Development of phage-containing hydrogel for treating Enterococcus faecalis-infected wounds

Abstract

Background Chronic wound infections caused by Enterococcus faecalis pose formidable challenges in clinical management, exacerbated by the emergence of vancomycin-resistant strains. Phage therapy offers a targeted approach but encounters delivery hurdles. Due to their biocompatibility and controlled release properties, hydrogels hold promise as carriers. Objective This study aimed to fabricate phage-containing hydrogels using sodium alginate (SA), carboxymethyl cellulose (CMC), and hyaluronic acid (HA) to treat E. faecalis-infected wounds. We assessed the efficacy of these hydrogels both in vitro and in vivo. Methods The hydrogel was prepared using SA-CMC-HA polymers. Phage SAM-E.f 12 was incorporated into the SA-CMC-HA hydrogel. The hydrogel’s swelling index was measured after 24 h, and degradation was assessed over seven days. Surface morphology and composition were analyzed using Scanning Electron Microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). Antibacterial activity was tested via optical density (OD) and disk diffusion assays. Phage release and stability were evaluated over a month. In vivo efficacy was tested in mice through wound healing and bacterial count assays, with histopathological analysis. Results Hydrogels exhibited a swelling index of 0.43, a water absorption rate of %30, and 23% degradation over seven days. FTIR confirmed successful polymer incorporation. In vitro studies demonstrated that phage-containing hydrogels significantly inhibited bacterial growth, with an OD of 0.3 compared to 1.1 for the controls. Hydrogels remained stable for four weeks. In vivo, phage-containing hydrogels reduced bacterial load and enhanced wound healing, as shown by improved epithelialization and tissue restoration. Conclusion Phage-containing hydrogels effectively treat wounds infected with E. faecalis-infected wounds, promoting wound healing through controlled phage release. These hydrogels can improve clinical outcomes in the treatment of infected wounds.