Poly Ether Urethane Research Articles

Influence of the molecular mass of soft segments on the thermodynamic stability and physicomechanical properties of plasticized polyether urethane

The physicomechanical properties and thermodynamic stability of segmented polyether urethane containing poly(tetramethylene oxide) segments of different molecular masses (М ∼ 1000, 1400, 1950) and plasticized with di(2-ethylhexyl) sebacate were analyzed in relation to the molecular mass of the soft segments, and the glass transition point of the soft phase of the polymer was determined. Based on the results obtained, a rapid method was suggested for experimental determination of the osmotic pressure (up to ∼1000 kPa) in the polymer–plasticizer system. The possibilities of preparing thermodynamically stable plasticized materials of high strength (up to 22–26 MPa) with the glass transition point as low as–95 to–100°С were demonstrated.

Characteristics of polyether urethanes with mixed soft segments, prepared by two- and three-step procedures

A three-step procedure for preparing polyurethanes with mixed polyether segments was suggested. It involves preparation of the “inverse” prepolymer by the reaction of one of oligodiisocyanates with 1,4-butanediol taken in a double excess, followed by the reaction with the other oligodiisocyanate. Polyurethanes with alternating poly(tetramethylene oxide) and poly(propylene oxide) soft segments were prepared by this procedure. Such materials surpass polyurethanes prepared from a mixture of oligodiisocyanates in the strength and softening point of the hard phase. In contrast to poly(tetramethylene oxide) urethane, elastomers with mixed polyether segments do not crystallize.

Fibronectin adsorption on surface-modified polyetherurethanes and their differentiated effect on specific blood elements related to inflammatory and clotting processes.

After the introduction of a medical device into the body, adhesive proteins such as fibronectin (Fn) will adsorb to the surface of the biomaterial. Monocytes (MCs) will interact with these adsorbed proteins, and adopt either a proinflammatory and/or prowound healing phenotype, thereby influencing many blood interaction events including thrombogenesis. In this work, Fn adsorption as well as subsequent MC response and thrombus formation were investigated on two surfaces-modified polyetherurethanes (PEUs) using different surface modifiers: an anionic/dihydroxyl oligomeric (ADO) additive, known to enable cell adhesion, and a fluorinated polypropylene oxide oligomer (PPO), known to reduce platelet adhesion. Results indicated that at 24 h of MC culture, PEU-ADO and PEU-PPO promoted an anti-inflammatory character relative to the base PEU. Longer clotting times, based on a free hemoglobin assay, were also found on the two surface-modified PEUs relative to the native one, suggesting their potential for the reduction of thrombus formation. In presence of a Fn monolayer, the surface-modified PEUs conserved a lower thrombogenic character than the base PEU, and was however significantly decreased when compared to prior protein adsorption. Furthermore, Fn coatings increased the MC production levels of tumor necrosis factor-α and interleukin-10 at 24 h, while not affecting the anti-inflammatory effect of the modifications relative to the base PEU. This finding was most prominent on PEU-PPO, suggesting that the interaction of the adsorbed Fn with blood cells was different for the two additives. Hence, the results highlighted differentiating effects of Fn adsorption on specific blood activating processes related to inflammatory and thrombotic responses.

Protein adsorption capability on polyurethane and modified-polyurethane membrane for periodontal guided tissue regeneration applications

Periodontal disease if left untreated can result in creation of defects within the alveolar ridge. Barrier membranes are frequently used with or without bone replacement graft materials for achieving periodontal guided tissue regeneration (GTR). Surface properties of barrier membranes play a vital role in their functionality and clinical success. In this study polyetherurethane (PEU) membranes were synthesized by using 4,4′-methylene-diphenyl diisocyanate (MDI), polytetramethylene oxide (PTMO) and 1,4-butane diol (BDO) as a chain extender via solution polymerization. Hydroxyl terminated polydimethylsiloxane (PDMS) due to having inherent surface orientation towards air was used for surface modification of PEU on one side of the membranes. This resulting membranes had one surface being PEU and the other being PDMS coated PEU. The prepared membranes were treated with solutions of bovine serum albumin (BSA) in de-ionized water at 37°C at a pH of 7.2. The surface protein adsorptive potential of PEU membranes was observed using Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), Raman spectroscopy and Confocal Raman spectroscopy. The contact angle measurement, tensile strength and modulus of prepared membranes were also evaluated. PEU membrane (89.86±1.62°) exhibited less hydrophobic behavior than PEU-PDMS (105.87±3.16°). The ultimate tensile strength and elastic modulus of PEU (27±1MPa and 14±2MPa) and PEU-PDMS (8±1MPa and 26±1MPa) membranes was in required range. The spectral analysis revealed adsorption of BSA proteins on the surface of non PDMS coated PEU surface. The PDMS modified PEU membranes demonstrated a lack of BSA adsorption. The non PDMS coated side of the membrane which adsorbs proteins could potentially be used facing towards the defect attracting growth factors for periodontal tissue regeneration. Whereas, the PDMS coated side could serve as an occlusive barrier for preventing gingival epithelial cells from proliferating and migrating into the defect space by facing the soft tissue flaps. This study demonstrates the potential of a dual natured PEU barrier membrane for use in periodontal tissue engineering applications and further investigations are required.

Environmental stress cracking performance of polyether and PDMS-based polyurethanes in an in vitro oxidation model.

Environmental stress cracking (ESC) was replicated in vitro on Optim™ (OPT) insulation, a polydimethylsiloxane-based polyurethane utilized clinically in cardiac leads, using a Zhao-type oxidation model. OPT performance was compared to that of two industry standard polyether urethanes: Pellethane® 80A (P80A), and Pellethane® 55D (P55D). Clinically relevant specimen configurations and strain states were utilized: low-voltage cardiac lead segments were held in a U-shape by placing them inside of vials. To study whether aging conditions impacted ESC formation, half of the samples were subjected to a pretreatment in human plasma for 7 days at 37°C; all samples were then aged in oxidative solutions containing 0.9% NaCl, 20% H2 O2 , and either 0 or 0.1M CoCl2 , with or without glass wool for 72 days at 37°C. Visual and SEM inspection revealed significant surface cracking consistent with ESC on all P80A and P55D samples. Sixteen of twenty P80A and 10/20 P55D samples also exhibited breaches. Seven of 20 OPT samples exhibited shallow surface cracking consistent with ESC. ATR-FTIR confirmed surface changes consistent with oxidation for all materials. The number average molecular weight decreased an average of 31% for OPT, 86% for P80A, and 56% for P55D samples. OPT outperformed P80A and P55D in this Zhao-type in vitro ESC model. An aging solution of 0.9% NaCl, 20% H2 O2 , and 0.1M CoCl2 , with glass wool provided the best combination of ESC replication and ease of use. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1544-1558, 2017.

Fibronectin adsorption on surface modified polyetherurethanes for blood-contacting applications

Event Abstract Back to Event Fibronectin adsorption on surface modified polyetherurethanes for blood-contacting applications Ludivine Hugoni1, 2, Vanessa Montaño-Machado1, 2, Emmanuel Pauthe2, Diego Mantovani1 and J Paul Santerre3 1 CHU de Québec Research Center, Laval University, Lab. Biomaterials and Bioengineering, CRC-I, Dept Min-Met-Materials Eng, Canada 2 University of Cergy Pontoise, Equipe de Recherche sur les Relations Matrice Extracellulaire-Cellules, France 3 University of Toronto, Institute of Biomaterials and Biomedical Engineering, Canada Introduction: After the implantation of a medical device, adhesive proteins such as fibronectin (FN) are adsorbed to the surface of the material[1]. These are the biomolecules that monocytes (MCs) will interact with, to adopt a pro-inflammatory or pro-wound healing phenotype[2]. Hence, it was desired to study FN coatings on two surface modified polyetherurethanes (PEUs) with potential blood-contacting applications, to mimic the biological environment. A fluorinated surface modifying oligomer (PPO212L), known to reduce platelet adhesion[3] and an anionic/dihydroxy oligomeric (ADO) additive, known to enable cell adhesion[4] were used to modify surface blood cell compatibility of a commercial PEU. FN adsorption and the subsequent MC inflammatory response was investigated on the two modified PEUs. Materials and Methods: The PEU was prepared by dissolving Tecoflex® 65D in 10 % (wt/v) chloroform. PPO212L or ADO was added at 0.5 % (wt/wt). Solutions were casted on PTFE for 24 h followed by 2 h in vacuum (30 mmHg), both at room temperature. Protein adsorption was performed with a FN solution (50 μg.mL-1 in HEPES 10 mM, pH 7.4) at 37 °C for 30 min. Surfaces were characterized by water contact angle (WCA), atomic force microscopy (AFM) and immunofluorescence staining (IFS). Adsorbed FN was quantified by a bicinchoninic acid assay. MCs, isolated from blood of healthy donors (University of Toronto ethics protocol #22203) were seeded on PEUs (106 cells.mL-1). After 72 h of culture, the viability of adhered MCs was evaluated by Alamar blue® assay and cell morphology was analyzed by scanning electron microscopy (SEM). Results were given as mean ± standard deviation (SD) and were statistically analyzed by one-way analysis of variance (ANOVA), with significant differences reported for p<0.05. Results and Discussion: On all PEUs, FN adsorption significantly decreased the WCA whereas surface roughness increased approximately 2 fold (Table 1). No statistically significant difference was observed for the amount of adsorbed FN (Table 1) corroborating the presence of a protein monolayer to surfaces[5]. The difference in WCA prior vs after FN adsorption was greatest for the base PEU and PEU-ADO. This result suggested a different FN conformation on PEU-PPO212L than on the two other surfaces. The availability of FN cell binding domains for all coated PEUs was observed after IFS (data not shown). Preliminary tests with MCs showed that all FN-coated PEUs significantly increased MC viability, without affecting cell morphology except for PEU-ADO (Figure 1). These results suggested that FN activated MCs more extensively on PEU-ADO than on the base PEU and PEU-PPO212L, which showed the least activated morphology of all surfaces. Conclusions: A comparative study of two surface modified PEUs, PEU-PPO212L and PEU-ADO, intended for blood-contacting applications was performed. Investigations suggested that FN-coated PEU-PPO212L has less influence on MC activation than FN-coated PEU-ADO. Further investigations are ongoing to determine the effect of FN coating on cell production of cytokines such as pro-inflammatory tumor necrosis factor-α (TNF-α) and anti-inflammatory interleukin 10 (IL-10). This work was supported by a MSc Scholarship from NSERC CREATE Program in Regenerative Medicine (www.ncprm.ulaval.ca), NSERC, CIHR, Fonds Samuel de Champlain, FQRS, and FQRNT; The authors would like to thank Pascale Chevallier and Lucie Levesque for their technical assistance

In-vitro study of the effects of oxidative degradants on thermoplastic polyurethanes

In-vitro study of the effects of oxidative degradants on thermoplastic polyurethanes

Thermal and nano-mechanical characterisation of polyurethane scaffolds: comparison of solvent cast, melt processed and electrospun forms

Event Abstract Back to Event Thermal and nano-mechanical characterisation of polyurethane scaffolds: comparison of solvent cast, melt processed and electrospun forms Milovan Cardona1, Davide Erbogasto1 and Richard A. Black1 1 University of Strathclyde, Department of Biomedical Engineering, United Kingdom Introduction: Cell behaviour is regulated by numerous environmental parameters related to the composition, surface topography and nano-mechanical properties of the extracellular matrix[1]. Cells grow preferentially on specialised microstructures that imitate their original extracellular matrix, the chemical and mechanical properties of which been tailored to mimic the cells’ original environment. This study aims to relate differences in microstructure of polyurethane scaffolds, prepared by means of three different processing techniques, to changes in mechanical properties measured on the micron and nano length scales. Materials and Methods: The following forms of medical grade polyurethane (b9 ‘A’ series thermoplastic poly-ether urethanes, Biomer Technology Ltd., Runcorn, UK) were compared: melt processed polymer, solvent-cast films and sub-micron fibres fabricated by electrospinning. Comparison of the thermal and mechanical properties was made by differential scanning calorimetry (DSC) and nanoindentation, whereas the fibre morphology and surface roughness were quantified by scanning electron (SEM) and atomic force microscopy (AFM), respectively. Results and Discussion: Thermal analysis of each of the polymer forms revealed differences in polymer microstructure (Fig. 1). Whereas two distinct endotherms of approximately equal size are evident in the thermograms of melt-processed samples, suggesting an equal distribution of type I and type II hard segment crystallites, solvent-cast films demonstrate a larger type I endotherm, indicating increased hard segment phase mixing. In contrast, the electrospun fibrous forms exhibit a larger type II endotherm, suggesting a greater degree of phase separation in those samples, which may be attributed to the manner in which the fibres are formed. Figure 1. Thermal analysis (DSC) of the same polyurethane processed by each method. A two-fold increase in stiffness, as measured by nanoindentation, was observed, with electrospun forms demonstrating an average modulus of 12.3 ± 5.8 GPa compared to solvent-cast films (5.88 ± 0.91 GPa). This increase may be attributed in part to differences in microstructure revealed by DSC. Figure 2. Comparison of electrospun and cast forms by means of AFM (top row), SEM (bottom left) and Nanoindentation (bottom right). Conclusion: Thermal analysis of polyurethane films cast from solvent, melt processed pellets and microfibrous scaffolds fabricated by means of electrospinning, reveal differences in polymer microstructure, which we attribute to the method of processing in each case. Further studies are warranted in order to determine the extent to which the degree of phase separation has on protein and cell-surface interactions. The findings of these studies may have a bearing on biomaterials selection and scaffold design. The authors acknowledge the support of the Scottish Funding Council and the UK Engineering & Physical Sciences Research Council (EPSRC) Doctoral Training Centre in Medical Devices, University of Strathclyde (EPSRC Grant Ref. EP/F50036X/1) for the studentships awarded to MC and DE, respectively

Effect of an organosilicon modifier on the structure of polyether urethanes

Structures of amorphous polyether urethanes modified with oligomeric organosilicon blocks are studied via AFM, SEM, and TEM. The main structural unit of the investigated polymers is found to be a globule. The effect the silicon modifier has on the polyether urethane structure is determined.

An Intravaginal Ring for the Simultaneous Delivery of an HIV-1 Maturation Inhibitor and Reverse-Transcriptase Inhibitor for Prophylaxis of HIV Transmission

Nucleocapsid 7 (NCp7) inhibitors have been investigated extensively for their role in impeding the function of HIV-1 replication machinery and their ability to directly inactivate the virus. A class of NCp7 zinc finger inhibitors, S-acyl-2-mercaptobenzamide thioesters (SAMTs), was investigated for topical drug delivery. SAMTs are inherently unstable because of their hydrolytically labile thioester bond, thus requiring formulation approaches that can lend stability. We describe the delivery of N-[2-(3,4,5-trimethoxybenzoylthio)benzoyl]-β-alaninamide (SAMT-10), as a single agent antiretroviral (ARV) therapeutic and in combination with the HIV-1 reverse-transcriptase inhibitor pyrimidinedione IQP-0528, from a hydrophobic polyether urethane (PEU) intravaginal ring (IVR) for a month. The physicochemical stability of the ARV-loaded IVRs was confirmed after 3 months at 40°C/75% relative humidity. In vitro, 25 ± 3 mg/IVR of SAMT-10 and 86 ± 13 mg/IVR of IQP-0528 were released. No degradation of the hydrolytically labile SAMT-10 was observed within the matrix. The combination of ARVs had synergistic antiviral activity when tested in in vitro cell-based assays. Toxicological evaluations performed on an organotypic EpiVaginal(™) tissue model demonstrated a lack of formulation toxicity. Overall, SAMT-10 and IQP-0528 were formulated in a stable PEU IVR for sustained release. Our findings support the need for further preclinical evaluation. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3426-3439, 2015.

Modeling of stress relaxation of a semi-crystalline multiblock copolymer and its deformation behavior.

Stress relaxation can strongly influence the shape-memory capability of polymers. Recently a modified Maxwell-Wiechert model comprising two Maxwell units and a single spring unit in parallel has been introduced to successfully describe the shape recovery characteristics of amorphous polyether urethanes. In this work we explored whether such a modified Maxwell-Wiechert model is capable to describe the stress relaxation behavior of a semi-crystalline multiblock copolymer named PCL-PIBMD, which consists of crystallizable poly(ɛ-caprolactone) (PCL) segments and crystallizable poly(3S-isobutylmorpholine-2,5-dione) (PIBMD) segments. The stress relaxation behavior of PCL-PIBMD was explored after uniaxial deformation to different strains ranging from 50 to 900% with various strain rates of 1 or 10 or 50 mm·min -1. The modeling results indicated that under the assumption that in PCL-PIBMD both PCL and PIBMD blocks have narrow molecular weight distributions and are arranged in sequence, the two relaxation processes can be related to the amorphous PCL and PIBMD domains and the spring element can be associated to the PIBMD crystalline domains. The first Maxwell unit representing the faster relaxation process characterized by the modulus E1 and the relaxation time τ1 is related to the amorphous PCL domains (which are in the rubbery state), while the second Maxwell unit (E2 ; τ2) represents the behavior of the amorphous PIBMD domains, which are in the glassy state at 50 °C. Increasing strain rates resulted in an increase of E1 and a significant reduction in τ1, whereas the elastic modulus as well as the relaxation time related to the amorphous PIBMD domains remained almost constant. When a higher deformation was applied (ɛ ≥ 200% ) lower values for the elastic moduli of the three model elements were obtained. In general the applied model was also capable to describe the relaxation behavior of PCL-PIBMD at a deformation temperature of 20 °C, where additional crystalline PCL domains are existent. The presented approach using a modified Maxwell-Wiechert model to analyze the stress relaxation behavior can be useful to understand the changes in structure-function relation of amorphous as well as semi-crystalline polymers occurring during its uniaxial deformation.

Development of polyether urethane intravaginal rings for the sustained delivery of hydroxychloroquine.

Hydroxychloroquine (HCQ) has been shown to demonstrate anti-inflammatory properties and direct anti-HIV activity. In this study, we describe for the first time the fabrication and in vitro evaluation of two types of intravaginal ring (IVR) devices (a surfaced-modified matrix IVR and a reservoir segmental IVR) for achieving sustained delivery (>14 days) of HCQ as a strategy for preventing male-to-female transmission of HIV. Both IVRs were fabricated by hot-melt injection molding. Surface-modified matrix IVRs with polyvinylpyrrolidone or poly(vinyl alcohol) coatings exhibited significantly reduced burst release on the first day (6.45% and 15.72% reduction, respectively). Reservoir IVR segments designed to release lower amounts of HCQ displayed near-zero-order release kinetics with an average release rate of 28.38 μg/mL per day for IVRs loaded with aqueous HCQ and 32.23 μg/mL per day for IVRs loaded with HCQ mixed with a rate-controlling excipient. Stability studies demonstrated that HCQ was stable in coated or noncoated IVRs for 30 days. The IVR segments had no significant effect on cell viability, pro-inflammatory cytokine production, or colony formation of vaginal and ectocervical epithelial cells. Both IVR systems may be suitable for the prevention of HIV transmission and other sexually transmitted infections.

Electrospun polyurethane as an alternative ventricular catheter and invitro model of shunt obstruction.

Intracranial pressure and volume vary considerably between hydrocephalic patients, and with age, health and haemodynamic status; if left untreated, intracranial pressure rises and the ventricular system expands to accommodate the excess cerebrospinal fluid, with significant morbidity and mortality. Cerebrospinal fluid shunts in use today have a high incidence of failure with shunt obstruction being the most serious. Conventional proximal shunt catheters are made from poly(dimethyl)siloxane, the walls of which are perforated with holes for the cerebrospinal fluid to pass through. The limited range of catheters, in terms of material selection and flow distribution, is responsible in large part for their poor performance.In this study, we present an alternative design of proximal catheter made of electrospun polyether urethane, and evaluate its performance in the presence of glial cells, which are responsible for shunt blockage. The viability and growth of cells on catheter materials such as poly(dimethyl)siloxane and polyurethane in the form of cast films, microfibrous mats and porous sponges were studied in the presence of proteins present in cerebrospinal fluid after 48 h and 96 h in culture. The numbers of viable cells on each substrate were comparable to untreated poly(dimethyl)siloxane, both in the presence and absence of serum proteins found in cerebrospinal fluid. A cell culture model of shunt obstruction was developed in which cells on electrospun polyether urethane catheters were subjected to flow during culture in vitro, and the degree of obstruction quantified in terms of hydraulic permeability after static and perfusion culture. The results indicate that a catheter made of electrospun polyether urethane would be able to maintain cerebrospinal fluid flow even with the presence of cells for the time period chosen for this study. These findings have implications for the design and deployment of microporous shunt catheter systems for the treatment of hydrocephalus.

Polyether Urethane Hydrolytic Stability after Exposure to Deoxygenated Water

A medical grade, commercially available polyether urethane, denoted PEU 80A, was exposed to both real time (37 °C) and temperature accelerated (55, 70, and 85 °C) hydrolysis conditions for a period...

Electrospun polyurethane/hydroxyapatite bioactive Scaffolds for bone tissue engineering: The role of solvent and hydroxyapatite particles

Polyurethane (PU) is a promising polymer to support bone–matrix producing cells due to its durability and mechanical resistance. In this study two types of medical grade poly-ether urethanes Z3A1 and Z9A1 and PU-Hydroxyapatite (PU–HA) composites were investigated for their ability to act as a scaffold for tissue engineered bone. PU dissolved in varying concentrations of dimethylformamide (DMF) and tetrahydrofuran (THF) solvents were electrospun to attain scaffolds with randomly orientated non-woven fibres.Bioactive polymeric composite scaffolds were created using 15wt% Z3A1 in a 70/30 DMF/THF PU solution and incorporating micro- or nano-sized HA particles in a ratio of 3:1 respectively, whilst a 25wt% Z9A1 PU solution was doped in ratio of 5:1. Chemical properties of the resulting composites were evaluated by FTIR and physical properties by SEM. Tensile mechanical testing was carried out on all electrospun scaffolds. MLO-A5 osteoblastic mouse cells and human embryonic mesenchymal progenitor cells, hES-MPs were seeded on the scaffolds to test their biocompatibility and ability to support mineralised matrix production over a 28 day culture period. Cell viability was assayed by MTT and calcium and collagen deposition by Sirius red and alizarin red respectively.SEM images of both electrospun PU scaffolds and PU–HA composite scaffolds showed differences in fibre morphology with changes in solvent combinations and size of HA particles. Inclusion of THF eliminated the presence of beads in fibres that were present in scaffolds fabricated with 100% DMF solvent, and resulted in fibres with a more uniform morphology and thicker diameters. Mechanical testing demonstrated that the Young׳s Modulus and yield strength was lower at higher THF concentrations. Inclusion of both sizes of HA particles in PU–HA solutions reinforced the scaffolds leading to higher mechanical properties, whilst FTIR characterisation confirmed the presence of HA in all composite scaffolds.Although all scaffolds supported proliferation of both cell types and deposition of calcified matrix, PU–HA composite fibres containing nano-HA enabled the highest cell viability and collagen deposition. These scaffolds have the potential to support bone matrix formation for bone tissue engineering.

Intravaginal flux controlled pump for sustained release of macromolecules.

To design a flux controlled pump (FCP) capable of 30-day, controlled release of macromolecules to the vaginal mucosa. The FCP is composed of a single chamber fabricated from a rigid thermoplastic with orifices and encloses a pellet of water-swellable polymer containing the drug substance. We performed testing both in vitro and in rabbits. To ensure vaginal retention in the rabbit, we designed and attached an oval shape-memory polyether urethane retainer to the FCP allowing for long-term intravaginal evaluation of a solid dosage form without invasive surgical implantation. The orifices and swelling properties of the polymer pellet control water entry for polymer hydration and expansion, and subsequent extrusion of the drug-containing gel from the orifice. A FCP device containing a pellet composed of hydroxypropyl cellulose compounded with a model macromolecule, achieved controlled in vitro release for 30days with an average release rate of 24 ± 2μg/day (mean ± SD) and range of 16 to 42μg/day. We observed a slightly lower average release rate in vivo of 20 ± 0.6μg/day (mean ± SD). The size of the orifice and nature of the swelling polymer controls the hydration rate and thereby macromolecule release rate and duration from this FCP.

In vivo quantitative and qualitative assessment of foreign body giant cell formation on biomaterials in mice deficient in natural killer lymphocyte subsets, mast cells, or the interleukin‐4 receptorα and in severe combined immunodeficient mice

In previous studies that explored the influence of cytokines on foreign body giant cell (FBGC) formation, we focused on interleukin (IL)-4 and IL-13, each of which was discovered to induce macrophage fusion leading to FBGC formation in vitro. Two correlative in vivo studies also confirmed that IL-4 plays a role in FBGC formation on implanted biomaterials, but that T lymphocytes are not the source of IL-4 or other cytokines that support this process. The present study focused on identification of the cellular source of macrophage fusion-inducing cytokines, including natural killer (NK) or NKT lymphocytes and mast cells using mouse models genetically deficient in each of these cell types, as well as IL-4 receptor alpha(IL-4Rα)-deficient and severe combined immunodeficient (SCID) mice. Polyetherurethane (PEU) and polyethylene terephthalate (PET) polymers were subcutaneously implanted and retrieved after 14, 21, or 28 days. FBGC formation was evaluated using quantitative and qualitative data from retrieved polymer surfaces. Both types of data indicate that, compared to normal control mice, neither NK or NKT lymphocytes nor mast cells are required for FBGC formation. Furthermore, FBGC formation on biomaterials can proceed in IL-4Rα-deficient and in SCID mice. Similar conclusions were made regarding FBGC formation on both PEU and PET biomaterials. These data suggest that other sources of IL-4/IL-13 and/or additional macrophage fusion-inducing cytokines can mediate FBGC formation on implanted biomaterials, or that, in the absence of normal primary pathways, FBGC formation is nevertheless supported by redundant innate mechanisms.

Photopolymerization Kinetics of Block Polyether Based Terminal Urethane Methacrylate with/without Cross‐Linker

ABSTRACTThe present work deals with the photopolymerization of difunctional macromonomer with a polyether chain and urethane methacrylate terminations. Macromonomeric formulations were prepared by mixing macromonomer with two different concentrations of photoinitiator. Formulations were also prepared by the addition of 10 wt% of soft‐segmented difunctional cross‐linker to the abovementioned macromonomic formulations. All formulations were then subjected to photopolymerization studies and the effects of light intensity on the photopolymerization kinetics were studied at two different isothermal conditions using photo differential scanning calorimetry (Photo DSC) with polychromatic radiation. The isothermal heat flow against time was recorded for all formulations and the kinetic parameters were noted. It was observed that the rate of maximum polymerization as well as peak maximum time showed a general trend. However, the ultimate conversion as well as the conversion at maximum rate did not show any trend due to diffusional restrictions imparted by the increase in viscosity with conversion. The photopolymerization of the formulations and curing kinetics including evaluation of autocatalytic model are discussed.

Engineering a Segmented Dual-Reservoir Polyurethane Intravaginal Ring for Simultaneous Prevention of HIV Transmission and Unwanted Pregnancy

The HIV/AIDS pandemic and its impact on women prompt the investigation of prevention strategies to interrupt sexual transmission of HIV. Long-acting drug delivery systems that simultaneously protect womenfrom sexual transmission of HIV and unwanted pregnancy could be important tools in combating the pandemic. We describe the design, in silico, in vitro and in vivo evaluation of a dual-reservoir intravaginal ring that delivers the HIV-1 reverse transcriptase inhibitor tenofovir and the contraceptive levonorgestrel for 90 days. Two polyether urethanes with two different hard segment volume fractions were used to make coaxial extruded reservoir segments with a 100 µm thick rate controlling membrane and a diameter of 5.5 mm that contain 1.3 wt% levonorgestrel. A new mechanistic diffusion model accurately described the levonorgestrel burst release in early time points and pseudo-steady state behavior at later time points. As previously described, tenofovir was formulated as a glycerol paste and filled into a hydrophilic polyurethane, hollow tube reservoir that was melt-sealed by induction welding. These tenofovir-eluting segments and 2 cm long coaxially extruded levonorgestrel eluting segments were joined by induction welding to form rings that released an average of 7.5 mg tenofovir and 21 µg levonorgestrel per day in vitro for 90 days. Levonorgestrel segments placed intravaginally in rabbits resulted in sustained, dose-dependent levels of levonorgestrel in plasma and cervical tissue for 90 days. Polyurethane caps placed between segments successfully prevented diffusion of levonorgestrel into the tenofovir-releasing segment during storage.Hydrated rings endured between 152 N and 354 N tensile load before failure during uniaxial extension testing. In summary, this system represents a significant advance in vaginal drug delivery technology, and is the first in a new class of long-acting multipurpose prevention drug delivery systems.

In vitro Endothelialization and Platelet Adhesion on Titaniferous Upgraded Polyether and Polycarbonate Polyurethanes.

Polycarbonateurethanes (PCU) and polyetherurethanes (PEU) are used for medical devices, however their bio- and haemocompatibility is limited. In this study, the effect of titaniferous upgrading of different polyurethanes on the bio- and haemocompatibility was investigated by endothelial cell (EC) adhesion/proliferation and platelet adhesion (scanning electron microscopy), respectively. There was no EC adhesion/proliferation and only minor platelet adhesion on upgraded and pure PCU (Desmopan). PEUs (Texin 985, Tecothane 1085, Elastollan 1180A) differed in their cyto- and haemocompatibility. While EC adhesion depended on the type of PEU, any proliferative activity was inhibited. Additional titaniferous upgrading of PEU induced EC proliferation and increased metabolic activity. However, adherent ECs were significantly activated. While Texin was highly thrombotic, only small amounts of platelets adhered onto Tecothane and Elastollan. Additional titaniferous upgrading reduced thrombogenicity of Texin, preserved haemocompatibility of Elastollan, and increased platelet activation/aggregation on Tecothane. In conclusion, none of the PUs was cytocompatible; only titaniferous upgrading allowed EC proliferation and metabolism on PEUs. Haemocompatibility depended on the type of PU.