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景的应用而受到越来越多的关注。由于细胞在体内所处的环境本质上是三维的，因此细胞对三维微力学环境的行为响应近年来引起了人们的特别兴趣。与相应的二维（2D）微机械环境相比，3D微机械环境在设计、制造、表征和应用于富有成效的细胞研究和应用方面更具挑战性。细胞将在其上生长的3D基底的曲率是该基底的主要几何参数之一，因此，创建曲率限定的3D细胞培养基底对于3D细胞机械生物学和生物工程至关重要。该团队发明了有史以来第一个独特而强大的3D曲率定义细胞培养基质-微玻璃球嵌入凝胶。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的机会。NSF I-Corps Teams项目的目标是开始推广和商业化这一新发明和专利技术的过程。NSF I-Corps Teams项目中引入的细胞培养基质，微玻璃球包埋凝胶，为研究细胞和组织对基质曲率和局部刚度的机械生物学响应提供了独特而有用的工具，以及其他相关的细胞和组织工程研究和生物医学应用。具体而言，该技术提供了有史以来第一个具有限定曲率的细胞培养基质。基底曲率的影响是当前前沿和非常热门的研究领域：细胞和组织机械生物学和生物工程中的基本方面之一。该技术还提供了有史以来第一个具有确定的纳米至微米尺度刚度模式的细胞培养基质。这些基板和类似的制备/制造相同的策略可以用于或扩展到任何其他研究，涉及微米和纳米复合材料和界面现象。该项目中介绍的制备/制造嵌入微玻璃球的凝胶的方法，开辟了一种新的策略，并且对于均匀或不均匀的规则或不规则形状（基板）表面或阵列或图案或复合材料的微米和纳米纤维具有变革性。

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.