In Situ Regulation Of Macrophage Polarization To Enhance Osseointegration Under Diabetic Conditions Using Injectable Silk/Sitagliptin Gel Scaffolds

As a chronic inflammatory disease, diabetes mellitus creates a proinflammatory microenvironment around implants, resulting in a high rate of implant loosening or failure in osteological therapies. In this study, macroporous silk gel scaffolds are injected to the bone-implant interface for in situ release of sitagliptin that can regulate macrophage response to create a prohealing microenvironment in diabetes mellitus disease. Notably, it is discovered for the first time that sitagliptin-induced macrophage polarization to the M2 phenotype and alleviated the impaired behaviors of osteoblasts on titanium (Ti) implants under diabetic conditions in a dose-dependent manner. The silk gel scaffolds loaded with sitagliptin elicite a stronger recruitment of M2 macrophages to the sites of Ti implants and a significant promotion of osteointegration, as compared to oral sitagliptin administration. The results suggest that injectable silk/sitagliptin gel scaffolds can be utilized to modulate the immune responses at the bone-implant interface, thus enhancing bone regeneration requires for successful implantation of orthopedic and dental devices in diabetic patients.