A visible light crosslinked angiogenic and anti-inflammatory GelMA microneedle array patch co-releasing nitric oxide and oxygen for diabetic wound healing

Diabetic wounds are a major healthcare challenge, as their slow or impaired healing often leads to amputations and fatalities. Among the many factors contributing to the poor healing of diabetic wounds are insufficient angiogenesis and dysregulated inflammatory responses. Nitric oxide (NO) and oxygen (O₂) can be promising therapeutic agents to induce angiogenic and anti-inflammatory activities. In this study, we developed a visible light-crosslinked Gelatin Methacryloyl (GelMA) microneedle (MN) array patch capable of simultaneously delivering NO and O₂ to diabetic wounds. The MN array patches were made based on micro molding technique using PDMS molds and visible light crosslinking based GelMA hydrogel. Scanning electron microscope (SEM) results revealed well-formed MNs with an average height of 650 μm. Under compression test, the MN array exhibited elastic behavior at forces below 150 mN per MN, which has been found to be adequate for penetration in human skin. In vitro degradation study in Phosphate buffered saline (PBS) solution revealed approximately 80 % degradation within 1 h, whereas in vivo degradation in rat skin tissue occurred at a slower rate, with around 50 % degradation after 24 h and complete dissolution observed after 48 h. In vitro cell proliferation assay indicated around 10 % increase in fibroblast proliferation and Scratch assay confirmed around 30 % higher cell migration with dual release MN array samples compared to control and blank samples. In vivo, the dual release MN array patches exhibited accelerated acute wound healing compared to untreated control group without showing any localized toxicity or inflammation over 14 days. Furthermore, diabetic wounds treated with the dual release MN array patches showed enhanced healing, confirmed by H&E and Masson's trichrome staining, along with reduced expression of inflammatory cytokine (TNF-α) and elevated expression of angiogenic (TGF-β) and anti-inflammatory (IL-10) biomarkers.