Three-dimensional Extracellular Platform by Revesrsal Nanoimprint with Surface Gradient Control

Description

It is highly desirable to develop microsystems to overcome impairment in motor and sensory skills. Artificial cell culture scaffold is a fundamental element that can lead to repair or replacement of defective tissues or organs. We propose to develop reversal nanoimprint technology to generate three-dimensional (3D) extracellular platform to guide cell migration and interactions. Previous studies are limited in resolution to reach the nanometer scale while forming a 3D platform with designed architecture for cell passages and sites for cell connections and interaction. Our approach providesprecisely controlled cell passages in 3D with nanostructures, interconnecting access ports, and cell-cell and cell-biomolecule reaction chambers. In addition, we will developsurface modification technology with nanometer precision to produce surface gradient of surface energy and biomolecule density along the cell passages in the 3D matrix. This surface gradient will serve as the driving force to guide the cells in the platform to the desired morphogenesis and metastasis.The ultimate goal of this project is to developa microsystem with high precision nanostructures, interconnecting cell passages and reaction sites, and surface gradient to guide the cell migration and adhesion in a 3D extracellular platform. In order to achieve this goal, we will explore several fundamental aspects related to this novel nanotechnology and cell control. These include (1) design and study the effects of 3D extracellular architecture with multiple layers and cell entrance ports on cell movement, interaction, and connection; (2) develop reversal nanoimprint technology with UV, dual mold, hybrid mold, and suitable surface treatment for stacking multiple layers to form a 3D platform; (3) investigate effects of plasma exposure, thin film coating, biomolecule deposition, and nanostructure density on cytoskeleton and substrate interaction; and (4) control gradient of surface energy and biomolecule concentration by varying the nanometer-scale pattern density to produce cell guidance in a 3D matrix. The research team will carry out the design, development, nanofabrication, and evaluation of these critical issues.We expect to establish a novel nanotechnology to allow flexible design of 3D extracellular platform with controlled access paths for cell guidance, connections, and interactions. The knowledge developed in this project will provide an entirely new paradigm in nanotechnology and extracellular platform for advancement in artificial cellular microenvironment. We have the unique capability of precise customization of the extracellular matrix architecture and cell guidance function to promote new matrix synthesis for regeneration and repair.