Copolymer Formulations Research Articles

Safety and biocompatibility of injectable vaccine adjuvants composed of thermogelling block copolymer gels

Injectable thermogelling polymers have been recently investigated as novel adjuvants and delivery systems for next generation vaccines. As research into natural and synthetic biocompatible polymers progresses, the safety and biocompatibility of these compounds is of paramount importance. We have developed cationic pentablock copolymer (PBC) vaccine adjuvants based on Pluronic F127, a thermogelling triblock copolymer that has been approved by the FDA for multiple applications, and methacrylated poly(diethyl amino)ethyl methacrylate outer blocks. These novel materials have been demonstrated to effectively create an antigen depot, minimally impact antigen stability, and enhance the immune response to antigens (i.e., adjuvanticity) in mice. In this work, we investigated the safety and biocompatibility of the parent triblock Pluronic gels and the cationic PBC gels in mice. Histological analysis showed no injection site reactions and no damage to the liver or kidneys was observed upon administering the block copolymer formulations. However, the subcutaneous injection of a thermogelling Pluronic solution induced increased levels of lipids in the blood, with no further deleterious effects observed from the addition of the cationic outer blocks. This hyperlipidemia resolved within 30 days after the administration of the Pluronic formulation. To mitigate this adverse effect, the vaccine adjuvant formulations were modified by adding poly(vinyl alcohol), which allowed gelation, while reducing the amount of Pluronic in the formulation. This modified formulation abrogated the observed hyperlipidemia and no adverse effects were observed in the serum through biomarker analysis or at the injection site (i.e., inflammation) in comparison to the responses induced by administration of saline or incomplete Freund's adjuvant. These studies provide a foundation to developing these gels as adjuvants for next generation vaccines. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1754-1762, 2019.

Influence of Homopolymer Addition in Templated Assembly of Cylindrical Block Copolymers.

Templated assembly of cylindrical block copolymers provides a promising strategy for patterning holes at the nanoscale. However, remaining challenges include the ability to achieve defect-free patterns and to generate architectures useful for device patterning. The aim of this work is to gain insight into the influence of homopolymer addition on the assembly of a cylindrical block copolymer in confined space. To do so, a concerted examination that relies on experiments and simulations is carried out for different block copolymer/homopolymer blends. It is shown that by adding a majority block homopolymer with low molecular weight (compared to the blocks that make up the block copolymer), the pattern quality is significantly improved and a larger defect-free window is obtained in terms of template dimensions for two-hole features in elliptical confinements. The redistribution of the homopolymer chains effectively enables the assembly of two cylinders, despite the geometrical mismatch between the elliptical shape of the confinement and the natural hexagonal ordering of the unguided block copolymer. Monte Carlo simulations show that the homopolymer segregates to the spaces in the template that are entropically unfavorable for the block copolymer. This work serves to highlight the importance of optimizing block copolymer formulation.

Effect of hardening parameters of wood preservatives based on tannin copolymers

AbstractAmongst polyphenols, tannins belong to the most effective chemical protection systems against biological attack on trees. Tannins are water-soluble and are thus leached out easily when used for wood protection.In situpolymerized tannin-hexamine wood preservatives have better leaching resistance (LR), but they do not resist weathering. In this study, tannin copolymer formulations were prepared with hexamine, formaldehyde, furfural, glyoxal, furfuryl alcohol and maleic anhydride, impregnated in wood, and cured at higher temperatures. The wood samples treated with these formulations were tested for their anti-swelling efficiency (ASE), leaching behavior, mechanical properties, and their resistance against fire, weathering and biological attack. Several tannin-treated specimens showed improved hardness and enhanced leaching and fire resistance. Some formulations also responded well to artificial weathering cycles, but natural weathering cycles deteriorated their performance. Samples treated with maleic anhydride showed improved leachability and high biological resistances, even without the addition of inorganic biocides. These organic and bio-friendly products can be considered as promising alternatives to heavy metal-based wood preservatives.

Evaluation of activity and potential for development of antimicrobial resistance to a new tinted 2% chlorhexidine gluconate/70% isopropyl alcohol film-forming sterile preoperative skin preparation

Chlorhexidine gluconate (CHG) is routinely used for skin antisepsis before surgery. Its activity may be affected by formulation ingredients and the presence of organic matter such as blood and proteins. This in vitro study was designed to evaluate the antimicrobial activity of a new CHG skin prep containing a film-forming copolymer, and detect its potential for developing resistance and the potential for cross-resistance to antibiotics after CHG exposure. Antimicrobial activity was evaluated in the presence and absence of serum in an in vitro time-kill study. Emergence of resistance to CHG and cross-resistance with antibiotic procedures were performed in vitro using 10 repository isolates from eight species and eight clinical isolate strains equal to the repository isolate strains (four isolates, two resistant and two non-resistant per species). A 5 log10 reduction (99.999%) for all organisms was observed using the copolymer formulation. The activity remained unchanged in the presence of serum. The minimum inhibitory concentration (MIC) did not increase for any of the strains evaluated for emergence of resistance. In addition, there was no change in MIC related to cross-resistance observed for any of the organism/antibiotic combinations tested. These results suggest that the film-forming copolymer and the tint in the new CHG skin prep did not interfere with antimicrobial efficacy, even in the presence of an organic soil load, and that the tested formulations showed no potential for developing resistance or cross-resistance with antibiotics.

Correction: Statistical degradation modelling of Poly(D,L-lactide-co-glycolide) copolymers for bioscaffold applications.

[This corrects the article DOI: 10.1371/journal.pone.0204004.].

Statistical degradation modelling of Poly(D,L-lactide-co-glycolide) copolymers for bioscaffold applications.

This methodology permits to simulate the performance of different Poly(D,L-lactide-co-glycolide) copolymer formulations (PDLGA) in the human body, to identify the more influencing variables on hydrolytic degradation and, thus, to estimate biopolymer degradation level. The PDLGA characteristic degradation trends, caused by hydrolysis processes, have been studied to define their future biomedical applications as dental scaffolds. For this purpose, the mass loss, pH, glass transition temperature (Tg) and absorbed water mass of the different biopolymers have been obtained from samples into a phosphate-buffered saline solution (PBS) with initial pH of 7.4, at 37°C (human body conditions). The mass loss has been defined as the variable that characterize the biopolymer degradation level. Its dependence relationship with respect to time, pH and biopolymer formulation has been modelled using statistical learning tools. Namely, generalized additive models (GAM) and nonlinear mixed-effects regression with logistic and asymptotic functions have been applied. GAM model provides information about the relevant variables and the parametric functions that relate mass loss, pH and time. Mixed effects are introduced to model and estimate the degradation properties, and to compare the PDLGA biopolymer populations. The degradation path for each polymer formulation has been estimated and compared with respect to the others for helping to use the proper polymer for each specific medical application, performing selection criteria. It was found that the mass loss differences in PDLGA copolymers are strongly related with the way the pH decay versus time, due to carboxylic acid groups formation. This may occur in those environments in which the degradation products remain relatively confined with the non degraded mass. This is the case emulated with the present experimental procedure. The results show that PDLGA polymers degradation degree, in terms of half life and degradation rate, is increasing when acid termination is included, when DL-lactide molar ratio is reduced, decreasing the midpoint viscosity, or when glycolide is not included.

Correlations between thermal and tensile behavior with friction coefficient in copolyamides 6/12

Although polyamide 6 (PA6) obtained from ε-caprolactame (CL) is an engineering polymer with outstanding properties used in sliding applications, it exhibits low impact strength and high water absorption. Those are some of the reasons why copolymerization between CL and laurolactame (LL) is desired. In this work, copolymers from 0–100wt% LL are prepared to evaluate crystallinity, melting behavior, tensile properties and those properties are correlated with coefficient of friction. Experimental results show that PA6 (0wt%) crystallinity and elasticity modulus are higher than those obtained from 100wt%LL (PA12), but friction coefficient in PA6 is lower than that of PA12. While with 60wt% LL crystallinity and elastic modulus reach a minimum value, with 350% elongation and coefficient of friction they register a maximum value. Our results suggest that crystallinity and elastic modulus are opposed to coefficient of friction. The absence of hydrogen bonds produces irregularities in the chain, reducing the crystal formation; such behavior is a consequence of copolymerization. Our findings will help to customize copolyamide, modulate the response between mechanical properties and friction behavior, as well as evaluate when it is necessary to add lubricants in the copolymer formulations.

Towards an antimicrobial 'microglove'.

A large proportion of hospital-related infections are acquired and spread due to the direct contacts between patients and healthcare workers. Accordingly, proper infection prevention measures, and especially hand hygiene, are key to limit the spread of infections in nosocomial settings. However, healthcare workers frequently experience difficulties in complying strictly to hand disinfection protocols. This study was therefore aimed at the development of a hand rub with antimicrobial activity that forms a protective film on the hand, a so-called microglove, in order to enhance hand hygiene. For this purpose, various co-polymer formulations consisting of different ratios of Polyvinylpyrrolidone (PVP) and a branched C20 derivatized maleate (M20) in combination with the known biocide benzalkonium chloride (BKC) were tested for their combined film-forming and antimicrobial activities. The results of a series of novel contamination and transmission assays show that a formulation of 80% PVP and 20% M20 co-polymer with 0.9% BKC fulfils the elementary requirements for an antimicrobial microglove.

New Polyacrylamide [PAM] Material Formulations for the Coagulation/Flocculation/Decantation Process

A new copolymers, high molecular weight poly(acrylamide) [AM2A0.01W20] and [AM1A0.1W20] were synthesized by radical adiabatic copolymerization in aqueous solution. The [AM2A0.01W20] copolymer was hydrolysed in basic medium by using sodium hydroxide solution and leads to a new hydrolysed poly(acrylamide) [AM3A0.01W20-H]. The structure and composition of the copolymers were established by 1H NMR, IRTF and conductivity. The molecular weights are obtained by size exclusion chromatography [SEC] and by viscosity. The variation of the reduced viscosity of aqueous copolymer solutions with copolymer concentration revealed a strong viscosity values showing very high [PAM] molecular weights. In the present work, several copolymer formulations are tested by the process of Coagulation/Flocculation/Decantation with a Jar-test, using a 30 mg L−1 clay suspension. The optimization process shows that the copolymers present different flocculation efficiencies. The copolymers with the best performances were tested on a semi-industrial experimental pilot for the Coagulation/Flocculation/Decantation process. Good Flocculation yield superior than 70 % are observed for the [AM3A0.01W20-H] with high molecular weight.

Combination of montmorillonite and a Schiff-base polyphosphate ester to improve the flame retardancy of ethylene-vinyl acetate copolymer

Abstract Different flame retardant ethylene-vinyl acetate copolymer (EVA) formulations were prepared to evaluate the synergistic effect between organo-montmorillonite (OMMT) and a Schiff-base polyphosphate ester (PAB) on the combustion behavior of EVA. X-ray diffraction (XRD) and transmission electron microscopy (TEM) results revealed that montmorillonite platelets selectively dispersed in the PAB phase. EVA/PAB/OMMT(80/15/5) had better thermal stability and flame retardancy than EVA/PAB(80/20), as indicated by the results of thermogravimetric analysis (TGA), limited oxygen index (LOI), vertical burning test (UL-94) and microscale combustion colorimeter (MCC), showing a synergism between OMMT and PAB. For example, the onset decomposition temperature (T 5%) increased from 233°C to 296°C, the char residue at 600°C increased from 6.6% to 11.0%, and the peak heat release rate (PHRR) decreased from 718.1 W/g to 706.6 W/g. This is caused by the silicoaluminophosphate (SAPO) structure formed by reactions between the phosphoric acid generated from PAB and OMMT.

Improved Mechanical Properties of Chemically Amplified, Positive Tone, Polynorbornene Dielectric

The mechanical properties of an aqueous developed, chemically amplified, polynorbornene-based permanent dielectric have been investigated. The previously reported hexafluoroisopropanol norbornene and tert-butyl ester norbornene copolymer has been modified via two routes to improve the mechanical properties of the polymer and enable thick-film deposition. First, a third monomer, butyl norbornene (ButylNB) was added to the polymer backbone. The inclusion of 24 mol% ButylNB lowered the elastic modulus from 2.64 to 2.35 GPa and raised the dielectric constant from 2.78 to 3.48. The second approach added a low molecular weight, plasticizing additive in the copolymer formulation. Many additives were immiscible with the resin or did not affect the mechanical properties. Trimethyololpropane ethoxylate (TMPEO) was found to be a miscible additive that improved mechanical properties and could participate in crosslinking the final dielectric material. TMPEO interacted with the PAG, lowering its decomposition temperature. An optimal formulation and processing scheme were determined. A formulation with 10 pphr TMPEO was measured to have a dielectric constant of 2.94, an elastic modulus of 1.95 GPa, a sensitivity at 365 nm of 175 mJ/cm2, and a contrast of 4.36.

Characterization of the influence of specimen thickness on the aging behavior of a polypropylene based model compound

Specimens with varying thickness of different polypropylene random copolymer formulations were oven aged in hot air at 135 °C. Besides macro-sized specimens die-punched from 2 mm thick extruded sheets, 50 μm, 200 μm and 500 μm thick micro-sized specimens, cut edgewise from the sheets by an automated planing procedure, were investigated. The formulations included a base stabilized reference compound and four formulations prepared with systematically varied additional contents of the primary antioxidants Naugard 445 and Irganox 1010 and the secondary antioxidants Irganox PS-800 and Irganox PS-802. Aging characterization was performed by tensile testing, differential scanning calorimetry and high performance liquid chromatography employing strain-at-break, oxidation onset temperature (OOT) and the content in phenolic antioxidants as aging indicators, respectively.Aging characterization revealed a systematic thickness dependence of the embrittlement time and the rate of the reduction in OOT as well as the reduction of phenolic antioxidants. The 50 μm thick specimens exhibited embrittlement times between 50% and 65% of the 2 mm thick macro-sized specimens. For low thicknesses, a high surface to volume ratio is presumably responsible for the fast physical loss of antioxidants, while for thick specimens, physical stabilizer loss is limited by the rate of stabilizer diffusion from the bulk to the surface. Hence, thicker specimens showed longer embrittlement times. Regarding stabilizer loss, Naugard 445 and Irganox PS-800 exhibited significantly higher loss rates than Irganox 1010 and Irganox PS-802.

Novel polymeric nanoparticles for intracellular delivery of peptide Cargos: antitumor efficacy of the BCL-2 conversion peptide NuBCP-9.

The preclinical development of peptidyl drugs for cancer treatment is hampered by their poor pharmacologic properties and cell penetrative capabilities in vivo. In this study, we report a nanoparticle-based formulation that overcomes these limitations, illustrating their utility in studies of the anticancer peptide NuBCP-9, which converts BCL-2 from a cell protector to a cell killer. NuBCP-9 was encapsulated in polymeric nanoparticles composed of a polyethylene glycol (PEG)-modified polylactic acid (PLA) diblock copolymer (NuBCP-9/PLA-PEG) or PEG-polypropylene glycol-PEG-modified PLA-tetrablock copolymer (NuBCP-9/PLA-PEG-PPG-PEG). We found that peptide encapsulation was enhanced by increasing the PEG chain length in the block copolymers. NuBCP-9 release from the nanoparticles was controlled by both PEG chain length and the PLA molecular weight, permitting time-release over sustained periods. Treatment of human cancer cells with these nanoparticles in vitro triggered apoptosis by NuBCP-9-mediated mechanism, with a potency similar to NuBCP-9 linked to a cell-penetrating poly-Arg peptide. Strikingly, in vivo administration of NuBCP-9/nanoparticles triggered complete regressions in the Ehrlich syngeneic mouse model of solid tumor. Our results illustrate an effective method for sustained delivery of anticancer peptides, highlighting the superior qualities of the novel PLA-PEG-PPG-PEG tetrablock copolymer formulation as a tool to target intracellular proteins.

Nano-Encapsulation of Plitidepsin: In Vivo Pharmacokinetics, Biodistribution, and Efficacy in a Renal Xenograft Tumor Model

Plitidepsin is an antineoplasic currently in clinical evaluation in a phase III trial in multiple myeloma (ADMYRE). Presently, the hydrophobic drug plitidepsin is formulated using Cremophor®, an adjuvant associated with unwanted hypersensitivity reactions. In search of alternatives, we developed and tested two nanoparticle-based formulations of plitidepsin, aiming to modify/improve drug biodistribution and efficacy. Using nanoprecipitation, plitidepsin was loaded in polymer nanoparticles made of amphiphilic block copolymers (i.e. PEG-b-PBLG or PTMC-b-PGA). The pharmacokinetics, biodistribution and therapeutic efficacy was assessed using a xenograft renal cancer mouse model (MRI-H-121 xenograft) upon administration of the different plitidepsin formulations at maximum tolerated multiple doses (0.20 and 0.25mg/kg for Cremophor® and copolymer formulations, respectively). High plitidepsin loading efficiencies were obtained for both copolymer formulations. Considering pharmacokinetics, PEG-b-PBLG formulation showed lower plasma clearance, associated with higher AUC and Cmax than Cremophor® or PTMC-b-PGA formulations. Additionally, the PEG-b-PBLG formulation presented lower liver and kidney accumulation compared with the other two formulations, associated with an equivalent tumor distribution. Regarding the anticancer activity, all formulations elicited similar efficacy profiles, as compared to the Cremophor® formulation, successfully reducing tumor growth rate. Although the nanoparticle formulations present equivalent anticancer activity, compared to the Cremophor® formulation, they show improved biodistribution profiles, presenting novel tools for future plitidepsin-based therapies.

TCT-212 Efficacy of the Novel BioMime Sirolimus-Eluting Stents with a Biodegradable Polymer in the Treatment of De Novo Coronary Lesions: An Angiographic Subanalysis of the Combined meriT-1 and meriT-2 Prospective Clinical Trials

The novel BioMime drug-eluting stent (Meril Life Sciences Pvt. Ltd., Gujarat, India) incorporates a L605 cobalt-chromium metallic platform that combines ultra-thin struts (65μm) with hybrid cell design and a bioabsorbable co-polymer (PLLA/PLGA) formulation (2μm thickness) which carries and

PEO-b-PCL–DPPC chimeric nanocarriers: self-assembly aspects in aqueous and biological media and drug incorporation

In this work, we report on the self assembly behavior and stability studies of mixed amphiphilic nanosystems consisting of DPPC (dipalmitoylphosphatidylcholine) and poly(ethylene oxide)-b-poly(e-caprolactone) (PEO-b-PCL) block copolymer in HPLC-grade water, phosphate buffer saline (PBS) and fetal bovine serum (FBS). These nanosystems are sterically stabilized nanovectors and can be utilized as chimeric advanced Drug Delivery nano Systems (aDDnSs) with stealth properties. A gamut of light scattering techniques (static, dynamic and electrophoretic) and fluorescence spectroscopy were used in order to extract information on the structure, morphology, size, effective charge and internal nanostructure of the nanoassemblies formed, as a function of block copolymer content, as well as temperature and concentration. The incorporation of PEO-b-PCL leads to nanoassemblies of smaller size. All the mixed formulations were found to retain their original physicochemical characteristics for the course of two weeks. The hydrodynamic radii (Rh) of mixed nanosystems decreased in the process of heating up to 50 °C. Gradual degradation of the polymeric chain in an acidic dispersion medium, which leads to gradual structural changes of the chimeric nanovectors, was observed. The micropolarity of the hydrocarbon region of nanocarriers changed significantly in HPLC-grade water and PBS with increasing block copolymer content. The incorporation of indomethacin (IND) led to a decreased size of chimeric nanocarriers. The incorporation efficiency of mixed liposomal–block copolymer formulations for IND was increased in PBS in comparison with the HPLC-grade water, due to electrostatic interactions between the drug molecule and choline headgroups. PEO-b-PCL grafted DPPC liposomes are found to be effective nanocontainers for the encapsulation of IND, especially at the highest molar ratio of the block copolymer.

RAFT dispersion polymerization in non-polar solvents: facile production of block copolymer spheres, worms and vesicles in n-alkanes

Well-defined poly(lauryl methacrylate-benzyl methacrylate) (PLMA-PBzMA) diblock copolymer nanoparticles are prepared in n-heptane at 90 °C via reversible addition–fragmentation chain transfer (RAFT) polymerization. Under these conditions, the PLMA macromolecular chain transfer agent (macro-CTA) is soluble in n-heptane, whereas the growing PBzMA block quickly becomes insoluble. Thus this dispersion polymerization formulation leads to polymerization-induced self-assembly (PISA). Using a relatively long PLMA macro-CTA with a mean degree of polymerization (DP) of 37 or higher leads to the formation of well-defined spherical nanoparticles of 41 to 139 nm diameter, depending on the DP targeted for the PBzMA block. In contrast, TEM studies confirm that using a relatively short PLMA macro-CTA (DP = 17) enables both worm-like and vesicular morphologies to be produced, in addition to the spherical phase. A detailed phase diagram has been elucidated for this more asymmetric diblock copolymer formulation, which ensures that each pure phase can be targeted reproducibly. 1H NMR spectroscopy confirmed that high BzMA monomer conversions (>97%) were achieved within 5 h, while GPC studies indicated that reasonably good blocking efficiencies and relatively low diblock copolymer polydispersities (Mw/Mn < 1.30) were obtained in most cases. Compared to prior literature reports, this all-methacrylic PISA formulation is particularly novel because: (i) it is the first time that higher order morphologies (e.g. worms and vesicles) have been accessed in non-polar solvents and (ii) such diblock copolymer nano-objects are expected to have potential boundary lubrication applications for engine oils.

Influence of PEG in PEG–PLGA microspheres on particle properties and protein release

The aim of the present study was to compare different commercial available types of Poly(d,l-lactide-co-glycolide) (PLGA), multiblock copolymers of PLGA and polyethylene gylcol (PEG) as well as blends of PLGA and PEG regarding the preparation of microparticles and the release behavior of encapsulated protein. Microspheres were prepared by the solvent evaporation technique using the same conditions for each formulation. The encapsulation rate of bovine serum albumin (BSA) was unaffected by the different polymer types, and the mean was 79±4%. Microspheres composed of blends of PLGA and PEG showed a porous structure, a higher specific surface area, an inhomogenous distribution of protein and a higher release rate of BSA than microspheres consisting of PLGA, whereas the release profiles were the same. The specific surface area of microparticle formulations composed of diblock copolymers was the highest with 8.57±0.07m2/g emphasized by a highly porous, sponge-like structure. The triblock copolymer formulation revealed nearly spherical particles with a slightly uneven surface. Although the triblock copolymer consists of 10% PEG, the specific surface area was the lowest of all formulations. The rapid hydration due to PEG leads to a swollen matrix, which released the protein in a slow and continuous way.

Nonvolatile copolymer compositions for fabricating gel element microarrays

By modifying polymer compositions and cross-linking reagents, we have developed a simple yet effective manufacturing strategy for copolymerized three-dimensional gel element arrays. A new gel-forming monomer, 2-(hydroxyethyl) methacrylamide (HEMAA), was used. HEMAA possesses low volatility and improves the stability of copolymerized gel element arrays to on-chip thermal cycling procedures relative to previously used monomers. Probe immobilization efficiency within the new polymer was 55%, equivalent to that obtained with acrylamide (AA) and methacrylamide (MA) monomers. Nonspecific binding of single-stranded targets was equivalent for all monomers. Increasing cross-linker chain length improved hybridization kinetics and end-point signal intensities relative to N,N-methylenebisacrylamide (Bis). The new copolymer formulation was successfully applied to a model orthopox array. Because HEMAA greatly simplifies gel element array manufacture, we expect it (in combination with new cross-linkers described here) to find widespread application in microarray science.

BioMime – A Sirolimus-eluting Coronary Stent System for the Treatment of Patients with De Novo Coronary Lesions – meriT-1 Report

Background:Since the first reported use of percutaneous transluminal coronary angioplasty, advances in the interventional cardiology arena have been fast paced. Developers and clinicians are adapting from the learning curve awarded by the time-course of drug-eluting stent (DES) evolution. BioMime™ sirolimus-eluting stent (SES) is a step towards biomimicry. The stent is built on a strut of ultra-low thickness (65μm), a cobalt–chromium platform using an intelligent hybrid of closed and open cells allowing for morphology-mediated expansion. It employs a well-known antiproliferative – sirolimus – that elutes from a known biodegradable copolymer formulation within 30 days. The resultant stent demonstrates almost 100% endothelialisation at 30 days in preclinical models.Methods:The meriT-1 was a prospective, single-arm, single-centre trial to evaluate the safety and efficacy of BioMime SES in 30 patients with a single de novo lesion in native coronary arteries. The primary safety and efficacy end-points were major adverse cardiac events (MACE) at 30 days and in-stent late lumen loss at eight months, as measured using quantitative coronary angiographic (QCA) method. Secondary safety and efficacy end-points included MACE at one and two years and angiographic binary restenosis at eight-month angiographic follow-up. Other end-points included the occurrence of stent thrombosis at acute, subacute, late and very late periods and the percentage of diameter stenosis by QCA.Results:No MACE were observed and the median in-stent late luminal loss in 20 (67%) subjects studied by QCA was 0.15mm, with 0% binary restenosis at eight-month follow-up. No stent thrombosis was observed up to one-year follow-up.Conclusions:In comparison to currently available DES, BioMime SES appears to have a considerable scientific basis for prevention of neointimal proliferation, restenosis and associated clinical events.