A novel endovenous scaffold for the treatment of chronic venous obstruction in a porcine model: Histological and ultrastructural assessment

Abstract

Objective

To investigate the biological effects of a novel endovenous scaffold in a porcine model.

Methods

Petalo is a compliant venous scaffold implanted into the internal jugular veins of 12 healthy pigs. The pigs were sacrificed at one, two, three, and six months, respectively. Microscopic investigations were performed at two blinded laboratories.

Results

Neo-intima formation progressively covering up the stent metallic bars was observed. The inflammatory response of the venous wall showed a peak after three months by the implant, followed by marked reduction after six months. The device induced a significant (p < 0.01) increase of the thickness respect to the control regions, but was comparable in sections obtained after three and six months.

Conclusions

The implant of Petalo compliant venous scaffold in the venous wall of this porcine model is characterized by neointima formation and by an inflammatory reaction which tends to decrease after six months. Our data point against the induction of smooth muscle cells proliferation and migration as confirmed by electronic transmission microscopy analyses.

Keywords

Venous stent animal model venous obstruction venous compliance large veins

Introduction

Recanalization and stenting of chronic venous obstruction have been increasingly executed over the last years^1–9 although no stents dedicated to venous pathology were available until very recently.^10–13 Chronic venous obstruction is currently treated by off label stents, widely used in the arterial system, that are designed to exert a uniform, continuous, and intense radial force against the arterial wall. The model of stents more frequently described in the venous system are the Wallstent^2,9 and various nitinol self-expanding stents.^10–13 A debated technical problem is the sizing of the venous stent. When adapted into the veins, there is the need to use an oversize stent diameter in order to avoid migration to the heart or to the lung circulation.^1–9 The permanent over dilatation may induce a slowdown of the flow possibly leading to progressive circumferential thrombosis, which occurs ranging from 3.5% to 10% of cases.^14,15 On the other hand, the use of an undersized stent or of a stent not covering all areas of disease facilitates the chronic occlusion.⁹ In addition, the transmission of a significant radial force to the delicate vein wall, exercising by available stent technology, promotes an intense inflammatory response up to fibrosis of the venous wall.¹⁴ Moreover, the devices currently used in veins adversely affect the compliance properties of the vein. The venous system needs to be compliant to the hydrostatic pressure, continuously modified by the postural changes of the body, leading to filled or empty veins. Venous compliance is an inherent mechanical property of the vein which of course is not contemplated by the current devices.^16–18

Quite recently, a compliant nitinol vein scaffold denominated “Petalo CVS,” demonstrated intriguing profiles of both safety and efficacy in a porcine model, but histological information about the interaction of the novel stent with the venous wall were completely lacking.¹⁹ Therefore, the purpose of the present pilot study was to evaluate the histologic and ultrastructural aspects of the jugular veins in response to “Petalo CVS” implant in a porcine model.

Methods

Characteristics of the experimented venous scaffold

The endovenous device Petalo CVS is an innovative compliant venous scaffold (CVS) with novel shape and configuration (Figure 1). The prototypes are fabricated by Admedes Schuessler GMBH (Pforzheim, Germany) using a cut laser nitinol technology. Petalo CVS has a substantially tubular convex shape, including four support modules joined by the transverse bridges.¹⁹ The modules are oriented longitudinally and extended along the entire length of the device’s body. The convexity of the four modules is oriented towards the vein wall. The support modules are internally empty, without bridges or other internal elements, to minimize the metal structure. The modules have a radial width in the distal extremity (peripheral respect to the heart) less than the central one (nearest to the heart), to adapt to vein anatomy and avoid proximal migration. Two transversal bridges join each support modules in the central part of the body, leaving the extremity of the modules free and open. The transversal bridges have a substantially gull wing shape. The joined bridges enhance the conformability of the device and reduce the radial force (Figure 1).

Figure 1.

Petalo CVS scaffold is composed by four modules, with the extremities of the modules externally oriented to reduce the contact area and minimize the risk of migration. The extremity close to the heart is larger respect to the peripheral one. Eight “V” shaped transversal bridges join the modules limitedly to the central part of the scaffold, leaving the extremity of the modules free and open to improve the collapsibility of the scaffold.

In the present study, the device had central and distal diameters of 14 mm and 12 mm, respectively. Two devices with different lengths (38 mm and 48 mm) with the above diameters were used for the study.

Animal model and device delivery

A total of 12 pigs of 90 kg of weight were used in the experimental trial. The study was approved by the Ethic Committee of University of Milan and finally approved by the Italian Minister of Health. The study was performed from November 2013 to May 2014 at Veterinary University Hospital of Lodi/University of Milan and conducted following the guide lines of good laboratories practices.

The procedures were conducted under general anesthesia using a standard protocol, monitoring cardiac and respiratory parameters.

The endovascular technique percutaneous approach to venous system and catheter venography was similar to those performed normally in humans, and already described.^17–19 Selective venography of the IJVs was performed by manual injection of a low-viscosity contrast medium (Iomeron 150; Bracco Imaging, Milano, Italy) in anterior–posterior projection. After that, at least one device was inserted in the lower or medium segment of the IJV or at site of valve apparatus, by a standard pull back delivery system. A new phlebography was performed to evaluate the patency of the vein and time of clearance of contrast dye as parameter of flow characteristics.¹⁷

The position of the device in the vein segment was checked. The same procedure was performed for the left jugular vein. At least two devices were inserted for each pig, eventually of different length. At the end of procedure, the inguinal introducer was removed and a light manual compression of the access site was performed. The procedure was now considered completed and the pig was extubated and was hosted to the animal house. All pigs received for one month a daily oral dose of 100 mg of acetylsalicylic acid. Every minor or major adverse events at the site access, or related to the procedure, or to the devices was accurately monitored in each pig. All pigs were monitored during awake and in the post-operative period to avoid adverse events and harms to them.

Sacrifice and tissue harvesting

The animals were sacrificed at different scheduled time: one month (four pigs), two months (two pigs), three months (two pigs), and six months (four pigs) after the implant. All pigs underwent a new endovascular procedure and an open surgery procurement of the target veins using the same anesthetic and endovascular protocols as previously described.

With the animals in general anesthesia, we performed a postoperative catheter venography followed by surgical dissection. We assessed: the position, the integrity, the patency of the device, as well as the presence of thrombosis and/or obstruction. Both IJVs, including the device and a 2 cm long portion of distal jugular vein used as segment for histological control, were removed to assess the macroscopic and microscopic changes of the vein wall in response to the device. This tract was opened longitudinally, submitted to gross examination and photographed. Another longitudinal section was performed and jugular veins were divided into two longitudinal fragments, one of them destined to histological analysis with optical microscopy and the other one to morphological analyses with scanning electron microscopy.

The pigs, at the end of the procedure, were sacrificed, under deep general anaesthesia, by the means of intravenous administration of Tanax.

All data related to the positioning and follow-up of the endovascular device, including the diagnostic procedures and open surgery harvesting of the target vein were recorded on electronic database and hard CRF.¹⁹ All the study procedures were entirely recorded by a video camera. A picture from all surgical specimens was taken and all specimens were classified accordingly. All surgical specimens were accurately stored for a definitive microscopic and macroscopic evaluation that was performed in two different laboratories (University of Ferrara and Milan), where a blind independent evaluation of the specimens was performed.

Histological analysis

For the histological analyses, samples were fixed in formalin 10% for 24 h at 4°C and subsequently rinsed in several changes of cold 70% ethanol. The tissues were dehydrated through an alcohol series and then paraffin embedded using a Shandon Citadel 2000 Tissue Processor. After blocking out, 5 µm thick sections were cut, stained with hematoxylin and eosin (Bio Optica SPA, Milano, Italy) and/or used for immunohistochemistry with the Ab anti-von Willebrand Factor (vWF) (FVIII) (Dako, Carpinteria, CA). In each slide, a negative control was obtained carrying out the immunohistochemistry procedure without the primary antibody. All the sections were acquired with a light microscope (Eclipse TE200 Inverted microscope; Nikon, Tokyo, Japan).²⁰ All metallic rods were removed to allow histological processing. For the wall thickness evaluation, different sections were acquired and digitalised with an Aperio ScanScope® slide scanner and the thickness values of the jugular walls were measured by using the Aperio ImageScope v11.1.2.760 software (Leica Biosystems, Nussloch, Germany). To assess the modification of the wall thickness induced by the stent, at least three different tissue sections were analyzed for each region (control, middle and distal) and the total wall thickness was obtained from at least three randomly selected areas within the slide in correspondence with the device and in the regions between stent.

All the hematoxylin and eosin-stained jugular vein sections were examined by the study pathologist for semi-quantitative and descriptive histopathology.

Electron microscopy

For scanning electron microscopy (SEM) analyses, samples were fixed by immersion in 2.5% glutaraldehyde in 0.1 M buffer phosphate pH 7.4 for 2 h at room temperature. A second fixation was performed in 1% OsO₄ in buffer phosphate for 1 h at room temperature, washed and dehydrated with ethanol series, substituted with propylene oxide 10′ for twice and dried with critical point dryer for 2 h at least. After coating with gold, samples were examined under a ZEISS EVO40 XVP scanning electron microscope.

For transmission electron microscopy (TEM) analyses, samples were fixed in 2% glutaraldehyde in 0.1 M cacodylate buffer 3 h at 48°C before post fixing in 1% osmium tetroxide in the same buffer 3 h. The specimens were dehydrated through a graded acetone series before being embedded in Epoxy resin mixture. Semithin sections (1.5 µm) were cut on a Reichert Om U 2 ultramicrotome using glass knives and stained with toluidine blue. Ultrathin sections (90 nm) were stained with 4% uranyl acetate solution in 50% ethanol and Reynold’s lead citrate and examined using a Hitachi H-800 electron microscope.

Statistical analysis

Statistical analysis data were calculated as median, mean±SD. Box plots were used to show the median and interquartile values for each group of data. The results were evaluated by using an ANOVA test applying a Bonferroni correction. Statistical significance was defined as p < 0.05.

Results

Gross examination

With the aim to investigate the modifications of the vein wall in response to the implant of the Venous Device Petalo CVS, in the first group of analysis, we have examined the morphology of the jugular veins derived from swine that have been implanted bilaterally up to six months. As shown in Figures 2 and 3, each jugular vein was cut into a different number of pieces identifying three areas named as control (A), distal (B) and middle (C) regions. At the gross examination, we did not find migration, fracture, thrombosis and/or obstruction of the scaffold, although the clinical results will be detailed in a separate paper.¹⁹ After one to three months by the implant, the central part of the metallic device was free, detached from the intimal surface; conversely, the two extremities of the implant were connected and surrounded by the intimal surface of the vein wall (Figure 2(a)). After six months, the distal region of the device was always enveloped in the intimal surface and in some cases also in the middle region (Figure 3(a)).

Figure 2.

Morphological analyses of internal jugular veins implanted with Petalo CVS for three months. After three months by the implant, the swine were sacrificed and IJVs were collected for morphological analyses. In (a), gross luminal view of the stent-grafted IJV at three months is shown; the exact location of control (A), distal (B) and middle (C) regions of the IJV is shown. In (b), representative histological images (hematoxylin-eosin stain), of the three regions are given. The neo-intimal tissue is completely covering up the stent metallic bars in the distal region *: Inflammatory area. **: empty spaces before occupied by metallic rods. Magnification 4×. In (c), a representative panel composed of images from control region (A), distal region (B) and the area between two metallic rods (D) is shown. Morphological investigation of the endothelium obtained from different regions of the luminal surface of the IJV was performed by SEM. The regular arrangement of the cells is clearly depicted. Arrow indicates the metallic bar of the device. Magnification 5000×.

Figure 3.

Morphological analyses of internal jugular veins implanted with Petalo CVS for six months. After six months by the implant, the swine were sacrificed and IJVs were collected for morphological analyses. In (a), gross luminal view of the stent-grafted IJV at six months is shown. In (b), representative histological images (hematoxylin-eosin stain) of control (A), distal (B) and middle (C) regions of the IJV are shown. Magnification 4×. **: empty spaces before occupied by metallic rods. *: inflammatory area. In (c), a representative panel composed of images from control region (A), distal/middle regions (B) and the area between two metallic rods (D) is shown. Morphological investigation of the endothelium obtained from different regions of the luminal surface of the IJV was performed by SEM. Arrow indicates the metallic bar of the device. Magnification 5000×.

Light microscopy

Histological examination (Figures 2(b) and 3(b)) of the jugular veins presented wall remodelling with neo-intima formation completely covering up the stent metallic bars in the distal region, after one to three months, and in both distal and middle regions after six months. Furthermore, in correspondence with the sites of incorporation, we have observed irregular wall thickening with intima and media disarrangement, collagen deposition and inflammatory cells infiltration and accumulation juxtaposed to the stent metallic bars (Figure 4). Of note, the inflammatory response showed a peak after three months by the implant, with a notable cells infiltration presenting mononuclear inflammatory cells adjacent to the stent area (Figure 4(c)); a marked reduction was observed after six months, with a slight reaction of the foreign body type, as indicated by the presence of few multinucleate giant cells with random arrangement of nuclei and presence of calcifications (Figure 4(d)). These observations were supported by the measurements of the surface area of inflammation at different time points. For the analysis, we have considered the areas of inflammation presenting 150 inflammatory cells/0.01 mm². As shown in Figure 5, after three months by the implant, we observed a peak in the size of the inflammatory cells infiltration area and a significant decrease after six months, suggesting an ongoing process of structural restoration at the device anchoring sites (Figure 5). Normal histological structure was present in the control areas and in the middle regions of the jugular veins without incorporated metallic device (Figures 2 and 3)

Figure 4.

Histologic examples of stent-inducted internal jugular veins. Representative histological images (hematoxylin-eosin stain) of the IJV wall implanted for 1 (a), 2 (b), 3 (c) or 6 (d) months are shown. Magnification 4× and 40× (inserts). *Indicates the presence of calcification. Arrowhead indicates a multinucleated giant cell.

Figure 5.

Measurement of the surface area of the inflammatory cells surrounding the metallic bar of the device. Multiple sections derived from swine implanted for three or six months were assessed to evaluate the surface area of the inflammatory cells localized around the incorporated metallic bar. Horizontal bars are median, upper and lower edges of box are 75th and 25th percentiles, and lines extending from the box are the 10th and 90th percentiles. *P < 0.05 respect to the distal region at three months.

Assessment of the morphology of the internal jugular vein endothelium

We have further assessed the morphology of the endothelium in order to evaluate the possible modifications induced by the presence of the stent in the endoluminal surface of the vein and/or changes linked with a modification of the flow regimen induced by the scaffold.

As shown in Figures 2(c) and 3(c), obtained by SEM analysis, the morphology of the tissue in the distal region close to the entry sites of the metallic rods was characterized by a smooth appearance with the presence of ruffled surfaces with fibrous feature. Of note, the tissues that are in the control regions and between two metallic rods, both in the distal and middle device areas, showed a preserved and more regular endothelial morphology suggesting that the implant minimally alters the hemodynamic flow of the IJV.

The cross sections of the stented IJV at six months after implant were also evaluated for the presence of an endothelial cells monolayer covering the lumen in correspondence of the incorporated metallic bars. Immuno-histologic examination with a specific antibody directed against von Willebrand Factor (FVIII), marker used for the identification of endothelial cells, showed the presence of an almost complete endothelium in the distal surface covering the device (Figure 6).

Figure 6.

Analysis of the endothelial cells monolayer in the luminal surface of the internal jugular vein. Immunohistochemical analyses were performed in different sections of IJVs by means of an antibody anti-von Willebrand Factor (FVIII). The figure shows selected panels of samples corresponding to the control region (a) and the region covering the device (b). *Empty space before occupied by metallic rod.

Wall thickness evaluation

For the wall thickness analysis, the jugular veins, obtained from swine implanted up to six months, were divided in control, distal and middle regions from which several sections were obtained and each measured in multiple points. The averages of all the measurements realized in the different regions are given in Figure 7(a) and (b).

Figure 7.

Comparative evaluation of jugular vein wall thickness. Wall thickness measurements of jugular vein from swine that have been implanted bilaterally three (a) or six (b) months before with a metallic device. As shown in panel (b), in the middle region after six months, the metallic bars could be surrounded (+) or not (−) by the vein wall. Multiple measurements were carried out in different sections of the samples. Horizontal bars are median, upper and lower edges of box are 75th and 25th percentiles, and lines extending from the box are the 10th and 90th percentiles. *P < 0.01 respect to the control region.

The presence of the device enveloped in the wall induced a significant (p < 0.01) increase of the thickness respect to the control regions both at three (Figure 7(a)) and six (Figure 7(b)) months after the implant. Of note, the thickness of the total wall and of the tissue covering the device in the distal and middle regions was comparable between sections obtained after three and six months by the implant (Figure 8), indicating that the neo-formation of the tissue around the device is a time-limited process. These results were also strengthened by the measurements of the wall between the adventitia and the stent demonstrating that no statistical differences existed in the distal region of the devices after three months (average: 1142 ± 612 µm; median: 1057 µm) and six months (average: 944 ± 469 µm; median: 910 µm) by the implant.

Figure 8.

Thickness evaluation of the tissue covering the device. The thickness of the tissue covering the device was measured after three or six months by the implant in several sections corresponding to distal or middle regions. Horizontal bars are median, upper and lower edges of box are 75th and 25th percentiles, and lines extending from the box are the 10th and 90th percentiles.

We also analyzed the ultrastructure assessment of the tissue covering the device. As shown in Figure 9, the tissue surrounding the metallic bar showed a fibrous appearance, with a prevalence of collagen fibres intermingled with fibroblasts, low prevalence of smooth muscle cells and few cells with histiocytic features.

Figure 9.

Ultrastructural assessment of tissue surrounding the device. IJVs derived from swine implanted for six months were examined by transmission electron microscopy (4000×). A representative panel composed of images from distal endoluminal surface (a) and areas surrounding the metallic bar (b, c and d) are shown. Larger cells with polypoid contours and optically empty vacuoles are histiocytes (H). The spindle-shaped cells visible in Panel c are smooth muscle cells (SMC). *Empty space before occupied by a metallic rod.

Discussion

The venous stenting is an under developed field of investigation of the endovascular therapy. In front of robust clinical reports, histological studies on the consequences of venous wall stenting are currently lacking.²¹ Particularly the compliance of the venous system is a mechanical factor which till now is underestimated in the available stent technologies.

The venous system needs high compliance because physiological postural changes determine big variations of hydrostatic pressure distribution. In the sub-diaphragmatic veins, when the subject is in standing posture, the gravity displaces approximately 70% of the overall blood below the diaphragmatic line.^22–25 Venous compliance of the lower extremity permits to increase the cross sectional area (CSA) in order to accommodate the redistribution of blood in the lower part of the body.

On the contrary, in the IJV, in up-right posture, the hydrostatic pressure is negative, around −30 mmHg, whereas in supine posture it accounts +5–7 mmHg.^26–28 Passing progressively from supine to upright, the hydrostatic pressure becomes negative because the IJV is placed above the heart. This means that the pressure external to the vein (atmospheric pressure) becomes prevalent, and squeezes the IJV which becomes smaller. It has been shown a dramatic reduction of the CSA of the jugular vein passing from supine to upright posture.²⁸ The variation in CSA expresses the volume modification respect to the variation of the hydrostatic pressure.

For the reason above mentioned, we investigated a novel concept of endo-venous scaffold, Petalo CVS. The latter is characterized by a reduced radial force as well as by mechanical properties which permit the vein to collapse (supplementary videoclip). The scaffold favorites the adaptation of the CSA of the vein to the reduction of blood volume in response to postural changes. In addition, the convex shape of the support modules was studied in order to “touch” but anchoring the vein wall only at the extremities.

Our hypothesis was to minimize the trauma and to respect the compliance function of the venous wall, both aimed to reduce the inflammatory response to the scaffold implantation. We choose the IJV because it is a real challenging area. The hydrostatic pressure is negative when the pig is upright, but becomes suddenly significantly higher when the pig tilts the head below the heart level to feed and drink.²⁹ Moreover, the IJVs is a pulsatile vein for the transmission of the changes in pressure of the right atrium due to cardiac revolution.³⁰ Finally, the stented IJVs are solicited by the muscles of neck of the pig.

Our study demonstrates that the inflammatory reaction in the first three months is intense, with significant increase in wall thickness. The infiltration of inflammatory cells, mostly lymphocytes and histiocytes (Figure 4(c)), shows a peak at the third month. The device is covered by a neointimal tissue, initially in the area of contact, and subsequently extended along the implant (Figure 2). The scanning electronic microscopy demonstrates the regular arrangement of the endothelial cells along the lines of flow direction, suggesting that the device does not create significant turbulences. In cases of implant at the level of the jugular valve, the stent was capable to press it against the venous wall, impeding the cusps to protrude into the lumen. This finding suggests that the device could be proposed in perspective to treat venous endoluminal defects.

The inflammatory reaction tends to burn out a long time, self-limiting at sox months, as confirmed by the levels of wall thickness. From a qualitative point of view, lymphocytes are decreased and, interestingly, few mononuclear giant cells were seen at six months, suggesting something like a mild foreign body reaction. At six months, the process of neo-intima remodeling is concluded, and the scaffold is almost completely covered along the implant.

A common process following open and endovascular procedures, including stenting, is myointimal hyperplasia (MH), characterized by augmented proliferation and migration of vascular smooth muscle cells and increased synthesis of components of the extracellular matrix.^31,32 Such cells and proteins might progressively obliterate the stent lumen. These biological events are the result of a dedifferentiation process of smooth muscle cells, which are capable of losing their contractile function and re-establishing a more undifferentiated phenotype, which makes them highly proliferative.³² Our data point against the induction on behalf of the novel stent of a consistent smooth muscle proliferation. This finding needs to be further investigated because the novel concept might alleviate the risk of post-procedural myointimal hyperplasia and subsequent in-stent restenosis.

Therefore, we did not observe an increased thickness of this tissue in the area of contact between the venous wall and the stent, suggesting that the radial force is enough to avoid migration but does not create myointimal hyperplasia. This is confirmed also by immunohistochemistry and by SEM observation, both showing consistently the absence of endothelial injury, as well as by TEM analyses showing the low prevalence of smooth muscle cells in the tissue covering the device. Moreover, the combination of the positive staining for Von Willebrand factor on the endothelial cells, with the absence of significant adhesion of platelets at electronic microscopy on the surface of the jugular vein contributes to explain us why in this study we did not observe venous thrombosis. The early stage of blood clotting in the venous system involves the adhesion of platelets to von Willebrand factor.^33,34 Both in swine and in humans, the adhesion probability of platelets to von Willebrand factor is strongly dependent on hematocrit and flow rate. Turbulences and flow rate largely different from flow regimen characteristic of a vein of certain CSA and district, demonstrated to be potentially pro-thrombotic in several experimental models, favoring the platelets interaction with von Willebrand factor.^33–35

This porcine model we adopted has some limitations to consider. Although moderate muscular compression of the jugular vein was noted in some animals, this was not of the same severity as is seen in most patients with symptomatic thoracic outlet syndrome, or of arterial compass of May–Thurner syndrome, etc. The healthy veins of pigs also cannot of course mimic venous obstruction of post-thrombotic condition, a further field of application of venous stenting procedures.

Another shortcoming of our study is the limited number of observations. There may be some interesting features that could not be identified due to the small sample size. Finally, the novel scaffold was not compared in this series to other devices currently used in large veins.

In this animal model, a novel stent did not experience thrombosis, migration, or obstruction at up to 180 days of follow-up. Histology and electronic microscopy clearly depicts the process of integration of the new scaffold in the venous wall of a porcine model. These data support the development of clinical trials to evaluate the safety and the efficacy of Petalo CVS in humans.

In conclusion, Petalo CVS implanted in the jugular wall of swine is characterized by neointima formation completely covering up the metallic bars in the region of anchorage, and by an inflammatory reaction which tends to decrease after six months. The latter appears a time-limited process, without the induction of smooth muscle cells proliferation and migration. There are a growing number of endovascular treatments for venous obstruction, but the current stents with a fixed diameter have clearly a compliance mismatch with respect to the mechanical properties of the venous wall. For instance, in the human internal jugular vein, the CSA ranges between 17 ± 8 mm² in upright and 106 ± 37 mm² in supine position; similar ranges are covered by the iliac veins and/or by the major deep veins of the lower limbs at postural changes.¹⁶ Differently from the current venous stent, Petalo CVS design has been developed to be more compliant to the change in CSA of the venous system. In addition, the novel configuration of the scaffold induces a biological response of the vein wall only in a limited area of contact. Although Petalo CVS was implanted at the valve site of a healthy vein and the efficacy of this device in cases of chronically occluded and scarred veins was not documented, the results of the present study encourage the use of the novel venous scaffold for future clinical applications.

Supplemental Material

sj-vid-1-phl-10.1177_0268355518805686 - Supplemental material for A novel endovenous scaffold for the treatment of chronic venous obstruction in a porcine model: Histological and ultrastructural assessment

Supplemental material, sj-vid-1-phl-10.1177_0268355518805686 for A novel endovenous scaffold for the treatment of chronic venous obstruction in a porcine model: Histological and ultrastructural assessment by Paolo Zamboni, Alessia Giaquinta, Erika Rimondi, Massimo Pedriali, Eugenio Scanziani, Pietro Riccaboni, Massimiliano Veroux, Paola Secchiero and Pierfrancesco Veroux in Phlebology

Supplemental Material

sj-vid-2-phl-10.1177_0268355518805686 - Supplemental material for A novel endovenous scaffold for the treatment of chronic venous obstruction in a porcine model: Histological and ultrastructural assessment

Supplemental material, sj-vid-2-phl-10.1177_0268355518805686 for A novel endovenous scaffold for the treatment of chronic venous obstruction in a porcine model: Histological and ultrastructural assessment by Paolo Zamboni, Alessia Giaquinta, Erika Rimondi, Massimo Pedriali, Eugenio Scanziani, Pietro Riccaboni, Massimiliano Veroux, Paola Secchiero and Pierfrancesco Veroux in Phlebology

Footnotes

Declaration of Conflicting Interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: PV gets the intellectual property of the patent of the venous scaffold Petalo.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study has been supported by the grant RF-2013-02358029 of the Italian Ministry of Health. Project: Development of a new endovascular device for the treatment of the large veins.

Ethical approval

The study was approved by the local ethics committee of University of Milan and the Italian Ministry of Health (MoH). The study was conducted following the guidelines of good laboratory practices.

Guarantor

PV.

Contributorship

CF and CV.

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