The dual-effects of PLGA@MT electrospun nanofiber coatings on promoting osteogenesis at the titanium–bone interface under diabetic conditions

The high failure risk of endosseous titanium implants under diabetes conditions appeals to strengthen the osteointegration on the titanium-bone (Ti-B) interface. Melatonin (MT) is a neurohormone involved in bone homeostasis, which can promote osteogenesis and inhibit ROS overproduction through multiple pathways, but its effects on the Ti-B interface in diabetes remain elusive. The biodegradable poly(lactic-co-glycolic acid) (PLGA) has excellent controlled and sustained release properties, low cytotoxicity, and biocompatibility. Our study fabricated a nanofiber in which MT was encapsulated in PLGA to generate a nanofiber coating on a polydopamine (PDA)-modified titanium surface using electrospinning technology. The surface characteristic showed that MT was fully encapsulated in the PLGA carrier, and PLGA@MT was strongly coupled to the titanium matrix. Furthermore, the PLGA@MT-Ti nanofiber could release MT for at least 30 days. In vitro cellular tests demonstrated that PLGA@MT-Ti directly stimulates osteogenesis on the Ti-B interface by activating the BMP-4/WNT pathway in a dose-dependent manner. The effect of suppressing diabetes-induced ROS overproduction and promoting cell proliferation was not proportional to the content of MT. In vivo experiments revealed that PLGA@MT-Ti screws promoted the bone formation and osteointegration in type 1 diabetes mellitus (T1DM) mice with tibial bone defects. Our findings demonstrate that PLGA@MT-Ti exerted dual effects through activating the BMP-4/WNT pathway and attenuating ROS overproduction to promote osteogenesis and osteointegration at the Ti-B interface, providing a novel strategy to fabricate biomaterial modification and biofunctionalization under diabetic conditions.