Implantation of biomedical devices is followed by immune response to the implant, as well as occasionally bacterial and yeast/fungi infections (1-3). 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 infected wounds. Such wounds are associated with high levels of pro-inflammatory cytokine secretion and iNOS production, contributing to non-healing phenotype.
We have previously described thin films made of hyaluronic acid (HA) and polyarginine (PAR) that can be applied to all kind of medical devices. Such films constructed by layer-by-layer assembly demonstrated antimicrobial and anti-inflammatory properties (4-6). Recently, we presented antibacterial HA-based hydrogels cross-linked with 1,4-butanediol diglycidyl ether (BDDE). In HA hydrogels cross-linked with BDDE, carboxylic groups are preserved, and can be used for complexation with positively-charged antibacterial polymers such as PAR (7). Now, we used this system for multifunctional HA-based hydrogels.
For the first time, we fabricated PAR/miRNA-loaded HA hydrogels with antibacterial and anti-inflammatory properties, which simultaneously act as miRNA delivery system (article submitted).
We demonstrate that PAR decreases inflammatory response of LPS-stimulated macrophages and accelerates fibroblast migration in macrophage/fibroblast co-culture system, suggesting a positive effect on wound healing. Furthermore, PAR allows to load miRNA into HA hydrogels, and then to deliver them into the cells. Potentially any miRNA can be used, making the system highly versatile. For instance, the hydrogels can be associated to different functional miRNAs, such as anti-inflammatory or angiogenic, to increase anti-inflammatory properties or to induce revascularization at the wound site.
To our knowledge, this study is the first describing miRNA-loaded hydrogels with antibacterial effect and anti-inflammatory features, making this system promising for infection treatment and foreign body response modulation. We believe that our system can become useful for the treatment of infected wounds such as diabetic ulcers, that are extremely difficult to heal and usually end up with amputations.
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