Zhou Mi, Smith Andrew M, Das Apurba K, Hodson Nigel W, Collins Richard F, Ulijn Rein V, Gough Julie E
Materials Science Centre, School of Materials, The University of Manchester, Grosvenor Street, Manchester M1 7HS, UK.
Biomaterials. 2009 May;30(13):2523-30. doi: 10.1016/j.biomaterials.2009.01.010. Epub 2009 Feb 7.
We report here the design of a biomimetic nanofibrous hydrogel as a 3D-scaffold for anchorage-dependent cells. The peptide-based bioactive hydrogel is formed through molecular self-assembly and the building blocks are a mixture of two aromatic short peptide derivatives: Fmoc-FF (Fluorenylmethoxycarbonyl-diphenylalanine) and Fmoc-RGD (arginine-glycine-aspartate) as the simplest self-assembling moieties reported so far for the construction of small-molecule-based bioactive hydrogels. This hydrogel provides a highly hydrated, stiff and nanofibrous hydrogel network that uniquely presents bioactive ligands at the fibre surface; therefore it mimics certain essential features of the extracellular matrix. The RGD sequence as part of the Fmoc-RGD building block plays a dual role of a structural component and a biological ligand. Spectroscopic and imaging analysis using CD, FTIR, fluorescence, TEM and AFM confirmed that FF and RGD peptide sequences self-assemble into beta-sheets interlocked by pi-pi stacking of the Fmoc groups. This generates the cylindrical nanofibres interwoven within the hydrogel with the presence of RGDs in tunable densities on the fibre surfaces. This rapid gelling material was observed to promote adhesion of encapsulated dermal fibroblasts through specific RGD-integrin binding, with subsequent cell spreading and proliferation; therefore it may offer an economical model scaffold to 3D-culture other anchorage-dependent cells for in-vitro tissue regeneration.
我们在此报告一种仿生纳米纤维水凝胶的设计，该水凝胶作为一种用于贴壁依赖性细胞的三维支架。基于肽的生物活性水凝胶通过分子自组装形成，其构建单元是两种芳香族短肽衍生物的混合物：Fmoc-FF（芴甲氧羰基-二苯基丙氨酸）和Fmoc-RGD（精氨酸-甘氨酸-天冬氨酸），它们是迄今为止报道的用于构建基于小分子的生物活性水凝胶的最简单自组装部分。这种水凝胶提供了一个高度水合、坚硬且纳米纤维状的水凝胶网络，该网络在纤维表面独特地呈现生物活性配体；因此，它模拟了细胞外基质的某些基本特征。作为Fmoc-RGD构建单元一部分的RGD序列起着结构成分和生物配体的双重作用。使用圆二色性（CD）、傅里叶变换红外光谱（FTIR）、荧光、透射电子显微镜（TEM）和原子力显微镜（AFM）进行的光谱和成像分析证实，FF和RGD肽序列自组装成由Fmoc基团的π-π堆积互锁的β-折叠。这产生了交织在水凝胶中的圆柱形纳米纤维，其纤维表面存在密度可调的RGD。观察到这种快速凝胶化材料通过特定的RGD-整合素结合促进包封的真皮成纤维细胞的粘附，随后细胞铺展和增殖；因此，它可能为三维培养其他贴壁依赖性细胞以进行体外组织再生提供一种经济的模型支架。
