Division of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, P.O. Box 56, FI-00014 University of Helsinki, Finland.
J Control Release. 2012 Dec 28;164(3):291-8. doi: 10.1016/j.jconrel.2012.06.039. Epub 2012 Jul 7.
Over the recent years, various materials have been introduced as potential 3D cell culture scaffolds. These include protein extracts, peptide amphiphiles, and synthetic polymers. Hydrogel scaffolds without human or animal borne components or added bioactive components are preferred from the immunological point of view. Here we demonstrate that native nanofibrillar cellulose (NFC) hydrogels derived from the abundant plant sources provide the desired functionalities. We show 1) rheological properties that allow formation of a 3D scaffold in-situ after facile injection, 2) cellular biocompatibility without added growth factors, 3) cellular polarization, and 4) differentiation of human hepatic cell lines HepaRG and HepG2. At high shear stress, the aqueous NFC has small viscosity that supports injectability, whereas at low shear stress conditions the material is converted to an elastic gel. Due to the inherent biocompatibility without any additives, we conclude that NFC generates a feasible and sustained microenvironment for 3D cell culture for potential applications, such as drug and chemical testing, tissue engineering, and cell therapy.
近年来,已经有多种材料被引入作为潜在的 3D 细胞培养支架。这些材料包括蛋白质提取物、肽两亲物和合成聚合物。从免疫学角度来看,首选没有人类或动物来源成分或添加生物活性成分的水凝胶支架。在这里,我们证明了来源于丰富植物资源的天然纳米原纤纤维素(NFC)水凝胶提供了所需的功能。我们展示了 1)流变学特性,可在简单注射后就地形成 3D 支架,2)无需添加生长因子的细胞生物相容性,3)细胞极化,以及 4)人肝细胞系 HepaRG 和 HepG2 的分化。在高剪切应力下,NFC 的水相具有较小的粘度,支持可注射性,而在低剪切应力条件下,该材料转变为弹性凝胶。由于没有任何添加剂的固有生物相容性,我们得出结论,NFC 为 3D 细胞培养生成了一个可行且可持续的微环境,适用于药物和化学测试、组织工程和细胞治疗等潜在应用。