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聚(富马酸丙二醇酯-共-乙二醇)水凝胶的体外和体内降解

In vitro and in vivo degradation of poly(propylene fumarate-co-ethylene glycol) hydrogels.

作者信息

Suggs L J, Krishnan R S, Garcia C A, Peter S J, Anderson J M, Mikos A G

机构信息

Institute of Biosciences and Bioengineering and Department of Chemical Engineering, Rice University, Houston, Texas 77251-1892, USA.

出版信息

J Biomed Mater Res. 1998 Nov;42(2):312-20. doi: 10.1002/(sici)1097-4636(199811)42:2<312::aid-jbm17>3.0.co;2-k.

Abstract

The degradation of poly(propylene fumarate-co-ethylene glycol) hydrogels was examined in vitro in phosphate-buffered saline at pH 7.4 and in vivo in a subcutaneous rat model. These hydrogels have potential application as biodegradable, injectable cardiovascular stents, and, as such, their mass loss, dimensional changes, mechanical properties, morphology, and biocompatibility over a 12-week time course were evaluated. Three formulations were fabricated: one base formulation consisting of 25% (w/w) PEG, molecular weight 4,600; one high weight percent PEG formulation with 50% (w/w) PEG; and one high molecular weight PEG formulation, molecular weight 10,500. All three formulations showed significant weight loss (between 40 and 60%) on the first day due to leaching of the uncrosslinked fraction. Further weight loss was observed only for the low weight percent PEG copolymers in the in vivo case, and a slight increase in volume was observed due to degradative swelling. The mechanical properties of the P(PF-co-EG) hydrogels decreased significantly in the first 3 weeks, showing the biphasic pattern typical of bulk degradation. In vitro, the hydrogels showed at least a 20% retention of their initial ultimate tensile stress after 3 weeks. The dynamic mechanical properties showed similar retention, with the in vivo mechanical properties differing from the in vitro properties only after 6 weeks of degradation. Differences in PEG molecular weight appeared to have little effect, but increasing the weight percent PEG decreased the rate of degradation both in vitro and in vivo. The morphology of the copolymer films, based on scanning electron microscopy observation, was not significantly different either among the three formulations or over the time course of the study, suggesting there were no macroscopic structural changes during this time period. The P(PF-co-EG) hydrogels demonstrated good initial biocompatibility, showing responses characteristic of biomaterial implants.

摘要

在pH 7.4的磷酸盐缓冲盐溶液中对聚(富马酸丙酯-共-乙二醇)水凝胶进行了体外降解研究,并在大鼠皮下模型中进行了体内降解研究。这些水凝胶作为可生物降解的可注射心血管支架具有潜在应用价值,因此,评估了它们在12周时间内的质量损失、尺寸变化、力学性能、形态和生物相容性。制备了三种配方:一种基础配方,由25%(w/w)分子量为4600的聚乙二醇组成;一种高重量百分比聚乙二醇配方,含50%(w/w)聚乙二醇;以及一种高分子量聚乙二醇配方,分子量为10500。由于未交联部分的浸出,所有三种配方在第一天都出现了显著的重量损失(40%至60%之间)。仅在体内情况下,低重量百分比聚乙二醇共聚物观察到进一步的重量损失,并且由于降解性肿胀观察到体积略有增加。聚(富马酸丙酯-共-乙二醇)水凝胶的力学性能在前三周显著下降,呈现出典型的本体降解双相模式。在体外,水凝胶在3周后至少保留了其初始极限拉伸应力的20%。动态力学性能表现出类似的保留情况,体内力学性能仅在降解6周后才与体外性能有所不同。聚乙二醇分子量的差异似乎影响不大,但增加聚乙二醇的重量百分比会降低体外和体内的降解速率。基于扫描电子显微镜观察,共聚物薄膜的形态在三种配方之间或在研究的时间过程中没有显著差异,表明在此时间段内没有宏观结构变化。聚(富马酸丙酯-共-乙二醇)水凝胶表现出良好的初始生物相容性,显示出生物材料植入物的典型反应。

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