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多的分子。它是构成我们的机械承重矩阵的主要组成部分。在应用中，胶原基质有望承载显著的拉伸载荷（如韧带，肌腱和角膜），胶原阵列是高度对齐的。目前试图“工程”替代这些高度组织结缔组织成分的尝试几乎没有成功，因为无法在适当的长度尺度上控制体外胶原纤维的形成。本研究提出了一种通过在纳米反应器阵列中控制胶原原纤维在纳米尺度上的自组装来构建强、排列的天然胶原基质的新方法。单个反应器的设计是受生物启发的，因为它们将被塑造成提供类似于在产生有组织的胶原基质的细胞中发现的“纤维支架”或表面“隐窝”的环境。在单个“织布机”芯片上的纳米反应器集群将用于“打印”高度组织化的二维或三维胶原蛋白阵列。生产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化，仅通过种植成纤维细胞进行有限的先验重塑即可植入。成功实施本提案目标的影响包括使可行和/或加速组织工程过程的能力，以临床上适合病变或受损的韧带，肌腱和角膜的替代品。纳米反应器阵列的生物灵感设计也将为了解胚胎发生、重塑和修复过程中的组织生成过程提供见解。最后，本研究旨在通过反应器阵列的可扩展性，将基本的纳米技术系统“转化”为宏观尺度的医疗设备。

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.