Pericardial Patch Angioplasty Heals via an Ephrin-B2 and CD34 Positive Cell Mediated Mechanism

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.

Covalent modification of pericardial patches for sustained rapamycin delivery inhibits venous neointimal hyperplasia

“…Recent studies from our laboratory showed that the pericardial patch may be a unique niche microenvironment that attracts endothelial progenitor cells after implantation, promoting incorporation into the host vessel that may be responsible for long term durability and clinical success1819. Although open venous surgery is performed less frequently compared to open arterial surgery, patches are also used in venous surgery20, as venous procedures are frequently complicated by aggressive neointimal hyperplasia and restenosis, possibly due to the lower shear stress in the venous system2122232425.…”

“…More specifically, we hypothesized that implantation of pericardial patches, with conjugated NP-containing therapeutics, would allow site-specific delivery of therapeutic agents ideally targeted to inhibit localized neointimal hyperplasia that forms on these implanted patches. Accordingly, we developed a venous model of patch angioplasty that shows stable and aggressive neointimal hyperplasia compared to that which develops in arteries17, based upon our previous experience with arterial patch angioplasty18. We conjugated rapamycin-containing NP (NP-rapamycin) to bovine pericardial patches, and determined the ability of the localized drug to inhibit neointimal hyperplasia that develops on the pericardial patch.…”

Pretreatment of pericardial patches with antibiotics does not alter patch healing in vivo

“…9 In brief, male Wistar rats (6-8 weeks) were anesthetized with isoflurane, and the infrarenal aorta exposed 3-5 mm below the level of the renal arteries. The aorta was clamped and a longitudinal 3 mm arteriotomy was made on the anterior wall of the aorta.…”

“…2, 3 Despite the structure of pericardial patches, with spaces present in between the collagen fibers allowing cell infiltration, 9 these patches have shown to be markedly resistant to infection. For example, in a recent series following 256 bovine pericardial patches over 12 years, there were no patch infections.…”

“…12, 13 We have previously shown that pericardial patches heal after implantation, with infiltration of CD68-positive macrophages and CD34/VEGFR2-dual positive arterial stem cells into the patch, providing a potential explanation for pericardial patch durability and resistance to infection. 2, 9 …”