Abstract

Background: Chronic wounds represent a significant clinical challenge due to impaired healing and persistent inflammation. Bioactive scaffolds made from natural polymers combined with the hydroalcoholic extract of Buddleja globosa have emerged as promising alternatives for promoting effective tissue regeneration. Methods: A biocomposite scaffold composed of gelatin, chitosan, and hyaluronic acid, incorporating B. globosa extract, was fabricated. The material was evaluated for its physicochemical properties, biocompatibility with human neonatal dermal fibroblasts, and regenerative capacity in a chronic ischemic wound model in aged rats. Results: The composite exhibited a uniform, porous structure with an average pore size of approximately 200 mu m and a high swelling capacity (>3000%) while preserving viscoelasticity with slight mechanical softening, thereby supporting optimal conditions for cell infiltration and exudate retention. The scaffold supported fibroblasts' adhesion and proliferation, showing good biocompatibility. Formulations containing 0.04 and 0.08 mg/mL B. globosa extract significantly increased fibroblast viability at 14 days. Additionally, fibroblasts cultured on the biocomposite showed elevated secretion of proangiogenic vascular endothelial growth factor (VEGF) and CXC motif chemokine ligand 12 (CXCL12), compared to fibroblast monolayer cultures. In vivo, histological analysis revealed enhanced vascularization and reduced epithelial hyperplasia in wounds treated with the biocomposite, suggesting better tissue organization and maturation. Conclusion: Incorporating B. globosa extract into a gelatin-chitosan-hyaluronic acid scaffold offers bioactive properties that support angiogenesis and skin tissue regeneration. These results highlight the biocomposite's potential as a multifunctional biomaterial with translational relevance for chronic wound therapy.