Modeling of degradation and drug release from a biodegradable stent coating

Biodegradable polymeric coatings on cardiovascular stents can be used for local delivery of therapeutic agents to diseased coronary arteries after stenting procedures. This can minimize the occurrence of clinically adverse events such as restenosis after stent implantation. A validated mathematical model can be a very important tool in the design and development of such coatings for drug delivery. The model should incorporate the important physicochemical processes responsible for the polymer degradation and drug release. Such a model can be used to study the effect of different coating parameters and configurations on the degradation and the release of the drug from the coating. In this paper, a simultaneous transport-reaction model predicting the degradation and release of the drug Everolimus from a polylactic acid (PLA) based stent coating is presented. The model has been validated using in vitro testing data and was further used to evaluate the influence of various parameters such as partitioning coefficient of water, autocatalytic effect of the lactic acid and structural change of the matrix, on the PLA degradation and drug release. The model can be used as a tool for predicting drug delivery from other coating configurations designed using the same polymer-drug combination. In addition, this modeling methodology has broader applications and can be used to develop mathematical models for predicting the degradation and drug release kinetics for other polymeric drug delivery systems.     

The short-term effects on restenosis and thrombosis of echinomycin-eluting stents topcoated with a hydrophobic heparin-containing polymer

Although drug-eluting stents (DESs) have become the most effective means of treating coronary artery disease, safety concerns regarding their thrombogenicities remain to be surmounted. Here, we report on a novel type of DES capable of preventing restenosis and thrombosis. The DES was prepared by coating a bare metal stent with echinomycin (an anti-proliferative drug) in polyurethane by a spray drying method. Hydrophobic heparinized polymer was then topcoated onto stent over echinomycin/PU layer by dipping to improve hemocompatibility. The two-layered stent was characterized regarding surface and cross-sectional morphology, drug release pattern, platelet adhesion in vitro, and restenosis in vivo. It was found that the heparin topcoat acts as a diffusion barrier that allows the controlled release of drug in a sustained manner. Also, the heparin coated layer effectively reduced platelet adhesion, indicating excellent hemocompatibility. From the animal test using pigs, it was evident that the developed DESs can minimize neointimal proliferation and thrombus formation. The devised hydrophobic heparinized polymer-coated DES effectively reduced both restenosis and thrombosis, suggesting that they have potential as tools for the treatment of coronary artery diseases.     

Development of a probucol-releasing antithrombogenic drug eluting stent

The success of drug eluting stents (DESs) has been challenged by the manifestation of late stent thrombosis after DES implantation. The incomplete regeneration of the endothelial layer poststenting triggers adverse signaling processes precipitating in thrombosis. Various approaches have been attempted to prevent thrombosis, including the delivery of biological agents, such as estradiol, that promote endothelialization, and the use of natural polymers as coating materials. The underlying challenge has been the inability to release the biological agent in synchronization with the temporal sequence of vascular wound healing in vivo. The natural healing process of the endothelium after an injury starts after a week and may take up to a month in humans. This article presents a novel DES formulation using a hemocompatible polyurethane (PU) matrix to sustain the release of probucol (PB), an endothelial agonist, by exploiting the greater difference in the solubility parameters of PB and PU. This results in the formation of crystalline PB aggregates retarding drug release from PU. The physicochemical properties of PB in PU were confirmed using differential scanning calorimetry and X-ray diffraction. Drug-polymer compatibility was examined using infrared spectral analysis. Also, in vitro studies using primary human aortic endothelial cells resulted in the selection of 5% w/w PB as the optimal dose, to be further tested in vitro and in vivo. This work develops and tests a promising new DES formulation to enable faster endothelial cell proliferation poststenting, potentially minimizing the incidence and severity of thrombotic events after DES implantation.     

Controlled delivery of paclitaxel from stent coatings using novel styrene maleic anhydride copolymer formulations

The controlled release of paclitaxel (PTx) from stent coatings comprising an elastomeric polymer blended with a styrene maleic anhydride (SMA) copolymer is described. The coated stents were characterized for morphology by scanning electron microscopy (SEM) and atomic force microscopy (AFM), and for drug release using high-performance liquid chromatography (HPLC). Differential scanning calorimetry (DSC) was used to measure the extent of interaction between the PTx and polymers in the formulation. Coronary stents were coated with blends of poly(b-styrene-b-isobutylene-b-styrene) (SIBS) and SMA containing 7% or 14% maleic anhydride (MA) by weight. SEM examination of the stents showed that the coating did not crack or delaminate either before or after stent expansion. Examination of the coating surface via AFM after elution of the drug indicated that PTx resides primarily in the SMA phase and provided information about the mechanism of PTx release. The addition of SMA altered the release profile of PTx from the base elastomer coatings. In addition, the presence of the SMA enabled tunable release of PTx from the elastomeric stent coatings, while preserving mechanical properties. Thermal analysis reveled no shift in the glass transition temperatures for any of the polymers at all drug loadings studied, indicating that the PTx is not miscible with any component of the polymer blend. An in vivo evaluation indicated that biocompatibility and vascular response results for SMA/SIBS-coated stents (without PTx) are similar to results for SIBS-only-coated and bare stainless steel control stents when implanted in the non-injured coronary arteries of common swine for 30 and 90 days.     

New stent surface materials: The impact of polymer-dependent interactions of human endothelial cells,smooth muscle cells,and platelets

Despite the development of new coronary stent technologies, in-stent restenosis and stent thrombosis are still clinically relevant. Interactions of blood and tissue cells with the implanted material may represent an important cause of these side effects. We hypothesize material-dependent interaction of blood and tissue cells. The aim of this study is accordingly to investigate the impact of vascular endothelial cells, smooth muscle cells and platelets with various biodegradable polymers to identify a stent coating or platform material that demonstrates excellent endothelial-cell-supportive and non-thrombogenic properties. Human umbilical venous endothelial cells, human coronary arterial endothelial cells and human coronary arterial smooth muscle cells were cultivated on the surfaces of two established biostable polymers used for drug-eluting stents, namely poly(ethylene-co-vinylacetate) (PEVA) and poly(butyl methacrylate) (PBMA). We compared these polymers to new biodegradable polyesters poly(l-lactide) (PLLA), poly(3-hydroxybutyrate) (P(3HB)), poly(4-hydroxybutyrate) (P(4HB)) and a polymeric blend of PLLA/P(4HB) in a ratio of 78/22% (w/w). Biocompatibility tests were performed under static and dynamic conditions. Measurement of cell proliferation, viability, glycocalix width, eNOS and PECAM-1 mRNA expression revealed strong material dependency among the six polymer samples investigated. Only the polymeric blend of PLLA/P(4HB) achieved excellent endothelial markers of biocompatibility. Data show that PLLA and P(4HB) tend to a more thrombotic response, whereas the polymer blend is characterized by a lower thrombotic potential. These data demonstrate material-dependent endothelialization, smooth muscle cell growth and thrombogenicity. Although polymers such as PEVA and PBMA are already commonly used for vascular implants, they did not sufficiently meet the criteria for biocompatibility. The investigated biodegradable polymeric blend PLLA/P(4HB) evidently represents a promising material for vascular stents and stent coatings.     

A mathematical model for predicting drug release from a biodurable drug-eluting stent coating

Drug-eluting stents (DESs) are drug-device combination products that have been commercialized and demonstrated to be safe and efficacious in treating coronary artery disease. They have been very effective in reducing the extent of neointimal hyperplasia and therefore in preventing or minimizing the occurrence of in-stent restenosis. In order to develop a successful DES, it is imperative that the coating be designed so as to deliver, after stent implantation, a therapeutic dose of the drug for the desired time duration at the site of the arterial blockage. Mathematical models are very valuable tools that can be used to study the effect of different coating parameters on drug delivery and can therefore help in coating design. We have developed a bimodal lumped-parameter mass transport model to describe the release of the drug everolimus from a biodurable fluoropolymer-based DES coating. We assume that the dispersed drug phase contributes to two discrete modes of drug transport through the coating. These are the fast mode (mode I) which is the release of the drug from a highly percolated structure of drug phase within the polymer, and the slow mode (mode II) which is the release of the drug from a nonpercolated, polymer-encapsulated phase of the drug within the coating. The three coefficients in the governing equations describing the model, i.e. the two effective diffusivities corresponding to each of the two modes and the fraction of the drug in one of the two modes, were determined by fitting with available DES release data. The predictive power of the model is demonstrated by comparing the release rate from different coating configurations (thickness and drug to polymer ratios) with experimental data. Also, it is demonstrated that if limited experimental data are available at early time points, the model can be used to predict drug release at subsequent time points.     

Controlled release of sirolimus from a multilayered PLGA stent matrix

The release of sirolimus from a bi-layer biodegradable polymeric film is reported in this study. Approved drug-eluting metal stents use a thin polymer coating to control drug release, but the degree of control is limited. In a fully polymeric stent, the use of multilayers allows a range of release kinetics. A bi-layer system, with PLLA as the supporting layer and PLGA as the drug-eluting layer, was used in this study to simulate release of sirolimus from a stent. The results show that the release of sirolimus is diffusion and degradation-controlled, and that the amount of sirolimus loading does not affect its release kinetics. The release of sirolimus is, however, accelerated by the addition of a plasticizer, such as PEG, as water uptake is increased. An increased water uptake increases polymer degradation, and changes the dominant mode of release to degradation-control. The release of sirolimus can, on the other hand, be retarded by using a coating of a biodegradable polyester with a lauryl ester end group. Therefore, multilayered systems offer many options for controlling sirolimus release over months.     

Protein-loaded bioresorbable fibers and expandable stents: Mechanical properties and protein release

There is an increasing interest in bioresorbable polymeric stents for coronary, urethral and tracheal applications. These stents can support body conduits during their healing process and release biologically active agents from an internal reservoir to the surrounding tissue. A removal operation is not needed. Bioresorbable poly(L-lactic acid) fibers were prepared through melt spinning accompanied by a postpreparation drawing process. Novel expandable bioresorbable stents were developed from these fibers. Bioresorbable microspheres containing albumin were prepared and attached to the stents, to serve as a protein reservoir coating. The controlled release of albumin from the microsphere-loaded stent was studied. The fibers combine high strength and modulus, together with good ductility and flexibility. An increase in draw ratio increases the tensile strength and modulus and decreases the ultimate strain. The stents demonstrated excellent initial radial compression strength and good in vitro degradation resistivity, which makes them applicable for supporting blood vessels for at least 20 weeks. Microspheres bound to these stents enable effective protein loading, without reducing the stent's mechanical properties. The protein release from the microsphere-loaded stent occurs by diffusion, is determined mainly by the initial molecular weight of the bioresorbable polymer and its erosion rate, and is strongly affected by the microsphere structure.     

Materials, fluid dynamics, and solid mechanics aspects of coronary artery stents: a state-of-the-art review

It is well known that, across all populations (based on geographic location, race, ethnicity, age, and sex), coronary artery disease (CAD) is the single most common cause of death. The commonly performed revascularization procedures for the treatment of symptomatic CAD are percutaneous transluminal coronary angioplasty (PTCA) by itself or followed by the deployment of either a bare-metal stent (BMS) or a drug-eluting stent (DES). In the latter type, a drug that is either embedded in polymeric or nonpolymeric coating(s) on the stent surface or directly attached to the stent surface elutes into the blood stream at a controlled rate over a period of time, typically 14-30 days. Over the years, there has been a steady decline in the use of PTCA and a concomitant sharp increase in the use of stents, with DESs being the predominant choice in the last 3 years. The present contribution represents a critical review of the literature on the materials, fluid dynamics, and solid mechanics aspects of both BMSs and DESs, with special reference to in-stent restenosis and in-stent thrombosis, these being risks that present commonly.     

Control of cilostazol release kinetics and direction from a stent using a reservoir-based design

Sustained release formulations of a potent antithrombotic drug, cilostazol, in poly-(lactic acid-co-glycolic acid) (PLGA) matrices were created for luminal release from a novel drug-eluting stent utilizing reservoirs (RES TECHNOLOGY?). The crystallinity of cilostazol and the morphology of the cilostazol/polymer matrix in the stent reservoirs were examined by cross-polarized optical microscopy and differential scanning calorimetry. An in vitro method was developed to study release kinetics of various cilostazol formulations and to examine correlation with in vivo release. Formulation parameters such as drug-to-polymer ratio and the use of a polymer barrier on the abluminal surface of the drug/polymer matrix were found to be effective in modulating drug release rate. Cilostazol/PLGA(75/25) in the weight ratio of 50/50 to 70/30 displayed first-order release kinetics for the majority of the drug load. Addition of an abluminal polymer barrier slowed cilostazol release rate when compared to the bidirectional reservoir design. Excellent correlation between cilostazol in vivo release profile from stents in a porcine coronary artery model and that measured in vitro in a modified USP-7 apparatus suggests that the in vitro release system is capable of predicting in vivo release of cilostazol from stent reservoirs.     

Development of a polymeric matrix metalloproteinase inhibitor as a bioactive stent coating material for prevention of restenosis

Drug-eluting stents have been developed to prevent restenosis derived from excessive growth of smooth muscle cells (SMCs) after stenting. In almost every case, however, less- or non-biocompatible polymers were selected for the platform material for impregnating drugs on the stent strut. Consideration was given principally to the physical properties of the polymers, such as their adhesion to the strut and the drug dispersibility in the polymeric matrix. In this study, we designed a matrix metalloproteinase inhibitor (MMPI)-derivatized hydrophobic polymer (PMMPI) for use as a bioactive material for stent coating. This was a copolymer of n-butylmethacrylate and a vinyl monomer of synthetic MMPI (N-Hydroxy-5-carboxyethylcarbonyloxy-2(S)-methy-4(S)-(4-phenoxybenzoyl)amino-pentanamide: ONO-M11-335) with a molecular weight of about 32,000 and MMPI content of 45 per molecule. The precursor of the MMPI monomer produced significant activity in temporally inhibiting SMC proliferation without any cellular damage. After coating with the PMMPI, adhesion and proliferation of SMCs were manifestly prevented even when a small amount of MMPI was released from the polymer. The MMPI-immobilized surface may thus be effective for inhibiting both adhesion and proliferation of SMCs, which is the first step toward in vivo experimentation. It is very much expected that coating stent struts with PMMPI containing an appropriate combination of impregnated drugs will provide a powerful tool for prevention of restenosis with little cytotoxicity.     

血管内生物可吸收支架现状与挑战

尽管目前介入用血管支架各类药物涂层技术较从前已经获得长足的进步,涂层支架的临床使用数量也远远超过裸支架,但远期疗效仍有待继续验证。无论何种药物涂层支架,当其被植入生物体内一段时间后,表面携带的功能药物涂层都会被生物体逐渐吸收而最终露出裸支架,带来晚期再狭窄及血栓的问题。因此,生物可吸收支架应运而生。由于其具有独特的可降解性,随着植入时间的延长而逐渐在生物体内被完全降解、吸收,最终代谢出体外;同时,血管自有的部分原始功能也得到一定恢复,如同从未被植入过支架一般。重点介绍国内外高分子聚合物、镁合金、纯铁、锌合金等几种不同材质的生物可吸收血管支架研究现状,并分析各材质可吸收支架现存的主要问题,希望对血管介入用生物可吸收支架的了解起到一定的作用。     

Stents: Biomechanics,Biomaterials, and Insights from Computational Modeling

Coronary stents have revolutionized the treatment of coronary artery disease. Improvement in clinical outcomes requires detailed evaluation of the performance of stent biomechanics and the effectiveness as well as safety of biomaterials aiming at optimization of endovascular devices. Stents need to harmonize the hemodynamic environment and promote beneficial vessel healing processes with decreased thrombogenicity. Stent design variables and expansion properties are critical for vessel scaffolding. Drug-elution from stents, can help inhibit in-stent restenosis, but adds further complexity as drug release kinetics and coating formulations can dominate tissue responses. Biodegradable and bioabsorbable stents go one step further providing complete absorption over time governed by corrosion and erosion mechanisms. The advances in computing power and computational methods have enabled the application of numerical simulations and the in silico evaluation of the performance of stent devices made up of complex alloys and bioerodible materials in a range of dimensions and designs and with the capacity to retain and elute bioactive agents. This review presents the current knowledge on stent biomechanics, stent fatigue as well as drug release and mechanisms governing biodegradability focusing on the insights from computational modeling approaches.     

Drug loading and elution from a phosphorylcholine polymer-coated coronary stent does not affect long-term stability of the coating in vivo

A drug eluting coronary stent was developed for use in preclinical and clinical trial evaluation. The stent was coated with a phosphorylcholine (PC)-based polymer coating containing the cell migration inhibitor batimastat. A pharmacokinetic study was conducted in a rabbit iliac model using (14)C-radiolabeled version of the drug; this showed the drug release to be first order with 94% of it being released within 28 days. Unloaded and drug-loaded stents were implanted in a porcine coronary artery model; a number were explanted at 5 days and scanning electron microscopy was used to show that the presence of the drug did not affect the rate of stent endothelialization. The remainder of the stents were removed after 6 months and the stents carefully removed from the arterial tissue. Fourier-transform infrared (FT-IR) spectroscopy (both attenuated total reflectance and microscopic imaging) was used to show the presence of the PC coating on control unloaded, drug-loaded and explanted stents, providing evidence that the coating was still present. This was further confirmed by use of atomic force microscopy (AFM) amplitude-phase, distance (a-p,d) curves which generated the characteristic traces of the PC coating. Further AFM depth-profiling techniques found that the thicknesses of the PC coatings on an control unloaded stent was 252+/-19 nm, on an control batimastat-loaded stent 906+/-224 nm and on an explanted stent 405+/-224 nm. The increase in thickness after the drug-loading process was a consequence of drug incorporation in the film, and the return to the unloaded dimensions for the explanted sample indicative of elution of the drug from the coating. The drug delivery PC coating was therefore found to be stable following elution of the drug and after 6 months implantation in vivo.     

Drug-eluting stents for coronary artery disease: a review

Over the past decade the introduction of drug-eluting stents (DESs) has revolutionised the treatment of coronary artery disease. However, in recent years concern has arisen over the long-term safety and efficacy of DESs due to the occurrence of late adverse clinical events such as stent thrombosis. With this concern in mind, research and development is currently centred on increasing the long-term safety and efficacy of DESs. The aim of this paper is to provide a thorough review of currently approved and promising investigational DESs. With dozens of companies involved in the development of new and innovative anti-restenotic agents, polymeric coatings and stent platforms, it is intended that this review paper will provide a clear indication of how DESs are currently evolving and prove a valuable reference tool for future research in this area.     

Coronary restenotic reduction of drug-eluting stenting may be due to its anti-inflammatory effects

The development of coronary stent has revolutionized the field of interventional cardiology by reducing the incidence of restenosis after balloon angioplasty. However, the stent has still associated with a serious complication, namely, in-stent restenosis. Although, restenosis following coronary stenting has long been attributed to neointimal proliferation, thrombosis, and negative remodeling, the inflammation may be a trigger for those vascular reactions following coronary stenting. Both experimental and clinical studies have demonstrated a marked activation of local and systemic inflammatory response following stent implantation, suggesting that inflammation may play an important role in determining in-stent restenosis via neointimal proliferation. The key role of inflammation in vascular healing and in-stent retsenosis has also been increasingly well understood. Recently, drug-eluting stents (DESs) have been shown to decrease in-stent restenosis in a large number of clinical studies. In addition to their anti-proliferative activity, DESs have been considered to possess an anti-inflammatory property, especially for sirolimus-eluting stent compared with bare metal stent. Moreover, the benefit of the anti-inflammatory therapy during the peri-procedural period and long-term follow-up by means of drug administration is also dependent on the inflammatory status during percutaneous coronary intervention. Measurement of cytokine and acute phase proteins, such as C-reactive protein, therefore, may be important to identify high-risk subjects and develop specific treatment tailored to the individual patients with stent restenosis. Thus, therapeutic approach should be further directed toward increasing local resistance to proliferative inflammatory stimuli by means of anti-proliferative, locally delivered drugs and reducing the magnitude and persistence of systemic inflammation.     

Survival of endothelial cells in vitro on Paclitaxel-loaded coronary stents

Coronary stents that are developed for use with balloon angioplasty are known to cause acute occlusion and long-term stenosis. It is likely that a controlled release of drugs at the site of stent implantation might inhibit the proliferation of vascular smooth muscle cells (VSMC) and reduce restenosis. However, if the drug is necrotic and affects cell survival near the implant, it may interrupt the local tissue regeneration. Different methods have been used for the immobilization of drugs with stents to get an effective concentration that inhibits cell proliferation. The objective of this study is to assess the effectiveness of Paclitaxel-loaded stents by immobilization with a biodegradable polymer, to inhibit cell proliferation. The cells used for the evaluation are human umbilical vein endothelial cells (HUVEC) and the proliferation rate of these cells on the drug-coated stent is compared against an uncoated stent for a 72-h period. Evaluations were also made to differentiate between cell apoptosis and necrosis to prove that the drug released is not deleterious to the surrounding tissue.While a similar initial cell adhesion is observed in bare and coated stents, the proliferation of HUVEC is negligible when grown on a drug-coated stent (p < 0.001). By specific staining techniques, the cells on the drug-coated stents are found to be apoptotic and not necrotic, throughout the evaluation period. In vitro leukocyte adhesion and platelet deposition on the drug-coated stents are found to be low when they are exposed to human blood and platelet-rich plasma (PRP), suggesting that the coated stents may not be thrombogenic in vivo. Therefore, drug coating of stents using the described technique may have a considerable promise for the prevention of neointimal proliferation, restenosis, and associated failure of angioplasty.     

Endoluminal hydrogel films made of alginate and polyethylene glycol: physical characteristics and drug-eluting properties

Drug-eluting stents signify a major achievement in reducing the incidence of coronary restenosis after percutaneous transluminal coronary angioplasty. However, where drug-eluting stents have been unsuccessful, endoluminal gel-paving strategies offer renewed optimism, mainly in a variety of vascular procedures requiring catheter-based sustained, localized delivery of therapeutic drugs, and biological factors. Despite promising results in animals, endoluminal paving has met with very limited clinical success because of the technical difficulties and stringent safety demands. The current study presents an alternative to gel paving using 40-mum-thick biodegradable polymeric films for deployment onto the artery wall during balloon angioplasty and stenting. The films are made from a durable yet compliant network of alginate and polyethylene glycol (PEG), and are securely held affixed to the vessel wall by the expanded stent struts. The alginate-based films are characterized by measuring their strength, elasticity, degree of swelling, degradability in water and saline, and drug release properties. The combination of alginate and PEG afforded the films sufficient strength and compliance for endoluminal deployment using an in vitro organ culture system. In characterizing the film degradability, it was discovered that the ionic concentration of the buffered saline was the main determinant in regulating the degradation kinetics and the release kinetics of the drug molecule Paclitaxel. These results suggest that the use of alginate-based, PEG-containing polymeric films for endoluminal coverage offers an alternative solution to conventional drug-eluting stents, with the added advantage of uniform endoluminal coverage of the treated segment and homogeneous endoluminal application of the active substance.     

冠状动脉药物涂层支架与置入后的血管再狭窄

背景：近年来随着药物涂层支架研究的增多及临床应用不断扩大,使冠状动脉内支架置入后再狭窄率显著降低,且在预防再狭窄中较裸支架具有独特应用价值。 目的：阐述药物涂层支架的临床应用进展,并探讨支架的涂层材料、类型与置入后再狭窄的关系及与宿主的相容性。 方法：作者以“冠脉支架,金属支架,药物涂层支架,再狭窄”为检索词,在中国期刊全文数据库及Medline 数据库中,采用电子检索的方式进行文献检索。排除Meta分析及重复性研究,共检索到27篇文献。 结果与结论：药物涂层支架的确是介入心脏病学的一项重要突破,使介入心脏病学进入了一个新的时代,但其远期效果仍需进一步观察。各种药物涂层支架所含药物或含量不同,其作用机制不同,而且药物释放的速率也不同,所以药物涂层支架临床应用后的效用和安全性需要由严谨和大量的临床研究来证实。现今药物支架的载体材料经过长时间的人体腐蚀,材料本身会老化、脱落,在血管组织内形成小块,从而可能引起晚期的不良反应。如果采用生物可降解的材料作为药物载体材料,那么就有可能减少晚期不良反应的出现。因此,开发一种理想的支架系统,目前主要的研究方向是可降解的低致炎性聚合物材料以及高效的药物控释体系。     

Development of high-performance stent: gelatinous photogel-coated stent that permits drug delivery and gene transfer

Hydrogel-coated metallic stents may provide supplementary functions such as local drug delivery and gene transfer in addition to mechanical dilation function. To this end, we used a photoreactive material consisting of gelatin macromer (multiple styrene-derivatized gelatin) and carboxylated camphorquinone (photo-initiator). A few minutes of visible light irradiation of a stent after dip-coating of an aqueous solution of the photoreactive material resulted in the formation of a homogeneously crosslinked gelatinous layer on the entire exterior surface of the stent. As the metal stent, gold stents under development were used. Rhodamine-conjugated albumin as a model drug or adenoviral vector expressing bacterial beta-galactosidase (AdLacZ) as a model gene were photo-immobilized in the gelatinous gel layer. In vitro experiments using hybrid tubular tissue, which is a self-shrinkaged, vascular smooth muscle cell-incorporated type-I collagen gel, as a vascular model, showed that the immobilized dye-derivatized albumin was released on and permeated into tissues, as observed by confocal laser microscopy, and that the cells transfected with immobilized AdLacZ produced beta-galactosidase up to almost 3 weeks, as observed by x-gal staining. In preliminary in vivo experiments these drug- or adenovirus-immobilized stents were implanted in rabbit common carotid arteries. Within 3 weeks of implantation, drug permeation and gene expression in the vascular tissues were observed, indicating that the gelatinous photogel effectively serves as a matrix or coating for a bioactive stent,which permits drug release as well as gene transfer. This intraluminal approach has the potential to realize drug and gene therapy in atherosclerotic plaque.