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携载外泌体的干细胞募集多肽水凝胶微载体用于骨关节炎治疗。

Stem cell recruitment polypeptide hydrogel microcarriers with exosome delivery for osteoarthritis treatment.

机构信息

Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.

Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001, China.

出版信息

J Nanobiotechnology. 2024 Aug 27;22(1):512. doi: 10.1186/s12951-024-02765-1.

Abstract

With the accelerated aging tendency, osteoarthritis (OA) has become an intractable global public health challenge. Stem cells and their derivative exosome (Exo) have shown great potential in OA treatment. Research in this area tends to develop functional microcarriers for stem cell and Exo delivery to improve the therapeutic effect. Herein, we develop a novel system of Exo-encapsulated stem cell-recruitment hydrogel microcarriers from liquid nitrogen-assisted microfluidic electrospray for OA treatment. Benefited from the advanced droplet generation capability of microfluidics and mild cryogelation procedure, the resultant particles show uniform size dispersion and excellent biocompatibility. Moreover, acryloylated stem cell recruitment peptides SKPPGTSS are directly crosslinked within the particles by ultraviolet irradiation, thus simplifying the peptide coupling process and preventing its premature release. The SKPPGTSS-modified particles can recruit endogenous stem cells to promote cartilage repair and the released Exo from the particles further enhances the cartilage repair performance through synergistic effects. These features suggest that the proposed hydrogel microcarrier delivery system is a promising candidate for OA treatment.

摘要

随着人口老龄化趋势的加速,骨关节炎(OA)已成为全球亟待解决的棘手公共健康问题。干细胞及其衍生的外泌体(Exo)在 OA 治疗中显示出巨大的潜力。该领域的研究倾向于开发用于干细胞和 Exo 递送的功能性微载体,以提高治疗效果。在此,我们开发了一种新型的外泌体包裹干细胞募集水凝胶微载体系统,通过液氮辅助微流控电喷雾用于 OA 治疗。受益于微流控技术先进的液滴生成能力和温和的冷冻凝胶化过程,所得颗粒具有均匀的粒径分布和优异的生物相容性。此外,通过紫外线照射,将丙烯酰化的干细胞募集肽 SKPPGTSS 直接交联在颗粒内,从而简化了肽偶联过程并防止其过早释放。经 SKPPGTSS 修饰的颗粒可以募集内源性干细胞,促进软骨修复,而从颗粒中释放的 Exo 通过协同作用进一步增强软骨修复性能。这些特性表明,所提出的水凝胶微载体递送系统是治疗 OA 的一种有前途的候选方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/656b/11348651/e6e09388ffcb/12951_2024_2765_Fig1_HTML.jpg

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