Vascular Compatibility Research Articles

Styrenic block copolymer‐based thermoplastic elastomers in smart applications: Advances in synthesis, microstructure, and structure–property relationships—A review

AbstractStyrenic block copolymers (SBC) have been gaining attention as a specialty material in elastomer and composite industries over an extended period. Its unique segmental architecture, controllable mechanical strength, ease of processing, oxidative, and environmental stability enable versatile applications. SBCs with other unique features like ion‐containing blocks, vascular compatibility, and biostability are gaining popularity in several new‐age applications. The review mainly displays the new synthetic strategies for SBC having superior thermal and environmental resistance and how their morphologies get affected by the invention of different synthesis and molecular designing technologies. It elaborates prospects and future of SBCs in other innovative application fields like sensors for wearable devices, next‐generation proton exchange membranes for fuel cells, portable power sources for electric vehicles, shape memory polymers, and so forth. Its potential in biomedical applications like heart valves, urinary tract devices, coating for coronary stents, implants, and drug delivery applications has also been discussed. It also analyses structure properties relationship which affects their performance in these fields, along with a brief introduction about the history of invention.

High-Efficient Vacuum Ultraviolet-Ozone Assist-Deposited Polydopamine for Poly(lactic-co-glycolic acid)-Coated Pure Zn toward Biodegradable Cardiovascular Stent Applications.

Zinc is a prospective metal for biodegradable cardiovascular stent applications, but the excessively released Zn2+ during degradation remains a huge challenge in biocompatibility. Considerable efforts have been made to develop a high-efficient surface modification method, while maintaining adhesion strength, mechanical support, and vascular compatibility. Biomimetic polydopamine (PDA) can adhere to Zn tightly, subsequently achieving robust chemical bonds with poly(lactic-co-glycolic acid) (PLGA) coating. However, the deposition of PDA on Zn depends on the controlled conditions such as a sensitive pH and a long period of time. Herein, we introduce vacuum ultraviolet-ozone (VUV/O3) assist-deposition technology to accelerate the polymerization of PDA on pure Zn, which shortens the process to 40 min at a moderate pH of 8.5 and improves the deposition rate by 1-2 orders of magnitude under sufficient active oxygen species (ROS). Additionally, PLGA/PDA coating enhances the corrosion resistance, and their effective protection maintains the mechanical properties after long-term corrosion. Moreover, the controlled Zn2+ release contributes to the superior in vitro biocompatibility, which inhibits the hemolysis rate and smooth muscle cell (SMC) proliferation. The enhanced endothelial cell (EC) proliferation is promising to promote the re-endothelialization, avoiding in-stent restenosis and neointimal hyperplasia. Such modified Zn might be a viable candidate for the treatment of cardiovascular diseases.

A combination strategy of functionalized polymer coating with Ta ion implantation for multifunctional and biodegradable vascular stents

Biodegradable stents made of magnesium (Mg) and its alloys have been developed to minimize persistent inflammation or in-stent restenosis, which are the main problems for permanent stents. However, their rapid corrosion behavior under physiological conditions leads to poor vascular compatibility and premature structural failure, which remains an important unsolved clinical problem. Herein, we demonstrate a new strategy for solving this problem by combining poly (ether imide) (PEI) coating and subsequent tantalum (Ta) ion implantation. The PEI coating covers the whole surface of the Mg stent uniformly via a spray coating technique and provides Mg with superior corrosion resistance and stable sirolimus-carrying ability. Ta ion implantation is conducted by a sputtering-based plasma immersion ion implantation technique only onto the luminal surface of the PEI-coated Mg stent. Its extremely short processing time (< 30 s) permits preservation of the PEI coating's corrosion protection ability and sirolimus loading characteristics. In addition, a Ta-implanted skin layer that forms on the topmost surface of the PEI coating plays an effective role in not only preventing a rapid release of sirolimus from the surface but also improving the PEI coating's surface hydrophilicity. Based on in vitro cellular response and blood compatibility tests, Ta ion implantation leads to the improvement of endothelial cell adhesion/proliferation and suppression of platelet adhesion/activation regardless of sirolimus loading. These results indicate that the combination of PEI coating and Ta ion implantation has significant innovative potential to provide excellent vascular compatibility and prevent in-stent restenosis and thrombosis.

Bifunctional poly (l-lactic acid)/hydrophobic silica nanocomposite layer coated on magnesium stents for enhancing corrosion resistance and endothelial cell responses

Biodegradable magnesium (Mg)-based vascular stents can overcome the limitations of conventional permanent metallic stents, such as late in-stent restenosis and thrombosis, but still have difficulty retarding degradation while providing adequate mechanical support to the blood vessel. We incorporated silica nanoparticles surface-functionalized with hexadecyltrimethoxysilane (mSiNP) into a poly (l-lactic acid) (PLLA) coating as a physical barrier to disturb the penetration of the corrosive medium as well as a bioactive source that releases silicon ions capable of stimulating endothelial cells. The corrosion resistance and biocompatibility of this bifunctional PLLA/mSiNP nanocomposite coating were investigated using different weight ratios of mSiNP. The nanocomposite coating containing more than 10 wt% of the mSiNP (PLLA/10mSiNP and PLLA/20mSiNP) significantly delayed the corrosion of the Mg substrate and exhibited favorable endothelial cell responses, compared to the pure PLLA coating. Specifically, the calculated corrosion rates of PLLA/10mSiNP and PLLA/20mSiNP decreased by half, indicating the durability of the coating after immersion in simulated body fluid for 12 days. Based on the in vitro cellular response, the incorporation of the mSiNPs into the PLLA coating significantly improved the endothelial cell responses to the Mg substrate, showing better initial cell surface coverage, migration, and proliferation rate than those of pure PLLA. These results indicate that the PLLA/mSiNP nanocomposite coatings have significant potential to improve the corrosion resistance and vascular compatibility of biodegradable Mg-based vascular stents.

An asymmetric surface coating strategy for improved corrosion resistance and vascular compatibility of magnesium alloy stents

Magnesium (Mg) and its alloys are promising materials for biodegradable drug-eluting stent applications, but their rapid corrosion remains a major challenge for clinical practice. Considerable efforts have been made to develop an efficient surface coating that can provide higher Mg stent corrosion resistance, sustained drug-delivery capability, and vascular compatibility. Herein, we introduce poly(ether imide) (PEI) and poly(lactic-co-glycolic acid) (PLGA) as surface coating polymers for WE43 Mg-alloy stent. Using a sequential spray-coating method, we developed a novel asymmetric stent coating comprising an inner surface coated with a PEI single layer and outer/side surfaces coated with sirolimus-loaded PLGA/PEI double layers. PEI coating layer has excellent adhesiveness to WE43 surface and considerably improves WE43 corrosion resistance and in vitro endothelial cell compatibility. PLGA/PEI double coating layer ensures a low release rate of sirolimus and stable surface morphology during drug-release process. Only vascular smooth muscle cells are directly affected by sirolimus owing to the asymmetric geometry of PLGA/PEI double coating, which has a satisfactory anti-proliferation effect. These results indicate that the developed asymmetrically PEI- and PLGA/PEI-coated WE43 stents have significant potential for achieving enhanced re-endothelialization and suppressed in-stent restenosis in vascular stent applications.

Large-bore arterial access in the era of structural cardiovascular disease.

Over the last two decades, the medical community witnessed an outstanding and accelerated development on minimally invasive therapies. The definition of what constitutes large bore access is subject to discussion, however within the field it is generally accepted to reflect a catheter diameter exceeding 8-French. We sought in this review to explore the evolution, characteristics and vascular compatibility of the current commercially available devices, analyze the devices along with access site-specific complications rates and finally review the present methods for percutaneous vascular closure.

In vitro and in vivo evaluation of a dextran-graft-polybutylmethacrylate copolymer coated on CoCr metallic stent.

Introduction: The major complications of stent implantation are restenosis and late stent thrombosis. PBMA polymers are used for stent coating because of their mechanical properties. We previously synthesized and characterized Dextrangraft-polybutylmethacrylate copolymer (Dex-PBMA) as a potential stent coating. In this study, we evaluated the haemocompatibility and biocompatibility properties of Dex-PBMA in vitro and in vivo. Methods: Here, we investigated: (1) the effectiveness of polymer coating under physiological conditions and its ability to release Tacrolimus®, (2) the capacity of Dex-PBMA to inhibit Staphylococcus aureus adhesion, (3) the thrombin generation and the human platelet adhesion in static and dynamic conditions, (4) the biocompatibility properties in vitro on human endothelial colony forming cells ( ECFC) and on mesenchymal stem cells (MSC) and in vivo in rat models, and (5) we implanted Dex-PBMA and Dex-PBMATAC coated stents in neointimal hyperplasia restenosis rabbit model. Results: Dex-PBMA coating efficiently prevented bacterial adhesion and release Tacrolimus®. Dex-PBMA exhibit haemocompatibility properties under flow and ECFC and MSC compatibility. In vivo, no pathological foreign body reaction was observed neither after intramuscular nor intravascular aortic implantation. After Dex-PBMA and Dex-PBMATAC coated stents 30 days implantation in a restenosis rabbit model, an endothelial cell coverage was observed and the lumen patency was preserved. Conclusion: Based on our findings, Dex-PBMA exhibited vascular compatibility and can potentially be used as a coating for metallic coronary stents.

First in human evaluation of the vascular biocompatibility and biomechanical performance of a novel ultra high molecular weight amorphous PLLA bioresorbable scaffold in the absence of anti-proliferative drugs: Two-year imaging results in humans.

In this first-in-human study, we prospectively studied the vascular compatibility and mechanical performance of a novel bare ultra-high molecular weight amorphous PLLA bioresorbable scaffold (BRS, FORTITUDE®, Amaranth Medical, Mountain View, California) up to two years after implantation using multimodality imaging techniques. The vascular biocompatibility of polymers used in BRS has not been fully characterized in the absence of anti-proliferative drugs. A total of 10 patients undergoing single scaffold implantation were included in the final analysis and were followed up using optical coherence tomography (OCT) at 2-years. All devices were implanted under angiographic and intravascular ultrasound (IVUS) guidance. Angiographic and IVUS follow up was performed at 6 months. Additionally, angiography and OCT imaging were performed at 2-years. At 6 months, mean intra-scaffold angiographic MLD slightly decreased from baseline procedural values. However, at 2 years, mean angiographic MLD increased (post procedure; 2.9 [2.7, 3.1] mm vs. 6 months; 2.1 [1.6, 2.5] vs. 2 years; 2.4 [2.1, 2.6], P = .001). Also, angiographic percent diameter stenosis decreased and late lumen gain increased between 6 months and 2 years follow up. Mean neointimal hyperplasia volume assessed by IVUS at 6 months was 26% [15.2, 29.3]. At 2 years OCT follow up neointimal hyperplasia volume was 24.2% [19.4, 28.9]. No presence of neoatherosclerosis was identified in any of the analyzed cases. At 2 years, this novel PLLA-based BRS induced expansive vascular remodeling from 6 to 24 months, a biological phenomenon that appears to be independent of the presence of anti-proliferative drugs.

Very Late Pathological Responses to Cobalt-Chromium Everolimus-Eluting, Stainless Steel Sirolimus-Eluting, and Cobalt-Chromium Bare Metal Stents in Humans.

BackgroundThe “very late” clinical outcomes for durable polymer drug‐eluting stents and bare metal stents (BMSs) have been shown to be dissimilar in clinical studies. Conceptually, the long‐term vascular compatibility of BMSs is still regarded to be superior to drug‐eluting stents; however, no pathologic study to date has specifically addressed this issue. We evaluated the very late (≥1 year) pathologic responses to durable polymer drug‐eluting stents (cobalt–chromium [CoCr] everolimus‐eluting stents [EESs] and stainless steel sirolimus‐eluting stents [SS‐SESs]) versus BMSs (CoCr‐BMSs).Methods and ResultsFrom the CVPath stent registry, we studied a total of 119 lesions (40 CoCr‐EESs, 44 SS‐SESs, 35 CoCr‐BMSs) from 92 autopsy cases with a duration ranging from 1 to 5 years. Sections of stented coronary segments were pathologically analyzed. Inflammation score and the percentage of struts with giant cells were lowest in CoCr‐EESs (median inflammation score: 0.6; median percentage of struts with giant cells: 3.8%) followed by CoCr‐BMSs (median inflammation score: 1.3 [P<0.01]; median percentage of struts with giant cells: 8.9% [P=0.02]) and SS‐SESs (median inflammation score: 1.7 [P<0.01]; median percentage of struts with giant cells: 15.3% [P<0.01]). Polymer delamination was observed exclusively in SS‐SESs and was associated with increased inflammatory and giant cell reactions. The prevalence of neoatherosclerosis with CoCr‐EESs (50%) was significantly less than with SS‐SESs (77%, P=0.02) but significantly greater than with CoCr‐BMSs (20%, P<0.01).ConclusionsCoCr‐EESs, SS‐SESs, and BMSs each demonstrated distinct vascular responses. CoCr‐EESs demonstrated the least inflammation, near‐equivalent healing to BMSs, and lower neointimal formation. These results challenge the belief that BMSs have superior biocompatibility compared with some polymeric coated drug‐eluting stents and may have implications for future stent design.

Plasma mediated protein immobilisation enhances the vascular compatibility of polyurethane with tissue matched mechanical properties

Polyurethanes are a diverse class of polymers, with independently tunable mechanical and biodegradation properties making them a versatile platform material for biomedical implants. Previous iterations have failed to adequately embody appropriate mechanical and biological properties, particularly for vascular medicine where strength, compliance and multifaceted biocompatibility are required. We have synthesized a new polyurethane formulation with finely tuned mechanical properties, combining high strength and extensibility with a low Young’s modulus. Additional cross-linking during synthesis enhanced stability and limits leaching. Under cyclic testing, hysteresis was minimal following completion of the initial cycles, indicating the robustness of the material. Building on this platform, we used plasma immersion ion implantation to activate the polymer surface and functionalized it with recombinant human tropoelastin. With tropoelastin covalently bound to the surface, human coronary endothelial cells showed improved attachment and proliferation. In the presence of heparinized whole blood, tropoelastin-coated polyurethane showed very low thrombogenicity in both static and flow conditions. Using this formulation, we synthesized robust, elastic prototype conduits which easily retained multiple sutures and were successfully implanted in a pilot rat aortic interposition model. We have thus created an elastic, strong biomaterial platform, functionalized with an important regulator of vascular biology, with the potential for further evaluation as a new synthetic graft material.

Plasma Ion Activated Expanded Polytetrafluoroethylene Vascular Grafts with a Covalently Immobilized Recombinant Human Tropoelastin Coating Reducing Neointimal Hyperplasia.

Expanded polytetrafluoroethylene (ePTFE) vascular conduits with less than or equal to 6 mm internal diameter typically occlude due to a combination of thrombus formation and neointimal hyperplasia. We hypothesized that by layering the polymerized elastin precursor, human tropoelastin, in the synthetic vessel lumen we could mimic the internal elastic lamina and so maintain low thrombogenicity while significantly reducing smooth muscle cell proliferation. The luminal surfaces of ePTFE conduits were activated with plasma immersion ion implantation (PIII) treatment to facilitate covalent attachment of tropoelastin. Multilayered tropoelastin vessels (2TE) enhanced endothelial cell attachment and proliferation in vitro and were superior to materials lacking the protein. In an ovine carotid interposition model of graft compatibility, partially tropoelastin coated vessels (1TE) thrombosed at a greater rate than control ePTFE, but 2TE maintained the same patency as controls. 2TE showed a significant reduction in neointimal area down to 9.7 ± 5.2% (p < 0.05) in contrast to 32.3 ± 3.9% for ePTFE alone. This reduction was due to a halving of the number of smooth muscle cells present and a corresponding reduction in their proliferation. 2TE, but not 1TE, enhanced the vascular compatibility of these materials: while both tropoelastin presentations increased in vitro endothelialization, only 2TE displayed the dual benefits of maintained hemocompatibility and simultaneously suppressed neointimal hyperplasia in vivo. We conclude that 2TE surface modification provides a significant improvement over ePTFE vascular conduits in a pilot large animal model study and presents an attractive path toward clinical applications for reduced diameter vessels.

Reprint of: Pendant allyl crosslinking as a tunable shape memory actuator for vascular applications

Thermo-responsive shape memory polymers (SMPs) can be programmed to fit into small-bore incisions and recover their functional shape upon deployment in the body. This property is of significant interest for developing the next generation of minimally-invasive medical devices. To be used in such applications, SMPs should exhibit adequate mechanical strengths that minimize adverse compliance mismatch-induced host responses (e.g. thrombosis, hyperplasia), be biodegradable, and demonstrate switch-like shape recovery near body temperature with favorable biocompatibility. Combinatorial approaches are essential in optimizing SMP material properties for a particular application. In this study, a new class of thermo-responsive SMPs with pendant, photocrosslinkable allyl groups, x%poly(ε-caprolactone)-co-y%(α-allyl carboxylate ε-caprolactone) (x%PCL-y%ACPCL), are created in a robust, facile manner with readily tunable material properties. Thermomechanical and shape memory properties can be drastically altered through subtle changes in allyl composition. Molecular weight and gel content can also be altered in this combinatorial format to fine-tune material properties. Materials exhibit highly elastic, switch-like shape recovery near 37°C. Endothelial compatibility is comparable to tissue culture polystyrene (TCPS) and 100%PCL in vitro and vascular compatibility is demonstrated in vivo in a murine model of hindlimb ischemia, indicating promising suitability for vascular applications. Statement of SignificanceWith the ongoing thrust to make surgeries minimally-invasive, it is prudent to develop new biomaterials that are highly compatible and effective in this workflow. Thermo-responsive shape memory polymers (SMPs) have great potential for minimally-invasive applications because SMP medical devices (e.g. stents, grafts) can fit into small-bore minimally-invasive surgical devices and recover their functional shape when deployed in the body. To realize their potential, it is imperative to devise combinatorial approaches that enable optimization of mechanical, SM, and cellular responses for a particular application. In this study, a new class of thermo-responsive SMPs is created in a robust, facile manner with readily tunable material properties. Materials exhibit excellent, switch-like shape recovery near body temperature and promising biocompatibility for minimally-invasive vascular applications.

Pendant allyl crosslinking as a tunable shape memory actuator for vascular applications

Thermo-responsive shape memory polymers (SMPs) can be programmed to fit into small-bore incisions and recover their functional shape upon deployment in the body. This property is of significant interest for developing the next generation of minimally-invasive medical devices. To be used in such applications, SMPs should exhibit adequate mechanical strengths that minimize adverse compliance mismatch-induced host responses (e.g. thrombosis, hyperplasia), be biodegradable, and demonstrate switch-like shape recovery near body temperature with favorable biocompatibility. Combinatorial approaches are essential in optimizing SMP material properties for a particular application. In this study, a new class of thermo-responsive SMPs with pendant, photocrosslinkable allyl groups, x%poly(ε-caprolactone)-co-y%(α-allyl carboxylate ε-caprolactone) (x%PCL-y%ACPCL), are created in a robust, facile manner with readily tunable material properties. Thermomechanical and shape memory properties can be drastically altered through subtle changes in allyl composition. Molecular weight and gel content can also be altered in this combinatorial format to fine-tune material properties. Materials exhibit highly elastic, switch-like shape recovery near 37°C. Endothelial compatibility is comparable to tissue culture polystyrene (TCPS) and 100%PCL in vitro and vascular compatibility is demonstrated in vivo in a murine model of hindlimb ischemia, indicating promising suitability for vascular applications. Statement of SignificanceWith the ongoing thrust to make surgeries minimally-invasive, it is prudent to develop new biomaterials that are highly compatible and effective in this workflow. Thermo-responsive shape memory polymers (SMPs) have great potential for minimally-invasive applications because SMP medical devices (e.g. stents, grafts) can fit into small-bore minimally-invasive surgical devices and recover their functional shape when deployed in the body. To realize their potential, it is imperative to devise combinatorial approaches that enable optimization of mechanical, SM, and cellular responses for a particular application. In this study, a new class of thermo-responsive SMPs is created in a robust, facile manner with readily tunable material properties. Materials exhibit excellent, switch-like shape recovery near body temperature and promising biocompatibility for minimally-invasive vascular applications.

Cooperative control of blood compatibility and re-endothelialization by immobilized heparin and substrate topography

A wide variety of environmental cues provided by the extracellular matrix, including biophysical and biochemical cues, are responsible for vascular cell behavior and function. In particular, substrate topography and surface chemistry have been shown to regulate blood and vascular compatibility individually. The combined impact of chemical and topographic cues on blood and vascular compatibility, and the interplay between these two types of cues, are subjects that are currently being explored. In the present study, a facile polydopamine-mediated approach is introduced for immobilization of heparin on topographically patterned substrates, and the combined effects of these cues on blood compatibility and re-endothelialization are systematically investigated. The results show that immobilized heparin and substrate topography cooperatively modulate anti-coagulation activity, endothelial cell (EC) attachment, proliferation, focal adhesion formation and endothelial marker expression. Meanwhile, the substrate topography is the primary determinant of cell alignment and elongation, driving in vivo-like endothelial organization. Importantly, combining immobilized heparin with substrate topography empowers substantially greater competitive ability of ECs over smooth muscle cells than each cue individually. Moreover, a model is proposed to elucidate the cooperative interplay between immobilized heparin and substrate topography in regulating cell behavior.

The use of plasma-activated covalent attachment of early domains of tropoelastin to enhance vascular compatibility of surfaces

All current metallic vascular prostheses, including stents, exhibit suboptimal biocompatibility. Improving the re-endothelialization and reducing the thrombogenicity of these devices would substantially improve their clinical efficacy. Tropoelastin (TE), the soluble precursor of elastin, mediates favorable endothelial cell interactions while having low thrombogenicity. Here we show that constructs of TE corresponding to the first 10 (“N10”) and first 18 (“N18”) N-terminal domains of the molecule facilitate endothelial cell attachment and proliferation equivalent to the performance of full-length TE. This N-terminal ability contrasts with the known role of the C-terminus of TE in facilitating cell attachment, particularly of fibroblasts. When immobilized on a plasma-activated coating (“PAC”), N10 and N18 retained their bioactivity and endothelial cell interactive properties, demonstrating attachment and proliferation equivalent to full-length TE. In whole blood assays, both N10 and N18 maintained the low thrombogenicity of PAC. Furthermore, these N-terminal constructs displayed far greater resistance to protease degradation by blood serine proteases kallikrein and thrombin than did full-length TE. When immobilized onto a PAC surface, these shorter constructs form a modified metal interface to establish a platform technology for biologically compatible, implantable cardiovascular devices.

The Supralimus® sirolimus-eluting stent

The use of biodegradable polymeric coatings has emerged as a potential bioengineering target to improve the vascular compatibility of coronary drug-eluting stents (DESs). This review summarizes the main features and scientific facts about the Supralimus® sirolimus-eluting stent (Sahajanand Medical Technologies Ltd, Surat, India), which is a biodegradable polymer-based, sirolimus-eluting metallic stent that was recently introduced for routine use in Europe. The novel stent is built on a stainless steel platform, coated with a blend of biodegradable polymers (poly-l-lactide, poly-dl-lactide-co-glycolide and polyvinyl pyrrolidone; coating thickness is 4–5 µm). The active agent is the antiproliferative sirolimus in a dose load of 1.4 µg/mm2, which is released within 48 days. The Supralimus stent was initially evaluated in the single-arm SERIES-I study, which showed binary angiographic restenosis rates of 0% (in-stent) and 1.7% (in-segment) and an in-stent late lumen loss of 0.09 ± 0.28 mm. The multicenter randomized PAINT trial compared two DESs with identical metallic platforms and biodegradable polymer carriers, but different agents (Infinnium® [Sahajanand Medical Technologies Pvt Ltd] paclitaxel-eluting stent or Supralimus sirolimus-eluting stent) against bare stents. After 3 years, the pooled DES population had similar rates of cardiac death or myocardial infarction (9 vs 7.1%; p = 0.6), but a lower risk of repeat interventions (10 vs 29.9%; p < 0.01) than controls with bare stents. The incidence of definite or probable stent thrombosis in the pooled DES group was 2.3% (1st year: 1.8%; 2nd year: 0.4% and 3rd year: 0%). These results demonstrate that the novel Supralimus stents are effective in reducing reintervention, while potentially improving the safety profile by decreasing the risk of late-term thrombosis, even though further studies would be necessary to confirm these findings.

Plasma-Based Biofunctionalization of Vascular Implants

Polymeric and metallic materials are used extensively in permanently implanted cardiovascular devices and devices that make temporary but often prolonged contact with body fluids and tissues. Foreign body responses are typically triggered by host interactions at the implant surface, making surface modifications to increase biointegration desirable. Plasma-based treatments are extensively used to modify diverse substrates; modulating surface chemistry, wettability and surface roughness, as well as facilitating covalent biomolecule binding. Each aspect impacts on facets of vascular compatibility including endothelialization and blood contact. These modifications can be readily applied to polymers such as Dacron and expanded polytetrafluoroethylene, which are widely used in bypass grafting and the metallic substrates of stents, valves and pacemaker components. Plasma modification of metals is more challenging given the need for coating deposition in addition to surface activation, adding the necessity for robust interface adhesion. This review examines the evolving plasma treatment technology facilitating the biofunctionalization of polymeric and metallic implantable cardiovascular materials.

Extracellular matrix molecules facilitating vascular biointegration.

All vascular implants, including stents, heart valves and graft materials exhibit suboptimal biocompatibility that significantly reduces their clinical efficacy. A range of biomolecules in the subendothelial space have been shown to play critical roles in local regulation of thrombosis, endothelial growth and smooth muscle cell proliferation, making these attractive candidates for modulation of vascular device biointegration. However, classically used biomaterial coatings, such as fibronectin and laminin, modulate only one of these components; enhancing endothelial cell attachment, but also activating platelets and triggering thrombosis. This review examines a subset of extracellular matrix molecules that have demonstrated multi-faceted vascular compatibility and accordingly are promising candidates to improve the biointegration of vascular biomaterials.

Comparison of the SYNERGY with the PROMUS (XIENCE V) and bare metal and polymer-only Element control stents in porcine coronary arteries

This study evaluated vascular compatibility of the novel platinum chromium alloy Element stent platform delivering abluminal everolimus from a poly-lactide-co-glycolide bioabsorbable polymer (SYNERGY stent), currently undergoing clinical trial, compared with the PROMUS (XIENCE V) and bare metal and polymer-only Element stents. Stents (n=161) were implanted one per coronary artery in 72 swine at a stent-to-artery ratio of 1.1:1. Similar numbers of each device group were explanted at each of 30, 90, 180, and 360 days (except no PROMUS (XIENCE V) stent at 360 days) for pathological analysis. There was no stent thrombosis, myocardial infarction, or strut fractures in any group. Vascular response was similar between the SYNERGY and PROMUS (XIENCE V) stents, with no thrombi and complete endothelialisation on both scanning electron microscopy and histology at 30, 90 and 180 days. There were no significant differences for the morphologic parameters of luminal thrombus, endothelial cell coverage, strut tissue coverage, inflammation, internal elastic lamina (IEL) disruption, external elastic lamina (EEL) disruption and medial smooth muscle cell loss across device groups or between time points, but there was mild but greater (p<0.0001) para-strut fibrin at 30 days for both drug-eluting stents (DES) compared with the bare and polymer-only controls; this difference completely dissipated by 90 days. Inflammation was predominantly minimal to mild for all device types. No morphometric parameters, including intimal thickness, stent profile-based area stenosis, and EEL area were significantly different when comparing the SYNERGY stent with the bare metal Element and polymer-only Element control stents at 90, 180 and 360 days. In this non-injured porcine coronary artery model, the bioabsorbable polymer SYNERGY stent demonstrated vascular compatibility equivalent to the PROMUS (XIENCE V) stent and to the bare metal and polymer-only Element stents.

Evaluation of a novel paclitaxel-eluting stent with a bioabsorbable polymeric surface coating in the porcine artery injury model

Purpose Drug-eluting stents (DES) are unique in allowing sustained release after a single short intervention. The challenge with DES still remaining is the optimal combination of a biocompatible drug-eluting matrix including an antiproliferative drug. We studied the role of a novel paclitaxel-eluting stent with a bioabsorbable polymer coating in preventing vascular restenosis in the porcine artery injury model.Material and methods Bare metal stents (BMS); polymer-coated-only stents (POLY); and polymer-based paclitaxel-eluting stents (PACL) were randomly implanted in pig femoral arteries. The dose density of paclitaxel was 1 μ g/mm2 with in vitro studies demonstrating a gradual elution overa course of 6 month.Results After 1-, 3- and 6-month follow-up, respectively, the animals underwent angiographic restudy and were terminated for histomorphometrical and histopathological analyses. At 1 month, the PACL group had the lowest histological percent stenosis when compared to the BMS and POLY groups (20 ± 4% vs 39 ± 6% and 41 ± 6%, respectively, P < 0.05). At 3 months, the PACL group still presents the lowest level of histological percent stenosis among the three groups (27 ± 6% vs 50 ± 10% and 46 ± 5%, respectively, P < 0.01). Six months later, the PACL group showed a similar histological percent stenosis as the BMS and POLY groups (44 ± 9% vs 56 ± 11% and 53 ± 9%, respectively, P= 0.145).Conclusions This study shows favourable vascular compatibility and effi cacy for a novel DES to inhibit in-stent neointima formation and preserve lumen area in the porcine artery model.