Chitooligosaccharides promote healing of diabetic wounds through mediating proliferation and migration of fibroblasts

Diabetic wound is difficult for healing due to disrupted cell repairing function and reduced angiogenesis, along with susceptibility to infection. Fibroblasts are crucial for wound healing by producing extracellular matrix (ECM) components and several growth factors, which are inhibited in the subjects of diabetic wounds. Chitooligosaccharides (COS), the intermediate products of chitosan degradation, are found efficient in promoting tissue repair, but less is known about their roles on diabetic wound healing. By treatment of mice diabetic wounds model, COS showed robust bioactivity in accelerating wound healing through promoting proliferation and migration of fibroblasts. COS also increased deposition of collagen III and angiogenesis at wound sites. Meanwhile, the oligosaccharides attenuated inflammatory activation by control of leukocyte infiltration and bacterial infection. Mechanistically, COS mediated cell events of fibroblasts through regulation of PI3K/Akt signaling pathway. The results have provided new bioactive material for chronic wound healing.