CN116570768B - 一种多层力学仿生缓释抗菌气管补片及其制备方法 - Google Patents

一种多层力学仿生缓释抗菌气管补片及其制备方法 Download PDF

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CN116570768B
CN116570768B CN202310227203.3A CN202310227203A CN116570768B CN 116570768 B CN116570768 B CN 116570768B CN 202310227203 A CN202310227203 A CN 202310227203A CN 116570768 B CN116570768 B CN 116570768B
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姚鑫骅
田李欣
叶健
苏炼
傅建中
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Zhejiang University ZJU
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Abstract

本发明公开了一种多层力学仿生缓释抗菌气管补片及制备方法。气管补片包括依次层叠的硅胶超材料结构层、水凝胶软基底层、抗菌涂层和多孔水凝胶层。方法包括：采用挤出式生物打印方式制备硅胶超材料结构层，加热加速硅胶固化；采用挤出式生物打印方式在硅胶超材料结构层上打印水凝胶软基底层使上下两层镶嵌；在水凝胶软基底层上喷涂抗菌涂层；浇铸多孔水凝胶层获得最终的气管补片。本发明可以提供与原生气管相匹配的非线性力学特性，解决因气管运动的复杂性导致补片拉伸脱落等问题，并设计多孔结构在不影响抗菌涂层释放银离子的同时使抗菌涂层不易脱落。

Description

一种多层力学仿生缓释抗菌气管补片及其制备方法
技术领域
本发明涉及了一种气管补片，具体涉及一种多层力学仿生缓释抗菌气管补片及其制备方法。
背景技术
人体气管壁由气管软骨，气管粘膜组成。气管软骨提供力学支撑，平滑肌胶原蛋白为气管提供非线性力学特性。气管损伤是由于外伤，气管镜使用，肿瘤的切除等病因导致的气管疾病。此时如果使用外科手术方式直接将气管纵向缝合，有造成医源性气管狭窄的风险，此时需要将气管切断再缝合。若是外科手术切除气管长度过大(大于6厘米)会导致吻合口张力过大。气管支架植入术相比传统手术拥有疗效确切，可迅速缓解症状，适用于各种原因气管狭窄以及减小患者痛苦等优点，但是气管支架因表面积较大，压迫气管内壁纤毛上皮细胞导致原有的清理粘液功能丧失。
目前最有临床应用前景的是运用补片治疗气管损伤，补片面积小，对气管内壁纤毛组织影响较小，由于人体运动的多样性和复杂性，补片由于不具备和原生气管匹配的非线性力学特性，容易在气管内移位或脱位。因气管与外界环境相同，外界微生物容易进入气管内，补片与损伤部位连接处容易炎症感染，因此大多补片都会有抗菌涂层减弱炎症，但抗菌涂层若是直接喷涂在表面容易脱落，采用模内转印方法制备的涂层不易脱落但抗菌效果较差。因此，亟需设计一种可以提供和原生气管相匹配的非线性力学特性并能拥有良好的抗菌性能的气管补片。
发明内容
为了解决背景技术中存在的问题，本发明所提供一种非线性力学抗菌气管补片。在提供与原生气管相匹配的非线性力学特性同时用多孔结构保证良好的抗菌效果。
本发明采用的技术方案是：
一、一种多层力学仿生缓释抗菌气管补片：
气管补片包括依次层叠的硅胶超材料结构层、水凝胶软基底层、抗菌涂层和多孔水凝胶层，硅胶超材料结构层、水凝胶软基底层、抗菌涂层和多孔水凝胶层均为片状结构，硅胶超材料结构层嵌入水凝胶软基底层的远离抗菌涂层的一侧面。气管补片在具体使用时将硅胶超材料结构层和水凝胶软基底层所在的一侧面作为贴附面。
所述的硅胶超材料结构层采用但不限于手性、内凹或正弦等力学超材料结构。
所述的硅胶超材料结构层采用生物相容的医用硅橡胶材料，具体为医用TPU材料，为了保证与人体气弹性模量相近并保证顺应性，选择中等硬度硅胶，邵氏A硬度为30°-50°；TPU力学超材料结构层的层厚小于等于0.5mm，避免内壁过厚。
所述的水凝胶软基底层采用多孔甲基丙烯酰化明胶GelMA材料；水凝胶载细胞层的层厚小于等于0.5mm，避免膜层太厚，优异的剪切变稀性质便于挤出打印。
所述的抗菌涂层采用纳米银抗菌剂；抗菌涂层的层厚小于等于100μm。
所述的多孔水凝胶层采用多孔甲基丙烯酰化明胶GelMA材料；多孔水凝胶层上分布若干贯通多孔水凝胶层的通孔；水凝胶载细胞层的层厚为0.1-0.3mm。
二、一种多层力学仿生缓释抗菌气管补片的制备方法：
方法包括如下步骤：
1)将医用硅橡胶材料加装到挤出生物3D平台中，挤出生物3D平台将医用硅橡胶材料采用挤出式生物打印方式气压挤出、活塞挤出或螺杆挤出打印成片状的硅胶超材料结构层，然后挤出生物3D平台加热至恒温后固化硅胶超材料结构层，硅胶超材料结构层固化完成后将温度降为常温；加热加速硅胶固化可以方便使水凝胶软基底层打印结束后能和硅胶超材料结构层互相镶嵌。
2)将多孔甲基丙烯酰化明胶GelMA材料加装到挤出生物3D平台中，挤出生物3D平台将多孔甲基丙烯酰化明胶GelMA材料采用挤出式生物打印方式气压挤出、活塞挤出或螺杆挤出打印为片状的水凝胶软基底层，水凝胶软基底层打印在在硅胶超材料结构层的一侧表面，使得上下两层相互镶嵌。
3)在水凝胶软基底层远离硅胶超材料结构层的一侧表面上均匀喷涂纳米银抗菌剂后获得抗菌涂层。
4)将多孔甲基丙烯酰化明胶GelMA材料装入预设的水凝胶模具中进行浇筑，在紫外灯下照射后获得多孔水凝胶层，将多孔水凝胶层自水凝胶模具中取出后贴附在抗菌涂层所在的一侧表面，获得最终的气管补片。
预设的水凝胶模具具体为根据抗菌涂层的银离子分布以及含量设计多孔结构的几何参数并设计的，所述的几何参数包括孔的直径、孔的数量和分布；根据银离子含量以及分布设计多孔结构的几何参数，孔过大过多容易造成抗菌涂层脱落，孔过小会造成银离子不好释放。
所述的步骤1)中，医用硅橡胶材料具体为医用聚氨酯TPU颗粒制备而成。
所述的步骤1)中，挤出生物3D平台加热至恒温具体为加热至60℃-100℃的恒温。
所述的步骤4)中，在紫外灯下照射后获得多孔水凝胶层，具体为在405nm、6w紫外灯下照射20-30s后获得多孔水凝胶层。
本发明的有益效果是：
本发明的一种非线性力学抗菌气管补片，下层硅酮超材料层提供非线性力学性能，可以提供与原生气管相匹配的非线性力学特性，解决因气管运动的复杂性以及力学性能不匹配导致的补片拉伸脱落等问题。抗菌涂层外部的多孔水凝胶膜层在不影响抗菌涂层释放的同时使抗菌涂层不易脱落。
附图说明
图1是本发明气管补片的结构示意图；
图2是本发明气管补片管壁截面图；
图3是本发明的制备方法流程图；
图中：1、硅胶超材料结构层，2、水凝胶软基底层，3、抗菌涂层，4、多孔水凝胶层。
具体实施方式
下面结合附图及具体实施例对本发明作进一步详细说明。
本发明的具体实施例如下：
如图1和图2所示，多层力学仿生缓释抗菌气管补片包括由下到上的四层结构：硅胶超材料结构层1、水凝胶软基底层2、抗菌涂层3和多孔水凝胶层4；如图2所示，为非线性力学抗菌气管补片壁截面图，硅胶超材料结构层1采用正弦力学超材料结构。硅胶超材料结构层1采用生物相容的医用硅橡胶材料，具体为医用TPU材料，为了保证与人体气弹性模量相近并保证顺应性，选择中等硬度硅胶，邵氏A硬度为40°；TPU力学超材料结构层1的层厚为0.5mm，避免内壁过厚。水凝胶软基底层2采用多孔甲基丙烯酰化明胶GelMA材料；水凝胶载细胞层2的层厚为0.5mm，避免膜层太厚，优异的剪切变稀性质便于挤出打印。抗菌涂层3采用纳米银抗菌剂；抗菌涂层3的层厚为90μm。多孔水凝胶层4采用多孔甲基丙烯酰化明胶GelMA材料；多孔水凝胶层4上分布若干贯通多孔水凝胶层4的通孔；水凝胶载细胞层2的层厚为0.1mm。多孔水凝胶层4根据抗菌涂层的银离子分布以及含量确定孔的各项几何参数，此几何参数包括孔径大小、位置分布和孔的数量。
如图3所示，本发明的多层力学仿生缓释抗菌气管补片的制备方法如下：
1)将医用聚氨酯TPU颗粒制备而成的医用硅橡胶材料加装到挤出生物3D平台中，挤出生物3D平台将医用硅橡胶材料采用挤出式生物打印方式气压挤出打印成片状的硅胶超材料结构层1，然后挤出生物3D平台加热至恒温80℃后固化硅胶超材料结构层1，硅胶超材料结构层1固化完成后将温度降为常温；加热加速硅胶固化可以方便使水凝胶软基底层2打印结束后能和硅胶超材料结构层1互相镶嵌。
2)将多孔甲基丙烯酰化明胶GelMA材料加装到挤出生物3D平台中，挤出生物3D平台将多孔甲基丙烯酰化明胶GelMA材料采用挤出式生物打印方式气压挤出打印为片状的水凝胶软基底层2，水凝胶软基底层2打印在在硅胶超材料结构层1的一侧表面，使得上下两层相互镶嵌。
3)在水凝胶软基底层2远离硅胶超材料结构层1的一侧表面上均匀喷涂纳米银抗菌剂后获得抗菌涂层3。
4)将多孔甲基丙烯酰化明胶GelMA材料装入预设的水凝胶模具中进行浇筑，在405nm、6w的紫外灯下照射30s后获得多孔水凝胶层4，将多孔水凝胶层4自水凝胶模具中取出后贴附在抗菌涂层3所在的一侧表面，获得最终的气管补片。
预设的水凝胶模具具体为根据抗菌涂层3的银离子分布以及含量设计多孔结构的几何参数并设计的，所述的几何参数包括孔的直径、孔的数量和分布；根据银离子含量以及分布设计多孔结构的几何参数，孔过大过多容易造成抗菌涂层脱落，孔过小会造成银离子不好释放。
以上所述的实施例对本发明的技术方案和有益效果进行了详细说明，应理解的是以上所述仅为本发明的具体实施例，并不用于限制本发明，凡在本发明的原则范围内所做的任何修改、补充和等同替换，均应包含在本发明的保护范围之内。

Claims (7)

1.一种多层力学仿生缓释抗菌气管补片，其特征在于：包括依次层叠的硅胶超材料结构层（1）、水凝胶软基底层（2）、抗菌涂层（3）和多孔水凝胶层（4），硅胶超材料结构层（1）、水凝胶软基底层（2）、抗菌涂层（3）和多孔水凝胶层（4）均为片状结构，硅胶超材料结构层（1）嵌入水凝胶软基底层（2）的远离抗菌涂层（3）的一侧面；
所述的硅胶超材料结构层（1）采用手性、内凹或正弦力学超材料结构；
所述的多孔水凝胶层（4）采用多孔甲基丙烯酰化明胶GelMA材料；多孔水凝胶层（4）上分布若干贯通多孔水凝胶层（4）的通孔；水凝胶软基底层（2）的层厚为0.1-0.3mm。
2.根据权利要求1所述的一种多层力学仿生缓释抗菌气管补片，其特征在于：所述的硅胶超材料结构层（1）采用医用硅橡胶材料邵氏A硬度为30°-50°；硅胶超材料结构层（1）的层厚小于等于0.5mm。
3.根据权利要求1所述的一种多层力学仿生缓释抗菌气管补片，其特征在于：所述的水凝胶软基底层（2）采用多孔甲基丙烯酰化明胶GelMA材料；水凝胶软基底层（2）的层厚小于等于0.5mm。
4.根据权利要求1所述的一种多层力学仿生缓释抗菌气管补片，其特征在于：所述的抗菌涂层（3）采用纳米银抗菌剂；抗菌涂层（3）的层厚小于等于100μm。
5.根据权利要求1-4任一所述的一种多层力学仿生缓释抗菌气管补片的制备方法，其特征在于：方法包括如下步骤：
1) 将医用硅橡胶材料加装到挤出生物3D平台中，挤出生物3D平台将医用硅橡胶材料采用挤出式生物打印方式气压挤出、活塞挤出或螺杆挤出打印成片状的硅胶超材料结构层（1），然后挤出生物3D平台加热至恒温后固化硅胶超材料结构层（1），硅胶超材料结构层（1）固化完成后将温度降为常温；
2) 将多孔甲基丙烯酰化明胶GelMA材料加装到挤出生物3D平台中，挤出生物3D平台将多孔甲基丙烯酰化明胶GelMA材料采用挤出式生物打印方式气压挤出、活塞挤出或螺杆挤出打印为片状的水凝胶软基底层（2），水凝胶软基底层（2）打印在硅胶超材料结构层（1）的一侧表面；
3) 在水凝胶软基底层（2）远离硅胶超材料结构层（1）的一侧表面上均匀喷涂纳米银抗菌剂后获得抗菌涂层（3）；
4) 将多孔甲基丙烯酰化明胶GelMA材料装入预设的水凝胶模具中进行浇筑，在紫外灯下照射后获得多孔水凝胶层（4），将多孔水凝胶层（4）自水凝胶模具中取出后贴附在抗菌涂层（3）所在的一侧表面，获得最终的气管补片。
6.根据权利要求5所述的一种多层力学仿生缓释抗菌气管补片的制备方法，其特征在于：所述的步骤1)中，挤出生物3D平台加热至恒温具体为加热至60℃-100℃的恒温。
7.根据权利要求5所述的一种多层力学仿生缓释抗菌气管补片的制备方法，其特征在于：所述的步骤4)中，在紫外灯下照射后获得多孔水凝胶层（4），具体为在405nm、6w紫外灯下照射20-30 s后获得多孔水凝胶层（4）。
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