CN111000661B - 一种复合型人造血管及其制备方法 - Google Patents
一种复合型人造血管及其制备方法 Download PDFInfo
- Publication number
- CN111000661B CN111000661B CN202010092160.9A CN202010092160A CN111000661B CN 111000661 B CN111000661 B CN 111000661B CN 202010092160 A CN202010092160 A CN 202010092160A CN 111000661 B CN111000661 B CN 111000661B
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- China
- Prior art keywords
- nanofiber
- layer
- nanofiber layer
- blood vessel
- artificial blood
- Prior art date
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- Health & Medical Sciences (AREA)
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- Materials For Medical Uses (AREA)
Abstract
本发明涉及一种复合型人造血管和制备该人造血管的制备方法,人造血管为双层管状结构,包括置于内层的第一纳米纤维层和置于外层的第二纳米纤维层,第一纳米纤维层与第二纳米纤维层贴合连接,第一纳米纤维层由一层、两层或多层纳米纤维膜卷制形成,第二纳米纤维层为一体成型结构,第一纳米纤维层和第二纳米纤维层上均设置有微孔结构,该人造血管使可降解纳米纤维小口径人造血管在纤维开始大量降解前实现自体细胞的三维渗入以及新生组织的再生,从而使血管在纤维大量降解时仍具有较好的强度和弹性。
Description
技术领域
本发明涉及一种人造血管,尤其涉及一种复合型人造血管及其制备方法。
背景技术
血管***包括心脏、血管和血液。心脏将新鲜的血液经大大小小的血管输送到身体各部位进行体内的营养成分和废物的交换,以确保各器官的正常功能。然而动脉粥样硬化、血管瘤和外力创伤等病因造成多种动脉和静脉血管缺损,需要通过外科手术采用不同直径的血管替代品进行对应病变血管部位置换、搭桥等修复治疗。血管替代品一般有自体血管、异种血管、同种异体血管和人造血管,由于自体血管常常受到患者年龄、已存在的血管疾病等因素的限制以及异种血管和同种异体血管的来源问题,临床上需要大量人造血管来对病变血管进行修护。
静电纺丝技术早在 1930 年代就被提出用于制备纳米纤维材料,但直到近些年才有较为成熟的应用。静电纺丝技术与传统纺织技术相比,可以得到更加纤细的纤维,并且可以有效地控制纤维的直径和纺织物的形状,除此之外,静电纺丝技术制备得到的纳米纤维材料具有较大的比表面积和较高的孔隙率,能够模拟细胞外基质的微结构,具有很好的生物相容性。有很多研究通过静电纺丝的方法制备可降解的纳米纤维小口径人造血管(直径2-5mm),期望用这种可降解人造血管使自体病变血管再生。但是,静电纺丝纳米纤维材料的平均孔径通常都小于2微米,而平滑肌细胞和成纤维细胞的直径都在10-50微米,在纤维大量降解并发生断裂前,平滑肌细胞和成纤维细胞都只能少量地渗入到血管壁中,难以大量地渗入并生成新的血管组织,这限制了血管再生的速度。人造血管植入体内后,其力学性能取决于血管壁中纳米纤维的力学性能和新生组织的力学能,当纳米纤维开始大量降解并发生断裂时,纤维已经基本丧失了其强度和弹性,此时若还未有具备一定力学性能的新生组织生成,人造血管的强度和弹性也会基本丧失。当人造血管不具备强度和弹性时,就会由于受到外界的压力而发生管壁塌陷或由于承受不了血流的压力而发生管壁破裂,从而使血管再生手术失败。
发明内容
本发明为了解决现有静电纺丝纳米纤维人造血管在纤维大量降解并发生断裂前,平滑肌细胞和成纤维细胞难以大量地渗入的问题,提供了一种复合型人造血管,该人造血管使可降解纳米纤维小口径人造血管在纤维开始大量降解前实现自体细胞的三维渗入以及新生组织的再生,从而使血管在纤维大量降解时仍具有较好的强度和弹性。
本发明所采取的技术方案为:一种复合型人造血管,人造血管为双层管状结构,包括置于内层的第一纳米纤维层和置于外层的第二纳米纤维层,所述第一纳米纤维层与所述第二纳米纤维层贴合连接,所述第一纳米纤维层由一层、两层或多层纳米纤维膜卷制形成,所述第二纳米纤维层为一体成型结构,所述第一纳米纤维层和第二纳米纤维层上均设置有微孔结构;
所述第一纳米纤维层厚度为50-100微米,微孔结构的平均孔径为0.6-1.2微米,所述第一纳米纤维层的纤维的平均直径为200-1000纳米;
所述第二纳米纤维层厚度为200-600微米,微孔结构的平均孔径为20-100微米,所述第二纳米纤维层的纤维的平均直径为500-1400纳米。
进一步的,形成所述第一纳米纤维层的纳米纤维膜的厚度为5-50微米。
进一步的,所述第一纳米纤维层为胶原蛋白和乳酸己内酯共聚物纳米纤维层。胶原蛋白具有良好的生物相容性和良好的亲水性。良好的生物相容性,可以降低人造血管使用时的排异反应;良好的亲水性,有利于内皮细胞的粘附,使人造血管快速内皮化,减少血栓形成。乳酸己内酯共聚物是一种可降解的高分子合成材料,其具有很好的生物相容性和力学性能,可以使纳米纤维层1具有很好的强度和弹性。
进一步的,所述第二纳米纤维层为乳酸己内酯共聚物纳米纤维层。乳酸己内酯共聚物是一种可降解的高分子合成材料,其具有很好的生物相容性和力学性能,可以使纳米纤维层2具有很好的强度和弹性。
进一步的,所述人造血管的直径为2-5mm,所述人造血管的壁厚为250微米-700微米。
进一步的,所述第二纳米纤维层通过浓度为30%-50%的纳米纤维溶液浇筑于模具中制备而成。
本发明还提供了上述复合型人造血管的制备方法,包括以下步骤
制备第一纺丝溶液,并使用第一纺丝溶液,通过静电纺丝的方法制备得到第一纳米纤维膜;
将设定层数的第一纳米纤维膜在模具棒上卷绕形成中空管状作为第一纳米纤维层,各层第一纳米纤维膜之间通过热压复合粘结;
制备第二纺丝溶液,并使用第二纺丝溶液,通过静电纺丝的方法制备第二纳米纤维膜;
将第二纳米纤维膜剪碎,置于去离子水中利用高速匀浆机将纤维在去离子水中分散均匀,得到纳米纤维溶液;
将中空管状的第一纳米纤维层置于模腔内,第一纳米纤维层外壁与模腔内壁之间设置有设定距离的间隙,将所述纳米纤维溶液浇注于所述模腔内,使纳米纤维溶液填充于所述第一纳米纤维层外壁与模腔内壁之间的间隙处,;
待纳米纤维溶液在模腔内成型后形成第二纳米纤维层,所述第二纳米纤维层与所述第一纳米纤维层连接形成人造血管;
脱模后对人造血管进行交联处理。
进一步的,所述第一纺丝溶液为胶原蛋白/乳酸己内酯共聚物共混的纺丝溶液,所述第二纺丝溶液为乳酸己内酯共聚物纺丝溶液,第一纺丝溶液和第二纺丝溶液的溶剂为六氟异丙醇。
进一步的,所述胶原蛋白/乳酸己内酯共聚物的质量比为50:50或25:75,所述第一纺丝溶液的浓度为6%-12%,所述第二纺丝溶液的浓度为6%-12%,所述纳米纤维溶液的浓度为30%-50%。
进一步的,在纳米纤维溶液浇注完成后将置有第一纳米纤维层和纳米纤维溶液的模具在低温下冷冻处理1-6小时,然后进行冷冻干燥;
交联处理后的人造血管用纯化水浸泡5-10分钟,随后用鼓风干燥箱烘干,烘干温度为40-55℃,干燥时间为30-120分钟制得最终所需的复合型人造血管。
进一步的,更详细的制备方法为:包括:
a. 制备胶原蛋白/PLCL共混的纺丝溶液,胶原蛋白/PLCL的质量比为50:50或25:75,纺丝溶液的浓度为6%-12%,溶剂为六氟异丙醇;
b. 使用步骤a制备得到的纺丝溶液,通过静电纺丝的方法制备得到厚度为5-50微米的纳米纤维膜,纺丝电压为8-20kV;
c. 使用步骤b制备得到的纳米纤维膜在不锈钢棒上根据纳米纤维层1的厚度卷绕一定层数的纳米纤维膜,通过45-55℃热压复合制备得到纳米纤维层1;
d. 制备PLCL纺丝溶液,纺丝溶液的浓度为6%-12%,溶剂为六氟异丙醇;
e. 使用步骤d制备得到的纺丝溶液,通过静电纺丝的方法制备得到PLCL纳米纤维膜,然后将PLCL纳米纤维膜剪碎,置于去离子水中利用高速匀浆机将纤维分散均匀,制备生成浓度为30%-50%的纳米纤维溶液,纳米纤维溶液使用前需进行真空脱气处理;
f.将步骤c制备得到的第一纳米纤维层套到血管模具的内芯上,套上血管模具外模包裹住第一纳米纤维层,将步骤e制备得到的纳米纤维溶液浇筑到第一纳米纤维层和血管模具外模之间的空隙。将血管制备装置静置固定并置于-80℃的低温冰箱,冷冻处理1-6小时,随后转移至冷冻干燥器中进行冷冻干燥;
g. 将冷冻干燥后的人造血管从血管模具中移除,使用京尼平溶液对人造血管进行交联处理,京尼平溶液浓度为0.5%-2.0%,京尼平溶液的溶解温度为37℃,溶剂为水和乙醇的共混物,水和乙醇的体积比为80:20。人造血管浸泡到京尼平溶液中进行交联,交联时间为0.5h-24h,交联温度为37℃。京尼平是一种天然的交联剂,主要以栀子为原料提取所得,其细胞毒性为传统交联剂戊二醛的1/10000,作为一种天然的交联剂,除具有与传统人工合成的化学交联剂相近的交联高效性外,还具有毒性低、细胞相容性好的优势。用京尼平进行交联后,胶原蛋白材料的生物降解性、力学性能都可以得到一定的提高;
h. 将步骤g制备得到的人造血管用纯化水浸泡5-10分钟,随后用鼓风干燥箱烘干,烘干温度为40-55℃,干燥时间为30-120分钟。
本发明所产生的有益效果包括:
1、本发明中的第二纳米纤维层的孔径相比于静电纺丝技术制备的普通纳米纤维材料的孔径要大很多,其孔径与平滑肌细胞和成纤维细胞的直径在同一个数量级,有利于在纤维开始大量降解前实现自体细胞的三维渗入以及新生组织的再生,使血管在纤维大量降解时仍具有较好的强度和弹性,提高血管再生手术的成功率。
2、良好的生物相容性,可以降低人造血管使用时的排异反应;良好的亲水性,有利于内皮细胞的粘附,使人造血管快速内皮化,减少血栓形成。乳酸己内酯共聚物是一种可降解的高分子合成材料,其具有很好的生物相容性和力学性能,可以使第一纳米纤维层具有很好的强度和弹性。乳酸己内酯共聚物是一种可降解的高分子合成材料,其具有很好的生物相容性和力学性能,可以使纳米纤维层2具有很好的强度和弹性。
3、本发明的一种复合型人造血管,可以使人造血管在纤维开始大量降解前实现自体细胞的三维长入以及新生组织的再生,从而使血管在纤维大量降解时仍具有较好的强度和弹性,提高血管再生手术的成功率。本发明的复合型人造血管有望在血管再生领域得到广泛应用。本方法操作简单,可重复性好,经济效益高。
附图说明
图1 血管横截面示意图;
图2 血管加工模具示意图。
图中1、第一纳米纤维层,2、第二纳米纤维层,3、内芯,4、外模。
具体实施方式
下面结合附图和具体实施例对本发明做进一步详细的解释说明,但应当理解为本发明的保护范围并不受具体实施例的限制。
如图1,本发明中的一种复合型人造血管为双层管状结构,包括置于内层的第一纳米纤维层1和置于外层的第二纳米纤维层2,第一纳米纤维层1与第二纳米纤维层2贴合连接,第一纳米纤维层1由一层、两层或多层纳米纤维膜卷制形成,第二纳米纤维层2为一体成型结构,第一纳米纤维层1和第二纳米纤维层2上均设置有微孔结构;
第一纳米纤维层1厚度为50-100微米,微孔结构的平均孔径为0.6-1.2微米,第一纳米纤维层1的纤维的平均直径为200-1000纳米;第二纳米纤维层2厚度为200-600微米,微孔结构的平均孔径为20-100微米,第二纳米纤维层2的纤维的平均直径为500-1400纳米。
形成第一纳米纤维层1的纳米纤维膜的厚度为5-50微米。第一纳米纤维层1为胶原蛋白和乳酸己内酯共聚物纳米纤维层。胶原蛋白具有良好的生物相容性和良好的亲水性。良好的生物相容性,可以降低人造血管使用时的排异反应;良好的亲水性,有利于内皮细胞的粘附,使人造血管快速内皮化,减少血栓形成。乳酸己内酯共聚物是一种可降解的高分子合成材料,其具有很好的生物相容性和力学性能,可以使第一纳米纤维层1具有很好的强度和弹性。
第二纳米纤维层2为乳酸己内酯共聚物纳米纤维层。乳酸己内酯共聚物是一种可降解的高分子合成材料,其具有很好的生物相容性和力学性能,可以使纳米纤维层2具有很好的强度和弹性。第二纳米纤维层2通过浓度为30%-50%的纳米纤维溶液浇筑于模具中制备而成。
人造血管的直径为2-5mm,人造血管的壁厚为250微米-700微米。
上述人造血管的制备方法为:包括:
a. 制备胶原蛋白/PLCL共混的纺丝溶液,胶原蛋白/PLCL的质量比为50:50或25:75,纺丝溶液的浓度为6%-12%,溶剂为六氟异丙醇;
b. 使用步骤a制备得到的纺丝溶液,通过静电纺丝的方法制备得到厚度为5-50微米的纳米纤维膜,纺丝电压为8-20kV;
c. 使用步骤b制备得到的纳米纤维膜在不锈钢棒上根据第一纳米纤维层1的厚度卷绕一定层数的纳米纤维膜,通过45-55℃热压复合制备得到纳米纤维层1;
d. 制备PLCL纺丝溶液,纺丝溶液的浓度为6%-12%,溶剂为六氟异丙醇;
e. 使用步骤d制备得到的纺丝溶液,通过静电纺丝的方法制备得到PLCL纳米纤维膜,然后将PLCL纳米纤维膜剪碎,置于去离子水中利用高速匀浆机将纤维分散均匀,制备生成浓度为30%-50%的纳米纤维溶液,纳米纤维溶液使用前需进行真空脱气处理;
f.将步骤c制备得到的第一纳米纤维层1套到血管模具的内芯3上,套上血管模具外模4包裹住第一纳米纤维层1,将步骤e制备得到的纳米纤维溶液浇筑到第一纳米纤维层1和血管模具外模4之间的空隙。将血管制备装置静置固定并置于-80℃的低温冰箱,冷冻处理1-6小时,随后转移至冷冻干燥器中进行冷冻干燥;
g. 将冷冻干燥后的人造血管从血管模具中移除,使用京尼平溶液对人造血管进行交联处理,京尼平溶液浓度为0.5%-2.0%,京尼平溶液的溶解温度为37℃,溶剂为水和乙醇的共混物,水和乙醇的体积比为80:20。人造血管浸泡到京尼平溶液中进行交联,交联时间为0.5h-24h,交联温度为37℃。京尼平是一种天然的交联剂,主要以栀子为原料提取所得,其细胞毒性为传统交联剂戊二醛的1/10000,作为一种天然的交联剂,除具有与传统人工合成的化学交联剂相近的交联高效性外,还具有毒性低、细胞相容性好的优势。用京尼平进行交联后,胶原蛋白材料的生物降解性、力学性能都可以得到一定的提高;
h. 将步骤g制备得到的人造血管用纯化水浸泡5-10分钟,随后用鼓风干燥箱烘干,烘干温度为40-55℃,干燥时间为30-120分钟。
实施例1
制备胶原蛋白/PLCL(乳酸己内酯共聚物)共混的纺丝溶液,胶原蛋白/PLCL的质量比为50:50,纺丝溶液的浓度为10% w/v,溶剂为六氟异丙醇。通过静电纺丝的方法制备得到厚度为10微米的纳米纤维膜,纺丝电压为12kV,将制备得到的纳米纤维膜在3.0mm不锈钢棒上卷绕7层,在50℃下热压复合制备得到第一纳米纤维层1,第一纳米纤维层1的厚度为56微米。
制备PLCL纺丝溶液,纺丝溶液的浓度为8%,溶剂为六氟异丙醇。通过静电纺丝的方法制备得到PLCL纳米纤维膜,然后将PLCL纳米纤维膜剪碎,置于去离子水中利用高速匀浆机将纤维分散均匀,制备生成浓度为35%的纳米纤维溶液,纳米纤维溶液使用前需进行真空脱气处理。
将制备得到的第一纳米纤维层1套到血管加工模具的内芯3上,然后套上血管模具外模4,使外模4包裹住第一纳米纤维层1,将35%的纳米纤维溶液浇筑到第一纳米纤维层1和血管模具外模4之间的空隙。将血管制备装置静置固定并置于-80℃的低温冰箱,冷冻处理3小时,随后转移至冷冻干燥器中进行冷冻干燥。
将冷冻干燥后的人造血管从血管模具中移除,使用京尼平溶液对人造血管进行交联处理,京尼平溶液浓度为1.0%,京尼平溶液的溶解温度为37℃,溶剂为水和乙醇的共混物,水和乙醇的体积比为80:20。人造血管浸泡到京尼平溶液中进行交联,交联时间为3h,交联温度为37℃。将交联处理后的人造血管用纯化水浸泡5-10分钟,随后置于鼓风干燥箱中烘干,烘箱温度为50℃,干燥时间为60分钟。
制备得到的复合型人造血管的内径为3.0mm,管壁厚度为350微米,第一纳米纤维层1的厚度为56微米,第二纳米纤维层2的厚度294微米。第一纳米纤维层1的孔径为0.8微米,第二纳米纤维层2的孔径为81微米。
实施例2
制备胶原蛋白/PLCL共混的纺丝溶液,胶原蛋白/PLCL的质量比为25:75,纺丝溶液的浓度为9% w/v,溶剂为六氟异丙醇。通过静电纺丝的方法制备得到厚度为10微米的纳米纤维膜,纺丝电压为12kV,将制备得到的纳米纤维膜在4.0mm不锈钢棒上卷绕8层,在50℃下热压复合制备得到第一纳米纤维层1,用激光测径仪测得第一纳米纤维层1的厚度为62微米。
制备PLCL纺丝溶液,纺丝溶液的浓度为8%,溶剂为六氟异丙醇。通过静电纺丝的方法制备得到PLCL纳米纤维膜,然后将PLCL纳米纤维膜剪碎,置于去离子水中利用高速匀浆机将纤维分散均匀,制备生成浓度为40%的纳米纤维溶液,纳米纤维溶液使用前需进行真空脱气处理。
将制备得到的第一纳米纤维层1套到血管加工模具的内芯3上,然后套上血管模具外模4,使外模4包裹住第一纳米纤维层1,将40%的纳米纤维溶液浇筑到第一纳米纤维层1和血管模具外模4之间的空隙。将血管制备装置静置固定并置于-80℃的低温冰箱,冷冻处理3小时,随后转移至冷冻干燥器中进行冷冻干燥。
将冷冻干燥后的人造血管从血管模具中移除,使用京尼平溶液对人造血管进行交联处理,京尼平溶液浓度为1.0%,京尼平溶液的溶解温度为37℃,溶剂为水和乙醇的共混物,水和乙醇的体积比为80:20。人造血管浸泡到京尼平溶液中进行交联,交联时间为3h,交联温度为37℃。将交联处理后的人造血管用纯化水浸泡5-10分钟,随后置于鼓风干燥箱中烘干,烘箱温度为50℃,干燥时间为60分钟。
制备得到的复合型人造血管的内径为4.0mm,管壁厚度为450微米,第一纳米纤维层1的厚度为62微米,第二纳米纤维层2的厚度388微米。第一纳米纤维层1的孔径为0.7微米,第二纳米纤维层2的孔径为59微米。
实施例3
制备胶原蛋白/PLCL共混的纺丝溶液,胶原蛋白/PLCL的质量比为25:75,纺丝溶液的浓度为9% w/v,溶剂为六氟异丙醇。通过静电纺丝的方法制备得到厚度为6微米的纳米纤维膜,纺丝电压为12kV,将制备得到的纳米纤维膜在2.5mm不锈钢棒上卷绕15层,在50℃下热压复合制备得到第一纳米纤维层1,用激光测径仪测得第一纳米纤维层1的厚度为78微米。
制备PLCL纺丝溶液,纺丝溶液的浓度为6%,溶剂为六氟异丙醇。通过静电纺丝的方法制备得到PLCL纳米纤维膜,然后将PLCL纳米纤维膜剪碎,置于去离子水中利用高速匀浆机将纤维分散均匀,制备生成浓度为50%的纳米纤维溶液,纳米纤维溶液使用前需进行真空脱气处理;
将制备得到的第一纳米纤维层1套到血管加工模具的内芯3上,然后套上血管模具外模4,使外模4包裹住第一纳米纤维层1,将50%的纳米纤维溶液浇筑到第一纳米纤维层1和血管模具外模4之间的空隙。将血管制备装置静置固定并置于-80℃的低温冰箱,冷冻处理3小时,随后转移至冷冻干燥器中进行冷冻干燥。
将冷冻干燥后的人造血管从血管模具中移除,使用京尼平溶液对人造血管进行交联处理,京尼平溶液浓度为1.0%,京尼平溶液的溶解温度为37℃,溶剂为水和乙醇的共混物,水和乙醇的体积比为80:20。人造血管浸泡到京尼平溶液中进行交联,交联时间为3h,交联温度为37℃。将交联处理后的人造血管用纯化水浸泡5-10分钟,随后置于鼓风干燥箱中烘干,烘箱温度为50℃,干燥时间为60分钟。
制备得到的复合型人造血管的内径为2.5mm,管壁厚度为260微米,第一纳米纤维层1的厚度为78微米,第二纳米纤维层2的厚度182微米。第一纳米纤维层1的孔径为0.7微米,第二纳米纤维层2的孔径为29微米。
如图2,上述实施例1-3所提到的血管加工模具包括内芯3和外模4,外模4为中空的柱状结构,内芯3穿设在外模4的中空腔体内,外模4的中空腔体与内芯3同轴,将第一纳米纤维层1套在内芯3上后,然后将内芯3置于外模4的中空腔体内,第一纳米纤维层1与中空腔体的内壁之间具有间隙,纳米纤维溶液即浇注于该间隙处进行成型。
上述仅为本发明的优选实施例,本发明并不仅限于实施例的内容。对于本领域中的技术人员来说,在本发明的技术方案范围内可以有各种变化和更改,所作的任何变化和更改,均在本发明保护范围之内。
Claims (11)
1.一种复合型人造血管的制备方法,其特征在于:包括以下步骤:
制备第一纺丝溶液,并使用第一纺丝溶液,通过静电纺丝的方法制备得到第一纳米纤维膜;
将设定层数的第一纳米纤维膜在模具棒上卷绕形成中空管状作为第一纳米纤维层,各层第一纳米纤维膜之间通过热压复合粘结;
制备第二纺丝溶液,并使用第二纺丝溶液,通过静电纺丝的方法制备第二纳米纤维膜;
将第二纳米纤维膜剪碎,置于去离子水中利用高速匀浆机将纤维在去离子水中分散均匀,得到纳米纤维溶液;
将中空管状的第一纳米纤维层置于模腔内,第一纳米纤维层外壁与模腔内壁之间设置有设定距离的间隙,将所述纳米纤维溶液浇注于所述模腔内,使纳米纤维溶液填充于所述第一纳米纤维层外壁与模腔内壁之间的间隙处;
待纳米纤维溶液在模腔内成型后形成第二纳米纤维层,所述第二纳米纤维层与所述第一纳米纤维层连接形成人造血管;
脱模后对人造血管进行交联处理。
2.根据权利要求1所述的复合型人造血管的制备方法,其特征在于:所述第一纺丝溶液为胶原蛋白/乳酸己内酯共聚物共混的纺丝溶液,所述第二纺丝溶液为乳酸己内酯共聚物纺丝溶液,第一纺丝溶液和第二纺丝溶液的溶剂为六氟异丙醇。
3.根据权利要求2所述的复合型人造血管的制备方法,其特征在于:所述胶原蛋白/乳酸己内酯共聚物的质量比为50:50或25:75,所述第一纺丝溶液的浓度为6%-12%,所述第二纺丝溶液的浓度为6%-12%,所述纳米纤维溶液的浓度为30%-50%。
4.根据权利要求1所述的复合型人造血管的制备方法,其特征在于:在纳米纤维溶液浇注完成后将置有第一纳米纤维层和纳米纤维溶液的模具在低温下冷冻处理1-6小时,然后进行冷冻干燥;
交联处理后的人造血管用纯化水浸泡5-10分钟,随后用鼓风干燥箱烘干,烘干温度为40-55℃,干燥时间为30-120分钟制得最终所需的复合型人造血管。
5.一种复合型人造血管,其特征在于:由权利要求1~4任一项所述方法制备而成。
6.根据权利要求5所述的复合型人造血管,其特征在于:人造血管为双层管状结构,包括置于内层的第一纳米纤维层和置于外层的第二纳米纤维层,所述第一纳米纤维层与所述第二纳米纤维层贴合连接,所述第一纳米纤维层由一层、两层或多层纳米纤维膜卷制形成,所述第二纳米纤维层为一体成型结构,所述第一纳米纤维层和第二纳米纤维层上均设置有微孔结构;
所述第一纳米纤维层厚度为50-100微米,微孔结构的平均孔径为0.6-1.2微米,所述第一纳米纤维层的纤维的平均直径为200-1000纳米;
所述第二纳米纤维层厚度为200-600微米,微孔结构的平均孔径为20-100微米,所述第二纳米纤维层的纤维的平均直径为500-1400纳米。
7.根据权利要求6所述的复合型人造血管,其特征在于:形成所述第一纳米纤维层的纳米纤维膜的厚度为5-50微米。
8.根据权利要求6所述的复合型人造血管,其特征在于:所述第一纳米纤维层为胶原蛋白和乳酸己内酯共聚物纳米纤维层。
9.根据权利要求6所述的复合型人造血管,其特征在于:所述第二纳米纤维层为乳酸己内酯共聚物纳米纤维层。
10.根据权利要求6所述的复合型人造血管,其特征在于:所述人造血管的直径为2-5mm,所述人造血管的壁厚为250微米-700微米。
11.根据权利要求6所述的复合型人造血管,其特征在于:所述第二纳米纤维层通过浓度为30%-50%的纳米纤维溶液浇筑于模具中制备而成。
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