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Abstract：
Cartilage tissue engineering aims to develop functional substitutes for treating cartilage defects and osteoarthritis. Traditional two-dimensional (2D) cell culture systems lack the complexity of native cartilage, leading to the development of 3D regenerative cartilage models. In this study, we developed a 3D model using Gelatin Methacryloyl (GelMA)-based hydrogels seeded with Y201 cells, a bone marrow mesenchymal stem cell line. The model investigated chondrogenic differentiation potential in response to Wnt3a stimulation within the GelMA scaffold and validated using known chondrogenic agonists. Y201 cells demonstrated suitability for the model, with increased proteoglycan content and upregulated chondrogenic marker expression under chondrogenic conditions. Wnt3a enhanced cell proliferation, indicating activation of the Wnt/β-catenin pathway, which plays a role in cartilage development. GelMA hydrogels provided an optimal scaffold, supporting cell viability and proliferation. The 3D model exhibited consistent responses to chondrogenic agonists, with TGF-β3 enhancing cartilage-specific extracellular matrix (ECM) production and chondrogenic differentiation. The combination of Wnt3a and TGF-β3 showed synergistic effects, promoting chondrogenic differentiation and ECM production. This study presents a 3D regenerative cartilage model with potential for investigating cartilage biology, disease mechanisms, and drug screening. The model provides insights into complex cartilage regeneration mechanisms and offers a platform for developing therapeutic approaches for cartilage repair and osteoarthritis treatment.
摘要：
软骨组织工程旨在开发用于治疗软骨缺损和骨关节炎的功能替代品。传统的二维（2D）细胞培养系统缺乏天然软骨的复杂性，导致3D再生软骨模型的发展。在这项研究中,我们使用接种有Y201细胞的明胶甲基丙烯酰（GelMA）基水凝胶开发了3D模型，骨髓间充质干细胞系。该模型研究了响应于GelMA支架内的Wnt3a刺激的软骨形成分化潜能,并使用已知的软骨形成激动剂进行验证。Y201细胞证明了该模型的适用性，在软骨形成条件下，蛋白聚糖含量增加和软骨形成标志物表达上调。Wnt3a增强细胞增殖，表明Wnt/β-catenin途径的激活，在软骨发育中起作用。GelMA水凝胶提供了最佳的支架，支持细胞活力和增殖。3D模型对软骨形成激动剂表现出一致的反应，TGF-β3可增强软骨特异性细胞外基质（ECM）的产生和软骨分化。Wnt3a和TGF-β3的组合显示出协同作用,促进软骨分化和ECM产生。本研究提出了一种3D再生软骨模型，具有研究软骨生物学的潜力。疾病机制,和药物筛选。该模型提供了对复杂软骨再生机制的见解，并为开发软骨修复和骨关节炎治疗的治疗方法提供了平台。
