Completely Biological Tubes of Cell-Produced Extracellular Matrix for Vascular Grafts and Tubular Heart Valves

We have developed a novel tissue-engineered vascular graft, which is allogeneic upon a decellularization performed prior to implantation and thus “off-the-shelf.” It is grown from remodeling of ovine dermal fibroblasts... [ view full abstract ]

We have developed a novel tissue-engineered vascular graft, which is allogeneic upon a decellularization performed prior to implantation and thus “off-the-shelf.” It is grown from remodeling of ovine dermal fibroblasts entrapped in a sacrificial fibrin gel into tissue tube that is then decellularized using sequential detergent treatments. The resulting cell-produced matrix tube possesses physiological strength, compliance, and alignment (circumferential).

We have shown excellent results implanting these tubes into the sheep femoral position at 6 months, including complete recellularization and positive remodeling) without mineralization, dilatation, or immune response (Syedain et al, 2015). Similar results have recently been obtained in a pivotal preclinical model as an AV graft for 6 months, including periodic access with a dialysis needle (Syedain et al, unpublished). We have also recently shown somatic growth of these tubes implanted into the pulmonary of young lambs for almost 50 weeks, through adulthood (Syedain et al, submitted).

Using the concept of a tubular valve, where the tube collapses inward upon back-pressure between 3 equi-spaced constraints placed around the periphery to create one-way valve action, we have reported unprecedented results implanting valves fabricated from these tubes mounted on 3-pronged crown frames into the sheep aortic position for 6 months (Syedain et al, 2015). We have also used the principle of a tubular heart valve to innovate a tubular pediatric heart valve based on attaching two tubes together with degradable suture to provide the constraints (Reimer et al, 2015) and developed initial experience in a young lamb model (Reimer et al, 2015).