Progress in Composite Hydrogels Enriched with Metformin for Bone Repair and Regeneration

The clinical repair of severe bone defects caused by trauma, tumor, infection, or systemic conditions such as osteoporosis and diabetes remains a major challenge in surgical treatment. It is one of the significant challenges in modern medicine. Although bone tissue possesses specific self-repair capabilities, artificial bone substitutes are still necessary for defects that exceed its self-repair capacity. Tissue engineering-related bone repair materials that mimic the structure, mechanics, and biological characteristics of natural bone have been widely applied to repair bone defects. Hydrogels loaded with drug molecules, as an ideal biomaterial for bone tissue engineering, are gradually gaining attention from researchers. Metformin(MET), a small-molecule biguanide compound extracted from French lilac, exhibits multiple bioactive properties, including osteogenesis promotion, anti-inflammatory effects, and anti-aging potential. This drug molecule shows broad application prospects, particularly in the field of artificial bone, where its localized application potential has attracted significant attention. This review summarizes the research progress on MET-loaded hydrogels in bone tissue engineering, focusing on the biological effects of MET, preparation strategies for hydrogels, the binding mechanisms between MET and hydrogels, and their potential applications in bone tissue repair. It provides theoretical foundations for designing biosafe biomimetic bone replacement materials and advancing their development and clinical translation.