A coenzyme-based "interface-welding" hydrogel coating for titanium implants promotes diabetic osseointegration by regulating mitochondrial dynamics.

The impaired bone healing and osseointegration in diabetes are largely driven by hyperglycemia-induced mitochondrial dysfunction in bone marrow mesenchymal stem cells (BMSCs). To rescue this cellular deficit and enhance bone repair, this study aimed to develop an adhesive, self-healing, mitochondrial coenzyme-based hydrogel coating for titanium (T) implants. We synthesized p(LA-AcAln) hydrogel through the copolymerization of α-lipoic acid (LA) and acrylated alendronate sodium (AcAln). This coating achieved robust "interface-welding" adhesion by forming a stable covalent "surface-S-S-gel" interface through dynamic thiol-disulfide exchange between the disulfide bonds (-S-S-) in p(LA) and the thiolated titanium surface. In vitro experiments demonstrated that the released LA monomers from the coating activate the Keap1/Nrf2 signaling pathway, suppress oxidative stress, restore the mitochondrial membrane potential of BMSCs, and significantly inhibit cell apoptosis in a hyperglycemic environment. Moreover, Ti/p(LA-AcAln) regulated mitochondrial dynamics by promoting fusion and inhibiting fission, thereby restoring ATP production and compensating for the energy deficit in bone formation. In vivo evaluations using a diabetic rat femoral defect model revealed that this coating can significantly improve bone osseointegration. This study not only developed a promising surface modification strategy for orthopedic implants but also provided a viable approach for the treatment of diabetic bone defects and mitochondrial-related orthopedic diseases.