Multifunctional alginate/polydeoxyribonucleotide hydrogels for promoting diabetic wound healing

A multifunctional alginate/PDRN hydrogel system by ionic crosslinking and the Schiff base reaction between oxidized alginate (OA) and PDRN was developed in the present study. Biocompatibility assessment of the PDRNloaded OA hydrogels showed a significant enhancement in cell viability in human dermal fibroblast (HDF) cells. In addition, hydrogels showed migratory, anti-inflammatory, intracellular reactive oxygen species scavenging, and anti-apoptotic activities. In vivo studies using a streptozotocin-induced diabetic Wister rat model indicated that OA-4PDRN had the highest percentage of wound closure (96.1 +/- 2.6 %) at day 14 compared to the control (79.0 +/- 2.3 %) group. This was accompanied by up-regulation of vascular endothelial growth factor (VEGF), interleukin-10 (IL-10), and transforming growth factor-beta (TGF-beta) accompanied by down-regulation of proinflammatory markers (IL-6, IL-1 beta). Following histopathological observations, PDRN-loaded OA hydrogel ensured tissue safety and induced wound healing with granular tissue formation, collagen deposition, reepithelialization, and regeneration of blood vessels and hair follicles. The downregulation of inflammatory cytokines (CD68) and expression of angiogenesis-related cytokines (CD31) in wound sites revealed the suppression of inflammation and increased angiogenesis, ensuring skin tissue regeneration in diabetic wound healing. In conclusion, the findings suggest that PDRN-loaded OA hydrogel has enormous therapeutic potential as a diabetic wound dressing.