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葡萄糖触发的一氧化氮释放涂层赋予骨科植入物增强的抗菌和血管扩张能力,以保障糖尿病患者的骨整合。

Glucose-triggered NO-evolving coating bestows orthopedic implants with enhanced anti-bacteria and angiectasis for safeguarding diabetic osseointegration.

作者信息

Shi Hongxing, Yang Hao, Wu Chao, Wang Song, He Shuai, Chen Lin, Chan Yau Kei, Lai Shuangquan, Liang Kunneng, Deng Yi

机构信息

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

Institute of Digital Medicine, Zigong Academy of Big Data for Medical Science and Artificial Intelligence, Department of Orthopedics, Zigong Fourth People's Hospital, Zigong, 643000, China.

出版信息

Biomaterials. 2025 Oct;321:123334. doi: 10.1016/j.biomaterials.2025.123334. Epub 2025 Apr 9.

DOI:10.1016/j.biomaterials.2025.123334
PMID:40239593
Abstract

As a common chronic metabolic disease, diabetes mellitus (DM) features a hyperglycemic micromilieu around implants, resulting in the critical implantation failure and high complications such as peri-implantitis and angiectasis disorder. To address the plaguing issue, we devise and develop a glucose-unlocked NO-evolving orthopedic implant consisted of polyetheretherketone (PEEK), glucose oxidase (GOx) and l-arginine (Arg) with enhanced angiogenesis for boosting diabetic osseointegration. Upon hyperglycemic niche, GOx on implants catalytically exhaust glucose to HO, which immediately reacts with Arg to in situ liberate nitric oxide (NO), resulting in enhanced angiogenesis and angiectasis around PEEK implant. Besides, the engineered implant exhibits great anti-bacterial properties against both Gram-positive and Gram-negative bacteria, as well as fortifies osteogenicity of osteoblasts in terms of cell proliferation, alkaline phosphatase activity and calcium matrix mineralization. Intriguingly, in vivo evaluations utilizing diabetic infectious bone defect models of rat further authenticate that the engineered implants substantially augment bone remodeling and osseointegration at weeks 4 and 8 through dampening pathogens, anti-inflammatory as well as promoting angiectasis. Altogether, this work proposed a new tactic to remedy stalled diabetic osseointegration with hyperglycemic micromilieu-responsive therapeutic gas-evolving orthopedic implants.

摘要

作为一种常见的慢性代谢性疾病,糖尿病(DM)的特征是植入物周围存在高血糖微环境,导致关键的植入失败以及诸如种植体周围炎和血管扩张紊乱等高并发症。为了解决这个困扰人的问题,我们设计并开发了一种由聚醚醚酮(PEEK)、葡萄糖氧化酶(GOx)和L-精氨酸(Arg)组成的葡萄糖解锁不释放一氧化氮的骨科植入物,其具有增强的血管生成作用以促进糖尿病患者的骨整合。在高血糖微环境下,植入物上的GOx催化消耗葡萄糖生成H₂O,H₂O立即与Arg反应原位释放一氧化氮(NO),从而导致PEEK植入物周围的血管生成和血管扩张增强。此外,这种工程化植入物对革兰氏阳性菌和革兰氏阴性菌均表现出强大的抗菌性能,并且在细胞增殖、碱性磷酸酶活性和钙基质矿化方面增强了成骨细胞的成骨能力。有趣的是,利用大鼠糖尿病感染性骨缺损模型进行的体内评估进一步证实,这种工程化植入物在第4周和第8周通过抑制病原体、抗炎以及促进血管扩张,显著增强了骨重塑和骨整合。总之,这项工作提出了一种新策略,即使用对高血糖微环境有反应的治疗性释放气体的骨科植入物来补救停滞的糖尿病骨整合。

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