Zhu Delong, Hu Ying, Kong Xiangkai, Luo Yuansen, Zhang Yi, Wu Yu, Tan Jiameng, Chen Jianwei, Xu Tao, Zhu Lei
Department of Dermatology & Plastic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
Department of the Second Plastic Surgery, The First People's Hospital of Foshan, Foshan 528000, China.
Regen Biomater. 2024 Mar 26;11:rbae035. doi: 10.1093/rb/rbae035. eCollection 2024.
Adipose mesenchymal stem cell (ADMSC)-derived exosomes (ADMSC-Exos) have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns. However, the low yield, easy loss after direct coating, and no suitable loading system to improve their availability and efficacy hinder their clinical application for wound healing. And few studies focused on the comparison of biological functions between exosomes derived from different culture techniques, especially in exosome-releasing hydrogel system. Therefore, we designed a high-performance exosome controllable releasing hydrogel system for burn wound healing, namely loading 3D-printed microfiber culture-derived exosomes in a highly biocompatible hyaluronic acid (HA). In this project, we compared the biological functions and in a burn model among exosomes derived from the conventional two-dimensional (2D) plate culture (2D-Exos), microcarrier culture (2.5D-Exos), and 3D-printed microfiber culture (3D-Exos). Results showed that compared with 2D-Exos and 2.5D-Exos, 3D-Exos promoted HACATs and HUVECs cell proliferation and migration more significantly. Additionally, 3D-Exos had stronger angiogenesis-promoting effects in tube formation of (HUVECs) cells. Moreover, we found HA-loaded 3D-Exos showed better burn wound healing promotion compared to 2D-Exos and 2.5D-Exos, including accelerated burn wound healing rate and better collagen remodeling. The study findings reveal that the HA-loaded, controllable-release 3D-Exos repair system distinctly augments therapeutic efficacy in terms of wound healing, while concurrently introducing a facile application approach. This system markedly bolsters the exosomal loading efficiency, provides a robust protective milieu, and potentiates the inherent biological functionalities of the exosomes. Our findings provide a rationale for more efficient utilization of high-quality and high-yield 3D exosomes in the future, and a novel strategy for healing severe burns.
脂肪间充质干细胞（ADMSC）衍生的外泌体（ADMSC-Exos）在再生医学中显示出巨大潜力，并已被证明有利于烧伤等伤口修复。然而，产量低、直接包被后易损失以及缺乏合适的负载系统来提高其可用性和功效，阻碍了它们在伤口愈合方面的临床应用。而且很少有研究关注不同培养技术衍生的外泌体之间的生物学功能比较，特别是在外泌体释放水凝胶系统中。因此，我们设计了一种用于烧伤伤口愈合的高性能外泌体可控释放水凝胶系统，即将3D打印微纤维培养衍生的外泌体负载于具有高度生物相容性的透明质酸（HA）中。在本项目中，我们比较了传统二维（2D）平板培养（2D-Exos）、微载体培养（2.5D-Exos）和3D打印微纤维培养（3D-Exos）衍生的外泌体在烧伤模型中的生物学功能。结果表明，与2D-Exos和2.5D-Exos相比，3D-Exos更显著地促进了HACATs和HUVECs细胞的增殖和迁移。此外，3D-Exos在（HUVECs）细胞的管腔形成中具有更强的促血管生成作用。而且，我们发现负载HA的3D-Exos与2D-Exos和2.5D-Exos相比，在促进烧伤伤口愈合方面表现更好，包括加快烧伤伤口愈合速度和更好的胶原重塑。研究结果表明负载HA的可控释放3D-Exos修复系统在伤口愈合方面显著增强了治疗效果，同时引入了一种简便的应用方法。该系统显著提高了外泌体的负载效率，提供了强大的保护环境，并增强了外泌体的固有生物学功能。我们的研究结果为未来更高效地利用高质量、高产量的3D外泌体提供了理论依据，并为治疗严重烧伤提供了一种新策略。
