中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (47): 8801-8804.doi: 10.3969/j.issn.1673-8225.2011.47.015

• 复合支架材料 composite scaffold materials • 上一篇    下一篇

碱性成纤维细胞生长因子/双层胶原基复合材料制备及其生物安全性

王建华1,李学敏1,陶晓军1,陈晖娟1,史佳巍1,刘玲蓉1,张其清1, 2   

  1. 1中国医学科学院生物医学工程研究所,天津市生物材料重点实验室,天津市  300192
    2厦门大学生物医学工程研究中心,材料学院生物材料系,福建省生物医学工程重点实验室,厦门市生物医学工程技术研究中心,福建省厦门市   361005
  • 收稿日期:2011-07-05 修回日期:2011-08-04 出版日期:2011-11-19 发布日期:2011-11-19
  • 通讯作者: 张其清,研究员,博士生导师,中国医学科学院生物医学工程研究所,天津市生物材料重点实验室,天津市 300192 zhangqiq@ xmu.edu.cn
  • 作者简介:王建华☆,男,1973年生,山东省临沂市人,汉族,2011年北京协和医学院毕业,博士,主要从事生物材料和组织工程研究。 mwangjianhua@yahoo.com.cn
  • 基金资助:

    天津市科技支撑计划重点项目(08ZCKFSF02100);博士点基金项目(20101106110042)。

Preparation and biological safety of basic fibroblast growth factor/double-layered collagen composite

Wang Jian-hua1, Li Xue-min1, Tao Xiao-jun1, Chen Hui-juan1, Shi Jia-wei1, Liu Ling-rong1, Zhang Qi-qing1,2   

  1. 1Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Peking Union Medical College, the Key Laboratory of Biomedical Material of Tianjin, Tianjin  300192, China
    2Research Center of Biomedical Engineering, Xiamen University, Xiamen  361005, Fujian Province, China
  • Received:2011-07-05 Revised:2011-08-04 Online:2011-11-19 Published:2011-11-19
  • Contact: Zhang Qi-qing, Researcher, Doctoral supervisor, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Peking Union Medical College, the Key Laboratory of Biomedical Material of Tianjin, Tianjin 300192, China; Research Center of Biomedical Engineering, Xiamen University, Xiamen 361005, Fujian Province, China zhangqiq@ xmu.edu.cn
  • About author:Wang Jian-hua☆, Doctor, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences, Peking Union Medical College, the Key Laboratory of Biomedical Material of Tianjin, Tianjin 300192, China mwangjianhua@ yahoo.com.cn
  • Supported by:

    the Tackle Key Program of Tianjin Municipal Science and Technology Commission, No. 08ZCKFSF02100*; Doctoral Station Foundation, No. 20101106110042*

摘要:

背景:胶原特殊的分子结构和生物活性有利于多种细胞黏附、增殖和分化,并可降解为新生组织提供足够空间。
目的:制备一种复合负载碱性成纤维细胞生长因子的壳聚糖-肝素纳米粒子双层胶原基复合材料,并评价其生物安全性。
方法:制备交联风干胶原膜和交联冻干胶原膜。将壳聚糖-肝素纳米粒滴于交联冻干胶原膜上,再将湿态交联风干胶原膜置于复合纳米粒子的交联冻干胶原膜上风干,即碱性成纤维细胞生长因子/双层胶原基复合材料。采用急性全身毒性试验、溶血试验、热原试验和细胞毒性试验评价其生物安全性。
结果与结论:碱性成纤维细胞生长因子/双层胶原基复合材料为双层结构,一侧表面致密,另一侧疏松多孔。在其中间负载碱性成纤维细胞生长因子的壳聚糖-肝素纳米粒子呈不规则球形分布于胶原膜内侧面;急性全身毒性试验、热原试验、溶血试验均为阴性,细胞毒性为0级。说明碱性成纤维细胞生长因子/双层胶原基复合材料具有良好的生物安全性,对机体无毒,符合ISO 10993-1评价标准。

关键词: 碱性成纤维细胞生长因子, 胶原, 壳聚糖, 肝素, 纳米粒子, 生物安全性

Abstract:

BACKGROUND: Collagen is a common used scaffold in tissue engineering, its specific molecular structure and biological activity are conducive to a variety of cell adhesion, proliferation and differentiation, and can speed up wound healing and degradation to provide sufficient space for new tissues.
OBJECTIVE: To prepare a kind of inhomogeneous double layered collagen composite incorporated with basic fibroblast growth factor (bFGF) loaded chitosan-heparin (CS-Hep) nanoparticles, and to evaluate its biological safety.
METHODS: The air-dried dense layer collagen membranes and freeze-dried loose layer collagen membrane were prepared respectively and then cross-linked by D-ribose (termed as CAM and CFM respectively). CS-Hep nanoparticles were prepared and then dropped on the surface of CFM. The wet CAM was laid on the surface of CFM with nanoparticles, and then air dried completely at 4 ℃. The obtained material was termed as bDM. Its physical and chemical properties were investigated. In addition, its bio-safety was also examined through acute systemic toxicity, pyrogen, hemolysis and cellular toxicity tests.
RESULTS AND CONCLUSION: The bFGF/double-layered collagen composite was made up of double layers with one dense layer (CAM) and another loose layer (CFM). As part of bDM, CS-Hep nanopartiles with irregular global shape were aligned in the scope of D-period structure of the inner surface of CFM; the bFGF/double-layered collagen composite had no systemic acute toxicity, no cytotoxicity and pyrogen reactions as well as no hemolytic effect. The bFGF/double-layered collagen composite is prepared and found to have good biocompatibility and safety. Moreover, this material conforms to the ISO 10993-1, and can be used as a basic scaffold material in tissue engineering.

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