Construction of cartilaginous organoids based on cartilage extracellular matrix microcarriers to promote articular cartilage regeneration through immune regulation

作者：Hongyu Jiang, Wei Liu, Jiajie Chen, Yue Tian, Zhibo Jia, Yanbin Wu, Yanjun Guan, Leijia Chen, Wenjing Xu, Haoye Meng, Yingjie Xiong, Jianting Ye, Cheng Huang, Ruichao He, Sice Wang, Yufei Ding, Wei Fan, Yunkang Yang, Jiang Peng, Aiyuan Wang · 发表于：Journal of Orthopaedic Translation · 年份：2025 · DOI：10.1016/j.jot.2025.05.005 · 被引用次数：7 · 研究领域：Osteoarthritis Treatment and Mechanisms、Tissue Engineering and Regenerative Medicine、Proteoglycans and glycosaminoglycans research

Objective: repair and regeneration of knee cartilage in SD rats. Methods: Cartilage extracellular matrix microcarriers (CEMMs) were created through a combination of decellularization, wet milling, and layered sieving methods. The evaluation of their biological function was conducted through live/dead staining, CCK-8 assay, scratch assay, and Transwell assay in a laboratory setting. The immune microenvironment was confirmed to be influenced by CEMMs through a conditioned culture involving rat macrophages. qRT-PCR and secretory function assays was conducted to evaluate the chondrogenic activity of CORGs. Gene expression profiles throughout the development of CORGs were analyzed using transcriptome sequencing. Immunodeficient mouse subcutaneous model to assess the ectopic chondrogenic capacity of CORGs. CORGs were implanted into the knee joint cartilage defects of SD rats to evaluate their effects on cartilage regeneration. Results: Successfully developed CEMMs with dimensions of 210.4 ± 56.89 um exhibited strong biocompatibility, the capacity to draw in stem cells, stimulate their growth and migration, and encourage macrophages to shift to the M2 type. Functionalized CORGs were successfully constructed based on CEMMs. Transcriptomics showed that CORGs had a gene expression pattern similar to mesodermal to chondrogenic development. CORGs successfully generated cartilaginous tissue subcutaneously in immunodeficient mice. Specifically, at 1 week postoperatively, CORGs were observe...