Direct laser writing to enable fundamental cell studies

Abstract

Over the last few decades, stereolithography has emerged as a leading additive manufacturing technique. More recently, a high-resolution (sub-micron) variant, direct laser writing (DLW) via two-photon polymerization (TPP), has become available. This advanced fabrication technique can be used to produce complex 3D microstructures out of polymer-based materials ranging from hydrogels to standard photoresists. It is a powerful prototyping method that enables researchers to iterate through many different designs that would otherwise be challenging to make using any other fabrication method. DLW is a particularly attractive approach for producing structures that can be used in tissue engineering studies because it provides the necessary resolution to explore the complicated relationships between cells and their surroundings. The structure of the cellular microenvironment is a critical component of healthy tissue function, but fabrication limitations often constrain researchers in their ability to study it with a high degree of design control.

The use of DLW to produce testbeds for fundamental cell studies is presented. Important considerations for fabricating testbed structures, such as interfacing between different materials and printing substrates, are addressed. Methods to introduce softness in structures made from intrinsically stiff materials are explored through incorporation of unique design features and variable fabrication parameters. To test the efficacy of using DLW in cell studies, devices are fabricated for monitoring endothelial cell migration over topographically complex surfaces. Finally, a microfluidic-based platform for studying cardiomyocyte behavior is designed and tested.