CN114681677A - 一种软骨支架材料及其在软骨支架构建中的应用 - Google Patents
一种软骨支架材料及其在软骨支架构建中的应用 Download PDFInfo
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Abstract
本发明提供了一种软骨支架材料及其在软骨支架构建中的应用，属于医用材料技术领域，所述软骨支架材料包括水凝胶、软骨碎块和软骨细胞球。本申请将软骨碎块与软骨细胞球混合打印，两者相辅相成：软骨碎块为软骨细胞球提供小生境，利于软骨细胞球成软骨分化；软骨细胞球成软骨后可填充软骨碎块之间空间，形成整体，具备更优的生物力学性能，能够用更少的软骨原材料形成具备更贴近自体软骨性质的生物工程软骨。
Description
技术领域
本发明涉及医用材料技术领域，尤其涉及一种软骨支架材料及其在软骨支架构建中的应用。
背景技术
弹性软骨作为一种轮廓填充材料，在整形外科及美容外科领域有着广泛的应用场景和重要的应用价值。以鼻整形为例，鼻再造及鼻部美容整形手术对于支架构造有较高的强度和形态要求，目前比较普遍使用的支架材料有有机合成物假体、耳软骨、肋软骨等。其中，有机合成物假体是由高分子有机化合物组成，由于外鼻相对缺少血供及覆盖皮肤较薄的特性，高分子有机化合物鼻假体可因排异反应而产生比较丰富血供区域更严重的炎症反应；而耳软骨、肋软骨为自体获取，会造成额外的疼痛、手术伤口及并发症风险。且软骨片需要在术中实时切割、雕刻、调整，以最大程度满足效果要求，因此在切割过程中，大量的耳软骨、肋软骨因塑形要求被剪裁，造成自体材料消耗量显著大于需要量，增加了患者的创伤和自体组织损耗。在行鼻再造以及鼻整形二次修复的病例中，甚至会有肋、耳软骨材料不足的情况。
同样，先天性小耳畸形的外耳再造当前通常使用自体肋软骨移植、假体重建或聚合物植入物作为重建材料。因肋软骨需求量较大，故患儿通常需生长发育至青少年期才可接受耳再造手术，长时间的外耳畸形往往对患儿心理健康产生较大的影响。
目前，耳、鼻软骨组织工程的主要障碍之一是软骨在体内无法保持其原有的大小和形状。此外，培养耳、肋软骨的种子细胞不足以增殖和完全取代支架。
发明内容
本发明的目的在于提供一种软骨支架材料及其在软骨支架构建中的应用，本申请将软骨碎块与软骨细胞球混合打印，能够用更少的软骨原材料形成具备更贴近自体软骨性质的生物工程软骨。
为了实现上述发明目的，本发明提供以下技术方案：
本发明提供了一种软骨支架材料，包括水凝胶、软骨碎块和软骨细胞球。
优选的，所述水凝胶包括丝素蛋白水凝胶、GelMA冻干粉或HAMA冻干粉。
优选的，所述软骨碎块的直径为0.5～1mm。
优选的，所述软骨碎块来源于人体或动物体的弹性软骨或透明软骨。
优选的，所述软骨细胞球的直径为100～500μm。
优选的，所述软骨碎块和软骨细胞球的体积比不低于1：1。
本发明还提供了上述方案所述的软骨支架材料在制备软骨支架中的应用。
优选的，所述应用包括以下步骤：
1)对软骨支架的待填充部位进行3D体表扫描，获得3D数据模型；
2)将权利要求1或2所述软骨支架材料和LAP光引发剂混合，得到打印原料；
3)按照所述3D数据模型将所述打印原料进行3D打印、光固化，得到软骨支架；
所述步骤1)和步骤2)之间没有时间顺序限制。
优选的，步骤3)中所述3D打印的方式包括蓝光3D打印。
本发明提供了一种软骨支架材料，包括水凝胶、软骨碎块和软骨细胞球。本申请将软骨碎块与软骨细胞球混合打印，两者相辅相成：软骨碎块为软骨细胞球提供小生境，利于软骨细胞球成软骨分化；软骨细胞球成软骨后可填充软骨碎块之间空间，形成整体，具备更优的生物力学性能，能够用更少的软骨原材料形成具备更贴近自体软骨性质的生物工程软骨。
附图说明
图1为普通软骨碎打印物作石蜡切片后的HE染色结果；
图2为普通软骨碎打印物作石蜡切片后的番红固绿染色结果；
图3为软骨碎块及软骨球混合打印物作石蜡切片后的HE染色结果；
图4为软骨碎块及软骨球混合打印物作石蜡切片后的番红固绿染色结果。
具体实施方式
本发明提供了一种软骨支架材料，包括水凝胶、软骨碎块和软骨细胞球。
本发明对所述水凝胶的具体类型没有特殊限制，采用本领域的用于软骨生物工程即可。在本发明中，所述水凝胶优选的包括丝素蛋白水凝胶、GelMA冻干粉或HAMA冻干粉。
在本发明中，所述软骨碎块的直径优选为0.5～1mm，更优选为0.8mm；，所述软骨碎块优选的来源于人体或动物体的弹性软骨或透明软骨。
在本发明中，所述软骨细胞球的直径为100～500μm。在本发明中，所述软骨细胞球优选的以人或动物的弹性软骨细胞或透明软骨细胞为原料经三维成球培养所得。
在本发明中，所述软骨碎块和软骨细胞球的体积比不低于1：1。
在本发明中，软骨碎块为软骨细胞球提供小生境，利于软骨细胞球成软骨分化；软骨细胞球成软骨后可填充软骨碎块之间空间，形成整体，具备更优的生物力学性能，能够用更少的软骨原材料形成具备更贴近自体软骨性质的生物工程软骨。
本发明还提供了上述方案所述软骨支架材料在制备软骨支架中的应用。
在本发明中，所述应用包括以下步骤：
1)对软骨支架的待填充部位进行3D体表扫描，获得3D数据模型；
2)将上述方案所述所述软骨支架材料和LAP光引发剂混合，得到打印原料；
3)按照所述3D数据模型将所述打印原料进行3D打印、光固化，得到软骨支架；
所述步骤1)和步骤2)之间没有时间顺序限制。
本发明首先对软骨支架的待填充部位进行3D体表扫描，获得3D数据模型；所述软骨支架的待填充部位优选的包括鼻子或者外耳廓。
本发明还将上述方案所述所述软骨支架材料和LAP光引发剂混合，得到打印原料。在本发明中，所述软骨支架材料和LAP光引发剂根据水凝胶的类型按照本领域的常规设置进行配比。
得到3D数据模型后，本发明按照所述3D数据模型将所述打印原料进行3D打印、光固化，得到软骨支架。在本发明中，所述3D打印的方式优选的包括蓝光3D打印。在本发明中，所述3D打印后即可光固化。
下面将结合本发明中的实施例，对本发明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发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，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，都属于本发明保护的范围。
实施例1
通过光固化12.5％w/v GelMA水凝胶混合直径约1mm的软骨碎块及直径约200μm的软骨球，共同打印后埋置于裸鼠皮下，经过三个月体内培养，发现相比于单纯软骨碎块，软骨碎块及软骨球混合打印组的软骨碎块间彼此连接，具有更好的生物性能。普通软骨碎打印物作石蜡切片后的HE染色结果参见图1。普通软骨碎打印物作石蜡切片后的番红固绿染色结果参加图2。软骨碎块及软骨球混合打印物作石蜡切片后的HE染色结果参见图3。软骨碎块及软骨球混合打印物作石蜡切片后的番红固绿染色结果参见图4。从图1～图4可以明显观察到软骨碎块及软骨球混合打印组软骨细胞外基质分泌增强，并且软骨块之间形成连接，构建了更整体的生物工程软骨组织。
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。
Claims (9)
1.一种软骨支架材料，包括水凝胶、软骨碎块和软骨细胞球。
2.根据权利要求1所述的软骨支架材料，其特征在于，所述水凝胶包括丝素蛋白水凝胶、GelMA冻干粉或HAMA冻干粉。
3.根据权利要求1所述的软骨支架材料，其特征在于，所述软骨碎块的直径为0.5～1mm。
4.根据权利要求1或3所述的软管支架材料，其特征在于，所述软骨碎块来源于人体或动物体的弹性软骨或透明软骨。
5.根据权利要求1所述的软骨支架材料，其特征在于，所述软骨细胞球的直径为100～500μm。
6.根据权利要求1、3、4、5所述的软骨支架材料，其特征在于，所述软骨碎块和软骨细胞球的体积比不低于1：1。
7.权利要求1～6任意一项所述的软骨支架材料在制备软骨支架中的应用。
8.软骨支架的制备方法，包括以下步骤：
1)对软骨支架的待填充部位进行3D体表扫描，获得3D数据模型；
2)将权利要求1～6任意一项所述的软骨支架材料和LAP光引发剂混合，得到打印原料；
3)按照所述3D数据模型将所述打印原料进行3D打印、光固化，得到软骨支架；
所述步骤1)和步骤2)之间没有时间顺序限制。
9.根据权利要求8所述的应用，其特征在于，步骤3)中所述3D打印的方式包括蓝光3D打印。
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| CN110124107A (zh) * | 2019-04-23 | 2019-08-16 | 哈尔滨医科大学 | 一种用于关节软骨修复的plga细胞支架及其制备方法和应用 |
| CN111588908A (zh) * | 2020-03-11 | 2020-08-28 | 南京市第一医院 | 用于改良AMIC技术软骨修复的生物3d打印的活性生物膜及其制备方法 |
| CN111671978A (zh) * | 2020-07-08 | 2020-09-18 | 四川大学 | 一种基于肋软骨的3d打印生物墨水及其制备方法与应用 |
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| CN111588908A (zh) * | 2020-03-11 | 2020-08-28 | 南京市第一医院 | 用于改良AMIC技术软骨修复的生物3d打印的活性生物膜及其制备方法 |
| CN111671978A (zh) * | 2020-07-08 | 2020-09-18 | 四川大学 | 一种基于肋软骨的3d打印生物墨水及其制备方法与应用 |
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