Bioactive Hydrogel for Regenerative Wound Healing: Evaluating Angiogenesis and Toxicity

Scar-free wound healing remains a major challenge in regenerative medicine. In this study, a carboxymethyl cellulose (CMC)-based hydrogel nanocomposite containing silver nanoparticles (CMC@Ag) was developed, along with a phytocompound-enriched variant (CMC@Ag+P) incorporating aloe vera, curcumin, and plantain peel extracts. The phytocompound-infused hydrogel exhibited enhanced antibacterial activity, biocompatibility, and scar-free healing potential, supporting tissue regeneration. An in vitro scratch assay using the A375 cell line showed 89% cell proliferation and migration at high doses and 69% at low doses of CMC@Ag+P. Zebrafish toxicity assays confirmed its safety, with hatchability rates of 82% (low dose) and 71% (high dose). The chorioallantoic membrane (CAM) assay demonstrated strong angiogenic activity, particularly in CMC@ Ag+P, indicating improved vascularization essential for tissue repair. Statistical analysis using the Student’s t-test revealed significant differences between hydrogel-treated groups and controls (p < 0.05), confirming the enhanced healing and scar-minimization effects. Previous animal studies further validated the scar-free wound healing potential of these hydrogel highlighting the synergistic role of phytocompounds in promoting effective tissue regeneration.