatory phenotype (M1). Besides, in vivo evaluations utilizing infected diabetic rat bone defect models at week 4 and 8 authenticate that the engineered implants considerably elevate osseointegration through pathogen elimination, inflammation dampening and osteogenesis promotion. Altogether, our present study puts forward a conceptually new tactic that arms orthopedic implants with glucose-primed antibacterial and osteogenic capacities for intractable diabetic osseointegration.

摘要

糖尿病感染微环境(DIME)常常由于其主要特点而导致种植体周围典型的高血糖和致病感染,从而导致骨整合的严重失败。为了解决这个问题,我们设计了一种由聚醚醚酮(PEEK)、Cu 螯合金属多酚网络(铠甲涂层)和葡萄糖氧化酶(GOx)组成的预载葡萄糖的骨科植入物,以增强糖尿病患者的骨整合。在 DIME 中,植入物上的 GOx 持续消耗葡萄糖产生 HO,而从铠甲涂层中释放的 Cu 催化 HO 生成具有高度杀菌作用的 •OH,通过光增强化学动力学疗法杀死致病菌。有趣的是,涂层的催化效率随着周转率(TON)提高到 0.284 s 而大大提高。此外,由于存在 Cu 和促进成骨的聚多巴胺涂层,工程化植入物表现出令人满意的细胞相容性并促进成骨作用。RNA-seq 分析表明,植入物能够通过对抗感染和抑制促炎表型(M1)来发挥作用。此外,在第 4 周和第 8 周利用感染性糖尿病大鼠骨缺损模型进行的体内评估证实,该工程化植入物通过消除病原体、抑制炎症和促进成骨作用,极大地提高了骨整合。总的来说,我们的研究提出了一种新概念,即用预载葡萄糖的抗菌和成骨能力武装骨科植入物,以解决难治性糖尿病骨整合问题。

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