Xiangdong Liu, Zijun Chen, Liu Yang, Wei Ma, Yiwen Liu, Yingliang Song, Mingchao Ding, Lei Tian, Mingkai Li
People with diabetes often have a high rate of oral implant failure and unstable long-term treatment effects. It is urgent to find the potential mechanisms and effective cure methods to address the increasing demand for dental restoration in recent years. This paper aims to find an influential factor, and a probable treatment resulting from it, to improve poor osseointegration and achieve favorable bone regeneration. To find out the influential factor of poor diabetic osseointegration, we compared marginal bone loss among patients taking different hypoglycemic drugs. To verify our pre-clinical findings, we performed in vitro experiments as well as micro-CT, fluorescence intensity, and histopathological analysis methods after establishing a diabetic rat model controlled by different systemic hypoglycemic drugs. To enhance implant osseointegration and find out the underlying mechanism, we proposed the GelMA-alogliptin hydrogel system and tested the scratch wound healing, cell adhesion, CCK-8, live-dead cell staining, osteogenesis, qPCR, and Western blot methods based on diabetic rat-derived BMSCs, HUVECs and BMMS, as well as the in vivo experiments in diabetic rats. People with diabetes under DPP4i (alogliptin) exhibit the lowest marginal bone loss. The systemic alogliptin and locally delivered peri-implant GelMA-alogliptin hydrogel treatment promoted bone regeneration around diabetic implants, enhanced diabetic-derived BMSC activity and migration through GLP1R/GSK3β/β-catenin and induced osteogenic differentiation, and promoted vascular regeneration and inflammation control. Alogliptin has positive effects on the oral implant health of people with diabetes. A locally delivered GelMA-alogliptin hydrogel system exhibits competitive ability to improve diabetic bone microenvironment and enhance implant osseointegration.