Wang, Jingsong ORCID: https://orcid.org/0000-0001-5002-2636 (2021) Cell-based meniscus characterization and regeneration: basic science, tissue engineering and clinical applications. Doctoral thesis, Keele University.

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Abstract

As a vital part of the knee joint, the meniscus acts to prevent the degeneration of articular cartilage and the onset of knee osteoarthritis (OA). Repairing meniscus injuries in the avascular region is still a challenge in orthopaedics. The current primary option is partial meniscectomy which can significantly increase the risk of developing knee OA. This unmet clinical need has shifted the research focus on the field towards novel cell-based tissue engineering approaches. In this thesis, the chondrogenic and immunomodulatory properties of regional meniscal cells from degenerative meniscus tissue have been investigated, in order to begin to understand more fully the changes in meniscal cells during knee degeneration. In addition, progenitor populations from human meniscus tissues have been isolated and the cell phenotypes characterised, and their proliferation rate and chondrogenic potency for meniscus regeneration analysed as compared their whole mixed population. Then moving to cell-based meniscus tissue engineering, a sheep explant model was used to examine the feasibility of utilising autologous avascular meniscal cells with a fibrin gel delivery system into a clinical grade polyurethane scaffold with the aim of promoting meniscus regeneration. A review has also been undertaken of the mid to long-term outcome of patients who had received combined autologous chondrocyte implantation (ACI) and meniscus allograft transplantation (n=20) or commercial meniscus scaffolds (n=8) treated at RJAH Orthopaedic Hospital (Oswestry).
Herein, it has been demonstrated that both avascular and vascular meniscal cells have chondrogenic capacity in vitro and the immunopositivity levels of the integrin markers CD49b and CD49c are valuable in distinguishing avascular, vascular meniscus cell and chondrocyte phenotypes. Histology of degenerated meniscus showed decreased vascularity in “tree-like” transverse collagen fibres, which may indicate that such structures are involved in the meniscus pathological process. This work has also demonstrated that the human meniscus contains a meniscal progenitor population in both the avascular and
vascular regions, based on clonogenicity and chondrogenic differentiation capacity. Results suggested that progenitor meniscal cells from vascular regions exhibit superior regenerative characteristics which are likely associated with the better meniscal healing properties noted in the vascular region of the tissue. The sheep explant experiment proved the feasibility of using fibrin gel to deliver autologous avascular meniscal cells in a clinical grade meniscus substitute in vitro. Further, the fibrin seeded scaffolds showed increased cell numbers and more matrix production compared to scaffolds seeded without fibrin.
In the clinical study, the data analysed showed for the first time that combining ACI with meniscal allograft transplantation or synthetic scaffold transplant to treat patients with cartilage defects and meniscal deficiency can provide successful mid-long term clinical outcomes, with 10-year survival rates of 71% in the MAT group and 83% in the scaffold group. Perhaps combining cells in fibrin in the scaffold could lead to even greater successes in the long term.

Item Type: Thesis (Doctoral)
Subjects: R Medicine > RC Internal medicine
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
Contributors: Wright, KT (Thesis advisor)
Roberts, S (Thesis advisor)
Depositing User: Lisa Bailey
Date Deposited: 26 Jul 2021 09:35
Last Modified: 26 Jul 2021 09:35
URI: https://eprints.keele.ac.uk/id/eprint/9864

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