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

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Orthopedic Surgery

Background:

• Diabetes mellitus impairs bone healing and osseointegration due to hyperglycemia-induced mitochondrial dysfunction in bone marrow mesenchymal stem cells (BMSCs).
• Existing orthopedic implants face challenges in achieving successful osseointegration in diabetic patients.
• There is a need for advanced biomaterials that can actively promote bone repair in a diabetic environment.

Purpose of the Study:

• To develop an adhesive, self-healing, hydrogel coating for titanium implants incorporating a mitochondrial coenzyme to enhance bone repair in diabetes.
• To investigate the mechanism by which the hydrogel coating rescues cellular deficits and improves bone formation.
• To evaluate the efficacy of the modified implants in promoting osseointegration in a diabetic animal model.

Main Methods:

• Synthesized a p(LA-AcAln) hydrogel via copolymerization of α-lipoic acid (LA) and acrylated alendronate sodium (AcAln).
• Developed a robust covalent interface ('surface-S-S-gel') on titanium (Ti) implants through thiol-disulfide exchange.
• Conducted in vitro studies on BMSCs under hyperglycemic conditions and in vivo evaluations using a diabetic rat femoral defect model.

Main Results:

• The Ti/p(LA-AcAln) coating demonstrated strong adhesion and released LA monomers that activated the Keap1/Nrf2 pathway, reducing oxidative stress and BMSC apoptosis.
• The coating restored mitochondrial membrane potential and normalized mitochondrial dynamics (fusion/fission balance) in BMSCs, enhancing ATP production.
• In vivo studies showed significantly improved osseointegration of the modified implants in diabetic rats.

Conclusions:

• The developed self-healing hydrogel coating effectively rescues mitochondrial dysfunction in BMSCs under hyperglycemic conditions.
• This surface modification strategy enhances bone formation and osseointegration for orthopedic implants in a diabetic setting.
• The study presents a promising approach for treating diabetic bone defects and related orthopedic conditions.