Injectable Chitosan‐Platelet‐Rich Plasma Hybrid Biomaterial Improves Skin Wound Healing in Diabetic Rats

ABSTRACT Diabetic foot ulcers are chronic wounds with poor healing outcomes, partly due to protease‐rich microenvironments that degrade regenerative cues. In this 28‐day study, a hybrid biomaterial combining fresh leukocyte‐rich platelet‐rich plasma with freeze‐dried chitosan (CS‐PRP) is used to treat full‐thickness skin excisional wounds in streptozotocin‐induced diabetic rats. CS‐PRP coagulates rapidly and chitosan remains detectable in the wound bed up to Day 28. Compared to control, CS‐PRP significantly accelerates wound closure throughout the study, including at Day 7 (52% vs. 37%, p < 0.001), with a more complete epidermal restoration. In addition, histological scoring reveals higher tissue quality in treated wounds at Day 28 (14.8±0.4 vs. 13.7±0.8, p < 0.01), with improved dermal reorganization. CS‐PRP enhances collagen deposition compared to control (59% vs. 24%, p < 0.001) and maturation while sustaining higher vascular density relative to native skin in all treated animals (1.1 to 3.1‐fold, p < 0.01) at Day 28. CS‐PRP supports diabetic wound healing across multiple tissue compartments. Indentation‐based mapping generates detailed spatial profiles of skin thickness and elasticity, which clearly highlight wound‐induced mechanical disruption but reveal no significant treatment‐related improvement. The simplicity, injectability, and biological activity of CS‐PRP position this product as a promising approach to enhance wound healing in diabetic skin.