Biological Characterization of Mupirocin–KGF Hydrogel and Its Regenerative Potential in Human Fibroblast-Mediated Wound Healing

This study presents a novel hydrogel formulation combining mupirocin, a broad-spectrum antibiotic, with keratinocyte growth factor (KGF) to enhance wound healing through antibacterial action and tissue regeneration. Mupirocin was encapsulated in hydroxypropyl β-cyclodextrin (HP-β-CD) and stabilized with poly(amidoamine) dendrimers (PAMAM). Molecular docking studies assessed mupirocin's binding to PAMAM and its interaction with isoleucyl-tRNA synthetase. Physicochemical properties-including zeta potential, particle size, and surface tension-were characterized, and drug release kinetics were evaluated using Franz diffusion cells. In vitro assays on human dermal fibroblasts (HS27) included proliferation, scratch wound healing, and flow cytometry to assess cellular behavior. Antibacterial efficacy was determined via the Kirby-Bauer disk diffusion method. Results showed strong binding of mupirocin to its target enzyme, enhanced by KGF. The hydrogel exhibited favorable properties: surface tension of 24.7 dyne/cm, zeta potential of -24.79 mV, and particle size of ~119 nm, indicating high stability. Franz diffusion revealed sustained drug release compared to commercial mupirocin. Cellular assays demonstrated significant fibroblast migration and proliferation, with flow cytometry confirming increased wound healing markers. The formulation showed potent antimicrobial activity, including against Methicillin-resistant Staphylococcus aureus (MRSA), highlighting its promise for infected wound treatment and advanced clinical wound care.