Polyarginine as a Simultaneous Antimicrobial, Immunomodulatory, and miRNA Delivery Agent within Polyanionic Hydrogel

Implantation of biomedical devices is followed by immune response to the implant, as well as occasionally bacterial, yeast, and/or fungal infections. In this context, new implant materials and coatings that deal with medical device-associated complications are required. Antibacterial and anti-inflammatory materials are also required for wound healing applications, especially in diabetic patients with chronic wounds. In this work, hyaluronic acid (HA) hydrogels with triple activity: antimicrobial, immunomodulatory, and miRNA delivery agent, are presented. It is demonstrated that polyarginine with a degree of polymerization of 30 (PAR30), which is previously shown to have a prolonged antibacterial activity, decreases inflammatory response of lipopolysaccharide-stimulated macrophages. In addition, PAR30 accelerates fibroblast migration in macrophage/fibroblast coculture system, suggesting a positive effect on wound healing. Furthermore, PAR30 allows to load miRNA into HA hydrogels, and then to deliver them into the cells. To the authors knowledge, this study is the first describing miRNA-loaded hydrogels with antibacterial effect and anti-inflammatory features. Such system can become a tool for the treatment of infected wounds, e.g., diabetic ulcers, as well as for foreign body response modulation.