Immunomodulatory exosomes loaded chitosan methacryloyl hydrogel combined with pro-chondrogenic microspheres for promoting articular cartilage regeneration

IF 7.9 2区材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Materials & Design Pub Date : 2025-05-01 Epub Date: 2025-03-28 DOI:10.1016/j.matdes.2025.113876

Ruoyu Liang , Zhaoxu Li , Qu Xu , Shengtao Wang , Dongxu Chen , Peng Gui , Mingzhou Chen , Wei Peng , Jian Su

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Abstract

A diverse range of biological materials has been widely used for the management of injuries to joint cartilage. However, suboptimal outcomes in cartilage repair are often due to inappropriate host immune responses and inadequate microenvironments for chondrogenesis. Therefore, there is a need to develop innovative hydrogel systems with immunomodulatory capabilities that promote a favorable environment for cartilage regeneration. In this study, we fabricated a Chitosan Methacryloyl (CSMA) hydrogel and incorporated exosomes derived from lipopolysaccharide (LPS)-activated NR8383 macrophages stimulated with Epigallocatechin gallate (EGCG) (EGCG-exo). Additionally, Kartogenin (KGN)-incorporated poly (lactic-co-glycolic acid) (PLGA) microspheres (KGN μS) were added to the hydrogel to stimulate chondrogenic differentiation of recruited BMSCs upon KGN release. The immunomodulatory and pro-chondrogenic properties of the CSMA-EGCG-exo@KGN μS microsphere-gel system were evaluated both in vitro and in vivo. The CSMA-EGCG-exo@KGN μS system not only demonstrated macrophage reprogramming properties but also enhanced BMSC recruitment and promoted chondrogenesis, leading to improved cartilage regeneration in a rabbit model of cartilage lesions. Looking forward, the CSMA-EGCG-exo@KGN μS microsphere-gel system holds significant potential for clinical translation as a pro-regenerative implant material for the treatment of cartilage injuries.

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免疫调节外泌体负载壳聚糖甲基丙烯酰水凝胶结合促软骨微球促进关节软骨再生

各种各样的生物材料已被广泛用于关节软骨损伤的治疗。然而，软骨修复的次优结果通常是由于不适当的宿主免疫反应和软骨形成的微环境不足。因此，有必要开发具有免疫调节能力的创新水凝胶系统，促进软骨再生的有利环境。在这项研究中，我们制备了一种壳聚糖甲基丙烯酰（CSMA）水凝胶，并加入了由脂多糖（LPS）激活的NR8383巨噬细胞衍生的外泌体，这些巨噬细胞受表没食子儿茶素没食子酸酯（EGCG）（EGCG-exo）刺激。此外，在水凝胶中加入Kartogenin （KGN）掺入的聚乳酸-羟基乙酸（PLGA）微球（KGN μS），在KGN释放后刺激募集的骨髓间充质干细胞成软骨分化。体外和体内评价CSMA-EGCG-exo@KGN μS微球-凝胶体系的免疫调节和促软骨形成特性。CSMA-EGCG-exo@KGN μS系统不仅表现出巨噬细胞重编程特性，还能增强骨髓间充质干细胞的募集，促进软骨形成，从而改善兔软骨病变模型的软骨再生。展望未来，CSMA-EGCG-exo@KGN μS微球凝胶系统作为软骨损伤治疗的促再生植入材料具有重要的临床应用潜力。

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来源期刊

Materials & Design Engineering-Mechanical Engineering

CiteScore

14.30

自引率

7.10%

发文量

1028

审稿时长

85 days

期刊介绍： Materials and Design is a multi-disciplinary journal that publishes original research reports, review articles, and express communications. The journal focuses on studying the structure and properties of inorganic and organic materials, advancements in synthesis, processing, characterization, and testing, the design of materials and engineering systems, and their applications in technology. It aims to bring together various aspects of materials science, engineering, physics, and chemistry. The journal explores themes ranging from materials to design and aims to reveal the connections between natural and artificial materials, as well as experiment and modeling. Manuscripts submitted to Materials and Design should contain elements of discovery and surprise, as they often contribute new insights into the architecture and function of matter.