Protein-based materials such as human serum albumin (HSA) have demonstrated significant potential for the development of novel wound management materials. For the first time, the formation of HSA-based hydrogels was proposed using a combination of thermal- and ethanol-induced approaches. The combination of phosphate-buffered saline (PBS) and limited (up to 20% v/v) ethanol content offers a promising strategy for fabricating human serum albumin-based hydrogels with tunable properties. The hydrogel formation was studied using in situ dynamic light scattering (DLS) for qualitative and semi-quantitative analysis of the patterns of protein hydrogel formation through thermally induced gelation. The rheological properties of human serum albumin-based hydrogels were investigated. Hydrogels synthesized via thermally induced gelation using a denaturing agent exhibit a dynamic viscosity ranging from 100 to 10,000 mPa·s. The biocompatibility, biodegradability, and structural stability of human serum albumin-based hydrogels were comprehensively evaluated in physiologically relevant media. These human serum albumin-based hydrogels represent a promising platform for developing topical therapeutic agents for wound management and tissue engineering applications. This study investigated the kinetics of tetracycline release from human serum albumin-based hydrogels in PBS and fetal bovine serum (FBS). All tested formulations of HSA-based hydrogels loaded with tetracycline (1 mg/mL) demonstrated antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, and Corynebacterium striatum strains.

The global proliferation of multidrug-resistant Pseudomonas aeruginosa stimulates the search for alternatives to conventional therapy. This study developed human serum albumin (HSA)-based hydrogels for the delivery of bacteriophage PA57. Matrices were fabricated via combined thermal- and ethanol-induced gelation. The release kinetic was dependent on protein concentration: 20% (w/v) HSA provided sustained release over 48 h, whereas 10–15% (w/v) HSA exhibited burst release effects. Combined systems effectively suppressed P. aeruginosa growth in vitro during the early and middle stages of incubation, maintaining low culture optical density for up to 28 h. Although late-stage bacterial regrowth was observed, the final bacterial load remained significantly lower than in the control. Furthermore, cytocompatibility assays with HaCaT keratinocytes and MRC-5 fibroblasts demonstrated high cell viability, confirming the safety of the hydrogel matrix for wound healing applications. These results demonstrate the promise of HSA-based hydrogels as a platform for localized phage therapy of infected wounds.