Showing papers in "Journal of Biomaterials Science-polymer Edition in 1995"
TL;DR: A review of the history of polyurethane in medicine can be found in this paper, where the authors discuss the use of these polymers as pacemaker lead insulators as well as those used to coat breast implants.
Abstract: Polyurethanes are very versatile materials which have been used in the body for over 20 years. In fact, there are probably more scientific papers describing these materials and modifications of these materials for medical use than any other material to date. Unfortunately, some formulations of these polymers are subject to biodegradation and have limited their application in the body. Extensive investigation of the biodegradation mechanisms of these polymers by many researchers in the field has led to the development of a new generation of what are now called 'biostable' polyurethanes. This article reviews the history of polyurethane in medicine, polyurethane nomenclature, the biodegradation of these materials, the proposed mechanisms of its degradation as well as the carcinogenicity associated with these materials. Included in the discussion are the polyurethanes used as pacemaker lead insulators as well as those used to coat breast implants. The article concludes with a review of the new generation of '...
246 citations
TL;DR: An important trend in related research and development is the synthesis of novel polymers, which would exhibit improved biocompatibility, and be bioresponsive.
Abstract: Biomaterials are used in prostheses and medical devices for different purposes. Polymers are the most diverse class of biomaterials. All biomaterials must meet certain criteria and regulatory requirements before they can be qualified for use in medical applications. Biocompatibility is one of the most important requirements. Both nondegradable polymers are designed to degrade in vivo in a controlled manner over a predetermined time. The main mechanism of in vivo degradation of polymers is 'hydrolytic degradation', in which enzymes may also play a role (i.e. 'enzymatic degradation'). Both natural e.g., collagen, and synthetic e.g., poly(alpha-hydroxy) acids, biodegradable polymers are used in biomedical applications. Many of the current polymers and processing techniques need to be improved in order to produce polymers with better performance in biological media. An important trend in related research and development is the synthesis of novel polymers, which would exhibit improved biocompatibility, and be bioresponsive.
203 citations
TL;DR: Poly(IPAAm-co-DMAAm) enabled 'on-off' drug release in response to smaller temperature changes around the body temperature and the molecular design to control transition temperature and thermosensitivity of gel was established.
Abstract: —Temperature-responsive copolymer (or ternary copolymer) gels of N-isopropylacrylamide (IPAAm) were synthesized with hydrophobic alkyl methacrylate (RMA), hydrophilic acrylamide (AAm), N,N'-dimethylacrylamide (DMAAm), and N-acryloylpyrrolidine (APy) as comonomers. The effects of these comonomers on the phase transition temperature (LCST) and the thermosensitivity have been discussed. The LCST of poly(IPAAm) gel in phosphate buffered saline (PBS) was lowered by the introduction of hydrophobic RMA, and the change in equilibrium swelling ratio with temperature change became smaller with an increase in RMA content. However, a stable skin layer to achieve complete 'on-off' regulation of drug release was formed at a higher temperature by RMA due to hydrophobic interaction of alkyl chains. The LCST of poly(IPAAm-co-AAm) gel increased with an increase in AAm content. However, the thermosensitivity of the gel became smaller. It was suggested that hydrophilic AAm prevented the formation of a dense skin layer at a h...
190 citations
TL;DR: The study demonstrated the possibility of incorporating biological macromolecules which are very sensitive to organic solvents, pH, temperature, ultrasound, etc. by a passive absorption technique to degradable biopolymer matrices thereby preserving their biological integrity.
Abstract: Bovine serum albumin (BSA) and diphtheria toxoid (DT) were loaded by passive absorption from aqueous solutions into preformed glutaraldehyde cross-linked chitosan microspheres. In vitro release of BSA under sink conditions at 37 degrees C showed that even though there was a large burst effect, there was a more or less steady increase with time thereafter for several days. Coating the BSA-loaded particles with paraffin oil or with a polymer, such as polylactic acid, modulated drug release. After the initial burst from PLA coated particles, the release rate increased with time for nearly 2 months. Preliminary immunogenicity studies on Wistar rats using DT loaded chitosan spheres showed that the antibody titres were fairly constant over a 5-month period, although very low compared to DT given on alum as control. Histological studies of placebo microspheres intramuscularly injected into rats demonstrated their tissue compatibility. Biodegradation was not complete in 6 months demonstrating the potential of cross-linked chitosan spheres as a long-acting drug delivery vehicle. The study demonstrated the possibility of incorporating biological macromolecules which are very sensitive to organic solvents, pH, temperature, ultrasound, etc. by a passive absorption technique to degradable biopolymer matrices thereby preserving their biological integrity. It is also shown that drugs passively absorbed into such matrices by taking advantage of their swelling behaviour need not necessarily be released completely in the initial 'burst' and a sustained release may be possible for macromolecules thus incorporated.
127 citations
TL;DR: Results showed that surfaces which had incorporated nitrogen were more effective than were oxygen-containing films in adsorbing sufficient serum Fn as to promote endothelial cell attachment, and similar results were seen for the attachment and spreading of fibroblasts as for the endothelial cells.
Abstract: Fluoropolymers modified by plasma modification were studied for their suitability as surfaces for the adhesion of cells. We compared films made by plasma modification of fluoroethylenepropylene (FEP) using nitrogen-containing gases (ammonia or dimethyl acetamide) with films deposited using oxygen-containing monomers (methanol, methyl methacrylate or sequential treatment with toluene then water). The surfaces were compared for the attachment and spreading of human vein endothelial cells and human dermal fibroblasts. The initial attachment and spreading of cultured fibroblasts and endothelial cells onto films deposited using nitrogen-containing gases were equivalent to that onto films deposited using oxygen-containing monomers, but there were some differences in the mechanism of attachment. With films deposited using oxygen-containing monomers, the initial attachment and spreading of endothelial cells failed when the medium contained 15% (v/v) serum from which both fibronectin (Fn) and vitronectin (Vn) had been removed. Similarly, initial attachment and spreading of endothelial cells onto films deposited using oxygen-containing monomers were reduced by 62-86% when the cells were seeded in medium containing Vn-depleted serum (which contained Fn). Endothelial cells attached and spread onto films made using oxygen-containing monomers, when seeded in medium containing Fn-depleted serum (which contained Vn). On films deposited using nitrogen-containing gases, the adhesion of endothelial cells was only slightly reduced in Vn-depleted medium (as compared to attachment in medium containing unmodified serum). Furthermore, surfaces which had incorporated nitrogen were more effective than were oxygen-containing films in adsorbing sufficient serum Fn as to promote endothelial cell attachment. Similar results were seen for the attachment and spreading of fibroblasts as for the endothelial cells. For fibroblasts, attachment and spreading onto oxygen-containing films and onto nitrogen-containing films were not simply dependent upon either the Vn content or the Fn content of the medium. Maximal attachment and spreading of fibroblasts were, however, dependent upon adsorption of both serum Vn and Fn.
126 citations
TL;DR: Some practical problems in preparation of PEO glycidyl ethers have been clarified, thus making these PEO derivatives more useful for surface modification.
Abstract: To understand better the origin of protein rejection observed with surface-bound poly(ethylene oxide) (or PEO), we have measured fibrinogen adsorption for a series of linear and branched, low-molecular-weight PEOs bound to solid polystyrene surfaces. The results show that a dependence on molecular weight is found below 1500 g mol-1 for linear PEO. Branched PEOs are less effective at protein rejection than linear PEOs. The branched PEOs have smaller exclusion volumes (from GPC) than the corresponding linear PEOs, consistent with restriction in conformational freedom for the branched compounds. The protein rejection results are interpreted in terms of entropy changes that result upon protein adsorption. In addition, some practical problems in preparation of PEO glycidyl ethers have been clarified, thus making these PEO derivatives more useful for surface modification.
110 citations
TL;DR: An attempt is made to generalize these findings to the whole family and to elaborate a map which could be used to predict degradation characteristics of LA/GA polymers from their initial composition and morphology.
Abstract: During the past 5 years, important advances have been accomplished in the understanding of the fate of aliphatic polyesters derived from lactic acid (LA) and glycolic acid (GA) in aqueous media. Hydrolysis of solid LA/GA polymers is now regarded as dependent upon a diffusion-reaction mechanism. Faster central degradation, degradation-induced composition, and morphology changes are three of the most important findings which appeared to be composition-dependent as deduced from the behavior of different LA/GA polymers. An attempt is made to generalize these findings to the whole family and to elaborate a map which could be used to predict degradation characteristics of LA/GA polymers from their initial composition and morphology.
93 citations
TL;DR: Permanency of the hydrophilic surfaces so generated was confirmed by surface contact angle experiments and total organic carbon leachables analysis of the aqueous contacting solutions, as determined by the Fluoraldehyde procedure.
Abstract: Low protein adsorbing polymer films have been prepared with which to fabricate intravenous containers, designed for compatibility with low concentrations of protein drugs. The material is economically manufactured utilizing physical melt blending of water-soluble surface-modifying polymers (PEO, PEOX, PVA, and PNVP) with a base polymer (EVA, PP, PETG, PMMA, SB, and nylon). Permanency of the hydrophilic surfaces so generated was confirmed by surface contact angle experiments and total organic carbon leachables analysis of the aqueous contacting solutions. Binding of IgG, albumin and insulin was studied. A sixfold reduction of protein adsorption was obtained by adding 5% PVA13K to EVA, for IgG at a bulk concentration of 2.5 ppm. Surface bound protein measured by micro-BCA colorimetry, agreed with the solution protein lost, as determined by the Fluoraldehyde procedure. Imaging of the protein exposed plastic surfaces by silver enhanced protein conjugated gold staining agreed with the quantitative assay determinations.
75 citations
TL;DR: The apparent dissociation constants of the complexes between saccharide (poly(GEMA), glucose, and mannose) and Con A were determined by affinity electrophoresis and indicated that Con A prefers to form a complex with free glucose or mannosed (but not galactose) rather than with the pendant glucose in poly( GEMA).
Abstract: The complex formation between Concanavalin A (Con A) and a polymer having pendant glucose groups was studied in order to design a glucose-sensitive polymer. The polymer having pendant glucose (poly(glucosyloxyethyl methacrylate) or (poly(GEMA)) forms a complex with Con A in tris HCl buffer (pH = 7.5). The solution then becomes turbid due to the multiple associations between poly(GEMA) and Con A. When free glucose or mannose are added to the turbid solution, the solution becomes transparent again. However, the addition of galactose does not cause the solution to be transparent. This indicates that Con A prefers to form a complex with free glucose or mannose (but not galactose) rather than with the pendant glucose in poly(GEMA). Therefore, the complex between poly(GEMA) and Con A is expected to be glucose- and mannose-sensitive. The apparent dissociation constants of the complexes between saccharide (poly(GEMA), glucose, and mannose) and Con A were also determined by affinity electrophoresis.
71 citations
TL;DR: It is suggested from the requirement of the Ca2+ ion, inhibition of galactosyl substances, and localization of receptors that the adhesion of hepatocytes to both low and high PVLA-density surfaces is mediated by galactose-specific interactions between PVLA and asialoglycoprotein receptors.
Abstract: Morphology and responses of hepatocytes are investigated using an artificial asialoglycoprotein model polymer-lactose-carrying polystyrene (PVLA) as a culture substratum, especially in focusing on the effect of the surface density of the PVLA substratum. The surface density of PVLA on polystyrene dishes was determined using fluorescein-labeled PVLA as a probe under a fluorescence laser microscope. PVLA-coated surfaces were observed by scanning electron microscope and atomic force microscopies under air and water, which showed that PVLA molecules were adsorbed patchily on low density surfaces and uniformly concentrated all over the dish on high density surfaces. It is suggested from the requirement of the Ca2+ ion, inhibition of galactosyl substances, and localization of receptors that the adhesion of hepatocytes to both low and high PVLA-density surfaces is mediated by galactose-specific interactions between PVLA and asialoglycoprotein receptors. At low PVLA densities (0.07 μg cm-2), the hepatocytes were ...
59 citations
TL;DR: The enzymatic attack on a radiolabelled 'hybrid biomembrane', a polyester-urethane (PUU-CAP), was investigated using two esterases and it was found that side chain length for the common substrates was twice more important for CE, than CXE activity.
Abstract: With the introduction of artificial implant devices, a new host of biomembrane-like structures have been introduced into the bio-media made up of the synthetic matrix, adsorbed proteins and lipids. Lysosomal hydrolases, e.g. cholesterol esterase (CE), are implicated during the tissue response near the tissue-implant interface. The enzymatic attack on a radiolabelled 'hybrid biomembrane', a polyester-urethane (PUU-CAP), was investigated using two esterases. Membrane stability was monitored by release of radiolabelled molecules. Although some radioactivity was released by buffer controls, upon the addition of CE, a burst of radiolabel release occurred which was due to an enzymatic reaction that could be saturated and inhibited by the specific esterase inhibitor, phenylmethylsulfonylfluoride. Carboxyl esterase (CXE) incubation with PUU-CAP caused less radiolabel release than CE which was similar to the latter's activity when common nitrophenyl ester substrates were used. When a factorial analysis was perform...
TL;DR: The changes in the expression of the putative platelet binding domains do not correlate with the declines in Platelet binding to plasma preadsorbed Biomer.
Abstract: Fibrinogen adsorbed to polymeric surfaces and then allowed to reside on the surface while it is kept in a buffer solution for a period of time (the 'residence time') undergoes postadsorptive changes that decrease its SDS elutability, displaceability by plasma, polyclonal antifibrinogen binding, and ability to support platelet adhesion (summarized in Chinn et al. J. Biomed. Mater. Res. 26, 757 (1992)). In order to better understand the nature of the changes in adsorbed fibrinogen, the binding of ten different monoclonal antifibrinogen molecules to fibrinogen adsorbed from plasma to Biomer and several other surfaces has been measured after increasing residence time in buffer. Three of the monoclonal antibodies used bind to sequences that have been implicated in platelet binding to fibrinogen. One of these (M1) binds to the C-terminal region of the gamma chain (402-411), another (R1) binds to the N-terminal region of the A alpha chain containing an RGDF sequence (95-98), and the third (R2) binds to the C-ter...
TL;DR: An 'optimum' plasma dilution for the detection of surface bound FG (the Vroman effect) was not found with the use of the ELISA on any of the surfaces except for the silicon oxide surface, in contrast to findings by others who had used isotope-labelled fibrinogen diluted in plasma.
Abstract: —Enzyme linked immunosorbent assay (ELISA) was used for the estimation of protein adsorption from blood plasma at some model solid surfaces. The majority of those surfaces were made in the wells of microtiterplates of polystyrene commonly used for ELISA purposes. Three of the model surfaces were made by radio frequency plasma discharge polymerization (RFPD) of the microtiterplates of polystyrene. The monomers we used were diaminocyclohexane, hexamethylenedisiloxane, and acrylic acid. Other surfaces investigated were: unmodified polystyrene, oxidized polystyrene, hydrophilic silicon oxide, and methylized silicon oxide. Two substances, Tween and bovine serum albumin (BSA), for the prevention of unintended adsorption of ELISA conjugate were also tested and the BSA method was found to be superior for this kind of investigation. Human blood plasma at different dilutions was incubated in the surface-modified microtiterplates followed by incubation of rabbit antibodies against fibrinogen (FG), fibronectin (FN), ...
TL;DR: D-H-D was physisorbed on polyethylene (PE) from aqueous solution, and the adhesion stability and resistance to protein adsorption was examined under static and dynamic flow conditions, using a modified rotating disk system.
Abstract: —A polysaccharide surfactant, dextran-[1,6 bis(2-hydroxypropyl-1-amine)hexane]-dextran, (D-H-D) was prepared by reacting dextran (Mw = 8200) with epichlorohydrin followed by reaction with 1,6-hexan...
TL;DR: PEGs conjugated onto collagen sponges stabilize the porous structure without deactivating the biological properties of collagen, suggesting these porous composite materials could function as a scaffold to organize tissue ingrowth.
Abstract: Collagen-based materials can be designed for use as scaffolds for connective tissue reconstruction. The goal of the present study was to evaluate the behavior of collagen materials as well as cell and tissue reactions after the conjugation of activated polyethylene glycols (PEGs) with collagen. It is known that proteins conjugated with PEGs exhibit a decrease in their biodegradation rate and their immunogenicity. Different concentrations and molecular weights of activated PEGs (PEG-750 and PEG-5000) were conjugated to collagen materials (films or sponges) which were then investigated by collagenase assay, fibroblast cell culture, and subcutaneous implantation. PEG-conjugated collagen sponge degradation by collagenase was delayed in comparison to untreated sponges. In culture, fibroblasts with a normal morphology reached confluency on PEG-conjugated collagen films. In vivo, the porous structure of non-modified sponges collapsed by day 15 with a few observable fibroblasts between the collagen fibers. In PEG-modified collagen sponges, the porous structure remained stable for 30 days. Cell infiltration was particularly enhanced in PEG-750-conjugated collagen sponges. In conclusion, PEGs conjugated onto collagen sponges stabilize the porous structure without deactivating the biological properties of collagen. These porous composite materials could function as a scaffold to organize tissue ingrowth.
TL;DR: The enhanced bioactivity of spacer-immobilized heparin, compared to direct-imm mobilization, may be attributed to the retention of ATIII binding.
Abstract: The immobilization of heparin onto polymeric surfaces using hydrophilic spacer groups has been effective in curtailing surface induced thrombus formation. In this study, the effect of hydrophilic spacers (PEO) on the binding kinetics of immobilized heparin with antithrombin III (ATIII) and thrombin was investigated. Monodispersed, low molecular weight heparin was fractionated on an ATIII affinity column to isolate high-ATIII affinity heparin. This high-ATIII affinity fraction was immobilized onto a styrene/p-amino styrene random copolymer surface using hydrophilic poly(ethylene oxide) (PEO) spacer groups. Styrene/p-amino styrene random copolymer was chosen as the model surface to provide quantitative and reproducible surface concentrations of available amine groups, grafted PEO spacers, and immobilized heparin. The polymer substrate was coated onto glass beads, tolylene diisocyanate modified PEO was covalently coupled to the surface, followed by heparin immobilization. The bioactivity of immobilized heparin was 16.2%, relative to free heparin, and a 1:1 binding ratio between heparin and PEO was achieved. The binding of ATIII and thrombin to control surfaces (no heparin), soluble heparin, heparin immobilized directly onto the surface, and heparin immobilized via spacer groups, were compared. Soluble heparin bound both thrombin and ATIII, while heparin immobilized directly onto the surface bound only thrombin. Spacer-immobilized heparin bound both ATIII and thrombin, although to a lesser extent than soluble heparin. Thus, the enhanced bioactivity of spacer-immobilized heparin, compared to direct-immobilization, may be attributed to the retention of ATIII binding.
TL;DR: Evidence accumulated in this work indicates that water transport in initially glassy poly(2-hydroxyethyl methacrylate) (PHEMA), an important water-swellable biomedical polymer, is controlled by Fickian diffusion.
Abstract: Water sorption which is not classically Fickian has been observed in a variety of polymers. Deviation from Fickian kinetics is widely assumed to be caused by rate-limiting polymer relaxation, despite minimal proof of this. To the contrary, the evidence accumulated in this work indicates that water transport in initially glassy poly(2-hydroxyethyl methacrylate) (PHEMA), an important water-swellable biomedical polymer, is controlled by Fickian diffusion. First of all, the fractional water uptake is initially linear and independent of sample thickness when plotted against the square root of time over initial thickness, as expected for a Fickian process. Furthermore, the moving solvent front also advanced with the square root of time. Temperature, polymer thermal history and initial solvent concentration all affected the sorption kinetics of PHEMA in manners consistent with a Fickian process. The invariably Fickian sorption mechanism is believed to be the consequence of the water molecule's small size and aff...
TL;DR: Adsorption of plasma proteins, adhesion of lymphocytes and the adhesion/activation of platelets were found to increase with increasing hard segment content of the polyurethane ureas, however, the monoclonal-antibody recognisable fibrinogen and the platelet activation were nearly constant with increasingHard segment content, if the urea content was kept constant.
Abstract: Segmented polyurethane ureas with different hard segment content and composition were synthesized using 4,4'-diphenylmethane diisocyanate and polytetramethylene glycols. Using polyols with different molecular weights, it was possible to synthesize polyurethane ureas with either: (i) a constant ratio of urethane to urea bonds; (ii) a constant urethane content; or (iii) a constant urea content. Bulk properties were assessed by dynamic mechanical analysis. Surface properties were estimated by contact angle measurements and streaming potential measurements. Haemocompatibility was evaluated in vitro by measuring the adsorption of human serum albumin (HSA) and fibrinogen (Fg), the adhesion of human peripheral blood lymphocytes (PBL), and the presence of activated platelets on the biomaterial surfaces. Enzyme immuno assays (EIA) have been specially developed for this purpose for the detection of antibody-recognizable plasma proteins and platelet surface membrane proteins. No simple correlation between chemical structure of the polymers and surface properties was found. Parameters of haemocompatibility correlated more closely with hard segment content and chemical composition than with the surface characteristics of the polymers. Adsorption of plasma proteins, adhesion of lymphocytes and the adhesion/activation of platelets were found to increase with increasing hard segment content of the polyurethane ureas. However, the monoclonal-antibody recognisable fibrinogen and the platelet activation were nearly constant with increasing hard segment content, if the urea content was kept constant.
TL;DR: The adhesion of HPL was shown to be dependent not only on the wettability but also on the protein preadsorbed, and vitronectin expressed not only a higher extent of adhesion under static conditions but also a stronger interaction with HPL.
Abstract: The adhesion of human peripheral lymphocytes (HPL) was studied after preadsorption of fibronectin (FN) and vitronectin (VN) on hydrophilic glass and hydrophobic octadecyl glass. The adhesion of HPL was shown to be dependent not only on the wettability but also on the protein preadsorbed. Vitronectin expressed not only a higher extent of adhesion under static conditions but also a stronger interaction with HPL, indicated by the low detachment under shear stress. The flow experiments also demonstrated that FN adsorbed on octadecyl glass may undergo conformational changes because HPL could be easily removed. Scanning electron microscopy revealed that HPL on both FN-and VN-coated glass spread well whereas particularly on FN-coated octadecyl glass less cell spreading was observed; moreover, some round cells were detected. The typing of adherent HPL by immunofluorescence microscopy showed that on FN- and VN-coated glass about 70% of all HPL were T-cells (CD 3+). However, on octadecyl glass, particularly on VN, ...
TL;DR: It was concluded that rifampicin release was both degradation- and diffusion-controlled, and much faster in the medium at basic pH (9.8) and at high temperatures (55 degrees C).
Abstract: —Rifampicin-loaded poly(D,L-lactide) (PDLLA) microspheres in the size range of 0.8-8.0μm were prepared by a modified solvent evaporation method. Rifampicin loading was changed by using different ty...
TL;DR: The aim of this presentation is to review some of the recent work mostly on poly(amidoamine)s (PAAs) and some other families of polymers structurally related to PAAs of medical interest.
Abstract: —The aim of this presentation is to review some of our recent work mostly on poly(amido-amine)s (PAAs) and some other families of polymers structurally related to PAAs of medical interest. PAAs are obtained by stepwise polyaddition of primary monoamines, or bis secondary amines, to bisacrylamides. There are several other ter-amino polymers structurally related to PAAs, such poly(amido phosphine)s (PAPs), poly(ester-amine)s (PEAs), poly(ketone-amine)s (PKAs), poly(amidothioeteramine)s (PATAs) poly(esterthioether amine)s (PTEAs), and poly(sulphone thioether-amine)s (PSTAs). Most of the PAAs exhibit heparin complexing ability. PAAs are also being considered as soluble carriers for delivering anti-cancer drugs. Some of these polymers have been studied as antimicrobial agents. PAAs with different structures degrade at different rates under physiological conditions. The degradation rate is also strongly influenced by pH. The quaternarized PATAs and PTEAs are reasonably stable over a period of some days, but ult...
TL;DR: Data obtained show that the intensity of the antitumoral effects of the CuX zeolite-CP system is similar as compared to that achieved by CP.
Abstract: Porous material of the CuX zeolite type has been synthesized and used as support for a classic antitumoral drug-cyclophosphamide (CP). The new material obtained represents a physical mixture of the two components. In vivo tests allowed biochemical and anatomopathological evaluation of antitumoral effects determined by oral administration of the CuX zeolite-CP system. Data obtained show that the intensity of the antitumoral effects of the CuX zeolite-CP system is similar as compared to that achieved by CP. A possible advantage of the CuX zeolite-CP system is the continual maintenance in the blood of a CP concentration ranging between 100 and 1000 ng ml-1 plasma.
TL;DR: The results indicate that site of implantation and age of recipient influence the degradation and associated effects on mechanical properties of absorbable implants.
Abstract: Absorbable polymeric orthopaedic pins (Orthosorb) of 2.0 mm diameter were implanted at different sites in mature (3.5 kg, >5 months) and immature (5 weeks old) rabbits (total 36) for 2, 4, and 5 weeks. The sites of implantation were the medullary canal of the femur, muscles of the thigh and subcutaneous tissue of the dorsum. In mature rabbits, 1.3 mm diameter pins were also implanted in the medullary canal of the femur. The shear strength of the pins harvested from the rabbits, was measured at each time period using a fixture that shears the pins into three parts symmetrically about the load axis. In both mature and immature rabbits the rate of degradation in mechanical properties was higher in the medullary canal of bone than in the muscle and in the subcutaneous tissue (p < 0.05). The strength retention was lower in immature than in mature rabbits after 4 and 5 weeks. The 1.3-mm pins had higher initial strength (174.7 ± 7 MPa), higher strength retention and slower degradation within the medullary canal ...
TL;DR: Neither changes in molecular weight nor in tensile properties provided a clear indication of early susceptibility to degradation by environmental stress cracking.
Abstract: A series of novel polyurethane elastomers based on methylenediphenyl diisocyanate, 1,4-butanediol and the macrodiols, poly(hexamethylene oxide), poly(octamethylene oxide), and poly(decamethylene oxide) were implanted subcutaneously in sheep for periods of 3 and 6 months. The specimens that were subjected to 3 months of implantation were strained to 250% of their resting length, while those implanted for 6 months had no applied external strain. SEM examination of the explanted specimens revealed that the novel materials displayed resistance to environmental stress cracking. Proprietary materials, Pellethane 2363-80A, Biomer and Tecoflex EG-80A, which had been implanted under identical conditions, showed evidence of significant stress cracking. The extent of stress cracking in the 3-month strained experiment was similar to that from the 6-month unstrained experiment. Stress cracking was also observed in Pellethane 2363-55D, when implanted for 6 months (unstrained). Neither changes in molecular weight nor in tensile properties provided a clear indication of early susceptibility to degradation by environmental stress cracking.
TL;DR: Although significant hydrolysis of the polymer occurred within the first day, the matrices remained intact and water-soluble tracers were slowly released for several days, and rates of tracer release from the matrix depended on tracer particle size.
Abstract: Polymeric matrices that slowly release macromolecules may be useful for the controlled delivery of proteins or polymer-drug conjugates for targeted drug delivery. Solid particles of fluorescein and fluorescently-labeled, size-fractionated dextran (4000-150,000 number average molecular weight) were dispersed in degradable polyanhydride matrices composed of a 1:1 copolymer of fatty acid dimers and sebacic acid. The release of macromolecules from the polymer matrix into buffered saline was measured; changes in the polymer during immersion were monitored by infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Although significant hydrolysis of the polymer occurred within the first day, the matrices remained intact and water-soluble tracers were slowly released for several days. During polymer hydrolysis and erosion, micron-sized pores developed throughout the 2 mm thick polymer matrix, permitting water penetration into the matrix and tracer diffusion out of the matrix. The rate of tracer release from the matrix depended on tracer particle size; rates of fluorescein isothiocyanate dextran release were controlled by adjusting the size of particles dispersed in the matrix.
TL;DR: In vitro evaluation of a new biomaterial using the human cell system characteristic of the tissue which it will be exposed to in vivo, and an intracellular uptake of both Cr and Co was detected, which will have physiological importance.
Abstract: The evaluation of a potential biomaterial is based on two approaches: firstly, the study of the local and systemic effects of the biomaterial implanted in the host; and secondly the study of the behaviour of the biomaterial itself with increasing time. The progress achieved in human cell culturing allows in vitro evaluation of a new biomaterial using the human cell(s) system(s) characteristic of the tissue which it will be exposed to in vivo. This kind of approach permits the assessment of the biodegradation of a biomaterial whatever it is: metal; alloy; ceramic; glass; polymer; with or without specialized coating.... The experimental approach is as follows: discs representative of the biomaterial (surface state, cleaning, sterilization process) are manufactured in order to cover the bottom of the culture wells. Thereafter, they are either brought in the presence of complete culture medium alone, or in the presence of a subconfluent cell layer. A kinetic analysis is performed using various incubation periods at 37 degrees C. Released biodegradation products are identified and quantified, in both the medium and cell compartment, and on the other hand cytotoxicity is assessed. A Co-Cr alloy was studied over a 9-day period according to the experimental schedule, and showed a higher corrosion rate in the presence of osteoblasts in the range of 25-30%. Moreover, an intracellular uptake of both Cr and Co was detected, which will have physiological importance.
TL;DR: The amount of phospholipid adsorbed on the MAPC copolymer from human plasma was larger than that on hydrophobic poly(BMA) and increased with the length of the methylene chain in theMAPC moiety, which corresponded to the reduction of platelet adhesion.
Abstract: To investigate the effects of the methylene chain length between the phospholipid polar group and the backbone on blood compatibility of a phospholipid polymer, copolymers of ω-methacryloyloxyalkyl phosphorylcholine (MAPC) with n-butyl methacrylate (BMA) were synthesized. The methylene chains were ethylene (n = 2), tetramethylene (n = 4), and hexamethylene (n = 6). Every MAPC copolymer with an MAPC mole fraction in the range of 0.1-0.3 was soluble in ethanol but only swelled in water, and the equilibrium water fraction of the water-swollen MAPC copolymer membrane decreased with the length of the methylene chain. When a rabbit platelet-rich plasma was applied on the MAPC copolymer surface with an 0.1 MAPC mol fraction for 180 min, the number of adhered platelets depended on the length of the methylene chain in the MAPC moiety of the copolymer. The amount of phospholipid adsorbed on the MAPC copolymer from human plasma was larger than that on hydrophobic poly(BMA) and increased with the length of the methyl...
TL;DR: It was concluded that the assembly of cell membranes, stabilized by water molecules, was disturbed by strong interaction with the polymer molecules having a strong hydration power, resulting in membrane fusion.
Abstract: The fusogenic activity of seven water-soluble polymers was investigated using L929 cells in a monolayer state. Among these polymers, only two, poly(ethylene glycol) (PEG) and EPAN 680 were capable of inducing the membrane fusion of L929 cells. EPAN 680 is an ABA type block copolymer composed of 80% ethylene oxide(A) and 20% propylene oxide(B) sequences with a total molecular weight of 8800. Evaluation of the polymer hydrophobicity indicated that there was no clear correlation between it and the fusogenic activity of the polymer, although highly hydrophobic polymers caused cell shrinkage without membrane fusion. Differential scanning calorimetry on these polymers strongly suggested that hydration of the polymers in culture medium had a large effect on their fusogenic activity. It was concluded that the assembly of cell membranes, stabilized by water molecules, was disturbed by strong interaction with the polymer molecules having a strong hydration power, resulting in membrane fusion.
TL;DR: The drug incorporation into the PECA microspheres increased with increasing initial drug concentration in the monomer phase and higher drug release rates were observed in the neutral and alkaline media as compared with the acidic medium.
Abstract: —Monosize, biodegradable poly(ethylcyanoacrylate) (PECA) microspheres with a diameter of 1.3μm were prepared by a relatively new polymerization method, the so-called phase inversion polymerization. The effects of pH and temperature on the degradation behavior of PECA particles were investigated. PECA microspheres were degraded mainly by surface erosion. The degradation rate increased with increasing pH temperature. A model drug, i.e. 2,4-dinitrophenylhydrazine (DNPH) was loaded into the monosize PECA microspheres during polymerization. The drug incorporation into the PECA microspheres increased with increasing initial drug concentration in the monomer phase. Drug release from the PECA microspheres was investigated at different pH. Higher drug release rates were observed in the neutral and alkaline media as compared with the acidic medium.
TL;DR: TheHeparin immobilized surface is nonthrombogenic and this technique can be used to bind heparin to various blood contacting medical devices.
Abstract: A method of functionalizing polymer surfaces of long small diameter tubes, using a water-oxygen RF plasma, is described. The objective was to introduce appropriate functional groups suitable for covalently binding bioactive agents, heparin in particular, through spacer molecules. A new means by which this can be accomplished on the inside surfaces of a long tube is also described. The heparin immobilized surface is nonthrombogenic and this technique can be used to bind heparin to various blood contacting medical devices. The heparinized surfaces were analyzed by X-ray photoelectron spectroscopy (XPS) and static secondary ion mass spectroscopy (SSIMS), before and after extraction in phosphate buffered saline and 4 M guanidine, to confirm the covalent binding of heparin.