Hyaluronic acid sustains platelet stability with prolonged growth factor release and accelerates wound healing by enhancing proliferation and collagen deposition in diabetic mice

Abstract

Platelet Rich Plasma (PRP) has gained significant attention in diabetic wound management due to the presence of growth factors. However, its short self-life ex vivo limits its clinical use. Among the biopolymers hyaluronic acid (HA), offers higher biocompatibity with bioactivity and ideal polymer properties for delivery of the cell based products. Hence, here HA gel matrix was prepared to hold PRP to prolong the growth factor stability. PRP prepared from healthy donors was used after characterizing total platelets (3.0 ± 0.17 × 106 cells/mL) and PDGF-BB levels (156.37 ± 1.73 ng/mL). This was subsequently entrapped in1:3 ratios of PRP:HA gel. The prepared gels were stored at different conditions to study growth factor stability. The prepared gels showed near neutral pH (6.99) with shear thickening properties. On the 15th day of storage at −20 °C temperature, the PDGF-BB levels in the PRP stored directly reduced by 35.98% while HA-PRP gels it reduced by 20.91%. Considerably higher cell proliferation (43.11%) and migration (85%) were observed on treatment with gels stored at −20 °C for 15 days compared to the PRP stored directly. Topical application of the gels on diabetic mice showed complete wound contraction by 15th day compared to untreated groups. Enhanced collagen and cytokeratin 10 depositions were observed owing to the synergistic effect of the polymer protein combination. These results are suggestive of HA-PRP gels as topical applicants for treating diabetic wounds and using PRP into a mainstream treatment strategy in clinical practices.