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Dissolvable Immunomodulatory Microneedles for Treatment of Skin Wounds
Pejman Ghelich1, Mohamadmahdi Samandari1, Alireza Hassani Najafabadi1
1Department of Biomedical Engineering, University of Connecticut Health Center, Farmington, CT, 06030, USA.
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.
Insights
Microneedle arrays delivering recombinant human Proteoglycan 4 (rhPRG4) effectively treat skin wounds by modulating macrophage polarization and reducing inflammation. This innovative approach promotes healing and reduces scarring.
Area of Science:
- Biomaterials Science
- Wound Healing Research
- Immunology
Background:
- Sustained inflammation impedes wound healing, with macrophages playing a critical role in regulating this process.
- Recombinant human Proteoglycan 4 (rhPRG4) has demonstrated potential in modulating macrophage polarization and preventing fibrosis.
- Current treatments for skin wounds often face challenges in delivering therapeutic agents effectively to promote regeneration.
Purpose of the Study:
- To engineer dissolvable microneedle arrays (MNAs) for the targeted delivery of rhPRG4 to skin wounds.
- To investigate the in vitro and in vivo efficacy of rhPRG4-loaded MNAs in promoting wound healing.
- To assess the impact of rhPRG4 delivery via MNAs on macrophage polarization and inflammatory markers.
Main Methods:
- Development of biodegradable MNAs using gelatin methacryloyl (GelMA) and a dissolvable gelatin backing.
- In vitro assessment of rhPRG4's effect on bone marrow-derived macrophage polarization.
- In vivo evaluation of rhPRG4-loaded MNAs in a murine model of impaired full-thickness skin wounds.
Main Results:
- In vitro studies confirmed rhPRG4's modulation of macrophage inflammatory functions.
- The developed MNAs successfully delivered high doses of rhPRG4, with sustained bioavailability.
- In vivo results showed reduced levels of inflammatory biomarkers (TNF-α, IL-6) and increased angiogenesis and collagen deposition in treated wounds.
Conclusions:
- rhPRG4-loaded microneedle arrays represent a promising platform for enhancing skin wound healing.
- This MNA system effectively delivers rhPRG4, reduces inflammation, and promotes tissue regeneration.
- The study highlights the potential of combining biomaterial engineering with targeted drug delivery for improved wound care outcomes.
