CN112957536A - 一种外周神经再生修复材料及其制备方法 - Google Patents

一种外周神经再生修复材料及其制备方法 Download PDF

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CN112957536A
CN112957536A CN202110306213.7A CN202110306213A CN112957536A CN 112957536 A CN112957536 A CN 112957536A CN 202110306213 A CN202110306213 A CN 202110306213A CN 112957536 A CN112957536 A CN 112957536A
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mixed solution
chitosan
polycaprolactone
tricalcium phosphate
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崔孟龙
李洪景
刘洋
仇志烨
宋天喜
朱艳泽
崔云
朱金亮
何志敏
胡艳丽
李良才
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Weifang Aojing Medical Research Co ltd
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Abstract

本发明公开了一种外周神经再生修复材料，其特征在于,所述材料是以溶于乙酸乙酯的聚乳酸为基质，添加壳聚糖、纳米β‑磷酸三钙、NGF冻干粉和聚已内脂粉末，再以超声波震荡混合溶液，混合溶液挥发成膜；通过添加壳聚糖和β‑磷酸三钙，中和聚乳酸降解过程中产生的酸性物质，添加聚已内酯控制材料的生物降解速率，神经生长因子促进神经的修复。

Description

一种外周神经再生修复材料及其制备方法
技术领域
本发明涉及一种外周神经再生修复材料及其制备方法，属于生物材料领域。
背景技术
周围神经的再生受神经趋化性、神经营养性和接触引导三者的影响，因此，现有技术中对于神经的修复一般是利用神经生长因子（NGF）的神经趋化性作用影响，配合神经导管，利用神经的再生能力，达到修复断离神经的目的。
合适的降解速度与神经再生的类型、位置及再生长度密切相关，同时材料的降解产物对神经再生的微环境不应有很大影响，对于生物可降解型神经导管，导管材料的降解速度是重要的可控因素。
聚乳酸是目前周围神经组织工程应用最广泛的一种可降解材料，具有良好的生物相容性，但聚乳酸作为导管材料存在降解速率难控制，降解后酸性产物可引起细胞损伤和无菌性炎症，因此需要复合一些其他材料，使导管的生物降解速率可控，并中和降解过程中产生的酸性产物。
发明内容
本发明的目的是针对以上问题提供一种外周神经再生修复材料及其制备方法，中和聚乳酸降解过程中的酸性产物，并使降解速率可控。
为达到上述目的本发明公开了一种外周神经再生修复材料及其制备方法，该修复材料是以溶于乙酸乙酯的聚乳酸为基质，添加壳聚糖、纳米β-磷酸三钙、NGF冻干粉和聚已内脂粉末，再以超声波震荡混合溶液，混合溶液挥发成膜；纳米β-磷酸三钙和壳聚糖能够中和聚乳酸降解过程中产生的酸性产物，聚已内酯可控制材料的生物降解速度，神经生长因子NGF促进神经的修复。
该外周神经再生修复材料的制备方法是，将聚乳酸溶于乙酸乙酯制成浓度10%的聚乳酸溶液，待聚乳酸完全溶解后，在聚乳酸溶液中加入β-磷酸三钙、壳聚糖、NGF冻干粉和聚已内脂粉末，混合溶液中β-磷酸三钙质量浓度为5wt%，壳聚糖的质量浓度为30wt%，NGF冻干粉按2000UNGF：1g聚乳酸的比例加入混合溶液中，聚已内酯的质量浓度为20wt%，在超声波震荡器中震荡30分钟，将混合溶液倒在膜具上，在温度20℃、湿度40%的条件下挥发成膜。
综上所述，本发明的有益效果在于：通过添加壳聚糖和β-磷酸三钙，中和聚乳酸降解过程中产生的酸性物质，添加聚已内酯控制材料的生物降解速率，神经生长因子促进神经的修复。
具体实施方式
下面结合实施例，对本发明的具体实施方式作进一步详细描述。以下实施例用于说明本发明，但不用来限制本发明的范围。
该外周神经再生修复材料的制备方法是，将聚乳酸溶于乙酸乙酯制成浓度10%的聚乳酸溶液，待聚乳酸完全溶解后，在聚乳酸溶液中加入β-磷酸三钙、壳聚糖、NGF冻干粉和聚已内脂粉末，混合溶液中β-磷酸三钙质量浓度为5wt%，壳聚糖的质量浓度为30wt%，NGF冻干粉按2000UNGF：1g聚乳酸的比例加入混合溶液中，聚已内酯的质量浓度为20wt%，在超声波震荡器中震荡30分钟，将混合溶液倒在膜具上，在温度20℃、湿度40%的条件下挥发成膜。
温度与挥发速度相关，挥发速度过快，膜表面会存在大量气泡，凹凸不平，而较低的温度下，形成均一、光滑的膜面，但是温度过低，挥发速度过慢，在20℃条件下，挥发速度较快，形成的膜表面内外均匀。
空气中的水分能加速膜面凝胶，导致膜面微孔孔径变大；相反，湿度大，溶剂挥发速率慢，可使膜表面的温度变化慢，这又使已聚集的大分子聚合物易于展开，导致膜表面的微孔孔径减小；若空气中湿度小，则溶剂挥发速率大，膜表面温度降低快，使膜面的大分子易于聚集，最佳的湿度条件为40%。
溶液的浓度对膜材料的影响主要表现在如下方面，膜的厚度和膜孔隙的分布状况；浓度小的溶液铺成的膜的厚度较小，制备的膜的表层孔隙率比浓度大的溶液制备的膜孔隙率大，孔径分布范围较大，大的溶液铺成的膜的厚度较大，而浓度较大的溶液制备的膜的孔隙率要少一些，并且孔径分布较集中，这主要是因为溶液的浓度直接影响其流动性的原因，经过确定，聚乳酸溶液浓度为10%时，形成的膜的厚度、孔隙率最合适。
聚乳酸是一种重要的生物可降解的聚合物，以其优良的生物相容性和生物可吸收性而广泛用于药物控制释放系统，聚乳酸最大的特点是在体液的水性环境中能靠酯键的简单水解而进行降解，而且降解的最终产物能够为人体新陈代谢生成二氧化碳和水而排出体外。
一般材料的亲水性越好，则材料的细胞亲和性就更好，聚乳酸富含疏水性酯键，缺乏亲水性基团，壳聚糖的加入能够改变聚乳酸的亲水性，同时，壳聚糖具有生物可降解性、生物相容性，能够加快伤口愈合能力，对受损伤的生物体能诱生特殊细胞，加快创伤愈合，特别是促进愈合张力的增长，这些特点对于断离神经的修复具有优势作用。
本修复材料作为生物可降解材料，能够避免压迫再生神经，同时薄壁导管有更好的弹性，可以抑制断端神经瘤生成，且材料可降解，制成神经导管的内径略大于损伤神经直径即可。
修复材料制成的生物导管在周围神经再生中的作用，主要是在损伤局部人为构建一个利于神经纤维生长的微环境，利用周围神经本身具有的修复功能对损伤进行修复。神经导管修复技术对神经再生的引导机理可能为接触引导，远端对神经再生具有趋向性引导作用。
在神经再生中暂时固定并支持损伤神经的两端，引导神经元的轴突轴向生长，避免外生和形成神经瘤，为神经再生提供一个相对隔绝的微环境，富集神经再生所需的神经营养因子，减少细胞入侵，防止疤痕的形成，用生物可降解材料制成的导管可在体内降解，无需二次手术去除，同时能避免使用非生物降解导管时可能出现的神经压迫等问题。
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，在不脱离本发明技术原理的前提下，还可以做出若干改进和替换，这些改进和替换也应视为本发明的保护范围。

Claims (2)

1.一种外周神经再生修复材料，其特征在于,所述材料是以溶于乙酸乙酯的聚乳酸为基质，添加壳聚糖、纳米β-磷酸三钙、NGF冻干粉和聚已内脂粉末，再以超声波震荡混合溶液，混合溶液挥发成膜。
2.如权利要求1所述的外周神经再生修复材料的制备方法，其特征在于，所述聚乳酸溶于乙酸乙酯制成浓度10%的聚乳酸溶液，待聚乳酸完全溶解后，在聚乳酸溶液中加入β-磷酸三钙、壳聚糖、NGF冻干粉和聚已内脂粉末，混合溶液中β-磷酸三钙质量浓度为5wt%，壳聚糖的质量浓度为30wt%，NGF冻干粉按2000UNGF：1g聚乳酸的比例加入混合溶液中，聚已内酯的质量浓度为20wt%，在超声波震荡器中震荡30分钟，将混合溶液倒在膜具上，在温度20℃、湿度40%的条件下挥发成膜。
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CN102727931B (zh) * 2012-07-06 2014-07-02 武汉理工大学 一种三维仿生电极化梯度孔神经导管的构建及其制备
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