Bioenergetic and Meniscus-Inspired Anisotropic Hydrogel Scaffolds Loaded with Synovial Mesenchymal Stem Cells for Enhanced Meniscus Tear Repair.

Meniscal tears have limited spontaneous healing due to poor vascularization and intrinsic repair capacity, often leading to post-traumatic osteoarthritis. Current clinical treatments fail to restore native meniscal structure and function, necessitating advanced regenerative strategies. Tissue-engineered scaffolds offer promise, yet conventional designs lack the anisotropic architecture and cannot mitigate the oxidative injury microenvironment. Herein, we developed a meniscus-inspired anisotropic hydrogel scaffold incorporating succinate for bioenergetic regulation and loaded with synovial mesenchymal stem cells (SMSCs) for repair of red-red and red-white transitional zones. The anisotropic structure was fabricated via freeze-casting to mimic native meniscal alignment, while succinate modification enabled bioenergetic regulation by reducing intracellular ROS levels, preserving mitochondrial homeostasis, and maintaining cellular energy status, thereby enhancing SMSC proliferation and migration. The scaffold improved SMSC behavior in vitro and promoted fibrocartilage-like meniscal repair while attenuating cartilage degeneration in a rabbit tear model. This bioenergetic, biomimetic scaffold integrates structural anisotropy, stem cell therapy, and metabolic regulation, representing a promising strategy for fibrocartilage-like meniscal repair and attenuation of secondary articular cartilage degeneration.