New biocompatible polymer surface coating for stents results in a low neointimal response.

Clinical studies indicate a more pronounced endothelial response after stent implantation than after balloon inflation. This might be related to the metal surface of the stent, and therefore it is speculated that coating of the stent might partially prevent hyperplasia. One coated and one noncoated Palmaz-Schatz stent were implanted in two separate coronary arteries of seven pigs. The coating was composed of methylmethacrylate (MMA) (hydrophobic, 70 mol %) and 2-hydroxyethyl methacrylate (HEMA) (hydrophilic 30 mol %). After sacrifice (3 weeks), cross sections were made of the stented areas. Vessel wall reaction was calculated both independently and dependently of local vessel wall injury due to the stent struts. Overall, vessel wall reaction of the coated stents was lower than that of the noncoated stents. The degree of hyperplasia was linearly related to the degree of stent-induced vessel wall injury. Analyses of all the struts showed that significantly less hyperplasia occurred in the coated versus noncoated stents. In this porcine coronary artery model, the MMA/HEMA stent coating resulted in significantly reduced vessel wall response. However, it remains to be determined whether this favorable outcome will also be present in humans.

Metallic wires with an adherent lubricious and blood-compatible polymeric coating and their use in the manufacture of novel slippery-when-wet guidewires: possible applications related to controlled local drug delivery.

A new procedure was developed for the controlled application of adherent hydrophilic and biocompatible coatings onto the surface of "endless" metallic wires. Use of copolymers of 1-vinyl-2-pyrrolidinone and alkylmethacrylates provided coatings with excellent adherence and lubricity, and markedly low thrombogenicity. Coated wires could be spiralized without damaging the coating; the resulting coils are potentially useful as lubricious guidewires for use in, for example, interventional cardiology or urology. This study demonstrates that the lubricity of the coating is dependent on the composition (hydrophilicity) of the coating biomaterial, as well as on the thickness of the coating. Furthermore, the results imply that the adherence of the hydrophilic coating is essentially due to entanglement of the binder polymer chains and the hydrophilic copolymer chains. Moreover, the idea to use the hydrophilic coating on the wire as a temporary depot for controlled local drug delivery was explored. The coating was loaded with the dye rhodamine, and release of the dye upon immersion of the coated wire in water was studied. This work revealed that release of the drug is dependent on the composition of the coating. The potential utility of such wires with a drug-charged coating for controlled local drug delivery is discussed briefly.

A versatile three-iodine molecular building block leading to new radiopaque polymeric biomaterials.

A methacrylic monomer containing three iodine atoms, 2- [2',3',5'-triiodobenzoyl]-ethyl methacrylate (compound 1), was prepared in pure form. Compound 1 can be reacted with other methacrylates, such as methyl methacrylate (MMA), and 2-hydroxyethyl methacrylate (HEMA) with high conversion. Typically, less than 0.5% of free monomer is left after polymerization. For example, compound 1 was reacted with MMA and HEMA in the molar ratio 7:73:20, respectively. This yielded a terpolymer with Tg = 86 degrees C, Mw = 47,000 g/ mol and Mn = 22,800 g/mol. This material was characterized by various physicochemical techniques, including gel permeation chromatography, differential scanning calorimetry, thermogravimetric analysis, and nuclear magnetic resonance (NMR) spectroscopy (1H at 400 MHz, DMSO-d6 solution). In addition the material was found to exhibit low surface thrombogenicity in vitro and a low propensity to activate contacting blood platelets. Furthermore it was found that the terpolymer is markedly radiopaque: even thin objects (< 0.5 mm) could be easily visualized using X-ray fluoroscopic techniques as are routinely used in the clinic, e.g., during coronary angiography. The combined results obtained with the present terpolymer (particularly its in vitro hemocompatibility and its radiopacity) leads to the suggestion that this type of polymer could be used as cardiovascular biomaterials, for instance for the construction of a new type of endovascular stents. These would be expected to show improved biocompatibility if compared with metallic stents which are currently used, for instance in conjunction with percutaneous transluminal coronary angioplasty (PTCA). A stent prototype, constructed from the present radiopaque terpolymer, is shown and discussed briefly.

Studies on radio-opaque polymeric biomaterials with potential applications to endovascular prostheses.

A new polymeric biomaterial, which uniquely combines radio-opacity (X-ray visibility) and low thrombogenicity, is described. First, preparation, purification, and identification of the essential monomeric building block, 2-[2'-iodobenzoyl]-ethyl methacrylate (3), are outlined. Second, [Figure: See text] the synthesis of the biomaterial, a terpolymer with composition MMA: HEMA: 3 = 65:15:20 (mole/mole/mole) is described. Third, the physico-chemical characteristics of the polymer (e.g. NMR spectroscopy, thermal behaviour) are given. Fourth, the in vitro thrombogenicity of the material was characterized by means of recent test assay. The combined results reveal that the terpolymer is very suitable for prosthetic applications in the cardiovascular system. A new prototype of an endovascular stent, made from the terpolymer, is presented. Stents find clinical use in interventional cardiology, in conjunction with percutaneous transluminal coronary angioplasty (PTCA). It is put forward that the stent prototype presented herein has, at least in principle, some advantages over existing (metallic) stents; these advantages are primarily owing to the unique combination of X-ray visibility and haemocompatibility which is presently achieved.

Studies on two new radiopaque polymeric biomaterials.

Two new polymeric materials (polymers A and B) containing covalently bound iodine were prepared. These polymers were evaluated with respect to their possible use as radiopaque implant biomaterials--that is, materials that are visible in a noninvasive manner using routine X-ray absorption imaging techniques. Polymer A is a copolymer of methyl methacrylate (MMA) and 1 (80 and 20 mol%, respectively). Polymer B was prepared from MMA, 1, and 2-hydroxyethyl methacrylate (HEMA) (mol ratio 65:20:15, respectively). Compound 1 was synthesized from 4-iodophenol and methacryloyl chloride. The resulting polymers were characterized with GPC, DSC, NMR, and by measuring both the advancing and receding contact angles. Thrombogenicity of the polymers was determined by an in vitro thrombin generation test procedure. The maximum concentration of free thrombin was 76 +/- 1 nM for polymer A, and 64 +/- 3 nM for polymer B. The lag times (i.e., time onset of thrombin generation) were 392 seconds for polymer A and 553 seconds for polymer B. For PVC-T, which is known as a passive material, a lag time of 583 seconds was found. This indicates that polymer B is comparable to PVC-T, and more passive than polymer A. Polymer A exhibited minor activation of platelets. Polymer B did not induce platelet activation at all. The polymers exhibited, even as fibers with a diameter of ca. 0.3 mm, good radiopacity with routine imaging X-ray techniques in the clinic.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on a new radiopaque polymeric biomaterial.

A new radiopaque polymeric biomaterial has been synthesized. The material, which actually represents an entire family of analogous radiopaque materials, is composed of 2-(p-iodobenzoyl)-ethyl methacrylate (compound 1, 21 mol%), methyl methacrylate (MMA, 60 mol%), and 2-hydroxyethyl methacrylate (HEMA, 19 mol%). The terpolymer was synthesized in a radical polymerization reaction at elevated temperature in N,N-dimethylformamide (DMF). The product was subjected to a set of physicochemical characterization techniques (gel permeation chromatography, 500 MHz 1H NMR in deuterated dimethylsulphoxide (d6-DMSO) solution, differential scanning calorimetry, dynamic water contact angle measurements), as well as to an in vitro thrombogenicity assay. Furthermore, scanning electron microscopy was used to study interactions of the material with blood platelets. The most important findings are: (a) the material is a genuine polymer with excellent X-ray visibility, even in the form of thin (0.4 mm) drawn fibres. This was established under realistic conditions. (b) The material exhibits low in vitro thrombogenicity, i.e. comparable to polyvinyl chloride, which is known as a passive material. These observations lead us to the suggestion that this type of radiopaque polymer holds promise with respect to application as a construction material for a new type of endovascular stent. This could be relevant in particular to stents to be used in conjunction with percutaneous transluminal coronary angioplasty (PTCA), also known as Dottering. Currently there is a clear trend away from metallic stents towards all-polymeric stents, since the latter have superior biocompatibility.(ABSTRACT TRUNCATED AT 250 WORDS)