CN107213139A - 一种脊髓治疗用双层膜 - Google Patents

一种脊髓治疗用双层膜 Download PDF

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CN107213139A
CN107213139A CN201710454979.3A CN201710454979A CN107213139A CN 107213139 A CN107213139 A CN 107213139A CN 201710454979 A CN201710454979 A CN 201710454979A CN 107213139 A CN107213139 A CN 107213139A
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duplicature
medullotherapy
cell
glass bead
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顾军
宋晓丽
冯晓军
范健
纪立军
徐林
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Xishan People's Hospital Of Wuxi
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Abstract

本发明提供一种脊髓治疗用双层膜，包括从上到下的致密外层、内层，所述致密外层为聚乳酸膜，所述内层为负载种子细胞和介孔生物活性玻璃小球的壳聚糖膜，所述介孔生物活性玻璃小球内负载了生物活性因子。双层膜为方型或者圆形。所述生物活性因子为神经生长刺激因子。以解决已经受到损伤（但未死亡）的单个神经束，现有技术无法修复和治疗的问题；现有载药系统不能实现药物的定向释放，无法保证损伤局部因子的高浓度的问题；多数载药系统易于降解，载药量低，药物释放不能贯穿于脊髓损伤修复过程始终的问题；载药系统体积过大，可能压迫脊髓，同时不有利于缝合硬脊膜，导致脑脊液漏形成的问题。

Description

一种脊髓治疗用双层膜
技术领域
本发明涉及到的是一种脊髓治疗用双层膜。
背景技术
目前促神经生长或神经再生药物的最常见给药途径为静脉或鞘内注射。也有以凝胶结合活性因子贴膜敷于脊髓表面、以L-多聚赖氨酸结合活性因子作为支架植入脊髓，以解决因子通过血脑屏障问题。
药物递送系统和干细胞生物支架都可用于治疗脊髓损伤，但目前未见两者结合使用。干细胞三维支架桥接神经的方法和材料中已经有类似的组合运用了如（一种用于桥接缺损神经的复合修复材料及其支架CN201510716279.8）。但是目前三维支架桥接神经的治疗方法，存在以下缺点：
一方面对已经受到损伤（但未死亡）的单个神经束，无法达到修复和治疗的目的；另一方面在桥接过程中，因为要对损伤处的脊髓剪切出一个和三维支架形状类似的——通常是管状——缺口，因此会对该处未损伤的神经细胞和已经受到损伤（但未死亡）的神经细胞进行清除，结果造成了该处脊髓细胞的进一步损失。
2、现有载药系统不能实现药物的定向释放，无法保证损伤局部因子的高浓度；
3，多数载药系统易于降解，载药量低，药物释放不能贯穿于脊髓损伤修复过程始终；
4，载药系统体积过大，可能压迫脊髓，同时不有利于缝合硬脊膜，导致脑脊液漏形成。
发明内容
本发明目的：
1，提供一种新的脊髓治疗用的载药系统，避免采用背景技术中传统的载药系统时，需要对该处未损伤的神经细胞和已经受到损伤（但未死亡）的神经细胞进行清除，以造成了该处脊髓细胞的进一步损失。
2，提供一种新的载药系统，解决药物的定向释放、载药量低的问题。
3，提供一种新的载药系统，解决药物释放不能贯穿于脊髓损伤修复过程始终的问题。
4，提供一种新的载药系统，解决现有载药系统体积过大，可能压迫脊髓，同时不有利于缝合硬脊膜的问题。
本发明采用的技术方案是：
一种脊髓治疗用双层膜，包括从上到下的致密外层、内层，所述致密外层为聚乳酸膜，所述内层为负载种子细胞和介孔生物活性玻璃小球的壳聚糖膜，所述介孔生物活性玻璃小球内负载了生物活性因子。
进一步的，双层膜为方型或者圆形。
进一步的，所述介孔生物活性玻璃小球负载的生物活性因子为神经生长刺激因子。
进一步的，所述神经生长刺激因子为bFGF、BD-NF、NT-3、IGF中的一种或者几种的组合。
进一步的，双层膜周边以不能够渗透神经生长刺激因子和干细胞的医用生物胶封闭。
进一步的，所述介孔生物活性玻璃小球替换为乙二醇乳酸共聚物（PEG-PLA）纳米微球。
进一步的，所述种子细胞为脐带源间充质干细胞，即HUMSCs。
进一步的，所述种子细胞选自：许旺细胞、骨髓间充质细胞、脂肪间充质干细胞、脐带间充质干细胞、神经干细胞或诱导多能干细胞中的一种或几种组合。
该技术方案将神经生长刺激因子双层膜载体与组织工程干细胞科学有机结合，以负载神经活性因子的双层膜支架结合种子细胞HUMSCs，希望更有效地修复脊髓损伤。该支架利用壳聚糖良好的组织相容性和干细胞易在其上粘附和增殖的特性，利用生物活性玻璃对生物活性因子（bFGF、BD-NF、NT-3、IGF）有效负载与控制持续以一定浓度释放特性，通过使其同时具备以下作用：
1，双层膜可以直接贴敷于损伤脊髓部位，一方面克服了生物活性因子不能通过血脑屏障的问题，另一方面不需要对损伤部位周边的脊髓进行清除，避免了该处脊髓细胞的进一步损失。
2，根据生物活性因子作用时限，修复周边脊髓细胞需要的有效浓度，科学设计介孔生物活性玻璃小球的载药总量和释放速度、浓度，提高作用效能；
3，致密外层无法通过活性因子及干细胞，使得活性因子及干细胞只能向内层方向（即损伤部位）定向释放，如图1中箭头。
4，双层膜周边以医用生物胶封闭，以保证活性因子及干细胞不从双层膜周围溢出，保证了载药系统一方面定向释放，另一方面保证的释放的时间和浓度；
5，双层膜具有超薄的特点（厚度不超过2mm），不会因为体积过大压迫脊髓，同时有利于缝合硬脊膜，防止脑脊液漏形成。
需要做一个特别说明的是，和本发明最接近的现有技术，为：一种用于桥接缺损神经的复合修复材料及其支架CN201510716279.8。其公开了一种用于桥接缺损神经的复合修复材料及其支架，包括：所述复合材料是由丝素层-胶原层-高分子聚合物层依次排列组成，高分子聚合层呈T型或长方形设计，应用时通过折叠或卷折形成丝素层为内层、胶原层为中层、高分子聚合物层为外层的神经桥接支架。但是其所要解决的技术问题，和起到的技术效果，和本发明是完全不一样的。
CN201510716279.8解决的技术问题是实现缺损神经快速桥接，其实质即为背景技术中介绍的“桥接截断的神经束”。其使用时，先将支架通过折叠或卷折形成丝素层为内层、胶原层为中层、高分子聚合物层为外层的神经桥接支架，其次将折叠或者券折后的支架两端和截断的神经束两端通过外科手术方法缝合。其中丝素层不仅引导神经修复，而且隔开不同神经，防止形成神经瘤。胶原层提供神经轴突生长/所需的各种养分。高分子聚合物层，具有良好的力学性能，提供手术缝合或吻合所需的力学强度，并且防止周围神经的侵入，防止纤维疤痕的形成。
本发明的双层膜，应用于修复截断或者部分受损的神经束，不需要缝合，直接将双层膜贴附在神经束的受损部位即可。其致密外层用于阻挡内层的活性因子及干细胞向该方面渗透并且通过该层膜向外界渗出；内层一方面用于在一定时间内，形成持续浓度药物的析出，另一方面向脊髓损伤处提供干细胞。本发明所要解决的技术问题，各层在双层膜中各自的作用和起到的技术效果，与CN201510716279.8完全不一样，具有创造性。
附图说明
图1是本发明结构和药物析出运动方向示意图。
具体实施方式
实施例1：
参考图1，一种脊髓治疗用双层膜，包括从上到下的致密外层1、内层2，所述致密外层1为聚乳酸膜，所述内层2为负载种子细胞和介孔生物活性玻璃小球的壳聚糖膜，所述介孔生物活性玻璃小球内负载了生物活性因子。所述生物活性因子为神经生长刺激因子。双层膜周边以医用生物胶封闭。所述种子细胞为脐带源间充质干细胞，即HUMSCs。致密外层1用于阻挡内层2的活性因子及干细胞向该方面渗透并且通过该层膜向外界渗出，此时，活性因子及干细胞只能向脊髓损伤处运动，达到只向脊髓损伤处提供干细胞和活性因子的目的。
实施例2：
和实施例1相比，实施例2的区别之处在于，所述介孔生物活性玻璃小球替换为乙二醇乳酸共聚物（PEG-PLA）纳米微球。

Claims (8)

1.一种脊髓治疗用双层膜，其特征为：包括从上到下的致密外层、内层，所述致密外层为聚乳酸膜，所述内层为负载种子细胞和介孔生物活性玻璃小球的壳聚糖膜，所述介孔生物活性玻璃小球内负载了生物活性因子。
2.如权利要求1所述的一种脊髓治疗用双层膜，其特征为：双层膜为方型或者圆形。
3.如权利要求1所述的一种脊髓治疗用双层膜，其特征为：所述生物活性因子为神经生长刺激因子。
4.如权利要求1所述的一种脊髓治疗用双层膜，其特征为：双层膜支架周边以不能够渗透神经生长刺激因子和干细胞的医用生物胶封闭。
5.如权利要求1所述的一种脊髓治疗用双层膜，其特征为：所述神经生长刺激因子为bFGF、BD-NF、NT-3、IGF中的一种或者几种的组合。
6.如权利要求1所述的一种脊髓治疗用双层膜，其特征为：所述介孔生物活性玻璃小球替换为乙二醇乳酸共聚物（PEG-PLA）纳米微球。
7.如权利要求1所述的一种脊髓治疗用双层膜，其特征为：所述种子细胞为脐带源间充质干细胞，即HUMSCs。
8.如权利要求1所述的一种脊髓治疗用双层膜，其特征为：所述种子细胞选自：许旺细胞、骨髓间充质细胞、脂肪间充质干细胞、脐带间充质干细胞、神经干细胞或诱导多能干细胞中的一种或几种组合。
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