o-HA Accelerates Skin Wound Healing in Mice by Enhancing Fibroblast Proliferation and Antioxidant Capacity

In recent years, various biomaterials based on hyaluronic acid (HA) have shown considerable promise for tissue repair, with their efficacy influenced by molecular weight. In this study, HA was enzymatically digested using hyaluronidase (HAase) to generate hyaluronic acid oligosaccharides (o-HA) with defined molecular weights. After determining the exact molecular weights, we evaluated the effects of HA fragments ranging from 40 to 2.8 kDa on 3T3 and L929 cells. The results indicated that HA3 (9.9 kDa) promoted the proliferation and migration of 3T3 cells, while HA4 (4.1 kDa) had the same effect on L929 cells. Both fragments alleviated oxidative damage induced by UVB irradiation. Furthermore, an animal wound model was used to verify the impact of o-HA in the 9.9–4.1 kDa range on wound healing. We found that o-HA within this molecular weight range significantly enhanced epithelial regeneration and collagen deposition in C57 mice. Western blot analysis indicated that after o-HA treatment, the expression levels of skin healing-related proteins, namely Collagen I, TGF-β1, and VEGFA, were elevated in the wounds of C57 mice, an effect associated with activation of the PI3K cell signaling pathway.