CN114874970A - 一种高分子三维支架及其制备方法 - Google Patents
一种高分子三维支架及其制备方法 Download PDFInfo
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Abstract
本发明涉及一种高分子三维支架及其制备方法，支架包括一层或多层人工合成的高分子三维纤维网格，纤维直径在50纳米‑2000纳米之间，单层纤维网格的厚度为100纳米到2000纳米之间，纤维间空隙在10纳米到25纳米之间，纤维实体成分占支架总空间的30％‑70％，支架表面通过化学修饰成能有效促进细胞的增殖和分化、组织的建构，支架承载添加剂；其制备方法包括以下步骤：(1)制备聚合物溶液；(2)采用静电纺丝制备单层纤维网格；(3)将单层纤维网格拼接成多层高分子三维支架。本发明提供一种高分子三维支架及其制备方法，引进了无毒和生物相容的材料构建三维空间，提供了一个模拟体内组织细胞生长的微环境或纳米环境，促进细胞的增殖分化及受损结构再生。
Description
技术领域
本发明涉及生物医学技术领域，特别涉及一种高分子三维支架及其制备方法。
背景技术
在调节细胞内基因表达的各种因素中，细胞类型、空间因素、化学触发和调控发挥了很大的作用。体内细胞的增殖和分化受到细胞外基质和细胞因子的调控，如生长因子和分化因子。特异的黏附分子和细胞因子，可作为一种信号促进细胞增殖、分化、迁移或者启动凋亡，而细胞依赖特异型受体对信号做出反应。由信号分子启动的信号传导依赖于细胞骨架的组织和结构，所以信号传导与细胞表面的信号分子、周围细胞和细胞外基质有关，在设计细胞和组织培养环境时要考虑到细胞之间的相互作用。且最近的研究表明，由纤维构成的具有3-D空间结构的微米和纳米微环境，如细胞外基质胶原成分或其他纤维是组织细胞黏附、信号转导、分化必不可少的条件。在传统平面培养基表面，细胞的贴壁和生长完全不同于体内组织中细胞的生长模式。在此情况下，一种无毒和生物相容的材料构建三维空间就显得尤为重要。
发明内容
针对现有技术中存在的上述缺陷，本发明提供一种高分子三维支架及其制备方法，引进了无毒和生物相容的材料构建三维空间，提供了一个模拟体内组织细胞生长的微环境或纳米环境，用于体内和体外细胞的增殖，从而促进细胞的增殖和分化及受损结构再生。此类三维结构可以根据所需修复的组织，通过改变纤维的直径、聚合物及添加剂的组成、高分子三维支架的理化和结构特点来实现不同的功能，可用于体外的细胞培养、组织工程、修复或替代体内的损伤组织及促进新的组织和器官生长。
本发明是通过以下技术方案达到上述目的：一种高分子三维支架，由一层或多层人工合成的高分子三维纤维网格构成，纤维直径在50纳米-2000纳米之间，单层纤维网格的厚度为100纳米到2000纳米之间，纤维间空隙在10纳米到25纳米之间，纤维实体成分占支架总空间的30％-70％，纤维是具有生物相容性的非细胞毒性的高分子聚合物，支架表面附着化学修饰，支架承载添加剂。其制备方法包括以下步骤：
(1)制备聚合物溶液，溶液包含0.25％至15％体积比的添加剂；
(2)采用静电纺丝制备的方法，使用聚合物溶液制备单层高分子三维纤维网格；
(3)将单层高分子三维纤维网格拼接成多层高分子三维支架。
作为优选，所述的单层及多层高分子纤维是可生物降解材料。
作为优选，所述的单层及多层高分子纤维是非生物降解材料。
作为优选，所述的添加剂包括一种及多种生长因子、分化因子、生物活性分子、生物大分子等脂质及亲脂性分子。
作为优选，所述的生长因子，包括血管内皮生长因子、表皮生长因子、胰岛素生长因子、血小板衍化生长因子、神经生长因子、成纤维细胞生长因子、转化生长因子。
作为优选，所述分化因子，包括经营养因子、集落刺激因子、转化生长因子。。
作为优选，所述的生物活性分子，包括脂质、碳水化合物、多糖、氨基酸、核酸、核苷酸、多核苷酸、杂交分子。
作为优选，所述的生物大分子，包括醇，醛，胺，羧基，巯基。
作为优选，所述的一种高分子三维支架设有荧光标记确定其物理和化学性质。
本发明的有益效果在于：
(1)本发明具有单层或多层高分子三维支架，高分子支架材料不含任何生物来源的成分，没有外源细胞和蛋白，避免发生免疫排斥及疾病传播的风险。
(2)本发明的高分子三维支架理化和结构特点包括质地，柔软度，粘性，孔径，弹性，比表面积，纤维直径，纤维溶解度，亲水或疏水性，纤维密度接近体内细胞外基质。
(3)本发明同时通过添加生物大分子或生物活性分子改变或修饰高分子三维支架，从而达到细胞增殖或分化所需的纳米或微米环境。
(4)本发明还提供荧光标记确立高分子三维支架的化学或物理性质，包括纤维直径、生物活性分子、功能团体、纤维降解率、聚合物组成、疏水性或亲水性的纤维组成、聚合物的毒性、生物活性分子的毒性等。
(5)本发明使用的高分子聚合物和添加剂来源充分，生产时间短，贮存运输简单，产品质量易于控制，生产标准容易实现，可实现低成本、高效率的产业化生产。
附图说明
图1是本发明的结构示意图；
图中：1表示纤维网格，2表示添加剂。
具体实施方式
下面通过具体实施例对本发明进行说明，但本发明并不局限于此。
实施例1：高分子三维支架由高分子聚合物材料制造而成，提供各种方向排列的纤维层，便于使用及质量控制，可为单层也可为多层。单层及多层高分子纤维可以是可生物降解材料，如聚酯，包括聚己内酯、聚乳酸、聚羟基乙酸；单层及多层高分子纤维也可以是非生物降解材料，如聚酰胺，包括尼龙。高分子三维支架的拓扑结构即网格的空间排列方式，是为了在体外高度仿真体内环境，提高同型或异型细胞在单层或多层环境中的兼容性及生长和分化能力。功能基团可以通过等离子技术，采用化学修饰的方法连接到高分子三维支架的外表面，功能基团上可以添加一种或多种生物活性分子。单层与多层纤维结构均可释放生长因子与分化因子，释放的速度由单层与多层高分子三维支架的溶解和降解速度决定
高分子三维支架的原材料可能采用多种聚合物或聚合物体系，聚合物或聚合物体系应该是非细胞毒性，不含胶原蛋白、纤维蛋白、纤维蛋白原、凝血酶及其混合物。聚合物溶液可以含有15％以上体积比的氯仿，本实施例采用聚己内酯－10％氯仿溶液。聚合物溶液可以包含从约0.25％到约15％体积比的添加剂组成。本实施例采用静电纺丝制备单层高分子三维支架，添加剂使聚合物在静电纺丝后产生了纤维的多向分散和多极性，也使高分子三维支架拥有了更多数量和更多比例的细纤维。较细纤维构成的高分子三维支架，为支架和细胞之间提供了更多的接触点，这种特点接近体内细胞与细胞外基质的接触情况。
荧光标记由有机染料的荧光团构成。在本实施例中，荧光标记可以添加到聚合物溶液，或通过功能基团连接到高分子三维支架表面，抑或通过生物活性分子结合到高分子三维支架表面。荧光标记可以由包含无机胶体的半导体纳米晶体构成，或由硒化镉核心和硫化锌帽构成。
实施例2：本实施例与实施例1的不同之处在于，本实施例的聚合物溶液采用胆固醇－聚己内酯－15％氯仿溶液。
实施例3：本实施例与实施例1的不同之处在于，本实施例的纤维表面乙酸处连接羧基和透明质酸。
实施例4：本实施例与实施例1的不同之处在于，本实施例的聚合物溶液采用聚己内酯－15％氯仿溶液，并使用等离子技术在支架外表面连接神经生长因子。
实施例5：本实施例与实施例1的不同之处在于，本实施例的聚合物溶液分别采用透明质酸－聚己内酯－10％氯仿溶液和神经生长因子－聚己内酯－15％氯仿溶液，并采用静电纺丝制备双层高分子三维支架。
实施例6：本实施例与上述实施例的不同之处在于，本实施例提供一种构造组织的方法，使用两个或两个分层的高分子三维支架，形成一个多层次的高分子三维支架聚合物。活细胞可以沉积在高分子三维支架结构中，一个高分子三维支架促进增殖，迁移的条件，另一个高分子三维支架提供分化的纳米或微米环境。
以上的所述乃是本实用新型的具体实施例及所运用的技术原理，若依本实用新型的构想所作的改变，其所产生的功能作用仍未超出说明书及附图所涵盖的精神时，仍应属本实用新型的保护范围。
Claims (10)
1.一种高分子三维支架，其特征在于，包括一层或多层人工合成的高分子三维纤维网格(1)，纤维直径在50纳米-2000纳米之间，单层纤维网格(1)的厚度为100纳米到2000纳米之间，纤维间空隙在10纳米到25纳米之间，纤维实体成分占支架总空间的30％-70％，纤维是具有生物相容性的非细胞毒性的高分子聚合物，支架表面附着化学修饰，支架承载添加剂(2)。
2.根据权利要求1所述的一种高分子三维支架，其特征在于，所述的单层及多层高分子纤维是可生物降解材料。
3.根据权利要求1所述的一种高分子三维支架，其特征在于，所述的单层及多层高分子纤维是非生物降解材料。
4.根据权利要求1所述的一种高分子三维支架，其特征在于，添加剂(2)包括一种及多种生长因子、分化因子、生物活性分子、生物大分子等脂质及亲脂性分子。
5.根据权利要求5所述的一种高分子三维支架，其特征在于，所述的生长因子，包括血管内皮生长因子、表皮生长因子、胰岛素生长因子、血小板衍化生长因子、神经生长因子、成纤维细胞生长因子、转化生长因子。
6.根据权利要求5所述的一种高分子三维支架，其特征在于，所述分化因子，包括经营养因子、集落刺激因子、转化生长因子。
7.根据权利要求5所述的一种高分子三维支架，其特征在于，所述生物活性分子，包括脂质、碳水化合物、多糖、氨基酸、核酸、核苷酸、多核苷酸、杂交分子。
8.根据权利要求5所述的一种高分子三维支架，其特征在于，所述生物大分子，包括醇，醛，胺，羧基，巯基。
9.根据权利要求1-8所述的一种高分子三维支架，其特征在于，设有荧光标记确定其物理和化学性质。
10.一种制备权利要求1-8任一权利要求所述的高分子三维支架的方法，其特征在于，包括以下步骤：
(1)制备聚合物溶液，溶液包含0.25％至15％体积比的添加剂(2)；
(2)采用静电纺丝制备的方法，使用聚合物溶液制备单层高分子三维纤维网格(1)；
(3)将单层高分子三维纤维网格(1)拼接成多层高分子三维支架。
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