Rapid gelation of oxidized hyaluronic acid and succinyl chitosan for integration with insulin-loaded micelles and epidermal growth factor on diabetic wound healing

Abstract

In this work, poly(ethylene glycol)-b-poly[3-acrylamidophenylboronic acid-co-styrene] (PEG-b-P(PBA-co-St) has been firstly synthesized for loading of insulin to form insulin-loaded micelles. Insulin-loaded micelles (ILM) and epidermal growth factor (EGF) are further embedded into the composite hydrogels that can be rapidly gelled by mixing of oxidized hyaluronic acid (OHA) and succinyl chitosan (SCS). Then, the morphology, rheology, degradation, swelling and cytotoxicity properties of the as-prepared composite hydrogels are further investigated to evaluate their physical properties and biocompatibility of as the wound dressing. The as-prepared composite hydrogels show the excellent cell compatibility and low toxicity. To evaluate the wound healing ability of as-prepared composite hydrogels, the tests of wound healing in vivo are conducted on streptozotocin-induced rat models. And the as-prepared composite hydrogels with ILM and EGF show an excellent wound healing performance for promotion of fibroblast proliferation and tissue internal structure integrity, as well as the deposition of collagen and myofibrils. These results suggest that the as-prepared composite hydrogels with loading of ILM and EGF could be a promising candidate for wound healing applications.

Keywords: Diabetic rats; Epidermal growth factor; Hydrogel; Insulin; Rapid gelation; Wound healing.