Enhanced wound healing in diabetic mice by hyaluronan/chitosan multilayer-coated PLLA nanofibrous mats with sustained release of insulin

The healing of wounds in diabetes mellitus patients remains a critical clinical challenge globally. To promote healing, the development of bioactive dressings that not only provide physical protection but also supply a favorable microenvironment for healing at the wound interface is urgently required. Herein, Michael addition reaction was first used for intrinsic-crosslinking of bioactive maleilated chitosan/thiolated hyaluronan (mCH/tHA) multilayer coatings on poly (L-lactic acid) (PLLA) nanofibrous mats (P-mCH/tHA) for a sustained release of insulin (IN) and compared that with pure PLLA and PLLA mats coated with native CH/HA (P-CH/HA) multilayers. The physicochemical studies showed that P-mCH/tHA have higher tensile strength, an accelerated degradation rate, more antibacterial activity and sustained release of insulin when compared to P-CH/HA and pure PLLA mats. Studies on bioactive properties of PLLA mats coated with either mCH/tHA or CH/HA indicated an improved adhesion, spreading and proliferation of mesenchymal stem cells on P-mCH/tHA_IN in comparison to the other PLLA mats. Most interestingly, in vivo investigations with a diabetes mouse model demonstrated fastest wound closure when using P-mCH/tHA_IN among all groups with facilitated re-epithelization, angiogenesis, and increased collagen deposition in the wounds, which makes this coating in combination with IN promising for development of new bioactive wound dressings.