Biomedical subjects

S L Cooper

Publications and source records attributed to S L Cooper.

At least 19 recordsLinked to original sources

PubMed1992

The ex vivo effect of preadsorbed vitronectin on platelet activation.

The activation of ex vivo canine platelets by preadsorbed vitronectin (VN) was sensitive not only to the polymer substrate utilized but also to the adsorption conditions employed. Lower levels of maximal platelet deposition were obtained for VN-coated silicone rubber (SR) than for other VN-coated substrates with comparable levels of adsorbed VN, but this effect was diminished with increased residence time of VN on the SR surface. Submonolayer and monolayer surface concentrations of VN elicited similar maximal levels of platelet deposition at both short (less than 3 h) and long (greater than 12 h) residence times, but thrombi were larger and more dense for the submonolayer surface concentrations. VN was also more effective in forming thrombi when adsorbed sequentially before albumin instead of after albumin. To further examine these differences in the nature of adsorbed VN between substrates and adsorption conditions, sodium dodecyl sulfate (SDS) elutability measurements and Fourier transform infrared spectroscopy with attenuated total reflectance optics (FTIR-ATR) evaluations of the adsorbed protein were performed. An SDS solution was able to remove a greater percentage of the VN which was adsorbed to a submonolayer than a monolayer surface concentration when SDS displacement was initiated immediately after adsorption was terminated. However, if the adsorbed protein was allowed to reside on the surface for a length of time before the introduction of the SDS displacing media, a greater percentage of the monolayer surface concentration was removed. The submonolayer surface concentration may be better able to increase its strength of contact with the surface during the added residence time than the monolayer surface concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗

PubMed1992

Effect of soft segment chemistry on the biostability of segmented polyurethanes. II. In vitro hydrolytic degradation and lipid sorption.

A series of segmented polyurethanes (SPUs) with various polyol soft segments was prepared and their hydrolytic degradation and degradation due to lipid sorption was investigated. The hydrolytic degradation of the SPUs was investigated in a papain solution, where it was shown that the SPU based on poly(ethyleneoxide) (PEO) soft segment was susceptible to hydrolytic degradation. X-ray photoelectron spectroscopic (XPS) data suggest dissociation of the urethane linkage by enzymatic degradation. Degradation by lipid sorption was observed for the SPU based on a poly(dimethylsiloxane) (PDMS) soft segment. This is ascribed to the high solubility of lipid in the PDMS segment of the SPU.

Absorption↗

PubMed1992

Anticoagulant effects of sulphonated polyurethanes.

Sulphonated polyurethanes have been shown to have excellent blood contacting properties. In this paper, similar polyurethanes which are water soluble have been investigated to determine their influence on thrombus formation. These polymers were shown to delay clotting times in the following ways: by direct complex formation between the polymer and thrombin; by interference with fibrin polymerization; and by complex interactions between polymer, thrombin, plasma antiproteases and fibrinogen in plasma.

Animals↗

PubMed1992

Endothelial cell adhesion on polyurethanes containing covalently attached RGD-peptides.

Peptides based on cell-adhesive regions of fibronectin, Arg-Gly-Asp-Ser (RGDS), and vitronectin, Arg-Gly-Asp-Val (RGDV), were covalently bound to a polyurethane backbone via amide bonds. Nuclear magnetic resonance (NMR) and Fourier-transform infrared (FTIR) spectroscopies were used to monitor the reactions. The amount of grafted peptide was determined by amino acid analysis. X-ray photoelectron spectroscopy (XPS) suggested the presence of the grafted peptide at the polymer-air interface in vacuo. Dynamic contact angle analysis showed that, in water, the peptide-grafted polyurethane surfaces were more polar than the underivatized polyurethane indicating enrichment of peptide groups at the surface. The attachment and spreading of human umbilical vein endothelial cells (HUVECs) on the underivatized and peptide-grafted polyurethanes was investigated. The GRGDSY- and GRGDVY-grafted substrates supported cell adhesion and spreading even without serum in the culture medium. The GRGDVY-grafted substrate supported a larger number of adherent cells and a higher extent of cell spreading than the GRGDSY-grafted substrate. These RGD-containing peptide-grafted polyurethane copolymers may be useful in providing an easily prepared cell-adhesive substrate for various biomaterial applications.

Amino Acids↗

PubMed1992

Synthesis of a novel polyurethane co-polymer containing covalently attached RGD peptide.

The synthesis of a novel polyurethane block co-polymer containing a covalently attached, well-oriented RGD (Arg-Gly-Asp) peptide was explored. A poly(tetramethylene oxide) (PTMO)-based polyurethane was synthesized, and a bimolecular nucleophilic substitution reaction was then employed to incorporate ethyl carboxylate groups onto the polymer backbone (i.e. carboxylated polyurethane). Elemental analysis was used to determine the extent of carboxylation. The hexapeptide H-Gly-Arg-Gly-Asp-Ser-Tyr-OH was coupled to the carboxylated polyurethane via the formation of an amide bond. The attachment of the peptide was controlled by a protection-deprotection scheme. Nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopies were used to monitor the reactions. Sakaguchi assay and amino acid analysis confirmed that the RGD-containing peptide was successfully grafted onto the carboxylated polyurethane. This reaction scheme provides a new route for grafting end-linked, bioactive peptides onto polyurethanes.

Amino Acid Sequence↗

PubMed1992

Biostability and blood-contacting properties of sulfonate grafted polyurethane and Biomer.

Sulfonate-containing polyurethanes were evaluated for in vivo biodegradation using subcutaneously implanted tensile bars. In addition, these anionically charged polyurethanes were evaluated for in vivo activation of human complement C3a and ex vivo platelet deposition in arteriovenously-shunted canines. The sulfonate derivatized polymers included laboratory synthesized polyurethane and Biomer. Other polymers used for references included Intramedic polyethylene, Silastic and a poly(ethylene oxide) based polyurethane. The biodegradation results indicated that Biomer and the laboratory sulfonated Biomer (both manufactured with stabilizers), remained mechanically stable, retaining both tensile strength and elasticity after 4 weeks of subcutaneous implantation. The unstabilized polyurethanes (with or without sulfonation), however, showed marked cracking and a loss of mechanical properties after the same period of subcutaneous implantation. Sulfonated polyurethanes depressed human complement C3a activation in plasma, as indicated by decreased levels of anaphylatoxin production. The results of canine ex vivo blood contacting experiments were conducted in both an acute and chronic model and demonstrated decreased platelet deposition and activation for the sulfonated polyurethanes.

Absorption↗

PubMed1992

Amantadine-resistant influenza A in a nursing facility.

Rapid index case treatment and amantadine prophylaxis were implemented in two nursing homes exposed to influenza A. Facility A had no isolation of cases, and 18 of 22 cases occurred after amantadine hydrochloride therapy was initiated. Three patients exhibited amantadine-resistant virus. Facility B had day 1 isolation of the index case. A facility-wide outbreak did not occur. The experience of these facilities suggests that concurrent amantadine treatment and prophylaxis without adequate case isolation may promote further influenza A infection in a nursing facility.

Aged↗

PubMed1991

Effect of soft segment chemistry on the biostability of segmented polyurethanes. I. In vitro oxidation.

A series of segmented polyurethanes (SPUs) containing various polyol soft segments was prepared and their resistance to oxidative degradation was investigated after aging in AgNO3 solution. The SPU with the polyether soft segment showed a large reduction in mechanical strength after exposure to the oxidative environment. Surface cracking was often observed for these specimens. XPS measurements revealed that scission of the ether linkage occurs upon oxidation. The oxidative resistance of SPUs containing aliphatic hydrocarbon soft segments was significantly improved over the poly(tetramethylene oxide) (PTMO) based polyurethane.

Calorimetry, Differential Scanning↗

PubMed1991

Competitive adsorption of vitronectin with albumin, fibrinogen, and fibronectin on polymeric biomaterials.

Vitronectin (VN) was competitively adsorbed with human serum albumin (HSA), fibrinogen (FGN), and fibronectin (FN) from binary component mixtures in order to compare the relative affinities of these proteins for various polymer materials. Competitive adsorption was monitored by incubating radiolabeled protein solutions inside 0.125-in. i.d. tubing of the polymers, flushing with buffer, and measuring the adherent radioactivity. Adsorption experiments at equal mass concentrations of the competing proteins revealed that VN comprises at least 75% by weight of the adsorbed protein when competitively adsorbed with HSA and approximately 50% by weight when competitively adsorbed with FGN and FN on all surfaces except a poly(ethylene oxide)-based polyurethane where it comprised closer to 80 wt%. When VN was competitively adsorbed in the presence of increasing amounts of HSA, FGN, and FN, the amount of VN adsorbed on a weight basis was diminished the most by FGN. HSA had the least inhibitory effect at low bulk concentrations and FN had the weakest effect at higher bulk concentration levels. When HSA, FGN, and FN were competitively adsorbed in the presence of increasing amounts of VN, VN diminished their adsorption on a weight basis in the order: HSA greater than FN greater than FGN.

Adsorption↗

PubMed1991

Effect of hydrophilic soft segment side chains on the surface properties and blood compatibility of segmented poly(urethaneureas).

Segmented poly(urethaneureas) with hydrophilic side chains were prepared from poly(tetramethylene oxide) (PTMO), 4,4'-diphenylmethane diisocyanate (MDI), ethylene diamine (ED) and a diol with a long hydrophilic side chain comprised of an ethylene oxide-proplene oxide copolymer. The end groups of the hydrophilic chains were either sodium sulfonate or methoxy groups. The state of microphase separation showed a small dependence on the fraction of long-chain hydrophilic diol. Surface analysis by means of static underwater contact angle and dynamic contact angle measurements revealed that the graft chains were at the aqueous interface in the hydrated state. An ex vivo A-V shunt experiment revealed that a more thrombogenic blood-material response was correlated with an increase in the concentration of polymeric hydrophilic side chain incorporation. The polyurethane containing a long chain diol with methoxy end groups exhibited a higher level of thrombogenicity than the similar polymers possessing a sulfonate terminated side chain.

Animals↗

PubMed1991

Physical and blood-contacting properties of polyurethanes based on a sulfonic acid-containing diol chain extender.

Polyurethanes chain extended with N,N-bis (2-hydroxyethyl)-2-aminoethane-sulfonic acid (BES) were synthesized. The effect of the sulfonic acid group on the polymers' bulk, surface, and blood-contacting properties was evaluated by comparing the BES-based polymers with polyurethanes based on N-ethyldiethanolamine (EDEA). In addition, the effect of soft-segment polarity was addressed by comparing polyurethanes based on polytetramethylene oxide (PTMO) (MW = 1000) with polymers based on polyethylene oxide (PEO) (MW = 1000). The EDEA control samples had physical properties similar to a viscous fluid. The presence of the sulfonic acid group dramatically enhanced the degree of microphase separation and the mechanical strength of all the polymers. The more polar PEO soft segment resulted in polymers which were more phase mixed than the PTMO-based polyurethanes. Surface characterization studies revealed that in vacuum, all the surfaces were enriched in the polyether soft-segment phase. After 24-h equilibration in water, all the surfaces had similar surface polarities independent of the SO3H content. The canine ex vivo blood-contacting results showed that the sulfonic acid group in the PTMO-based polymers significantly reduced the number and activation of the adherent platelets. Fibrinogen deposition, however, increased with increasing sulfonic acid content. In contrast, platelet and fibrinogen deposition on the sulfonic acid-containing PEO-based polymers was greatly enhanced.

Adsorption↗

PubMed1991

Effect of surface hydrophilicity on ex vivo blood compatibility of segmented polyurethanes.

The relationship between surface, bulk and ex vivo blood-contacting properties of segmented polyurethanes with various polyol soft segment was investigated. The polyols used in this study were poly(ethylene oxide), poly(tetramethylene oxide), hydrogenated poly(butadiene), poly(butadiene) and poly(dimethylsiloxane). The hard segment of these segmented polyurethanes was composed of 4,4' diphenylmethane diisocyanate and 1,4 butanediol, present at 50 wt%. An experimental polyurethane, Biostable PUR, which has shown excellent biostability, was used in this study. The segmented polyurethanes based on the hydrophobic polyols such as poly(dimethylsiloxane) and hydrogenated poly(butadiene) showed distinct microphase separation between hard and soft segments. X-ray photoelectron spectroscopy revealed the surface enrichment of the hydrophobic component at the air-solid interface. Dynamic contact angle measurements indicated that the poly(dimethylsiloxane)-based segmented polyurethane possessed a hydrophobic surface in water. The poly(dimethylsiloxane)-based segmented polyurethane had the lowest platelet adhesion among the segmented polyurethanes investigated in this study, whilst the platelet deposition on the poly(ethylene oxide)-based polymer increased with time.

Animals↗

PubMed1991

Effect of carboxylate and/or sulphonate ion incorporation on the physical and blood-contacting properties of a polyetherurethane.

Propyl sulphonate and ethyl carboxylate groups were grafted on to the backbone of a polytetramethylene oxide-based polyurethane (PEU). The effects of ion type and ion content on the polymer's bulk, surface, and blood-contacting properties were evaluated. Ion incorporation disrupted the packing of the hard segment but had little effect on the overall microphase separation of the polymers. The mechanical properties of the ionomers were improved relative to the base PEU, although the carboxylate-containing ionomers were weaker than the sulphonate-containing polymers. As expected, the polymer's water absorption and surface polarity increased with increasing ion content. Dynamic and static contact angle analysis indicated that the propyl sulphonate-containing polymers were more polar than the ethyl carboxylate-containing polymers at the same ion content which is attributed to the higher ionic strength of the sulphonate ion. The carboxylate-containing polymers had no statistically significant effect on the polymer's canine ex vivo blood-contacting response. At the same ion content, propyl sulphonate incorporation significantly reduced platelet deposition for very short blood-contacting times. When both ion types were present in the polymer, the propyl sulphonate group appeared to be the primary factor determining the polymer's blood-contacting response. The polymer containing 20 mol% propyl sulphonate groups significantly reduced platelet deposition and activation while also exhibiting enhanced fibrinogen deposition.

Animals↗

PubMed1991

Physical and blood contacting characteristics of propyl sulphonate grafted Biomer.

Propyl sulphonate groups were grafted on to the backbone of Biomer, a polyetherurethaneurea, in an attempt to improve its blood-contacting properties. The bulk, surface and blood-contacting properties of this series of sulphonated polymers were evaluated. Differential scanning calorimetry and dynamic mechanical analysis indicated that propyl sulphonate incorporation increased the microphase separation of the polymers. The ultimate tensile strength was also increased with sulphonation at the expense of the polymer's extensibility. Dynamic contact angle analysis showed that, in water, the sulphonated Biomer surfaces were more polar than the Biomer sample indicating the propyl sulphonate groups were enriched at the surface. Canine ex vivo blood-contacting results showed that the incorporation of propyl sulphonate groups dramatically reduced the number and activation of platelets adherent to the polymer surface. In addition, fibrinogen deposition increased with increasing sulphonate content, despite the low level of platelet activation.

Animals↗

PubMed1991

The effects of substrate-adsorbed albumin on platelet spreading.

Adsorbed albumin appears to passivate nearly all materials, minimizing platelet adhesion and thrombus formation. Since in vitro platelet spreading can be an indicator of in vivo reactivity leading to thrombosis, and as in vitro platelet adhesion investigations are routinely done in the presence of bovine or human serum albumin (BSA or HSA), we examined the influence of albumin on platelet reactivity to material substrates. Platelet spreading was examined subsequent to adherence onto several related polyurethanes, and to Formvar, in the presence of bulk albumin concentrations sufficient to form an adsorbed monolayer or a multilayer. No other exogenous proteins were present. The spreading behavior of adherent platelets was analyzed using generalized linear interactive modeling (GLIM). The models showed that the polymer type always influenced platelet responses, irrespective of the albumin concentration. In many experiments, platelet behavior could be adequately modeled without including the effects of albumin. Thus, the polymer type appeared to be the primary determinant of platelet shape-change with adsorbed albumin producing a secondary effect. Additionally, somewhat different effects on spreading were observed with HSA and BSA, suggesting qualitatively different interactions between human platelets and HSA, than with BSA, which is commonly used in platelet preparations.

Adsorption↗

PubMed1991

A comparison of the adsorption of three adhesive proteins to biomaterial surfaces.

The adsorption of three cell adhesive proteins with known thrombogenic activity [fibrinogen (FGN), fibronectin (FN), and vitronectin (VN)] was quantified from mono-component protein solutions, from a quaternary-component protein solution, and from plasma and diluted plasma in order to compare their potential for adsorption to polymeric substrates from solutions of varying complexity. The surfaces studied included polyethylene (PE), silicone rubber (SR), Teflon-FEP (FEP), and two polyetherurethanes: one with a poly(tetramethylene oxide) soft segment (PTMO-PU) and one with a poly(ethylene oxide) soft segment (PEO-PU). The adsorption of these proteins from single-component solutions followed the Freundlich isotherm and the adhesive proteins showed similar trends in Freundlich parameters for surfaces of similar surface wettability. Adsorption from a quaternary-component solution composed of physiological molar ratios of the three proteins and human serum albumin (HSA) revealed a significant enrichment of adsorbed vitronectin as determined from ratios of the adsorbed surface fraction of each protein to its respective bulk fraction. The other proteins' adsorption was enriched to a lesser extent in the decreasing order of FGN greater than FN greater than HSA for all surfaces. The relative enrichment of VN from plasma was also high as compared with its bulk concentration, whereas the enrichment of FGN, FN, and HSA was much lower and of approximately the same magnitude. Compared with the three other proteins, VN showed a resistance to displacement from the polymer substrates as either the plasma concentration was increased or the length of contact with plasma and diluted plasma was increased.

Adsorption↗

PubMed1991

Comparison of pharmacokinetic and safety profiles of amantadine 50- and 100-mg daily doses in elderly nursing home residents.

Pharmacokinetic and adverse event profiles of 50- and 100-mg amantadine doses administered daily for up to 21 days for influenza prophylaxis were compared in 82 elderly nursing home residents (mean age 85 yrs, 68% female). We sought to determine if a standard daily dose of 50 mg would achieve mean steady-state trough serum concentrations (CPSSt) of 300 ng/ml and be associated with a lower frequency of adverse events than 100-mg doses. Statistically significant relationships were found between CPSSt and dosage (in mg/kg/day) and serum creatinine. Adverse events were more common with the 100-mg dose (24% vs 14%); 94% occurred in women. Amantadine CPSSt and apparent clearance were not significantly different between sexes. Thirty-nine residents (89%) receiving 50 mg daily achieved CPSSt below 300 ng/ml compared to 42% receiving 100 mg. Standard daily amantadine doses of 50 mg may not achieve adequate CPSSt in elderly nursing home residents, but 100 mg may lead to excessive CPSSt and adverse events, especially in the presence of renal impairment.

Aged↗

PubMed1990

Series shunt evaluation of polyurethane vascular graft materials in chronically AV-shunted canines.

Well characterized, laboratory-synthesized polymeric materials which have been extensively tested for biocompatibility via initial platelet and protein deposition in an acute ex vivo canine model were placed as interpositional series shunts in canines with chronically implanted iliac arteriovenous shunts ex vivo. Platelet deposition was measured on a base polyurethane block copolymer, a sulfonated ionic derivative, an alkyl grafted (C18) derivative, Biomer, polyethylene, and polydimethylsiloxane for 24 h using radiolabeled platelets. Platelet survival and in vitro aggregation were determined to investigate the effects of the shunting procedure on experimental animals. The viability of adopting a chronic arteriovenous (iliac) shunted canine model for use with series shunts to evaluate polyurethanes having applications as materials in vascular graft construction was investigated and the results compared with acute model data.

Animals↗