Cell-Based Microarrays Using Superhydrophobic Platforms Patterned with Wettable Regions.

The use of patterned platforms to print cellular arrays enables the high-throughput study of cell behavior under a multitude of different conditions. This rapid, cost-saving and systematic way of acquiring biologically relevant information has found application in diverse scientific and industrial fields. In an initial stage of development, platforms targeting high-throughput cellular studies were restricted to standard two-dimensional (2D) setups. The design of novel platforms compatible with three-dimensional (3D) cell culture arose after the elucidation of the extreme importance of culturing cells in matrices resembling the native extracellular matrix-cells and cell-cell interactions. This need for biomimetic environments has been established in fields like drug discovery and testing, disease model development, and regenerative medicine. Here, we provide a description of the processing of flat platforms based on wettability contrast, compatible with the high-throughput generation and study of cell response in 3D biomaterials, including cell-laden hydrogels and porous 3D scaffolds. The application of the aforementioned platforms to produce 3D microtissues, which may find application as tissue models for drug screening or as biomimetic building blocks for tissue engineering, is also addressed. In this chapter, a description of the steps for (1) high-throughput platform processing, (2) deposition of cell and biomaterial arrays, and (3) image-based results screening is provided.

[1]  Carmen Alvarez-Lorenzo,et al.  Superhydrophobic chips for cell spheroids high-throughput generation and drug screening. , 2014, ACS applied materials & interfaces.

[2]  João F Mano,et al.  Combinatorial cell-3D biomaterials cytocompatibility screening for tissue engineering using bioinspired superhydrophobic substrates. , 2012, Integrative biology : quantitative biosciences from nano to macro.

[3]  A. I. Neto,et al.  In vivo high-content evaluation of three-dimensional scaffolds biocompatibility. , 2014, Tissue engineering. Part C, Methods.

[4]  Ming-Rong Zhang,et al.  High-throughput screening with nanoimprinting 3D culture for efficient drug development by mimicking the tumor environment. , 2015, Biomaterials.

[5]  Richard O. Hynes,et al.  The Extracellular Matrix: Not Just Pretty Fibrils , 2009, Science.

[6]  João F Mano,et al.  High-throughput screening for integrative biomaterials design: exploring advances and new trends. , 2014, Trends in biotechnology.

[7]  Jeffrey A Hubbell,et al.  Biomaterials science and high-throughput screening , 2004, Nature Biotechnology.

[8]  A. Khademhosseini,et al.  Surface-tension-driven gradient generation in a fluid stripe for bench-top and microwell applications. , 2011, Small.

[9]  M. Lutolf,et al.  Artificial niche microarrays for probing single stem cell fate in high throughput , 2011, Nature Methods.

[10]  D. Bojanic,et al.  Impact of high-throughput screening in biomedical research , 2011, Nature Reviews Drug Discovery.

[11]  D. Pereira,et al.  Origin and evolution of high throughput screening , 2007, British journal of pharmacology.

[12]  A. I. Neto,et al.  High-throughput evaluation of interactions between biomaterials, proteins and cells using patterned superhydrophobic substrates , 2011 .

[13]  Robert Langer,et al.  High throughput methods applied in biomaterial development and discovery. , 2010, Biomaterials.

[14]  Lorenz M Mayr,et al.  The Future of High-Throughput Screening , 2008, Journal of biomolecular screening.

[15]  Todd C. McDevitt,et al.  Materials as stem cell regulators. , 2014, Nature materials.

[16]  Daniel G. Anderson,et al.  Nanoliter-scale synthesis of arrayed biomaterials and application to human embryonic stem cells , 2004, Nature Biotechnology.

[17]  Sara M. Oliveira,et al.  High‐Throughput Topographic, Mechanical, and Biological Screening of Multilayer Films Containing Mussel‐Inspired Biopolymers , 2016 .

[18]  S. Bhatia,et al.  An extracellular matrix microarray for probing cellular differentiation , 2005, Nature Methods.

[19]  Wenlong Song,et al.  Two-Dimensional Open Microfluidic Devices by Tuning the Wettability on Patterned Superhydrophobic Polymeric Surface , 2010 .

[20]  J. Enghild,et al.  Combinatorial Biomolecular Nanopatterning for High‐Throughput Screening of Stem‐Cell Behavior , 2016, Advanced materials.

[21]  S. Biswal,et al.  Wettability control and patterning of PDMS using UV-ozone and water immersion. , 2011, Journal of colloid and interface science.

[22]  Kristi S Anseth,et al.  Three-Dimensional High-Throughput Cell Encapsulation Platform to Study Changes in Cell-Matrix Interactions. , 2016, ACS applied materials & interfaces.

[23]  J. Mano,et al.  Combinatorial on-chip study of miniaturized 3D porous scaffolds using a patterned superhydrophobic platform. , 2013, Small.

[24]  Mark W. Tibbitt,et al.  High throughput screening for discovery of materials that control stem cell fate , 2016 .

[25]  Thomas C. Ferrante,et al.  A combinatorial cell-laden gel microarray for inducing osteogenic differentiation of human mesenchymal stem cells , 2014, Scientific Reports.

[26]  B Cox,et al.  Application of high-throughput screening techniques to drug discovery. , 2000 .

[27]  Hans-Joachim Böhm,et al.  A guide to drug discovery: Hit and lead generation: beyond high-throughput screening , 2003, Nature Reviews Drug Discovery.