Harvard MIT Division of Health Sciences and Technology and Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Biomacromolecules. 2010 Aug 9;11(8):2053-9. doi: 10.1021/bm100413w.
Fibroblast growth factor 2 (FGF-2) is a potent mediator of stem cell differentiation and proliferation. Although FGF-2 has a well-established role in promoting bone tissue formation, flaws in its delivery have limited its clinical utility. Polyelectrolyte multilayer films represent a novel system for FGF-2 delivery that has promise for local, precisely controlled, and sustained release of FGF-2 from surfaces of interest, including medical implants and tissue engineering scaffolds. In this work, the loading and release of FGF-2 from synthetic hydrolytically degradable multilayer thin films of various architectures is explored; drug loading was tunable using at least three parameters (number of nanolayers, counterpolyanion, and type of degradable polycation) and yielded values of 7-45 ng/cm(2) of FGF-2. Release time varied between 24 h and approximately five days. FGF-2 released from these films retained in vitro activity, promoting the proliferation of MC3T3 preosteoblast cells. The use of biologically derived counterpolyanions heparin sulfate and chondroitin sulfate in the multilayer structures enhanced FGF-2 activity. The control over drug loading and release kinetics inform future in vivo bone and tissue regeneration models for the exploration of clinical relevance of LbL growth factor delivery films.
成纤维细胞生长因子 2(FGF-2)是一种有效的干细胞分化和增殖调节剂。尽管 FGF-2 在促进骨组织形成方面具有明确的作用,但由于其传递方式存在缺陷,限制了其临床应用。聚电解质多层膜是一种新型的 FGF-2 传递系统,有望实现局部、精确控制和持续释放 FGF-2,适用于包括医疗植入物和组织工程支架在内的感兴趣表面。在这项工作中,研究了各种结构的合成可水解降解多层薄膜中 FGF-2 的加载和释放情况;通过至少三个参数(纳米层的数量、抗衡离子和可降解聚阳离子的类型)来调节药物负载,得到了 7-45ng/cm(2)的 FGF-2 负载量。释放时间在 24 小时至大约五天之间变化。从这些薄膜中释放的 FGF-2 在体外保持活性,促进 MC3T3 前成骨细胞的增殖。在多层结构中使用生物衍生的抗衡离子肝素硫酸盐和硫酸软骨素增强了 FGF-2 的活性。对药物负载和释放动力学的控制为体内骨和组织再生模型提供了信息,以探索 LbL 生长因子传递膜的临床相关性。