Wu Yongjie, Jia Zenghui, Sun Kang, Zhou Guangdong, Tao Ke
State Key Lab of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China.
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, Shanghai, 200011, PR China; Research Institute of Plastic Surgery, Shandong Second Medical University, Weifang, Shandong, 261053, PR China.
Biomaterials. 2025 Nov;322:123393. doi: 10.1016/j.biomaterials.2025.123393. Epub 2025 May 5.
Reconstructing the zonal organization of articular cartilage, including the heterogeneity in matrix distribution and chondrocyte status, remains a significant challenge. In this study, we developed a compression technique to engineer artificial cartilage architecture. By controlling the orientation of fibers within a collagen hydrogel, we obtained a gradient from parallel alignment in the surface layer to random distribution in deeper layers. Simultaneously, we established a diverse concentration gradient of chondroitin sulfate to mimic cartilage composition. Encapsulating chondrocytes within this construct yielded a "cartilage organoid." In vitro culture demonstrated that the plastic compression achieved an increased density, parallel alignment, and a flattened morphology of cells in the surface layer. Especially, type II collagen and superficial zone protein (SZP), which are crucial for the functional durability of articular cartilage, were specifically excreted by the regulated cells within the surface region. Subcutaneous implantation of the cartilage organoid confirmed the stable retention of these specific features of the organoid in vivo, accompanied by further tissue maturation. Following implantation into articular cartilage defects, successful regeneration of well-integrated cartilage tissue with region-specific characteristics was achieved. These findings suggest a biomimetic cartilage organoid fully mimicking the factors in the structure and composition of natural cartilages, which may be a promising candidate for cartilage reconstruction and functional regeneration.
重建关节软骨的分层组织结构，包括基质分布和软骨细胞状态的异质性，仍然是一项重大挑战。在本研究中，我们开发了一种压缩技术来构建人工软骨结构。通过控制胶原水凝胶内纤维的取向，我们获得了从表层平行排列到深层随机分布的梯度。同时，我们建立了硫酸软骨素的不同浓度梯度以模拟软骨组成。将软骨细胞封装在这种构建物中产生了一种“软骨类器官”。体外培养表明，塑性压缩使表层细胞密度增加、平行排列且形态扁平。特别是，对关节软骨功能耐久性至关重要的II型胶原蛋白和浅表区蛋白（SZP），由表层区域内受调控的细胞特异性分泌。皮下植入软骨类器官证实了该类器官在体内这些特定特征的稳定保留，并伴随着进一步的组织成熟。将其植入关节软骨缺损后，成功实现了具有区域特异性特征的良好整合软骨组织的再生。这些发现表明，一种仿生软骨类器官完全模仿了天然软骨结构和组成中的因素，这可能是软骨重建和功能再生的有希望的候选者。
