Biodegradable Oxygen-Generating Microneedle Patches for Regenerative Medicine Applications

IF 4 Q2 ENGINEERING, BIOMEDICAL
Lindsay Barnum, Mohamadmahdi Samandari, Yasir Suhail, Steven Toro, Ashkan Novin, Pejman Ghelich, Jacob Quint, Farnooosh Saeedinejad, Manu Komma,  Kshitiz, Ali Tamayol
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Abstract

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.

Abstract Image

用于再生医学的可生物降解产氧微针贴片
损伤后,再生皮肤代谢活跃,需要氧气来完成与伤口愈合相关的生理过程。这种过程在慢性伤口中常见的缺氧条件下可以停止。微针阵列(MNAs)已被证明可以改善治疗递送和伤口愈合。最近,很少有研究探索释放氧的MNAs的使用;然而,它们涉及复杂的制造和处理,并且不能消除细胞毒性副产物。为了应对这些挑战,开发了可生物降解的机械坚固的明胶甲基丙烯基MNAs,它可以穿透组织并在暴露于间质液和伤口渗出液时释放氧气。对所制备的不同组成的MNAs的氧释放速率和生物相容性进行了评价和优化。有趣的是,体外研究表明,优化的组合物可以释放治疗水平的氧气,并显着提高慢性缺氧细胞的活力,以达到正常缺氧细胞的水平。体内研究进一步证实,在小鼠急性皮肤损伤模型中,优化的产氧MNAs不会造成任何伤害或损害愈合。此外,转录组学分析显示,与成纤维细胞运动、脂质代谢和炎症信号显著减少相关的关键通路上调,所有这些都有助于改善伤口愈合。开发的策略可以引入新的机会,消除缺氧,从而治疗慢性伤口。
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来源期刊
Advanced Nanobiomed Research
Advanced Nanobiomed Research nanomedicine, bioengineering and biomaterials-
CiteScore
5.00
自引率
5.90%
发文量
87
审稿时长
21 weeks
期刊介绍: Advanced NanoBiomed Research will provide an Open Access home for cutting-edge nanomedicine, bioengineering and biomaterials research aimed at improving human health. The journal will capture a broad spectrum of research from increasingly multi- and interdisciplinary fields of the traditional areas of biomedicine, bioengineering and health-related materials science as well as precision and personalized medicine, drug delivery, and artificial intelligence-driven health science. The scope of Advanced NanoBiomed Research will cover the following key subject areas: ▪ Nanomedicine and nanotechnology, with applications in drug and gene delivery, diagnostics, theranostics, photothermal and photodynamic therapy and multimodal imaging. ▪ Biomaterials, including hydrogels, 2D materials, biopolymers, composites, biodegradable materials, biohybrids and biomimetics (such as artificial cells, exosomes and extracellular vesicles), as well as all organic and inorganic materials for biomedical applications. ▪ Biointerfaces, such as anti-microbial surfaces and coatings, as well as interfaces for cellular engineering, immunoengineering and 3D cell culture. ▪ Biofabrication including (bio)inks and technologies, towards generation of functional tissues and organs. ▪ Tissue engineering and regenerative medicine, including scaffolds and scaffold-free approaches, for bone, ligament, muscle, skin, neural, cardiac tissue engineering and tissue vascularization. ▪ Devices for healthcare applications, disease modelling and treatment, such as diagnostics, lab-on-a-chip, organs-on-a-chip, bioMEMS, bioelectronics, wearables, actuators, soft robotics, and intelligent drug delivery systems. with a strong focus on applications of these fields, from bench-to-bedside, for treatment of all diseases and disorders, such as infectious, autoimmune, cardiovascular and metabolic diseases, neurological disorders and cancer; including pharmacology and toxicology studies.
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