Zhu Bofan, Li Wen, Lewis Randolph V, Segre Carlo U, Wang Rong
Department of Biological and Chemical Sciences, ‡Department of Physics, Illinois Institute of Technology , Chicago, Illinois 60616, United States.
Biomacromolecules. 2015 Jan 12;16(1):202-13. doi: 10.1021/bm501403f. Epub 2014 Dec 1.
Biocomposite matrices with high mechanical strength, high stability, and the ability to direct matrix-specific stem cell differentiation are essential for the reconstruction of lesioned tissues in tissue engineering and cell therapeutics. Toward this end, we used the electrospinning technique to fabricate well-aligned composite fibers from collagen and spider dragline silk protein, obtained from the milk of transgenic goats, mimicking the native extracellular matrix (ECM) on a similar scale. Collagen and the dragline silk proteins were found to mix homogeneously at all ratios in the electrospun (E-spun) fibers. As a result, the ultimate tensile strength and elasticity of the fibers increased monotonically with silk percentage, whereas the stretchability was slightly reduced. Strikingly, we found that the incorporation of silk proteins to collagen dramatically increased the matrix stability against excessive fiber swelling and shape deformation in cell culture medium. When human decidua parietalis placental stem cells (hdpPSCs) were seeded on the collagen-silk matrices, the matrices were found to support cell proliferation at a similar rate as that of the pure collagen matrix, but they provided cell adhesion with reduced strengths and induced cell polarization at varied levels. Matrices containing 15 and 30 wt % silk in collagen (CS15, CS30) were found to induce a level of neural differentiation comparable to that of pure collagen. In particular, CS15 matrix induced the highest extent of cell polarization and promoted the development of extended 1D neural filaments strictly in-line with the aligned fibers. Taking the increased mechanical strength and fiber stability into consideration, CS15 and CS30 E-spun fibers offer better alternatives to pure collagen fibers as scaffolds that can be potentially utilized in neural tissue repair and the development of future nanobiodevices.
具有高机械强度、高稳定性以及能够引导特定基质干细胞分化的生物复合基质,对于组织工程和细胞治疗中受损组织的重建至关重要。为此,我们采用静电纺丝技术,从转基因山羊乳汁中提取的胶原蛋白和蜘蛛拖牵丝蛋白制备出排列良好的复合纤维,在相似尺度上模拟天然细胞外基质(ECM)。研究发现,胶原蛋白和拖牵丝蛋白在静电纺(E纺)纤维中以各种比例均匀混合。结果,纤维的极限拉伸强度和弹性随丝蛋白百分比单调增加,而拉伸性略有降低。引人注目的是,我们发现将丝蛋白掺入胶原蛋白中可显著提高基质在细胞培养基中抵抗过度纤维肿胀和形状变形的稳定性。当将人蜕膜胎盘干细胞(hdpPSCs)接种到胶原 - 丝基质上时,发现该基质支持细胞增殖的速率与纯胶原基质相似,但它们提供的细胞黏附强度降低,并在不同程度上诱导细胞极化。发现在胶原蛋白中含有15 wt%和30 wt%丝蛋白的基质(CS15、CS30)诱导的神经分化水平与纯胶原蛋白相当。特别是,CS15基质诱导了最高程度的细胞极化,并促进了与排列的纤维严格成直线的延伸一维神经丝的发育。考虑到机械强度和纤维稳定性的提高,CS15和CS30 E纺纤维作为支架,为纯胶原纤维提供了更好的替代品,可潜在地用于神经组织修复和未来纳米生物器件的开发。