Stent Coatings Research Articles

Coronary Stent Materials and Coatings: A Technology and Performance Update.

This paper reviews the current state of the art for coronary stent materials and surface coatings, with an emphasis on new technologies that followed on from first-generation bare metal and drug-eluting stents. These developments have been driven mainly by the need to improve long term outcomes, including late stent thrombosis. Biodegradable drug-eluting coatings aim to address the long term effects of residual durable polymer after drug elution; the SYNERGY, BioMatrix, and Nobori stents are all promising devices in this category, with minimal polymer through the use of abluminal coatings. Textured stent surfaces have been used to attached drug directly, without polymer; the Yukon Choice and BioFreedom stents have some promising data in this category, while a hydroxyapatite textured surface has had less success. The use of drug-filled reservoirs looked promising initially but the NEVO device has experienced both technical and commercial set-backs. However this approach may eventually make it to market if trials with the Drug-Filled Stent prove to be successful. Non-pharmacological coatings such as silicon carbide, carbon, and titanium-nitride-oxide are also proving to have potential to provide better performance than BMS, without some of the longer term issues associated with DES. In terms of biological coatings, the Genous stent which promotes attachment of endothelial progenitor cells has made good progress while gene-eluting stents still have some practical challenges to overcome. Perhaps the most advancement has been in the field of biodegradable stents. The BVS PLLA device is now seeing increasing clinical use in many complex indications while magnesium stents continue to make steady advancements.

Conjugation, Identification and Bionomics Analysis of EGFR Targeting Drug TGF α-Saporin as a Bioactive Stent Coating Material

Objective: To identify and testify the cytotoxicity of the EGFR targeting drug TGFa-SAP conjugated and synthesized with N-succinimidyl-3 (2-pyridyldithio) propionate on human hepatoma cell line BEL-7404 cells and proliferating vascular smooth muscle cells. Methods: Conjugation of saporin with TGFa was accomplished after derivatization of TGFa and saporin with N-succinimidyl-3 (2-pyridyldithio) proprionate and the purification of the conjugate was achieved through Eppendorf Centrifugal Filter. Cytotoxicity assays were measured by MTS assays. The value of Thymidine incorporation in BEL-7404 cells was measured by 3H-thymidine uptake. Results: Cytotoxicity assays testified that TGFa-SAP conjugate could remarkably inhibit the proliferation of human hepatoma cell line BEL-7404 cells in vitro. The value of thymidine incorporation of BEL-7404 cells in TGFa-SAP groups significantly decreased compared with the control group (P<0.05), and it had dose-dependence on TGFa-SAP’s concentration. But Saporin could not affect BEL-7404 cells even at higher level (10-5). TGFa-SAP conjugate had effective cytotoxicity on proliferating vascular smooth muscle cells, also. Conclusion: The results indicated that the conjugated EGFR targeting drug TGFa-SAP had effective cytotoxicity not only on BEL-7404 cells, but also on proliferating vascular smooth muscle cells, as a potential bioactive stent coating material.

Covalent Polyisobutylene-Paclitaxel Conjugates for Controlled Release from Potential Vascular Stent Coatings.

The development of covalent polyisobutylene (PIB)-paclitaxel (PTX) conjugates as a potential approach to controlling drug release from vascular stent coatings is described. PIB-PTX materials containing ∼24 and ∼48 wt % PTX, conjugated via ester linkages, were prepared. The PTX release profiles were compared with those of physical mixtures of PTX with carboxylic acid-functionalized PIB and with the triblock copolymer polystyrene-b-PIB-b-polystyrene (SIBS). Covalent conjugation led to significantly slower drug release. Atomic force microscopy imaging of coatings of the materials suggested that the physical mixtures exhibited multiple domains corresponding to phase separation, whereas the materials in which PTX was covalently conjugated appeared homogeneous. Coatings of the conjugated materials on stainless steel surfaces suffered less surface erosion than the physically mixed materials, remained intact, and adhered well to the surface throughout the thirty-five day study. Tensile testing and rheological studies suggested that the incorporation of PTX into the polymer introduces similar physical changes to the PIB as the incorporation of a glassy polystyrene block does in SIBS. Cytotoxicity assays showed that the coatings did not release toxic levels of PTX or other species into a cell culture medium over a 24 h period, yet the levels of PTX in the materials were sufficient to prevent C2C12 cells from adhering to and proliferating on them. Overall, these results indicate that covalent PIB-PTX conjugates have promise as coatings for vascular stents.

Fabrication of Polymeric Coatings with Controlled Microtopographies Using an Electrospraying Technique.

Surface topography of medical implants provides an important biophysical cue on guiding cellular functions at the cell-implant interface. However, few techniques are available to produce polymeric coatings with controlled microtopographies onto surgical implants, especially onto implant devices of small dimension and with complex structures such as drug-eluting stents. Therefore, the main objective of this study was to develop a new strategy to fabricate polymeric coatings using an electrospraying technique based on the uniqueness of this technique in that it can be used to produce a mist of charged droplets with a precise control of their shape and dimension. We hypothesized that this technique would allow facile manipulation of coating morphology by controlling the shape and dimension of electrosprayed droplets. More specifically, we employed the electrospraying technique to coat a layer of biodegradable polyurethane with tailored microtopographies onto commercial coronary stents. The topography of such stent coatings was modulated by controlling the ratio of round to stretched droplets or the ratio of round to crumped droplets under high electric field before deposition. The shape of electrosprayed droplets was governed by the stability of these charged droplets right after ejection or during their flight in the air. Using the electrospraying technique, we achieved conformal polymeric coatings with tailored microtopographies onto conductive surgical implants. The approach offers potential for controlling the surface topography of surgical implant devices to modulate their integration with surrounding tissues.

Friction Reduction at a Superhydrophilic Surface: Role of Ordered Water

Low-friction but superhydrophilic materials are urgently needed in biomedical and engineering fields because of their nonfouling property and biocompatibility, particularly when the surfaces are definitely superhydrophilic, such as metal or TiO2 as the surface coatings of the intravascular stents. However, generally, there is a higher friction coefficient on the superhydrophilic surfaces than on the hydrophobic surfaces. On the basis of molecular dynamics simulations, we show that the friction on the superhydrophilic surface with appropriate charge patterns is evidently reduced, where the lower friction is similar to that of a rather hydrophobic surface with a contact angle of water droplet of ∼44°. This reduction is attributed to the existence of an ordered water monolayer on the superhydrophilic surface with appropriate charge patterns, and the friction between this ordered water monolayer and the water molecules above is small.

A transferable non-destructive method for the quantification of coronary stent coating components using Raman spectroscopy

Drug content of coronary stents is destructively evaluated using high pressure liquid chromatography. The method involves the dissolution of the coating from the stent into a solution and the analysis and quantification of the solvents' drug content. Quantification of the components of drug by Raman has been demonstrated with most recent methods using multivariate techniques. However, the calibration models generated as part of these methods are not easily transferable because they are developed using defined mixtures. In this work, we demonstrate a transferable non-destructive Raman method for the evaluation and quantification of the drug coating components by developing a model from the pure samples of the coating constituents. Using the designed experiment, the transferable Raman method is equivalence tested with the standard high pressure liquid chromatography approach and compares favorably as a non-destructive viable alternative. A method of dealing with the microheterogeneity of stent coatings is presented by spectral sample collection through the rotation of the stent. Knowledge of the coating formation and substrates is required in order to correctly interpret the results. Copyright © 2015 John Wiley & Sons, Ltd.

Application of quality by design (QbD) approach to ultrasonic atomization spray coating of drug-eluting stents.

The drug coating process for coated drug-eluting stents (DES) has been identified as a key source of inter- and intra-batch variability in drug elution rates. Quality-by-design (QbD) principles were applied to gain an understanding of the ultrasonic spray coating process of DES. Statistically based design of experiments (DOE) were used to understand the relationship between ultrasonic atomization spray coating parameters and dependent variables such as coating mass ratio, roughness, drug solid state composite microstructure, and elution kinetics. Defect-free DES coatings composed of 70% 85:15 poly(DL-lactide-co-glycolide) and 30% everolimus were fabricated with a constant coating mass. The drug elution profile was characterized by a mathematical model describing biphasic release kinetics. Model coefficients were analyzed as a DOE response. Changes in ultrasonic coating processing conditions resulted in substantial changes in roughness and elution kinetics. Based on the outcome from the DOE study, a design space was defined in terms of the critical coating process parameters resulting in optimum coating roughness and drug elution. This QbD methodology can be useful to enhance the quality of coated DES.

In vitro hemocompatibility and cytocompatibility of dexamethasone-eluting PLGA stent coatings

Drug-eluting stents (DESs) have been an important breakthrough for interventional cardiology applications since 2002. Though successful in reducing restenosis, some adverse clinical problems still emerged, which were mostly caused by the bare-metal stents and non-biodegradable polymer coatings, associated with the delayed endothelialization process. In this study, dexamethasone-loaded poly (lactic-co-glycolic acid) (PLGA) coatings were developed to explore the potential application of dexamethasone-eluting stents. Dexamethasone-eluting PLGA stents were prepared using ultrasonic atomization spray method. For other tests like stability and cytocompatibility and hemocompatibility tests, dexamethasone loaded coatings were deposited on 316L SS wafers. Fourier transform-infrared spectroscopy (FT-IR) results demonstrated that there was no chemical reaction between PLGA and dexamethasone. The balloon expansion experiment and surface morphology observation suggested that the stent coatings were smooth and uniform, and could also withstand the compressive and tensile strains imparted without cracking after stent expansion. The drug release behavior in vitro indicated that dexamethasone existed burst release within 1 day, but it presented linear release characteristics after 6 days. In vitro platelets adhesion, activation test and APTT test were also done, which showed that after blending dexamethasone into PLGA, the hemocompatibility was improved. Besides, dexamethasone and dexamethasone-loaded PLGA coatings could significantly inhibit the attachment and proliferation of smooth muscle cells.

Hydroxybutyl Chitosan Polymer-Mediated CD133 Antibody Coating of Metallic Stents to Reduce Restenosis in a Porcine Model of Atherosclerosis.

Antibody-coated stents to capture circulating endothelial progenitor cells (EPCs) for re-endothelialization appear to be a novel therapeutic option for the treatment of atherosclerotic disease. Hydroxybutyl chitosan (HBC), a linear polysaccharide made from shrimps and other crustacean shells, is biocompatible, nontoxic, and hydrophilic, making it ideal for biomedical applications. In this study, HBC was explored for the immobilization of anti-CD133 antibodies. We demonstrated that CD133 antibodies mediated by HBC were successfully coated on cobalt-chromium alloy discs and metal stents. The coating was homogeneous and smooth as shown by electronic microscopy analysis. Balloon expansion of coated stents did not cause cracking or peeling. The HBC discs promoted CD133+ EPCs and human umbilical vein endothelial cell growth in vitro. The CD133 antibody-coated but not bare discs bound CD133+ EPCs in vitro. Implantation of CD133 antibody-coated stents significantly inhibited intimal hyperplasia and reduced restenosis compared with implantation of bare stents in a porcine model of atherosclerosis. These findings suggest HBC is a valuable anchoring agent that can be applied for bioactive coating of stents and that CD133 antibody-coated stents might be a potential therapeutic alternative for the treatment of atherosclerotic disease.

A mechanistic model for drug release in PLGA biodegradable stent coatings coupled with polymer degradation and erosion.

Biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) coating for applications in drug-eluting stents has been receiving increasing interest as a result of its unique properties compared with biodurable polymers in delivering drug for reducing stents-related side effects. In this work, a mathematical model for describing the PLGA degradation and erosion and coupled drug release from PLGA stent coating is developed and validated. An analytical expression is derived for PLGA mass loss that predicts multiple experimental studies in the literature. An analytical model for the change of the number-average degree of polymerization [or molecular weight (MW)] is also derived. The drug transport model incorporates simultaneous drug diffusion through both the polymer solid and the liquid-filled pores in the coating, where an effective drug diffusivity model is derived taking into account factors including polymer MW change, stent coating porosity change, and drug partitioning between solid and aqueous phases. The model is used to describe in vitro sirolimus release from PLGA stent coating, and demonstrates the significance of simultaneous sirolimus release via diffusion through both polymer solid and pore space. The proposed model is compared to existing drug transport models, and the impact of model parameters, limitations and possible extensions of the model are also discussed.

Modeling and analysis of drug-eluting stents with biodegradable PLGA coating: consequences on intravascular drug delivery.

Increasing interests have been raised toward the potential applications of biodegradable poly(lactic-co-glycolic acid) (PLGA) coatings for drug-eluting stents in order to improve the drug delivery and reduce adverse outcomes in stented arteries in patients. This article presents a mathematical model to describe the integrated processes of drug release in a stent with PLGA coating and subsequent drug delivery, distribution, and drug pharmacokinetics in the arterial wall. The integrated model takes into account the PLGA degradation and erosion, anisotropic drug diffusion in the arterial wall, and reversible drug binding. The model simulations first compare the drug delivery from a biodegradable PLGA coating with that from a biodurable coating, including the drug release profiles in the coating, average arterial drug levels, and arterial drug distribution. Using the model for the PLGA stent coating, the simulations further investigate drug internalization, interstitial fluid flow in the arterial wall, and stent embedment for their impact on drug delivery. Simulation results show that these three factors, while imposing little change in the drug release profiles, can greatly change the average drug concentrations in the arterial wall. In particular, each of the factors leads to significant and yet distinguished alterations in the arterial drug distribution that can potentially influence the treatment outcomes. The detailed integrated model provides insights into the design and evaluation of biodegradable PLGA-coated drug-eluting stents for improved intravascular drug delivery.

TCT-442 Comparison of contemporary DES of different stent geometry and Absorb in a Swine Carotid – Jugular Thrombogenicity Shunt Model

Polymer coatings of drug eluting stents (DES) have been shown to offer a protective barrier against acute thrombus formation compared with bare metal stents (BMS). While this anti-thrombotic function has been assigned to contemporary DES utilizing permanent polymeric coatings, the impact of

TCT-27 Comparison of Novel Zotarolimus-Eluting Cobalt-Chromium Stents and Everolimus-Eluting Platinum-Chromium Stents in Patients of the Randomized DUTCH PEERS Trial Presenting with Acute Myocardial Infarction

Background: Biocompatible durable polymer coatings for drug-eluting stents (DES) were developed to reduce the risk of stent thrombosis, which is generally increased in the setting of acute myocardial infarction (MI). These coatings are used on novel, flexible, and highly deliverable third-generation DES, investigated in the randomized, multicenter, all-comer DUTCH PEERS (TWENTE II) trial. Of the 1,811 eligible all-comer patients of DUTCH PEERS, 817 (45%) were treated in the setting of acute MI. Methods: We assessed the one-year safety and efficacy of the Resolute Integrity zotarolimus-eluting stent (ZES) (Medtronic, Santa Rosa, CA, USA) and Promus Element everolimus-eluting stent (EES) (Boston Scientific, Natick, MA, USA) in 817 DUTCH PEERS patients who were treated for acute MI. One-year follow-up data of all patients were obtained; adverse events were externally adjudicated by an independent committee. The primary endpoint was target vessel failure (TVF) at 1-year, a composite of cardiac death, target vessel related MI, and clinically indicated target vessel revascularization. Secondary endpoints included all the individual components of the primary endpoint, the incidence of stent thrombosis (ST), and the patient-oriented clinical endpoint (POCE). Results: Patient and lesion characteristics did not differ between groups with the only exception being higher proportions of severely calcified lesions (87/548(16%) vs. 108/500(22%), p=0.02) and stent postdilatation in EES (402/548 (73%) vs. 400/500 (80%), p=0.01). At one year, TVF did not differ significantly between the two stent arms (20/421(5%) vs. 15/396 (4%, p=0.50). In addition, POCE was 8% (32/421) for ZES and 6% (23/396) for EES (p=0.31). Definite-or-probable ST rates were very low and similar in both groups (2/421 (0.5%) vs. 1/396 (0.3%), p=1.00). Conclusions: One-year follow-up of DUTCH PEERS patients, who were treated for acute MI, demonstrated excellent clinical results with a similar and sustained safety and efficacy of the Resolute Integrity ZES and the Promus Element EES.

New Generations of Drug-Eluting Stents – A Brief Review

This review focuses on describing new generations of drug-eluting stents (DES) based on the use of novel stent platforms, coatings, and carrier systems, developed to enhance DES safety. Examples of various DES classes among the most clinically-used DES are briefly discussed.

Improved Biocompatibility of Poly(lactic-co-glycolic acid) and Poly-L-Lactic Acid Blended with Nanoparticulate Amorphous Calcium Phosphate in Vascular Stent Applications

Biodegradable polymers used as vascular stent coatings and stent platforms encounter a major challenge: biocompatibility in vivo, which plays an important role in in-stent restenosis (ISR). Co-formulating amorphous calcium phosphate (ACP) into poly(lactic-co-glycolic acid) (PLGA) or poly-L-lactic acid (PLLA) was investigated to address the issue. For stent coating applications, metal stents were coated with polyethylene-co-vinyl acetate/poly-n-butyl methacrylate (PEVA/PBMA), PLGA or PLGA/ACP composites, and implanted into rat aortas for one and three months. Comparing with both PEVA/PBMA and PLGA groups after one month, the results showed that stents coated with PLGA/ACP had significantly reduced restenosis (PLGA/ACP vs. PEVA/PBMA vs. PLGA: 21.24 +/- 2.59% vs. 27.54 +/- 1.19% vs. 32.12 +/- 3.93%, P < 0.05), reduced inflammation (1.25 +/- 0.35 vs. 1.77 +/- 0.38 vs. 2.30 +/- 0.21, P < 0.05) and increased speed of re-endothelialization (1.78 +/- 0.46 vs. 1.17 +/- 0.18 vs. 1.20 +/- 0.18, P < 0.05). After three months, the PLGA/ACP group still displayed lower inflammation score (1.33 +/- 0.33 vs. 2.27 +/- 0.55, P < 0.05) and higher endothelial scores (2.33 +/- 0.33 vs. 1.20 +/- 0.18, P < 0.05) as compared with the PEVA/PBMA group. Moreover, for stent platform applications, PLLA/ACP stent tube significantly reduced the inflammatory cells infiltration in the vessel walls of rabbit iliac arteries relative to their PLLA cohort (NF-kappaB-positive cells: 23.31 +/- 2.33/mm2 vs. 9.34 +/- 1.35/mm2, P < 0.05). No systemic biochemical or pathological evidence of toxicity was found in either PLGA/ACP or PLLA/ACP. The co-formulation of ACP into PLGA and PLLA resulted in improved biocompatibility without systemic toxicity.

Biolimus-Eluting Stents With Biodegradable Polymer Versus Bare-Metal Stents in Acute Myocardial Infarction

This study sought to determine whether the 1-year differences in major adverse cardiac event between a stent eluting biolimus from a biodegradable polymer and bare-metal stents (BMSs) in the COMFORTABLE trial (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) were sustained during long-term follow-up. A total of 1161 patients were randomly assigned to biolimus-eluting stent (BES) and BMS at 11 centers, and follow-up rates at 2 years were 96.3%. A subgroup of 103 patients underwent angiography at 13 months. At 2 years, differences in the primary end point of cardiac death, target-vessel myocardial infarction, and target lesion revascularization continued to diverge in favor of BES-treated patients (5.8%) compared with BMS-treated patients (11.9%; hazard ratio = 0.48; 95% confidence interval, 0.31-0.72; P < 0.001) with a significant risk reduction during the second year of follow-up (hazard ratio 1-2 years = 0.45; 95% confidence interval, 0.20-1.00; P = 0.049). Differences in the primary end point were driven by a reduction in target lesion revascularization (3.1% versus 8.2%; P < 0.001) and target-vessel reinfarction (1.3% versus 3.4%; P = 0.023). The composite of death, any reinfarction and revascularization (14.5% versus 19.3%; P = 0.03), and cardiac death or target-vessel myocardial infarction (4.2% versus 7.2%; P = 0.036) were less frequent among BES-treated patients compared with BMS-treated patients. The 13-month angiographic in-stent percent diameter stenosis amounted to 12.0 ± 7.2 in BES- and 39.6 ± 25.2 in BMS-treated lesions (P < 0.001). Among patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, BES continued to improve cardiovascular events compared with BMS beyond 1 year. http://www.clinicaltrials.gov. Unique identifier: NTC00962416.

Gallic Acid Tailoring Surface Functionalities of Plasma-Polymerized Allylamine-Coated 316L SS to Selectively Direct Vascular Endothelial and Smooth Muscle Cell Fate for Enhanced Endothelialization

The creation of a platform for enhanced vascular endothelia cell (VEC) growth while suppressing vascular smooth muscle cell (VSMC) proliferation offers possibility for advanced coatings of vascular stents. Gallic acid (GA), a chemically unique phenolic acid with important biological functions, presents benefits to the cardiovascular disease therapy because of its superior antioxidant effect and a selectivity to support the growth of ECs more than SMCs. In this study, GA was explored to tailor such a multifunctional stent surface combined with plasma polymerization technique. On the basis of the chemical coupling reaction, GA was bound to an amine-group-rich plasma-polymerized allylamine (PPAam) coating. The GA-functionalized PPAam (GA-PPAam) surface created a favorable microenvironment to obtain high ECs and SMCs selectivity. The GA-PPAam coating showed remarkable enhancement in the adhesion, viability, proliferation, migration, and release of nitric oxide (NO) of human umbilical vein endothelial cells (HUVECs). The GA-PPAam coating also resulted in remarkable inhibition effect on human umbilical artery smooth muscle cell (HUASMC) adhesion and proliferation. These striking findings may provide a guide for designing the new generation of multifunctional vascular devices.

Basic Fibroblast Growth Factor as a Potential Stent Coating Material Inducing Endothelial Cell Proliferation

The use of drug-eluting stents has reduced the incidence of in-stent restenosis following percutaneous coronary intervention; however, almost all drugs eluting from polymers on stents induce antiproliferative effects on vascular endothelial and vascular smooth muscle cells. Due to injury of the endothelium and delayed reendothelialization, the risk of thrombosis increases over time. Enhancing rapid reendothelialization after stent placement is important for solving these problems. Basic fibroblast growth factor (bFGF) is one of the most important growth factors involved in vascular lesion formation. In this study, we evaluated the potential of bFGF as a stent coating promoting endothelial cell proliferation. Human umbilical vein endothelial cells (HUVECs) and human aortic smooth muscle cells (HASMCs) were cultured with various doses of bFGF in vitro, and the effects of bFGF on the degree of cell proliferation and migration were monitored. We also investigated the effects of bFGF on the protein expression of endothelial nitric oxide synthase (eNOS) in HUVECs using Western blotting. Cell proliferation and migration were promoted in HUVECs by bFGF in a dose- and time-dependent manner. On the other hand, bFGF stimulation had little effect on the HASMCs. Basic FGF increased the eNOS protein levels in the HUVECs, with a maximum at 10 ng/mL followed by a decline at 100 ng/mL. Basic FGF is a possible candidate stent coating and/or eluting drug material stimulating endothelial cell proliferation and early reendothelialization without excessive vascular smooth muscle cell proliferation.

Photoactivated titania-based nanomaterials for potential application as cardiovascular stent coatings

Intravascular stenting of atherosclerotic coronary arteries is a life-saving, widely used procedure in interventional cardiology. Adverse clinical outcomes such as restenosis highlight the importance of meeting the excellent biocompatibility by cardiovascular implants. Many attempts have been made to improve the safety profile of implant surface. We for the first time developed the photoactive intravascular titania-based nanomaterials for the application as cardiovascular stent coating. Photoactive biomaterial deposited on the cardiovascular stent surface demonstrated promising features, making it an excellent substrate for endothelial cells growth and proliferation. The biocompatibility of these coatings has been compared with 316L stainless steel surfaces typically used in commercial coronary stents production. The results of the study proved that the innovative titania-based coatings have better biocompatibility characteristics than the 316L stainless steel and in regard of its antithrombotic potential provided protection against restenosis. Furthermore, the titania coating supported endothelial cells attachment and proliferation, and induced prolonged plasma recalcification time in comparison with stainless steel surface. Innovative photoactive titania coating can be an important factor to prevent the process of the restenosis in the place of implantation.

Dual Drug-Eluting Stents Coated with Multilayers of Hydrophobic Heparin and Sirolimus

Polymer coatings for stents are considered one of the key factors that lead to adverse cardiac events after coronary arterial stenting. This study presents a dual drug-eluting stent (DES) that is coated with multilayers of Duraflo heparin and sirolimus but containing no other organic polymers. The hydrophobic Duraflo heparin coating was used to improve the hemocompatibility of the stent and serve as a drug reservoir for the controlled release of sirolimus, thus avoiding inflammatory reactions induced by the conventional polymers. The Duraflo heparin and sirolimus were coated layer-by-layer onto the stent surface using a homemade spray-coating device. The drug loading amount can be easily controlled by adjusting the numbers of layers applied and the concentration of the drug solution, indicating the developed coating process is reproducible and well-controlled. After balloon expansion, the coating did not crack or peel off, which demonstrates that the sirolimus/Duraflo heparin coating layers tightly adhere to the stent surface. The activated partial thromboplastin time (APTT) assay showed that the Duraflo heparin coating significantly prolonged the APTT from 27.3 ± 0.3 s to 69.7 ± 6.2 s, demonstrating the anticoagulant ability of the coated stents. The dual DES exhibited a nearly linear sustained-release profile of Duraflo heparin and an initial burst release followed by a slow release of sirolimus. Less than 15% of heparin was released from the DES within 14 days, indicating the stent can maintain its antithrombotic surface for a long time. Because of the layer-by-layer structure, the most outer layer of Duraflo heparin coating may act as a diffusion barrier to retard sirolimus release from the stent. These results confirm that the dual DESs enable simultaneous delivery of antithrombotic and antiproliferative drugs and have potential for the treatment of coronary artery disease.