Abstract
ObjectivePericardial patches are commonly used in vascular surgery to close arteriotomies. The mechanism of early healing after patch implantation is still not well defined. We used a rat aortic patch model to assess pericardial patch healing and examined Ephrin-B2, a marker of arterial identity, expression within the post-implantation patch. We also determined whether endothelial progenitor cells (EPC) are associated with early patch healing in the arterial environment.MethodsWistar rats (200–250 grams) underwent infrarenal aortic arteriotomy and then closure via bovine or porcine pericardial patch angioplasty. Control groups included subcutaneously implanted patches. Patches were harvested at 0–30 days and analyzed by histology, immunohistochemistry, immunofluorescence and Western blot as well as quantitative PCR.ResultsPrior to implantation, pericardial patches are largely composed of collagen and are acellular. Following arterial implantation, increasing numbers of CD68-positive cells as well as Ephrin-B2 and CD34 dual-positive cells are found within both bovine and porcine pericardial patches, whereas the infiltrating cells are negative for vWF and α-actin. Porcine patches have a luminal monolayer of cells at day 7, compared to bovine patches that have fewer luminal cells. Subcutaneously implanted patches do not attract Ephrin-B2/CD34-positive cells. By day 30, both bovine and porcine pericardial patches develop a neointima that contains Ephrin-B2, CD34, and VEGFR2-positive cells.ConclusionBoth CD68-positive and Ephrin-B2 and CD34 dual-positive cells infiltrate the pericardial patch early after implantation. Arteriotomy closure via pericardial patch angioplasty shows patch adaptation to the arterial environment that may involve a foreign body response as well as localization of EPC. Arterial remodeling of pericardial patches support endothelialization and may represent a paradigm of healing of scaffolds used for tissue engineering.
Highlights
Following arterial implantation, increasing numbers of CD68-positive cells as well as Ephrin-B2 and CD34 dual-positive cells are found within both bovine and porcine pericardial patches, whereas the infiltrating cells are negative for vWF and a-actin
The use of patch angioplasty during carotid endarterectomy and other arterial closure has become standard in vascular surgery as patch use is associated with improved patient outcomes including reduced risk of restenosis [1,2,3]
We have previously shown that arterialized vein grafts show increased cellularity and matrix in all layers of the vessel wall, as well as diminished expression of the venous marker Eph-B4, yet they fail to express Ephrin-B2, a marker of arterial identity [11]
Summary
The use of patch angioplasty during carotid endarterectomy and other arterial closure has become standard in vascular surgery as patch use is associated with improved patient outcomes including reduced risk of restenosis [1,2,3]. Despite use of bovine pericardial patches in human patients for almost two decades, long-term results for this biomaterial remain poorly documented, and the mechanism of healing after patch implantation likewise remains unknown. It is not even known whether cells infiltrate the patch or whether these patches support endothelialization when placed into the arterial circulation
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