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

Abstract

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.

Structures, Properties, and Bioengineering Applications of Alginates and Hyaluronic Acid

“…Increasing the content of HA not only enhances the mechanical properties of HA-PL hydrogels, but also improves the cellular biocompatibility without exhibiting any cytotoxicity [46]. This finding is consistent with the research of Aunina [47]. Due to the large number of carboxyl and hydroxyl groups in the hyaluronic acid molecule, this allows hyaluronic acid to absorb exudates and enhance cell adhesion [55].…”

Antibacterial activity of epsilon-poly-l-lysine produced by Stenotrophomonas maltophilia HS4 and Paenibacillus polymyxa HS5, alone and in combination with bacteriophages

“…Remarkable properties, such as biodegradability, heat stability, and water solubility along with a wide range of antimicrobial properties encourage the use of ε -PL in various industrial and pharmaceutical fields, including agriculture, food, chemistry, and biomedical [35]. In recent years, ε-PL has become a great candidate to use as suture or dressing material when conjugated with other biomaterials such as cellulose, hyaluronic acid, and chitosan due to its exhibited antimicrobial and antibiofilm ability without inducing an inflammatory response [36–40].…”

Bovine Serum Albumin/Polyvinyl Alcohol Double‐Network Hydrogel Containing ϵ‐Polylysine for Antibacterial Performance

“…When PVA and EPL were added at the same time, the mechanical properties of BPE hydrogel prepared by adding PVA and EPL were reduced to a certain extent. The data show that when the strain reaches 85 %, no hydrogel breakage occurs, and the hydrogel can withstand a stress of 2.16 MPa, considering the effect of electrostatic interaction between EPL and BP [31,32] . The above data indicated that the prepared BPE hydrogel had excellent mechanical properties and could provide strong mechanical support for the application of wound dressing.…”

“…As shown in Figure 5c, the addition of EPL can reduce the mechanical properties of BPE double network hydrogel, which may be caused by the electrostatic interaction between EPL and hydrogel network [31,32] . However, it can be seen from the figure that when EPL concentration reaches 5 %, the yield stress can still reach about 500 Pa, which ensures that the hydrogel can load more antibacterial substances and improve the antibacterial activity of the hydrogel.…”

“…EPL combined with hydrogel network through electrostatic interaction and hydrogen bonding, and endowing hydrogel with certain antibacterial activity, which may provide the basis for the application of BPE hydrogel in the field of wound dressing. [31,32] FTIR Spectra…”