Biomaterials for diabetic bone repair: Influencing mechanisms, multi-aspect progress and future prospects

Disturbed glucose metabolism in diabetes mellitus (DM) patients affects bone metabolism and its microenvironment, which significantly impaired bone regeneration, making bone defect repair in DM patients a big challenge. Although autologous and allogeneic bone grafts are common therapeutic approaches, they do not achieve the desired therapeutic outcome, especially when targeting the complex pathologic microenvironment at the lesion site in DM patients. Therefore, various biomaterials have been developed to facilitate DM bone repair. With advances in bone tissue engineering, the focus of the study has transitioned from biologically inert to bioactive biomaterials. However, due to the lack of a comprehensive understanding of the pathologic microenvironment of diabetic bone defects, many biomaterials have not achieved satisfactory therapeutic results. Here, the mechanisms by which the pathological microenvironment affects bone regeneration are dissected. Then, recent advances in biomaterial therapeutic strategies based on these pathological microenvironments are comprehensively reviewed from seven aspects. Finally, current limitations that still need to be addressed are discussed, and feasible strategies for improvement and perspectives are presented. This review will certainly spark new ideas to develop more high-performance versatile biomaterials to improve the repair of bone defects under pathological conditions.