2. Academic Validation
  3. 3D-bioprinted BMSC-laden biomimetic multiphasic scaffolds for efficient repair of osteochondral defects in an osteoarthritic rat model

3D-bioprinted BMSC-laden biomimetic multiphasic scaffolds for efficient repair of osteochondral defects in an osteoarthritic rat model

  • Biomaterials. 2021 Dec:279:121216. doi: 10.1016/j.biomaterials.2021.121216.
Yanzhi Liu 1,  Liuqi Peng 2,  Lingli Li 3,  Cuishan Huang 3,  Keda Shi 3,  Xiangbo Meng 3,  Pinpin Wang 2,  Mingming Wu 2,  Ling Li 3,  Huijuan Cao 3,  Kefeng Wu 4,  Qingqiang Zeng 3,  Haobo Pan 2,  William Weijia Lu 5,  Ling Qin 6,  Changshun Ruan 7,  Xinluan Wang 8
Affiliations

Affiliations

  • 1 Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China; Guangdong Key Laboratory for Research and Development of Natural Drugs, Marine Medical Research Institute, Guangdong Medical University, Zhanjiang, 524023, China.
  • 2 Research Center for Human Tissue and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
  • 3 Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
  • 4 Guangdong Key Laboratory for Research and Development of Natural Drugs, Marine Medical Research Institute, Guangdong Medical University, Zhanjiang, 524023, China.
  • 5 Research Center for Human Tissue and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China; Department of Orthopaedic and Traumatology, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.
  • 6 Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China; Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address: [email protected].
  • 7 Research Center for Human Tissue and Organs Degeneration, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. Electronic address: [email protected].
  • 8 Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. Electronic address: [email protected].
PMID: 34739982 DOI: 10.1016/j.biomaterials.2021.121216
Abstract

Osteochondral defect repair in osteoarthritis (OA) remains an unsolved clinical problem due to the lack of enough seed cells in the defect and chronic inflammation in the joint. To address this clinical need, we designed a bone marrow-derived mesenchymal stem cell (BMSC)-laden 3D-bioprinted multilayer scaffold with methacrylated hyaluronic acid (MeHA)/polycaprolactone incorporating kartogenin and β-TCP for osteochondral defect repair within each region. BMSC-laden MeHA was designed to actively introduce BMSCs in situ, and diclofenac sodium (DC)-incorporated matrix metalloproteinase-sensitive peptide-modified MeHA was induced on the BMSC-laden scaffold as an anti-inflammatory strategy. BMSCs in the scaffolds survived, proliferated, and produced large amounts of cartilage-specific extracellular matrix in vitro. The effect of BMSC-laden scaffolds on osteochondral defect repair was investigated in an animal model of medial meniscectomy-induced OA. BMSC-laden scaffolds facilitated chondrogenesis by promoting Collagen II and suppressed interleukin 1β in osteochondral defects of the femoral trochlea. Congruently, BMSC-laden scaffolds significantly improved joint function of the injured leg with respect to the ground support force, paw grip force, and walk gait parameters. Therefore, this research demonstrates the potential of 3D-bioprinted BMSC-laden scaffolds to simultaneously inhibit joint inflammation and promote cartilage defect repair in OA joints.

Keywords

3D bioprinting; BMSC-Laden scaffolds; Cartilage defect; Osteoarthritis; Osteochondral regeneration.

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