Dissolvable Immunomodulatory Microneedles for Treatment of Skin Wounds
Pejman Ghelich, Mohamadmahdi Samandari, Alireza Hassani Najafabadi, Adam P. Tanguay, Jacob Quint, Nikhil Menon, Delaram Ghanbariamin, Farnoosh Saeedinejad, Fatemeh Alipanah, Ramaswamy M. Chidambaram, Roman Krawetz, Kristo Nuutila, Steven Toro, Lindsay Barnum, Gregory D. Jay, Tannin A. Schmidt, Ali Tamayol
Abstract
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) is shown to modulate macrophage polarization and to prevent fibrosis and scarring in ear wound healing. Here, dissolvable microneedle arrays (MNAs) carrying rhPRG4 are engineered for the treatment of skin wounds. The in vitro experiments suggest that rhPRG4 modulates the inflammatory function of bone marrow-derived macrophages. Degradable and detachable microneedles are developed from gelatin methacryloyl (GelMA) attach to a dissolvable gelatin backing. The developed MNAs are able to deliver a high dose of rhPRG4 through the dissolution of the gelatin backing post-injury, while the GelMA microneedles sustain rhPRG4 bioavailability over the course of treatment. In vivo results in a murine model of full-thickness wounds with impaired healing confirm 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.