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海藻酸钠水凝胶与负载无细胞脂肪提取物的核壳纳米纤维和月经血干细胞衍生的外泌体共同封装,用于加速关节软骨再生。

Sodium alginate hydrogels co-encapsulated with cell free fat extract-loaded core-shell nanofibers and menstrual blood stem cells derived exosomes for acceleration of articular cartilage regeneration.

作者信息

Zhang Hongtao, Yan Jingchuan, Ma Qiong, Lin Li, Pilehvar Younes, Zarghami Nosratollah, Liang Lizhuo, Xu Kui, Zhang Xiaoping, Yan Kang, Long Hua, Liao Bo

机构信息

Department of Orthopedics, Tangdu Hospital, Air Force Military Medical University, Xi'an, Shaanxi, China.

Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Science, Urmia, Iran.

出版信息

Int J Biol Macromol. 2024 Sep 21;280(Pt 3):135851. doi: 10.1016/j.ijbiomac.2024.135851.

DOI:10.1016/j.ijbiomac.2024.135851
PMID:39307503
Abstract

This study presents a novel scaffold system comprising sodium alginate hydrogels (SAh) co-encapsulated with cell-free fat extract (CEFFE)-loaded core-shell nanofibers (NFs) and menstrual blood stem cell-derived exosomes (EXOs). The scaffold integrates the regenerative potential of EXOs and CFFFE, offering a multifaceted strategy for promoting articular cartilage repair. Coaxially electrospun core-shell NFs exhibited successful encapsulation of CEFFE and seamless integration into the SAh matrix. Structural modifications induced by the incorporation of CEFFE-NFs enhanced hydrogel porosity, mechanical strength, and degradation kinetics, facilitating cell adhesion, proliferation, and tissue ingrowth. The release kinetics of growth factors from the composite scaffold demonstrated sustained and controlled release profiles, essential for optimal tissue regeneration. In vitro studies revealed high cell viability, enhanced chondrocyte proliferation, and migration in the presence of EXOs/CEFFE-NFs@SAh composite scaffolds. Additionally, in vivo experiments demonstrated significant cartilage regeneration, with the composite scaffold outperforming controls in promoting hyaline cartilage formation and defect bridging. Overall, this study underscores the potential of EXOs and CEFFE-NFs integrated into SAh matrices for enhancing chondrocyte viability, proliferation, migration, and ultimately, articular cartilage regeneration. Future research directions may focus on elucidating underlying mechanisms and conducting long-term in vivo studies to validate clinical applicability and scalability.

摘要

本研究提出了一种新型支架系统,该系统由与负载无细胞脂肪提取物(CEFFE)的核壳纳米纤维(NFs)和月经血干细胞衍生外泌体(EXOs)共包封的海藻酸钠水凝胶(SAh)组成。该支架整合了EXOs和CFFFE的再生潜力,为促进关节软骨修复提供了多方面的策略。同轴电纺核壳纳米纤维成功包封了CEFFE,并无缝整合到SAh基质中。CEFFE-NFs的掺入引起的结构修饰提高了水凝胶的孔隙率、机械强度和降解动力学,促进了细胞粘附、增殖和组织向内生长。复合支架中生长因子的释放动力学显示出持续且可控的释放曲线,这对最佳组织再生至关重要。体外研究表明,在EXOs/CEFFE-NFs@SAh复合支架存在的情况下,细胞活力高,软骨细胞增殖和迁移增强。此外,体内实验证明了显著的软骨再生,复合支架在促进透明软骨形成和缺损桥接方面优于对照组。总体而言,本研究强调了将EXOs和CEFFE-NFs整合到SAh基质中以增强软骨细胞活力、增殖、迁移以及最终促进关节软骨再生的潜力。未来的研究方向可能集中在阐明潜在机制以及进行长期体内研究以验证临床适用性和可扩展性。

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