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

点击翻译按钮获取中文摘要

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.