CN108619576A - 一种软骨修复用复合多孔支架材料的制备方法 - Google Patents
一种软骨修复用复合多孔支架材料的制备方法 Download PDFInfo
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Abstract
本发明公开一种软骨修复用复合多孔支架材料的制备方法,属于生物医学材料技术应用领域,采用聚乙烯醇和硫酸软骨素为原料,采用静电纺丝法制备出聚乙烯醇/硫酸软骨素复合多孔支架材料,该制备方法能够连续制备纳米级或亚微米级超细纤维,制备出的软骨多孔支架具有独特的微观结构和适当的力学性能,细胞实验表明,该材料具有优良的生物性能,可被用于软骨修复领域中。
Description
技术领域
本发明涉及一种软骨修复用复合多孔支架材料的制备方法,属于生物医用材料领域。
背景技术
关节软骨是软骨之间的结合部分,由特异的细胞外基质包绕稀少的软骨细胞形成,具有复杂的生物力学特征和高度的耐用性,然而其自身修复能力有限,自然退变或创伤引起的缺损会导致其结构与功能上不可逆的损害。这主要是因为关节软骨中没有血供,且软骨细胞缺乏迁移能力,无法移动到损伤部位参与修复,且缺乏细胞分化所必须的母细胞及细胞迁移所必须的理想环境,因此软骨缺损难以自然修复。
目前临床上用于软骨损伤治疗的方法主要有微骨折术、软骨下骨钻孔术、软骨下骨磨削术、自体软骨移植和自体软骨细胞移植术等。然而,研究结果表明,这些方法只能暂时缓解疼痛等症状,最终结局还是修复部位的软骨退化或者坏死。随着组织工程技术的兴起,软骨缺损的修复已经有了一定的研究进展。
骨及软骨组织工程包括3个关键因素:生长因子、支架材料和种子细胞。其中支架材料的选择是骨及软骨组织工程的核心问题,而应用于临床是其最终目的,因此,理想的软骨支架材料应具备以下条件:良好的生物相容性,不易发生炎症反应,且利于细胞黏附;有一定的力学强度;良好的生物活性;其结构有利于营养物质的输入及代谢废物的排出,从而有利于软骨细胞的新陈代谢;良好的生物降解性,有利于细胞增殖,且支架的降解速率应与细胞的增值速率相匹配。
目前,骨及软骨组织工程支架材料主要分为三类:生物衍生材料、无机材料和高分子材料。天然衍生材料主要有胶原、几丁质、藻酸盐、纤维蛋白等,这类材料能促进细胞黏附、增殖并分泌基质,生物相容性好,但不易大规模生产并缺乏强度。无机材料主要是生物陶瓷类和生物活性玻璃。生物陶瓷主要有硫酸钙陶瓷、碳酸钙陶瓷、磷酸钙陶瓷及其同分异构体。以羟基磷灰石为代表的磷酸钙陶瓷是广泛应用的骨替代材料之一,它们都具有良好的生物相容性、生物降解性、骨传导性。但存在脆性大,柔韧性不够,在体内降解困难,影响了新骨的长入和后期改建等问题。以聚乳酸、聚羟基乙酸及其共聚物等为代表的高分子材料应用非常广泛。这类生物高分子材料具有良好的生物可降解性、生物相容性、安全无毒性及一定的力学性能,通过模塑、挤压、溶剂浇铸等技术可加工成各种结构形状。可根据需要制成纤维支架、多孔泡沫及管状结构等,从而使新生的骨组织具有理想的形态。然而,目前骨组织工程支架材料众多,每种支架材料各有其优缺点,现有的支架材料仅能达到理想支架材料要求的一部分,随着研究的不断深入,复合支架材料成为目前的研究热点之一。
聚乙烯醇(PVA)是一种常见的分子结构规整,分子链柔顺的水溶性高分子,具有半结晶结构的白色的粉末状树脂。医用级聚乙烯醇对人体无毒,无副作用,并具有良好的弹性、亲水性和生物相容性,已广泛应用于软骨组织工程。
硫酸软骨素(CS)是一种由N-乙酰半乳糖胺和葡萄糖醛酸组成的硫酸化糖胺聚糖(GAG),由于其抗炎,抗氧化和抗凋亡作用,数十年来被广泛用作骨关节炎的膳食补充剂。硫酸软骨素是许多结缔组织,特别是皮肤,骨骼,滑液和软骨的细胞外基质的主要成分,在医学上主要用于治疗关节疾病,具有止痛,促进软骨再生的功效,可以从根本上改善关节问题。
发明内容
本发明提供一种软骨修复用复合多孔支架材料的制备方法,将天然高分子硫酸软骨素与人工合成高分子聚乙烯醇共混,并采用戊二醛的乙醇溶液接收纺丝纤维,通过静电纺丝技术制备具有1~20微米大孔的纳米纤维支架材料,其中聚乙烯醇含量为60%~90%,硫酸软骨素含量为10~40%,另外含结合水0.1%~2%。
一种软骨修复用复合多孔支架材料的制备方法,具体包括以下步骤:
(1)在80℃~100℃下,按照聚乙烯醇与去离子水的质量体积比g:mL为5~10:100的比例,将聚乙烯醇溶于去离子水中,磁力搅拌2h~3h,记为A液;
(2)在室温下,按照硫酸软骨素与乙酸水溶液质量体积比g:mL为1~3:100的比例,将硫酸软骨素溶于体积浓度为4%~6%的乙酸水溶液中,记为B液;
(3)将A液和B液按照体积比为(1~3):1混合,在室温下磁力搅拌2~3h,配制成纺丝液;
(4)采用真空干燥器对步骤(3)所得的纺丝液进行负压脱泡处理;
(5)采用戊二醛的乙醇溶液作为液体接收器,电源正极接针头处,负极接钢板,钢板设置在液体接收器底部,取步骤(4)所得的纺丝液进行静电纺丝得到纺丝纤维,纺丝纤维在液体接收器中静置2h后取出,水洗后冷冻干燥,得到软骨修复用复合多孔支架材料。
步骤(4)所述负压脱泡的条件为:在400~760mm汞柱的负压下脱泡10~20h。
步骤(5)所述戊二醛的乙醇溶液是戊二醛与乙醇按照体积比为1:99~249,将戊二醛和乙醇进行混合得到,所述戊二醛为质量分数25%戊二醛水溶液。
步骤(5)所述静电纺丝条件为:所用针头为17~20号,纺丝液的推进速度为0.1~0.2mm/min,正电压为16~20KV,针头与接收装置的距离为10~20cm。
步骤(5)所述冷冻干燥是在-35℃~-40℃干燥1~5h。
本发明的有益效果:
(1)本发明所用原料聚乙烯醇、硫酸软骨素均无细胞毒性,具有良好的生物相容性,并且通过改变两者之间的的配比,使静电纺丝的成丝性可调。
(2)本发明通过改变静电纺丝相关参数,能较好地控制纤维质量及纤维直径分布,且该结构适合细胞黏附生长以及营养物质运输。
(3)本发明所述方法制备得到的软骨修复支架厚度可调,通过纺丝时间即可实现。
(4)本发明采用戊二醛的乙醇溶液接收纺丝纤维,能实现边纺丝边交联,同时所得支架的耐水性提高。
附图说明
图1是本发明实施例2得到的软骨修复用复合多孔支架材料的显微形貌图;
图2是本发明实施例3得到的软骨修复用复合多孔支架材料的显微形貌图;
图3是本发明实施例3得到的软骨修复用复合多孔支架材料的红外光谱图;
图4是本发明实施例4得到的软骨修复用复合多孔支架材料的显微形貌图。
具体实施方式
下面结合附图和具体实施例对本发明作进一步详细说明,但本发明的保护范围并不限于所述内容。
实施例1
本实施例一种软骨修复用复合多孔支架材料的制备方法,具体包括以下步骤:
(1)在80℃下,将1.5g聚乙烯醇溶于30mL去离子水中,磁力搅拌2h,配置成5%聚乙烯醇溶液,记为A液;
(2)将1mL冰乙酸加入24mL去离子水中,配制成4%的乙酸水溶液,在室温下将0.25g硫酸软骨素溶于该乙酸水溶液中,配置成1%硫酸软骨素的乙酸溶液,记为B液;
(3)将上述A、B溶液按照体积比为1:1混合,在室温下磁力搅拌2h,配制成共混静电纺丝液;
(4)采用真空干燥器对步骤(3)所得的纺丝液在400mm汞柱的负压下脱泡10h;
(5)将1mL25%戊二醛溶液加入249mL乙醇中作为液体接收器,采用17号针头,设定正电压为16kv,纺丝液的推注速度为0.1mm/min,针头与接收装置的距离为10cm,电源正极接针头处,负极接钢板,钢板设置在液体接收器底部,取步骤(4)所得的纺丝液进行静电纺丝,得到纺丝纤维,纺丝纤维在液体接收器中静置2h后取出,水洗3次后-35℃冷冻干燥5h,得到软骨修复用复合多孔支架材料。
本实施例得到的软骨修复用复合多孔支架材料纤维丝的直径分布在200~500nm,交联度为40%,拉伸强度为5.2MPa,细胞毒性为0级,即无细胞毒性。
实施例2
本实施例一种软骨修复用复合多孔支架材料的制备方法,具体包括以下步骤:
(1)在85℃下,将2.4g聚乙烯醇溶于30mL去离子水中,磁力搅拌2h,配置成8%聚乙烯醇溶液,记为A液;
(2)将1mL冰乙酸加入19mL去离子水中,配制成5%的乙酸水溶液,在室温下将0.4g硫酸软骨素溶于该乙酸水溶液中,配置成2%硫酸软骨素的乙酸溶液,记为B液;
(3)将上述A、B溶液按照体积比为2:1混合,在室温下磁力搅拌2h,配制成共混静电纺丝液;
(4)采用真空干燥器对步骤(3)所得的纺丝液在560mm的汞柱的负压下脱泡15h;
(5)将1mL25%戊二醛溶液加入166mL乙醇中作为液体接收器,采用18号针头,设定正电压为18kv,纺丝液的推注速度为0.15mm/min,针头与接收装置的距离为15cm,电源正极接针头处,负极接钢板,钢板设置在液体接收器底部,取步骤(4)所得的纺丝液进行静电纺丝,得到纺丝纤维,纺丝纤维在液体接收器中静置2h后取出,水洗3次后-40℃冷冻干燥1h,得到软骨修复用复合多孔支架材料。
如图1所示,本实施例得到的软骨修复用复合多孔支架材料纤维丝的直径分布在150~400nm,交联度为47%,拉伸强度为6.5MPa,细胞毒性为0级,即无细胞毒性。
实施例3
本实施例一种软骨修复用复合多孔支架材料的制备方法,具体包括以下步骤:
(1)在95℃下,将2.4g聚乙烯醇溶于30mL去离子水中,磁力搅拌3h,配置成8%聚乙烯醇溶液,记为A液;
(2)将1mL冰乙酸加入19mL去离子水中,配制成5%的乙酸水溶液,在室温下将0.4g硫酸软骨素溶于该乙酸水溶液中,配置成2%硫酸软骨素的乙酸溶液,记为B液;
(3)将上述A、B溶液按照体积比为3:1混合,在室温下磁力搅拌3h,配制成共混静电纺丝液;
(4)采用真空干燥器对步骤(3)所得的纺丝液在560mm的汞柱的负压下脱泡20h;
(5)将1mL25%戊二醛溶液加入124mL乙醇中作为液体接收器,采用19号针头,设定正电压为16kv,纺丝液的推注速度为0.20mm/min,针头与接收装置的距离为20cm,电源正极接针头处,负极接钢板,钢板设置在液体接收器底部,取步骤(4)所得的纺丝液进行静电纺丝,得到纺丝纤维,纺丝纤维在液体接收器中静置2h后取出,水洗3次后-36℃冷冻干燥3h,得到软骨修复用复合多孔支架材料。
如图2所示,本实施例得到的软骨修复用复合多孔支架材料纤维丝的直径分布在200~500nm,交联度为50%,拉伸强度为5.5MPa,细胞毒性为0级,即无细胞毒性,图3为红外光谱图,分析可知,软骨修复用复合多孔支架材料与PVA的红外谱图相比没有发生明显的偏移,说明静电纺丝对PVA的性质影响不大,而共混后CS的特征峰移动较大,这可能是由于静电纺丝过程中发生了分子链的缠结。
实施例4
本实施例一种软骨修复用复合多孔支架材料的制备方法,具体包括以下步骤:
(1)在95℃下,将2.4g聚乙烯醇溶于30mL去离子水中,磁力搅拌3h,配置成8%聚乙烯醇溶液,记为A液;
(2)将1mL冰乙酸加入19mL去离子水中,配制成5%的乙酸水溶液,在室温下将0.4g硫酸软骨素溶于该乙酸水溶液中,配置成2%硫酸软骨素的乙酸溶液,记为B液;
(3)将上述A、B溶液按照体积比为3:1混合,在室温下磁力搅拌3h,配制成共混静电纺丝液;
(4)采用真空干燥器对步骤(3)所得的纺丝液在760mm的汞柱的负压下脱泡20h;
(5)将1mL25%戊二醛溶液加入99mL乙醇中作为液体接收器,采用19号针头,设定正电压为20kv,纺丝液的推注速度为0.20mm/min,针头与接收装置的距离为20cm,电源正极接针头处,负极接钢板,钢板设置在液体接收器底部,取步骤(4)所得的纺丝液进行静电纺丝,得到纺丝纤维,纺丝纤维在液体接收器中静置2h后取出,水洗3次后-38℃冷冻干燥2h,得到软骨修复用复合多孔支架材料。
如图4所示,本实施例得到的软骨修复用复合多孔支架材料纤维丝的直径分布在400~700nm,交联度为53%,拉伸强度为6.8MPa,细胞毒性为0级,即无细胞毒性。
实施例5
本实施例一种软骨修复用复合多孔支架材料的制备方法,具体包括以下步骤:
(1)在100℃下,将3g聚乙烯醇溶于30mL去离子水中,磁力搅拌3h,配置成10%聚乙烯醇溶液,记为A液;
(2)将3mL冰乙酸加入47mL去离子水中,配制成6%的乙酸水溶液,在室温下将1.5g硫酸软骨素溶于该乙酸水溶液中,配置成3%硫酸软骨素的乙酸溶液,记为B液;
(3)将上述A、B溶液按照体积比为3:1混合,在室温下磁力搅拌3h,配制成共混静电纺丝液;
(4)采用真空干燥器对步骤(3)所得的纺丝液在560mm的汞柱的负压下脱泡20h;
(5)将1mL25%戊二醛溶液加入99mL乙醇中作为液体接收器,采用20号针头,设定正电压为20kv,推注速度为0.20mm/min,针头与接收装置的距离为20cm,电源正极接针头处,负极接钢板,钢板设置在液体接收器底部,取步骤(4)所得的纺丝液进行静电纺丝,得到纺丝纤维,纺丝纤维在液体接收器中静置2h后取出,水洗3次后-40℃冷冻干燥2h,得到软骨修复用复合多孔支架材料。
本实施例得到的软骨修复用复合多孔支架材料纤维丝的直径分布在200~500nm,交联度为54%,拉伸强度为7.0MPa,细胞毒性为0级,即无细胞毒性。
Claims (5)
1.一种软骨修复用复合多孔支架材料的制备方法,其特征在于,具体包括以下步骤:
(1)在80℃~100℃下,按照聚乙烯醇与去离子水的质量体积比g:mL为5~10:100的比例,将聚乙烯醇溶于去离子水中,磁力搅拌2h~3h,记为A液;
(2)在室温下,按照硫酸软骨素与乙酸水溶液质量体积比g:mL为1~3:100的比例,将硫酸软骨素溶于体积浓度为4%~6%的乙酸水溶液中,记为B液;
(3)将A液和B液按照体积比为(1~3):1混合,在室温下磁力搅拌2~3h,配制成纺丝液;
(4)采用真空干燥器对步骤(3)所得的纺丝液进行负压脱泡处理;
(5)采用戊二醛的乙醇溶液作为液体接收器,电源正极接针头处,负极接钢板,钢板设置在液体接收器底部,取步骤(4)所得的纺丝液进行静电纺丝得到纺丝纤维,纺丝纤维在液体接收器中静置2h后取出,水洗后冷冻干燥,得到软骨修复用复合多孔支架材料。
2.根据权利要求1所述软骨修复用复合多孔支架材料的制备方法,其特征在于,步骤(4)所述负压脱泡的条件为:在400~760mm汞柱的负压下脱泡10~20h。
3.根据权利要求1所述软骨修复用复合多孔支架材料的制备方法,其特征在于,步骤(5)所述戊二醛的乙醇溶液是戊二醛与乙醇按照体积比为1:99~249,将戊二醛和乙醇进行混合得到,所述戊二醛为质量分数25%戊二醛水溶液。
4.根据权利要求1所述软骨修复用复合多孔支架材料的制备方法,其特征在于,步骤(5)所述静电纺丝条件为:所用针头为17~20号,纺丝液的推进速度为0.1~0.2mm/min,正电压为16~20KV,针头与接收装置的距离为10~20cm。
5.根据权利要求1所述软骨修复用复合多孔支架材料的制备方法,其特征在于,步骤(5)所述冷冻干燥是在-35℃~-40℃干燥1~5h。
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CN110540404A (zh) * | 2019-10-17 | 2019-12-06 | 广州润虹医药科技股份有限公司 | 一种具有中空贯通结构的磷酸钙骨水泥、制备方法及其应用 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102677391A (zh) * | 2012-05-07 | 2012-09-19 | 东华大学 | 一种高选择性纳米纤维膜的制备方法 |
CN103225172A (zh) * | 2013-04-23 | 2013-07-31 | 常州大学 | 硫酸软骨素基纳米纤维无纺布及其制备方法和医用用途 |
CN104069536A (zh) * | 2014-07-11 | 2014-10-01 | 江苏开源康达医疗器械有限公司 | 一种制备海藻酸钠-壳聚糖纳米级医用敷料的制备方法 |
CN104998302A (zh) * | 2015-08-31 | 2015-10-28 | 中原工学院 | 一种以取向纳米纤维毡为骨架的纳米软骨修复材料及其制备方法 |
CN106474556A (zh) * | 2016-11-15 | 2017-03-08 | 昆明理工大学 | 一种多孔软骨修复用支架材料及其制备方法 |
-
2018
- 2018-04-27 CN CN201810389257.9A patent/CN108619576A/zh active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102677391A (zh) * | 2012-05-07 | 2012-09-19 | 东华大学 | 一种高选择性纳米纤维膜的制备方法 |
CN103225172A (zh) * | 2013-04-23 | 2013-07-31 | 常州大学 | 硫酸软骨素基纳米纤维无纺布及其制备方法和医用用途 |
CN104069536A (zh) * | 2014-07-11 | 2014-10-01 | 江苏开源康达医疗器械有限公司 | 一种制备海藻酸钠-壳聚糖纳米级医用敷料的制备方法 |
CN104998302A (zh) * | 2015-08-31 | 2015-10-28 | 中原工学院 | 一种以取向纳米纤维毡为骨架的纳米软骨修复材料及其制备方法 |
CN106474556A (zh) * | 2016-11-15 | 2017-03-08 | 昆明理工大学 | 一种多孔软骨修复用支架材料及其制备方法 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110540404A (zh) * | 2019-10-17 | 2019-12-06 | 广州润虹医药科技股份有限公司 | 一种具有中空贯通结构的磷酸钙骨水泥、制备方法及其应用 |
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