CN111282019A - 一种医用钛种植体及其制备方法 - Google Patents
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Abstract
本发明公开了一种医用种植体及其制备方法;该方法是:首先构建具有孔隙的特殊记忆形变高分子材料,再将其固定在种植体本体表面,通过记忆形变高分子材料自身受光照或温度刺激可发生体积膨胀得到可降解膨胀种植体。相对于现有的医用种植体,本发明的种植体由外层可形变材料及内部种植体本体共同构成,其在种植体植入骨质后,通过可人为调控的方式使种植体外层高分子材料膨胀达到种植体较强的初期稳定性。材料自身的可降解性以及生长因子搭载能力,可以有效的促进骨类细胞碱性磷酸酶的合成和含钙矿物质沉积,诱导骨生成,从而最终实现种植体快速有效的骨整合作用。
Description
技术领域
本发明涉及一种医用钛种植体及其表面功能性结构制备方法。
背景技术
20世纪60年代瑞士的生物学家Branemark发现植入的钛金属能够与兔骨牢固的结合在一起,此外结合其有强大的力学性能,生物相容性和耐腐蚀等特性,钛金属植入物被广泛的运用于骨相关方面,运用前景巨大。[1]
然种植体植入的成功与否与其早期的初期稳定性有着极为重要的联系。在现在的研究中主要通过的是生物学的方式在种植体表面添加生长促进因子涂层促进种植体的早期骨整合以达到更强的初期稳定性。大部分研究都是通过对钛金属表面进行适合的改性,以使其有利于细胞组织,特别是成骨样细胞的快速表面粘附,提高骨整合效率。
种植体早期的机械稳定性是维持其稳定的主要方式,无论是通过何种表面改性(物理,化学,生物)的方式都难以达到迅速的加固稳定的方法。形状记忆聚合物(ShapeMemory Polymers,SMP)作为一种高分子材料,热致型的形状记忆高分子能够感知外界温度的变化,从一种临时的形状回复到原始的形状。至今其在医疗设备,传感器以及一些航空领域等,在生物领域温度响应的可降解形状记忆聚合物是最近些年的研究热点。
形状记忆聚合物具有两大特点,其一是具有结晶温度,其二是具有网络状的结构,这两者的共同作用使其具有记忆形状的能力。制备生物型形状记忆高分子通过有机合成的方式能够调控分子链段的长短和分子链上基团的数量使其拥有特殊功能并优化作用,而这种能够生产具有不同的玻璃化转变温度或熔融温度的聚合物,已经成为现今发展的一种主流方法。有学者制作的记忆形变可吸收缝线已经在临床上运用了,其能够在初期缝合宽松的创口通过加热变得紧密,减少了很多手术中的意外。在人体的环境下使用这种材料,必须具有一定的温度开关和组织相容性。
各种生长因子的引入使得现今生物材料领域有了长足的进步,通过表面的修饰能够使得材料具有更优良的生物学特性。目前的种植体脱落常出现在种植体植入后数日时间内,其由于旋入后种植体与备孔间存在一定的空隙或由于挤压导致早期骨吸收,种植体无法维持稳定的状态。
参考文献:
[1]T.R.Rautray,R.Narayanan and K.H.Kim.Ion implant of tiatanium basedbiomaterials[J].Progress in Materials Science,2011,56(8):1137-1177.
发明内容
本发明的目的在于提供一种具有强大功能性涂层的医用钛种植体及其制备方法。本发明的医用种植体可以采用国际标准的SLA处理后的钛种植体,经过表面涂层制备、复合种植体去离子水浸泡、高温下压膜冷却、细胞因子溶液沉降等过程得到具有温度阈刺激膨胀功能的医用种植体。
本发明的一种医用钛种植体的制备方法,包括以下步骤:
1)制备形状记忆聚合物材料前驱液
①将分子量为2000的聚己内酯与三乙胺、丙烯酰氯混合,溶于甲苯中,80℃反应8小时;抽滤后滤液在正己烷溶液中析出晶体,得到第一种双端带碳碳双键的聚己内酯PCLDA;
将分子量为10000的聚己内酯与三乙胺、丙烯酰氯混合,按照上述同样的方法制得第二种PCLDA;
②将第一种PCLDA与第二种PCLDA按照质量比1:1混合,加入光引发剂i2959,80℃加热混匀得到共混液;之后加入制孔剂,获得前驱液;
2)制备功能性涂层种植体
①准备两个模具,模具1为材料预混液的塑性容器,材质可为玻璃,具有很好的透光性,模具2为材料涂层标准化压缩容器,材质为不锈钢(针对实例的种植钉,模具1的具体参数可见附图1,模具2的具体参数可见图3);模具1和2均由镜像对称的两部分构成,两部分合模后形成一个与种植钉表面适配的槽,优选的,种植体放入模具1内时槽壁与种植体表面间隙为0.5mm-1mm;
②将SLA处理后的种植体置于模具1中,并在种植体与模具1之间注入前驱液,在UV光线照射下共聚,得到一层锚定在种植体表面的功能性聚合物层,厚度为0.5mm,之后将制作好的复合种植体放置在蒸馏水中浸泡除去多余的制孔剂;
③将复合种植体置于模具2中,放置在80℃的烘箱中,利用模具2将复合种植体固定并加压使种植体表面涂层压缩,降温至25℃后取出种植体;紫外光消毒灭菌后浸泡于含有生长因子的溶液中。
上述技术方案中,进一步的,步骤1)中分子量为2000的聚己内酯与三乙胺、丙烯酰氯的摩尔比为2:3:3。分子量为10000的聚己内酯与三乙胺、丙烯酰氯的摩尔比为1:3:3。通过过滤、结晶等方式获得的产物经过抽除多余溶剂的方式,得到较为纯净的PCLDA。通过上述两种组分的PCLDA按照质量比1:1及光引发剂混合搅拌后在80℃下加热形成均匀熔融的混合物,可以达到在46℃具有结晶溶解回复原始形状的状态,更好的应用于种植体。
进一步的,步骤1)中共混液中光引发剂i2959的质量分数为1%。
进一步的,步骤2)中所述的制孔剂为无机盐或糖类,无机盐包括氯化钠、氯酸钠,糖类包括蔗糖。通过浸泡在双蒸水中能够使制孔剂溶解,孔隙50um-200um。
步骤2)中所述的生长因子包括FN、RGD、VEGF、FGF。将生长因子按照1:200-1:1000的浓度溶解在PBS溶液中,将种植体浸泡在其中充分粘附渗入高分子层中,放置4-12h。
本发明的有益效果是:
本发明采用双端带双键的聚己内酯材料,通过调控其组分、分子量及通过不同分子量互混的方式达到转变温度在人体温度附近。通过高温下固定暂时外形后冷却至室温达到压缩表面功能涂层的目的。本发明通过材料的膨胀机械加固种植体与骨,可以有效维持早期的种植体稳定性,此外功能性涂层具有孔隙结构能够充分诱导细胞向内部生长,其具有可降解性在作用一段时间后可以完全被新生的骨质所替代。本发明的种植体涂层是一种高效功能性的涂层材料,生长因子等的引入加快了骨整合的过程,使种植体具有更加快速恢复功能的作用。
附图说明
图1是医用膨胀种植体的制备流程示意图。
图2是种植体外膨胀涂层塑性制作的示意图。
图3是种植体外涂层内晶体通过浸泡获得具有空隙的涂层的示意图。
图4是种植体外涂层通过加热加压记忆临时压缩外形的示意图及操作方法a)模具2加热挤压固定;b)模具2俯视图;c)挤压固定后涂层内空隙变小。
图5是该种种植体植入人体后发挥作用的示意图。
具体实施方式
下面将结合附图,对本申请实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本申请一部分实施例,而不是全部的实施例。基于本申请中的实施例,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,都属于本申请保护的范围。
本实例的医用种植体的制备方法如下:
1)首先制备两种模具,通过扫描标准种植体外形后建模设计获得模具1和模具2外形结构示意图,构建玻璃质模具1及不锈钢材质模具2,模具1、2均由镜像对称的两部分构成,两部分合模后形成一个与种植体表面适配的槽,内部接触面光滑。
2)形状记忆聚合物材料的制备
1.按下述方法制备两种基于不同分子量PCL的PCLDA:将聚己内酯(PCL)溶解于200ml甲苯溶液中放置于圆底烧瓶内,加入三乙胺并逐滴加入丙烯酰氯(具体配比见后方描述)共混,溶于甲苯中,80℃下磁珠搅拌,反应8h,得浑浊液。抽滤漏斗抽滤3遍后得澄清滤液,在500ml正己烷溶液中倒入滤液见晶体析出,0℃冰箱中放置2h,倒去上层溶液得沉淀,放置于20℃真空烘箱中24h抽去余留溶剂。通过氢谱验证所得产物分子量是否与预期相符。若符则得到对应双端带碳碳双键的聚己内酯(PCLDA)。
其中:2k分子量的聚己内酯按聚己内酯:三乙胺:丙烯酰氯的摩尔比2:3:3共混;10k分子量的聚己内酯是聚己内酯:三乙胺:丙烯酰氯按摩尔比1:3:3共混。
2.将上述制得的2k分子量对应PCLDA和10k分子量对应PCLDA按照1:1质量比混合,并加入占共混液质量分数1%的光引发剂i2959以及NaCl晶体,120℃搅拌加热混匀,真空烘箱70-80℃,放置30min,抽去内部残留气泡。得到澄清的预混液,即前驱液。
3)功能性涂层种植体的制备,具体流程如图1所示:
1.将SLA标准处理后的种植钉(3.3mm×3.3mm×8cm)放置于自设计的模具1(70-80℃烘箱中预热)中,向模具1中倒入预混液(图2),在UV(365nm)光下照射5min-10min,拆开模具1得到一层锚定在种植体表面的功能性聚合物层,厚度0.5mm左右。将制作好的种植体放置在500ml蒸馏水中2天(图3),每天换液除其中的制孔剂,得到复合种植体,其表面为具有均匀孔隙的高分子层(孔隙50um-200um)。
2.将种植体固定在模具2中,放置于70-80℃的烘箱中预热30min,将外部螺丝旋紧,加压使外部涂层压缩后固定模具(图4),降温至25℃,1-3h,使模具2与种植体逐渐降温,后取出种植体。种植前消毒灭菌后(低温保存0-20℃)。将种植体浸泡在含有FN,VEGF等因子的溶液中(浓度为1:200-1:1000)
如图5所示,在该种植体植入后,能够通过外界不拆除种植体的前提下,定时给予种植体早期固位的效果,增加种植体植入后的成功率(如图5,通过上端加热棒加热10s热传导完成下部高分子材料受热形变回复膨胀)。本发明将特制的高分子材料固定在种植体表面,记忆形变高分子材料自身受光照或温度刺激可发生体积膨胀;通过此系统可以得到可降解膨胀种植体。相对于现有的医用钛种植体,本发明的种植体由外层可形变材料及内部种植体本体共同构成,其在种植体植入骨质后,通过46℃金属的热传导作用刺激内部被压缩的可形变材料回复增加与骨的接触强度从而提高了种植体初期稳定性。材料自身的可降解性以及生长因子搭载能力,可以有效的促进骨类细胞碱性磷酸酶的合成和含钙矿物质沉积,诱导骨生成,从而最终实现种植体快速有效的骨整合作用。
Claims (7)
1.一种医用钛种植体的制备方法,其特征在于,包括如下步骤:
1)制备形状记忆聚合物材料前驱液
①将分子量为2000的聚己内酯与三乙胺、丙烯酰氯混合,溶于甲苯中,80℃反应8小时;抽滤后滤液在正己烷溶液中析出晶体,得到第一种双端带碳碳双键的聚己内酯PCLDA;
将分子量为10000的聚己内酯与三乙胺、丙烯酰氯混合,按照上述同样的方法制得第二种PCLDA;
②将第一种PCLDA与第二种PCLDA按照质量比1:1混合,加入光引发剂i2959,80℃加热混匀得到共混液;之后加入制孔剂,获得前驱液;
2)制备功能性涂层种植体
①准备两个模具,模具1和2均由镜像对称的两部分构成,两部分合模后形成一个与种植体表面适配的槽;其中,模具1材质透光,用于作为材料预混液的塑性容器,模具2用于作为材料涂层压缩容器,材质为不锈钢;
②将SLA处理后的种植体置于模具1中,并在种植体与模具1之间注入前驱液,在UV光线照射下共聚,得到一层锚定在种植体表面的功能性聚合物层,厚度为0.5mm,之后将制作好的复合种植体放置在蒸馏水中浸泡除去多余的制孔剂;
③将复合种植体置于模具2中,放置在80℃的烘箱中,利用模具2将复合种植体固定并加压使种植体表面涂层压缩,降温至25℃后取出种植体;紫外光消毒灭菌后浸泡于含有生长因子的溶液中4-12h。
2.根据权利要求1所述的医用钛种植体的制备方法,其特征在于,步骤1)中分子量为2000的聚己内酯与三乙胺、丙烯酰氯的摩尔比为2:3:3。
3.根据权利要求1所述的医用钛种植体的制备方法,其特征在于,步骤1)中分子量为10000的聚己内酯与三乙胺、丙烯酰氯的摩尔比为1:3:3。
4.根据权利要求1所述的医用钛种植体的制备方法,其特征在于,步骤1)中共混液中光引发剂的质量分数为1%。
5.根据权利要求1所述的医用钛种植体的制备方法,其特征在于,步骤2)中所述的制孔剂为无机盐或糖类,无机盐包括氯化钠、氯酸钠,糖类包括蔗糖。
6.根据权利要求1所述的医用钛种植体的制备方法,其特征在于,步骤2)中所述的生长因子包括FN、RGD、VEGF、FGF。
7.根据权利要求1所述的医用钛种植体的制备方法,其特征在于,种植体放入合模后的模具1内时槽壁与种植体表面间隙为0.5mm-1mm。
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