Physiological Mechanical Loading Is Crucial for Chondrogenesis and Cartilage Formation by Human Synovium-Derived Stem Cells Stimulated by Kartogenin

Meniscus injuries, prevalent among osteoarthritis patients, the aging population, and athletes, present ongoing challenges in terms of repair and regeneration. As a result, the tissue-engineered meniscus (TEM) has become a prominent focus in regenerative medicine. Mechanical loading is hypothesized to be a critical stimulus for effective cartilage regeneration by mesenchymal stem cells (MSCs). Although Kartogenin (KGN) has been shown to promote chondrogenic differentiation in MSCs, its regenerative efficacy may be contingent upon the presence of biomechanical cues that simulate the native joint environment. Therefore, in tissue engineering strategies for meniscal repair, the synergistic application of biochemical stimulation (via KGN) and mechanical loading may be essential for functional cartilage regeneration. In this study, an in vitro TEM platform was developed with the capability of applying controlled dynamic mechanical loading. Human synovium-derived stem cells (hSDSCs), a readily accessible MSC population, were selected as the cellular component of the TEM. Constructs were evaluated for cartilage-specific extracellular matrix (ECM) production. In vivo, a mouse model of meniscal defects was employed to compare repair outcomes between unloaded and exercise-stimulated groups. Mechanical loading in vitro significantly enhanced ECM secretion, including collagen type II and aggrecan, compared with static culture. Correspondingly in vivo, mice subjected to normal exercise exhibited markedly improved meniscal repair at the defect site, whereas the unloaded group showed delayed and incomplete healing. These findings support the hypothesis that mechanical loading is essential for effective cartilage regeneration in TEM with KGN and hSDSC. Incorporating physiologically relevant mechanical stimulation may be the key to optimizing tissue-engineered therapies for meniscal repair.