Showing papers in "Journal of Biomaterials Science-polymer Edition in 1997"

Mechanical properties of dense polylactic acid structures fabricated by three dimensional printing.

Abstract: Polylactic acid (PLA) is a bioresorbable polymer that is used in a number of clinical situations. Complex shapes of PLA are commonly machined for bone fixation and reconstruction. Solid free from fabrication methods, such as 3D printing, can produce complex-shaped articles directly from a CAD model. This study reports on the mechanical properties of 3D-printed PLLA parts. 3D printing is a solid free-form fabrication process which produces components by ink-jet printing a binder into sequential powder layers. Test bars were fabricated from low and high molecular weight PLA powders with chloroform used as a binder. The binder printed per unit line length of the powder was varied to analyze the effects of printing conditions on mechanical and physical properties of the PLA bars. Furthermore, cold isostatic pressing was performed after printing to improve the mechanical properties of the printed bars. The maximum measured tensile strength for the low molecular weight PLLA (53 000) is 17.40 +/- 0.71 MPa and for high molecular weight PLLA (312 000) is 15.94 +/- 1.50 MPa.

Embolic materials for endovascular treatment of cerebral lesions

Abstract: Recently developed soft microcatheters can be maneuvered endovascularly into the brain, permitting treatment of lesions without conventional neurosurgery. Progress in biomaterial science has contributed significantly to the development of this new therapeutic modality termed intravascular neurosurgery or interventional neuroradiology. Although embolic materials play an important role, ideal materials have yet to be devised. Various embolic materials in clinical use are reviewed, such as cyanoacrylates, ethylene-vinyl alcohol copolymer mixtures, Ethibloc, ethanol, estrogen, poly(vinyl acetate), cellulose acetate polymer, poly(vinyl alcohol), gelatin sponges, microfibrillar collagen, surgical silk sutures, detachable balloons, and coils. The materials are reviewed in the context of treatment application for various brain lesions, such as arteriovenous malformations, cerebral aneurysms, and head and neck tumors. Further developments in biomaterial polymer science can bring about progress against brain diseases.

Synthesis, characterization, biodegradation, and drug delivery application of biodegradable lactic/glycolic acid polymers: I. Synthesis and characterization.

Abstract: A series of lactic/glycolic acid polymers with various molar ratios of lactic to glycolic acid and various molecular weights were synthesized using the ring-opening polymerization method The polymerization conditions for the lactic/glycolic acid polymer synthesis were as follows: 150 degrees C, 700 microm Hg, 3 h, 003 wt% of catalyst (stannous 2-ethyl-hexanoate) concentration The molecular weight of these polymers was controlled by using a molecular weight controller, lauryl alcohol The synthesized polymers have been characterized with respect to polymer composition, molecular weight, inherent viscosity, and glass transition temperature The characterization experiments show a good correlation between the polymer compositions and the feed ratios of lactic to glycolic acid The molecular weight of the lactic/glycolic polymers, ranging from 10,876 to 166,630 D and the intrinsic viscosity of the polymers, ranging from 016 to 086 dl g(-1), are controlled by the amount of molecular weight controller used The effect of the amount of the molecular weight controller on the polymer molecular weight and the polymer inherent viscosity was studied Results indicate that the molecular weight and inherent viscosity of the polymers have a log-log linear relationship with the amount of molecular weight controller used The lactic/glycolic acid polymers are amorphous, glassy, and transparent The glass transition temperature of the polymers range from 2195 to 5129 degrees C, depending on the polymer molecular weight and the composition

Protein release from poly(ε-caprolactone) microspheres prepared by melt encapsulation and solvent evaporation techniques: A comparative study

Abstract: Poly(e-caprolactone) (PCL) microspheres containing c. 3% bovine serum albumin (BSA) were prepared by melt encapsulation and solvent evaporation techniques. PCL, because of its low Tm, enabled the melt encapsulation of BSA at 75°C thereby avoiding potentially toxic organic solvents such as dichloromethane (DCM). Unlike the solvent evaporation method, melt encapsulation led to 100% incorporation efficiency which is a key factor in the microencapsulation of water-soluble drugs. Examination of the stability of the encapsulated protein by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that protein integrity was unaffected by both methods of encapsulation. In vitro release of the protein into phosphate buffer examined at 37 °C from microspheres prepared by both techniques showed that the release rate from melt-encapsulated microspheres was somewhat slower compared to the release from solvent-evaporated spheres. Both released around 20% of the incorporated protein in 2 weeks a...

Temperature- and pH-sensitive terpolymers for modulated delivery of streptokinase

Abstract: Controlled release devices were designed which respond to changes in pH and temperature by reversibly swelling and deswelling to control release of streptokinase. Copolymer hydrogels composed of N-isopropylacrylamide (NIPAAm) and methacrylic acid (MAA) as well as terpolymer hydrogels containing NIPAAm, acrylic acid (AA), and 2-hydroxyethyl methacrylate (HEMA) were synthesized. Hydrogels containing NIPAAm display a change in swelling behavior across the lower critical solubility temperature of PNIPAAm, whereas hydrogels with MAA and AA swelled only at high pH values due to the ionization of carboxylic pendant groups. HEMA was chosen as a third component to add mechanical strength and integrity to the hydrogel. Pulsatile pH- and temperature-dependent swelling studies were performed to determine the extent and rate at which the hydrogels swell in response to changing conditions. Results showed that increasing the NIPAAm concentration in the copolymers or terpolymers resulted in a higher degree of temperature...

Enhanced hydrogel adhesion by polymer interdiffusion: Use of linear poly(ethylene glycol) as an adhesion promoter

Abstract: The fracture energy required to separate layers of hydrogel films was investigated to evaluate the impact of bulk polymer diffusion on hydrogel/hydrogel adhesion and to obtain molecular information on the fracture energy in polymer mucoadhesion. Poly(ethylene glycol) (PEG) was incorporated in a hydrogel and was used as an adhesion promoter. The influence of PEG molecular weight and contact time on PEG diffusion across the hydrogel/hydrogel interface was investigated by using tensiometric studies and near-field FTIR microscopy. These experiments indicated that linear PEG diffusion enhanced the adhesion between the two hydrogel layers. The enhanced adhesion could not be explained by surface wetting phenomena alone. These results indicated that bulk diffusion of linear polymers such as PEG (adhesion promoter) incorporated into polymer networks (hydrogels) was an effective technique for enhancing gel/gel adhesion in various applications including polymer/mucus interactions in mucoadhesion and development of mucoadhesive controlled drug delivery systems.

Characterization of partially saturated poly(propylene fumarate) for orthopaedic application

Abstract: A partially saturated linear polyester based on poly(propylene fumarate) (PPF) was synthesized for potential application in filling skeletal defects. The synthesis was carried out according to a two-step reaction scheme. Propylene glycol and fumaryl chloride were first combined to form an intermediate fumaric diester. The intermediate was then subjected to a transesterification to form the PPF-based polymer. This method allowed for production of a polymer with a number average molecular weight up to 1500 and a polydispersity index of 2.8 and below. The polymeric backbone structure was investigated through the use of FTIR and NMR. Kinetic studies of the transesterification allowed mapping of the molecular weight increase with reaction time. The final product was also characterized by thermal and solubility analysis.

Rifampicin carrying polyhydroxybutyrate microspheres as a potential chemoembolization agent

Abstract: In this study, we attempted to prepare microspheres from a microbial biodegradable polyester, i.e. polyhydroxybutyrate (PHB) as a potential chemoembolization agent. The drug loaded PHB microspheres were prepared by a solvent evaporation technique, in which methylene chloride, distilled water, and polyvinyl alcohol were utilized as the solvent, dispersion medium, and emulsifier, respectively. Microspheres were obtained within a size range of 5-100 microns by changing the initial polymer/solvent ratio, emulsifier concentration, stirring rate, and initial drug concentration. It was possible to obtain PHB with very narrow size distributions by applying gravity field-flow fractionation technique. Very high drug loadings of up to 407.6 mg rifampicin/g PHB were achieved. Drug release rates were very rapid. Almost 90% of the drug loaded was released in about 24 h. Both the size and drug content of PHB microspheres were found to be effective in controlling the drug release from these microspheres.

Synthesis and characterization of biodegradable polyrotaxane as a novel supramolecular-structured drug carrier.

Abstract: Polyrotaxanes were synthesized as novel biodegradable polymers with supramolecular assembly and their properties evaluated in vitro. The synthesis of biodegradable polyrotaxanes consists of three steps: preparation of an inclusion complex consisting of alpha-cyclodextrins (alpha-CDs) and amino-terminated poly(ethylene glycol) (PEG); introduction of L-phenylalanine (L-Phc) at each complex terminal via peptide linkages: and hydroxypropylation of alpha-CDs in the polyrotaxanes. Succinimide ester of benzyloxycarbonyl-L-Phe was condensed with the terminal amino groups of the inclusion complex. 1H-NMR and GPC results showed that alpha-CDs were threaded onto a PEG chain and L-Phe moieties were introduced at each terminal of the PEG chain. Further, the amount of threaded alpha-CDs was found to be governed by the molecular weight of PEG. The hydroxypropylation of alpha-CDs improved the solubility of the polyrotaxanes in PBS (pH 7.4). The hydroxypropylated (HP-) polyrotaxanes were characterized by terminal peptide cleavage using papain. In vitro degradation of HP-polyrotaxanes revealed that HP-alpha-CDs threaded onto a PEG chain were released only when terminal peptide linkages were cleaved. Moreover, threaded HP-alpha-CDs onto a PEG chain was found to be completely released. Kinetics of terminal peptide cleavage were also evaluated by catalytic efficiency (kcat/K(m)). The kcat/K(m) values were found to be independent of the molecular weight of HP-polyrotaxanes but to be affected by terminal hydrophobic moieties. It is proposed that our designed polyrotaxanes are feasible as novel drug carriers.

Stabilization of nerve growth factor in controlled release polymers and in tissue

Abstract: We have studied the release of nerve growth factor (NGF), a protein under consideration for treatment of Alzheimer's Disease, from polymer matrices and microspheres to characterize the stability of NGF, the dynamics of NGF release, and the distribution of NGF within the brain interstitium. Poly(ethylene-co-vinyl acetate) (EVAc) disks and poly(L-lactic acid) (PLA) microspheres were formed by codispersing NGF with one of a variety of molecules. The mass of mouse NGF (mNGF) detected following release from EVAc disks into buffered saline varied five-fold over the range of codispersants studied, with carboxymethyldextran providing optimal release, while the mass of recombinant human NGF (rhNGF) released varied four-fold from both EVAc disks and PLA microspheres, with albumin and carboxymethyldextran providing optimal release. Variation of the codispersant species significantly affected NGF release into buffered saline; it also had a noticeable, but small, effect of the amount of NGF found in the brain tissue following implantation of a polymer device. To improve NGF retention in tissue, NGF was conjugated to 70,000 molecular weight dextran and incorporated into a polymeric device. The distribution of NGF was enhanced by conjugation; comparison of NGF concentrations in the brain to a mathematical model of diffusion and elimination suggested that the elimination rate of NGF-dextran conjugate in the tissue was over seven times slower than the elimination rate of NGF. These results indicate that variation of the properties of the controlled release system may be useful in regulating the time course of NGF delivery to tissue, and that modification of the NGF itself can improve penetration and retention in the brain.

Surface modification of chitosan membranes by complexation-interpenetration of anionic polysaccharides for improved blood compatibility in hemodialysis

Abstract: Chitosan membrane surface was modified by complexation and interpenetration of anionic polysaccharides--heparin and dextran sulfate--for improved blood compatibility in hemodialysis. Electron spectroscopy for chemical analysis results showed a characteristic sulfur (S) and sodium (Na) peaks after modification with dextran sulfate. The sulfur/carbon (S/C) atomic composition ratio increased from 0.03 to 0.08 when the bulk dextran sulfate concentration used for modification was increased from 2.5 to 10 mg ml-1. The permeability of urea and creatinine did not change significantly upon modification with heparin or dextran sulfate. Surface modification, however, did decrease the permeability coefficients of glucose, vitamin B-2, and vitamin B-12. Unlike Cuprophan, chitosan and surface-modified chitosan membranes did not significantly activate the complement system as measured by the serum iC3b concentration. Compared to forty and sixty fully-activated platelets present on control surfaces, surface modification with heparin and dextran sulfate significantly reduced the number of adherent platelets per 25,000 microns 2 area and the extent of platelet activation. Surface modification with anionic polysaccharides, however, did significantly shorten the plasma recalcification time leading to fibrin clot formation. The results of this study show that chitosan membrane surface can be modified by complexation-interpenetration of anionic modifying agents. The modified membranes do resist complement activation and platelet adhesion and activation.

Structural characterization and hydrolytic degradation of a zn metal initiated copolymer of l-lactide and epsilon -caprolactone

Abstract: A bioresorbable aliphatic polyester was synthesized by bulk copolymerization of a 1/1 M/M L,L-lactide/e-caprolactone mixture using zinc metal as initiator. The actual composition of the copolymer was found to be 1.5/1 as deduced from 1H NMR spectra obtained in DMSO-d6 solutions where higher resolution was obtained as compared with chlorinated solvents. Resonances due to L-lactyl units (L) exhibited triads stereosensitivity, e-oxycaproyl units (C) being sensitive to dyads. Average lengths of both poly(lactic acid) and polycaprolactone sequences were evaluated and showed the presence of rather long PLA blocks. Furthermore, no CLC triad signal was found, suggesting the absence of transesterification rearrangements. 10 x 10 x 2 mm specimens made of the copolymer were allowed to age in isoosmolar pH = 7.4 phosphate buffer at 37°C. Degradation was monitored by various analytical techniques such as SEC, X-ray diffractometry, DSC, and 1H NMR. Data were compared with the behaviour of PCL and PLA homopolymers allow...

Fibronectin matrix formation by human fibroblasts on surfaces varying in wettability.

Abstract: The spatial organization of extracellular fibronectin on biomaterial surfaces might be important for interaction with tissue cells. In previous investigations we have demonstrated that hydrophilic materials s bind preadsorbed fibronectin that can easily be reorganized by fibroblasts in a specific matrix-like structure, while on less wettable materials (possessing water contact angles above 60 deg) the cells were unable to do this. As the cells continuously produce their fibronectin matrix, we tried in this study to answer the question of how the surface wettability of biomaterials influences the endogenous fibronectin matrix formation and its subsequent organization on the substrate. We cultured fibroblasts for 72 h on five different wettable surfaces: glass, aminopropyltriethoxysilane, pellethane, polyvinylchloride, and silicone, with water-contact angles gradually ranging from 25 to 105 deg. We demonstrated that the decreasing wettability of the materials significantly reduced endogenous fibronectin dep...

Neural cell pattern formation on glass and oxidized silicon surfaces modified with poly(N-isopropylacrylamide)

Abstract: Control over the adsorption of proteins and over the adsorption and spatial orientation of mammalian cells onto surfaces has been achieved by modification of glass and other silicon oxide substrates with poly(N-isopropylacrylamide) (PNIPAM). The functionalization of the substrates was achieved either by a polymer-analogous reaction of aminosilanes with reactive N-(isopropylacrylamide) (NIPAM)-copolymers and by copolymerization of NIPAM with surface-bound methacrylsilane. The obtained coatings were characterized by FT-IR, ellipsometry, and surface plasmon resonance measurements. The adsorption of two proteins-fibrinogen and ribonuclease A-on these surfaces was studied in situ by real time surface plasmon resonance measurements. The PNlPAM-grafted surfaces prepared by either chemical procedure inhibited the adsorption of both proteins. More importantly they prevented the adhesion of neuroblastomaXglioma hybrid cells cultured either in serum-free medium or in a medium containing serum proteins. Deep-UV irrad...

Blood protein interactions with titanium surfaces.

Abstract: Protein adsorption and complement activation were studied on thin evaporated films of titanium (Ti). The surfaces were cleaned in either a radio frequency (RF) plasma unit, or washed sequentially in trichloroethylene, acetone, ethanol, and water. Both methods resulted in hydrophilic surface with low carbon contamination on the outermost oxide (approximately 11-13 at%). In situ ellipsometry suggested that Ti is an intrinsic coagulation activator in vitro, since significant amounts of factor XII (F XII) and high molecular weight kininogen (HMWK) were found on the surfaces after 1 min incubation in heparin plasma. Ellipsometry, performed after serum incubations ranging from 15 s to 30 min showed that the total amount of serum proteins and the deposition of antibodies to complement factor 3c (C3c) increased with serum incubation time. ELISA methods showed increased levels of free iC3b in serum after 10 min incubation of the surfaces, but no detectable amounts of C3 convertase fractions C4d or Bb. Ellipsometric results indicated, however, an increased deposition of antibodies to CIq and IgG on Ti after short serum incubation times. The combined results indicate that Ti-surfaces initially activate complement through the classical pathway. The activation then continues via a positive amplification loop where increased amounts of C3 are deposited on the surfaces via the alternative pathway.

Morphological evidence for a different fibronectin receptor organization and function during fibroblast adhesion on hydrophilic and hydrophobic glass substrata

Abstract: A polyclonal antibody against the β1 subunit of the fibronectin (FN) receptor was used to mimic the early events of integrin receptor functioning to study the initial cellular processes during the organization of FN matrix on biomaterials. Hydrophilic glass and hydrophobic octadecylsilane (ODS) surfaces have been applied as models for different biocompatible materials. By immunofluorescence we could demonstrate that FN receptors organize on the dorsal cell surface of adhering fibroblasts in a specific linear pattern along with actin filaments, but only if the cells were attached to hydrophilic glass. In contrast, FN receptors were not reorganized on hydrophobic octadecylsilane (ODS). In parallel experiments, FN matrix formation after 72 h of incubation on the same substrata has been analyzed microscopically, and quantified by cell ELISA, in order to be further correlated with the integrin receptor functioning in contact with the biomaterials. It was found that FN structuring and the amount of FN matrix ha...

Double-stimuli-responsive degradation of hydrogels consisting of oligopeptide-terminated poly(ethylene glycol) and dextran with an interpenetrating polymer network

Abstract: Biodegradable hydrogels consisting of oligopeptide-terminated poly(ethylene glycol) (PEG) and dextran (Dex) with an interpenetrating polymer network (IPN) structure were prepared as models of novel biomaterials exhibiting a double-stimuli-response function. The IPN-structured hydrogels were synthesized by sequential cross-linking reaction of N-methacryloyl-glycylglycylglycyl-terminated PEG and Dex. In vitro degradation of the IPN-structured hydrogels was examined using papain and dextranase as model enzymes of hydrolyzing oligopeptide and Dex, respectively. Specific degradation in the presence of papain and dextranase was observed in the IPN-structured hydrogel with a particular composition of oligopeptide-PEG and Dex. This same hydrogel was not degraded by one of the two enzymes. The IPN-structured hydrogels were characterized by water content, thermal mechanical analysis, and wide-angle X-ray diffraction, and the results were compared with those of co-cross-linked hydrogels consisting of N-methacryloyl-...

Effect of reduced protein adsorption on platelet adhesion at the phospholipid polymer surfaces

Abstract: We prepared polymers having a phospholipid polar group, poly [omega-methacryloyloxyalkyl phosphorylcholine (MAPC)-co-n-butyl methacrylate(BMA)], as new biomedical materials and evaluated their blood compatibility with attention to protein adsorption and platelet adhesion. The total amount of proteins adsorbed on the polymer surface from human plasma was determined, and the distribution of adsorbed proteins on the plasma-contacting surface was analyzed. The amount of proteins adsorbed on every poly (MAPC-co-BMA) was small compared with that observed on polymers without the phospholipid polar group. However, there was no significant difference in the amount of adsorbed proteins on the poly(MAPC-co-BMA) even when the methylene chain length between the phospholipid polar group and the backbone in the MAPC moiety was altered. Platelet adhesion on the polymer surface from a platelet suspension in a buffered solution was evaluated with and without plasma treatment on the surface. When a rabbit platelet suspension was brought into contact with the poly(BMA) surface after treatment with plasma, many platelets adhered and aggregated. However, a reduced amount of platelet adhered on the poly(BMA) was found in the case of direct contact with the platelet suspension. On the other hand, the poly(MAPC-co-BMA)s could inhibit platelet adhesion under both conditions. Based on these results, it can be concluded that the proteins adsorbed on the surface play an important role in determining the platelet adhesion and suppression of the protein adsorption on the surface, which is one of the most significant ways of inhibiting platelet adhesion.

Injectable microcapsules prepared with biodegradable poly(alpha-hydroxy) acids for prolonged release of drugs.

Abstract: In this paper, microencapsulation techniques for the preparation of drug-containing monolithic microcapsules for prolonged release using biodegradable poly(alpha-hydroxy) acids, such as polylactic acid, poly(lactide-co-glycolide) and copoly(lactic/glycolic) acid are reviewed. Phase separation, solvent evaporation, and spray drying procedures are discussed. In order to achieve controlled-release formulations of highly water-soluble drugs that are entrapped efficiently, various manufacturing techniques and procedures have been developed. Degradation of poly(alpha-hydroxy) acids is altered by the copolymer ratio and molecular weight of the polymer used to make microcapsules and the amounts of released microencapsulated drugs correlate almost linearly with polymer degradation, indicating that controlled-release formulations, which release drugs over different times, can be prepared using suitable poly(alpha-hydroxy) acids with different degradation rates.

Acetylsalicylic acid loaded poly(vinyl alcohol) hemodialysis membranes: effect of drug release on blood compatibility and permeability

Abstract: Membranes developed from poly(vinyl alcohol) (PVA) have superior permeability because of the highly hydrophilic character of PVA. However, its blood compatibility needs to be further improved. For this we have developed acetylsalicylic acid (ASA, aspirin) loaded PVA membranes. It seems that the slow release of aspirin from the membrane provides a surface concentration of aspirin sufficient for partially inhibiting platelet adhesion. PVA membrane with 531 μg cm-2 of ASA loaded, may be selected for hemodialysis applications. This may help to reduce the amount of heparin infused during hemodialysis, thereby reducing the side-effects associated with the systemic administration of heparin.

Surface studies of albumin immobilized onto PE and PVC films.

Abstract: The aim of this study is to evaluate the thrombogenic behaviour of the low density polyethylene and poly(vinyl chloride) modified by radiation-grafting technique. After copolymerization with acrylic acid by y-rays from a 60Co source, BSA was immobilized onto functionalized graft copolymers. The biological interaction between these materials and blood was studies by in vitro methods. The BSA immobilization effectively suppressed the adhesion and activation of platelets when it contacted whole blood.

Controlled release of cytarabine from poly(2-hydroxyethyl methacrylate-co-n-vinyl-2-pyrrolidone) hydrogels

Abstract: Controlled release of cytarabine (ara-C) from poly(2-hydroxyethyl methacrylate-co-N-vinyl-2-pyrrolidone) [p(HEMA-co-VP)] hydrogels cross-linked with ethylene glycol dimethacrylate (EGDMA) is reported. Three compositions of copolymer, each one with a different cross-linking degree, have been studied: H50/VP50, H75/VP25, and H80/VP20. Ara-C (5-25 mg by disc) was trapped in the gels by including it in the polymerization feed mixture. The ara-C release time was between 1 day from H50/VP50/E0.5 discs and 16 days from H80/VP20/E15 discs. In all cases there is a time period for which the drug release rate is constant.

Adsorbed serum protein mediated adhesion and growth behavior of bovine aortic endothelial cells on polyamine graft copolymer surfaces

Abstract: Polyamine-brushed substrata for cell culture were designed by solvent casting of polystyrene-graft-polyamine copolymer (SA) on hydrophobically modified glass surface, and adhesion, spreading, and proliferation of bovine aortic endothelial cells (BAEC) on these substrata were evaluated. Adhesion and spreading of BAEC increased with increasing polyamine content in the copolymer. Close correlation was found between cellular spreading and subsequent cell growth; the surface inducing better spreading of adhered cells showed higher endothelial cell growth. Adhesion and spreading of BAEC were significantly influenced by fetal calf serum (FCS)-pretreatment of the SA copolymer surfaces, being increased with increasing polyamine content, whereas on bovine serum albumin (BSA)-preadsorbed surfaces, BAEC adhesion was considerably prevented and eventually no cell spreading was observed. Then, adsorption of cell-adhesion proteins, fibronectin (FN), and vitronectin (VN), out of FCS onto SA copolymer surfaces were evaluat...

Phase transition parameters of potential thermosensitive drug release systems based on polymers of N-alkylmethacrylamides.

Abstract: The phase separation and its thermohysteresis in dilute aqueous solutions of polymeric components of potential drug release systems (homopolymers and copolymers of N-isopropylacrylamide, N-isopropylmethacrylamide, N-propylmethacrylamide, N-sec-butylmethacrylamide, and N-(2-hydroxypropyl)methacrylamide) was studied, both on heating and cooling. Plots of light transmittance vs temperature were constructed and the parameters characterizing them were correlated with polymer structures. Qualitative information was obtained on the rate of formation of the concentrated phase on heating and its disappearance on cooling. Attention has been drawn to the improper identification of the cloud-point temperature, measured at an arbitrary concentration, with the lower critical solution temperature (LCST) as is frequently found in papers dealing with biomedical applications of thermosensitive polymers.

Immobilization of functionalized alkyl-poly(ethylene oxide) surfactants on poly(ethylene) surfaces by means of an argon plasma treatment

Abstract: Alkyl-poly(ethylene oxide) (PEO) surfactants containing a terminal hydroxyl, sulfate, or carboxylate group were grafted at the surface of poly(ethylene) (PE) samples to improve their blood compatibility. Grafting was achieved by immobilizing PEO surfactants on PE using an argon plasma treatment. The sulfate group containing PEO surfactant was synthesized by sulfating polyoxyethylene(20)stearylether (Brij78®; B) with chlorosulfonic acid. A carboxylate-terminated surfactant was synthesized by a substitution reaction of the sodium alkoxide form of B with sodium iodoacetate. XPS analysis of the modified PE samples showed that at short plasma treatment times of up to 5 s the structure of the immobilized surfactants is largely retained. When plasma treatment times longer than 30 s were applied, the PEO chains of the surfactants were degraded. The wettability of the modified PE samples was improved compared to the unmodified PE samples. The wettability of the modified samples did not change when they were stored...

Development of new wound dressing composed of spongy collagen sheet containing dibutyryl cyclic AMP.

Abstract: Al though cyclic AMP has been considered to regulate cell proliferation, the mechanism of this function is largely unknown. Recent studies suggest that cyclic AMP promotes the proliferation of skin cells in a dose-dependent manner. An ointment containing dibutyryl cyclic AMP has been used in the treatment of skin ulcers and found to be effective in promoting tissue repair. To search more efficacious wound management, the authors developed a new wound dressing composed of a spongy atelo-collagen sheet containing dibutyryl cyclic AMP. This wound dressing was evaluated in two types of animal tests. One is the application of the wound dressing to a full-thickness skin defect in order to evaluate the granulation tissue formation and the wound size reduction. The wound dressing was found to promote the granulation tissue formation and naturally reduce the wound size. The other test was the application of the wound dressing to the full-thickness skin defect, leaving behind a skin island in a central portion, in ...

Protein adsorption and platelet adhesion on polymer surfaces having phospholipid polar group connected with oxyethylene chain.

Abstract: We evaluated the blood compatibility of various amphiphilic polymers, that is, n-butyl methacrylate (BMA) copolymers with methacrylates having a phosphorylcholine (PC), hydroxy (OH) or methoxy (MeO) group as an end polar group in the oxyethylene side chain. The amount of proteins adsorbed on the PC-polymer from human plasma was smaller than that on not only the poly(2-hydroxyethyl methacrylate) and poly(methyl methacrylate) but also the OH-polymer and MeO-polymer. The PC group could weaken the interaction between plasma proteins and polymer surfaces. The amount of adsorbed proteins on the PC-polymer decreased with an increase in the mole fraction of the PC units in the polymers. We could observe an effect of the oxyethylene chain length (n is the number of repeating units of oxyethylene) on protein adsorption between n = 2 and n = 3. The platelet adhesion on these polymer surfaces was evaluated using rabbit platelet-rich plasma. On the polymers without the PC group, that is, poly(BMA), OH-polymer, and MeO-polymer, many platelets adhered and a considerable shape change in the adherent platelets occurred. On the other hand, the PC-polymers could effectively suppress platelet adhesion. The platelet adhesion behavior on the polymers was strongly dependent on the adsorbed proteins. Platelet adhesion was completely inhibited on all of the PC-polymers studied having a 0.3 PC unit mole fraction. However, it was observed that the oxyethylene chains on the PC-polymers with a 0.1 PC unit mole fraction affected platelet adhesion.

Changes in binding affinity of a monoclonal antibody to a platelet binding domain of fibrinogen adsorbed to biomaterials

Abstract: Previously, we found that when fibrinogen-coated polyurethanes resided in a buffer for a period of time (the 'residence time') platelet adhesion to these materials decreased. Other changes in adsorbed fibrinogen such as decreases in polyclonal antibody binding and SDS elutability supported the conclusion that fibrinogen undergoes postadsorptive conformational changes. Subsequently we measured the binding of monoclonal antibodies to the three putative platelet binding sites on fibrinogen, using a single mid-range concentration of antibody. We found that binding of a monoclonal antibody to the platelet binding site at the C-terminus of the gamma chain of fibrinogen changed little with residence time, while binding of monoclonal antibodies to the other two putative binding sites on fibrinogen either increased with residence time (RGDF at A alpha 95-98), or first increased and then decreased with residence time (RGDS at A alpha 572-575). In the current study, we measured antibody binding affinity, Ka, by measuring antibody binding at a series of antibody concentrations. This is a more sensitive method for detecting changes in adsorbed fibrinogen than measuring antibody binding from a single antibody concentration. The Ka was determined for two antibodies, M1 (4A5), which binds to a platelet binding domain of fibrinogen (gamma 402-411) and R1 (155 B 1616), which binds to residues 87-100 of the A alpha chain (containing an RGDF site). A summary of the results for the M1 antibody are as follows. The Ka was higher for M1 binding to fibrinogen adsorbed to Immulon I than to Biomer, Biospan or poly(ethylene terephthalate), suggesting that fibrinogen adsorbed to Immulon I is more platelet adhesive than fibrinogen adsorbed to the other polymers. On Biospan, the Ka decreased from 2.8 x 10(9) to 1.0 x 10(9) M-1 after a 24 h 37 degrees C residence time, which correlated with the decrease in platelet adhesiveness of adsorbed fibrinogen observed previously under these conditions. The change in Ka was greater when adsorbed fibrinogen was kept under denaturing conditions. For example, the Ka decreased from 2.8 x 10(9) to 0.8 x 10(9) M-1 after a 1 h 70 degrees C residence time whereas it remained approximately the same, 2.9 x 10(9) M-1, after a 24 h 0 degree C residence time.

Cell activation by the micropatterned surface with settling particles

Abstract: Surface topography plays an important role in cell orientation and morphogenesis. In this study, we prepared a micropatterned surface with settling particles to obtain more detailed information about the cell recognition against the microstructured surface. Core-shell type particles having a poly-(N-isopropylacrylamide) (polyNIPAM) shell were prepared by seeded polymerization. Particles were settled on a polystyrene (PSt) flat dish by the spinner to prepare a micropatterned surface with settling particles. It could be seen that the polyNIPAM shell shrunk above and swelled below the LCST. For comparison, a thermosensitive flat surface was prepared by the graft polymerization of NIPAM. No morphologic change of cells contacting the both surfaces was observed with either an optical or a scanning electron microscope. Moreover, particles could move or roll on these surfaces when shaking the dishes. The weak interaction between neutrophil-like cells and the micropatterned surface with settling particles or the polyNIPAM-grafted surface was estimated by measurement of active oxygen released by cells. A little release could be observed at both 25 and 35 degrees C. The amount of released active oxygen at 35 degrees C was slightly larger than at 25 degrees C. When the temperature was suddenly changed, the dynamic changes of particle shape and size resulted in the excess release of active oxygen from cells contacting the micropatterned surface with settling particles. Meanwhile no stimulation could be observed in the polyNIPAM-grafted surface even if the temperature is suddenly changed. These results indicate that the micropatterned surface with settling particles can induce the dynamic stimulus at a patterned input mode.

Contact activation of plasmatic coagulation on polymeric membranes measured by the activity of kallikrein in heparinized plasma

Abstract: Kallikrein is involved in the generation of bradykinin during extracorporal circulation, that is believed to play an important role in cases of anaphylactic shock during hemodialysis. Therefore, a method for the assessment of kallikrein generation was developed, based on the chromogenic substrate S-2302. Comparison of kallikrein-like activity on glass using citrate or heparinized plasma demonstrated enhanced activity in the presence of heparin. The applicability of the assay, and the time course of kallikrein generation was demonstrated with glass and cuprophan. Membranes based on pure polyacrylonitrile, or its copolymers differing in their content of acrylic acid, 2-hydroxyethyl acrylate, and allylsulphonate were investigated with respect to kallikrein-like activity, and physicochemical surface properties. It was found that high content in 2-hydroxyethyl acrylate, and acrylic acid caused a substantial activation of the contact system while low content in allylsulphonate (less than 2 mol%) did not result in enhanced kallikrein-like activity. The activating materials were characterized to be highly wettable, and had the most negative zeta potentials.