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.
ABSTRACT
Despite the bone ability of self-regeneration, large bone defects require surgical intervention. Likewise, when it comes to osteoporotic bone fractures, new approaches should be considered a supportive mechanism for the surgery. In recent years, more and more attention has been attracted to advanced drug delivery systems for local osteoporosis treatment, combining appropriate biomaterials with antiosteoporotic drugs, allowing simultaneously to regenerate the bone and locally treat the osteoporosis. Within the current research, hyaluronic acid/strontium ranelate (HA/SrRan), HA/calcium phosphate nanoparticles (HA/CaP NPs), and HA/CaP NPs/SrRan hydrogels were prepared. The effect of CaP and SrRan presence in the composites on the swelling behavior, gel fraction, molecular structure, microstructure, and SrRan and Sr2+ release, as well as in vitro cell viability was evaluated. Obtained results revealed that the route of CaP nanoparticle incorporation into the HA matrix had a significant effect on the hydrogel gel fraction, rheological properties, swelling behavior, and microstructure. Nevertheless, it had a negligible effect on the release kinetics of SrRan and Sr2+. The highest cell (3T3) viability (>80%) was observed for HA hydrogels, with and without SrRan. Moreover, the positive effect of SrRan on 3T3 cells was also demonstrated, showing a significant increase (up to 50%) in cell viability if the used concentrations of SrRan were in the range of 0.05-0.2 µg/ml.
ABSTRACT
The design of multifunctional hydrogels based on bioactive hyaluronic acid (HA) and antibacterial cationic polymer É-poly-l-lysine (ε-PL) is a promising tool in tissue engineering applications. In the current study, we have designed hyaluronic acid and É-polylysine composite hydrogel systems with antibacterial and cell attractive properties. Two distinct crosslinking approaches were used: the physical crosslinking based on electrostatic attractions and the chemical crosslinking of charged functional groups (-NH2 and -COOH). The impact of the crosslinking strategy on fabricated hydrogel molecular structure, swelling behavior, gel fraction, morphology, porosity, viscoelastic properties, antibacterial activity, and in vitro biocompatibility was evaluated. Both chemically and physically crosslinked HA/Ô-PL hydrogels demonstrated fast swelling behavior and long-term stability for at least 28 days, as well as similar order of stiffness (10-30 kPa). We demonstrated that physically crosslinked hydrogels inhibited over 99.999% of Gram-negative E. coli, while chemically crosslinking strategy led to the antibacterial efficiency decrease. However, cell viability was significantly improved, confirming the importance of the applied crosslinking approach to the antibacterial activity and in vitro biocompatibility. The distinct differences in the physicochemical and biological properties of the developed materials provide new opportunities to design next-generation functional composite hydrogel systems.
