CN112545710A - 一种基于3d打印的多孔聚氨酯支架 - Google Patents
一种基于3d打印的多孔聚氨酯支架 Download PDFInfo
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Abstract
本发明公开了一种基于3D打印的多孔聚氨酯支架，所述支架由β‑TCP粉末和聚氨酯颗粒通过快速成型技术形成。按照如下步骤：(1)搭建聚氨酯/β‑TCP增材制造系统；(2)进行聚氨酯/β‑TCP支架打印耗材的制备；(3)3D打印多孔聚氨酯支架。本发明的支架材料用不可降解材料作为内支撑材料，不仅可以构建形态更加完美的软骨组织，还能减少对种子细胞数目的要求。
Description
技术领域
本发明属于3D打印的技术领域，利用3D打印技术个性化制造聚氨酯/β-TCP新型半降解复合材料耳廓支架，结合干细胞技术，在软骨脱细胞基质作用下，实现耳廓软骨再生。
背景技术
目前临床上耳廓修复方法包括赝复体修复(义耳)和外科手术。赝复体修复简单快速，价格低廉。但是存在仿真效果差、材料老化变色、固位困难等问。外科手术植入物有人工假体和自体肋软骨两种，对于这两种手术方法一直存在争议。人工假体的优点是植入体为预定形态，缩短了手术时间；主要缺点是与皮肤组织结合较差，易导致假体外露及感染的发生。自体肋软骨是应用最为广泛并作为全耳重建的首选材料，但是再造耳外形与对侧耳廓不一致，严重依赖整形医生的个人技术水平，手术操作时间长，以及患者胸廓损伤畸形是自体肋软骨移植的缺点。
随着再生医学技术的飞速发展，组织工程耳廓软骨的研究成为替代上述耳廓重建可能的方法。以往的研究者在裸鼠体内或是通过体外培养的方法，构建了具有耳廓形态的组织工程软骨，比如90年代国外实验室培育的“人耳鼠”一度引起世界生物学界和医学界的轰动，但其有明显的缺点：①利用人工合成的可吸收性的外源性的支架材料，其不能精确控制降解速率，随着时间的延长都或多或少发生了变形；②支架材料的酸性降解产物易导致较严重的炎症反应，而且动物模型采用的是缺乏正常免疫力的裸鼠动物模型，缺乏在具有正常免疫力的大动物身上安全应用的实验数据支持。实际上，国内外至今还没有合适的组织工程耳廓软骨，能够替代正常耳廓软骨的弹性和形状。因此，要解决上述几种耳廓重建方法的缺点，构建精确形态并且不随时间而变形的耳廓软骨，加快组织工程向临床应用转化需要新的思路与方法。
目前大部分研究学者多采用将干细胞体外分化为软骨后，种植于载体材料之上构建组织工程软骨。根据国内外文献的报道,发现体外诱导分化的干细胞易在体外形成软骨结节,不易进行分离,即使勉强分离后细胞活性严重下降；而且因为未分化脂肪干细胞的优势生长作用而抑制了分化后软骨细胞的增殖能力,乃至凋亡,加之种植于支架载体后细胞外微环境的剧烈改变、繁琐的操作过程增加了细胞污染的几率等诸多原因,使得软骨再生的效果很不理想。
发明内容
本发明公开了一种多孔聚氨酯支架及其用途，由多孔聚氨酯和β-TCP(β-磷酸三钙)组成的支架，本发明采用不可降解材料作为内支撑材料，不仅可以构建形态更加完美的软骨组织，还能减少对种子细胞数目的要求。本发明请求保护的是一种基于3D打印的多孔聚氨酯支架，不保护这种支架用于疾病的诊断和治疗的方法。
一种基于3D打印的多孔聚氨酯支架，所述支架由β-TCP粉末和聚氨酯颗粒通过快速成型技术形成。
按照如下步骤：
(1)搭建聚氨酯/β-TCP增材制造系统；
(2)进行聚氨酯/β-TCP支架打印耗材的制备；
(3)3D打印多孔聚氨酯支架。
步骤(2)：通过对β-TCP表面修饰的方法，提升β-磷酸三钙的分散性；将β-TCP粉末和聚氨酯颗粒在混料机内以一定比例共混，制备出聚氨酯/β-TCP打印耗材。
一种多孔聚氨酯支架的用途：
所述多孔聚氨酯支架用于作为人耳廓形态支架。
所述多孔聚氨酯支架的制备方法，以头颅的三维CT扫描技术为基础，进行颅面部三维重建，然后以健侧的耳廓软骨为模板，将其镜像翻转至缺损侧，在计算机重建软件内调整后，导出三维重建数据，然后将打印耗材热熔后，在快速成型机内精确成型具有人耳廓形态的多孔聚氨酯支架。
有益效果
适宜的支架材料是决定耳廓软骨组织再生的重要因素。以往的组织工程支架是采用可降解的支架材料，随着软骨细胞沿着支架生长，支架材料逐步在体内降解，最终构建出完整的软骨组织。但是这种方式构建出来的软骨组织稳定性较差，由于缺乏支架材料的支撑，再生的软骨形态会发生改变，这对于临床上美观要求严格的耳廓来说影响较大。此外，支架材料的酸性降解产物易导致较严重的炎症反应，从而影响耳廓软骨重建的效果和患者的健康。用不可降解材料作为内支撑材料，不仅可以构建形态更加完美的软骨组织，还能减少对种子细胞数目的要求。
具体实施例
一种基于3D打印的多孔聚氨酯支架，所述支架由β-TCP粉末和聚氨酯颗粒通过快速成型技术形成。
按照如下步骤：
(1)搭建聚氨酯/β-TCP增材制造系统；
(2)进行聚氨酯/β-TCP支架打印耗材的制备；
(3)3D打印多孔聚氨酯支架。
步骤(2)：通过对β-TCP表面修饰的方法，提升β-磷酸三钙的分散性；将β-TCP粉末和聚氨酯颗粒在混料机内以一定比例共混(1：1)，制备出聚氨酯/β-TCP打印耗材。
一种多孔聚氨酯支架的用途：
所述多孔聚氨酯支架用于作为人耳廓形态支架。
所述多孔聚氨酯支架的制备方法，以头颅的三维CT扫描技术为基础，进行颅面部三维重建，然后以健侧的耳廓软骨为模板，将其镜像翻转至缺损侧，在计算机重建软件内调整后，导出三维重建数据，然后将打印耗材热熔后，在快速成型机内精确成型具有人耳廓形态的多孔聚氨酯支架。
按照如下步骤：
1.搭建聚氨酯/β-TCP增材制造系统：
聚氨酯/β-TCP增材制造系统主要由运动模块、温度控制模块、挤出模块三部分构成。运动模块实现挤出喷头在三维空间内任意位置的运动；温度控制模块主要是控制系统中喷头、成形基板等部件的温度，维持成形过程中温度场的稳定，降低成形过程中的热应力；挤出模块是实现打印耗材供给、熔融挤出等功能。在LabVIEW软件平台上所开发的聚氨酯/β-TCP增材制造系统上位机软件的协调下，实现各个系统间的协同工作，完成任意形状材料的增材制造。
2.进行聚氨酯/β-TCP支架打印耗材的制备：
通过对β-TCP表面修饰的方法，提升β-磷酸三钙的分散性。将β-TCP粉末和聚氨酯颗粒在混料机内以一定比例共混，制备出聚氨酯/β-TCP打印耗材。
3.打印人耳廓形态支架
应用在计算机控制下的快速成型技术(热熔堆积)精确成型具有人耳廓形态的多孔聚氨酯/β-TCP支架。简要步骤为：以头颅的三维CT扫描技术为基础，进行颅面部三维重建，然后以健侧的耳廓软骨为模板，将其镜像翻转至缺损侧，在计算机重建软件内调整至医生和患者满意后，导出三维重建数据，然后将打印耗材热熔后，在快速成型机内精确成型具有人耳廓形态的多孔聚氨酯支架。
设计、制备在计算机控制下的通过快速成型技术(热熔堆积)精确成型的具有人耳廓形态的多孔聚氨酯/β-TCP支架，将其作为支柱结构，用以维持组织工程耳廓软骨长期稳定的三维复杂形态；支架内部的多孔结构为移植的种子细胞和软骨脱细胞基质复合物提供依附和软骨发育的场所。
分离培养患者来源的脂肪干细胞，为了提高了种子细胞移植后的生存率、增加移植细胞的有效数量、保持其正常的生物活性，我们将脂肪干细胞在体外诱导为脂肪干细胞膜片，在此基础上制备脂肪干细胞聚集体。提前一段时间在患者缺损耳区皮下注入水囊，进行皮肤扩张，一切准备完备后，最后由颌面外科医生将人耳廓形态聚氨酯支架/人脂肪干细胞膜片片段/猪软骨脱细胞基质复合体结构移植入耳部皮下，调整位置，精确缝合，做好术后消毒、护理工作。
Claims (5)
1.一种基于3D打印的多孔聚氨酯支架，其特征在于：所述支架由β-TCP粉末和聚氨酯颗粒通过快速成型技术形成。
2.如权利要求1所述的多孔聚氨酯支架，其特征在于，按照如下步骤：
(1)搭建聚氨酯/β-TCP增材制造系统；
(2)进行聚氨酯/β-TCP支架打印耗材的制备；
(3)3D打印多孔聚氨酯支架。
3.如权利要求2所述的多孔聚氨酯支架，其特征在于，步骤(2)：通过对β-TCP表面修饰的方法，提升β-磷酸三钙的分散性；将β-TCP粉末和聚氨酯颗粒在混料机内共混，制备出聚氨酯/β-TCP打印耗材。
4.一种多孔聚氨酯支架的用途，其特征在于：
所述多孔聚氨酯支架用于作为人耳廓形态支架。
5.如权利要求2所述多孔聚氨酯支架的制备方法，其特征在于：以头颅的三维CT扫描技术为基础，进行颅面部三维重建，然后以健侧的耳廓软骨为模板，将其镜像翻转至缺损侧，在计算机重建软件内调整后，导出三维重建数据，然后将打印耗材热熔后，在快速成型机内精确成型具有人耳廓形态的多孔聚氨酯支架。
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