The Role of a Multifunctional Polysaccharide-Based Hydrogel with Biofunctionalized Hyaluronic Acid and Asiaticoside-Loaded Niosomes in Wound Healing.

Abstract

Advanced wound dressings that modulate the wound microenvironment, enable sustained therapeutic delivery, and limit pathological scarring remain an ongoing challenge in regenerative medicine. A multifunctional nanocomposite hydrogel was prepared using iota and lambda carrageenan followed by ionic crosslinking with CaCl2. This hydrogel was further functionalized with hyaluronic acid grafted with l-arginine (HA-Arg) for enhanced cellular response. Niosomes packed with asiaticoside were additionally incorporated into the hydrogel to provide therapeutic biochemical signaling at the nanoscale. The niosomes formed showed nanometric size (±160 nm), low polydispersity (0.30 ± 0.04), stable negative surface charge, high encapsulation efficiency (up to 82%), and sustained release of loaded drugs for 72 h. As determined by various structural and physicochemical characterizations, stable hydrogel formation with favorable porous architecture, swelling behavior, thermal stability, and homogeneous distribution of nanovesicles was well established. The hydrogel, which was studied in vitro, exhibited excellent biocompatibility, hemocompatibility, and enhanced cell-material interactions. The in vivo niosome-loaded formulation shows about 80% closure of wounds on day 14 compared with 70% in controls. Histopathological analysis revealed a trend toward less inflammation, more blood vessels, more fibroblasts, and better organization of collagen formation, indicating the potential for advanced wound care products.