State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
School of Chemical Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China.
Adv Sci (Weinh). 2021 Oct;8(20):e2101778. doi: 10.1002/advs.202101778. Epub 2021 Aug 16.
As a chronic metabolic disease, diabetes mellitus (DM) creates a hyperglycemic micromilieu around implants, resulting inthe high complication and failure rate of implantation because of mitochondrial dysfunction in hyperglycemia. To address the daunting issue, the authors innovatively devised and developed mitochondria-targeted orthopedic implants consisted of nutrient element coatings and polyetheretherketone (PEEK). Dual nutrient elements, in the modality of ZnO and Sr(OH) , are assembled onto the sulfonated PEEK surface (Zn&Sr-SPEEK). The results indicate the synergistic liberation of Zn and Sr from coating massacres pathogenic bacteria and dramatically facilitates cyto-activity of osteoblasts upon the hyperglycemic niche. Intriguingly, Zn&Sr-SPEEK implants are demonstrated to have a robust ability to recuperate hyperglycemia-induced mitochondrial dynamic disequilibrium and dysfunction by means of Dynamin-related protein 1 (Drp1) gene down-regulation, mitochondrial membrane potential (MMP) resurgence, and reactive oxygen species (ROS) elimination, ultimately enhancing osteogenicity of osteoblasts. In vivo evaluations utilizing diabetic rat femoral/tibia defect model at 4 and 8 weeks further confirm that nutrient element coatings substantially augment bone remodeling and osseointegration. Altogether, this study not only reveals the importance of Zn and Sr modulation on mitochondrial dynamics that contributes to bone formation and osseointegration, but also provides a novel orthopedic implant for diabetic patients with mitochondrial modulation capability.
作为一种慢性代谢性疾病,糖尿病(DM)在植入物周围创造了一个高血糖微环境,导致由于高血糖引起的线粒体功能障碍,植入物的并发症和失败率很高。为了解决这个令人畏惧的问题,作者创新性地设计并开发了一种基于线粒体靶向的骨科植入物,由营养元素涂层和聚醚醚酮(PEEK)组成。两种营养元素,以 ZnO 和 Sr(OH)2 的形式,被组装到磺化 PEEK 表面(Zn&Sr-SPEEK)上。结果表明,涂层协同释放 Zn 和 Sr 可以杀死致病菌,并显著促进高血糖微环境下成骨细胞的细胞活性。有趣的是,Zn&Sr-SPEEK 植入物被证明具有强大的能力,可以通过下调 Dynamin-related protein 1 (Drp1) 基因、恢复线粒体膜电位 (MMP) 和消除活性氧 (ROS),来恢复高血糖诱导的线粒体动态失衡和功能障碍,最终增强成骨细胞的成骨能力。在 4 周和 8 周的糖尿病大鼠股骨/胫骨缺损模型的体内评估进一步证实,营养元素涂层可以显著促进骨重塑和骨整合。总的来说,这项研究不仅揭示了 Zn 和 Sr 对线粒体动力学的调节在骨形成和骨整合中的重要性,而且为具有线粒体调节能力的糖尿病患者提供了一种新型骨科植入物。