Biomedical subjects

J R Frautschi

Publications and source records attributed to J R Frautschi.

7 recordsLinked to original sources

PubMed1996

Calcification of polyurethanes implanted subdermally in rats is enhanced by calciphylaxis.

Calcification complicates the use of the polymer polyurethane in cardiovascular implants. To date only costly experimental circulatory animal models have been useful for investigating this disease process. In this paper we report that polyurethane calcification in rat subdermal implants is enhanced by overdosing with a vitamin-D analog. The calcification-prone state, known as calciphylaxis, was induced in 4-week old rats by oral administration of a vitamin-D analog, dihydrotachysterol. We studied two commercially available polyurethanes (Biomer and Mitrathane) and two proprietary polyurethanes (PEU-2000 and PEU-100). PEU-100 is unique because it is derivatized with ethanehydroxy-bisphosphonate (EHBP) for calcification resistance. Polyurethane calcium and phosphate levels and morphological changes due to calciphylaxis were compared with those of control rat subdermal explants in 60-day studies. Increased polyurethane mineralization was observed due to calciphylaxis with 60-day rat subdermal explants of Biomer, Mitrathane, and PEU-2000 (calcium levels, respectively, 4.13 +/- 0.56, 18.61 +/- 2.73, and 3.37 +/- 0.22 microgram/mg, mean +/- standard error) as compared to control explants (calcium levels, respectively, 1.22 +/- 0.1, 12.57 +/- 0.86, and 0.20 +/- 0.86 microgram/mg). The study also demonstrated that with 60-day implants calciphylaxis had no side effects on somatic growth and serum calcium levels. Explant surface morphology of these polyurethane explants examined by scanning electron microscopy, back scattering electron imaging coupled with energy dispersive X-ray spectroscopy, and light microscopy demonstrated the presence of predominantly surface-oriented calcification. PEU-100, derivatized with 100 n.moles/ mg of EHBP, resisted calcification with explant calcium levels 0.51 +/- 0.01 (calciphylaxis) and 0.38 +/- 0.01 (control) microgram/mg. It is concluded that calciphylaxis enhances superficial polyurethane calcification in rat subdermal implants and that an EHBP-modified polyurethane resists calcification despite calciphylaxis. Rat subdermal implants using calciphylaxis may be generally useful for evaluating the calcification potential of various biomedical polymers.

Animals↗

PubMed1996

Alkylation of cellulosic membranes results in reduced complement activation.

4-Vinyl pyridine was grafted to the surface of the cellulosic membrane Cuprophan, and subsequently alkylated with both C10 and C16 aliphatic chains. Complement activation of heparinized human blood, corrected for anaphylatoxin adhesion, was measured by radioimmunoassay. The surface treatments both yielded substantial reductions in C5a activity, with a lessor reduction in C3a and C4a activity. Alkylation with 10 and 16 carbon chains resulted both in enhancements of albumin adsorption and stability. These enhancements as well as the reductions in complement activation were statistically indistinguishable between the two treatments. The reduction in complement activation was influenced more by adsorption of endogenous albumin and possibly by the vinyl pyridine graft, than the removal of surface active hydroxyl groups from Cuprophan.

Adsorption↗

PubMed1995

Alkylated cellulosic membranes with enhanced albumin affinity: influence of competing proteins.

4-Vinyl pyridine was grafted to the surface of the cellulosic membrane Cuprophan, and subsequently alkylated with both non-fatty acid-like C10 (GVP-C10) and fatty acid-like C16 (GVP-C16) aliphatic chains. In vitro albumin adsorption studies from single and binary protein solutions, as well as from dilute plasma demonstrated a significant enhancement (1.4-3.89 times) of albumin binding to both the GVP-C10 and GVP-C16 surfaces, relative to unmodified Cuprophan. It is speculated that enhanced albumin adsorption to a surface may improve surface thromboresistance. Further, these results suggest that there is no difference between the enhanced albumin adsorption of the fatty acid and nonfatty like alkyl chains, C10 and C16.

Adsorption↗

PubMed1994

Phosphonated polyurethanes that resist calcification.

Cardiovascular implant mineralization involving bioprosthetic materials, such as glutaraldehyde cross linked porcine aortic valves or synthetic materials such as polyurethanes, is an important problem that frequently leads to clinical failure of bioprosthetic heart valves, and complicates long-term experimental artificial heart device implants. Novel, proprietary, calcification resistant polyetherurethanes (PEU) as an alternative to bioprosthetic materials were the subject of these investigations. A series of PEU was derivatized through a proprietary reaction mechanism to achieve covalent binding of 100 to 500 nM/mg of bisphosphonate (2-hydroxyethane bisphosphonic acid, HEBP). The stability of HEBP (physically dispersed or covalently bound) verified by studying the release kinetics in physiological buffer (pH 7.4) at 37 degrees C, demonstrated the covalent binding reaction to be stable, efficient, and permanent. Surface (FTIR-ATR, ESCA, SEM/EDX) and bulk (solubility, GPC) properties demonstrated that the covalent binding of HEBP occurs in the soft segment of the PEU, reduces surface degradation, and does not affect the original material properties of the PEU (prior to derivatization). In vitro calcium diffusion of the derivatized PEU showed a decrease in calcium permeation as the concentration of HEBP covalent binding was increased. In vivo properties of underivatized and derivatized PEU (containing 100 nM of covalently bound HEBP) were studied with rat subdermal implants for 60 days. Explants demonstrated calcification resistance due to the covalently bound HEBP without any side effects. It is concluded that a PEU containing HEBP might serve as a calcification resistant candidate material for the fabrication of a heart valve prosthesis and other implantable devices.

Animals↗

PubMed1987

Influence of endogenous albumin binding on blood-material interactions.

A method has been developed to enhance the albumin affinity of a number of medical polymers, based on alkylation of the surface with straight-chain 16- or 18-carbon alkyl groups. This method has been demonstrated to induce the rapid binding of albumin from single and binary protein solutions, from plasma, and apparently, from whole blood. The bound albumin resists fluid shear or chemically induced desorption. Fibrinogen adsorption is inhibited in vitro and in vivo. Complement protein C3 activation from plasma is inhibited. Fibrin formation and platelet aggregation is inhibited in short-term in vivo experiments. Long-term catheter implant studies suggest that the C18 alkylation is more effective than most, if not all, currently available treatments for the retention of a clean, biocompatible, blood-contacting surface. No data have been obtained to date that conflict with the hypothesis that a renewable albumin layer, so formed, blocks the adsorption or conformational alteration of plasma proteins that otherwise might initiate or participate in various host defenses.

Animals↗

PubMed1983

Alkyl derivatized cellulose acetate membranes with enhanced albumin affinity.

Alkylation techniques have been developed for C16 derivatization of cellulose acetate membranes. High yields of alkylated cellulose acetate were obtained which led to correspondingly high yields in albumin adsorption. Centrifugation improved impurity removal and enhanced albumin binding to the membrane. The affinity of the alkylated membranes for albumin diminished with increasing degrees of alkylation, which we attribute to steric hindrance effects. The results suggest that improved thromboresistance may be obtained by such means for hemodialysis, plasmapheresis and other filtration applications.

Adsorption↗

PubMedDate not supplied

Enhanced albumin affinity of silicone rubber.

The authors have developed a method to increase the albumin affinity of silicone rubber-containing medical devices. A vinyl-methyl silicone co-monomer was hydroxylated via an oxymercuration-demercuration reaction and then film-coated on a silicone rubber sheet. C16 acylation of the -OH coated sheet was carried out by an esterification reaction catalyzed by 4-DMAP. FTIR spectroscopy confirmed the presence of -OH groups following the hydroxylation reaction, and (CH2)n groups following the acylation reaction. 125I-labeled albumin binding studies indicated graded enhancements, according to reagent concentration, with maximal 2.7X and 2.5X increases for 20% -OH coated and 20% -OH/C16 acylated surfaces, respectively. Incubation with a protein denaturant, sodium dodecyl sulfate (SDS), removed 73% of adsorbed albumin from unmodified controls, with only 25 and 34% removal from 20% -OH coated and 20% -OH/C16 acylated surfaces, respectively. These results suggest that -OH and C16 modified surfaces not only preferentially adsorb albumin, but also retain it in a more stable configuration; this is an unexpected finding for -OH modified surfaces. Based on similar albumin affinities for biocompatible C18 alkylated and C16 acylated polyether polyurethanes, the authors expect significant improvements in thromboresistance and complement-activating potential for this modified silicone rubber.

Acylation↗