Girton T S, Dubey N, Tranquillo R T
Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN.
Methods Mol Med. 1999;18:67-73. doi: 10.1385/0-89603-516-6:67.
The use of reconstituted type I collagen gel as a scaffold for engineered soft tissues is a highly attractive prospect, given that collagen is the principal component of the extracellular matrix (ECM) in vivo, providing a mechanically suitable and information-rich scaffold for cell-ECM interactions. It has the advantage that cells can be directly entrapped within the comprising collagen fibrils as they grow into an entangled network from a cell containing solution of monomeric type I collagen. These tissue equivalents have the further advantage that the collagen fibrils can be aligned by applying a magnetic field during fibrillogenesis. Then, through a process termed "contact guidance," the cells align with the fibrils by directing their motility. Such alignment is characteristic of many tissues, and may provide microstructural and mechanical cues for regulation of cell phenotype and function, as well as influence the gross mechanical properties of the tissues. Recent research in our laboratory has used magnetic-induced alignment in the fabrication of tissue-equivalents, notably circumferential alignment in tubes, and longitudinal alignment in rods (patent pending). The former is aimed at reproducing the architecture of the arterial media; the latter is aimed at providing a bridge that promotes directed axonal growth between severed nerve ends. These tissue engineering applications exploit the finding of Torbet and Ronziere (1) in their cell-free studies that forming fibrils tend to align in the plane normal to the direction of the field (because of the negative diamagnetic anisotropy of collagen) and parallel to the mold surfaces (because of an uncharacterized interfacial effect).
鉴于胶原蛋白是体内细胞外基质（ECM）的主要成分，能为细胞与ECM的相互作用提供机械性能适宜且信息丰富的支架，因此使用重构的I型胶原蛋白凝胶作为工程化软组织的支架极具吸引力。其优势在于，当细胞从含单体I型胶原蛋白的溶液中生长成缠结网络时，可直接被困在构成的胶原纤维内。这些组织等效物还有一个优势，即在原纤维形成过程中施加磁场可使胶原纤维排列整齐。然后，通过一个称为“接触导向”的过程，细胞通过引导其运动与纤维排列一致。这种排列是许多组织的特征，可能为细胞表型和功能的调节提供微观结构和力学线索，还会影响组织的整体力学性能。我们实验室最近的研究在组织等效物的制造中采用了磁诱导排列，特别是在管中进行周向排列，在棒中进行纵向排列（专利申请中）。前者旨在重现动脉中膜的结构；后者旨在提供一座促进切断的神经末梢之间轴突定向生长的桥梁。这些组织工程应用利用了Torbet和Ronziere（1）在无细胞研究中的发现，即形成的原纤维倾向于在垂直于磁场方向的平面内排列（由于胶原蛋白的负抗磁各向异性），并平行于模具表面排列（由于一种未明确的界面效应）。
