Abstract 5839: Living Tissue Engineered Heart Valves Based On A Composite Self-Expandable Sandwich-Structured Scaffold And Autolgous Adult Stem Cells: First In Vivo Experiences Towards A Complete Minimally Invasive Approach
Background: A clinically relevant heart valve tissue engineering concept requires minimally invasive techniques for both cell harvest and valve implantation. Here, we present first experiences with autologous tissue engineered heart valves fabricated from composite self-expandable biodegradable scaffolds and adult stem cells implanted by minimally invasive procedures in a sheep model.
Methods: Sandwich-structured heart valve scaffolds (n= 12) were fabricated from non-woven PLDLA meshes coated with electrospun PLDLA nanofibers and integrated in self-expanding nitinol stents. Scaffolds were seeded with either autologous ovine bone marrow (BMC; n= 4) or jugular vein-derived cells (JVC; n= 8) and cultured in bioreactors. After 9d, heart valves were endothelialized with autologous peripheral blood-derived endothelial progenitor cells and jugular vein-derived endothelial cells, respectively. After additional 3d, heart valves (n= 6) were implanted trans-apically in pulmonary position. Controls were analysed (n= 6) as to tissue formation and composition (histology, biochemical assays). Mechanical properties were determined by tensile tests. In vivo performance was assessed by echocardiography up to 4 weeks.
Results: Histology revealed cell attachment and ingrowth into the scaffold material resulting in layered tissues with endothelialized, eNOS positive surfaces. Amounts of GAG and cell number were similar in all heart valves, comparable to native tissues. Collagen production was higher in BMC based heart valves compared to JVC-derived tissues (Hydroyproline amount 34% vs. 20% of native tissues). Mechanical profiles demonstrated physiological tissue strength (max. tensile stress 0.41± 0.21 MPa) but less elasticity (E-Moduli 1.89± 0.79 MPa) independent of the cell source. Echocardiography displayed in vivo functionality (transvalvular mean pressure gradient 10.36± 3.17 mm/Hg) with more flexibility of BMC based heart valves leaflets.
Conclusions: These results demonstrate that heart valve tissue engineering based on a minimally invasive technique for both cell harvest and valve implantation is feasible. This clinically relevant approach is currently investigated in long-term animal studies.