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

IF 12.8 1区 医学 Q1 ENGINEERING, BIOMEDICAL
Hongxing Shi , Hao Yang , Chao Wu , Song Wang , Shuai He , Lin Chen , Yau Kei Chan , Shuangquan Lai , Kunneng Liang , Yi Deng
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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 H2O2, 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.
葡萄糖触发的no进化涂层赋予骨科植入物增强抗菌和血管扩张,以保护糖尿病骨整合
糖尿病(diabetes mellitus, DM)是一种常见的慢性代谢性疾病,其特点是种植体周围存在高血糖微环境,导致种植体严重失败,种植体周围炎、血管扩张障碍等并发症发生率高。为了解决这个问题,我们设计并开发了一种葡萄糖解锁的no进化骨科植入物,该植入物由聚醚醚酮(PEEK)、葡萄糖氧化酶(GOx)和l-精氨酸(Arg)组成,具有增强血管生成的功能,以促进糖尿病骨整合。在高血糖生态位时,植入物上的GOx催化将葡萄糖排出为H2O2, H2O2立即与Arg反应,原位释放一氧化氮(NO),从而增强PEEK植入物周围的血管生成和血管扩张。此外,工程种植体对革兰氏阳性菌和革兰氏阴性菌均表现出良好的抗菌性能,并在细胞增殖、碱性磷酸酶活性和钙基质矿化方面增强成骨细胞的成骨性。有趣的是,利用大鼠糖尿病感染性骨缺损模型的体内评估进一步证实,工程植入物通过抑制病原体、抗炎和促进血管扩张,在第4周和第8周显著增强骨重塑和骨整合。总之,这项工作提出了一种新的策略来治疗停滞的糖尿病骨整合与高血糖微环境反应性治疗气体进化骨科植入物。
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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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