Exploring the Interplay of Antimicrobial Properties and Cellular Response in Physically Crosslinked Hyaluronic Acid/ε-Polylysine Hydrogels

The reduction of tissue cytotoxicity and the improvement of cell viability are of utmost significance, particularly in the realm of green chemistry. Despite substantial progress, the threat of local infections remains a concern. Therefore, hydrogel systems that provide mechanical support and a harmonious balance between antimicrobial efficacy and cell viability are greatly needed. Our study explores the preparation of physically crosslinked, injectable, and antimicrobial hydrogels using biocompatible hyaluronic acid (HA) and antimicrobial ε-polylysine (ε-PL) in different weight ratios (10 wt% to 90 wt%). The crosslinking was achieved by forming a polyelectrolyte complex between HA and ε-PL. The influence of HA content on the resulting HA/ε-PL hydrogel physicochemical, mechanical, morphological, rheological, and antimicrobial properties was evaluated, followed by an inspection of their in vitro cytotoxicity and hemocompatibility. Within the study, injectable, self-healing HA/ε-PL hydrogels were developed. All hydrogels showed antimicrobial properties against S. aureus, P. aeruginosa, E. coli, and C. albicans, where HA/ε-PL 30:70 (wt%) composition reached nearly 100% killing efficiency. The antimicrobial activity was directly proportional to ε-PL content in the HA/ε-PL hydrogels. A decrease in ε-PL content led to a reduction of antimicrobial efficacy against S. aureus and C. albicans. Conversely, this decrease in ε-PL content in HA/ε-PL hydrogels was favourable for Balb/c 3T3 cells, leading to the cell viability of 152.57% for HA/ε-PL 70:30 and 142.67% for HA/ε-PL 80:20. The obtained results provide essential insights into the composition of the appropriate hydrogel systems able to provide not only mechanical support but also the antibacterial effect, which can offer opportunities for developing new, patient-safe, and environmentally friendly biomaterials.