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

SGER：开发胶原蛋白“Nanoloom”，用于生成组织工程的 2 维和 3 维生物模板

• 批准号: 0541707
• 负责人: Jeffrey Ruberti
• 金额: $ 5.98万
• 依托单位: Northeastern University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0541707&HistoricalAwards=false
• 关键词: SGER; Development; Collagen; Nanoloom; Generation

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.

胶原蛋白是动物体内最丰富的分子。它是构成我们构造的机械承载矩阵的主要组成部分。在预期胶原基质承载显著拉伸载荷的应用中（即韧带、肌腱和角膜），胶原阵列高度对齐。目前试图“工程”替代这些高度组织化的结缔组织成分，但几乎没有成功，因为无法在体外控制适当长度尺度的胶原原纤维形成。这项研究提出了一种新的方法来构建强大的，对齐的天然胶原蛋白基质，通过控制在纳米反应器阵列中的纳米级胶原蛋白原纤维的自组装。单个反应器的设计是生物启发的，因为它们将被塑造成提供与在产生有组织的胶原基质的细胞中发现的“纤维定位器”或表面“隐窝”类似的环境。单个“织机”芯片上的纳米反应器簇将用于“打印”高度组织化的胶原蛋白阵列，无论是二维还是三维。产生高度排列的胶原阵列的能力可以允许工程化天然基质，所述天然基质具有足够的机械强度以仅通过接种的成纤维细胞进行有限的先验重塑而被植入。成功实施本提案中的目标的影响包括使患病或受损韧带的临床合适替代物的组织工程化可行和/或加速组织工程化过程的能力，肌腱和角膜纳米反应器阵列的生物启发设计还应该提供对胚胎发生，重塑和修复期间组织生成过程的洞察。最后，这项研究的目的是，通过反应器阵列的可扩展性，“翻译”一个基本的纳米技术系统到一个宏观尺度的医疗设备。