Li Bin, Shu Rui, Dai Wenyu, Yang Fan, Xu Hui, Shi Xiuyuan, Li Yunfei, Bai Ding, Yang Weizhong, Deng Yi
College of Biomedical Engineering, School of Chemical Engineering, West China Hospital of Stomatology, State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, 610065, P. R. China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics and Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, 610065, P. R. China.
Small. 2022 Nov;18(45):e2203619. doi: 10.1002/smll.202203619. Epub 2022 Sep 9.
Diabetic infectious micromilieu (DIM) leads to a critical failure rate of osseointegration by virtue of two main peculiarities: high levels of topical glucose and inevitable infection. To tackle the daunting issue, a bioheterojunction-engineered orthopedic polyetheretherketone (PEEK) implant consisting of copper sulfide/graphene oxide (CuS/GO) bioheterojunctions (bioHJs) and glucose oxidase (GOx) is conceived and developed for DIM enhanced disinfection and boosted osseointegration. Under hyperglycemic micromilieu, GOx can convert surrounding glucose into hydrogen peroxide (H O ). Then, upon infectious micromilieu, the bioHJs enable the catalyzation of H O to highly germicidal hydroxyl radical (·OH). As a result, the engineered implants massacre pathogenic bacteria through DIM twin-engine powered photo-chemodynamic therapy in vitro and in vivo. In addition, the engineered implants considerably facilitate cell viability and osteogenic activity of osteoblasts under a hyperglycemic microenvironment via synergistic induction of copper ions (Cu ) and GO. In vivo studies using bone defect models of diabetic rats at 4 and 8 weeks further authenticate that bioHJ-engineering PEEK implants substantially elevate their osseointegration through biofilm elimination and vascularization, as well as macrophage reprogramming. Altogether, the present study puts forward a tactic that arms orthopedic implants with DIM twin-engine powered antibacterial and formidable osteogenic capacities for diabetic stalled osseointegration.
糖尿病感染微环境(DIM)由于两个主要特点导致骨整合的关键失败率:局部葡萄糖水平高和不可避免的感染。为了解决这一艰巨问题,构思并开发了一种由硫化铜/氧化石墨烯(CuS/GO)生物异质结(bioHJs)和葡萄糖氧化酶(GOx)组成的生物异质结工程化骨科聚醚醚酮(PEEK)植入物,用于DIM增强消毒和促进骨整合。在高血糖微环境下,GOx可将周围的葡萄糖转化为过氧化氢(H₂O₂)。然后,在感染性微环境中,生物异质结能够将H₂O₂催化为高杀菌性的羟基自由基(·OH)。结果,这种工程化植入物通过DIM双引擎驱动的光动力疗法在体外和体内杀灭病原菌。此外,通过铜离子(Cu²⁺)和GO的协同诱导,工程化植入物在高血糖微环境下显著促进成骨细胞的细胞活力和成骨活性。使用糖尿病大鼠骨缺损模型进行的4周和8周体内研究进一步证实,生物异质结工程化PEEK植入物通过消除生物膜和血管生成以及巨噬细胞重编程,显著提高了它们的骨整合能力。总之,本研究提出了一种策略,为骨科植入物配备DIM双引擎驱动的抗菌和强大的成骨能力,以解决糖尿病患者骨整合停滞的问题。