In Situ Cardiovascular Tissue Engineering

Abstract

In this thesis, the feasibility of in situ TE for vascular and valvular purposes were tested with the use of different materials, and animal models. First, the feasibility of a decellularized biological scaffold (pSIS-ECM) as pulmonary heart valve prosthesis is examined in sheep (Chapter 2). Next, various synthetic scaffolds are tested. In Chapter 3, a new small animal model to test vascular synthetic scaffolds in rats is presented. Small animal models currently used are difficult to extrapolate because trans-anastomotic, and transmural ingrowth of cells from neighboring tissue occurs abundantly in small animal models, but sparsely in humans. By shielding aortic interposition grafts in rats with Gore-Tex, in-growth from adjacent tissue was prevented. This method enabled us to study circulating cells as the predominant origin of cellularization, and subsequent neotissue formation. This animal model is used in Chapters 4, 5, and 6 to assess possible bioactive chemokines for neotissue formation. Such as Monocyte Chemotactin Protein-1 (a key mediators for inflammation-mediated remodeling), Stromal cell Derived Factor 1α (a chemoattractant of progenitor cells with an important role in tissue repair), and poly(ethylene glycol) (a non-cell adhesive molecule for selective cell binding). In Chapter 7, Iodine is added to the synthetic scaffold to determine if scaffold degradation could be visualized with a non-invasive imaging modality (CT scanning). Finally, two polymers are tested as heart valve prosthesis in a large animal model in Chapter 8 and 9. Conclusions are drawn and future perspectives described in Chapter 10.