中国组织工程研究

中国组织工程研究 ›› 2019, Vol. 23 ›› Issue (26): 4230-4236.doi: 10.3969/j.issn.2095-4344.1365

• 材料生物相容性 material biocompatibility • 上一篇    下一篇

藻酸盐-羟基磷灰石-聚乙二醇复合水凝胶支架的制备及其生物相容性

李轩泽1，2，3，舒莉萍3，4，陈  娇4，5，孙  宇4，邹  强2，王伟宇4，刘  鋆4，杨  龙2，马敏先4，5，叶  川2，3，4
  

  1. 1贵州医科大学，贵州省贵阳市  550004；2贵州医科大学附属医院骨科，贵州省贵阳市  550004；3贵州医科大学细胞工程生物医药技术国家地方联合工程实验室，贵州省贵阳市 550004；4贵州医科大学组织工程与干细胞实验中心，贵州省贵阳市  550004；5贵州医科大学附属口腔医院口腔修复科，贵州省贵阳市  550004
  • 收稿日期:2019-04-22 出版日期:2019-09-18 发布日期:2021-04-29
  • 通讯作者: 叶川，主任医师，贵州医科大学附属医院骨科，贵州省贵阳市 550004；贵州医科大学细胞工程生物医药技术国家地方联合工程实验室，贵州省贵阳市 550004；贵州医科大学组织工程与干细胞实验中心，贵州省贵阳市 550004
  • 作者简介:李轩泽，男，1994年生，湖北省咸宁市人，汉族，贵州医科大学在读硕士，医师，主要从事组织工程支架、生物材料、干细胞研究。
  • 基金资助:

    国家自然科学基金资助项目(81360232)，项目负责人：叶川；贵阳市科技局创新团队资助项目([2017]5-17)，项目负责人：叶川；中国医学科学院成体干细胞转化重点实验室开放课题资助项目(2018YB04)，项目负责人：杨龙；贵州省教育厅项目资助(黔教合KY字[2017]161)，项目负责人：杨龙 

Preparation of sodium alginate-hydroxyapatite-polyethylene glycol composite hydrogel scaffold and its biocompatibility

Li Xuanze1, 2, 3, Shu Liping3,4, Chen Jiao4, 5, Sun Yu4, Zou Qiang2, Wang Weiyu4, Liu Jun4, Yang Long2, Ma Minxian4, 5, Ye Chuan2, 3, 4
  


  • Received:2019-04-22 Online:2019-09-18 Published:2021-04-29
  • Contact: Ye Chuan, Chief physician, Department of Orthopedics, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, China; National-Guizhou Joint Engineering Laboratory of Cell Engineering and Biomedicine Technique, Guiyang 550004, Guizhou Province, China; Research Center of Tissue Engineering and Stem Cell Technique, Guizhou Medical Univesity, Guiyang 550004, Guizhou Province, China
  • About author:Li Xuanze, Master candidate, Physician, Guizhou Medical University, Guiyang 550004, Guizhou Province, China; Department of Orthopedics, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou Province, China; National-Guizhou Joint Engineering Laboratory of Cell Engineering and Biomedicine Technique, Guiyang 550004, Guizhou Province, China
  • Supported by:

    the National Natural Science Foundation of China, No. 81360232 (to YC); Guiyang Science and Technology Bureau Innovation Team Project, No. [2017]5-17 (to YC); an Open Project of Key Laboratory of Adult Stem Cell Transplantation of Chinese Academy of Medical Sciences, No. 2018YB04 (to YL); a Project of Guizhou Provincial Department of Education, No. qianjiaohe-KY[2017]161 (to YL)

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摘要：

文章快速阅读：

 

文题释义：
聚乙二醇：为环氧乙烷水解产物的聚合物，无毒、无刺激性，被广泛应用于各种药物制剂中；聚乙二醇是非离子型的水溶性聚合物，能与许多极性较高的物质配伍。
真空冷冻干燥技术：在低温低压条件下利用水的升华性能，使物料低温脱水而达到干燥的新型干燥手段，处理过程无液态水存在，水分以固体状态直接升华，使物料原有结构和形状得到最大程度保护，最终获得外观和内在品质兼备的优质干燥制品。
 
摘要
背景：聚乙二醇作为医用高分子共聚材料被广泛用于药物缓释，若将其制备成复合水凝胶，可作为具备一定力学性能且生物相容性良好的支架材料。
目的：探索藻酸盐-羟基磷灰石-聚乙二醇藻酸盐-羟基磷灰石-聚乙二醇(sodium alginate-hydroxyapatite- polyethylene glycol，SA-HA-PEG)复合水凝胶支架材料的理化性能及生物相容性。
方法：超声混匀水凝胶后，加入2价阳离子溶液交联，分别得到海藻酸-羟基磷灰石(A组)、SA-HA-3%PEG(B组)、SA-HA-5%PEG(C组)、SA-HA-8%PEG(D组)4组支架，后3组支架中PEG的质量浓度分别为30，50，80 g/L，利用动态机械分析仪分析凝胶支架的压缩应力和弹性模量；将支架置于溶菌酶溶液中，测定其体外降解率；真空冷冻干燥后，采用扫描电镜观察凝胶支架的三维结构。将4组水凝胶支架分别与骨髓间充质干细胞混匀交联后，CCK-8检测培养1，3，5，7 d后的细胞增殖情况，Live/Dead荧光染色观察培养7 d后的细胞活性。
结果与结论：①B、C、D组支架的压缩应力与弹性模量高于A组(P < 0.05)，C、D组支架的压缩应力与弹性模量高于B组(P < 0.05)，C、D组压缩应力与弹性模量比较差异无显著性意义(P > 0.05)；②C、D组支架降解率低于A、B组(P < 0.05)，B组支架降解率低于A组(P < 0.05)，C、D组支架降解率比较差异无显著性意义(P > 0.05)；③扫描电镜显示，C组支架呈现孔隙率高、孔径大小一致的生物凝胶结构，A、B、D组支架的孔径大小不规则、孔隙率低；④B、C、D组培养3-7 d的细胞增殖速率快于A组(P < 0.05)，前3组间比较差异无显著性意义(P > 0.05)；⑤复合培养7 d后，B、C、D组细胞存活率高于A组(P < 0.05)，C组高于B、D组(P < 0.05)；⑥结果表明，SA-HA-PEG复合水凝胶支架具有良好的力学性能与生物相容性。
ORCID: 0000-0002-4493-4046(李轩泽)

关键词: 生物材料, SA-HA-PEG, 藻酸盐, 羟基磷灰石, 聚乙二醇, 水凝胶, 组织工程支架, 复合水凝胶支架

Abstract:

BACKGROUND: Polyethylene glycol, as a medical polymer copolymer, is widely used in sustained-release of drugs. If it is prepared into composite hydrogel, it can be used as a scaffold material with certain mechanical properties and good biocompatibility.
OBJECTIVE: To investigate the physical and chemical properties and biocompatibility of sodium alginate-hydroxyapatite-polyethylene glycol (SA-HA-PEG) composite hydrogel scaffold material.
METHODS: Bivalent cationic solution was added to the ultrasound treated hydrogel for crosslinking. Four groups of scaffold were obtained: SA-HA scaffold (group A), SA-HA-3%PEG (group B), SA-HA-5%PEG (group C), SA-HA-8%PEG (group D). The mass concentration of PEG in the later three groups was 30, 50, and 80 g/L. The compressive stress and elastic modulus of the hydrogel scaffold were analyzed using a dynamic mechanical analyzer. The scaffold was placed in lysozyme solution to determine its degradation rate in vitro. After vacuum freeze-drying, the three-dimensional structure of the hydrogel scaffold was observed by scanning electron microscopy. Four groups of hydrogel scaffold were cross-linked with bone marrow mesenchymal stem cells. Cell proliferation was detected using CCK8 assay at 1, 3, 5 and 7 days of culture. After 7 days of culture, cell viability was detected using Live/Dead fluorescence staining.
RESULTS AND CONCLUSION: The compressive stress and elastic modulus in the groups B, C and D were significantly higher than those in the group A (P < 0.05). The compressive stress and elastic modulus in the groups C and D were significantly higher than those in the group B (P < 0.05). There were no significant differences in compressive stress and elastic modulus between groups C and D (P > 0.05). The degradation rate of hydrogel scaffold in the groups C and D were significantly lower than that in the groups A and B (P < 0.05). The degradation rate of hydrogel scaffold in the group B was significantly lower than that in the group A (P < 0.05). There was no significant difference in the degradation rate of hydrogel scaffold between groups C and D (P > 0.05). Scanning electron microscopy showed that hydrogel scaffold in the group C had the structure with high porosity and consistent pore size; hydrogel scaffold in the groups A, B and D had the structure with low porosity and inconsistent pore size. After 3-7 days of culture, cells in the groups B, C and D proliferated more rapidly than those in the group A (P < 0.05). There was no significant difference in cell proliferation rate between groups B, C and D (P < 0.05). After 7 days of culture, cell viability in the groups B, C and D was significantly higher than that in the group A (P < 0.05), and cell viability in the group C was significantly higher than that in the groups B and D (P < 0.05). These results suggest that SA-HA-PEG composite hydrogel scaffold exhibit good mechanical property and encouraging biocompatibility.  

Key words: biomaterial, SA-HA-PEG, sodium alginate, hydroxyapatite, polyethylene glycol, hydrogel, tissue-engineered scaffold, composite hydrogel scaffold

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