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Biomedical subjects

B D Ratner

Publications and source records attributed to B D Ratner.

86 records · Page 5Linked to original sources

Characterization of graft polymers for biomedical applications.

Graft copolymer systems have frequently been suggested for biomedical applications. Since the properties of polymers are altered by the grafting process, thorough characterization is critical, particularly for the surface region of these copolymers. This review briefly discusses the grafting process and then describes characterization procedures for graft copolymers. Gravimetric characterization, thermodynamic measurements, surface chemistry analysis, and surface topographical analysis are considered in detail. Also, the relevance of materials characterization for predicting and understanding the biocompatibility response is discussed. Most of the analytical techniques described are applicable to all biomaterials and should be considered for the routine characterization of materials which will be interfaced with biological systems.

Biocompatible Materials↗

The thrombogenicity of radiation grafted polymers as measured by the vena cava ring test.

Radiation grafted hydrogels on silicone rubber with water contents ranging from 10--90% have been evaluated by the vena cava ring test. All hydrogel grafted materials were found to accumulate less thrombus than ungrafted silicone rubber, and graft level was found to have little effect on thrombus accumulation. Acrylamide grafts demonstrated superior thromboresistance by this test. Poly (2-hydroxyethyl methacrylate-ethyl methacrylate (HEMA/EMA) copolymers were examined along with pure HEMA and EMA grafts. At two weeks implantation, intermediate HEMA/EMA copolymers were found to have the least thrombus accumulation of any of the polymers in this series. EMA grafted rings were highly thrombogenic. The results from these studies indicate that the sensitivity of the vena cava ring test for detecting certain differences in polymer structure is poor. Also, the significance of the vena cava ring test for evaluating materials for use in contact with flowing human blood is questionable, based upon comparisons of results for similar materials tested in other blood compatibility evaluation systems.

Acrylamides↗

Cell adhesion to polymeric materials: implications with respect to biocompatibility.

The adhesion of radio-labeled chick embryo muscle cells to the surfaces of radiation grafted hydrogels and other polymeric materials was measured in vitro. The degree of adhesion was determined by measuring the percentage of cells which remained adherent to the surfaces after 180 min of contact time (plating efficiency). Plating efficiency was found to vary between 2 and 94% depending on the nature of the surface. Preadsorption of albumin, gamma-globulin or fibrinogen markedly affected subsequent adhesion of cells. Radiation grafted poly(2-hydroxyethyl methacrylate) and poly(N-vinyl-2-pyrrolidone) hydrogels on silicone rubber demonstrated exceptionally low adhesiveness in this assay. The potential for using this cell adhesion assay as a general screening test for biomaterials is discussed.

Adsorption↗

The engineering of biomaterials exhibiting recognition and specificity.

Although synthetic materials are now widely used in implanted medical devices, they are not engineered for recognition and specificity. This article considers the design of polymer surfaces that might be specifically recognized and trigger normal healing pathways. The technological advances that will contribute to biorecognition biomaterials include surfaces to inhibit non-specific interactions, self-assembly to create ordered surface structures and strategies to place recognition sites on surfaces by random arrays of groups and by templates.

Animals↗

Rat peritoneal macrophage adhesion to hydroxyethyl methacrylate-ethyl methacrylate copolymers and hydroxystyrene-styrene copolymers.

Macrophage adhesion to a wide variety of substrates has been measured, but no systematic study of the influence of specific substrate chemical properties on adhesion is available. These studies were conducted using two series of materials, copolymers of hydroxyethyl methacrylate (HEMA) and ethyl methacrylate (EMA) and copolymers of hydroxystyrene and styrene, to determine the effect of a single chemical property, polar character, on adhesion. Rat peritoneal macrophages were allowed to contact polymer substrates for periods ranging from 1 to 240 min before being subjected to a shear stress of 60-120 dynes/cm2 in a thin-channel flow cell. Percentage adhesion was calculated from the number of cells that remained adherent to the substrate after 30 s of applied shear stress. Macrophages remained adherent to 100% EMA and all hydroxystyrene-styrene copolymer surfaces after only 1 min of contact. In copolymers of the HEMA-EMA series, the time required to attain peak adhesion levels increased with increasing substrate hydrophilicity (increasing HEMA content). Cells did not attach to the 20% EMA/80% HEMA copolymer and the 100% HEMA polymer. The results demonstrate that there is a time delay between contact and adhesion of the cells to surfaces of increasing hydrophilicity within the HEMA-EMA series and no time delay with the hydroxystyrene-styrene series. The time delay is thought to be a function of the excluded volume provided by polymers that are able to undergo significant chain rotation and or swelling in the solvent, water. Small excluded volumes present in copolymers of high EMA content and all hydroxystyrene-styrene copolymers offer little or no resistance to formation of adhesive bonds by macrophages, whereas copolymers with large excluded volumes (high HEMA content) prevent contact and/or adhesion. A mechanism based on the net excluded volumes of both the cell and substrate surface macromolecule is proposed to explain this phenomenon.

Animals↗

Glucose-sensitive membranes containing glucose oxidase: activity, swelling, and permeability studies.

The development of membranes that swell in response to glucose is reported. The membranes may prove to be useful in glucose monitoring or glucose-dependent insulin delivery. The polymers were synthesized by the radiation-induced polymerization of frozen solutions containing hydroxyethylmethacrylate, N,N-dimethylaminoethyl methacrylate, tetraethylene glycol dimethacrylate, ethylene glycol, water, and glucose oxidase. The polymers were hydrogels, with water contents in the range of 60-90%, depending on the pH or glucose concentration. Changes in swelling and permeability of the hydrogel were caused by exposure to glucose solutions. The gluconic acid formed by the glucose oxidase catalyzed oxidation of glucose in the membrane lowered the pH of the system and thus caused the changes in the membrane. The retention of enzyme activity by the membranes in vitro and in vivo is also reported. The large differences in properties among membranes made with different chemical formulations suggest that glucose-sensitive membranes with performance characteristics needed for an artificial pancreas may be an achievable goal.

Acrylates↗

The kinetics of baboon fibrinogen adsorption to polymers: in vitro and in vivo studies.

Fibrinogen adsorption on polymers from blood may mediate or potentiate thrombosis because of its involvement in both the intrinsic clotting system and the formation of platelet aggregates. While the kinetics of fibrinogen adsorption from plasma in vitro have previously been found to be very different on polar and nonpolar surfaces [T. A Horbett, "The kinetics of adsorption of plasma proteins to a series of hydrophilic-hydrophobic copolymers," ACS Org. Coat. Plas. Chem. 40, 642-646 (1979)] the significance of this difference with respect to thrombogenesis in vivo has not been clarified. In this study, the kinetics of deposition of baboon 125I fibrinogen from plasma in vitro or from blood in vivo on a series of polymers was measured. The polymers chosen for this study had previously been found to have a large range in surface polarity and reactivity in the in vivo baboon shunt model. The kinetics of fibrinogen adsorption in vitro were observed to be of three types, depending on the polymer: high initial adsorption decreasing to a lower steady state value; constant throughout the time course; low initial adsorption rising steadily to a plateau value. In vivo, fibrinogen deposition kinetics were of two types: low, constant deposition throughout the time course, independent of heparinization; low deposition initially followed by a second phase of greatly increased deposition (probably as fibrin) which was prevented or greatly decreased by heparinizing the animals. Polymers for which fibrinogen adsorption increased to a plateau in vitro were found to have a heparin inhibitable second phase of enhanced in vivo fibrinogen deposition. These polymers also have been found in previous studies to enhance the rate of platelet destruction when used as in vivo shunts on baboons. Conversely, most polymers with high initial in vitro fibrinogen adsorption followed by a decrease had low fibrinogen deposition behavior in vivo and were also minimally destructive of platelets. The adsorption kinetics of fibrinogen to polymers from blood in vivo and in vitro and the consumption of platelets in vivo induced by the polymers all vary with polymer polarity. More polar polymers had in vitro fibrinogen kinetics characterized by a rise to a plateau, in vivo fibrinogen deposition characterized by a second stage of great increase inhibitable by heparin, and enhanced platelet consumption. The correlation of three separate indicators of surface thrombogenicity with surface polarity suggests that more polar materials may be more thrombogenic because of an influence on the way in which fibrinogen interacts with these surfaces.

Adsorption↗

The biocompatibility of solution cast and acetone-extracted cast Biomer.

The cellular response to films of cast Biomer and acetone-extracted Biomer were investigated over a 21-day implantation period, using an in vivo cage implant system. Film samples were characterized by scanning electron microscopy (SEM), attenuated total reflectance infrared (ATR-IR), electron spectroscopy for chemical analysis (ESCA) and by contact angle measurements before implantation, and by SEM and ESCA after implantation and cleaning. Cellular and protein components of the inflammatory response were analyzed at periodic observation points after implantation. In addition, film samples were retrieved at 4, 7, and 21 days after implantation and analyzed for leukocyte adhesion by light microscopy and SEM. The results demonstrated that cast Biomer contains an extractable fraction, which when removed significantly improves the biocompatibility of the material.

Animals↗