Magnetically-guided self-assembly of fibrin matrices with ordered nano-scale structure for tissue engineering
Magnetically-guided self-assembly of fibrin matrices with ordered nano-scale structure for tissue engineering
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DOI：
10.1089/ten.2006.12.3247
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发表时间：
2006-11-01
影响因子：
--
通讯作者：
Ingber, Donald E.
中科院分区：
文献类型：
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作者：
Alsberg, Eben;Feinstein, Efraim;Ingber, Donald E.
用于组织工程和再生医学应用的有效生物支架材料的开发取决于向特定细胞群提供精确环境线索以指导其位置和功能的能力。天然细胞外基质具有有序的纳米级结构，可以调节对发育控制至关重要的细胞行为，包括定向细胞运动。在这里，我们描述了一种方法，用于制造纤维蛋白凝胶与定义的架构在纳米尺度上，其中磁力被用来定位凝血酶包被的磁性微珠在一个定义的二维阵列，从而引导纤维蛋白原纤维的自组装通过催化裂解可溶性纤维蛋白原基板。延时和共聚焦显微镜证实，纤维蛋白原纤维成核附近的表面的凝血酶包被的珠，并在径向方向延伸，以形成这些凝胶。当使用受控磁场将珠粒定位在六边形阵列中时，从珠粒聚合的纤维蛋白纳米原纤维以测地线（最小路径）图案优先沿着珠粒-珠粒轴取向。这些生物相容性支架支持人微血管内皮细胞的粘附和扩散，其表现出内部肌动蛋白应力纤维与细胞周边的一些膜延伸内的下层纤维蛋白纳米原纤维的共对齐。这种磁引导的、生物启发的微制造系统是独特的，因为可以用很少的起始材料形成大的支架，因此它可能在未来的体内组织工程应用中有用。
The development of effective biological scaffold materials for tissue engineering and regenerative medicine applications hinges on the ability to present precise environmental cues to specific cell populations to guide their position and function. Natural extracellular matrices have an ordered nano-scale structure that can modulate cell behaviors critical for developmental control, including directional cell motility. Here we describe a method for fabricating fibrin gels with defined architecture on the nanometer scale in which magnetic forces are used to position thrombin-coated magnetic micro-beads in a defined 2-dimensional array and thereby guide the self-assembly of fibrin fibrils through catalytic cleavage of soluble fibrinogen substrate. Time-lapse and confocal microscopy confirmed that fibrin fibrils nucleate near the surface of the thrombin-coated beads and extend out in a radial direction to form these gels. When controlled magnetic fields were used to position the beads in hexagonal arrays, the fibrin nano-fibrils that polymerized from the beads oriented preferentially along the bead-bead axes in a geodesic ( minimal path) pattern. These biocompatible scaffolds supported adhesion and spreading of human microvascular endothelial cells, which exhibited co-alignment of internal actin stress fibers with underlying fibrin nano-fibrils within some membrane extensions at the cell periphery. This magnetically-guided, biologically-inspired microfabrication system is unique in that large scaffolds may be formed with little starting material, and thus it may be useful for in vivo tissue engineering applications in the future.