Biodegradable Polymer Coatings Research Articles

Electrochemical and Biological Performance of Biodegradable Polymer Coatings on Ti6Al7Nb Alloy.

The inhibition of the corrosion of metal implants is still a challenge. This study aimed to increase the corrosion resistance of Ti6Al7Nb alloy implants through surface modification, including grinding, sandblasting, and anodic oxidation followed by the deposition of a polymer coating. The aim of the work was to determine the influence of biodegradable polymer coatings on the physico-chemical properties of a Ti6Al7Nb alloy used for short-term implants. Biodegradable coatings prepared from poly(glycolide-caprolactone) (P(GCap)), poly(glycolide ε-caprolactone-lactide) (P(GCapL)), and poly(lactide-glycolide) (PLGA) were applied in the studies. The dip-coating method with three cycles of dipping was applied. Corrosion resistance was assessed on the basis of potentiodynamic studies. The studies were carried out on samples after 30, 60, and 90 days of exposure to Ringer’s solution. Surface topography, wettability, and cytotoxicity studies were also carried out. The degradation process of the base material was evaluated on the basis of the mass density of the metal ions released to the solution. The results indicated the influence of the coating type on corrosion resistance. In addition, a beneficial effect of the polymer coating on the reduction of the density of the released metal ions was found, as compared to the samples without polymer coatings. The obtained results provide basic knowledge for the development of polymer coatings enriched with an active substance. The presence of ciprofloxacin in the coating did not reduce the corrosion resistance of the metal substrate. Moreover, the cytotoxicity test using the extract dilution method demonstrated that the implants’ coatings are promising for further in vitro and in vivo studies.

Изучение кинетических закономерностей и моделирование тепло- и массопереноса в процессе сушки джекфрута

В последнее время в мире приобретает популярность плод хлебного дерева (джекфрут), особенно среди вегетарианцев, вследствие того, что его плоды придают энергию из-за наличия в нем простых сахаров (фруктозы и сахарозы), при этом он не содержит жиров и вредного холестерина, что делает его превосходным источником энергии. С целью консервирования данного продукта рекомендовано применение биоразлагаемых полимерных покрытий для повышения сроков годности с максимальным сохранением пищевой ценности. Целью работы является разработка рациональных режимных параметров сушки ломтиков джекфрута с защитным биопокрытием и моделирование тепло- и массопереноса. Для достижения поставленной цели установлены кинетические закономерности процесса конвективной сушки ломтиков джекфрута, как двухслойного объекта и построены кривые скорости удаления воды. При варьировании в рамках технологических ограничений параметров, влияющих на интенсивность обезвоживания, определена, зависящая от их величины удельная производительность процесса и ее рациональное значение. Опираясь на анализ закономерностей протекания процессов переноса тепловой энергии и вещества выявлены их специфические особенности при удалении влаги из двухслойного объекта. Численно решена модель переноса тепловой энергии и вещества и рассчитана эволюция полей температур в образце при сушке. Полученные результаты позволили определить рациональные режимы обезвоживания, обеспечивающие устойчивость на поверхности ломтика нанесенного защитного покрытия, что способствует увеличению сроков его хранения при конечной влажности 25%, а также снижению энергоемкости реализуемого процесса консервации обезвоживанием. Обоснована возможность использования биополимерного покрытия на основе альгината натрия при сушке ломтиков джекфрута.

Polylactide-Based Stent Coatings: Biodegradable Polymeric Coatings Capable of Maintaining Sustained Release of the Thrombolytic Enzyme Prourokinase.

The novelty of the study is the development, creation, and investigation of biodegradable polymeric membranes based on polylactide, that are capable of directed release of large molecular weight biomolecules, particularly, prourokinase protein (MW = 46 kDa). Prourokinase is a medication with significant thrombolytic activity. The created membranes possess the required mechanical properties (relative extension value from 2% to 10%, tensile strength from 40 to 85 MPa). The membranes are biodegradable, but in the absence of living cells in a water solution they decompose by less than 10% in half a year. The created membranes are capable of controlled prourokinase release into intercellular space, and the total enzymatic activity of prourokinase does not decrease by more than 12%. The daily release of prourokinase from one square centimeter of the membrane ranges from 1 to 40 μg per day depending on the technique of membrane preparation. The membranes have no acute toxic effect on cells accreting these surfaces de novo. The number of viable cells is at least 96%−97% of the overall cell count. The mitotic index of the cells growing on the surface of the polymeric films comprised around 1.5%. Histological examination did not reveal any disorders in tissues of the animals after the implantation of polymer membranes based on polylactide, both alone and as components of stent cover. Implantation of stents covered with prourokinase-containing polymers led to the formation of a mature connective tissue capsule that is thicker than in the case of uncovered stents. Thus, various polylactide-based biodegradable polymeric membranes possessing the required mechanical properties and capable of prolonged and directed release of prourokinase macromolecules are developed and investigated in the study.

Biodegradable Conducting Polymer Coating to Mitigate Early Stage Degradation of Magnesium in Simulated Biological Fluid: An Electrochemical Mechanistic Study

AbstractThe application of a biodegradable conducting polymer coating based on a polythiophene composite (PTC) to mitigate degradation of magnesium in an in vitro environment is reported. The rationale behind the study is to advance a bioactive coating to control the rapid early stage degradation of the magnesium and prevent inflammatory reactions and physiological complications, while, in the long term, the coating degrades, followed by the full degradation of the magnesium implant. The conducting polymer in this study is deposited on a bioabsorbable medical grade magnesium alloy, AZNd, through layer‐by‐layer deposition, and the degradation behavior in simulated biological fluid is studied electrochemically. The possibility of a synergistic effect by combining praseodymium conversion coating together with the conducting polymer coating in protecting magnesium is also examined. Results show that the highest level of corrosion mitigation is afforded by the combination of praseodymium conversion and the conducting polymer coating layers. Electrochemical models are advanced to explain the electroactivity of the conducting polymer across the film as well as at the interface with electrolyte and substrate. Based on the physical and electrochemical evidence, the barrier effect is proposed as the main protection mechanism.

Synthesis, characterization and strengthening mechanism of modified and unmodified porous diopside/baghdadite scaffolds

Abstract In recent decades, porous silica-based bioceramic scaffolds have received great attention for treatment of bone defects. One of the main drawbacks of these scaffolds is their inherent brittle nature and high degradation rate. Recently, using bioactive and biodegradable polymer coatings on the surface of scaffolds improves their mechanical properties and the ability to control their degradation rate. In this work, highly porous diopside/baghdadite composite scaffolds with and without surface modification were prepared by space holder method. Compressive strength, compressive modules, porosity and the pore size of the different scaffolds with different diopside contents were in the range of 0.28–1.33 MPa, 15.35–155 MPa, 64–78%, and 300–500 μm, respectively. The results showed that applying a PCLF cross-linked polymer coating on the scaffolds improved their compressive strength and modulus from 1.09 ± 0.1 and 139.3 ± 1.1 to 1.63 ± 0.2 and 189.1 ± 1 MPa, respectively. A negligible reduction in porosity and pore size was observed.

Electrophoretic Deposition of Bioadaptive Drug Delivery Coatings on Magnesium Alloy for Bone Repair

Biodegradable polymer coatings on magnesium alloys are attractive, as they can provide corrosion resistance as well as additional functions for biomedical applications, e.g., drug delivery. A gelatin nanospheres/chitosan (GNs/CTS) composite coating on WE43 substrate was fabricated by electrophoretic deposition with simvastatin (SIM) loaded into the GNs. Apart from a sustained drug release over 28 days,an anticorrosion behavior of the coated WE43 substrates wasconfirmed by electrochemical tests. Both the degradation and corrosion rates of the coated substrate were significantly minimized in contrastto bare WE43. The cytocompatibility of the coated samples was analyzed both quantitatively and qualitatively. Additionally, the osteogenic differentiation of MC3T3-E1 cells on SIM-containing coatings was assessed by measuring the expression of osteogenic genes and related proteins, alkaline phosphatase (ALP) activity, and extracellular matrix mineralization, showing that the SIM-loaded composite coating could upregulate the expression of osteogenic genes and related proteins, promote ALP activity, and enhance extracellular matrix mineralization. In summary, the SIM-loaded GNs/CTS composite coatings were able to enhance the corrosion resistance of the WE43 substrate and promote osteogenic activity, thus demonstrating a promising coating system for modifying the surface of magnesium alloys targeted for orthopedic applications.

Biodegradable polymer coatings on Ti6Al7Nb alloy

The aim of the study was to determine the influence of long term exposure to Ringer's solution of biodegradable polymer coatings containing an active substance on the Ti6Al7Nb alloy substrate on the physical and chemical properties of the coatings and the degradation process of the metal substrate. The studies used poly(L-lactide-co-trimethylene carbonate) P(L/TMC), poly(L-lactide-co-trimethylene carbonate-glycolide) P(L/TMC/G) and poly(D,L-lactide-glycolide) (PLGA) coatings applied to the anodically oxidized Ti6Al7Nb alloy by means of dipping method (1, 2 and 3 dips). The polymer coatings contained ciprofloxacin. Roughness and wettability tests were carried out on the substrate and polymer coatings, the pitting corrosion resistance of the substrate and samples with polymer coating was determined, the number of metallic ions released to the solution from the coated and uncoated samples was determined as well as the adhesion of polymer coatings. The research was supplemented by microscopic observations. The results of the research indicate different influence of exposure to Ringer's solution on the physical and chemical properties of biodegradable polymer coatings containing ciprofloxacin and the course of the degradation process of the metal substrate.

Designing pH-Responsive Biodegradable Polymer Coatings for Controlled Drug Release via Vapor-Based Route.

We present the design of a novel pH-responsive drug release system that is achieved by solventless encapsulation of drugs within a microporous membrane using a thin capping layer of biodegradable poly(methacrylic anhydride) (PMAH) coating. The coating was synthesized via a mild vapor polymerization process, namely, initiated chemical vapor deposition, which allowed perfect retention of the anhydride groups during deposition. The synthesized polyanhydride underwent degradation upon exposure to aqueous buffers, resulting in soluble poly(methacrylic acid). The degradation behavior of PMAH is highly pH-dependent, and the degradation rate under pH 10 is 15 times faster than that under pH 1. The release profile of a model drug rifampicin clearly exhibited two stages: the initial stage when the coatings were being degraded but the drugs were well stored and the second stage when drugs were gradually exposed to the medium and released. The drug release also showed strong pH responsiveness where the duration of the initial stage under pH 1 was more than 7 and 3 times longer than that under pH 10 and 7.4, respectively, and the release rates at pH 7.4 and 10 were significantly faster than that at pH 1. The pH-dependent degradation of the encapsulant thus enabled good preservation of drugs under low-pH environment but high drug release efficiency under neutral and alkaline environment, suggesting potential applications in site-specific drug delivery systems.

Randomised comparison of vascular response to biodegradable polymer sirolimus eluting and permanent polymer everolimus eluting stents: An optical coherence tomography study

BackgroundDrug-eluting stents with biodegradable polymer coatings have shown promising outcomes in randomised studies. MethodsWe compared neointimal healing patterns including strut coverage and assessed neointimal maturity using a novel algorithm in coronary lesions treated with sirolimus-eluting stents with biodegradable polymer coating (BP-SES) or everolimus eluting stents with permanent polymer coating (PP-EES) using optical coherence tomography after 6months. ResultsA total of 39 patients were randomised to BP-SES (n=19) or PP-EES (n=20) for the treatment of coronary lesions. Of those, 29 patients (14 BP-SES and 15 PP-EES) underwent optical coherence tomography (OCT) and angiography at 6-month follow-up. Tissue coverage and apposition were assessed in a total of 6162 struts (BP-SES, n=2889; PP-EES, n=3273). Neointimal maturity was assessed in 3672 neointimal regions above struts using grey scale intensity analysis. OCT analysis showed neointimal coverage of 2433 (BP-SES) vs. 2702 (PP-EES) struts (84.2% vs. 82.6%, p=0.70), whereas the remainder was uncovered after 6months. Mean neointimal thickness did not differ significantly between groups (54.3±7.8μm vs. 80±14.6μm, p=0.12). The rate of malapposed struts was comparable between groups (1.3% vs. 2.2%, p=0.27). Grey scale signal intensity analysis showed mature tissue coverage of struts in 46.2% in BP-SES vs. 31.8% in PP-EES (p=0.31) of neointimal regions. ConclusionThe present study showed comparable early vascular healing response characterised by neointimal coverage with mainly immature neointima in both BP-SES and PP-EES.

Optimized polymer coating for magnesium alloy-based bioresorbable scaffolds for long-lasting drug release and corrosion resistance

Magnesium (Mg) alloy-based bioresorbable scaffolds (BRSs) are attracting interest as next-generation stents. However, because medical Mg alloy materials degrade relatively quickly in physiological media, surface corrosion protection via biodegradable polymer coatings is important for clinical applications. Herein, the influence of biodegradable polymer coatings on the BRS corrosion was investigated. First, elution of the drug sirolimus (SRL) from various biodegradable polymers was estimated, including poly(d,l-lactic acid) (PDLLA), poly(d,l-lactic acid-co-ε-caprolactone) (PLCL) and poly(ε-caprolactone) (PCL). Among these, the PDLLA polymer exhibited the slowest release and the best character as a drug reservoir because of its slow degradation rate and semi-glass state in a biological environment. However, the corrosion rate of the PDLLA-coated Mg alloy (AZ31)-based platform was as rapid as the non-coated platform, while critical defects, cracking and desorption were observed in the PDLLA layer. Coatings comprising PCL and PLCL exhibited a prolonged platform corrosion resistance compared with that of PDLLA. To combine the advantages of each polymer, therefore, a pre-coating of PCL or PLCL was applied to the interface between the platform and the external SRL-loaded PDLLA layer. This layering exhibited an enhanced platform corrosion resistance, and will be an important foundational procedure for the development of a coronary scaffold comprising magnesium alloys.

Comparison Study on Four Biodegradable Polymer Coatings for Controlling Magnesium Degradation and Human Endothelial Cell Adhesion and Spreading.

Magnesium (Mg)-based bioresorbable cardiovascular scaffold (BCS) is a promising alternative to conventional permanent cardiovascular stents, but it faces the challenges of rapid degradation and poor endothelium recovery after device degradation. To address these challenges, we investigated poly(l-lactic acid) (PLLA), poly(lactic-co-glycolic acid) (PLGA) (90:10), PLGA (50:50), and polycaprolactone (PCL) coatings on Mg, respectively, and evaluated their surface and biological properties. Intact polymer coatings with complete coverage on Mg substrate were achieved. The biological performance of the materials was evaluated by culturing with human umbilical vein endothelial cells (HUVECs) in vitro using the direct culture method. The pH of the culture media and Mg2+ and Ca2+ ion concentrations in the media were measured after culture to characterize the degradation rate of the materials in vitro. The results showed that the PLGA (50:50) coating improved the adhesion and spreading of HUVECs the most among the four polymer coatings. Moreover, we found three possible factors that promoted HUVECs directly attached on the surface of PLGA (50:50)-coated Mg: (1) the higher concentration of Mg2+ ions released into culture media with a concentration range of 9-15 mM; (2) the lower Ca2+ ion concentration in culture media at 1.3-1.6 mM; and (3) the favorable surface conditions of PLGA (50:50), when compared with the other sample groups. This in vitro study provided the first evidence that the PLGA (50:50) is a promising coating material for Mg-based biodegradable metals toward potential cardiovascular or neurovascular applications.

Very thin strut biodegradable polymer everolimus-eluting and sirolimus-eluting stents versus durable polymer zotarolimus-eluting stents in allcomers with coronary artery disease (BIO-RESORT): a three-arm, randomised, non-inferiority trial

In patients with coronary artery disease, treated with durable polymer-coated drug-eluting stents, the life-long presence of the polymer might delay arterial healing. Novel very thin strut biodegradable polymer stents, which leave only a bare metal stent after polymer resorption, might improve long-term outcome. We investigated in allcomers the safety and efficacy of three stents eluting either everolimus, sirolimus, or zotarolimus, often clinically used but never compared, of which the biodegradable polymer everolimus-eluting stent was never before assessed in allcomers. The large-scale, investigator-initiated, multicentre, assessor and patient blinded, three-arm, randomised, BIO-RESORT non-inferiority trial was done at four clinical sites in the Netherlands. All-comer patients were aged 18 years or older, capable of providing informed consent, and required a percutaneous coronary intervention with drug-eluting stent implantation according to clinical guidelines or the operators' judgment. Exclusion criteria were: participation in another randomised drug or device study before reaching the primary endpoint of that study; planned surgery necessitating interruption of dual antiplatelet therapy within the first 6 months; known intolerance to components of the investigational product or medication required; uncertainty about the adherence to follow-up procedures or an assumed life expectancy of less than 1 year; or known pregnancy. Web-based computer-generated allocation sequences randomly assigned patients (1:1:1) to treatment with very thin strut biodegradable polymer everolimus-eluting or sirolimus-eluting stents (which differ substantially in type, amount, distribution, and resorption speed of their respective coating), or thin strut durable polymer zotarolimus-eluting stents. The primary endpoint was a composite of safety (cardiac death or target vessel-related myocardial infarction) and efficacy (target vessel revascularisation) at 12 months of follow up with a very thin strut biodegradable polymer of either everolimus-eluting or sirolimus-eluting stents, compared with durable polymer zotarolimus-eluting stents, analysed by intention to treat (non-inferiority margin 3·5%). This trial was registered with ClinicalTrials.gov, number NCT01674803. From Dec 21, 2012, to Aug 24, 2015, 3514 patients were enrolled and analysed, of whom 2449 (70%) had acute coronary syndromes, which included 1073 (31%) ST-elevation myocardial infarctions. 12 month follow-up of 3490 (99%) patients (three lost to follow-up; 21 withdrawals) was available. The primary endpoint was met by 55 (5%) of 1172 patients assigned to everolimus-eluting stents, 55 (5%) of 1169 assigned to sirolimus-eluting stents and 63 (5%) of 1173 assigned to zotarolimus-eluting stents. Non-inferiority of the everolimus-eluting stents and sirolimus-eluting stents compared with zotarolimus-eluting stents was confirmed (both -0·7% absolute risk difference, 95% CI -2·4 to 1·1; upper limit of one sided 95% CI 0·8%, pnon-inferiority<0·0001). Definite stent thrombosis (defined by the Academic Research Consortium) occurred in four (0·3%) of 1172 patients who were allocated to everolimus-eluting stents, four (0·3%) of 1169 patients who were allocated to sirolimus-eluting stents, and three (0·3%) of 1173 patients who were allocated to zotarolimus-eluting stents (log-rank p=0·70 for both comparisons with zotarolimus-eluting stents). At 12 month follow-up, both very thin strut drug-eluting stents with dissimilar biodegradable polymer coatings (eluting either everolimus or sirolimus) were non-inferior to the durable polymer stent (eluting zotarolimus) in treating allcomers with a high proportion of patients with acute coronary syndromes. The absence of a loss of 1 year safety and efficacy with the use of these two biodegradable polymer-coated stents is a prerequisite before assessing their potential longer-term benefits. Biotronik, Boston Scientific, and Medtronic.

Bioactivity of dexamethasone-releasing coatings on polymer/magnesium composites

We developed biodegradable polymeric coatings loaded with increasing amounts of dexamethasone on composites based on polylactic acid and Mg particles for bone repair. Incorporation of Mg particles into the polymeric matrix improves the compressive behaviour of the polymer. Mg-containing composites release Mg2+ ions into the culture medium and improve mesenchymal stem cell (MSC) viability, enhance their osteogenic potential and promote the release of angiogenic factors. Dexamethasone-loaded coatings deposited on composites delay Mg2+ ion dissolution while releasing controlled amounts of the drug, which are highly dependent on initial payload. Release kinetic of dexamethasone from the coatings exhibits a fast initial release of the drug followed by a slower secondary release. Bioactivity of the released dexamethasone was explored by monitoring dose-dependent responses of MSCs and macrophages. Biological effects exerted by the released drug are similar to those observed in cells treated with solutions of the glucocorticoid, indicating that the method employed for inclusion of dexamethasone into the coatings does not impair its bioactive behaviour. Culturing MSCs on dexamethasone-releasing coatings enhances extracellular matrix production and initial induction to osteogenic commitment as a function of drug payload. Dexamethasone incorporated into the coatings presents anti-inflammatory activity, as shown by the decrease in the production of cytokines and angiogenic factors by macrophages and MSCs. Deposition of dexamethasone-releasing coatings on polymer/Mg composites appears to be a promising approach to delay composite degradation at the early stage of implantation and may be useful to attenuate inflammation and adverse foreign body reactions.

Bioresorbable scaffolds are here, please handle with care

Magnesium (Mg) alloy-based bioresorbable scaffolds (BRSs) are attracting interest as next-generation stents. However, because medical Mg alloy materials degrade relatively quickly in physiological media, surface corrosion protection via biodegradable polymer coatings is important for clinical applications. Herein, the influence of biodegradable polymer coatings on the BRS corrosion was investigated. First, elution of the drug sirolimus (SRL) from various biodegradable polymers was estimated, including poly(d,l-lactic acid) (PDLLA), poly(d,l-lactic acid-co-ε-caprolactone) (PLCL) and poly(ε-caprolactone) (PCL). Among these, the PDLLA polymer exhibited the slowest release and the best character as a drug reservoir because of its slow degradation rate and semi-glass state in a biological environment. However, the corrosion rate of the PDLLA-coated Mg alloy (AZ31)-based platform was as rapid as the non-coated platform, while critical defects, cracking and desorption were observed in the PDLLA layer. Coatings comprising PCL and PLCL exhibited a prolonged platform corrosion resistance compared with that of PDLLA. To combine the advantages of each polymer, therefore, a pre-coating of PCL or PLCL was applied to the interface between the platform and the external SRL-loaded PDLLA layer. This layering exhibited an enhanced platform corrosion resistance, and will be an important foundational procedure for the development of a coronary scaffold comprising magnesium alloys.

Evolution of Drug-Eluting Stent Drug Elution Profile: Is a Crystalline Drug Form the Ideal Solution?

Since its introduction into clinical practice, coronary angioplasty has seen game-changing advances incomparable to any other medical technology. In particular, the progression from balloon angioplasty to stent technology has not only seen significant advances in technology but, more importantly, improved patient outcomes. The introduction of the drug-eluting stent (DES) has further pushed the technology to a new standard of care. However, even in the current day, top performing DESs still have several limitations. Their safety has been limited by suboptimal polymer biocompatibility, delayed stent re-endothelialisation, and local drug toxicity, leading to adverse clinical outcomes such as very late stent thrombosis, allergic reactions, and chronic inflammation. In addition, current DESs have a consistent yearly increase in late restenosis and revascularisations. Furthermore, durable polymer coatings used in first-generation DESs have been associated with mechanical complications and non-uniform coating, resulting in drug loss and poor distribution. As a consequence, in recent years, the focus of research has been on the development of novel drug carrier systems including absorbable (or biodegradable) polymer coatings and non-polymeric stent surfaces. Additional improvements have included the development of more modern stent platforms. Optimised drug delivery requires a combination of refined stent designs and drug delivery technology. The combination of highly-refined bare-metal stent designs and polymer coating materials have been two areas of focus for the development and improvement of next-generation DESs. Despite all the changes in stent design and polymer materials, there has been little done in the past 15 years to improve drug elution profiles. The need for new advancements in DES design to overcome late event occurrence, and possibly even improve on the clinical outcomes of current DESs, has led to interest in moving away from the standard drug elution profile to explore alternatives. A new manufacturing technique that may have overcome traditional limitations has led to the development of a novel stent platform. This review will explore the principles, device technology, and clinical data to date on a crystalline form of the anti-restenotic drug for stent implantation. This approach could truly be game changing due to an improved elution pharmacokinetic profile, as well as reduced local toxicity and improved long-term biologic arterial wall response.

Influence of biodegradable polymer coatings on corrosion, cytocompatibility and cell functionality of Mg-2.0Zn-0.98Mn magnesium alloy

Four kinds of biodegradable polymers were employed to prepare bioresorbable coatings on Mg-2.0Zn-0.98Mn (ZM21) alloy to understand the relationship between polymer characteristics, protective effects on substrate corrosion, cytocompatibility and cell functionality. Poly-l-lactide (PLLA), poly(3-hydroxybutyrate) (PHB), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) or poly(lactic-co-glycolic) acid (PLGA) was spin-coated on ZM21, obtaining a smooth, non-porous coating less than 0.5μm in thickness. Polymer coating characterization, a degradation study, and biocompatibility evaluations were performed. After 4 w of immersion into cell culture medium, degradation of PLGA and PLLA coatings were confirmed by ATR-FTIR observation. The coatings of PLLA, PHB and PHBV, which have lower water permeability and slower degradation than PLGA, provide better suppression of initial ZM21 degradation and faster promotion of human osteosarcoma cell growth and differentiation.

Surface Modification of Biodegradable Polymers towards Better Biocompatibility and Lower Thrombogenicity

PurposeDrug-eluting stents (DES) based on permanent polymeric coating matrices have been introduced to overcome the in stent restenosis associated with bare metal stents (BMS). A further step was the development of DES with biodegradable polymeric coatings to address the risk of thrombosis associated with first-generation DES. In this study we evaluate the biocompatibility of biodegradable polymer materials for their potential use as coating matrices for DES or as materials for fully bioabsorbable vascular stents.Materials and MethodsFive different polymers, poly(L-lactide) PLLA, poly(D,L-lactide) PDLLA, poly(L-lactide-co-glycolide) P(LLA-co-GA), poly(D,L-lactide-co-glycolide) P(DLLA-co-GA) and poly(L-lactide-co-ε-caprolactone), P(LLA-co-CL) were examined in vitro without and with surface modification. The surface modification of polymers was performed by means of wet-chemical (NaOH and ethylenediamine (EDA)) and plasma-chemical (O2 and NH3) processes. The biocompatibility studies were performed on three different cell types: immortalized mouse fibroblasts (cell line L929), human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC). The biocompatibility was examined quantitatively using in vitro cytotoxicity assay. Cells were investigated immunocytochemically for expression of specific markers, and morphology was visualized using confocal laser scanning (CLSM) and scanning electron (SEM) microscopy. Additionally, polymer surfaces were examined for their thrombogenicity using an established hemocompatibility test.ResultsBoth endothelial cell types exhibited poor viability and adhesion on all five unmodified polymer surfaces. The biocompatibility of the polymers could be influenced positively by surface modifications. In particular, a reproducible effect was observed for NH3-plasma treatment, which enhanced the cell viability, adhesion and morphology on all five polymeric surfaces.ConclusionSurface modification of polymers can provide a useful approach to enhance their biocompatibility. For clinical application, attempts should be made to stabilize the plasma modification and use it for coupling of biomolecules to accelerate the re-endothelialization of stent surfaces in vivo.

TCT-483 “Real world use of ultra-thin sirolimus-eluting stent with biodegradable polymers. 9-month results from the FLEX-registry.”

Durable polymer-based drug-eluting stents have been reported to adversely affect the safety profile and are also suspected to cause serious long-term complications. It has been proposed that the biodegradable polymer coatings may reduce such late-stage adverse effects. The purpose of this registry

An update on drug-eluting stents versus bare-metal stents in PCI treatment: are there any remaining indications for BMS use?

Drug-eluting stents (DES) are recognized as a breakthrough technology in the treatment of coronary artery disease, primarily due to substantial reduction in the risk of repeat revascularization as compared with bare-metal stents (BMS). During the last decade new DES – with thinner stent struts, novel durable or biodegradable polymer coatings, and new limus antiproliferative agents – have been developed to address the limitations of earlier generation DES. Randomized trials, observational studies and meta-analyses have shown a marked improvement in clinical safety and efficacy with new-generation DES as compared with BMS, as well as early-generation DES, in a wide spectrum of patients. The objective of this article is to review whether there are any indications left for the use of BMS in clinical practice based on available evidence.

Biodegradable polymer drug-eluting stents: ready for US prime time?

Drugmatrix coatings play the critical role in determining the clinical efficacy of drug-eluting stent (DES) devices. In fact, although various surface modifications have been investigated as a means of facilitating loading and controlling release of the active drug, most success has been seen with matrix coatings that combine active drug with a polymeric carrier [1]. Effective DES devices are typically characterized by controlled drug release: approximately 50% of the drug load is eluted in the first 10–14 days and the bulk of the remainder in the first 30–60 days. DES platformswithout polymer usually exhibit a release kinetic that is too rapid in the initial weeks after implantation, and this results in a suboptimal suppression of neointimal hyperplasia [2]. Indeed, to date all DESs that have been approved for use in the United States have made use of nonerodable polymer coatings [3]. Although the clinical effects of DES result from interplay of various design elements, including stent backbone, matrix coating, and drug load and concentration, nonerodable polymer coatings have been implicated as a central factor contributing to the delayed arterial healing that seems to occur systematically with DES therapy [4]. The most likely mechanistic explanation is that chronic inflammatory reaction to the polymer layer that remains on the DES after the active drug has been eluted delays endothelial regeneration [5]. In fact, delayed healing underlies a spectrum of adverse events ranging from late stent thrombosis to delayed catch-up restenosis. In addition, it is likely an important trigger for the development of de novo in-stent atherosclerosis [6]. These observations have provided the impetus for the development of newer generation DES devices that do not depend on durable polymer matrices. One successful approach to target the problem of delayed arterial healing has been to use DES coated with biodegradable polymer. In fact, although DES with biodegradable polymer are not approved for use in the United States at present, we and other investigators began testing these devices in clinical trials about 10 years ago with largely encouraging results [2,7]. The hypothesized clinical advantage is intuitively attractive: biodegradable polymer coatings that are made of polylactic acid (PLA) or polylactic-co-glycolic acid control the elution of drug in the critical initial weeks after stent implantation and then degrade to carbon dioxide and water after their useful function has been served. As a result, the long-term footprint of the device is expected to be similar to that of a bare metal stent. Moreover, as some nonclinical evidence suggests that certain nonerodable methacrylate-based polymer coatings may improve stent-blood interactions directly after stent implantation [8], patients might still