Self-Integrating Multifunctional Amyloidogenic Protein–Fenugreek Composite Hydrogel Patch and Ointment for Accelerated Deep Muscle Wound Healing in Rabbit Model

Deep muscle wound healing presents significant clinical challenges due to the complex architecture of tissues, high susceptibility to infection, and often prolonged regenerative processes, particularly following trauma or surgical interventions. To overcome limitations associated with conventional dressings such as poor adherence, mechanical weakness, and frequent replacements, we developed a self-adhering multifunctional composite hydrogel system integrating amyloidogenic bovine serum albumin (BSA) fibrils with fenugreek seed extract (FE). The hydrogel was engineered in two topical formulations: a mechanically robust patch and a spreadable ointment. This multifunctional platform combines the structural integrity and biocompatibility of amyloid fibrils with the bioactive antioxidant, anti-inflammatory, and antimicrobial properties of fenugreek phytochemicals. Comprehensive physicochemical characterization confirmed successful hydrogelation with porous microstructures (50-200 μm) conducive to cellular infiltration and moisture retention. FTIR and rheological analyses revealed significant intermolecular interactions and tunable viscoelastic solid-like behavior. The patch demonstrated superior mechanical strength and adhesion, whereas the ointment offered facile application to irregular wound contours. Both formulations exhibited approximately 87% free radical scavenging capacity, potent antibacterial efficacy against <i>Escherichia coli</i> and <i>Bacillus subtilis</i>, and excellent biocompatibility with >95% viability of human embryonic kidney (HEK) cells. In a rabbit full-thickness muscle wound model, both treatments accelerated wound closure, achieving complete epithelialization by day 21, with minimal fibrosis and well-organized collagen regeneration. Importantly, the patch's self-adhering property obviated the need for secondary dressings. This study introduces a promising therapeutic hydrogel system with potential for clinical translation in managing complex musculoskeletal wounds.