Hyaluronan oligosaccharides promote diabetic wound healing by increasing angiogenesis

Background: Hyaluronan (also known as hyaluronic acid) oligosaccharides (O-HA) can promote angiogenesis and wound healing; however, there are few reports on whether O-HA also plays a role in healing wounds of diabetic patients. Methods: In this study, we prepared a special ointment containing a mixture of hyaluronan fragments from 2 to 10 disaccharide units and investigated its effects on healing the wounds of diabetic rats. Results: We found that O-HA significantly increases proliferation, migration, and tube formation of endothelial cells under high glucose conditions, and topical administration of O-HA ointment promotes wound healing by increasing angiogenesis in the wounded area of the skin. The underlying mechanisms are that O-HA increases the phosphorylation of Src and ERK, and expression of TGF beta1, thereby increasing angiogenesis. Conclusions: This suggests that topical application of O-HA could be a useful method by which to treat diabetic wounds in clinical practice. (C) 2016 Published by Elsevier Sp. z o.o. on behalf of Institute of Pharmacology, Polish Academy of Sciences.