Injectable photo-crosslinked hyaluronic acid/carboxymethyl cellulose hydrogel for the sustained delivery of rhFGF2 and accelerated wound healing

This study developed a photo-crosslinkable injectable hydrogel combining hyaluronic acid-catechol (HAC) and carboxymethylcellulose-methacrylate (CMCAM) as an advanced wound dressing. HAC and CMCAM were functionalized using carbodiimide reaction. The hydrogels were formed via photopolymerization of HAC and CMCAM, using crosslinkers and a photo-initiator under 365 nm UV light. A Box-Behnken design optimized the constituent concentrations including, HAC (0.5-1% w/v), CMCAM (0.5-1% w/v), and polyethylene glycol diacrylate (PEGDA, 0-1% w/v), with fixed N,N'-methylenebis(acrylamide) (MBA, 5.0% w/v), and a photo-initiator (0.01% w/v). The mechanical properties, water content, water absorption, %erosion, and water vapor transmission rate of the hydrogels were examined. Cytocompatibility and drug release characteristics were confirmed using FTIC-BSA as a model drug. Furthermore, the hydrogel was infused with recombinant human fibroblast growth factor 2 (rhFGF2) to assess the migratory, proliferation effect, and in vivo cutaneous wound healing. The optimized formulation (HAC:CMCAM:PEGDA at 0.94:1.00:0.19 w/v) exhibited promising tensile strength, high water absorption, minimal erosion. Encapsulation efficiency was high and protein release was sustained. Incorporation of rhFGF2 into the optimized hydrogel significantly enhanced cell proliferation, migration, and wound healing effect. In conclusion, rhFGF2-loaded HAC/CMCAM hydrogel was successfully engineered with promising mechanical and biological properties, demonstrating its efficacy as an advanced biomaterial for enhanced wound regeneration.