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Title: The cellular biology of tendon grafting and graft integration
Author: Alam, Nawsheen
ISNI:       0000 0004 2708 3483
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2011
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Background: Prolonged recovery after tendon injury has given rise to the need for innovative therapy including tendon engineering and cell based therapies. The role of cells in grafted or engineered tendon is poorly understood. Clarifying the persistence of grafted tissue is fundamentally important to ensure that tissue engineering strategies are fit for clinical application. We have devised a murine model for tendon grafting that allows for cell tracking and the assessment of tendon integration and engineered construct integration. Materials and methods: We studied the macroscopic and microscopic architecture of the mouse Achilles tendon to investigate its properties as a study model. Using microsurgical techniques, transgenic tendon grafting procedures were then carried out between C57B/L6 wild type and GFP (Green Fluorescent Protein) mice Achilles tendon. The temporal and spatial fate of the cells in the graft was assessed using quantitative serial histology and immunohistochemistry with Three Dimensional reconstruction. Markers for proliferation, collagen synthesis, cell death and inflammatory infiltrate were used. The Achilles tendon model was also applied to test its applicability to investigate tissue engineered tendon constructs developed in vitro. Results: GFP positive graft cells were seen at Day 3 and Day 21 but disappeared by Day 90. At Day 21both graft cells and the cells of the recipient tendon showed intense collagen synthetic activity. At the same time both graft and host tendon cells began to show signs of apoptosis which continued till Day 90. Subcutaneous tissue and paratenon maintained a much higher level of cellularity, cell proliferation, collagen synthesis and apoptosis at all time. The interplay between cell activity and cell death appear to play central role in the integration of the tendon graft. The persistence of tissue engineered tendon constructs was far less than syngenic or autografts. The Achilles tendon model proved to be a robust and economically viable model for testing of biomaterials particularly at the early stage of their development. Conclusion: The cells of tendon grafts persist only for a finite time before being repopulated by host cells. Tissue engineered cell-based constructs do not provide sufficient persistence to substitute in place of syngenic or autologous graft options. Future designs of engineered tendon should facilitate tendon integration and aim to persist for longer periods of time in order to participate in the healing process.
Supervisor: Mcgrouther, Duncan ; Wong, Jason Sponsor: The Royal College of Surgeons of England (RCSEng) ; British Society for Surgery of the Hands (BSSH)
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Tendon graft ; Tendon Engineering