葡萄糖引发PEEK骨科植入物用于抗菌治疗和保护糖尿病骨整合。

IF 12.8 1区 医学 Q1 ENGINEERING, BIOMEDICAL Biomaterials Pub Date : 2023-11-04 DOI:10.1016/j.biomaterials.2023.122355
Miaomiao He , Hao Wang , Qiuyang Han , Xiuyuan Shi , Shuai He , Jiyu Sun , Zhuoli Zhu , Xueqi Gan , Yi Deng
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引用次数: 0

摘要

糖尿病感染性微环境(DIME)由于其主要特点,包括典型的高血糖和植入物周围的致病性感染,经常导致骨整合的严重失败。为了解决这一难题,我们设计了一种由聚醚醚酮(PEEK)、铜螯合金属多酚网络(hauberk涂层)和葡萄糖氧化酶(GOx)组成的葡萄糖引发的骨科植入物,用于促进糖尿病骨整合。在DIME中,植入物sostenuto上的GOx消耗葡萄糖产生H2O2,而从hauberk涂层中释放的Cu催化H2O2产生高度杀菌的•OH,通过光增强化学动力学疗法杀死致病菌。有趣的是,涂层的催化效率大大提高,周转数(TON)为0.284s-1。此外,由于Cu和促骨聚多巴胺涂层的存在,工程植入物表现出令人满意的细胞相容性并促进成骨性。RNA-seq分析显示,植入物能够对抗感染并抑制促炎表型(M1)。此外,在第4周和第8周利用感染的糖尿病大鼠骨缺损模型进行的体内评估证实,工程植入物通过消除病原体、抑制炎症和促进成骨显著提高了骨整合。总之,我们目前的研究提出了一种概念性的新策略,即为骨科植入物提供葡萄糖引发的抗菌和成骨能力,以治疗顽固性糖尿病骨整合。
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Glucose-primed PEEK orthopedic implants for antibacterial therapy and safeguarding diabetic osseointegration

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 H2O2, and Cu liberated from hauberk coating catalyzes the H2O2 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−1. 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.

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来源期刊
Biomaterials
Biomaterials 工程技术-材料科学:生物材料
CiteScore
26.00
自引率
2.90%
发文量
565
审稿时长
46 days
期刊介绍: Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.
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