CN117297830A - 一种多功能复合人工血管及其制备方法 - Google Patents
一种多功能复合人工血管及其制备方法 Download PDFInfo
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- CN117297830A CN117297830A CN202311299668.6A CN202311299668A CN117297830A CN 117297830 A CN117297830 A CN 117297830A CN 202311299668 A CN202311299668 A CN 202311299668A CN 117297830 A CN117297830 A CN 117297830A
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- Prior art keywords
- layer
- blood vessel
- artificial blood
- spinning
- electrostatic spinning
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- Pending
Links
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Classifications
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- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
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- A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2210/0076—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof multilayered, e.g. laminated structures
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- A—HUMAN NECESSITIES
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- A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
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- A—HUMAN NECESSITIES
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- A61F2250/0014—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Transplantation (AREA)
- Engineering & Computer Science (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Textile Engineering (AREA)
- Vascular Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Mechanical Engineering (AREA)
- Biomedical Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Molecular Biology (AREA)
- Materials For Medical Uses (AREA)
Abstract
本发明公开了一种多功能复合人工血管及其制备方法,所述人工血管为三层结构,包括内层、中层和外层,所述内层、中层、外层两两之间紧密结合不可分离,所述人工血管端口为中空圆柱结构,所述内层为亲水性内层,所述中层由致密层和螺旋环状支撑结构组成,所述外层为静电纺丝层。所述复合人工血管包括三层复合而成:内层为血液相容性好的静电纺丝层;中层为提供力学性能的致密层,为人造血管提供一定的力学强度;外层为与组织接触的纤维层。本发明所提供的复合人工血管具有较好的防渗漏和抗弯折性能,此外,比起传统的ePTFE血管,该血管具有优异的血液相容性,柔顺性良好。本发明提供的方法操作简便,适于商业化规模生产,内径尺寸范围可调。
Description
技术领域
本发明涉及医疗器械技术领域,具体涉及一种多功能复合人工血管及其制备方法。
背景技术
临床上一般采用自身血管进行造瘘,但大多数情况病人自身血管条件较差,当自体瘘不能用于血液透析时,通常采用膨体聚四氟乙烯(ePTFE)类的人工血管,例如Gore、Bard人工血管等。膨体聚四氟乙烯材料为非弹性体,在植入的弯曲部位血管由于应力而变形。如GORE-Acuseal(国械注进20153462072)采用内外双层均是膨体聚四氟乙烯,中间层是低透血的硅胶层。虽然力学性能满足穿刺需求,但是材料本身细胞亲和性较差、无法降解,该产品的内外层空隙较小难以使内皮细胞长入管壁,导致该血管不能与人体组织完美融合;且血管的周向弹性一般,血管壁整体较厚,植入后不良反应较多。在临床应用过程中多层结构易出现分层从而引起假性动脉夹层等现象。再者如PROPATEN系列产品,主要设计思想是通过间歇性调节ePTFE管壁的密度变化来实现抗弯折性能,通过调控不同区段的膨化率,从而实现材料自身的加强环结构,其内层通过CBAS技术接枝肝素可实现更长期的抗凝效果。虽能较高精度地控制管壁的密度,以达到优良的抗扭结性能,但内壁加强环区仍是高度致密结构,其内表面内皮化程度不均一且较困难,待肝素失去效用后,仍存在较高的血栓堵塞风险。此外,波士顿科学产品则通过对热挤出的膨体聚四氟乙烯管进行缠绕和再加热定形,制备出螺纹管状的血管内壁易出现螺纹凹凸纹理,不平整的内膜结构易出现血栓等并发症。
现有技术中,多层结构人造血管由于层间空隙较大,粘接效果不佳从而易出现层间剥离现象,即在临床上出现假性动脉瘤。而最小口径血管主要的问题依然是内皮化进程,临床医生建议的内皮化周期约为1个月内,大多ePTFE管内表面致密,导致内皮化进程较长而出现内膜增厚、血栓等其它并发症。因此,需要开发一种内表面能促进内皮化进程,且各项力学性能较优的复合人工血管是有必要的。
发明内容
本发明的目的在于提供一种新型防渗漏、抗弯折、抗凝血及促内皮化的多功能复合人工血管及其制备方法,以解决上述的技术问题。
为实现上述目的,本发明提供了以下技术方案:
本发明提供的一种多功能复合人工血管,所述人工血管为三层结构,包括内层、中层和外层,所述内层、中层、外层两两之间紧密结合不可分离,所述人工血管端口为中空圆柱结构,所述内层为亲水性内层,所述中层由致密层和螺旋环状支撑结构组成,所述外层为静电纺丝层。
进一步的,所述内层厚度为1μm~1000μm,所述外层厚度为1μm~500μm,所述致密层厚度为1μm~1000μm。
进一步的,所述螺旋环状支撑结构其螺旋环直径为0.1~2mm,环间距为1~5mm。
一种多功能复合人工血管的制备方法,包括以下步骤:
S1、将高分子化合物溶于溶剂中,分别得到w/v为5~30%的纺丝液和w/v为1~60%的电喷液;
S2、将纺丝液置于芯轴装置上,进行双侧静电纺丝,所述纺丝包含两种纤维丝堆叠而成,获得多孔的静电纺丝纤维内层,且孔隙由内到外成递减形式,适当干燥,去除残留溶剂;
S3、将内层作为接收面,采用电喷液进行初步喷涂,得到内部致密薄膜层;
S4、以内部致密层为接触面,设置接触面的运动规律,将高分子聚合物粒料进行热挤出,得到螺旋环状支撑结构,使内部致密层和螺旋环状支撑结构形成一体化结构;
S5、在S4获得的表面结构上继续进行间歇电喷,得到外部致密层;
S6、将外部致密层作为接受面,利用纺丝液进行静电纺丝涂覆,控制接收转轴转速,干燥,获得多孔的取向规则的静电纺丝纤维外层,最终得到复合人工血管。
进一步的,所述S1中高分子化合物选自明胶、丝素蛋白、肝素钠、聚己内酯、聚丙交酯、聚氨酯和聚(丙交酯-己内酯)中的一种或多种;所述溶剂选自甲酸,N ,N-二甲基甲酰胺,N ,N-二甲基乙酰胺,丙酮,四氢呋喃,六氟异丙醇中的一种或多种;所述明胶、丝素蛋白分子量在1万~30万,所述的聚己内酯、聚丙交酯及聚氨酯的重均分子量为1万~100万,聚己内酯、聚丙交酯特性粘度为0.5-2.0dL/g。
更进一步的,所述的聚己内酯的重均分子量为6万~30万,所述的聚丙交酯的重均分子量为5万~50万;所述的聚氨酯的重均分子量为6万~50万。
进一步的,所述S2、S6采用的纺丝液成分不同,步骤S2中采用PU、PCL和PLA等混纺液,此外添加天然高分子化合物辅料如明胶、肝素等;步骤S6中采用PU、PLCL等混纺液进行纺丝的方式制备外层。
进一步的,所述S2、S6采用的纺丝方式不同,步骤S2中采用双侧共轭静电纺丝,该方式可以引入多种生物活性成分,提高生物相容性,便于体内细胞快速浸润,同时利用不同降解周期材料实现梯度降解,维持内层结构稳定;步骤S6则采用普通静电纺丝制备即可。
进一步的,所述S2中静电纺丝纤维内层含有明胶、丝素蛋白、肝素钠其中的一种或几种;静电纺丝纤维其孔隙大小由内到外逐渐递减。
进一步的,所述S2、S6中所述静电纺丝的参数为:调节喷丝头与芯轴接收装置之间的距离为5~30cm;纺丝的环境温度为15~60℃,环境湿度15~70%RH,调节电压至10~30kV,溶液的给料速度为0 .1~6mL/h,辊筒转速为50~1000rad/min。
更进一步的,所述S2中静电纺丝的参数为:调节喷丝头与芯轴接收装置之间的距离为5~20cm;纺丝的环境温度为15~60℃,环境湿度15~60%RH,调节电压至10~30kV,溶液的给料速度为0 .1~5mL/h,辊筒转速为50~500rad/min。
更进一步的,所述S6中静电纺丝的参数为:溶液给料速率为2~6mL/h,接收距离8~15cm,辊筒转速为500~1000 rad/min,环境温度为25~40℃,环境湿度30~60% RH,调节电压至10~20 kV;所述S6中纤维直径为50nm~5000nm。
进一步的,所述S2中,静电纺丝时间为1~30h;所述步骤S6,静电纺丝时间为0 .5~15h。
更进一步的,所述S2中,静电纺丝时间为1-10h。
进一步的,所述S3中电喷的参数为:溶液给料速率为2~5mL/h,接收距离5~10cm,辊筒转速为50~200rad/min,环境温度为25~40℃,环境湿度30~60% RH,调节电压至8~15kV。
进一步的,所述S4的所述螺旋环状支撑结构采用的高分子聚合物粒料为聚氨酯、聚己内酯、聚丙交酯、全氟乙烯丙烯共聚物(FEP)和聚四氟乙烯(PTFE)中一种或几种。
进一步的,所述S5的电喷的参数为:溶液给料速率为1~4mL/h,接收距离8~12cm,辊筒转速为100~500rad/min,环境温度为25~40℃,环境湿度30~60%RH,调节电压至8~15kV。
进一步的,所述S6中静电纺丝纤维外层为周向环绕取向规则的静电纺丝结构。
基于上述技术方案,本发明实施例至少可以产生如下技术效果:
(1)本发明提供的多功能复合人工血管,内层为血液相容性好的静电纺丝纤维层,采用共轭静电纺丝的形式,对多种降解周期不同的材料进行复合,其静电纺丝支架孔径更大,生物相容性更好,细胞浸润速度更快,引入肝素成分纺丝一定程度可实现抗凝效果,加速内皮化进程。部分材料降解后,内壁仍能维持较好的稳定性,防止多层结构剥离而出现临床上假性动脉瘤的现象。
(2)本发明提供的多功能复合人工血管,中层由致密层和螺旋环状支撑结构组成,其致密层不仅起到粘接内外层的作用,其相对致密的结构有利于血管的耐穿刺性能,大大提高了整体的防渗漏性;此外,血管部分区域镶嵌的螺旋支撑环该螺旋环为中层高密度结构,由于中层多个致密层的多重加固作用,镶嵌在其中,相比较周围电喷结构,其较高的硬度和密度进一步提高了血管壁在弯折部分的径向支撑力实现抗弯折、抗扭结性能。
(3)本发明提供的多功能复合人工血管,外层结构为纺丝取向规则的静电纺丝层,通过调整纺丝工艺,所述周向环绕纺丝结构进一步改善血管整体的抗弯折性,使其具有更小的扭结半径,稳定性更强。此外纺丝结构有利于提高血管与周围组织相容性,加速细胞浸润。
(4)本发明提供的多功能复合人工血管,根据临床需求,临床医生可适当裁剪应用于不同的场景,所述血管可用于体内血管移植手术,动静脉造瘘或心脏搭桥手术等,如在动静脉造瘘应用过程中,可大大缩短瘘成熟期,耐穿刺性能好,可实现即刻穿刺。
附图说明
为了更清楚地说明本发明或现有技术中的技术方案,下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图仅仅是本发明的一些实施例,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图示出的结构获得其他的附图。
图1为本发明制备的复合人工血管内层纤维膜的纤维形貌图;
图2为本发明制备的复合人工血管截面图(不含螺旋支撑环结构);
图3为本发明制备的复合人工血管截面示意图;
图4为本发明制备的人工血管的外层纤维膜的纤维形貌图;
图5是本发明实施例的示意图;
图6是本发明实施例的示意图;
图7是本发明实施例的示意图;
图中:1、内层;2、中层;3、外层;4、螺旋环状支撑结构。
具体实施方式
应当理解,此处所描述的具体实施例仅用以解释本发明,并不用于限定本发明。
为使本发明的目的、技术方案和优点更加清楚,下面将结合本发明实施例,对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
由于带环结构不利于血管的穿刺操作,在冠脉搭桥部位也不适用。针对此问题螺旋环结构可选在血管合适的区段进行挤出,实现部分结构具有较强的抗弯折性能,控制合适的区段长度,既能满足临床穿刺所需长度要求,又能实现血管在特殊部位的抗弯折扭结性。
步骤S5间歇性电喷过程中,由于单次电喷所含有的溶质不足以形成一定厚度的致密膜,而连续长时间电喷容易出现溶剂过量渗透内部,造成结构破坏,所以需要间歇重复多次,达到完整覆盖的目的的同时能使电喷溶液的溶剂有足够时间挥发。
初次电喷考虑到内层纤维膜的破坏作用,电喷液浓度范围均须在电喷技术可接受的范围内,应使用较高浓度的电喷液,防止溶剂对内层的过度损伤。待表面成膜后,再进行热挤出螺旋环步骤及后续间歇性电喷,电喷可采用更低浓度进行操作,通过溶剂与初次电喷膜的二次溶解及整合,实现对螺旋环的稳定粘接和包载加固。
实施例1
一种多功能复合人工血管的制备方法,包括以下步骤:
(1)溶液的配制:将PLCL(特性粘度约1.0~1.5dL/g)溶于HFIP中,过夜搅拌均匀,得到浓度为20%(w/v)的①号电纺液;将PCL(特性粘数1.2~1.7dL/g)和PU(分子量约6~8万)溶解于HFIP中,其中重量比PCL:PU=20:80,40℃水浴加热搅拌12小时,得到浓度为10%(w/v)的②号电纺溶液,两溶液用于共轭电纺丝备用;将PU(分子量6~8万)溶于N ,N二甲基甲酰胺(DMF)与丙酮(体积比为5/5)的混合溶剂中,40℃水浴加热过夜搅拌,得到浓度为8、15%(w/v)的溶液,用于电喷备用。
(2)共轭静电纺丝:将(1)得到的两种电纺溶液分别注入10mL的注射器中,加上21G号不锈钢针头,分别置于接收轴两端。调节喷丝头与辊筒之间的距离为10~15cm;纺丝的环境温度为25~40℃,环境湿度30~60%RH,双侧纺丝调节正/负电压至±12~18kV,辊筒转速为100rad/min,溶液的给料速度为2~6mL/h,纺丝1h,将获得的纤维膜干燥12小时,去除过多的残留溶剂,获得复合血管的静电纺丝内层结构。
(3)初步电喷:a)调节PU溶液浓度为15%(w/v),给料速率为3.0mL/h,电喷距离为5~10cm之间,辊筒转速为50rad/min,环境温度为40℃,环境湿度50%RH,电压10kV,进行电喷30min后停止20min。待微量的电喷液在内层纤维表面附着并与纤维进行融合,减小纤维层孔隙率;同时,表面形成的一层薄薄的PU膜有利于隔绝热挤出环对于静电纺丝内层的损伤。
(4)3D打印热挤出:通过热挤出方式制备螺旋支撑环,原材料采用ePTFE(重均分子量为15万)材料,调节热挤出参数:温度330℃,主机挤出速率2Hz,以步骤(3)所获得的第一层致密膜作为接收面,致密膜与热挤出机的挤出头距离8cm,致密膜接收面运动的规律为:旋转速率16Hz,以2cm/s速率由左至右平行移动5s后,制成螺旋环套结构。
(5)二次间歇性电喷::将上述步骤(4)所获得的结构表面作为接收面,调节浓度为8%(w/v),给料速率为3.0mL/h,辊筒转速为50rad/min,电喷30min消除孔隙率并形成较薄的致密电喷膜,同时,使其螺旋环支撑结构被完全包覆及紧紧贴合,防止松动情况发生。中间间歇性停止烘干,再进行下一次电喷以达到指定厚度,放置烘箱干燥形成一定厚度的致密层。
(6)将步骤(5)所获得的致密中层结构作为接受面,采用PU/PCL(8:2)共混溶液作为纺丝液,调节喷丝头与转轴之间的距离为12cm;纺丝的环境温度为40℃,环境湿度30~40%RH,调节电压至15kV,辊筒转速为600rad/min,溶液的给料速度为4mL/h,纺丝2h,得到取向有序的静电纺丝纤维外层,真空干燥过夜烘干,最后获得本发明三层多功能复合结构人造血管。
实施例2
一种多功能复合人工血管的制备方法,包括以下步骤:
(1)溶液的配制:将PLCL(特性粘度约1.0~1.5dL/g)和明胶(胶强度250 g bloom)按照(5:1比例)溶于HFIP中,过夜搅拌均匀,得到浓度为18%(w/v)的①号电纺液;将PLCL(特性粘度约1.0~1.5dL/g)和PU(分子量约6~8万)溶解于HFIP中,其中质量比PLCL:PU=20:80,40℃水浴加热搅拌12小时,得到浓度为10%(w/v)的②号电纺溶液,两溶液用于共轭静电纺丝备用;将PU(分子量6~8万)溶于N ,N二甲基甲酰胺(DMF)与丙酮(体积比为8/2)的混合溶剂中,40℃水浴加热过夜搅拌,得到浓度为5、10%(w/v)的溶液,用于电喷备用。
(2)共轭静电纺丝:将(1)得到的两种电纺溶液分别注入10mL的注射器中,加上21G号不锈钢针头,分别置于接收轴两端。调节喷丝头与辊筒之间的距离为10~15cm;纺丝的环境温度为25~40℃,环境湿度30~40%RH,调节正电压至12~18kV,负电压至-12~18kV,辊筒转速为100rad/min,溶液的给料速度为2~6mL/h,纺丝1h,将获得的纤维膜干燥12小时,去除过多的残留溶剂,获得复合血管的静电纺丝内层结构。
(3)初步电喷:a)调节PU溶液浓度为10%(w/v),给料速率为3.0mL/h,电喷距离为8~12cm之间,辊筒转速为50rad/min,环境温度为40℃,环境湿度50%RH,电压10kV,进行电喷30min后停止20min。待微量的电喷液在内层纤维表面附着并与纤维进行融合,减小纤维层孔隙率;同时,表面形成的一层致密PU膜有利于隔绝热挤出环对于静电纺丝内层的热损伤。
(4)3D打印热挤出:通过热挤出方式制备螺旋支撑环,原材料采用PU(重均分子量为20万)材料,调节热挤出参数:温度200℃,主机挤出速率2Hz,以步骤(3)所获得的内部致密膜作为接收面,致密膜与热挤出机的挤出头距离8cm,致密膜接收面运动的规律为:旋转速率16Hz,以1.5cm/s速率由左至右平行移动3s后,制成部分螺旋环套结构。
(5)二次电喷::将上述步骤(4)所获得的结构表面作为接收面,调节浓度为5%(w/v),给料速率为4.0mL/h,辊筒转速为50rad/min,电喷30min消除孔隙率并形成较薄的致密电喷膜,同时,使其螺旋环支撑结构被完全包覆及紧紧贴合,防止松动情况发生。放置烘箱干燥形成一定厚度的致密层。
(6)将(5)所获得的致密中层结构作为接受面,采用PU/PLCL(8:2)共混溶液作为纺丝液,调节喷丝头与转轴之间的距离为12cm;纺丝的环境温度为40℃,环境湿度30~40%RH,调节电压至15kV,辊筒转速为600rad/min,溶液的给料速度为4mL/h,纺丝2h,得到取向有序的静电纺丝纤维外层,真空干燥过夜烘干,最后获得本发明三层复合结构人造血管。
实施例3
一种多功能复合人工血管的制备方法,包括以下步骤:
(1)溶液的配制:将PCL(特性粘度约0.8~1.2dL/g)和明胶(胶强度250 g bloom)按照(3:1比例)溶于HFIP中,得到浓度为20%(w/v)的溶液,将肝素钠(>150U/mg)按照200mg/ml浓度溶于甲酸溶液中,过夜搅拌均匀,将PCL/明胶溶液与肝素钠溶液按照体积比8:2充分混合得到①号电纺液;将PCL(特性粘度约0.8~1.2 dL/g)和PU(分子量约10~15万)溶解于HFIP中,其中质量比PCL:PU=20:80,40℃水浴加热搅拌12小时,得到浓度为10%(w/v)的②号电纺溶液,两溶液用于共轭静电纺丝备用;将PU(分子量10~15万)溶于N ,N二甲基甲酰胺(DMF)与丙酮(体积比为8/2)的混合溶剂中,40℃水浴加热过夜搅拌,得到浓度为3、8、15%(w/v)的溶液,用于电喷备用。
(2)共轭静电纺丝:将(1)得到的两种电纺溶液分别注入10mL的注射器中,加上21G号不锈钢针头,分别置于接收轴两端。调节喷丝头与辊筒之间的距离为10~15cm;纺丝的环境温度为25~40℃,环境湿度30~40%RH,调节正电压至12~18kV,负电压至-12~18kV,辊筒转速为100rad/min,溶液的给料速度为2~6mL/h,纺丝1h,将获得的纤维膜干燥12小时,去除过多的残留溶剂,获得复合血管的静电纺丝内层结构。
(3)初步电喷:a)调节PU溶液浓度为15%(w/v),给料速率为2.0mL/h,电喷距离为5~10cm之间,辊筒转速为50rad/min,环境温度为40℃,环境湿度50%RH,电压8~10kV,进行电喷20min后停止20min。待微量的电喷液在内层纤维表面附着并与纤维进行融合,减小纤维层孔隙率;同时,表面形成的一层致密PU膜有利于隔绝热挤出环对于静电纺丝内层的热损伤。
(4)3D打印热挤出:通过热挤出方式制备螺旋支撑环,原材料采用PLA(特性粘数3.2 dL/g)材料,调节热挤出参数:温度180℃,主机挤出速率4Hz,以步骤(3)所获得的内部致密膜作为接收面,致密膜与热挤出机的挤出头距离8cm,致密膜接收面运动的规律为:旋转速率16Hz,以3cm/s速率由左至右平行移动10s后,制成螺旋环套结构。
(5)二次电喷::将上述步骤(4)所获得的结构表面作为接收面,调节浓度为8%、5%(w/v),给料速率为4.0mL/h,辊筒转速为50rad/min,电喷30min消除孔隙率并形成较薄的致密电喷膜,同时,采用间歇性喷涂,中间待溶剂挥发再进行下一次喷涂,使其螺旋环支撑结构被完全包覆及紧紧贴合,防止松动情况发生。放置烘箱干燥形成一定厚度的致密层。
(6)将(5)所获得的致密中层结构作为接受面,采用PU/PCL(8:2)共混溶液作为纺丝液,调节喷丝头与转轴之间的距离为12cm;纺丝的环境温度为40℃,环境湿度30~40%RH,调节电压至15kV,辊筒转速为800rad/min,溶液的给料速度为4mL/h,纺丝1h,得到取向有序的静电纺丝纤维外层,真空干燥过夜烘干,最后获得本发明三层复合结构人造血管。
将本发明实施例1-3制得的血管移植物用于体内血管移植手术中,植入后基本稳定,未出现血栓及层间剥离等并发症,血管在体内能稳定存在,无不良反应,长期效果验证中。
最后应说明的是:
以上各实施例仅用以说明本发明的技术方案,而非对其限制;尽管参照前述各实施例对本发明进行了详细的说明,本领域的普通技术人员应当理解:其依然可以对前述各实施例所记载的技术方案进行修改,或者对其中部分或者全部技术特征进行等同替换;而这些修改或者替换,并不使相应技术方案的本质脱离本发明各实施例技术方案的范围。
Claims (10)
1.一种多功能复合人工血管,其特征在于,所述人工血管为三层结构,包括内层(1)、中层(2)和外层(3),所述内层(1)、中层(2)、外层(3)两两之间紧密结合不可分离,所述人工血管端口为中空圆柱结构,所述内层(1)为亲水性内层,所述中层(2)由致密层和螺旋环状支撑结构(4)组成,所述外层(3)为静电纺丝层。
2.根据权利要求1所述的多功能复合人工血管,其特征在于,所述内层(1)厚度为1μm~1000μm,所述外层(3)厚度为1μm~500μm,所述致密层厚度为1μm~1000μm。
3.根据权利要求1所述的多功能复合人工血管,其特征在于,所述螺旋环状支撑结构(4)其螺旋环直径为0.1~2mm,环间距为1~5mm。
4.一种多功能复合人工血管的制备方法,其特征在于,包括以下步骤:
S1、将高分子化合物溶于溶剂中,分别得到w/v为5~30%的纺丝液和w/v为1~60%的电喷液;
S2、将纺丝液置于芯轴装置上,进行双侧静电纺丝,所述纺丝包含两种纤维丝堆叠而成,获得多孔的静电纺丝纤维内层,且孔隙由内到外成递减形式,适当干燥,去除残留溶剂;
S3、将内层作为接收面,采用电喷液进行初步喷涂,得到内部致密薄膜层;
S4、以内部致密层为接触面,设置接触面的运动规律,将高分子聚合物粒料进行热挤出,得到螺旋环状支撑结构,使内部致密层和螺旋环状支撑结构形成一体化结构;
S5、在S4获得的表面结构上继续进行电喷,得到外部致密层;
S6、将外部致密层作为接受面,利用纺丝液进行静电纺丝涂覆,控制接收转轴转速,干燥,获得多孔的取向规则的静电纺丝纤维外层,最终得到复合人工血管。
5.根据权利要求4所述的一种多功能复合人工血管的制备方法,其特征在于,所述S1中高分子化合物选自明胶、丝素蛋白、肝素钠、聚己内酯、聚丙交酯、聚氨酯和聚(丙交酯-己内酯)中的一种或多种;所述溶剂选自甲酸,N ,N-二甲基甲酰胺,N ,N-二甲基乙酰胺,丙酮,四氢呋喃,六氟异丙醇中的一种或多种;所述明胶、丝素蛋白分子量在1万~30万,所述的聚己内酯、聚丙交酯及聚氨酯的重均分子量为1万~100万,聚己内酯、聚丙交酯特性粘度为0.5-2.0 dL/g。
6. 根据权利要求4所述的一种多功能复合人工血管的制备方法,其特征在于,所述S2、S6中所述静电纺丝的参数为:调节喷丝头与芯轴接收装置之间的距离为5~30cm;纺丝的环境温度为15~60℃,环境湿度15~70%RH,调节电压至10~30kV,溶液的给料速度为0 .1~6mL/h,辊筒转速为50~1000rad/min,所述S2中,静电纺丝时间为1~30h;所述步骤S6,静电纺丝时间为0 .5~15h。
7.根据权利要求4所述的一种多功能复合人工血管的制备方法,其特征在于,所述S2、S6采用的纺丝液成分不同,步骤S2中采用PU、PCL和PLA等混纺液进行双侧共轭静电纺丝,此外混纺液中添加天然高分子化合物辅料如明胶、肝素等加强亲水性及短期抗凝性;步骤S6中采用PU、PLCL等混纺液进行单侧纺丝的方式制备外层。
8.根据权利要求4所述的一种多功能复合人工血管的制备方法,其特征在于,所述S3中初次电喷的参数为:溶液给料速率为2~5mL/h,接收距离5~10cm,辊筒转速为50~200rad/min,环境温度为25~40℃,环境湿度30~60%RH,调节电压至8~15kV。
9.根据权利要求4所述的一种多功能复合人工血管的制备方法,其特征在于,所述S4的螺旋环状支撑结构采用的高分子聚合物粒料为聚氨酯、聚己内酯、聚丙交酯、全氟乙烯丙烯共聚物(FEP)和聚四氟乙烯(PTFE)中一种或几种。
10. 根据权利要求4所述的一种多功能复合人工血管的制备方法,其特征在于,所述S5的二次电喷的参数为:溶液给料速率为1~4mL/h,接收距离8~12cm,辊筒转速为100~500rad/min,环境温度为25~40℃,环境湿度30~60%RH,调节电压至8~15kV。
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CN117752463B (zh) * | 2024-02-20 | 2024-05-14 | 北京阿迈特医疗器械有限公司 | 一种可植入人工血管或人工气管及其制备装置和方法 |
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