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

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.