Surg Infect (Larchmt). 2025 Dec 19. doi: 10.1177/10962964251409563. Online ahead of print.
ABSTRACT
Introduction: Surgical site infections continue to pose a major challenge in healthcare, contributing to prolonged hospitalizations and increased morbidity and mortality. Despite advancements in antimicrobial agent treatments, bacterial resistance remains an important obstacle. Among various antimicrobial agents, silver compounds have been re-evaluated for their broad-spectrum efficacy. Previous studies, have demonstrated the potential of silver carboxylate embedded in a titanium dioxide/polydimethylsiloxane (TiO2/PDMS) matrix as a material of biomedical relevance. This study aims to expand upon these findings by examining the cytotoxicity profile of silver carboxylate in four human cell lines that play a crucial role in wound healing. Hypothesis: Controlled silver elution from the TiO2/PDMS matrix produces a cytotoxicity profile comparable with commonly used antibiotic agents at clinically relevant exposures. Methods: In this study, silver carboxylate beads were prepared using a modified method, whereby silver neodecanoate was incorporated into a TiO2/PDMS matrix. The modification involved adjusting the concentration ratios to optimize the release profile for controlled silver elution. Primary human osteoblasts (OBs), keratinocytes (KTs), skeletal muscle cells (SkMs), and endothelial cells (ETs) were cultured under standard conditions and, after 24 h, were exposed to specific silver carboxylate concentrations (1×, 10×, and 100%) without additional washing steps before exposure. In addition, we included a comparative analysis with newly developed silver formulations (silver nanoparticles at 10 and 30 nM, and colloidal silver at 100 and 300 nM) and a panel of conventional antibiotic agents, including vancomycin (5 and 50 µg/mL), tobramycin (5 and 50 µg/mL), linezolid (2 and 20 µg/mL), and polymyxin E (2 µg/mL). Cell viability following exposure was measured using the MTT assay, and the results were analyzed statistically using analysis of variance followed by post hoc Tukey tests. Results: OBs exhibited marked cytotoxicity at higher silver carboxylate concentrations, particularly at the 10× condition, with viability comparable with that observed with higher dose antibiotic agents such as vancomycin 50 µg/mL and tobramycin 50 µg/mL. SkMs and ETs demonstrated limited sensitivity at 1× exposure but showed substantial loss of viability at 10×, consistent with dose-dependent toxicity. KTs were the most sensitive cell type, displaying decreased viability even at 1× exposure. The modified TiO2/PDMS matrix demonstrated an enhanced controlled release mechanism, resulting in lower cytotoxicity compared with both early silver formulations and conventional antibiotic agents. Conclusion: This study builds upon previous investigations on silver carboxylate and provides new insights into its cytotoxic effects across additional human cell lines, including ETs and SkMs. The enhanced controlled release from the modified TiO2/PDMS matrix reduces cytotoxicity compared with previous formulations and commonly used antibiotic agents. These results highlight the importance of concentration-dependent toxicity and support further evaluation of this material in future in vivo and translational studies. The cytotoxicity profile of silver carboxylate embedded in a modified TiO2/PDMS matrix shows variability across different human cell types, but may be relevant for future evaluation in models that require a detailed assessment of biocompatibility. This study expands on previous research by introducing additional cell lines and optimizing the release mechanism of silver carboxylate to enhance its cytotoxicity profile and safety. Addressing current limitations, including lactate dehydrogenase (LDH) interference, will be essential for a comprehensive evaluation and for establishing safe concentration thresholds for future in vivo applications. Future research should focus on validating these findings in animal models and evaluating the systemic effects of prolonged silver exposure.
PMID:41468057 | DOI:10.1177/10962964251409563
