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Biomedical subjects

B D Ratner

Publications and source records attributed to B D Ratner.

At least 37 records · Page 2Linked to original sources
PubMed1999

Mice that lack the angiogenesis inhibitor, thrombospondin 2, mount an altered foreign body reaction characterized by increased vascularity.

Disruption of the thrombospondin 2 gene (Thbs2) in mice results in a complex phenotype characterized chiefly by abnormalities in fibroblasts, connective tissues, and blood vessels. Consideration of this phenotype suggested to us that the foreign body reaction (FBR) might be altered in thrombospondin 2 (TSP2)-null mice. To investigate the participation of TSP2 in the FBR, polydimethylsiloxane (PDMS) and oxidized PDMS (ox-PDMS) disks were implanted in TSP2-null and control mice. Growth of TSP2-null and control skin fibroblasts in vitro also was evaluated on both types of disks. Normal fibroblasts grew as a monolayer on both surfaces, but attachment of the cells to ox-PDMS was weak and sensitive to movement. TSP2-null fibroblasts grew as aggregates on both surfaces, and their attachment was further compromised on ox-PDMS. After a 4-week implantation period, both types of PDMS elicited a similar FBR with a collagenous capsule in both TSP2-null and control mice. However, strikingly, the collagenous capsule that formed in TSP2-null mice was highly vascularized and thicker than that formed in normal mice. In addition, abnormally shaped collagen fibers were observed in capsules from mutant mice. These observations indicate that the presence or absence of an extracellular matrix component, TSP2, can influence the nature of the FBR, in particular its vascularity. The expression of TSP2 therefore could represent a molecular target for local inhibitory measures when vascularization of the tissue surrounding an implanted device is desired.

Animals↗
PubMed1999

Quantitative detection of silicone in skin by means of electron spectroscopy for chemical analysis (ESCA).

BACKGROUND: Evaluation of silicone-induced morbidity in skin has been hampered by the difficulty of detecting silicone in tissue because conventional methods are nonquantitative and insensitive. OBJECTIVE: We attempted to determine whether silicone could be identified and quantitated in skin by means of electron spectroscopy for chemical analysis (ESCA). METHODS: Skin biopsy specimens were obtained from the nose, chin, malar region, and inner arm of a patient who had received injections of silicone gel in his nose and chin. Frozen sections were dried under vacuum and examined by means of ESCA. Contiguous sections were examined by light microscopy. RESULTS: The surface concentrations of silicone were as follows: chin, 20.6% +/- 3.6%; nose, 19.0%; malar region, 2.6% +/- 1.6%; inner arm, 0.0% +/- 0.0%. Light microscopy revealed homogeneous "globules" consistent with silicone in the chin and nose sections only; the malar region and inner arm sections showed no evidence of silicone. CONCLUSION: ESCA can be used to detect silicone in skin in a specific, highly sensitive, and quantitative manner. This is the first report of quantification of silicone in skin by means of ESCA.

Arm↗
PubMed1998

Glow discharge plasma deposition (GDPD) technique for the local controlled delivery of hirudin from biomaterials.

PURPOSE: Biomaterials which release locally high concentrations of antithrombotic agents should lessen the thrombogenicity of the materials. To evaluate this approach, we prepared novel polyurethane matrices loaded with hirudin and coated them with 2-hydroxyethyl methacrylate (HEMA) by glow discharge plasma deposition (GDPD) to reduce the release rate. METHODS: Polyurethane (BioSpan) matrices containing hirudin and pore former (d-mannitol or BSA) were prepared by the solvent casting method. HEMA plasma deposition was then applied using GDPD technique to create a diffusional barrier film on the surface of the matrices. The effect of pore former and HEMA plasma coating on the release of hirudin was systematically investigated. Surface properties of matrices was also studied using Scanning Electron Microscopy (SEM) and Electron Spectroscopy for Chemical Analysis (ESCA). RESULTS: The release of hirudin from BioSpan matrix could be controlled by changing the weight fraction and particle size of pore former. HEMA plasma treatment of matrices produced a thin, highly cross-linked film on the surface. The initial burst and subsequent release of hirudin was significantly reduced after HEMA plasma coating, which suggested that the plasma disposition acted as a diffusional barrier and limited the release of hirudin incorporated in the polyurethane matrix. CONCLUSIONS: The plasma coating served as a diffusional barrier, and could work to control the release kinetics of hirudin by changing the various plasma coating conditions. Local delivery of hirudin using these biomaterials at the site of cardiovascular diseases can have the advantage of regional high levels of hirudin, as well as lowering systemic hirudin exposure, thereby minimizing the possibility of side effects.

Antithrombins↗
PubMed1998

Rapid postadsorptive changes in fibrinogen adsorbed from plasma to segmented polyurethanes.

Fibrinogen adsorbed to biomaterials plays a key role in mediating platelet interactions that can lead to blood clotting so its behavior on surfaces is of fundamental interest. In previous work showing that fibrinogen adsorbed to surfaces quickly becomes non-displaceable upon exposure to blood plasma, the fibrinogen was adsorbed from buffer, so we performed new studies in which the displaceability of fibrinogen adsorbed from plasma was characterized. Fibrinogen was adsorbed from 1% plasma to seven different surfaces for 1-64 min and then transferred to 100% plasma lacking radiolabeled fibrinogen and the amount adsorbed before and after transfer measured. The surfaces were glass, Silicone rubber, and five different polyurethanes. As adsorption time increased, the fibrinogen became increasingly resistant to displacement during the 100% plasma step, but the rate of increase in resistance varied greatly with surface type. Fibrinogen adsorbed from 1% plasma evidently undergoes rapid, surface dependent transitions. This work shows that the transitions that occur when the fibrinogen is adsorbed from blood plasma are similar to what we have previously observed for fibrinogen adsorbed from buffer.

Adsorption↗
PubMed1997

Scanning probe microscopy for the characterization of biomaterials and biological interactions.

The scanning probe microscopies provide a unique view of biological and biomedical systems at a nanoscale appropriate to appreciate molecular events. The advent of these methods has brought the ability to acquire quantitative information at the molecular level. Given the proliferation of microscopes and associated methods, the probability for important discoveries is high. If tempered with an appreciation for the potential for artifacts, the SPMs may revolutionize our view of biological systems and biomaterials interactions with those systems.

Animals↗
PubMed1997

A new method for straightening DNA molecules for optical restriction mapping.

We have developed an improved method of straightening DNA molecules for use in optical restriction mapping. The DNA was straightened on 3-aminopropyltriethoxysilane-coated glass slides using surface tension generated by a moving meniscus. In our method the meniscus motion was controlled mechanically, which provides advantages of speed and uniformity of the straightened molecules. Variation in the affinity of the silanized surfaces for DNA was compensated by precoating the slide with single-stranded non-target blocking DNA. A small amount of MgCl2 added to the DNA suspension increased the DNA-surface affinity and was necessary for efficient restriction enzyme digestion of the straightened surface-bound DNA. By adjusting the amounts of blocking DNA and MgCl2, we prepared slides that contained many straight parallel DNA molecules. Straightened lambda phage DNA (48 kb) bound to a slide surface was digested by EcoRI restriction endonuclease, and the resulting restriction fragments were imaged by fluorescence microscopy using a CCD camera. The observed fragment lengths showed excellent agreement with their predicted lengths.

Bacteriophage lambda↗
PubMed1995

Investigating the relationship between surface chemistry and endothelial cell growth: partial least-squares regression of the static secondary ion mass spectra of oxygen-containing plasma-deposited films.

The relationship between endothelial cell growth and surface properties of plasma-deposited films (PDFs) was investigated using partial least-squares regression (PLS). PDFs of oxygen-containing precursors were prepared under various conditions, and bovine arterial endothelial cells (BAECs) were grown on these substrates. Secondary ion mass spectrometry (SIMS) in the static mode was used to characterize the surface chemistry of these substrates. The growth of BAECs on the PDFs was correlated to the positive and negative static SIMS spectra of the PDFs by PLS. A good correlation between the SIMS spectra of PDFs and endothelial cell growth was obtained. Qualitative information was also extracted from the multivariate model, giving some information as to the most important variables influencing BAEC growth.

Animals↗
PubMed1995

Direct measurement of hydrogen bonding in DNA nucleotide bases by atomic force microscopy.

We have used self-assembled purines and pyrimidines on planar gold surfaces and on gold-coated atomic force microscope (AFM) tips to directly probe intermolecular hydrogen bonds. Electron spectroscopy for chemical analysis (ESCA) and thermal programmed desorption (TPD) measurements of the molecular layers suggested monolayer coverage and a desorption energy of about 25 kcal/mol. Experiments were performed under water, with all four DNA bases immobilized on AFM tips and flat surfaces. Directional hydrogen-bonding interaction between the tip molecules and the surface molecules could be measured only when opposite base-pair coatings were used. The directional interactions were inhibited by excess nucleotide base in solution. Nondirectional van der Waals forces were present in all other cases. Forces as low as two interacting base pairs have been measured. With coated AFM tips, surface chemistry-sensitive recognition atomic force microscopy can be performed.

Adenine↗
PubMed1995

Surface modification of polymers: chemical, biological and surface analytical challenges.

Surface modification methods can optimise the biocompatibility or the specificity of biointeraction of a biosensor or medical device. With only the surface modified, the manufacture and implantation protocol remain unchanged. This review article summarises some of the chemical, surface analytical and biological challenges associated with surface modification of biosensors and biomedical devices.

Biocompatible Materials↗
PubMed1995

The relationship between ligand-binding thermodynamics and protein-ligand interaction forces measured by atomic force microscopy.

The interaction forces between biotin and a set of streptavidin site-directed mutants with altered biotin-binding equilibrium and activation thermodynamics have been measured by atomic force microscopy. The AFM technique readily discriminates differences in interaction force between the site-directed (Trp to Phe or Ala) mutants. The interaction force is poorly correlated with both the equilibrium free energy of biotin binding and the activation free energy barrier to dissociation of the biotin-streptavidin complex. The interaction force is generally well correlated with the equilibrium biotin-binding enthalpy as well as the enthalpic activation barrier, but in the one mutant where these two parameters are altered in opposite directions, the interaction force is clearly correlated with the activation enthalpy of dissociation. These results suggest that the AFM force measurements directly probe the enthalpic activation barrier to ligand dissociation.

Bacterial Proteins↗
PubMed1995

Silicone derivatives for contact lenses: functionalization, chemical characterization, and cell compatibility assessment.

Epoxy ring-opening functionalization of polymers at random sites along chains with various chemical groups has been demonstrated. The reaction is performed in an aqueous solution under mild conditions in order to minimize degradation of the macromolecular chains. Silicone lenses made of copolymers with epoxy side chains were functionalized with 4-hydroxybutyric acid, sodium salt. The carboxylated silicone derivatives were characterized by ESCA and radiotracers. A mean value of 30% reaction yield was concluded, based upon data from both methods; nevertheless, the latter can be improved up to 50% or more if the conditions of preparation of the epoxydized silicone lenses are optimized. Derivatized silicones were coated in the wells of culture plates to evaluate the cell compatibility of these new polymers with a fibroblast cell line (McCoy's). No cellular toxicity was observed.

Benzylamines↗
PubMed1994

In vitro study of the intrinsic toxicity of synthetic surfaces to cells.

A trypan blue inclusion assay was used to measure cell death on poly(dimethyl siloxane) (PDMS), polyethylene (PE), poly(methyl methacrylate) (PMMA), polyurethanes, glass, and glow-discharge-treated polystyrene or poly(ethylene terephthalate). Cell lines used were bovine aortic endothelial, 3T3, mouse peritoneal macrophage, and BHK cells. In the absence of proteins in the media, PDMS, PE, PMMA, and some polyurethanes were consistently found to induce cell death. This toxic effect disappeared if the cells were seeded in serum-containing medium or if concentrated solutions of proteins (albumin, IgG, or fibronectin) were preadsorbed on the materials. The substrate toxicity appeared to be due to the physical properties of the substrate and not to the release of toxic leachables.

3T3 Cells↗
PubMed1994

Developing correlations between fibrinogen adsorption and surface properties using multivariate statistics. Student Research Award in the Doctoral Degree Candidate Category, 20th annual meeting of the Society for Biomaterials, Boston, MA, April 5-9, 1994.

A multivariate model based on the partial least squares algorithm (PLS) was constructed in order to establish a correlation between the surface properties of common polymeric materials and the amount and retention of fibrinogen absorbed from a complex mixture. Surface characterization was performed by means of static secondary ion mass spectroscopy (SIMS), electron spectroscopy for chemical analysis (ESCA), and by contact angle measurements of several liquids on those materials. 125I-fibrinogen was adsorbed from a 1% plasma solution in buffer and the amount adsorbed after 2 h was determined. After 5 days of residence time in buffer, the adsorbed fibrinogen was eluted with a 1% solution of the surfactant sodium dodecyl sulfate (SDS). The percent of fibrinogen that remained on the surfaces after elution is referred to as fibrinogen retention. Correlations between surface properties and the amounts of fibrinogen adsorbed or fibrinogen retention were established. These models also show the most important variables that are related to the protein behavior on these surfaces.

Adsorption↗
PubMed1994

Oxidative degradation of Biomer fractions prepared by using preparative-scale gel permeation chromatography.

The possibility that some macromolecular chains within a chemically heterogeneous polyether-urethane (PEU) may be more susceptible to degradation than others has been investigated. Preparative scale gel permeation chromatography has been used to separate chemically different fractions of a sample of the commercial PEU, Biomer. The fractions were characterized and then tested for susceptibility to oxidative degradation by exposing them to hydrogen peroxide. After exposure to hydrogen peroxide, the samples were analyzed using high pressure gel permeation chromatography (HPGPC), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). By using these methods, we were able to identify chemical changes in some of the Biomer fractions but not in others. Clear differences in the chemistry and reactivity of the fractions were observed. Changes in the weight average molecular weight varied from a decrease of 55.8% to an increase of 3.9%. A decrease in hard segment content at the surface and in the bulk was observed in some samples, but opposite trends were observed in others. The evidence suggests that there may be a number of mechanisms by which hydrogen peroxide can react with PEUs. Some fractions separated from the Biomer were not significantly affected by concentrated hydrogen peroxide solutions. This suggests an intrinsic stability in some PEUs and points the way to the development of more degradation-resistant PEUs.

Biocompatible Materials↗
PubMed1993

Static secondary ion mass spectrometric investigation of the surface chemistry of organic plasma-deposited films created from oxygen-containing precursors. 3. Multivariate statistical modeling.

Partial least squares (PLS) multivariate statistical models were developed to predict the surface composition and chemistry of a set of model homopolymers based on their static SIMS fragmentation patterns. In the calibration or model-building step, the positive and negative ion static SIMS spectra of different classes of model homopolymers were related to specific chemical attributes of the polymers. The models were then used to examine the surface chemistry of oxygen-containing plasma-deposited films prepared from a variety of precursors. PLS models were developed to predict the surface oxygen concentration and H/C ratios. The results obtained from the PLS models were compared with experimental results.

Analysis of Variance↗
PubMed1993

Static secondary ion mass spectrometry of adsorbed proteins.

Static secondary ion mass spectrometry (SIMS) was used to analyze proteins adsorbed to biomaterial surfaces. A spectral interpretation protocol was established by examining homopolymers of 16 amino acids. This protocol allows for the assignment of peaks unique to the various amino acids. Static SIMS was used to analyze plasma proteins adsorbed to titanium. The various factors that contributed to the relative intensities observed in the spectra were explored. The potential application of the technique for studying protein-fouled materials was investigated by analyzing a fouled sensor membrane.

Adsorption↗