I-Corps: 3D Curvature-Defined Microenvironments for Cell and Tissue Culturing

细胞工程(干细胞技术和细胞分选)由于其在疾病诊断和治疗、组织工程和再生医学中的广泛和有前途的应用而受到越来越多的关注。细胞对三维微机械环境的行为响应近年来引起了人们的特别关注，因为体内细胞的环境本质上是三维的。与相应的二维微机械环境相比，三维微机械环境在设计、制造、表征和应用于卓有成效的细胞研究和应用方面具有更大的挑战性。细胞在其上生长的3D基质的曲率是该基质的主要几何参数之一，因此，创建曲率定义的3D细胞培养基质对于3D细胞机械生物学和生物工程是至关重要的。该团队发明了有史以来第一种独特而强大的3D曲率定义的细胞培养基质-微型玻璃球嵌入凝胶。这项技术为细胞和组织工程及其生物医学应用领域开辟了无数机会。NSF I-Corps Team项目的目标是启动这项新发明和专利技术的推广和商业化进程。在NSF I-Corps Teams项目中引入的细胞培养基质-微玻璃球嵌入凝胶为研究细胞和组织对基质曲率和局部硬度的机械生物学响应以及其他相关细胞和组织工程研究和生物医学应用提供了一个独特而有用的工具。具体地说，这项技术提供了有史以来第一个具有定义曲率的细胞培养基质。底物曲率效应是当前细胞和组织机械生物学和生物工程等前沿和非常热门的研究领域中的一个基本方面。这项技术还首次为细胞培养基质提供了定义的纳米到微米级的僵硬模式。这些衬底和用相同方法制备的类似衬底可以用于或扩展到任何其他涉及微纳米复合材料和界面现象的研究中。本项目中介绍的制备/制备微玻璃球嵌入凝胶的方法开启了一种新的策略，并对均匀或不均匀的规则或不规则形状(衬底)表面或阵列或图案或复合材料的微米和纳米制造具有变革性意义。

Cell engineering (stem cell technology and cell sorting) has been receiving increased attention due to its wide and promising applications in disease diagnosis and treatment, tissue engineering, and regenerative medicine. The behavioral responses of cells to three-dimensional (3D) micromechanical environments are of special interest in recent years because the environments of cells in vivo are 3D in nature. 3D micromechanical environments are much more challenging to design, fabricate, characterize, and apply for fruitful cell studies and applications compared with the corresponding two-dimensional (2D) ones. The curvature of a 3D substrate on which a cell will be growing is one of the major geometrical parameters of this substrate, and therefore, creating curvature-defined 3D cell culture substrates is crucial for 3D cell mechanobiology and bioengineering. This team has invented a first-ever unique and powerful class of 3D curvature-defined cell culture substrates - micro glass ball embedded gels. This technology opens up countless opportunities for the field of cell and tissue engineering and its biomedical applications. The objective of this NSF I-Corps Teams project is to start the process to promote and commercialize this newly-invented and patented technology.The class of cell culture substrates, micro glass ball embedded gels, introduced in this NSF I-Corps Teams project provides a unique and useful tool for studying cell and tissue mechanobiological responses to substrate curvatures and local stiffness, and for other related cell and tissue engineering researches and biomedical applications. Specifically, this technology provides the first-ever cell culture substrates with defined curvatures. The effect of substrate curvature is one of the fundamental aspects in the currently cutting-edge and very hot area of research: cell and tissue mechanobiology and bioengineering. This technology also provides the first-ever cell culture substrates with defined nanometer to micrometer scale stiffness patterns. These substrates and the similar ones prepared/fabricated by the same strategy can be used in or extended to any other studies involving micro- and nanocomposites and interfacial phenomena. The method, introduced in this project, to prepare/fabricate micro glass ball embedded gels, opens a new strategy and is transformative for micro- and nanofabrication of even or uneven regular or irregular shaped (substrate) surfaces or arrays or patterns or composites.