具有管中管结构复合神经导管的制备及材料性能研究
发布时间：2018-07-15 11:55
【摘要】：随着神经损伤发生率的大幅度上升,神经移植已不能很好地满足需要,新方向的探索变得尤为重要,神经导管作为一种新的治疗方法应运而生。神经导管组织工程支架可以为神经的生长提供良好的微环境,理想的神经导管还能促进受损神经的愈合或为神经的生长提供导向作用。本文设计了一种管中管新构型的神经导管,详细讨论了各部分材料的基本性能,对管中管结构神经导管的可行性进行初步探索,期望复合结构的神经导管会对神经再生起到积极作用。 通过静电纺丝法制备得到的纳米纤维,由于具有较高的孔隙率、较大的比表面积及高表面能等优势,能够从纳米尺度来模仿天然细胞外基质,被广泛地应用于组织工程支架材料、伤口敷料及药物载体等方面。因此本文首先采用静电纺丝技术制备神经导管的外管支架,通过旋转接收装置、优化纺丝参数,制备得到仿细胞外基质的有序纳米纤维支架,作为细胞生长的支撑,促进细胞的迁移及增殖。另外,湿法中空纤维成型是一步法连续制备中空纤维导管的有效途径,在制备管内部纤维导管时采用湿法纺丝技术。 本文选用脂肪族聚碳酸丁二脂(PBC)、甲壳素纳米晶须(ChW)、高密度壳聚糖(HCS)及表面功能化的多壁碳纳米管(f-MWNTs)作为基本支架材料,通过静电纺丝接收装置的改进、材料组合、表面改性等,系统地研究评价了这类材料用作神经修复组织工程材料的力学性能、细胞相容性及降解性能等。主要研究工作如下： 1.通过静电纺丝法制备无规和有序PBC纳米纤维,研究了接收线速度对纳米纤维基本性能的影响。之后研究了低温等离子表面改性技术对纤维表面亲水性的影响,并通过等离子改性方法诱导纤维表面接枝明胶,以增强纤维表面的生物相容性。研究表明,PBC可以均匀地溶解于甲酸、DMF、六氟异丙醇及氯仿等有机溶剂中,但仅溶解于甲酸能够得到表面光滑、粗细均匀的纳米级纤维；通过转轴法可以成功制备得到PBC有序纳米纤维,随着旋转线速度的增大,纤维的排列有序度、晶区及分子链的取向度、结晶度以及力学性能都有所增大。 2.为了进一步提高外管有序纳米纤维的力学性能。首先通过酸解法制备得到纳米级甲壳素晶须,然后将其与PBC进行共混复合,通过静电纺丝法制备得到纳米级复合纤维,研究发现利用酸解法制得的甲壳素晶须的长度范围为180-680nm,直径分布范围为15-30nm,平均长径比为14.7,且将晶须分散到甲酸中24h后对表面形貌的观察发现,在短时间内甲酸并不会影响到晶须形貌,为下一步实验提供了依据；对将不同含量的晶须添到PBC中制得复合纳米纤维的研究表明,当晶须含量为5.0wt%时,制得的纳米纤维表面光滑、直径分布均匀且随着晶须的加入结晶度、热稳定性及力学性能得到显著提高。之后采用低温等离子技术对表面进行改性处理并用明胶接枝以赋予纤维表面新的生物相容性,使其亲水性得到了很大的提高,且更有利于神经细胞RSC96的黏附与增殖。 3.采用高密度壳聚糖(HCS)来制备导管内部的中空纤维。首先研究了HCS质量分数以及温度等对纺丝浆液稳定性的影响；而后进行湿法纺丝制备了中空纤维,并对HCS中空纤维的化学结构、晶体结构和热性能进行了研究。结果表明,HCS的固含量为5wt%时,纺丝过程顺利进行,挤出的浆液在凝固浴中形成的初生纤维结构均匀,不会出现断丝情况。纺丝温度应控制在20-30℃；凝固浴浓度为3wt%时所得的中空纤维热力学及结构性能较好。因此,在后续的实验研究中,将采用质量分数为5wt%HCS纺丝浆液,以质量分数为3wt%的NaOH-乙醇溶液作为凝固浴制备中空纤维。 4.采用碳纳米管来增强HCS中空纤维的力学和电学性能。为了提高碳管在HCS溶液中的分散性及与HCS基体之间的相容性,通过表面沉积交联法对碳管进行表面修饰得到f-MWNTs。然后与HCS进行混合制得复合中空纤维,并对其性能进行了研究分析。研究发现,经过表面修饰得到的f-MWNTs的管身变得平直,缠结状态也有所缓解,且在水中的分散性就明显优于MWNTs;对复合中空纤维的研究发现当f-MWNTs的含量达到0.5wt%时,f-MWNTs在HCS基体中的分布最为均匀,中空纤维的断面形貌也最为致密；且复合纤维的拉伸强度和弹性模量均达到最大值,分别为9.33MPa和2.34GPa；在含水率相同的条件下,随着碳管含量的增加复合纤维的电导率也增加。经过等离子预处理和明胶接枝改性后,复合膜在各个压力下的水通量都有了明显的提高,且更有利于细胞的黏附与增殖。 5.管中管结构的神经导管外层通过将静电纺有序纳米纤维沿一定直径的芯棒卷绕成管状结构,内部填充中空纤维,得到内部通道不同的导管。对导管的压缩性能的研究表明,5-通道神经导管在形变量为25%时,负荷力高达201cN,完全能够满足神经导管径向支撑力的要求；管中管结构的神经导管在受到外界压力时,形状发生变化后能够自然恢复,即形变后也能承担一定的支撑作用,符合神经导管力学性能的要求。 因此本文所制备的管中管复合型神经导管在亲水性、降解性及细胞相容性上都有所提高,同时具有良好的机械性能,有望成为新一代的神经修复组织工程支架。
[Abstract]:Neurovascular tissue engineering stent can provide a good microenvironment for the growth of nerve , and the ideal nerve catheter can promote the healing of damaged nerve or provide guidance for the growth of nerve .
The nano - fiber prepared by the electrostatic spinning method has the advantages of high porosity , larger specific surface area and high surface energy and the like , can imitate the natural extracellular matrix from nano - scale , is widely applied to tissue engineering scaffold materials , wound dressings and drug carriers and the like .
In this paper , the mechanical properties , cell compatibility and degradation properties of this kind of materials used as nerve repairing tissue engineering materials were systematically studied by using aliphatic polycarbonate ( PBC ) , chitin nano whisker ( ChW ) , high density chitosan ( HCS ) and surface functionalized multi - walled carbon nanotubes ( f - MWCNTs ) as the basic scaffold materials . The main research work is as follows :
1 . The influence of receiving linear velocity on the basic properties of nanofibers was studied by electrostatic spinning . The effect of low temperature plasma surface modification on fiber surface hydrophilicity was studied . The surface grafting gelatin was induced by plasma modification to enhance the biocompatibility of the fiber surface . The results showed that PBC could be dissolved in formic acid , DMF , hexafluoroisopropanol and chloroform , but only dissolved in formic acid to obtain the nano - fiber with smooth surface and uniform thickness .
By using the rotating shaft method , the PBC ordered nanofibers can be successfully prepared . With the increase of the rotating linear velocity , the arrangement order of the fibers , the orientation degree of the crystal region and the molecular chain , the crystallinity and the mechanical properties are increased .
2 . In order to further improve the mechanical properties of the ordered nano - fibers , the nano - sized chitin whiskers were prepared by an acid hydrolysis method . The nano - scale composite fibers were prepared by electrostatic spinning . The results showed that the length of the chitin whiskers prepared by acid hydrolysis was 180 - 680 nm , the diameter distribution range was 15 - 30 nm , the average length - to - diameter ratio was 14.7 , and the morphology of the whisker was not affected after 24 h in the formic acid .
It is shown that when the whisker content is 5.0 wt % , the surface of the prepared nanofiber is smooth , the diameter distribution is uniform and the crystallinity , the thermal stability and the mechanical property of the whisker are remarkably improved . The surface is modified by low - temperature plasma technology , and the surface is grafted with gelatin to give new biocompatibility to the surface of the fiber , so that the hydrophilicity is greatly improved , and the adhesion and proliferation of the nerve cell RSC96 are more favorable .
3 . High density chitosan ( HCS ) was used to prepare the hollow fiber inside the catheter . The effect of HCS mass fraction and temperature on the stability of spinning slurry was studied .
The hollow fibers were prepared by wet spinning , and the chemical structure , crystal structure and thermal properties of HCS hollow fibers were studied . The results showed that when the solid content of HCS was 5 % by weight , the spinning process proceeded smoothly .
Therefore , in the subsequent experimental study , the hollow fiber was prepared by using an HCS spinning slurry with mass fraction of 5 wt % and a NaOH - ethanol solution with a mass fraction of 3 wt % as a coagulation bath .
4 . Carbon nanotubes were used to enhance the mechanical and electrical properties of HCS hollow fibers . In order to improve the dispersion of carbon nanotubes in HCS solution and compatibility with HCS matrix , the surface modification of carbon nanotubes was carried out by surface deposition crosslinking method .
and the tensile strength and the elastic modulus of the composite fiber reach the maximum value , which is 9.33MPa and 2.34GPa , respectively ;
Under the condition of the same water content , the conductivity of the composite fiber increases with the increase of the content of the carbon tube . After plasma pretreatment and gelatin grafting modification , the water flux of the composite membrane under each pressure is obviously improved , and the cell adhesion and proliferation are more favorable .
5 . The outer layer of the nerve conduit of the tube structure of the tube is wound into a tubular structure along a mandrel with a certain diameter by the electrospun ordered nanofibers , and hollow fibers are filled in the tube to obtain different catheters of the inner channel .
When the nerve conduit in the tube is subjected to external pressure , the shape of the nerve conduit can be restored naturally after the shape is changed , that is , the nerve conduit of the tube structure can bear a certain supporting effect after deformation , and conforms to the requirements of the mechanical property of the nerve catheter .
therefore , the composite nerve conduit in the tube prepared in the present invention has improved hydrophilicity , degradability and cell compatibility , and has good mechanical properties , and is expected to be a new generation of nerve repair tissue engineering scaffold .
【学位授予单位】：东华大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R318.08;TB383.1
本文编号：2123990
[Abstract]:Neurovascular tissue engineering stent can provide a good microenvironment for the growth of nerve , and the ideal nerve catheter can promote the healing of damaged nerve or provide guidance for the growth of nerve .
The nano - fiber prepared by the electrostatic spinning method has the advantages of high porosity , larger specific surface area and high surface energy and the like , can imitate the natural extracellular matrix from nano - scale , is widely applied to tissue engineering scaffold materials , wound dressings and drug carriers and the like .
In this paper , the mechanical properties , cell compatibility and degradation properties of this kind of materials used as nerve repairing tissue engineering materials were systematically studied by using aliphatic polycarbonate ( PBC ) , chitin nano whisker ( ChW ) , high density chitosan ( HCS ) and surface functionalized multi - walled carbon nanotubes ( f - MWCNTs ) as the basic scaffold materials . The main research work is as follows :
1 . The influence of receiving linear velocity on the basic properties of nanofibers was studied by electrostatic spinning . The effect of low temperature plasma surface modification on fiber surface hydrophilicity was studied . The surface grafting gelatin was induced by plasma modification to enhance the biocompatibility of the fiber surface . The results showed that PBC could be dissolved in formic acid , DMF , hexafluoroisopropanol and chloroform , but only dissolved in formic acid to obtain the nano - fiber with smooth surface and uniform thickness .
By using the rotating shaft method , the PBC ordered nanofibers can be successfully prepared . With the increase of the rotating linear velocity , the arrangement order of the fibers , the orientation degree of the crystal region and the molecular chain , the crystallinity and the mechanical properties are increased .
2 . In order to further improve the mechanical properties of the ordered nano - fibers , the nano - sized chitin whiskers were prepared by an acid hydrolysis method . The nano - scale composite fibers were prepared by electrostatic spinning . The results showed that the length of the chitin whiskers prepared by acid hydrolysis was 180 - 680 nm , the diameter distribution range was 15 - 30 nm , the average length - to - diameter ratio was 14.7 , and the morphology of the whisker was not affected after 24 h in the formic acid .
It is shown that when the whisker content is 5.0 wt % , the surface of the prepared nanofiber is smooth , the diameter distribution is uniform and the crystallinity , the thermal stability and the mechanical property of the whisker are remarkably improved . The surface is modified by low - temperature plasma technology , and the surface is grafted with gelatin to give new biocompatibility to the surface of the fiber , so that the hydrophilicity is greatly improved , and the adhesion and proliferation of the nerve cell RSC96 are more favorable .
3 . High density chitosan ( HCS ) was used to prepare the hollow fiber inside the catheter . The effect of HCS mass fraction and temperature on the stability of spinning slurry was studied .
The hollow fibers were prepared by wet spinning , and the chemical structure , crystal structure and thermal properties of HCS hollow fibers were studied . The results showed that when the solid content of HCS was 5 % by weight , the spinning process proceeded smoothly .
Therefore , in the subsequent experimental study , the hollow fiber was prepared by using an HCS spinning slurry with mass fraction of 5 wt % and a NaOH - ethanol solution with a mass fraction of 3 wt % as a coagulation bath .
4 . Carbon nanotubes were used to enhance the mechanical and electrical properties of HCS hollow fibers . In order to improve the dispersion of carbon nanotubes in HCS solution and compatibility with HCS matrix , the surface modification of carbon nanotubes was carried out by surface deposition crosslinking method .
and the tensile strength and the elastic modulus of the composite fiber reach the maximum value , which is 9.33MPa and 2.34GPa , respectively ;
Under the condition of the same water content , the conductivity of the composite fiber increases with the increase of the content of the carbon tube . After plasma pretreatment and gelatin grafting modification , the water flux of the composite membrane under each pressure is obviously improved , and the cell adhesion and proliferation are more favorable .
5 . The outer layer of the nerve conduit of the tube structure of the tube is wound into a tubular structure along a mandrel with a certain diameter by the electrospun ordered nanofibers , and hollow fibers are filled in the tube to obtain different catheters of the inner channel .
When the nerve conduit in the tube is subjected to external pressure , the shape of the nerve conduit can be restored naturally after the shape is changed , that is , the nerve conduit of the tube structure can bear a certain supporting effect after deformation , and conforms to the requirements of the mechanical property of the nerve catheter .
therefore , the composite nerve conduit in the tube prepared in the present invention has improved hydrophilicity , degradability and cell compatibility , and has good mechanical properties , and is expected to be a new generation of nerve repair tissue engineering scaffold .
【学位授予单位】：东华大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R318.08;TB383.1
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