Prevention of neointimal hyperplasia associated with modified stretch expanded polytetrafluoroethylene hemodialysis grafts (Gore) in an experimental preclinical study in swine

Gessaroli, M.; Bombardi, Cristiano; Giunti, Massimo; Bacci, Maria Laura

doi:10.1016/j.jvs.2011.07.076

Cited by 15 publications

(20 citation statements)

References 39 publications

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“…When the diameter of a host vessel reduces below 6 mm, the physical occlusion of grafts caused by thrombosis becomes unresolvable . Moreover, grafting a construct frequently causes disturbed flow, which induces stenosis . The diameter of conventional constructs cannot be customized to fit various vessel diameters, which results in vascular wall damage (Figure S1 and Video S1, Supporting Information).…”

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Development of a Shape‐Memory Tube to Prevent Vascular Stenosis

et al. 2019

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Figure S1 and Video S1, Supporting Information). Vessel-damage-free deployment requires the shape recovery of a graft through circumferential tube expansion by ≈40%-50% to fit the host vessel after insertion (Videos S1-S3, Supporting Information). Hence, a new class of shape memory polymer (SMP) library was synthesized through ring opening polymerization [3] with ε-caprolactone (CL) and glycidyl methacrylate (GMA) monomers (Figure 1a; Figure S2, Supporting Information). Vessel property-matching optimization necessitated a combinatorial design strategy [4] to produce tunable SMP properties through a series of development steps (Figure 1b-g). First, the idea of decreasing the shape recovery temperature, which was represented by melting temperature (T m ), to the body temperature range was validated [5] by the differential scanning calorimetry (DSC) (Figure 1b). T m decreased from the temperature of the base poly(ε-caprolactone) (PCL) to that of our SMPs because crosslinking reduced the crystallinity of PCL. This effect was more dominant compared to the increase in the tightness of the polymer chains owing to Inserting a graft into vessels with different diameters frequently causes severe damage to the host vessels. Poor flow patency is an unresolved issue in grafts, particularly those with diameters less than 6 mm, because of vessel occlusion caused by disturbed blood flow following fast clotting. Herein, successful patency in the deployment of an ≈2 mm diameter graft into a porcine vessel is reported. A new library of property-tunable shape-memory polymers that prevent vessel damage by expanding the graft diameter circumferentially upon implantation is presented. The polymers undergo seven consecutive cycles of strain energy-preserved shape programming. Moreover, the new graft tube, which features a diffuser shape, minimizes disturbed flow formation and prevents thrombosis because its surface is coated with nitric-oxide-releasing peptides. Improved patency in a porcine vessel for 18 d is demonstrated while occlusive vascular remodeling occurs. These insights will help advance vascular graft design. Biomedicine

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Development of a Shape‐Memory Tube to Prevent Vascular Stenosis

et al. 2019

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“…Considering the potential of perivascular cells in the field of regenerative medicine (10) and cardiovascular physiopathology (21) and the usefulness of pig as an animal model in these fields (16,18,28,40,48,52,53), we recently isolated and characterized a population of MSC-like cells from porcine aorta. We named these cells porcine aortic vascular precursor cells (pAVPCs) for their differentiation potential and for their pericyte-like proprieties in vitro (51).…”

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In vitro differentiation of porcine aortic vascular precursor cells to endothelial and vascular smooth muscle cells

Zaniboni

Bernardini

Bertocchi

et al. 2015

American Journal of Physiology-Cell Physiology

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Recent findings suggest that progenitor and multipotent mesenchymal stromal cells (MSCs) are associated with vascular niches. Cells displaying mesenchymal properties and differentiating to whole components of a functional blood vessel, including endothelial and smooth muscle cells, can be defined as vascular stem cells (VSCs). Recently, we isolated a population of porcine aortic vascular precursor cells (pAVPCs), which have MSC- and pericyte-like properties. The aim of the present work was to investigate whether pAVPCs possess VSC-like properties and assess their differentiation potential toward endothelial and smooth muscle lineages. pAVPCs, maintained in a specific pericyte growth medium, were cultured in high-glucose DMEM + 10% FBS (long-term medium, LTM) or in human endothelial serum-free medium + 5% FBS and 50 ng/ml of hVEGF (endothelial differentiation medium, EDM). After 21 days of culture in LTM, pAVPCs showed an elongated fibroblast-like morphology, and they seem to organize in cord-like structures. qPCR analysis of smooth muscle markers [α-smooth muscle actin (α-SMA), calponin, and smooth muscle myosin (SMM) heavy chain] showed a significant increment of the transcripts, and immunofluorescence analysis confirmed the presence of α-SMA and SMM proteins. After 21 days of culture in EDM, pAVPCs displayed an endothelial cell-like morphology and revealed the upregulation of the expression of endothelial markers (CD31, vascular endothelial-cadherin, von Willebrand factor, and endothelial nitric oxide synthase) showing the CD31-typical pattern. In conclusion, pAVPCs could be defined as a VSC-like population considering that, if they are maintained in a specific pericyte medium, they express MSC markers, and they have, in addition to the classical mesenchymal trilineage differentiation potential, the capacity to differentiate in vitro toward the smooth muscle and the endothelial cell phenotypes.

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“…Overall, due to its anatomy and physiology, the pig is a relevant animal model for studying cardiovascular physiopathology (21,22,61,63,64) and for preclinical studies on MSC therapy (23,24,35,52).…”

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Cells derived from porcine aorta tunica media show mesenchymal stromal-like cell properties in in vitro culture

Zaniboni

Bernardini

Alessandri

et al. 2014

American Journal of Physiology-Cell Physiology

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Several studies have already described the presence of specialized niches of precursor cells in vasculature wall, and it has been shown that these populations share several features with mesenchymal stromal cells (MSCs). Considering the relevance of MSCs in the cardiovascular physiopathology and regenerative medicine, and the usefulness of the pig animal model in this field, we reported a new method for MSC-like cell isolation from pig aorta. Filling the vessel with a collagenase solution for 40 min, all endothelial cells were detached and discarded and then collagenase treatment was repeated for 4 h to digest approximately one-third of the tunica media. The ability of our method to select a population of MSC-like cells from tunica media could be ascribed in part to the elimination of contaminant cells from the intimal layer and in part to the overnight culture in the high antibiotic/antimycotic condition and to the starvation step. Aortic-derived cells show an elongated, spindle shape, fibroblast-like morphology, as reported for MSCs, stain positively for CD44, CD56, CD90, and CD105; stain negatively for CD34 and CD45; and express CD73 mRNA. Moreover, these cells show the classical mesenchymal trilineage differentiation potential. Under our in vitro culture conditions, aortic-derived cells share some phenotypical features with pericytes and are able to take part in the formation of network-like structures if cocultured with human umbilical vein endothelial cells. In conclusion, our work reports a simple and highly suitable method for obtaining large numbers of precursor MSC-like cells derived from the porcine aortic wall.

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Prevention of neointimal hyperplasia associated with modified stretch expanded polytetrafluoroethylene hemodialysis grafts (Gore) in an experimental preclinical study in swine

Abstract: Data provide evidence of the efficacy of modified stretch ePTFE grafts with an added radial stretch cuff for the prevention of NH in swine models and support the hypothesis of the pivotal role of mismatch compliance between the graft and the vein wall in NH development.

Cited by 15 publications

References 39 publications

Development of a Shape‐Memory Tube to Prevent Vascular Stenosis

Development of a Shape‐Memory Tube to Prevent Vascular Stenosis

In vitro differentiation of porcine aortic vascular precursor cells to endothelial and vascular smooth muscle cells

Cells derived from porcine aorta tunica media show mesenchymal stromal-like cell properties in in vitro culture

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