Meniscal fibrocartilage regeneration inspired by meniscal maturational and regenerative process

作者：Wenqiang Yan, Maihemuti Maimaitimin, Yue Wu, Yifei Fan, Shuang Ren, Fengyuan Zhao, Chenxi Cao, Xiaoqing Hu, Jin Cheng, Yingfang Ao · 发表于：Science Advances · 年份：2023 · DOI：10.1126/sciadv.adg8138 · 被引用次数：39 · 研究领域：Knee injuries and reconstruction techniques、Tendon Structure and Treatment、Signaling Pathways in Disease

Meniscus is a complex and crucial fibrocartilaginous tissue within the knee joint. Meniscal regeneration remains to be a scientific and translational challenge. We clarified that mesenchymal stem cells (MSCs) participated in meniscal maturation and regeneration using MSC-tracing transgenic mice model. Here, inspired by meniscal natural maturational and regenerative process, we developed an effective and translational strategy to facilitate meniscal regeneration by three-dimensionally printing biomimetic meniscal scaffold combining autologous synovium transplant, which contained abundant intrinsic MSCs. We verified that this facilitated anisotropic meniscus-like tissue regeneration and protected cartilage from degeneration in large animal model. Mechanistically, the biomechanics and matrix stiffness up-regulated Piezo1 expression, facilitating concerted activation of calcineurin and NFATc1, further activated YAP-pSmad2/3-SOX9 axis, and consequently facilitated fibrochondrogenesis of MSCs during meniscal regeneration. In addition, Piezo1 induced by biomechanics and matrix stiffness up-regulated collagen cross-link enzyme expression, which catalyzed collagen cross-link and thereby enhanced mechanical properties of regenerated tissue.