Nutrient Element Decorated Polyetheretherketone Implants Steer Mitochondrial Dynamics for Boosted Diabetic Osseointegration
Hao Wang, Xinliang Fu, Jiacheng Shi, Limei Li, Jiyu Sun, Xidan Zhang, Qiuyang Han, Yi Deng, Xueqi Gan
Abstract
Abstract 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) 2 , are assembled onto the sulfonated PEEK surface (Zn&Sr‐SPEEK). The results indicate the synergistic liberation of Zn 2+ and Sr 2+ 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 2+ and Sr 2+ 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.