2. Academic Validation
  3. Physiological Mechanical Loading Is Crucial for Chondrogenesis and Cartilage Formation by Human Synovium-Derived Stem Cells Stimulated by Kartogenin

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

  • ACS Biomater Sci Eng. 2026 Mar 9;12(3):1647-1662. doi: 10.1021/acsbiomaterials.5c00877.
Jiawei Li 1 2,  Yixi Li 1 2,  Haoran Feng 2 3 4,  Kunhua Yang 1 2,  Yang Liu 1 2 5,  Qiang Lian 6,  Hongzhi Liu 1 2,  Yuanhao Fan 1 2,  Hang Zhou 1 2,  Bingtong Yan 1 2,  Yiming Chen 1 2,  Assanali Sultanbekov 1 2,  Yuxuan Liang 1 2,  Ying Wang 1 2,  Jianqun Wu 7,  Hongmei Liu 1 2,  Guibing Fu 3,  Decheng Wu 1 2,  Chao Liu 1 2
Affiliations

Affiliations

  • 1 Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen 518055, China.
  • 2 Guangdong Provincial Key Laboratory of Advanced Biomaterials, Southern University of Science and Technology, Shenzhen 518055, China.
  • 3 Shenzhen Children's Hospital, Shenzhen 518038, China.
  • 4 Shenzhen Pediatrics Institute of Shantou University Medical College, Shenzhen 518038, China.
  • 5 Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, 321 Zhongshan Road, Nanjing 210008, China.
  • 6 The Second Clinical Medical College of Jinan University, Shenzhen 518020, China.
  • 7 Department of Traumatic Surgery, Center for Orthopedic Surgery, the Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.
PMID: 41717818 DOI: 10.1021/acsbiomaterials.5c00877
Abstract

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.

Keywords

biomechanical loading; kartogenin; meniscus defect; synovial-derived mesenchymal stem cell; tissue-engineered meniscus.

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