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Decellularized Extracellular Matrix Hydrogels as a Delivery Platform for MicroRNA and Extracellular Vesicle Therapeutics

机译:脱细胞的细胞外基质水凝胶作为MicroRNA和细胞外囊泡治疗的传递平台

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摘要

In the last decade, the use of microRNA (miRNA) and extracellular vesicle (EV) therapies has emerged as an alternative approach to mitigate the negative effects of several disease pathologies ranging from cancer to tissue and organ regeneration; however, delivery approaches towards target tissues have not been optimized. To alleviate these challenges, including rapid diffusion upon injection and susceptibility to degradation, porcine-derived decellularized extracellular matrix (ECM) hydrogels are examined as a potential delivery platform for miRNA and EV therapeutics. The incorporation of EVs and miRNA antagonists, including anti-miR and antago-miR, in ECM hydrogels results in a prolonged release as compared to the biologic agents alone. In addition, individual in vitro assessments confirm the bioactivity of the therapeutics upon release from the ECM hydrogels. This work demonstrates the feasibility of encapsulating miRNA and EV therapeutics in ECM hydrogels to enhance delivery and potentially efficacy in later in vivo applications.
机译:在过去的十年中,已经出现了使用microRNA(miRNA)和细胞外囊泡(EV)疗法作为减轻癌症,组织和器官再生等多种疾病病理学的负面影响的替代方法。然而,针对靶组织的递送方法尚未优化。为了缓解这些挑战,包括注射时迅速扩散和易于降解,将猪源性脱细胞细胞外基质(ECM)水凝胶作为miRNA和EV治疗剂的潜在递送平台进行了研究。与单独的生物制剂相比,在ECM水凝胶中掺入EV和miRNA拮抗剂(包括抗miR和antago-miR)会导致释放时间延长。另外,单独的体外评估证实了从ECM水凝胶中释放后治疗剂的生物活性。这项工作证明了在ECM水凝胶中封装miRNA和EV治疗剂以增强递送和在以后的体内应用中的潜在功效的可行性。

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