Carbon dots efficiently promote vascularization for enhanced repairing of orthopedic diseases with diabetic mellitus based on nanocatalytic medicine

Abstract

Insufficient angiogenesis, a prominent characteristic of diabetic mellitus, significantly affected the reparative capacity of orthopedic diseases. Imbalanced redox caused by excessive reactive oxygen species is one of the crucial factors in weakening vascularization. Conditions such as implant osseointegration failure and delayed wound healing in orthopedic diseases are significantly influenced by the vascularization deficits in diabetic mellitus. Promoting angiogenesis by modulating endothelial function is considered as an effective therapy for diabetes, yet current efforts remain insufficient. Nanocatalytic medicine has emerged as promising candidates for therapy. Herein, carbon dots (CDs) with preferable catalytic effect by mimicking both superoxide dismutase (SOD) and catalase (CAT)-like activity were designed and synthesized using anhydrous citric acid and ethane diamine. CDs effectively scavenged superoxide anion (O2•−) and hydrogen peroxide (H2O2) with excellent biocompatibility. Meanwhile, CDs promoted the proliferation, migration, and angiogenesis capacity of human umbilical vein endothelial cells with enhanced SOD and CAT activity in simulated oxidative stress of diabetes. Notably, CDs promoted vascularization by activate PI3K-AKT signaling pathway in impaired endothelial cells, which was demonstrated through transcriptome sequencing, western blot, and reverse transcription-polymerase chain reaction. The therapeutic effect of CDs based on promoting vascularization was found in orthopedic disease models of subcutaneous implant and wound healing of diabetic rat. These findings highlight a promising clinical application for CDs as a nanocatalytic medicine in enhancing vascularization for diabetic mellitus.