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Title: Extracellular matrix remodelling of autologous tissue engineered conduits implanted in a growing animal model
Author: Cummings, Ian Gustavus
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2010
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Abstract Background Living, autologous vascular grafts with the ability to remodel , repair and grow may overcome the limitations of contemporary available options. In this thesis we investigate the ability for autologous, tissue engineered pulmonary artery (PA) conduits to remodel and grow in vivo. Methods and Results Vascular grafts fabricated from biodegradable scaffolds were sequentially seeded with autologous vascular derived cells and grown in vitro under biomimetic conditions. These tissue engineered vascular grafts were surgically implanted as main PA replacements in 12 lambs divided into four study groups sacrificed at 20, 50, 80 and 100 weeks post implantation. Transoesophageal echocardiography (TOE) and Computed tomography (CT) angiography was performed in all animals to further assess function and in vivo growth of the tissue engineered PA. Tissue analyses of the conduits were carried out and compared to native tissue over the 2 year study period. The tissue engineered PA showed good functional performance on TOE and CT. There was a significant increase in diameter of the tissue engineered PA of up to 30% and length increases of up to 45%. Histological analysis of tissue engineered PA showed tissue formation comparable to native. Biochemical analysis revealed the cell number and proteoglycan content comparable to native tissue and a significant increase in collagen content over time. The biomechanical analysis showed stronger but less elastic tissue properties compared to native tissue. Matrix metalloproteinases (MMP) as markers for tissue remodelling showed increased active MMP-2 and MMP-9 activity as compared to native tissue. • Conclusion There is on-going remodelling of the tissue engineered PA with increased haemodynamic demands of the growing model.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available