CN113384755A - 一种生物活性可降解镁合金引导骨再生膜及其密集孔的加工方法 - Google Patents

一种生物活性可降解镁合金引导骨再生膜及其密集孔的加工方法 Download PDF

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CN113384755A
CN113384755A CN202110515709.5A CN202110515709A CN113384755A CN 113384755 A CN113384755 A CN 113384755A CN 202110515709 A CN202110515709 A CN 202110515709A CN 113384755 A CN113384755 A CN 113384755A
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郭传瑸
韩建民
谭成文
李介博
郭雨竹
刘冠旗
陈良伟
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Peking University School of Stomatology
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Abstract

本发明涉及一种生物活性可降解镁合金引导骨再生膜及其密集孔的加工方法,包括:屏障膜,其形状贴合缺损区周围的骨组织,屏障膜分为上下两部分,屏障膜上设计有骨架结构区和按规则排布的通孔区通孔的排布规则为疏密相间分布,骨架结构处不设置通孔,通孔区为多个0.5‑5mm的圆形区域,在上述圆形区域内均匀分布多个小于或等于0.2mm的密集孔,密集孔的间距根据实际使用材料的腐蚀速率及所需求的腐蚀效果调整。屏障膜还包括深度为0.05mm‑0.25mm的盲孔,在盲孔处负载药物。本发明的通孔能起到排出降解气体、透过体液、营养物质、红细胞且阻碍软组织细胞透过的作用;通孔区的密集孔主要起到阻挡早期软组织长入,同时可在植入的同时,即可发生降解,释放镁离子,发挥成骨作用;屏障膜上设计有骨架结构,骨架结构处不设置通孔,可表面修饰缓慢降解,维持在骨修复过程中屏障膜的机械支撑作用,能够解决现有屏障膜通孔间的材料快速降解、通孔相互连接后使整个屏障膜过早失去机械支撑,不利于骨缺损区修复的技术问题。

Description

一种生物活性可降解镁合金引导骨再生膜及其密集孔的加工 方法
技术领域
本发明属于口腔医疗器械技术领域,特别涉及一种生物活性可降解镁合金引导骨再生膜及其密集孔的加工方法。
背景技术
当前牙周疾病是最常见的口腔疾病之一,且患者数量仍在持续增长。牙周疾病可导致牙周膜和牙龈组织受损,严重时可能导致患者尤其是老年患者的牙齿脱落和牙槽骨吸收。牙槽骨骨量不足就无法进行口腔种植等操作,因此在这种情况下,需要首先重建牙槽骨缺损区域。随着可降解医用金属材料和医疗技术的发展,引导骨再生(GBR)和引导组织再生(GTR)技术成为骨增量的应用热点。GBR和GTR是将生物材料膜植入骨缺损处的软、硬组织之间,起到阻隔软组织中细胞(如成纤维细胞)长入骨缺损区,帮助缺损区骨组织修复的作用。理想的口腔引导骨组织再生屏障膜材料需要具备以下性能:良好的生物相容性,可促进骨组织再生;屏障阻隔能力,防止成纤维细胞长入骨缺损区;足够的支撑能力,抵抗因咀嚼食物对屏障膜的压力,防止骨缺损区塌陷,为骨缺损区的骨生长提供良好的空间环境;骨诱导性能:具有一定的骨诱导性,增加骨缺损修复的程度和速度;一定的抗菌能力,预防植入初期的伤口感染;临床植入易操作等。
GBR屏障膜可分为可降解和不可降解屏障膜两类。可降解屏障膜通常分为由人工合成的聚合膜和动物源性胶原膜两种,该类屏障膜优点是不需要二次手术取出,但是它们的机械强度低,不能提供足够结构强度,无法为骨组织再生提供稳定的空间从而导致治疗失败。不可降解的屏障膜包括四氟乙烯膜、钛加强型聚四氟乙烯膜、钛膜和微孔滤膜等,是当前骨组织修复中最常用的材料。这些材料具有足够的机械强度,能够为骨组织再生提供稳定的空间,且生物相容性好。但是它们不可降解,不具有骨诱导性,且在骨修复后需要进行二次手术取出,增加患者痛苦和细菌感染的风险,同时存在因翻瓣导致再生的牙槽嵴顶骨组织发生再吸收的风险。
基于以上的问题,人们开发了可降解镁合金引导组织再生屏障膜。镁合金作为常见的生物医用材料,具有以下优点:生物相容性好,对人体无害;有一定的机械强度,足以抵抗粘膜的牵拉力和口腔咀嚼力;可完全降解吸收,不用二次手术取出,且降解释放的镁离子有优异的骨诱导性;临床使用方便,易于根据患者实际情况将膜片弯折、用剪刀修剪;镁合金降解产物有一定的抗菌性能,这些优点使镁合金成为目前最为理想的引导骨组织再生的材料。对此,申请人申请了可降解镁合金引导组织再生膜专利(专利号201710202694.0),但是在使用的过程中,发现还有如下问题:为了抑制镁合金的早期降解,往往采用表面涂层的方式,但成骨诱导性能又与镁合金降解产生的镁离子等降解产物成正相关,因此,当前的表面涂层等手段遏制了镁合金的早期成骨活性,导致当前镁合金难以兼顾早期抑制镁合金降解和降解产生的镁离子发挥成骨性能;其次,仍然缺乏镁合金材料孔洞大小的临界数据,即镁合金膜上多大的孔洞牙龈软组织不能长入;最后是镁合金膜孔洞的设计,如何用最少的材料起到屏障的作用。
发明内容
本发明的目的是提供一种生物活性可降解镁合金引导骨再生膜,克服现有技术中屏障膜的设计因为没有考虑到通孔的大小会影响软组织细胞迁移以及屏障膜的降解速率,通孔孔径太大会导致软组织细胞长入骨缺损区,阻碍骨组织修复;通孔孔径太小会导致屏障膜降解产生的气体无法顺利排出、加工难度增大;且设计的通孔基本排布于整个屏障膜上,没有疏密分布的规则,导致屏障膜通孔间的材料快速降解、通孔相互连接后使整个屏障膜过早失去机械支撑,不利于骨缺损区修复等技术问题。
为了解决上述技术问题,本发明采用的技术方案如下:
一种生物活性可降解镁合金引导骨再生膜,包括:屏障膜,其形状贴合缺损区周围骨组织,屏障膜分为上下两部分,屏障膜上设计有骨架结构区和按规则排布的通孔区,其特征在于:通孔的排布规则为疏密相间分布,骨架结构处不设置通孔,通孔区为多个0.5-5mm的圆形区域,在上述圆形区域内均匀分布多个小于或等于0.2mm的密集孔,密集孔的间距根据实际使用材料的腐蚀速率及所需求的腐蚀效果调整。
进一步地,屏障膜的厚度为0.08-0.30mm。
进一步地,屏障膜还包括深度为0.05mm-0.25mm的盲孔,在盲孔处负载药物。
进一步地,屏障膜的上部设置有大螺孔,下部设置有多个小螺孔。
进一步地,大螺孔的直径为1-3mm,小螺孔的直径为1-2mm,小螺孔共有四个,分为上下两排,每排两个。
进一步地,密集孔的孔径为0.01mm-0.2mm。
进一步地,密集孔的加工方法为在氢氧化钠溶液中采用飞秒激光加工,激光波长为800-1000nm,光斑直径为20-60μm,功率为2-10W,重复频率为1-5kHz,脉宽为100-150fs。
一种密集孔的加工方法,所述密集孔位于所述的生物活性可降解镁合金引导骨再生膜上,在氢氧化钠溶液中采用飞秒激光加工,激光波长为800-1000nm,光斑直径为20-60μm,功率为2-10W,重复频率为1-5kHz,脉宽为100-150fs。
与现有技术相比,本发明具有以下有益效果:
1.设计了可降解镁合金口腔屏障膜结构,该屏障膜形状贴合颌骨,易于根据实际应用情况将其弯曲与裁剪成合适的形状与规格;
2.屏障膜上设计有不同排布规则的通孔,使通孔起到排出降解气体、透过体液、营养物质、红细胞且阻碍软组织细胞透过的作用;通孔区的密集孔主要起到阻挡早期软组织长入,同时可在植入的同时,即可发生降解,释放镁离子,发挥成骨作用;屏障膜上设计有骨架结构,骨架结构处不设置通孔,可表面修饰缓慢降解,维持在骨修复过程中屏障膜的机械支撑作用,能够解决现有屏障膜通孔间的材料快速降解、通孔相互连接后使整个屏障膜过早失去机械支撑,不利于骨缺损区修复的技术问题;
3.设计了屏障膜盲孔,可在盲孔处载药,盲孔在体内降解可逐步释放药物,起到药物缓释作用,帮助治疗炎症,提高屏障膜引导组织再生的治疗效果。
4.在氢氧化钠溶液中用飞秒激光加工密集孔,能够使得孔周圆滑,基本没有熔铸层,孔的质量佳。
附图说明
图1为屏障膜基础形状及规格的示意图。
图2为通孔直径为0.5mm的屏障膜的示意图。
图3为密集孔直径为0.2mm的屏障膜的示意图。
图4为密集孔直径为0.1mm的屏障膜的示意图。
图5为密集孔直径为0.05mm的屏障膜的示意图。
图6为带盲孔的屏障膜的示意图。
图7为孔径为0.5mm和0.2mm的屏障膜大鼠颅骨骨缺损屏障膜降解1个月后情况对比图。(a)、(b)孔径为0.5mm的屏障膜;(c)、(d)孔径为0.2mm的屏障膜。
图8为激光打孔孔周扫描电镜图像,(a)、(b)空气中微秒激光加工;(c)、(d)空气中飞秒激光加工;(e)、(f)NaOH溶液中飞秒激光加工。
附图标记:1大螺孔;2小螺孔。
具体实施方式
口腔屏障膜基础形状及规格如图1所示(单位mm),厚度为0.08-0.30mm。大螺孔1与小螺孔2均为与螺钉连接固定屏障膜用。直径为1.2mm的小螺孔2共有四个,分为上下两排,每排两个,当患者牙槽骨较小时,可将下排小螺孔2周围材料剪除,以适应患者牙槽骨大小。
实施例1
为方便在大鼠体内进行预实验,评价屏障膜阻隔软组织长入效果和降解程度,将屏障膜模型简化为直径8mm,厚度0.08-0.30mm的带有通孔区的圆片。密集孔均分布在标准直径为0.5mm的圆形区域内,密集孔的直径为0.2mm,密集孔的分布如图3所示(单位:mm)。密集孔规格与分布规则可直接用于图1中的口腔屏障膜。
实施例2
其他与实施例1相同,不同之处在于密集孔的直径为0.1mm,密集孔的分布如图4所示(单位:mm)
实施例3
其他与实施例1相同,不同之处在于密集孔的直径为0.05mm,密集孔的分布如图5所示(单位:mm)
实施例4
在屏障膜上设置深度为0.1mm的盲孔,在盲孔处负载药物,盲孔在体内降解可以逐步释放药物,起到药物缓释作用,帮助治疗炎症,提高屏障膜引导组织再生的治疗效果;盲孔降解为穿孔后,可继续起到排气、阻隔软组的作用,带有盲孔的屏障膜立体示意图如图6所示。
对比例1
其他与实施例1相同,不同之处在于通孔区为单独的直径为0.5mm的通孔,分布图如图2所示。
将实施例1和对比例1中简化后的MgZnYNd屏障膜植入大鼠颅骨骨缺损处。植入体内一个月后降解及软组织长入情况如图7所示。经过对比可以得到,通孔孔径为0.5mm的屏障膜无法阻隔软组织,而密集孔孔径为0.2mmm的屏障膜可以阻隔软组织细胞长入孔内。并且屏障膜可以在一个月内基本保持骨架完整。
实施例6
分别采用介质为空气的微秒激光、介质为空气的飞秒激光、介质为氢氧化钠溶液的飞秒激光对屏障膜的密集孔进行加工。表1为上述3种不同加工方式的工作参数。
表1激光加工密集孔参数设置
Figure BDA0003061935320000041
图8是不同的激光加工条件下用扫描电镜观察的密集孔形貌。由图8可知,在空气中微秒激光加工,可看到孔洞周边不规则,呈锯齿状,放大以后可看到有90-100度的三角形凹陷,且熔铸层较厚;在空气中用飞秒激光加工,孔周相对比较规则,熔铸层也较薄;在氢氧化钠溶液中用飞秒激光加工,孔周圆滑,基本没有熔铸层,孔的质量最佳。

Claims (8)

1.一种生物活性可降解镁合金引导骨再生膜,包括:屏障膜,其形状贴合缺损区周围骨组织,屏障膜分为上下两部分,屏障膜上设计有骨架结构区和按规则排布的通孔区,其特征在于:通孔的排布规则为疏密相间分布,骨架结构处不设置通孔,通孔区为多个0.5-5mm的圆形区域,在上述圆形区域内均匀分布多个小于或等于0.2mm的密集孔,密集孔的间距根据实际使用材料的腐蚀速率及植入组织所需求的腐蚀效果调整。
2.根据权利要求1所述的生物活性可降解镁合金引导骨再生膜,其特征在于:屏障膜的厚度为0.08-0.30mm。
3.根据权利要求1或2所述的生物活性可降解镁合金引导骨再生膜,其特征在于:屏障膜还包括深度为0.05mm-0.25mm的盲孔,在盲孔处负载药物。
4.根据权利要求1或2所述的生物活性可降解镁合金引导骨再生膜,其特征在于:屏障膜的上部设置有大螺孔,下部设置有多个小螺孔。
5.根据权利要求4所述的生物活性可降解镁合金引导骨再生膜,其特征在于:大螺孔的直径为1-3mm,小螺孔的直径为1-2mm,小螺孔共有四个,分为上下两排,每排两个。
6.根据权利要求1或2所述的生物活性可降解镁合金引导骨再生膜,其特征在于:密集孔的孔径为0.01mm-0.2mm。
7.根据权利要求1或2所述的生物活性可降解镁合金引导骨再生膜,其特征在于:密集孔的加工方法为在氢氧化钠溶液中采用飞秒激光加工,激光波长为800-1000nm,光斑直径为20-60μm,功率为2-10W,重复频率为1-5kHz,脉宽为100-150fs。
8.一种密集孔的加工方法,所述密集孔位于权利要求1-6中任一项所述的生物活性可降解镁合金引导骨再生膜上,其特征在于:在氢氧化钠溶液中采用飞秒激光加工,激光波长为800-1000nm,光斑直径为20-60μm,功率为2-10W,重复频率为1-5kHz,脉宽为100-150fs。
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