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PubMed2003

A new method to prepare multicellular spheroids in cancer cell lines using a thermo-reversible gelation polymer.

The purpose of this study is to utilize the thermo-reversible gelation polymer in which the sol-gel transitting phase is reversibly changed by temperature in a three-dimensional culture system. Human cancer cells have been observed to form multicellular spheroids, whereas fibroblasts slowly develop into small spheroids with the culture medium including this polymer. This polymer has some advantages for use as a culture material, as follows: first, cancer cells grow three-dimensionally in the aqueous solution of this polymer; second, it is easy to harvest cells or spheroids in the aqueous solution of this polymer by simply cooling down the temperature; and third, the culture medium including this polymer is so translucent that the cells or spheroids can be observed through a phase-contrast microscope. We thus conclude that this polymer is a very useful material for three-dimensional cultures.

Cell Culture Techniques↗

PubMed2007

Effects of lengthscales and attractions on the collapse of hydrophobic polymers in water.

We present results from extensive molecular dynamics simulations of collapse transitions of hydrophobic polymers in explicit water focused on understanding effects of lengthscale of the hydrophobic surface and of attractive interactions on folding. Hydrophobic polymers display parabolic, protein-like, temperature-dependent free energy of unfolding. Folded states of small attractive polymers are marginally stable at 300 K and can be unfolded by heating or cooling. Increasing the lengthscale or decreasing the polymer-water attractions stabilizes folded states significantly, the former dominated by the hydration contribution. That hydration contribution can be described by the surface tension model, DeltaG = gamma(T)DeltaA, where the surface tension, gamma, is lengthscale-dependent and decreases monotonically with temperature. The resulting variation of the hydration entropy with polymer lengthscale is consistent with theoretical predictions of Huang and Chandler [Huang DM, Chandler D (2000) Proc Natl Acad Sci USA 97:] that explain the blurring of entropy convergence observed in protein folding thermodynamics. Analysis of water structure shows that the polymer-water hydrophobic interface is soft and weakly dewetted, and is characterized by enhanced interfacial density fluctuations. Formation of this interface, which induces polymer folding, is strongly opposed by enthalpy and favored by entropy, similar to the vapor-liquid interface.

Hydrophobic and Hydrophilic Interactions↗

PubMed1980

Determination of deoxyhemoglobin S polymer in sickle erythrocytes upon deoxygenation.

We have used 13C/1H magnetic double-resonance spectroscopy to measure the amount of sickle hemoglobin polymer within sickle erythrocytes as a function of oxygen saturation. We previously showed that the methods of cross-polarization and scalar decoupling could be used to measure accurately the polymer fraction in deoxygenated sickle hemoglobin solutions [Noguchi, C.T., Torchia, D.A. & Schechter, A.N. (1979) Proc. Natl. Acad. Sci. USA 76, 4936-4940]. Our measurements show that the amount of intracellular deoxyhemoglobin S polymer increases monotonically with decreasing oxygen saturation. Polymer can be detected at oxygen saturation values above 90%. This result can be theoretically explained by the excluded volume effect of the oxyhemoglobin S in the cell. The very high total intracellular hemoglobin concentration (34 g/dl) reduces the amount of soluble deoxyhemoglobin S to about 3 g/dl at 90% oxygen saturation. The agreement between theory and experiment indicates that the equilibrium properties of intracellular polymerization can be described by the analyses resulting from studies of concentrated sickle hemoglobin solutions. The curve for polymer formation as a function of oxygen saturation is roughly hyperbolic whereas that for cell sickling is sigmoidal; the difference is most apparent for measurements at pH 7.65. Intracellular polymer formation may in general have a different relationship to oxygen saturation than cell sickling and may be a more meaningful parameter of the pathophysiological process in sickle cell anemia than cell morphology. In addition, measurements of intracellular polymer should be useful in evaluating potential therapeutic agents.

Anemia, Sickle Cell↗

PubMed2000

Macroporous polymer foams by hydrocarbon templating.

Porous polymeric media (polymer foams) are utilized in a wide range of applications, such as thermal and mechanical insulators, solid supports for catalysis, and medical devices. A process for the production of polymer foams has been developed. This process, which is applicable to a wide range of polymers, uses a hydrocarbon particulate phase as a template for the precipitation of the polymer phase and subsequent pore formation. The use of a hydrocarbon template allows for enhanced control over pore structure, porosity, and other structural and bulk characteristics of the polymer foam. Polymer foams with densities as low as 120 mg/cc, porosity as high as 87%, and high surface areas (20 m(2)/g) have been produced. Foams of poly(l-lactic acid), a biodegradable polymer, produced by this process have been used to engineer a variety of different structures, including tissues with complex geometries such as in the likeness of a human nose.

Biocompatible Materials↗

PubMedDate not supplied

Formulation and characterization of immunoreactive tetanus toxoid biodegradable polymer particles.

Poly lactide-co-glycolide and polylactide polymer particles entrapping immunoreactive tetanus toxoid (TT) were prepared with a view to developing a single shot controlled release vaccine formulation. Denaturation of TT by dichloromethane (DCM) during primary emulsification stage of particle formulation was minimized by incorporation of an optimal amount of rat serum albumin (RSA) in the internal aqueous phase. Incorporation of RSA as a stabilizer during the primary emulsification stage of polymer particle formulation protected the immunoreactivity of TT, enhanced its encapsulation efficiency and also led to uniform polymer particle formation. Use of sonication, both during primary and secondary emulsification processes, resulted in formation of nanoparticles whereas microparticles were formed when the secondary emulsion was carried out by homogenization. Immunoreactive TT particles made from different polymers incorporating stabilizers released antigen continuously for more than four months in vitro. Single injection of both type of particles encapsulating stabilized TT elicited anti-TT antibody titers in rats for more than five months, which was higher than that obtained with TT injected in saline. Anti-TT antibody titers in vivo were in accordance with the in vitro release characteristics of immunoreactive TT from the particles. Immune responses with hydrophobic polymer particles were better than those made using hydrophilic polymers. These results indicate the importance of protecting the immunoreactivity of TT during formation of polymer particles for sustained and improved antibody response.

Animals↗

PubMed1965

ANTIGENICITY OF POLYPEPTIDES (POLY ALPHA AMINO ACIDS). 13. IMMUNOLOGICAL STUDIES WITH SYNTHETIC POLYMERS CONTAINING ONLY D- OR D- AND L-ALPHA-AMINO ACIDS.

It has been demonstrated that polymers consisting solely of D-alpha-amino acids are not immunogenic in rabbits, guinea pigs, man, and mouse, whereas the same polymers of L-alpha-amino acids are very effective antigens. This has been attributed to the importance of metabolizability of a polymer in contributing to its immunogenicity. In the glu-lys-ala series of polymers, the immunogenicity of a polymer of 2 L-amino acids and a D-amino acid appears to be governed by the immunogenicity of the 2 L-amino acids. However, some of the specificity may be directed towards configurations containing the D-amino acid. It has been noted that injections of rabbits with polymers of D-amino acids has resulted in a reduced response against the isomeric L polymer.

Amino Acids↗

PubMed1993

Changes in levels of ADP-ribose polymers in rat liver during 2-acetylaminofluorene-induced hepatocarcinogenesis.

The exposure of rats to the carcinogen 2-acetylaminofluorene (2-AAF) results in the accumulation of DNA-damaging adducts. The inability of cells to repair such damage adequately is a putative causal event in chemical carcinogenesis. It has been shown that one cellular response to DNA damage that leads to DNA repair is poly(ADP-ribosyl)ation of nuclear proteins. To examine the possible existence of an altered poly(ADP-ribosyl)ation response to 2-AAF-mediated damage of rat liver DNA, tissue ADP-ribose polymer levels were determined during various stages of 2-AAF-mediated carcinogenesis. 2-AAF was administered to rats in a discontinuous feeding regimen comprised of five consecutive cycles, each cycle consisting of 3 weeks on 2-AAF diet followed by 1 week of recovery on a control diet without 2-AAF. During cycle one of 2-AAF administration, rat liver ADP-ribose polymer levels increased 3-fold over that found in livers of rats fed only the control diet. In contrast, when rats were administered the non-genotoxic liver mitogen 4-AAF for one cycle, no significant elevation occurred in ADP-ribose polymer levels. Elevated ADP-ribose polymer production was also observed during cycles two and three of 2-AAF administration. However, during cycles four and five of 2-AAF administration, a period when rats administered 2-AAF acquire a high risk for hepatocarcinogenesis, an altered pattern of ADP-ribose polymer production occurred in rat livers. ADP-ribose polymer levels in these rat livers remained low, similar to levels found in control rat livers, despite the administration of 2-AAF. When the livers from rats fed either one or five cycles of 2-AAF were analyzed for possible decreases in the levels of tissue NAD+, the substrate for poly(ADP-ribose) polymerase, no changes in relative abundance were found. In addition, analysis of poly(ADP-ribose) polymerase activity showed no decrease at five cycles of 2-AAF administration. These results indicated that at late stages of 2-AAF-induced hepatocarcinogenesis, 2-AAF does not induce an expected increase in ADP-ribose polymer levels, and suggested that significant changes in DNA repair may occur at a time just preceding an increased risk for developing liver cancer.

2-Acetylaminofluorene↗

PubMed2002

Dynamics of a protein polymer: the assembly and disassembly pathways of the MuB transposition target complex.

MuB assembles into a polymer on DNA in the presence of ATP and is directly involved in the selection of an appropriate site on the Escherichia coli chromosome for the insertion of the bacteriophage Mu genome. We have developed an assay using fluorescently tagged proteins to monitor the polymeric state of MuB via fluorescence resonance energy transfer. We show that polymer assembly is initiated by the formation of an ATP-MuB complex. MuB then self-associates into a protomer before binding to DNA. Upon binding to DNA, a dramatic increase in energy transfer is observed, suggesting a conformational change within MuB. Polymer disassembly is much slower than assembly and is greatly stimulated by the MuA transposase. Additionally, MuB is readily exchanged between polymers, and ATP hydrolysis is directly coupled to polymer disassembly. Our data support a model in which a combination of rapid polymer assembly, MuA-mediated disassembly, followed by rapid reassembly of the polymer allows MuB to sample multiple DNA targets until an appropriate site is located for the insertion of the bacteriophage genome.

Adenosine Triphosphate↗

PubMed2000

The influence of glucan polymer structure and solution conformation on binding to (1-->3)-beta-D-glucan receptors in a human monocyte-like cell line.

Glucans are (1-3)-beta-D-linked polymers of glucose that are produced as fungal cell wall constituents and are also released into the extracellular milieu. Glucans modulate immune function via macrophage participation. The first step in macrophage activation by (1-3)-beta-D-glucans is thought to be the binding of the polymer to specific macrophage receptors. We examined the binding/uptake of a variety of water soluble (1-3)-beta-D-glucans and control polymers with different physicochemical properties to investigate the relationship between polymer structure and receptor binding in the CR3- human promonocytic cell line, U937. We observed that the U937 receptors were specific for (1-->3)-beta-D-glucan binding, since mannan, dextran, or barley glucan did not bind. Scleroglucan exhibited the highest binding affinity with an IC(50)of 23 nM, three orders of magnitude greater than the other (1-->3)-beta-D-glucan polymers examined. The rank order competitive binding affinities for the glucan polymers were scleroglucan>>>schizophyllan > laminarin > glucan phosphate > glucan sulfate. Scleroglucan also exhibited a triple helical solution structure (nu = 1.82, beta = 0.8). There were two different binding/uptake sites on U937 cells. Glucan phosphate and schizophyllan interacted nonselectively with the two sites. Scleroglucan and glucan sulfate interacted preferentially with one site, while laminarin interacted preferentially with the other site. These data indicate that U937 cells have at least two non-CR3 receptor(s) which specifically interact with (1-->3)-beta-D-glucans and that the triple helical solution conformation, molecular weight and charge of the glucan polymer may be important determinants in receptor ligand interaction.

Animals↗

PubMed1985

Availability to rats of iron in ferric hydroxide polymers.

Availability to rats of Fe in isolated ferric hydroxide polymers was assessed. Polymers were prepared by hydrolyzing an 59Fe-labeled ferric nitrate solution with base (KHCO3). After isolation by gel filtration, the polymers were characterized by spectrophotometric, dialysis, and ultracentrifugation methods. In a split-plot design experiment, Fe-adequate (Hb 11.4-14.0 g/dl) or Fe-deficient (Hb 4.7-9.6 g/dl) male Sprague-Dawley rats (10/treatment) were dosed by stomach tube with one of the following 59Fe-labeled solutions: polymers, Fe(NO3)3 (low-molecular-weight control), polymers + citrate, or Fe(NO3)3 + citrate. As expected, Fe-deficient animals absorbed more Fe than adequate animals (P less than 0.01). There was no difference in absorption of Fe between polymers and low-molecular-weight control doses (P greater than 0.05). In Fe-adequate animals, citrate significantly depressed the uptake of Fe both from Fe(NO3)3 and polymers. These results indicate 1) that polymerization of Fe species prior to ingestion is not a likely means by which Fe is rendered unavailable and 2) that the effect of citrate on Fe absorption may depend on the Fe status of the animal.

Absorption↗

PubMed1998

Survival and function of hepatocytes on a novel three-dimensional synthetic biodegradable polymer scaffold with an intrinsic network of channels.

OBJECTIVE: To evaluate the survival and function of hepatocytes (HCs) on a novel three-dimensional (3D) synthetic biodegradable polymer scaffold with an intrinsic network of interconnected channels under continuous flow conditions. SUMMARY BACKGROUND DATA: The authors' laboratory has investigated HC transplantation using 3D biodegradable polymers as scaffolding as an alternative approach to treatment of end-stage liver disease. Previous studies have demonstrated survival of HCs transplanted on polymer discs in peripheral tissue sites and partial correction of single enzyme liver defects. One of the major limitations has been the insufficient survival of an adequate mass of transplanted cells; this is thought to be caused by inadequate oxygen diffusion. METHODS: HCs and nonparenchymal liver cells from Lewis rats were seeded onto 3D biodegradable polymer scaffolds. Microporous 3D polymers were created using 3D printing on copolymers of polylactide-coglycolide. The cell/polymer constructs were placed in static culture or continuous flow conditions. The devices were retrieved after 2 days and examined by scanning electron microscopy and histology. Culture medium was analyzed for albumin by enzyme-linked immunosorbent assay (ELISA). Differences in culture parameters including pH, PCO2, PO2, glucose, lactate, and HCO3 were examined. RESULTS: Scanning electron microscopy revealed successful attachment of HCs on the 3D polymer in both static and flow conditions. Histology demonstrated viable HCs in both conditions. ELISA demonstrated a significantly higher mean concentration of albumin in flow conditions than in static conditions. Culture parameter analysis revealed a significantly higher PO2 and glucose level, and a more physiologic pH in flow conditions than in static conditions. CONCLUSIONS: HCs cocultured with nonparenchymal cells can attach to and survive on the 3D polymer scaffolds in both static and flow conditions in the size and configuration used in this study. Flow conditions may provide a more conducive environment for HC metabolism and albumin synthesis than static conditions. The authors hypothesize that flow through directed channels will be necessary for the transfer of large masses of cells when implantation studies are initiated.

Animals↗

PubMed1983

Mixtures of whole blood and hydroxyethyl starch--hemoglobin polymers.

This study examines some of the biophysical properties of mixtures of whole blood with 3 different hydroxyethyl starch-hemoglobin (HES-Hgb) polymer blood substitutes. The polymers have about a 3-fold range of number average molecular weight and intrinsic viscosity range. The range dependent rheologic studies with a 60 g/L of polymer solution showed that all 3 blood substitutes were very effective hemodiluents paralleling the hemorheologic properties of the starting HES polymers. The 2 higher molecular weight polymers enhanced the erythrocyte sedimentation rates (ESR) at an 8:1 blood to polymer dilution; however, the lowest molecular weight sample actually retarded the settling. The kinetics of malonamide-induced hemolysis indicated that these new polymers do not increase the rate of hemolysis but rather, offer some protection in a manner similar to stroma-free Hgb (SFH) solutions. The oxygen transport properties determined by biotonometry during an exchange transfusion showed that the P50 values decreased and were dependent upon the Hct. However, these samples were able to maintain rats at an Hct level of 10%.

Animals↗

PubMed2006

DNA charge neutralization by linear polymers. II. Reversible binding.

We model the way in which polymers bind to DNA and neutralize its charged backbone by analyzing the dynamics of the distribution of gaps along the DNA. We generalize existing theory for irreversible binding to construct deterministic models which include polymer removal, movement along the DNA, and allow for binding with overlaps. We show that reversible binding alters the capacity of the DNA for polymers by allowing the rearrangement of polymer positions over a longer time scale than when binding is irreversible. When the polymers do not overlap, allowing reversible binding increases the number of polymers adhered and hence the charge that the DNA can accommodate; in contrast, when overlaps occur, reversible binding reduces the amount of charge neutralized by the polymers.

Binding Sites↗

PubMed2000

Evaluation of a novel antimicrobial polymer for the control of porcine postweaning colibacillosis.

OBJECTIVE: To determine whether CHEMYDERTM polymer has potential for use in the control of porcine postweaning colibacillosis (PWC). PROCEDURE: Two experiments were conducted in which 50 young pigs, either receiving CHEMYDERTM polymer in their food or not, were challenged orally with cultures of beta-haemolytic Escherichia coli immediately after weaning. Their response in terms of development of diarrhoea, and the extent of colonisation of the intestinal tract by the bacteria was monitored. In a third experiment CHEMYDERTM polymer was added to the water supply of a group of 15 pigs on a piggery where PWC was an ongoing clinical problem. The response of these pigs was compared with that of pigs vaccinated against PWC or left unmedicated. RESULTS: In both experimental infection trials the pigs receiving CHEMYDERTM polymer showed significantly reduced intestinal colonisation with the challenge strain of E coli, and, in trial 2, significantly less diarrhoea after weaning compared to pigs not receiving CHEMYDERTM polymer. In the field trial the pigs receiving CHEMYDERTM polymer had significantly less diarrhoea and required significantly less antibiotic treatment than the other two groups of pigs. CONCLUSION: CHEMYDERTM polymer has potential for use in the control of PWC.

Acrolein↗

PubMed1987

Inhibition of secretory granule discharge during exocytosis in sea urchin eggs by polymer solutions.

1. We have investigated the effects of the osmotic pressure exerted by polymer solutions on exocytosis in sea urchin eggs. 2. Exocytosis is prevented by including a variety of polymers of different chemical composition and molecular weight in the sea water surrounding the eggs. Inhibition is complete at a polymer osmolality of 250 mosmol/kg. 3. The increase in membrane capacitance which occurs during exocytosis and which corresponds to the fusion of secretory granules with the plasma membrane is not substantially altered by inhibitory concentrations of polymer. 4. In the absence of the ions present in sea water, these polymers inhibit exocytosis at an osmolality of 950 mosmol/kg. 5. Calcium, magnesium and sodium ions reduce the polymer osmolality required to prevent exocytosis. 6. A comparison of the effects of monovalent and divalent ions indicates that the divalent ions bind to and stabilize the secretory granule contents. 7. These results demonstrate that polymers prevent exocytosis by preventing dispersal of the granule contents once fusion of the secretory granule with the plasma-lemma has occurred. The ions present in sea water do not promote dispersal, rather, they hinder it. The contribution of ionic fluxes to granule swelling during exocytosis is discussed.

Animals↗

PubMed2006

Basic investigations on the performance of a normoxic polymer gel with tetrakis-hydroxy-methyl-phosphonium chloride as an oxygen scavenger: reproducibility, accuracy, stability, and dose rate dependence.

Magnetic resonance (MR)-based polymer gel dosimetry using normoxic polymer gels, represents a new dosimetric method specially suited for high-resolution three-dimensional dosimetric problems. The aim of this study was to investigate the dose response with regard to stability, accuracy, reproducibility, and the dose rate dependence. Tetrakis-hydroxy-methyl-phosphonium chloride (THPC) is used as an oxygen scavenger, and methacrylic acid as a monomer. Accuracy, reproducibility, and dose resolution were determined for MR protocols at low spatial resolution (typical for clinical scanners), medium, and microimaging-resolution protocols at three different dose levels. The dose-response stability and preirradiation-induced variations in R2, related to the time interval between preparation and irradiation of the polymer gel, were investigated. Also postirradiation stability of the polymer gel was considered. These experiments were performed using a 60Co beam (E = 1.2 MV) in a water phantom. Moreover, we investigated the dose rate dependence in the low, medium, and saturation dose region of the normoxic polymer gel using a linear accelerator at photon energy of 25 MV. MR scanning was performed on a 3 T whole body scanner (MEDSPEC 30/80, BRUKER BIOSPIN, Ettlingen, Germany) using several coils and different gradient systems adapted to the acquired spatial resolution investigated. For T2-parameter selective imaging and determination of the relaxation rate R2 = 1/T2, a multiple spin echo sequence with 20 equidistant echoes was used. With regard to preirradiation induced variations R2 increases significantly with the increasing time interval between the polymer gel preparation and irradiation. Only a slight increase in R2 can be observed for varying the postirradiation-time solely. The dose reproducibility at voxel volumes of about 1.4 x 1.4 x 2 mm3 is better than 2%. The accuracy strongly depends on the calibration curve. THPC represents a very effective oxygen scavenger in methacrylic acid and gelatin. Polymer gels containing THPC offer high sensitivity to dose but their dose response also strongly depends on dose rate in the medium and high dose region.

Animals↗

PubMed2005

Generation of rituximab polymer may cause hyper-cross-linking-induced apoptosis in non-Hodgkin's lymphomas.

PURPOSE: Although Rituximab has produced significant tumor regressions in lymphoma patients, only 50% respond. Clinically, it has been shown that the major mechanism of action of Rituximab is antibody-dependent cytotoxicity requiring presentation by Fc-bearing cells. To improve the clinical efficacy of Rituximab for the treatment of CD20+ lymphomas, we now describe a new formulation of Rituximab, which, on direct binding to target, can induce apoptosis. METHODS: In this report, enhanced apoptosis was observed by treating CD20+ lymphoma cells with a new polymer formulation of Rituximab. The polymer was produced by formation of a peptide bond using the sugar moiety of dextran (MW 6,000) to generate a clinically relevant reagent for use in vivo. RESULTS: Comparison of Rituximab with a previously described dimer and the newly generated polymer shows that the polymer induced apoptosis more effectively in CD20+ cells as shown by the terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling assay (Rituximab, 3%; dimer, 3%; polymer, 58%). Consistent with these results, the polymer produced marked regression in CD20+ lymphoma xenografts, whereas the dimer and monomer reagents showed little effect. In addition, we were able to show that the level of apoptosis induced in human lymphoma cell lines was in accordance with the extent of both surface CD20 clustering and caspase-3 activation. CONCLUSIONS: These data suggest that hyper-cross-linking-induced apoptosis can be simulated by the use of a dextran polymer of Rituximab, which, when used in vivo, can directly kill CD20+ lymphoma cells and improve the clinical efficacy of this important therapeutic for human B-cell lymphomas.

Animals↗

PubMed1996

Marked inflammatory sequelae to implantation of biodegradable and nonbiodegradable polymers in porcine coronary arteries.

BACKGROUND: With the thrombogenic tendency and permanent implant nature of metallic stents, synthetic polymers have been proposed as candidate materials for stents and local drug delivery designs. We investigated the biocompatibility of several synthetic polymers after experimental placement in the coronary artery. METHODS AND RESULTS: Five different biodegradable polymers (polyglycolic acid/polylactic acid [PGLA], polycaprolactone [PCL], polyhydroxybutyrate valerate [PHBV], polyorthoester [POE], and polyethyleneoxide/polybutylene terephthalate [PEO/ PBTP]) and three nonbiodegradable polymers (polyurethane [PUR], silicone [SIL], and polyethylene terephthalate [PETP]) were tested as strips deployed longitudinally across 90 degrees of the circumferential surface of coil wire stents. Appropriately sized polymer-loaded stents were implanted in porcine coronary arteries of 2.5- to 3.0-mm diameter. Four weeks after implantation, stent patency was assessed by angiography followed by microscopic examination of the coronary arteries. The biodegradable PCL, PHBV, and POE and the nonbiodegradable PUR and SIL evoked extensive inflammatory responses and fibrocellular proliferation (thickness of tissue response: 0.79 +/- 0.22, 1.12 +/- 0.01, 2.36 +/- 0.60, 1.24 +/- 0.36, and 1.43 +/- 0.15 mm, respectively). Less but still severe responses were observed for the biodegradable PGLA and PEO/PBTP (0.46 +/- 0.18 and 0.61 +/- 0.23 mm, respectively) and for the nonbiodegradable PETP (0.46 +/- 0.11 mm). CONCLUSIONS: An array of both biodegradable and nonbiodegradable polymers has been demonstrated to induce a marked inflammatory reaction within the coronary artery with subsequent neointimal thickening, which was not expected on the basis of in vitro tests. The observed tissue response may be attributable to a combination of parent polymer compound, biodegradation products, and possibly implant geometry.

Animals↗