Chemical and Physical Characterization of a Novel Poly(Carbonate Urea) Urethane Surface with Protein Crosslinker Sites

Abstract

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.

Covalent Linkage of Recombinant Hirudin to a Novel Ionic Poly(Carbonate) Urethane Polymer with Protein Binding Sites: Determination of Surface Antithrombin Activity

“…The synthesis of the biodurable polycarbonate‐based polyurethane containing carboxylic acid groups was performed as previously described ( 19). Briefly, the polymer was synthesized by a two step procedure utilizing the following: formation of diisocyanate terminated prepolymer, based on poly(1,6‐hexyl‐coz‐1,2‐ethyl carbonate) diol (PC1000, 1,000 daltons molecular weight) and 4,4′‐diphenylmethane diisocyanate (MDI), followed by chain extension with 2,2‐bis(hydroxymethyl)propionic acid (DHMPA).…”

“…Covalent linkage of sulfo‐SMCC to BSA was performed as previously described ( 14, 19). Briefly, 2 BSA solutions with concentrations of 1.1 m M and 0.54 m M were prepared.…”

“…Concurrently, 1 cm 2 segments of Mitrathane (Polymedica Industries, Golden, CO, U.S.A.) (which contain no carboxylic acid groups) and cPU (in which BSA would not be reacted with sulfo‐SMCC) as well as the test segments were cut and weighed (n =60 segments/test group). These segments were placed into borosilicate test tubes (4 segments/tube) and reacted with 3 ml of a 10 mg/ml EDC solution prepared in 50% ethanol as previously outlined ( 19).…”

“…The BSA‐SMCC complex was then covalently bound to a novel polyurethane surface containing surface bound carboxylic acid groups (cPU) via the crosslinker 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide hydrochloride (EDC). The proper ratio of alcohol solvent (50% ethanol) to dissolve the crosslinker EDC to yield the maximum BSA‐SMCC linkage (336 ng/cm 2 cPU) without compromising polymer integrity was previously determined ( 19).…”

Novel elastomeric polyurethanes with pendant epoxy groups as highly reactive auxiliary groups for further derivatizations

“…However, a restricted number of methods are known to provide a polyurethane macromolecule (which itself lacks highly reactive groups) with auxiliary groups suitable for the further modifications. Mostly, these methods rely on prepolymerization strategies, with the use of various functionalized blocks (usually, chain extenders) containing either sterically hindered carboxy groups8, 9 (to prevent undesirable interactions with isocyanates in the course of polymerization) or protected amino groups 10. Both variants are suboptimal: sterically hindered carboxy groups (derived from 2,2‐dimethylolpropionic acid) are poorly reactive in the further transformations, whereas the deprotection of amino groups can damage the polyurethane backbone.…”