(447a) Delivery of Immunostimulatory Biologics for Skin Tissue Repair

The management of dermal wound healing at a chronic stage is a major medical burden. Dysregulation of wound healing processes can lead to chronic wounds and increased morbidity and mortality. An impaired immune system significantly delays the wound healing process. Timely delivery of the relevant therapeutics to stimulate the immune response in the wound area is crucial for an orchestrated response to injury needed for a faster healing process. In this work, we explored the role of a natural biopolymer along with an immunostimulatory nucleic acid (iNA) to induce a robust innate immune response aiding in skin wound healing. A splinted dermal wound healing mouse model was used to investigate wound healing in immunocompetent Balb/c mice to better reproduce the granulation and re-epithelialization characteristics of human wound healing. The iNA was delivered at the wound site alone or in combination with the natural biopolymer. On day 7, mice were euthanized, and tissue was collected for immunohistochemical analysis. Trans-epidermal water loss (TEWL) data, indicative of skin barrier function, were recorded with a VapoMeter (Delfin). On each day, including days without tissue collection, photographs were collected for planimetric analysis of the wound area. Individual treatment of the immunomodulatory natural biopolymer and the therapeutic biologic produced from the iNA resulted in significant wound closure. In the case of the delivered drug without the biopolymer, we found significantly high localization of the delivered therapeutic at day 1 which was transiently expressed at the wound area and maintained the expression level till day 7. However, in the case of the drug delivered from the biopolymer, the availability of the localized therapeutics was reduced and tended to last for shorter days compared to the individual drug treatment alone. The TEWL data for the natural biopolymer and iNA alone showed significantly higher barrier function recovery compared to the untreated open wounds. In summary, delivery of immunomodulatory biopolymers and iNA derived therapeutics resulted in significant enhancement of wound healing in immunocompetent mice, thereby opening new avenues for tissue repair.