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Biomedical subjects

M Szycher

Publications and source records attributed to M Szycher.

At least 19 recordsLinked to original sources
PubMed1999

End-stage renal disease (ESRD) and vascular access grafting: a critical review.

End-Stage Renal Disease (ESRD) is a major disease state, costing the U.S. $9.5 billion in 1992, and increasing 10% yearly. The growth in the number of ESRD patients can be attributed principally to demographic trends: the aging of the general population and the improved treatment and increased survival rate of patients with diabetes, hypertension, and other illnesses that lead to ESRD. Moreover, improved dialysis technology has enabled older patients and those who previously could not tolerate dialysis due to other illnesses to benefit from this treatment. Three modalities exist for the treatment of ESRD: hemodialysis, peritoneal dialysis, and kidney transplant. This article reviews the medical treatments and the synthetic polymers used in the manufacture of vascular access grafts. We report on the development of a new, polyurethane-based microporous vascular graft, which displays self-sealing and improved compliance characteristics for use in vascular access grafting.

Biocompatible Materials↗
PubMed1998

Covalent linkage of recombinant hirudin to a novel ionic poly(carbonate) urethane polymer with protein binding sites: determination of surface antithrombin activity.

Surface thrombus formation on implantable biomaterials such as polyurethane is a major concern when utilizing these materials in the clinical setting. Thrombin, which is responsible for thrombus formation and smooth muscle cell activation, has been the target of numerous surface modification strategies in an effort to prevent this phenomenon from occurring. The purpose of this study was to covalently immobilize the potent, specific antithrombin agent recombinant hirudin (rHir) onto a novel polyurethane polymer synthesized with carboxylic acid groups which served as protein attachment sites. The in vitro efficacy of thrombin inhibition by this novel biomaterial surface was then evaluated. Bovine serum albumin (BSA), which was selected as the basecoat protein, was reacted with sulfo-SMCC in a 1:50 molar ratio. This BSA-SMCC complex was then covalently linked to the carboxylated polyurethane (cPU) surface via the crosslinker EDU (cPU-BSA-SMCC). This cPU-BSA-SMCC surface was then reacted with Traut's-modified 125I-rHir, a procedure which created free sulfhydryl groups on rHir (cPU-BSA-SMCC-S-125I-rHir). Using these crosslinking procedures, the cPU-BSA-SMCC-S-125I-rHir segments bound 188 +/- 40 ng/cm2 (n = 60) whereas the controls with non-specifically bound 125I-rHir (Mitrathane + EDC + BSA + 125I-rHir-SH and cPU-BSA + 125I-rHir-SH) bound 13 +/- 8 ng/cm2 and 4 +/- 8 ng/cm2, respectively. Evaluation of these cPU-BSA-SMCC-S-125I-rHir segments for 131I-thrombin inhibition using a chromogenic assay for thrombin showed that a maximum of 2.64 NIHU thrombin was inhibited in contrast to the controls which inhibited bound 0.76 and 0.70 NIHU. Controls with nonspecifically bound 125I-rHir also had 0.31 and 0.76 NIHU 131I-thrombin adherent to their respective surfaces whereas the maximum 131I-thrombin binding to the cPU-BSA-SMCC-S-rHir segments was 1.51 NIHU. Exposure to 131I-thrombin did not result in any release of covalently bound 125I-rHir from the cPU-BSA-SMCC-S-125I-rHir segments. Thus, these results demonstrate that rHir can be covalently bound to this novel polyurethane surface and still maintain potent antithrombin activity.

Antithrombins↗
PubMed1998

In vitro and in vivo biodurability of a compliant microporous vascular graft.

Polyurethanes have unique mechanical and biologic properties that make them ideal for many implantable devices. However, certain polyurethanes are affected by some in vivo degradation mechanisms. For example, poly(ester)urethanes are subject to hydrolytic degradation and are no longer used in long-term implanted devices. Poly(ether)urethanes while hydrolytically stable, are subject to oxidative degradation in several forms, including environmental stress cracking and metal ion oxidation. We have developed a second-generation poly(carbonate)urethane with superior biostability. This material has been fabricated by our patented method into small diameter microporous vascular grafts. We evidenced the biodurability of our vascular graft by in vitro qualification tests which compared the poly(carbonate)urethane with a traditional poly(ether)urethane. This poly(carbonate)urethane graft has also proven to be biodurable in in vivo experimental implants up to twenty months duration with no evidence of hydrolysis or environmental stress cracking (ESC).

Animals↗
PubMed1997

Chemical and physical characterization of a novel poly(carbonate urea) urethane surface with protein crosslinker sites.

A major complication which occurs with implantable polyurethane biomaterials is bioincompatibility between blood and the biomaterial surface. Development of a novel biodurable polyurethane surface to which biological agents, such as growth factors or anticoagulants could be covalently bound, would be beneficial. The purpose of this study was to synthesize a novel poly(carbonate urea) urethane polymer with carboxylic acid groups which would serve as "anchor" sites for protein attachment. Physical characteristics such as tensile strength, initial modulus, ultimate elongation, tear strength, water/alcohol uptake and water vapor permeation were then evaluated and compared to other biomedical-grade polyurethanes. Covalent linkage of the blood protein albumin to this novel surface was then examined. A biodurable polycarbonate-based polyurethane containing carboxylic acid groups (cPU) was synthesized using a two step procedure incorporating the chain extender 2,2-bis(hydroxymethyl)-propionic acid (DHMPA). Tensile strength of this cPU film was 2.7 and 2.6 fold greater than both a polycarbonate-based polyurethane synthesized with a 1,4-butanediol chain extender (bdPU) and Mitrathane (Mit) controls, respectively. The cPU polymer also possessed 7.8 and 31 fold greater structural rigidity upon evaluation of initial modulus as compared to the bdPU and Mit, respectively. Ultimate elongation for the bdPU films was slightly higher than the cPU and Mit films, which had comparable elongation properties. The force required to tear the bdPU film was 1.9 and 32 fold greater than the cPU and Mit films, respectively. Alcohol solution uptake by all of the polyurethane segments increased with increasing alcohol concentrations, with the cPU having the greatest uptake. Water uptake was minimal for all the polyurethanes examined and was not affected by altering pH. Water vapor permeation was lowest for the cPU films as compared to both bdPU and Mit. Swelling the cPU in 50% ethanol prior to evaluation slightly increased water vapor permeation through the films. Covalent linkage of the radiolabelled blood protein albumin (125I-BSA) to the cPU segments incubated with the heterobifunctional crosslinker 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) was greatest in the higher percent of ethanol as compared to controls. These results serve as foundation for developing a novel poly(carbonate urea) urethane with physical characteristics comparable to other medical-grade polyurethanes while having protein binding capabilities.

Adsorption↗
PubMed1996

Resistance to biodegradative stress cracking in microporous vascular access grafts.

Degradative cracking, more commonly known as "environmental stress cracking" (ESC) has been observed in many implanted polyetherurethane elastomers. This phenomenon has been attributed to biochemical and cellular interactions at the surface of the implanted material causing polymer chain cleavage. This may result in surface fissuring followed by the deep cracking associated with considerable biodegradation of the polymer, resulting in loss of mechanical strength and the formation of aneurysms in an in vivo situation. These cracking effects are believed to be due to mechanical stress combined with the oxidising actions of macrophages and giant cells, as surface cracking has been observed to occur directly under adherent macrophages on a polyetherurethane implant. These cells form part of the body's immune response which uses enzymes and reactive oxygen species (O2, O2-, and HO. and H2O2) to degrade foreign material. We describe a modification of an in vitro test method developed by Zaho et al. [1] using glass wool and a Hydrogen Peroxide/Cobalt (II) Chloride (H2O2/CoCl2) mixture to replicate the oxidising effects of macrophages in vivo. The modifications were made to establish a routine testing system for resistance to biodegradation which could be used to screen a range of polymers designed for use in microporous vascular grafts. The grafts are pre-stressed by a method devised by Stokes et al. [2] where each graft is stretched to a predetermined elongation over a mandrel and the strain is fixed by tying PTFE tape around each end of the mandrel.

Biocompatible Materials↗
PubMed1992

Modern wound dressings: a systematic approach to wound healing.

The advent of modern wound care management constitutes one of the most innovative applications of medical device technology. The foundation for wound care recent advances has been built upon the developments achieved in polymer technology over the last three decades. New and unique materials have been engineered to provide properties with significant technical and clinical benefits. These new wound care products were made possible by the convergence of three interrelated disciplines: (1) more complete understanding of the underlying principles of dermal wound healing processes, (2) new elastomeric polymers capable of being fabricated into protective dressings, and (3) advances in breathable adhesive technology. The following discussion provides a critical review of the current status of technology and the worldwide opportunities for improved wound management products. Particular attention is focused on the clinical applications of the newer, breathable dressing products, which approximate a temporary synthetic artificial skin.

Bandages↗
PubMed1992

Biostable polyurethane elastomers.

The generic term polyurethane represents the most versatile family of synthetic polymers. The unsurpassed physical and chemical properties of polyurethanes, coupled with their biocompatibility, have led to their use in a wide range of biomedical applications. Although polyurethanes have been shown to be stable in vitro for many years, they can undergo rapid microcracking when implanted. These microcracks not only weaken the polymer but also serve as nucleation sites for thrombus formation and lead to catastrophic failure. In this article, the authors report on the development and testing of a new ether-free polyurethane that does not exhibit surface microcracking under accelerated in vivo condition.

Animals↗
PubMed1991

Polyurethane-covered mammary prosthesis: a nine year follow-up assessment.

We have examined ten tissue capsules from patients ranging from five months to nine years of mammary implantation. Contrary to published reports of polyurethane foam "fragmentation" or "disappearance" in the capsules evaluated, the polyurethane foam was still present and embedded in the surrounding tissue capsule. The foam was nearly always invisible by gross observation, or manual palpation. Only after enzymatic digestion of the tissue capsule did the foam become clearly visible as continuous sheets. ESCA analyses show that explanted foams are devoid of nitrogen peaks. Only carbon, oxygen and silicone signals are observed. The same foams do show nitrogen peaks (due to urethane linkages) when probed by FTIR. Since ESCA only analyzes the first 40-50 Angstroms of a surface, we believe that a "protective coating" composed of soft segments has formed. Beneath this "coating" the original polyurethane composition is still present as evidenced by FTIR analysis. Three possible explanations are advanced: (1) The surface hydrolysis, which takes place within the soft segment of the polyurethane polymer, results in the formation of oligomer(s). These oligomers, devoid of urethane linkages, appear to protect the polymer from further bioresorption, by significantly retarding the rate of additional surface hydrolysis. (2) Chain cleavage occurs in the soft segment producing a hydrophilic polyester chain end which orients into the interfacial area. These chain ends then produce a skin effect which increases the distance from the surface to the hard segments, or urethane-containing linkages. (3) Macromolecular motion in the soft segment phases of the polymer could be reorienting under the influence of the in vivo environment, thus producing a surface layer or "coating" which is predominantly soft segment in composition. Regardless of which of the three hypotheses proves to be most plausible, we interpret the data as showing that the polyurethane foam cover undergoes very slow bioresorption, even after 9 years of human implantation. The data further suggests that the in vivo surface of the polyurethane foam cover is biocompatible and interfacial interactions with inflammatory cells are downregulated or reduced because of the apparent biocompatibility of the material.

Biocompatible Materials↗
PubMed1991

An assessment of 2,4 TDA formation from Surgitek polyurethane foam under simulated physiological conditions.

Samples of polyurethane foam used in the manufacture of mammary prostheses were enzymatically treated for a total of thirty days. Papain (a plant thiol endopeptidase which has similar activity to the human lysosomal enzyme cathepsin B) was our enzyme of choice since it has both amidase as well as esterase activity. The experiment was conducted under physiological conditions closely simulating the microenvironment likely to be found around an implanted mammary prosthesis. In our tests, 2,4 TDA was formed during enzymatic attack of this TDI-based polyurethane foam for the first four (4) days, reaching a maximum of 8.3 parts per million. After the initial burst, no further TDA was observed within the limits of detection of the experiment (10 parts per billion). Based on standard risk assessment, this amount of TDA translates into a risk of developing cancer of one in four hundred million.

Animals↗