Interpenetrating gelatin/sodium alginate hydrogel with controlled PRP lysate delivery for accelerating diabetic wound healing with reduced scarring

Abstract

Hyperglycemia induced growth factor deficiency in diabetic wounds confines the wound healing process to chronic inflammation and impairs effective healing. Platelet rich plasma lysate (PL) biomolecules (growth factors and cytokines) have shown efficacy in triggering effective wound healing signals in diabetic wounds. However, PL injection at the wound site causes early degradation of the biomolecules by the wound enzymes, underlining the necessity of a controlled biomaterial based delivery platform. In this study, an interpenetrating polymer network (IPN) hydrogel composed of natural polymers, gelatin, and sodium alginate (Gel/SA) was introduced to overcome the limitations of natural polymers and as a delivery medium for PL. The IPN was developed through simultaneous covalent crosslinking of gelatin and ionic crosslinking of sodium alginate, forming a dense network. The Gel/SA IPN hydrogel provides accessible favorable functional groups of the polymers which offer better swelling, water retention and more controlled diffusion dominated PL delivery than the conventional Gel/SA hydrogels. The Gel/SA IPN hydrogel exhibited the required wound dressing properties, such as swelling properties, gel fraction (80%), water retention capacity, water vapor transmission rate, hemolysis, blood clotting, and antibacterial properties. The ATR-FTIR spectra confirmed successful IPN formation, which provided controlled network degradation, offered the sustained release (70%) of PL, and optimized their susceptibility to wound enzymes. The results showed that the Gel/SA@PL hydrogel provided effective blood clotting and wound healing properties with enhanced growth factor mediated hemostasis, re-epithelialization, adipocyte formation to regulate granulation tissue formation, uniform collagen deposition, and minimal scar formation in the diabetic wound model.