Barnum Lindsay, Samandari Mohamadmahdi, Suhail Yasir, Toro Steven, Novin Ashkan, Ghelich Pejman, Quint Jacob, Saeedinejad Farnooosh, Komma Manu, Tamayol Ali
Department of Biomedical Engineering University of Connecticut Health Center Farmington CT 06030 USA.
Department of Biomedical Engineering University of Connecticut Storrs CT 06269 USA.
Adv Nanobiomed Res. 2025 Jan;5(1):2400093. doi: 10.1002/anbr.202400093. Epub 2024 Nov 27.
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.
受伤后，再生皮肤代谢活跃，伤口愈合相关的生理过程需要氧气。在慢性伤口常见的缺氧条件下，这些过程可能会停止。微针阵列（MNAs）已被证明可改善治疗药物递送和伤口愈合。最近，很少有研究探索使用释氧微针阵列；然而，它们涉及复杂的制造和处理，并且无法消除细胞毒性副产物。为应对这些挑战，开发了可生物降解且机械性能强大的甲基丙烯酰化明胶基微针阵列，其能够穿透组织并在接触组织液和伤口渗出液时释放氧气。对不同组成的已开发微针阵列的氧气释放速率和生物相容性进行了评估和优化。有趣的是，体外研究表明，优化后的组成能够以治疗水平释放氧气，并显著提高长期缺氧细胞的活力，使其与常氧细胞的活力相当。体内研究进一步证实，优化后的产氧微针阵列在急性皮肤损伤小鼠模型中不会造成任何伤害或损害愈合。此外，转录组分析显示与成纤维细胞运动、脂质代谢相关的关键通路上调，炎症信号显著减少，所有这些都有助于改善伤口愈合。所开发的策略可为消除缺氧从而治疗慢性伤口带来新的机遇。
