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Implantation of Various Cell-Free Matrixes Does Not Contribute to the Restoration of Hyaline Cartilage within Full-Thickness Focal Defects.

ABSTRACT: Articular cartilage is a highly organized tissue that has a limited ability to heal. Tissue engineering is actively exploited for joint tissue reconstruction in numerous cases of articular cartilage degeneration associated with trauma, arthrosis, rheumatoid arthritis, and osteoarthritis. However, the optimal scaffolds for cartilage repair are not yet identified. Here we have directly compared five various scaffolds, namely collagen-I membrane, collagen-II membrane, decellularized cartilage, a cellulose-based implant, and commercially available Chondro-Gide^® (Geistlich Pharma AG, Wolhusen, Switzerland) collagen membrane. The scaffolds were implanted in osteochondral full-thickness defects, formed on adult Wistar rats using a hand-held cutter with a diameter of 2.0 mm and a depth of up to the subchondral bone. The congruence of the articular surface was almost fully restored by decellularized cartilage and collagen type II-based scaffold. The most vivid restoration was observed 4 months after the implantation. The formation of hyaline cartilage was not detected in any of the groups. Despite cellular infiltration into scaffolds being observed in each group except cellulose, neither chondrocytes nor chondro-progenitors were detected. We concluded that for restoration of hyaline cartilage, scaffolds have to be combined either with cellular therapy or morphogens promoting chondrogenic differentiation.

SUBMITTER: Ibragimova SI

PROVIDER: S-EPMC8745283 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Implantation of Various Cell-Free Matrixes Does Not Contribute to the Restoration of Hyaline Cartilage within Full-Thickness Focal Defects.

Ibragimova Shabnam I SI Medvedeva Ekaterina V EV Romanova Irina A IA Istranov Leonid P LP Istranova Elena V EV Lychagin Aleksey V AV Nedorubov Andrey A AA Timashev Peter S PS Telpukhov Vladimir I VI Chagin Andrei S AS

International journal of molecular sciences 20211228 1

Articular cartilage is a highly organized tissue that has a limited ability to heal. Tissue engineering is actively exploited for joint tissue reconstruction in numerous cases of articular cartilage degeneration associated with trauma, arthrosis, rheumatoid arthritis, and osteoarthritis. However, the optimal scaffolds for cartilage repair are not yet identified. Here we have directly compared five various scaffolds, namely collagen-I membrane, collagen-II membrane, decellularized cartilage, a ce ...[more]

PMID: 35008719

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Project description:BackgroundCartilage repair has been a challenge in the field of orthopaedics for decades, highlighting the significance of investigating potential therapeutic drugs. In this study, we explored the effect of the SHP2 inhibitor SHP099, a small-molecule drug, on cartilage repair.MethodsHuman synovial mesenchymal stem cells (SMSCs) were isolated, and their three-way differentiation potential was examined. After treatment with chondrogenic medium, the chondrogenic effect of SHP099 on SMSCs was examined by western blot, qPCR, and immunofluorescence (IF). Micro-mass culture was also used to detect the effect of SHP099. To explore the chondrogenic effects of SHP099 in vivo, full-thickness cartilage defects with microfractures were constructed in the right femoral trochlea of New Zealand White rabbits. Intraarticular injection of SHP099 or normal saline was performed twice a week for 6 weeks. Cartilage repair was evaluated by haematoxylin and eosin (HE) staining and safranin O/fast green staining. Immunohistochemistry (IHC) for collagen II (COL2) was also conducted to verify the abundance of cartilage extracellular matrix after SHP099 treatment. The mechanism involving yes-associated protein (YAP) and WNT signalling was investigated in vitro.ResultsSMSCs isolated from human synovium have optimal multi-differentiation potential. SHP099 increased chondrogenic marker (SOX9, COL2) expression and decreased hypertrophic marker (COL10, RUNX2) expression in SMSCs. In micro-mass culture, the SHP099-induced cartilage tissues had a better result of Safranin O and Toluidine blue staining and are enriched in cartilage-specific collagen II. Inhibition of YAP and WNT signalling was also observed. Moreover, compared to the normal saline group at 6 weeks, intraarticular injection of SHP099 resulted in better defect filling, forming increased hyaline cartilage-like tissue with higher levels of glycosaminoglycan (GAG) and COL2.ConclusionSHP099 promotes the repair of rabbit full-thickness cartilage defects, representing a potential therapeutic drug for cartilage repair.The translational potential of this articleThis study provides evidence that SHP2 inhibition promotes chondrogenesis and the repair of cartilage in defect area, which could be a novel therapeutic approach for cartilage repair.

Dataset Information

Implantation of Various Cell-Free Matrixes Does Not Contribute to the Restoration of Hyaline Cartilage within Full-Thickness Focal Defects.

Publications

Implantation of Various Cell-Free Matrixes Does Not Contribute to the Restoration of Hyaline Cartilage within Full-Thickness Focal Defects.

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