Kelulut Honey-Incorporated Hybrid Gelatin-PVA Hydrogel for Wound Healing: Fabrication and In Vitro Characterization

Hydrogels are attractive biomaterials for skin replacement and tissue regeneration, offering advantages over split-skin grafts for large or irregular wounds. Honey-containing hydrogels are of particular interest, combining honey's natural healing properties with the versatility of hydrogel matrices. This study aimed to develop a biocompatible, biodegradable, and mechanically stable hydrogel as a cutaneous substitute. To achieve this, different formulations were prepared using gelatin (GE), polyvinyl alcohol (PVA), and Kelulut honey (KH). The formulations were designated as: GE-PVA (6% (<i>w</i>/<i>v</i>) GE: 5% (<i>w</i>/<i>v</i>) PVA, without KH), GE-PVA-H1 (containing 1% (<i>v</i>/<i>v</i>) KH), GE-PVA-H5 (containing 5% (<i>v</i>/<i>v</i>) KH), and GE-PVA-H10 (containing 10% (<i>v</i>/<i>v</i>) KH). All formulations were crosslinked with 0.1% (<i>w</i>/<i>v</i>) genipin (GNP). GE-PVA-H1 and GE-PVA-H1-GNP showed swelling ratios of 110.18 ± 20.14% and 86.31 ± 14.27%, lower than GE-PVA-H5 (125.79 ± 23.76%), GE-PVA-H10 (132.79 ± 20.86%), and their crosslinked counterparts. All formulations had WVTR <1500 g/m^-2h^-1, with GE-PVA-H1-GNP at 501.21 ± 41.35 g/m^-2h^-1, GE-PVA-H5-GNP at 473.77 ± 44.10 g/m^-2h^-1, and GE-PVA-H10-GNP at 467.51 ± 73.59 g/m^-2h^-1. GE-PVA-H1-GNP exhibited the slowest biodegradation (0.0036 ± 0.0003 g/h vs. 0.0096-0.0206 g/h for other groups). Contact angle was lowest for GE-PVA-H1-GNP (38.46° ± 3.89°), confirming higher hydrophilicity compared with GE-PVA-H5/H10 groups. Resilience (98.85% ± 1.03%) and compression strength (77.42% ± 7.17%) of GE-PVA-H1-GNP were comparable to GE-PVA-H5-GNP and GE-PVA-H10-GNP. MTT assays confirmed cytocompatibility across all groups. Collectively, GE-PVA-H1-GNP emerged as the optimal formulation, combining mechanical stability, hydrophilicity, and biocompatibility for wound healing applications.