Patch angioplasty is commonly performed after carotid endarterectomy. Although patch angioplasty is known for reduction in perioperative and long-term stroke rates as well as restenosis compared to primary closure, the ultimate patch in terms of performance and tissue remodeling is yet to be identified. This study evaluated the performance and remodeling potential of a novel tissue-engineered collagen scaffold (VascuCel) in an ovine carotid model. Cross-bred sheep (n = 6; body weight, 35-55 kg) were randomized into two groups (n = 3 animals per group). Implants were explanted at two different time points. In group 1, implants (n = 3) were explanted at 30 days and in group 2, implants (n = 3) explanted at 180 days. Computed tomography angiograms were performed at the end of each time point. Explants were assessed by means of macroscopic appearance, tensile characteristics, and histology (hematoxylin and eosin, trichrome, Von Kossa, and picrosirius red). All animals survived the entire study period without any vascular adverse events. Macroscopically, both early and late explants demonstrated smooth, intimal surfaces with well-incorporated native tissue on the edges of the scaffold (Fig 1). No signs of thromboembolic-related deposits were visible on the intimal surface (n = 12 grafts). Tensile strength of explants demonstrated acceptable vascular strength (full thickness = 8.14 ± 1.68 MPa; neointima = 2.9 ± 0.41 MPa). Histology in early explants showed a partially endothelialized neointima on the luminal side and presence of granulation tissue on the outside and the scaffold between these two layers. Computed tomography angiographic assessment of animals in the late follow-up group demonstrated normal blood flow in all implanted carotids without any signs of vessel wall thickening (stenosis). Histology of late explants demonstrated unique transdifferentiation of the scaffold into three distinctive layers, which consisted of a completely endothelialized neointima with smooth muscle cells, the scaffold saturated with host fibroblasts resembling the media, and an external layer consisting of loose collagen fibers resembling the adventitia (Fig 2). Normal flow dynamics, optimal tensile properties, and effective incorporation of the VascuCel patch by surrounding host tissue suggest ultimate function and reliability of the VascuCel patch in the carotid position. Superior transdifferentiation and remodeling demonstrated enhanced biocompatibility which resulted in site-specific transformation of the VascuCel patch into the ideal repaired vascular construct.Fig 2View Large Image Figure ViewerDownload Hi-res image Download (PPT)