SGER: Development of a Collagen "Nanoloom" for the Generation of 2 and 3 Dimensional Biological Templates for Tissue Engineering

胶原蛋白是动物体内含量最丰富的分子。它是组成机械承重矩阵的主要组成部分，我们就是从这个矩阵构造出来的。在胶原基质需要承载显著拉伸负荷(即韧带、肌腱和角膜)的应用中，胶原蛋白阵列高度排列。目前“设计”这些高度组织化的结缔组织成分的替代物的尝试几乎没有成功，因为无法在体外控制适当长度的胶原纤维生成。这项研究提出了一种新的方法，通过在一系列纳米反应器中控制胶原纤维在纳米尺度上的自组装来构建坚固、排列整齐的天然胶原基质。单个反应堆的设计是生物启发的，因为它们将被塑造成提供类似于在细胞中发现的产生有组织的胶原蛋白基质的“纤维阳性物”或表面“隐窝”的环境。单个“织布机”芯片上的纳米反应器集群将被用来“打印”高度有序的胶原蛋白阵列，无论是二维还是三维。能够产生高度排列的胶原蛋白阵列的能力可以使具有足够机械强度的天然基质工程被植入，而种子成纤维细胞只需有限的先验重建。成功实现这一建议的目标的影响包括使组织工程学成为临床上适合疾病或受损的韧带、肌腱和角膜的替代的能力和/或加速的能力。纳米反应器阵列的生物灵感设计也应该提供对胚胎发生、重塑和修复过程中组织生成的洞察。最后，这项研究旨在通过反应堆阵列的可伸缩性，将一个根本上的纳米技术系统“转化”为一个大规模的医疗设备。

Collagen is the most abundant molecule in animals. It is the major component comprising the mechanical load-bearing matrix from which we are constructed. Inapplications where collagenous matrices are expected to carry significant tensile loads (i.e. ligament, tendon and cornea), the collagen arrays are highly-aligned. Current attempts to "engineer" replacements for these highly-organized connective tissue components have met with little success because of the inability to control collagen fibrillogenesis in vitro at appropriate length scales. This research presents a novel approach to constructing strong, aligned natural collagen matrices by controlling the self-assembly of collagen fibrils on the nanoscale in an array of nanoreactors. The design of the individual reactors is bioinspired in that they will be fashioned to provide a similar environment to that of "fibropositors" or surface "crypts" found in cells which produce organized collagenous matrices. Clusters of nanoreactors on a single "loom" chip will be used to "print" highly organized collagen arrays in either two or three-dimensions. The ability to produce highly-aligned arrays of collagen could permit the engineering of natural matrices which have adequate mechanical strength to be implanted with only limited a priori remodeling by seeded fibroblast cells.The impact of successful implementation of the aims in this proposal includes the ability to make feasible and/or accelerate the process of tissue engineering a clinically suitable replacement of diseased or damaged ligament, tendons and corneas. The bioinspired design of the arrays of nanoreactors should also provide insight into the process of tissue generation during embryogenesis, remodeling and repair. Finally, this research is designed, through the scalability of the reactor arrays, to "translate" a fundamentally nanotechnological system into a macroscale medical device.