Bui Van Dat, Son Soyoung, Xavier Wilbin, Nguyen Van Quy, Jung Jae Min, Lee Jungmi, Shin Sol, Um Wooram, An Jae Yoon, Kim Chan Ho, Song Yeari, Li Yuce, Park Jae Hyung
School of Chemical Engineering, College of Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea.
School of Chemical Engineering, College of Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, Republic of Korea.
Biomaterials. 2022 Aug;287:121644. doi: 10.1016/j.biomaterials.2022.121644. Epub 2022 Jun 21.
Extracellular vesicles (EVs) have shown great potential in disease diagnosis and treatment; however, their clinical applications remain challenging due to their unsatisfactory long-term stability and the lack of effective delivery strategies. In this study, we prepared human adipose stem cell-derived EV (hASC-EV)-loaded hyaluronic acid dissolving microneedles (EV@MN) to investigate the feasibility of EVs for their clinical applications. The biological activities of the EVs in this formulation were maintained for more than six months under mild storage conditions, especially at temperatures lower than 4 °C. Moreover, the EV@MN enabled precise and convenient intradermal delivery for sustained release of EVs in the dermis layer. Therefore, EV@MN significantly improved the biological functions of hASC-EVs on dermal fibroblasts by promoting syntheses of proteins for the extracellular matrix such as collagen and elastin, enhancing fibroblast proliferation, and regulating the phenotype of fibroblast, compared with other administration methods. This research revealed a possible and feasible formulation for the clinical application of EVs.
细胞外囊泡（EVs）在疾病诊断和治疗中已显示出巨大潜力；然而，由于其长期稳定性不尽人意且缺乏有效的递送策略，其临床应用仍然具有挑战性。在本研究中，我们制备了负载人脂肪干细胞来源的细胞外囊泡（hASC-EV）的透明质酸溶解微针（EV@MN），以研究细胞外囊泡临床应用的可行性。在温和的储存条件下，尤其是在低于4°C的温度下，该制剂中细胞外囊泡的生物活性可维持六个多月。此外，EV@MN能够实现精确且便捷的皮内递送，使细胞外囊泡在真皮层中持续释放。因此，与其他给药方法相比，EV@MN通过促进胶原蛋白和弹性蛋白等细胞外基质蛋白质的合成、增强成纤维细胞增殖以及调节成纤维细胞表型，显著改善了hASC-EV对真皮成纤维细胞的生物学功能。本研究揭示了一种细胞外囊泡临床应用的可能且可行的制剂。
