CN114848921A - 一种用3d打印可再生功能梯度骨骼支架的制备方法 - Google Patents

一种用3d打印可再生功能梯度骨骼支架的制备方法 Download PDF

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CN114848921A
CN114848921A CN202210532245.3A CN202210532245A CN114848921A CN 114848921 A CN114848921 A CN 114848921A CN 202210532245 A CN202210532245 A CN 202210532245A CN 114848921 A CN114848921 A CN 114848921A
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bone
powder
porosity
porous
scaffold
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CN114848921B (zh
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徐淑波
胡馨支
张森
潘悦飞
任国成
韩娟娟
郑伟
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Shandong Jianzhu University
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Abstract

一种3D打印可再生功能梯度骨骼支架的制备方法，本发明通过CT扫描设备对骨缺损处进行三维扫描获取图像数据，设计出可以移植骨头的尺寸及形态，以钛合金材料作为多孔骨骼支架材料，利用3D打印SLM成形出环状多孔功能梯度结构，外层为体心立方结构，内芯为十字形蜂窝结构，孔隙率由外向内减小，更好地模拟了天然骨的实际孔隙率变化特征，再将含有壳聚糖、羟基磷灰石、淫羊藿苷的混合溶液注射到多孔钛支架的孔隙中，得到功能梯度多孔仿生复合支架，本发明打印出的支架具有可降解、可修复、良好生物相容性和良好骨传导性，并使细胞能够更好地黏附生长，促进骨愈合。

Description

一种用3D打印可再生功能梯度骨骼支架的制备方法
技术领域
本发明涉及一种多孔梯度骨骼支架，具体涉及一种3D打印可再生功能梯度骨骼支架的制备方法。
背景技术
由于疾病（如癌症）、意外损伤（创伤或损伤）和手术（如肿瘤切除术、翻修手术）可能会导致骨骼缺陷，对于大规模骨缺损（主要是骨折），常常会出现骨吸收和骨不愈合的情况，骨缺损即无法自行愈合，将严重影响患者生活质量。随着骨肿瘤发病率的增高及车祸等高能量创伤导致的骨缺损的增加，在可预见的未来，临床上可以见到越来越多的骨缺损患者，所以需要探索出对于大段骨缺损有效的治疗手段，以改善患者生活质量。
目前临床治疗骨缺损的方法主要是包括：取髂骨等自体骨移植、同种异体骨移植、Masquelet技术、Ilizarov 骨延长技术等。但是这些技术都存在不同的缺陷。自体骨移植取材有限，存在出血、感染等供区并发症；同种异体骨移植存在相关疾病传播、诱发免疫反应等缺陷。Ilizarov 骨延长技术需要较长时间的外固定治疗，还存在针道感染、关节僵硬等风险。Masquelet技术的缺点包括二次手术，术后存在植骨吸收、骨不愈合，下肢应力性骨折等。
本发明打印的骨骼支架，以具有良好的生物相容性和耐腐蚀性的钛合金作为基体材料，加入骨修复、可降解材料，避免了二次手术取出带来的伤害，采用梯度多孔结构，多孔结构降低了弹性模量，可以与宿主骨良好适配，减少骨吸收，促进骨植入体界面上骨快速的形成与整合，梯度结构可以更好地模拟天然骨的实际孔隙率变化特征，从而实现仿生骨科植入物的结构设计，不仅能满足结构的模量、强度匹配，而且能适应体内外人体体液的流速，能有效保证骨再生过程中氧气和废物的运输，促进骨愈合过程。
发明内容
本发明提供了一种利用3D打印技术对骨缺损处实行可再生、可降解、具有良好生物相容性和耐腐蚀性的功能梯度多孔结构骨骼支架的制备方法，通过该方法，降低了因弹性模量不匹配所导致的应力遮挡效应，提高了植入物与宿主骨的匹配度，并且在传统多孔支架的基础上提出了梯度多孔结构，外层为体心立方结构，内芯为十字形蜂窝结构，实现了单一孔隙率的突破，更好的模拟了天然骨的实际孔隙率变化特征，从而实现仿生骨科植入物的结构设计。
本发明是通过如下技术方案来实现：
1. 骨骼支架建模
通过CT扫描设备对骨缺损处进行三维扫描获取图像数据，根据破损骨头，利用三维软件重新设计出可以移植骨头的尺寸及形态。用UG三维制图软件设计出多功能梯度模型，将模型与健康骨骼进行比对，校验模型尺寸是否合适，有无偏差，支架采用环状多层结构设计，模型的外层为体心立方结构，孔隙率为80%，孔径为800μm，内芯为十字形蜂窝结构，孔隙率为50%，孔径为400μm，支架外层结构占整体结构60%的体积，内芯占整体结构的40%体积。
2. 钛合金粉末制备
采用气体雾化法制备Ti6Al4V球形粉末，用高频感应线圈进行加热将钛合金原料熔化，使熔液滴流，再用高速的氩气喷射熔液流，使金属液成喷雾状，冷凝后生成Ti6Al4V粉末。
钛及其合金具有密度低、强度高、耐腐蚀、生物力学性能好和良好的软硬组织生物相容性的特点，加之钛元素含量丰富，分布广泛，广泛用于骨科临床，成为目前骨科内植入物材料的优先选择。并且钛合金弹性模量低（杨氏模量7-30 GPa）较骨科之前主要使用的不锈钢、钴铬合金等金属的弹性模量要低，更接近于人体骨骼的弹性模量，其弹性模量不匹配所导致的应力遮挡效应要小很多，钛植入物与宿主骨的匹配度也较高，骨吸收、植入物的松动的发生几率也相应减小。
3. 多孔钛支架的打印
将预先设计好的功能梯度多孔支架模型导入SLM打印机中，将Ti6Al4V粉末放入供粉仓中，打印过程中激光功率为250W，扫描速度为1000mm/s，激光直径为50μm，扫描间距为0.1mm，其中支架外层为体心立方结构，孔隙率为80%，孔径为800μm，内芯为十字形蜂窝结构，孔隙率为50%，孔径为400μm。取出后采用无水乙醇清洗去除部分易清除的未熔融粉末，再采用超声清洗，通过超声振动将孔隙间残留的剩余粉末去除。
4. 多孔钛-壳聚糖-羟基磷灰石-淫羊藿苷复合支架的制备
所用的试剂：壳聚糖、羟基磷灰石、乙酸、淫羊藿苷。
制备过程：在100ml规格的烧杯中注入0.2mol/L的乙酸99ml，称取1g 壳聚糖粉末加入乙酸溶液中，在50℃环境下搅拌约30min后形成浓度为1%的壳聚糖溶液。然后加入0.3g的羟基磷灰石粉末，0.1g的淫羊藿苷，继续搅拌直至均匀混合，将配置好的混合液放在室温下进行冷却。将多孔钛支架置于24孔培养板中，用一次性注射器将配置好的混合溶液注射到多孔钛支架的孔隙中，直至溶液将多孔钛支架完全覆盖，注射时应避免气泡的进入，室温静置1h后放入-20℃环境进行冷冻处理，冷冻12h。最后置入冷冻干燥机冻干。
壳聚糖：可以使伤口更快愈合，具有药物活性以及消炎的作用，并且它降解之后的产物是氨基葡萄糖，对人体组织没有伤害和刺激，在人工皮肤方面有着很大应用。
羟基磷灰石：骨组织及牙齿中的主要无机成分，具有优良的生物相容性、生物活性和骨传导性。人工合成羟基磷灰石的成分、结构与人体骨组织的无机质成分结构相类似，它具有无毒、无刺激性、无致敏性、无致突变性和致癌性，是一种生物相容性材料，可与骨发生化学作用，具有良好的骨传导性。
淫羊藿苷：具有抗衰老等功效，还具有促进造血功能、增加心脑血管血流量、免疫功能和骨代谢功能，可促进骨髓间充质干细胞增殖和成骨分化。
附图说明：
图1为大规模骨缺损植入多孔功能支架的正面剖视图，图中1为外层体心立方结构，图中2为内芯十字形蜂窝结构。
图2为大规模骨缺损植入多孔功能支架的俯视图，图中3为孔隙率为80%，孔径为800μm的外层结构，图中4为孔隙率为50%，孔径为400μm的内层结构。
图3为多孔功能支架外层体心立方结构单元体示意图。
图4为多孔功能支架内芯十字形蜂窝结构的正面剖视图。
具体实施方式：
1. 骨骼支架建模
通过CT扫描设备对骨缺损处进行三维扫描获取图像数据，根据破损骨头，利用三维软件重新设计出可以移植骨头的尺寸及形态。用UG三维制图软件设计出多功能梯度模型，将模型与健康骨骼进行比对，校验模型尺寸是否合适，有无偏差，支架采用环状多层结构设计，模型的外层为体心立方结构，孔隙率为80%，孔径为800μm，内芯为十字形蜂窝结构，孔隙率为50%，孔径为400μm，支架外层结构占整体结构60%的体积，内芯占整体结构的40%体积。
2. 制备钛合金粉末
采用气体雾化法制备Ti6Al4V球形粉末，用高频感应线圈进行加热将钛合金原料熔化，使熔液滴流，再用高速的氩气喷射熔液流，使金属液成喷雾状，冷凝后生成Ti6Al4V粉末。
3. 打印多孔钛支架
将预先设计好的功能梯度多孔支架模型导入SLM打印机中，将Ti6Al4V粉末放入供粉仓中，打印过程中激光功率为250W，扫描速度为1000mm/s，激光直径为50μm，扫描间距为0.1mm，其中支架外层为体心立方结构，孔隙率为80%，孔径为800μm，内芯为十字形蜂窝结构，孔隙率为50%，孔径为400μm。取出后采用无水乙醇清洗去除部分易清除的未熔融粉末，再采用超声清洗，通过超声振动将孔隙间残留的剩余粉末去除。
4. 制备多孔钛-壳聚糖-羟基磷灰石-淫羊藿苷复合支架
所用的试剂：壳聚糖、羟基磷灰石、乙酸、淫羊藿苷。
制备过程：在100ml规格的烧杯中注入0.2mol/L的乙酸99ml，称取1g壳聚糖粉末加入乙酸溶液中，在50℃环境下搅拌约 30min后形成浓度为1%的壳聚糖溶液。然后加入0.3g的羟基磷灰石粉末，0.1g的淫羊藿苷，继续搅拌直至均匀混合，将配置好的混合液放在室温下进行冷却。将多孔钛支架置于24孔培养板中，用一次性注射器将配置好的混合溶液注射到多孔钛支架的孔隙中，直至溶液将多孔钛支架完全覆盖，注射时应避免气泡的进入，室温静置1h后放入-20℃环境进行冷冻处理，冷冻12h。最后置入冷冻干燥机冻干。

Claims (3)

1.一种3D打印可再生功能梯度骨骼支架的制备方法，其特征是通过CT扫描设备对骨缺损处进行三维扫描获取图像数据设计出可以移植骨头的尺寸及形态，用UG三维制图软件设计出多功能梯度模型，以钛合金材料作为多孔骨骼支架材料，利用3D打印SLM成形出环状多功能梯度多孔支架结构，孔隙率由外向内减小，再将梯度多孔支架置于含有壳聚糖、羟基磷灰石、淫羊藿苷的混合溶液中，得到功能梯度多孔仿生复合支架，通过该方法制备的骨骼植入物实现了单一孔隙率的突破，更好的模拟了天然骨的实际孔隙率变化特征；其制备过程如下：
（a）通过CT扫描设备对骨缺损处进行三维扫描获取图像数据，根据破损骨头，利用三维软件重新设计出可以移植骨头的尺寸及形态；用UG三维制图软件设计出多功能梯度模型，将模型与健康骨骼进行比对，校验模型尺寸是否合适，有无偏差，支架采用环状多层结构设计，模型的外层为体心立方结构，孔隙率为80%，孔径为800μm，内芯为十字形蜂窝结构，孔隙率为50%，孔径为400μm，支架外层结构占整体结构60%的体积，内芯占整体结构的40%体积；
（b）采用气体雾化法制备Ti6Al4V球形粉末，用高频感应线圈进行加热将钛合金原料熔化，使熔液滴流，再用高速的氩气喷射熔液流，使金属液成喷雾状，冷凝后生成Ti6Al4V粉末；
（c）将预先设计好的功能梯度多孔支架模型导入SLM打印机中，将Ti6Al4V粉末放入供粉仓中，打印过程中激光功率为250W，扫描速度为1000mm/s，激光直径为50μm，扫描间距为0.1mm，其中支架外层为体心立方结构，孔隙率为80%，孔径为800μm，内芯为十字形蜂窝结构，孔隙率为50%，孔径为400μm；取出后采用无水乙醇清洗去除部分易清除的未熔融粉末，再采用超声清洗，通过超声振动将孔隙间残留的剩余粉末去除；
（d）在100ml规格的烧杯中注入0.2mol/L的乙酸99ml，称取1g壳聚糖粉末加入乙酸溶液中，在50℃环境下搅拌约 30min后形成浓度为1%的壳聚糖溶液；然后加入0.3g的羟基磷灰石粉末，0.1g的淫羊藿苷，继续搅拌直至均匀混合，将配置好的混合液放在室温下进行冷却；将多孔钛支架置于24孔培养板中，用一次性注射器将配置好的混合溶液注射到多孔钛支架的孔隙中，直至溶液将多孔钛支架完全覆盖，注射时应避免气泡的进入，室温静置1h后放入-20℃环境进行冷冻处理，冷冻12h，最后置入冷冻干燥机冻干，得到多孔钛-壳聚糖-羟基磷灰石-淫羊藿苷复合支架。
2.根据权利要求1所述的一种3D打印可再生功能梯度骨骼支架的制备方法，其特征在于，支架采用环状多层结构设计，模型的外层为体心立方结构，孔隙率为80%，孔径为800μm，内芯为十字形蜂窝结构，孔隙率为50%，孔径为400μm，支架外层结构占整体结构60%的体积，内层占整体结构的40%体积。
3.根据权利要求1所述的一种3D打印可再生功能梯度骨骼支架的制备方法，其特征在于，将预先设计好的功能梯度多孔支架模型导入SLM打印机中，将Ti6Al4V粉末放入供粉仓中，打印过程中激光功率为250W，扫描速度为1000mm/s，激光直径为50μm，扫描间距为0.1mm。
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