红粘土/聚氨酯复合材料的制备及生物相容性、生物稳定性的研究
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摘要
聚氨酯(PU)由于具有良好的力学性能和生物相容性而在生物医学领域得到广泛应用,聚氨酯的医用制品包括人工心脏、人工血管、医用薄膜、弹性绷带、医用导管等的需求量正逐年增加。但是,作为长期植入体内的材料,聚氨酯的力学性能、生物相容性和生物稳定性仍无法满足要求,长期植入体内存在降解现象,限制了这类材料在长期植入领域中的应用。因此,提高聚氨酯的力学性能、生物相容性及生物稳定性对其在生物医用领域的应用具有重要意义。
本研究中,采用华南地区广泛存在的矿物粘土-红粘土,将其提纯分散后获得超浓缩微纳米级的红粘土,采用溶剂法制备红粘土/PU复合材料。利用激光散射仪和透射电镜研究红粘土的粒度及微结构,利用扫描电镜及原子力显微镜研究复合材料的表面性能,并测定了复合材料的力学性能。分别采用四唑盐比色法(即MTT法)、直接接触细胞培养法、溶血率试验和凝血时间试验评价复合材料的细胞毒性及血液相容性。采用H_2O_2/CoCl_2体系,结合木瓜蛋白酶降解体系模拟聚氨酯在体内生理环境中的降解。使用扫描电镜、红外光谱仪和电子拉力机研究复合材料降解前后的表面形貌、分子结构及力学性能的变化,探讨复合材料的生物稳定性。取得了以下结论:
1.红粘土原土平均粒度为1609nm,呈现叠聚式-辐射式粒团结构。经过提纯分散后,红粘土的平均粒度为227.8nm,以数量分析,提纯红粘土中以48nm组分的土粒数量最多,透射电镜下可观察到十几纳米的粘土粒子。对复合材料的微观结构研究显示,红粘土粒子均匀分散于PU基体中,与聚氨酯之间界面作用良好。红粘土含量5wt%PU复合材料的表面粗糙度与纯的PU膜比较,由14.23nm降低为9.626nm,有望减小材料表面对血液成分中的小分子物质的吸附。
2.对复合材料的力学性能研究显示:红粘土含量小于10wt%时,红粘土/PU复合材料的拉伸强度和断裂伸长率随着红粘土的含量增加而呈现增长趋势。纯PU膜拉伸强度和断裂伸长率分别为37.67MPa和610.6%,红粘土含量5wt%的复合材料拉伸强度和断裂伸长率均达最大值,为42.62MPa和673.10%,与纯PU相比分别提高了13%和10%。当红粘土含量大于10wt%时,红粘土/PU复合材料的拉伸强度及断裂伸长率均下降。
3.首次对红粘土类矿物填充PU制备的复合材料进行细胞毒性的研究,结果表明:纯PU的细胞毒性级别为1级,而红粘土/PU复合材料各个浓度组的细胞毒性级别均为0级,无细胞毒性,细胞与材料共培养后生长状态良好。红粘土/PU复合材料溶血率均低于空白PU膜的溶血率,低于国际标准规定值,符合作为植入材料应用于人体中。特别的,红粘土含量2wt%的复合材料的溶血率最低达0.31%,血液相容性最佳。
4.首次对红粘土类矿物填充PU制备的复合材料的生物稳定性的研究,结果表明,红粘土/PU复合材料在加速氧化降解及酶降解后,表面出现裂纹和小洞,而纯PU表面几乎降解脱层。红外光谱分析表明,氧化自由基使得纯PU膜的聚醚软段氧化为酸和醇。而加入红粘土的复合材料的聚醚吸收峰强度不变,聚酯的C=O及C-O吸收峰未发现峰位移动现象,表明复合材料未氧化或氧化程度较小。加速氧化降解后,复合材料的拉伸强度并未降低,反之有少许上升,而酶降解后则有少许下降,降幅均比纯PU小。
综上所述,红粘土在改善聚氨酯的力学性能、提高聚氨酯的生物相容性和生物稳定性有着明显的作用,能弥补PU在应用上的不足。由红粘土填充聚氨酯制备红粘土/PU复合材料综合性能优越,有望成为一种新型的生物材料应用于生物医学工程领域。
Polyurethane (PU) has been widely used in the biomedical field owing to good mechanical properties and biocompatibility. The demand of PU medical products including artificial heart, artificial blood vessels, medical films, elastic bandages, medical catheters, and so on is increasing year by year. However, as a long-term implantation materials, the mechanical properties, biocompatibility and biological stability of PU are still unable to meet the requirements yet. The degradation of PU productions in vivo limits its applications. Therefore, to improve the mechanical properties, biocompatibility and bio-stability of PU, was meaningful and significant.
In this paper, the mineral clay - red clay which widely exists in the South China region was introduced to improve the properties of PU. Due to its chemical and physical characteristics, it is supposed to be an efficacy modification. After being purified and dispersed, a super-concentrated system of micro-nano-red clay was got. And then, this micro-nano-red clay was added into the PU solution by a certain percentage of solvent to make different red clay/PU composites.
Laser diffractometer and transmission electron microscopy (TEM) were introduced to investigate particle size and micro-structure of red clay. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to analyze the surface properties of different red clay/PU composites. Electronic universal testing machine was applied to measure the mechanical properties of this composite. The hemolytic rate, clotting time test, cytotoxicity test and direct contact method was introduced to evaluate the biocompatibility of them. The H_2O_2/CoCl_2 system together with papain degradation solution was published to simulate the degradation of PU in vivo. To find out the difference of surface morphology, molecular structure and mechanical properties before and after degradation, SEM, infrared spectrometer (FTIR) and the electronic universal testing machine were introduced. The results as below:
1. The original red clay presented a structure of stacked-radiation type. The average particle size of original red clay was 1609nm. After purification and dispersion, the average particle size of red clay was reduced to 227.8nm. The largest number of purificatory red clay was in 48nm components, 17nm size of particles could be observed under TEM. Red clay particles uniformly dispersed in the matrix, and possess good interface interaction between the PU. Compared with pure PU, the surface roughness of 5wt% red clay content of PU composite was reduced, which is from 14.23nm to 9.626nm. The results indicate that red clay is conducive in reducing the surface adsorption of small molecules in blood components and improving the blood compatibility of PU.
2. When the red clay content lower than 10wt%, the tensile strength and elongation at break of red clay/PU composite increasing with the increase of content of red clay. Tensile strength and elongation at break of pure PU were 37.67MPa and 610.6%. Especially, 5wt% red clay content of PU composite reached the peak which is 673.10% and 42.62MPa. There are 13% and 10% growth comparing with pure PU. Over the peak that the red clay content is 10wt%, the tensile strength and elongation at break of red clay / PU composite start to fall.
3. Level of cytotoxicity of pure PU was 1. Various contents of the red clay/PU composite were 0, which indicates the cell toxicity is on low level or none. Hemolytic rates of red clay/PU composite were lower than pure PU, less than 5% of international standards. Especially, hemolytic rate of 3wt% red clay content of PU composite was the lowest which was 0.31%. Base on these results, the red clay/PU composite is supposed to be an efficacy modification in improving the biocompatibility of PU.
4. After accelerate oxidative degradation and enzymatic degradation, cracks and holes could be observed on the surface of red clay/PU composite, however, the surface of pure PU almost delaminating. FTIR showed that free radical oxidation makes the ether bond of soft segments of pure PU depredates to carboxylic acid and alcohol. In the red clay/PU composite, any displacement of C=O and the C-O absorption peak of ester bond couldn't be found, which indicated the red clay/PU composite didn't depredate or depredate slightly. After accelerate oxidative degradation, the tensile strength of the composite didn't reduce, on the contrary, there was a little rise; After the enzyme degradation, the tensile strength was slightly declined but the decreasing amplitude was smaller than pure PU. All mentioned above indicate that composites with better bio-stability would be acquired by adding red clay into PU.
In a word, red clay/PU composite not only improve the mechanical properties but also get better biocompatibility and biological stability than matrix, which has shown strengths and great potential in preparation of new modified PU medical products.
本研究中,采用华南地区广泛存在的矿物粘土-红粘土,将其提纯分散后获得超浓缩微纳米级的红粘土,采用溶剂法制备红粘土/PU复合材料。利用激光散射仪和透射电镜研究红粘土的粒度及微结构,利用扫描电镜及原子力显微镜研究复合材料的表面性能,并测定了复合材料的力学性能。分别采用四唑盐比色法(即MTT法)、直接接触细胞培养法、溶血率试验和凝血时间试验评价复合材料的细胞毒性及血液相容性。采用H_2O_2/CoCl_2体系,结合木瓜蛋白酶降解体系模拟聚氨酯在体内生理环境中的降解。使用扫描电镜、红外光谱仪和电子拉力机研究复合材料降解前后的表面形貌、分子结构及力学性能的变化,探讨复合材料的生物稳定性。取得了以下结论:
1.红粘土原土平均粒度为1609nm,呈现叠聚式-辐射式粒团结构。经过提纯分散后,红粘土的平均粒度为227.8nm,以数量分析,提纯红粘土中以48nm组分的土粒数量最多,透射电镜下可观察到十几纳米的粘土粒子。对复合材料的微观结构研究显示,红粘土粒子均匀分散于PU基体中,与聚氨酯之间界面作用良好。红粘土含量5wt%PU复合材料的表面粗糙度与纯的PU膜比较,由14.23nm降低为9.626nm,有望减小材料表面对血液成分中的小分子物质的吸附。
2.对复合材料的力学性能研究显示:红粘土含量小于10wt%时,红粘土/PU复合材料的拉伸强度和断裂伸长率随着红粘土的含量增加而呈现增长趋势。纯PU膜拉伸强度和断裂伸长率分别为37.67MPa和610.6%,红粘土含量5wt%的复合材料拉伸强度和断裂伸长率均达最大值,为42.62MPa和673.10%,与纯PU相比分别提高了13%和10%。当红粘土含量大于10wt%时,红粘土/PU复合材料的拉伸强度及断裂伸长率均下降。
3.首次对红粘土类矿物填充PU制备的复合材料进行细胞毒性的研究,结果表明:纯PU的细胞毒性级别为1级,而红粘土/PU复合材料各个浓度组的细胞毒性级别均为0级,无细胞毒性,细胞与材料共培养后生长状态良好。红粘土/PU复合材料溶血率均低于空白PU膜的溶血率,低于国际标准规定值,符合作为植入材料应用于人体中。特别的,红粘土含量2wt%的复合材料的溶血率最低达0.31%,血液相容性最佳。
4.首次对红粘土类矿物填充PU制备的复合材料的生物稳定性的研究,结果表明,红粘土/PU复合材料在加速氧化降解及酶降解后,表面出现裂纹和小洞,而纯PU表面几乎降解脱层。红外光谱分析表明,氧化自由基使得纯PU膜的聚醚软段氧化为酸和醇。而加入红粘土的复合材料的聚醚吸收峰强度不变,聚酯的C=O及C-O吸收峰未发现峰位移动现象,表明复合材料未氧化或氧化程度较小。加速氧化降解后,复合材料的拉伸强度并未降低,反之有少许上升,而酶降解后则有少许下降,降幅均比纯PU小。
综上所述,红粘土在改善聚氨酯的力学性能、提高聚氨酯的生物相容性和生物稳定性有着明显的作用,能弥补PU在应用上的不足。由红粘土填充聚氨酯制备红粘土/PU复合材料综合性能优越,有望成为一种新型的生物材料应用于生物医学工程领域。
Polyurethane (PU) has been widely used in the biomedical field owing to good mechanical properties and biocompatibility. The demand of PU medical products including artificial heart, artificial blood vessels, medical films, elastic bandages, medical catheters, and so on is increasing year by year. However, as a long-term implantation materials, the mechanical properties, biocompatibility and biological stability of PU are still unable to meet the requirements yet. The degradation of PU productions in vivo limits its applications. Therefore, to improve the mechanical properties, biocompatibility and bio-stability of PU, was meaningful and significant.
In this paper, the mineral clay - red clay which widely exists in the South China region was introduced to improve the properties of PU. Due to its chemical and physical characteristics, it is supposed to be an efficacy modification. After being purified and dispersed, a super-concentrated system of micro-nano-red clay was got. And then, this micro-nano-red clay was added into the PU solution by a certain percentage of solvent to make different red clay/PU composites.
Laser diffractometer and transmission electron microscopy (TEM) were introduced to investigate particle size and micro-structure of red clay. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to analyze the surface properties of different red clay/PU composites. Electronic universal testing machine was applied to measure the mechanical properties of this composite. The hemolytic rate, clotting time test, cytotoxicity test and direct contact method was introduced to evaluate the biocompatibility of them. The H_2O_2/CoCl_2 system together with papain degradation solution was published to simulate the degradation of PU in vivo. To find out the difference of surface morphology, molecular structure and mechanical properties before and after degradation, SEM, infrared spectrometer (FTIR) and the electronic universal testing machine were introduced. The results as below:
1. The original red clay presented a structure of stacked-radiation type. The average particle size of original red clay was 1609nm. After purification and dispersion, the average particle size of red clay was reduced to 227.8nm. The largest number of purificatory red clay was in 48nm components, 17nm size of particles could be observed under TEM. Red clay particles uniformly dispersed in the matrix, and possess good interface interaction between the PU. Compared with pure PU, the surface roughness of 5wt% red clay content of PU composite was reduced, which is from 14.23nm to 9.626nm. The results indicate that red clay is conducive in reducing the surface adsorption of small molecules in blood components and improving the blood compatibility of PU.
2. When the red clay content lower than 10wt%, the tensile strength and elongation at break of red clay/PU composite increasing with the increase of content of red clay. Tensile strength and elongation at break of pure PU were 37.67MPa and 610.6%. Especially, 5wt% red clay content of PU composite reached the peak which is 673.10% and 42.62MPa. There are 13% and 10% growth comparing with pure PU. Over the peak that the red clay content is 10wt%, the tensile strength and elongation at break of red clay / PU composite start to fall.
3. Level of cytotoxicity of pure PU was 1. Various contents of the red clay/PU composite were 0, which indicates the cell toxicity is on low level or none. Hemolytic rates of red clay/PU composite were lower than pure PU, less than 5% of international standards. Especially, hemolytic rate of 3wt% red clay content of PU composite was the lowest which was 0.31%. Base on these results, the red clay/PU composite is supposed to be an efficacy modification in improving the biocompatibility of PU.
4. After accelerate oxidative degradation and enzymatic degradation, cracks and holes could be observed on the surface of red clay/PU composite, however, the surface of pure PU almost delaminating. FTIR showed that free radical oxidation makes the ether bond of soft segments of pure PU depredates to carboxylic acid and alcohol. In the red clay/PU composite, any displacement of C=O and the C-O absorption peak of ester bond couldn't be found, which indicated the red clay/PU composite didn't depredate or depredate slightly. After accelerate oxidative degradation, the tensile strength of the composite didn't reduce, on the contrary, there was a little rise; After the enzyme degradation, the tensile strength was slightly declined but the decreasing amplitude was smaller than pure PU. All mentioned above indicate that composites with better bio-stability would be acquired by adding red clay into PU.
In a word, red clay/PU composite not only improve the mechanical properties but also get better biocompatibility and biological stability than matrix, which has shown strengths and great potential in preparation of new modified PU medical products.
引文
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