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具有蛋白质交联位点的新型聚(碳酸酯脲)聚氨酯表面的化学和物理特性

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

作者信息

Phaneuf M D, Quist W C, LoGerfo F W, Szycher M, Dempsey D J, Bide M J

机构信息

Beth Israel Deaconess Medical Center/Harvard Medical School, Department of Surgery, Boston, MA 02115, USA.

出版信息

J Biomater Appl. 1997 Oct;12(2):100-20. doi: 10.1177/088532829701200202.

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.

摘要

可植入聚氨酯生物材料出现的一个主要并发症是血液与生物材料表面之间的生物不相容性。开发一种新型的生物耐久性聚氨酯表面,使生长因子或抗凝血剂等生物制剂能够共价结合在上面,将是有益的。本研究的目的是合成一种带有羧酸基团的新型聚(碳酸酯脲)聚氨酯聚合物,该聚合物将作为蛋白质附着的“锚定”位点。然后评估了其拉伸强度、初始模量、极限伸长率、撕裂强度、水/醇吸收量和水蒸气透过率等物理特性,并与其他生物医学级聚氨酯进行了比较。随后研究了血液蛋白白蛋白与这种新型表面的共价连接。使用两步法并加入扩链剂2,2-双(羟甲基)丙酸(DHMPA)合成了一种含有羧酸基团的生物耐久性聚碳酸酯基聚氨酯(cPU)。这种cPU薄膜的拉伸强度分别比用1,4-丁二醇扩链剂合成的聚碳酸酯基聚氨酯(bdPU)和Mitrathane(Mit)对照高2.7倍和2.6倍。与bdPU和Mit相比,在评估初始模量时cPU聚合物的结构刚性分别高7.8倍和31倍。bdPU薄膜的极限伸长率略高于cPU和Mit薄膜,后两者具有相当的伸长性能。撕裂bdPU薄膜所需的力分别比cPU和Mit薄膜大1.9倍和32倍。所有聚氨酯片段对醇溶液的吸收量随醇浓度的增加而增加,其中cPU的吸收量最大。所有检测的聚氨酯的吸水率都很低,且不受pH值变化的影响。与bdPU和Mit相比,cPU薄膜的水蒸气透过率最低。在评估前将cPU在50%乙醇中溶胀会使薄膜的水蒸气透过率略有增加。与对照相比,在较高百分比的乙醇中,用异双功能交联剂1-乙基-3-(3-二甲基氨基丙基)碳二亚胺盐酸盐(EDC)处理后,放射性标记的血液蛋白白蛋白(125I-BSA)与cPU片段的共价连接程度最高。这些结果为开发一种新型的聚(碳酸酯脲)聚氨酯奠定了基础,该聚氨酯具有与其他医用级聚氨酯相当的物理特性,同时具有蛋白质结合能力。

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