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Background Neointima formation and atherosclerosis compromise long-term graft patency in aortocoronary vein bypass grafts. We investigated the effect on neointima formation in porcine saphenous vein grafts of periadventitial application of immortalized human mesenchymal stem cells transduced with the gene for the peptide glucagon-like peptide-1, which have been shown to induce angiogenesis in previous studies and are protected from immune-mediated destruction by encapsulation in alginate microbeads (CellBeads). Methods and results Periadventitial application of CellBeads was compared with alginate beads only or vehicle control in pig vein-into-artery interposition grafts. CellBeads significantly reduced neointimal area and total wall area compared with both control groups. This was associated with a significant increase in vein graft adventitial neoangiogenesis. CellBeads had no effect on vessel inward or outward remodeling and promoted adventitial collagen deposition. Alginate beads without stem cells reduced graft patency (6/15 grafts patent) versus CellBead-treated (6/7 grafts patent) or untreated grafts (7/8 grafts patent) (Fisher exact test, P = 0.052). There was no evidence of an inflammatory or cellular immune reaction to either the CellBeads or the alginate-only beads. Conclusions Periadventitial treatment of porcine vein grafts with human stem cells inhibits neointima formation in association with accelerated adventitial angiogenesis. The alginate vehicle alone appeared to promote graft failure and is therefore not the optimal vehicle for stem cell delivery to vein grafts.

DC Bead is a FDA cleared embolisation device for the treatment of hypervascular tumours and arteriovenous malformations. This product is currently evaluated in a number of centres in Europe as an embolic device for transarterial chemoembolisation (TACE). The beads consist of poly(vinyl alcohol) microspheres modified with sulfonic acid groups and are available at different size ranges varying from 100 to 900 microm in diameter. The beads were shown to actively sequester doxorubicin hydrochloride (dox) from solution in a time dependent upon the dose of the drug and size of the beads. Drug uptake was by an ion-exchange mechanism, and in the absence of other ions in solution, the beads could load a maximum of around 40 mg dox/mL hydrated beads, with99% of drug being sequestered from the solution. A loading of 25 mg dox/mL beads was recommended as providing a practical therapeutic dose and optimum handling characteristics. There was a decrease in equilibrium water content of the beads with increasing dox loading, which resulted in a decrease in the average diameter of the beads and an increase in the compressive modulus. The deliverability properties, however, were not affected after drug loading. Using a variety of microscopic methods, the drug was shown to be distributed throughout the bead structure, but concentrated in the outer 20 microm surface layer, a feature related to the method of synthesis. This study characterises the properties of DC Bead loaded with dox with respect to important characteristics in embolisation and demonstrates the potential of this drug device combination for the treatment of hypervascular tumours such as hepatocellular carcinoma.

PURPOSE The purpose of this investigation is to present the in vitro characterization and detailed drug-loading procedure for DC Bead, a microsphere product that can be loaded with chemotherapeutic agents for embolization. MATERIALS AND METHODS DC Bead is an embolic microsphere product that is capable of being loaded with anthracycline drugs such as doxorubicin just before administration in a transarterial chemoembolization (TACE) procedure. Beads can be loaded from solutions prepared from doxorubicin powder or the doxorubicin HCl formulation. In this evaluation, bead sizes were measured by optical microscopy with video imaging. Gravimetric analysis demonstrated the effect of drug loading on bead water content, and its consequent impact on bead compressibility was determined. The subsequent deliverability of the beads was assessed by mixing the beads with contrast medium and saline solution and passing the beads through an appropriately sized microcatheter. A T-cell apparatus was used to monitor the in vitro elution of the drug from the beads over a period of 24 hours in various elution media. RESULTS DC Bead spheres could be easily loaded with doxorubicin to a recommended level of 25 mg/mL of hydrated beads by immersion of the beads in the drug solution for 10–120 minutes depending on microsphere size. Other commercial embolic microspheres were shown not to load doxorubicin to the same extent or release it in the same fashion and were considered unsuitable for local drug delivery. Maximum theoretic capacity for DC Bead was approximately 45 mg/mL. Increase in doxorubicin loading resulted in a concomitant decrease in water content and consequential increase in bead resistance to compression force. Drug loading also resulted in a decrease in the average size of the beads, which was dependent on bead size and drug dose. This did not impact bead delivery at any drug loading level to a maximum of 37.5 mg/mL. Beads 100–700 μm in size could be delivered through 2.7-F microcatheters, whereas the 700–900-μm range required 3-F catheters. Modeling of the kinetics of drug elution from the beads in vitro at a loading dose of 25 mg/mL yielded calculated half-lives of 150 hours for the 100–300-μm range to a maximum of 1,730 hours for the 700–900-μm size range, which was dependent on the ionic strength of the elution medium. For comparison, there was a rapid loss of drug from an unstable Lipiodol emulsion with a half-life of approximately 1 hour. CONCLUSIONS DC Bead can be loaded with doxorubicin to provide an accurate dosage of drug per unit volume of beads. Drug elution is dependent on ion exchange with the surrounding environment and is controlled and sustained, unlike the rapid separation of the drug from Lipiodol. Drug loading has no impact on the handling and deliverability of the beads, making them suitable for superselective TACE.

Background— Drug-eluting stents represent a useful strategy for the prevention of restenosis using various antiproliferative drugs. These strategies share the liability of impairing endothelial recovery, thereby altering the natural biology of the vessel wall and increasing the associated risk of stent thrombosis. Accordingly, we tested the hypothesis that local delivery via gene-eluting stent of naked plasmid DNA encoding for human vascular endothelial growth factor (VEGF)-2 could achieve similar reductions in neointima formation while accelerating, rather than inhibiting, reendothelialization. Methods and Results— phVEGF 2-plasmid (100 or 200 μg per stent)–coated BiodivYsio phosphorylcholine polymer stents versus uncoated stents were deployed in a randomized, blinded fashion in iliac arteries of 40 normocholesterolemic and 16 hypercholesterolemic rabbits. Reendothelialization was nearly complete in the VEGF stent group after 10 days and was significantly greater than in control stents (98.7±1% versus 79.0±6%, P 2 , P P Conclusions— Acceleration of reendothelialization via VEGF-2 gene–eluting stents provides an alternative treatment strategy for the prevention of restenosis. VEGF-2 gene–eluting stents may be considered as a stand-alone or combination therapy.

There has been a move towards surface treatments for metallic coronary stents in an effort to improve their compatibility within the body and to provide a vehicle for the delivery of therapeutics. The BiodivYsio™ range of stents is characterised by a biocompatible coating comprised of a crosslinked phosphorylcholine (PC)-based polymer. In addition to a review of some of the data collected to support safety and efficacy of this device, this paper also describes a number of techniques that have been employed to both visualise and quantify the coating on the stent. Explantation of both coated and uncoated stents from porcine coronary arteries revealed that both coated and uncoated stents were >90% endothelialised after 5 days. Typical histological analysis of stented vessel sections after 4 and 12 weeks implantation showed the presence of cell types characteristic of the inflammatory response associated with the trauma caused by stent placement, with no evidence for any additional coating-related adverse inflammatory sequelae. Finally, it was demonstrated by AFM and SEM that both the thickness and force required to remove the coating were essentially unchanged after 6 months implantation. Thus, both the long-term stability and relative biological inertness of the coating has been confirmed in vivo, supporting its use as a vehicle for local drug delivery.

Copolymers of 2-methacryloyloxyethylphosphorylcholine (MPC) and lauryl methacrylate (LMA) of molar ratios MPC: LMAX where x = 1, 2 or 4, have been synthesised by two different free-radical polymerisation techniques. The solubility characteristics of the resulting materials were investigated in a variety of water: alcohol solvent mixtures and found to be influenced not only by the molar ratio of MPC: LMA, but also the method of synthesis. A window of solubility was observed for certain copolymers and the alcohol used in the solvent mixture was also found to have a profound influence on the solubility profile of the polymers. These materials were soluble in a wider range of aqueous methanol mixtures compared to aqueous mixtures of higher aliphatic alcohols, such as ethanol or isopropyl alcohol, which was rationalised in terms of the affinity of the phosphorylcholine headgroup for the various alcohols relative to water. 1H nuclear magnetic resonance spectroscopy was used to further examine the solution properties of the copolymers in various solvents. The copolymer MPC: LMA2 was coated onto a variety of substrates from both alcohol-only and water: alcohol solvent systems and the surface properties of the films compared by static and dynamic contact angle, atomic force microscopy (AFM) and attenuated internal reflectance Fourier transform infrared spectroscopy (ATR-IR). The coating formed from the water: alcohol solvent was found to be hydrophilic in nature, possessing spontaneous wettability, whereas films formed from alcohol-only solvents were hydrophobic, and only on conditioning with water were more wettable surfaces attained. This phenomenon was applied in the coating of leukocyte filtration material, where the aqueous-based systems demonstrated lower critical wetting surface tension (CWST) and shorter wetting times relative to both uncoated filters and those coated from alcohol-only systems. The haemocompatibility of the coated filters was equivalent for both coating solvent systems. employed, and far superior when compared to the uncoated control.

Cell therapy is a field of growing interest in the prevention of post acute myocardial infarction (AMI) heart failure. Stem cell retention upon local delivery to the heart, however, is still unsatisfactory. CellBeads were recently developed as a potential solution to this problem. CellBeads are 170-μm alginate microspheres that contain mesenchymal stem cells (MSCs) genetically modified to express glucagon-like peptide-1 (GLP-1) supplementary to inherent paracrine factors. GLP-1 is an incretin hormone that has both antiapoptotic and cardioprotective effects. Transplanting CellBeads in the post-AMI heart might induce cardiomyocyte salvage and ultimately abrogate adverse cardiac remodeling. We aimed to investigate the feasibility of intracoronary infusion of CellBeads in a large animal model of AMI. Four pigs were used in a pilot study to assess the maximal safe dose of CellBeads. In the remaining 21 animals, an AMI was induced by balloon occlusion of the left circumflex coronary artery for 90 min. During reperfusion, 60,000 CellBeads ( n = 11), control beads ( n = 4), or lactated Ringers' ( n = 6) were infused. Animals were sacrificed after 2 or 7 days, and the hearts were excised for histological analyses. Intracoronary infusion did not permanently affect coronary flow in any of the groups. Histological analysis revealed CellBeads containing viable MSCs up to 7 days. Viability and activity of the MSCs was confirmed by qPCR analysis that showed expression of recombinant GLP-1 and human genes after 2 and 7 days. CellBeads reduced inflammatory infiltration by 29% ( p = 0.001). In addition, they decreased the extent of apoptosis by 25% ( p = 0.001) after 2 days. We show that intracoronary infusion of 5 million encapsulated MSCs is safe and feasible. Also, several parameters indicate that the cells have paracrine effects, suggesting a potential therapeutic benefit of this new approach.

PURPOSE To present the pathologic and pharmacokinetic findings from hepatic embolization in a porcine model comparing doxorubicin-eluting beads with bland embolization and to correlate these findings with in vitro release kinetics. MATERIALS AND METHODS Drug-eluting beads (DEB; 100–300 μm and 700–900 μm) loaded with 37.5 mg doxorubicin per milliliter hydrated beads were used to embolize the hepatic artery feeding the left lobe of the liver in young adult Yucatan pigs ( n = 5 per group). Control animals underwent embolization with bland beads (100–300 m; n = 5). Systemic plasma levels of doxorubicin were measured and correlated to in vitro drug release. Blood sampling and histopathologic examination were performed during the 90-day follow-up. RESULTS All animals underwent successful embolization, and the treatment was well tolerated. Mean volumes of beads administered were 2.0–3.4 mL, with mean doses of 127.5 mg and 78.7 mg of doxorubicin for the 100- to 300-μm and 700- to 900-μm DEB groups, respectively. Gross pathologic examination revealed no effects on organs other than the liver. There was a transient increase in liver enzyme levels, particularly in the groups of animals who underwent embolization with 100- to 300-μm DEB. Histopathologic study showed mostly nonnecrotic changes with bland beads, whereas the effects of DEB were more severe, with large areas of pannecrosis evident with the 100- to 300-μm DEB. Maximum plasma concentrations were 651 ng/mL and 42.8 ng/mL for the 100- to 300-μm and 700- to 900-μm DEB groups, respectively, observed at 1 minute for both groups. Correlation with in vitro data showed a strong linear relationship. CONCLUSIONS Hepatic arterial embolization with DEB was shown to be safe and well tolerated. The locoregional delivery of doxorubicin from DEB caused targeted tissue damage with minimal systemic impact and could be a promising new approach to transarterial chemoembolization of solid tumors.

DC Bead is a sulfonate-modified, PVA-based microspherical embolisation agent approved for the treatment of hypervascular tumours and arterio-venous malformations. The beads have previously been shown to actively sequester oppositely charged drugs, such as doxorubicin hydrochloride (dox) by an ion-exchange mechanism. In order to characterise the release kinetics and predict the in vivo behaviour of drug eluting beads (DEB), two elution methods were utilised. The first, an application of the USP dissolution method Type II - Apparatus, enables study of the complete elution of loaded DC Bead in less than 4 h, allowing relatively rapid comparison to be made between different products and formulations. Release data obtained using this method were fitted to first order kinetics (R (2) > 0.998) and the elution constants shown to increase with the total surface area of the beads exposed to the elution medium. Diffusion coefficients were calculated adopting the Fickian diffusion model, which predicted slow elution rates under physiological conditions. The second method involved the use of a T-Apparatus where the drug experiences an element of diffusion through a static environment. This method was developed to resemble the in vivo situation in embolisation procedures more closely. Slow release of dox from DC Bead with half-lives over 1,500 h were predicted for all size ranges using a slow release model. A strong linear relationship was found between the release data from T-Apparatus and pharmacokinetic data obtained from patients treated with DC Bead loaded with dox in transarterial chemoembolisation (TACE) procedures. These data indicated a Level A in vitro-in vivo correlation (IVIVC) for the first 24 h post embolisation. Both systems developed were automated and good reproducibility was obtained for all samples, demonstrating the usefulness of these elution techniques for product development and comparative testing.

Drug eluting beads that release irinotecan in a controlled manner may be useful for application in the chemoembolization of colorectal cancer metastases to the liver. In this study, irinotecan drug eluting beads were prepared with loadings up to 50 mg drug/mL hydrated beads. Drug loading was via an ion-exchange mechanism with sulfonate binding sites in the bead. Release in vitro was shown to be sustained and dependent upon the presence of ions in the elution medium, drug loading and bead size. Drug elution in PBS was controlled by solute diffusion within the beads and gave rise to values for the diffusion coefficient, D, of between 2.4x10(-9) and 1.4x10(-7) cm(2)s(-1). The beads were shown to decrease in size (by a maximum 25-30%), and concomitantly their modulus of compression increased (from approximately 27 kPa to a maximum of about 49 kPa), with increasing drug loading. This did not however, influence their ability to be suspended homogeneously in contrast agent or delivered through a microcatheter. Following porcine hepatic artery embolization, maximum plasma levels were 70-75% lower for both irinotecan and SN-38 compared to intraarterial bolus administration, with peak levels observed at 2 and 5 min after completion of the embolization procedure. The in vivo data were shown to correlate well with the in vitro release measured using a T-apparatus model of embolization.

Phospholipid-like polymers based on 2-methacryloyloxyethyl phosphorylcholine containing varying amounts of the cationically charged monomer choline methacrylate (CMA) from 0 to 30 wt% have been prepared. Substrates coated with these materials were shown to bind significantly lower amounts of specific proteins compared to the uncoated control. ELISA assays demonstrated that fibrinogen did not bind appreciably to coatings containing 0-30% CMA, whereas albumin binding was seen to increase significantly as the CMA content of the coating increased. Platelet activation assays, measurement of plasma coagulation time and whole blood contact scanning electron micrography demonstrated that the haemocompatibility of the coatings was shown to be unaffected by the CMA component. The CMA polymer coatings have been shown to absorb/adsorb many different drug compounds covering a wide range of molecular weights and release these in a controlled fashion. The range of cationic polymers assessed can interact with the net negative charge found in many large therapeutic biomolecules, such as DNA fragments used in gene therapy, that may be of interest in the preventative treatment of conditions such as restenosis. Coronary stents coated with 6% or 20% CMA-containing polymers have been shown to load and release this type of genetic material irrespective of molecular weight of the biomolecule. Ex vivo and in vivo studies have shown that these compounds can be delivered to the stented section of the vessel with very low quantities delivered outside the vessel target area.

The preparation and characterisation of a new phosphorylcholine (PC)-coated silicone hydrogel contact lens for use in extended wear is described. The Michael-type addition of amines to acrylates forms the basis of the synthesis of a novel silicone-based macromer with hydrophilic functionality. It is demonstrated that this macromer can be combined with other silicone-based monomers, hydrophilic monomers and crosslinker to produce a contact lenses formulation. Examples of lenses with water contents of 33% and 46% are illustrated and their properties compared to other commercially available lenses. Materials with comparatively low modulus (0.3 MPa) and adequate tear strength (2-4MPa) with excellent elongation to break (200%) can be obtained using this technology. In addition to the mechanical aspects. both the oxygen and solute permeabilities of the material can be controlled by the hydrophilic: hydrophobic monomer balance in the formulation. to obtain materials with attributes suitable for extended wear use. The PC coating is achieved by means of an in-mould coating (IMC) technique that produces a uniform and stable surface as determined by staining and XPS. The coating imparts both improved lens wettability (advancing contact angle of approximately 50 with virtually no hysteresis) and lower protein adsorption relative to the uncoated lens.

Glucagon-like peptide-1 (GLP-1) is a gut incretin hormone with cardioprotective effects. Human stem cells secreting a GLP-1 fusion protein and encapsulated in an alginate matrix (GLP-1 CellBeads) have been developed as a novel therapeutic agent. This study investigated the effects of GLP-1 CellBeads on post-myocardial infarction (MI) healing in a porcine model. GLP-1 CellBeads were delivered to the left anterior descending coronary artery to create micro-infarcts, with cell-free beads as controls. Hearts were explanted at 1 and 4 weeks post-MI. Gross infarct size was measured as a percentage of left ventricular area. Tissue was analysed for inflammation (number of MAC 387 positive cells/mm 2 ), apoptosis (% TUNEL positive cells) and collagen (% picrosirius red staining). Compared with controls (n=4), the GLP-1-treated group (n=6) exhibited less infarct at one (6.21%±0.64 vs 9.78%±1.80% 2LV, p=NS) and 4 weeks post-MI (4.7%±2.1 vs 21.8%±4.8% LV, p=0.02). Within the infarct there was increased inflammation in GLP-1-treated groups at both time points (1 week: 97.22%±19.62 vs 36.67%±7.78, p=0.01; 4 weeks: 24.2%±4.57 vs 12.3%±3.16, p=0.03). At 1 week, apoptosis rates in the infarct area were similar in both groups (1.46 %±0.57 vs 1.47 %±0.17, p=NS), with less apoptosis in the GLP-1-treated group at 4 weeks (0.51%±0.18 vs 1.84%±0.62, p=NS). Collagen content at 1 week was lower (5.14%±1.19 vs 9.95%±1.42, p=0.05) and at 4 weeks higher in the treated group (20.89%±8.25 vs 6.87%±2.92, p=NS). GLP-1 CellBeads have an effect on post-MI infarct size, inflammation and ventricular remodelling. These findings require further validation before clinical translation.

2-Methacryloyloxyethyl phosphorylcholine (MPC) was synthesised and then used in the preparation of crosslinked polymer membranes with lauryl methacrylate, hydroxypropyl methacrylate and trimethoxysilylpropyl methacrylate (crosslinker) comonomers. Some physical aspects of the membrane properties were evaluated in order to establish the basis for the synthesis of a series of post-crosslinkable polymers. These materials were made by copolymerisation of the constituent monomers via a free radical method, and characterised using NMR, FT-IR, viscometry and elemental analysis. The optimum crosslink density and conditions required for curing coatings of these polymers were investigated using atomic force microscopy (AFM) and showed the inclusion of 5 mol% silyl crosslinking agent to be ideal. A nanoindentation technique was employed to determine if the coating developed elasticity upon crosslinking. The biological properties of the coatings were evaluated using a variety of protein adsorption assays and blood contacting experiments, and an enzyme immunoassay was developed to detect E. coli in order to assess the level of bacterial adhesion to these biomaterials. Polymers of this type were shown to be very useful as coating materials for improving the biocompatibility of, or reducing the levels of adherent bacteria to medical devices.

This study attempts to prevent neointimal hyperplasia by coating the graft luminal surface with a derivative of phosphorylcholine (PC), thereby providing a biocompatible surface with the assumption of limiting pannus tissue ingrowth from the graft anastomoses. Bilateral carotid artery bypass grafts were placed in six dogs using expanded polytetrafluoroethylene (ePTFE). In each animal, one carotid arterial-arterial conduit was constructed using a graft having a PC coating over the entire luminal surface of the graft. On the contralateral side, uncoated graft served as a control. The processed specimens were analyzed for graft neointimal area and neointimal thickness. Cell proliferation was assessed by staining for bromodeoxyuridine (BrdU) incorporation. All grafts were patent except one control graft that was occluded at 4 weeks. There was a significant reduction in the anastomotic graft neointimal area between the treated and control groups (0.27 +/- 0.17 mm2 versus 0.53 +/- 0.13 mm2, respectively; p = 0.008). Furthermore, the BrdU labeling index in the graft neointimal tissues was significantly smaller (p0.001) in the treated group (2.64 +/- 0.77%) as compared with the control group (5.07 +/- 0.83%). These data demonstrate that PC coating of ePTFE significantly reduces graft neointimal hyperplasia and cell proliferation in a canine carotid artery bypass model. The application of PC within the ePTFE graft effectively blocks tissue ingrowth from the adjacent native vessel, thereby preserving the anastomosis luminal diameter.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone with cardioprotective effects. Human stem cells (hMSCs) secreting a GLP-1 fusion protein and encapsulated in alginate (GLP-1 CellBeads) have been developed as a novel therapeutic. This study investigated the effects of GLP-1 CellBeads on post-MI healing in a porcine model. GLP-1 CellBeads were delivered to coronary artery branches, creating micro-infarcts and mild LV dysfunction. Cell-free beads (empty) and CellBeads containing hMSCs but not secreting GLP-1 (hMSC-beads) were delivered as controls. Left ventricular (LV) function, infarct size, myocyte cross-sectional area, total collagen content (picrosirius red staining) and collagen -1 and -3 levels (qRT-PCR) were analysed to determine therapeutic potential. Four weeks post-MI, only GLP-1 CellBead treatment produced significantly improved LV function compared to 30 min post-MI (44.00%±1.29% vs 49.75%±1.03%, p

Rational for the Study Long term patency of autologous saphenous vein coronary bypass grafts is limited by neointima formation and atherosclerosis. Neointima is promoted by adventitial hypoxia. Hence we investigated the effect on neointima in pig vein-into-artery interposition grafts of peri-adventitial application of immortalised human mesenchymal stem cells that express the angiogenic peptide, Glucagon Like Peptide-1. Cells were protected from immune mediated destruction by encapsulation in alginate microbeads. Methodology Cellbeads (20 000cell/cm 2 ) were applied onto adventitia in Ringer9s solution during grafting and were compared to alginate beads without stem cells or vehicle treated grafts. Results CellBeads significantly reduced neointima area after 4 weeks compared to alginate beads (mean difference 4.1 mm 2 , 95% CI 0.3 to 7.9, p=0.033) or vehicle (mean difference 4.0 mm 2 , 95% CI 0.3 to 7.7, p=0.030). CellBeads provoked a significant increase in vein graft adventitial neoangiogenesis vs alginate beads (mean difference 16.8 vessels/ mm 2 95% CI 3.4 to 30.3, p=0.012) or vehicle (mean difference 18.0 vessels/ mm 2 95% CI 5.1 to 31.0, p=0.006). CellBeads had no effect on vessel inward or outward remodelling and promoted adventitial collagen deposition. CellBeads treated grafts had higher patency (6/7) than alginate beads without stems cells (6/17, Fisher9s Exact test p=0.052) and similar to vehicle-treated grafts (7/8 grafts patent), There was no evidence of an inflammatory (macrophage) or immune (lymphocyte) reaction to either CellBeads or alginate beads. Conclusions Periadventitial human stem cells inhibit early neointima formation and accelerate adventitial angiogenesis in experimental porcine vein grafts. The alginate beads alone exhibited unexpected graft failure which will need to be understood before further translational development.

Stainless steel stents have been developed to perform their primary purpose of providing sufficient physical support to an artery following percutaneous transluminal coronary angioplasty (PTCA) in order to prevent vessel recoil. Early clinical problems, largely caused by subacute thrombosis (SAT), have been significantly reduced with a new generation of antiplatelet agents. Despite improved pharmacological control of SAT in many patients, the potential for stent occlusion remains a life-threatening problem for those with more complex lesions. One strategy for dealing with this is to improve the hemocompatibility of the stent surface with coatings. A phosphorylcholine (PC)-based stent coating has been designed for this purpose; we describe in detail the evaluation of the device, in vitro, through preclinical and early clinical data. We discuss studies that demonstrate that the PC-coated stent may offer some clinical advantage over uncoated counterparts. The extensive experience with this PC-coated device supports its nonthrombogenic nature, excellent acceptance by arterial tissue, and long-term stability in vivo. These characteristics, together with its ability to load and release a variety of therapeutic agents, also make the device a natural choice of platform for future stent-mediated drug delivery for treating restenosis.