Ginsenoside CK Hybrid Exosome Composited Injectable Macroporous Hydrogel Scaffold for Cartilage Regeneration via Endogenous Bone Marrow Mesenchymal Stem Cells Recruitment and Fate Modulation.

IF 9.6 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Luoming Yang, Yajuan He, Dan Zeng, Caiyun Zhong, Yong Liu, Shihong Shen, Daidi Fan
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Abstract

Osteoarthritis (OA)-induced cartilage repair critically relies on bone marrow mesenchymal stem cells (BMSCs). Three key challenges persist in OA therapy: efficient recruitment of BMSCs to lesions, sustained retention in defects, and inhibition of chondrocyte hypertrophy under inflammatory conditions. This study proposes a multidimensional repair strategy coordinating the entire process of "endogenous BMSCs recruitment-retention/proliferation-differentiation-postdifferentiation fate-regulation." Accordingly, a ginsenoside CK (CK)-hybridized exosome (HyExo@CK) composite injectable microporous hydrogel scaffold (HyExo@CK/SiCH) is developed by integrating material strategies for multifunctional synergy. Detailly, the HyExo@CK enables endogenous BMSCs recruitment. The hydrogel scaffold, formed by in situ polysiloxane crosslinking of silane-modified recombinant collagen (functioning as surfactant-like foaming agent) and hyaluronic acid (serving as a high-viscosity rheological modifier and foam stabilizer), features interconnected macropores (171.40 ± 7.37 µm) that offer an optimal niche for BMSCs retention and proliferation. Cellular assays demonstrated HyExo@CK/SiCH significantly promoted BMSCs proliferation, migration, and chondrogenic differentiation. Computational modeling and OA-mimicking transcriptomic analysis revealed that CK competitively binds to the ligand-binding domain of SDF-1, effectively inhibiting the chondrocyte hypertrophy-associated SDF-1/CXCR4 signaling pathway to regulate BMSCs fate postdifferentiation. In rabbit OA cartilage defect models, HyExo@CK/SiCH achieved complete cartilage regeneration within 12 weeks postimplantation, demonstrating superior endogenous BMSCs recruitment and whole-cycle fate regulation capabilities.

人参皂苷CK杂交外泌体复合注射用大孔水凝胶支架内源性骨髓间充质干细胞募集及命运调控软骨再生。
骨关节炎(OA)诱导的软骨修复严重依赖于骨髓间充质干细胞(BMSCs)。骨性关节炎治疗仍然存在三个关键挑战:BMSCs向病变的有效募集,缺损的持续保留,炎症条件下软骨细胞肥大的抑制。本研究提出了一种多维修复策略,协调“内源性骨髓间充质干细胞招募-保留/增殖-分化-分化后命运调节”的整个过程。因此,通过整合材料策略,开发了人参皂苷CK (CK)-杂交外泌体(HyExo@CK)复合可注射微孔水凝胶支架(HyExo@CK/SiCH)。具体来说,HyExo@CK使内源性骨髓间充质干细胞募集成为可能。水凝胶支架由硅烷修饰的重组胶原蛋白(作为表面活性剂样发泡剂)和透明质酸(作为高粘度流变调节剂和泡沫稳定剂)原位聚硅氧烷交联而成,具有相互连接的大孔(171.40±7.37µm),为骨髓间充质干细胞的保留和增殖提供了最佳的生态位。细胞分析显示HyExo@CK/SiCH显著促进骨髓间充质干细胞的增殖、迁移和软骨分化。计算模型和模拟ova的转录组学分析显示,CK竞争性地结合SDF-1的配体结合域,有效抑制软骨细胞肥大相关的SDF-1/CXCR4信号通路,调节骨髓间充质干细胞分化后的命运。在兔OA软骨缺损模型中,HyExo@CK/SiCH在植入后12周内实现了完全的软骨再生,显示出优越的内源性骨髓间充质干细胞募集和全周期命运调节能力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Advanced Healthcare Materials
Advanced Healthcare Materials 工程技术-生物材料
CiteScore
14.40
自引率
3.00%
发文量
600
审稿时长
1.8 months
期刊介绍: Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.
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