Dissolvable Immunomodulatory Microneedles for Treatment of Skin Wounds.

Sustained inflammation can halt or delay wound healing, and macrophages play a central role in wound healing. Inflammatory macrophages are responsible for the removal of pathogens, debris, and neutrophils, while anti-inflammatory macrophages stimulate various regenerative processes. Recombinant human Proteoglycan 4 (rhPRG4) has been shown to modulate macrophage polarization and to prevent fibrosis and scarring in ear wound healing. Here, we engineered dissolvable microneedle arrays (MNAs) carrying rhPRG4 for the treatment of skin wounds. The in vitro experiments suggested that rhPRG4 modulates the inflammatory function of bone marrow-derived macrophages. We developed degradable and detachable microneedles from gelatin methacryloyl (GelMA) attached to a dissolvable gelatin backing. The developed MNAs were able to deliver a high dose of rhPRG4 through the dissolution of the gelatin backing post-injury, while the GelMA microneedles sustained rhPRG4 bioavailability over the course of treatment. In vivo results in a murine model of full-thickness wounds with impaired healing confirmed a decrease in inflammatory biomarkers such as TNF-α and IL-6, and an increase in angiogenesis and collagen deposition. Collectively, these results demonstrate rhPRG4-incorporating MNA is a promising platform in skin wound healing applications. This article is protected by copyright. All rights reserved.