Abstract 10105: Right Ventricular Outflow Tract Replacement: Towards Cell-Free Cell Therapy ?
Background: We have shown in an ovine model that a polydioxanone (PDO) patch seeded with mesenchymal stem cells (MSC) and implanted across the pulmonary annulus was predominantly repopulated by host cells while the grafted ones were cleared. We now tested whether the MSC-associated homing factors could be mimicked by an acellular biomimetic scaffold.
Methods: Thirty-nine rats underwent a partial replacement of the inferior vena cava (IVC) with an acellular electrospun PDO (n=18) or polyurethane (PU, n=21) patch. Electrospinning settings (applied voltage, flow rate, solvent, polymer concentration, collection time) were systematically varied to optimize the properties of the resultant patches which were then used for in vivo studies. After 6 wks (extended to 3 mo. in 6 rats), rats underwent MRI to assess potential luminal changes. After sacrifice, specimens encompassing the native IVC and the patches were processed for the presence of endothelial cells, the total macrophage pool and macrophages involved in vascular remodeling (von Willebrand, ED1 and ED2 immunostaining, respectively).
Results: The electrospun patches were found to comprise uniform meshes of 1-D polymer strands, with acceptable pore sizes, as assessed by scanning electron microscopy. Manual inspection confirmed they had appropriate robustness, performance under tensile stress, and ease of suturing. MRI did not detect significant luminal changes (stenosis, occlusion, dilatation) in either group. Histologically, both polymers were evenly lined by von Willebrand-positive endothelial cells but elicited markedly different inflammatory responses. At 6 wks, the PDO group yielded a major infiltration of macrophages (predominantly ED1-positive) which had almost completely disappeared by 3 mo. where the patch could no longer be detected and distinguished from the native IVC wall. Conversely, PU patches remained clearly visible and insulated from the surrounding tissue by clustered ED-1-positive macrophages.
Conclusion: The ability of an appropriately designed acellular electrospun biomaterial to leverage natural healing mechanisms could represent an important translational step in the development of a bioengineered conduit for right ventricular outflow tract replacement.
- © 2013 by American Heart Association, Inc.