Biodegradable Oxygen‐Generating Microneedle Patches for Regenerative Medicine Applications

Upon injury, regenerating skin is metabolically active and requires oxygen for physiological processes related to wound healing. Such processes can be halted in hypoxic conditions common in chronic wounds. Microneedle arrays (MNAs) have been demonstrated to improve therapeutic delivery and wound healing. Recently, few studies have explored the use of oxygen-releasing MNAs; however, they involve complex manufacturing and handling and fail to eliminate cytotoxic byproducts. To address these challenges, biodegradable and mechanically robust gelatin methacryloyl-based MNAs are developed that can penetrate the tissue and release oxygen upon exposure to interstitial fluid and wound exudates. The oxygen release rate and biocompatibility of the developed MNAs with different compositions are evaluated and optimized. Interestingly, in vitro studies demonstrate that the optimized compositions can release oxygen at therapeutic levels and significantly increase viability of chronically hypoxic cells to match that of normoxic cells. In vivo studies further confirm that the optimized oxygen-generating MNAs do not cause any harm or impair healing in a murine model of acute skin injury. Additionally, transcriptomic analysis reveals upregulation of key pathways related to fibroblast motility, lipid metabolism, and a marked reduction in inflammatory signaling, all of which contribute to improved wound healing. The developed strategy can introduce new opportunities in elimination of hypoxia and therefore treatment of chronic wounds.