User-friendly 3D bioassays with cell-containing hydrogel modules: narrowing the gap between microfluidic bioassays and clinical end-users' needs

Abstract

Cell-containing hydrogel modules as cell-hydrogel microunits for creating a physiologically relevant 3D in vivo-like microenvironment with multiple cell types and unique extracellular matrix (ECM) compositions facilitate long-term cell maintenance and bioassays. To date, there have been many important advances in microfluidic bioassays, which incorporate hydrogel scaffolds into surface-accessible microchambers, driven by the strong demand for the application of spatiotemporally defined biochemical stimuli to construct in vivo-like conditions and perform real-time imaging of cell-matrix interactions. In keeping with the trend of fostering collaborations among biologists, clinicians, and microfluidic engineers, it is essential to create a simpler approach for coupling cell-containing hydrogel modules and an automated bioassay platform in a user-friendly format. In this article, we review recent progress in hydrogel-incorporated microfluidics for long-term cell maintenance and discuss some of the simpler and user-friendly 3D bioassay techniques combined with cell-containing hydrogel modules that can be applied to mutually beneficial collaborations with non-engineers. We anticipate that this modular and user-friendly format interfaced with existing laboratory infrastructure will help address several clinical questions in ways that extend well beyond the current 2D cell-culture systems.

3D-printed microfluidic chips with patterned, cell-laden hydrogel constructs

“…The progress in commercially available, inexpensive, desktop 3D printing technologies and the increasing range of printable materials will further increase accessibility to advanced microfluidic technologies. 3D printing technology has the potential to significantly impact the way microfluidic devices are fabricated and ultimately make microfluidic technology more accessible to researchers in engineering as well as basic science and clinical fields [8].…”

“…Incorporation of these 3D constructs into microfluidic devices allows for continuous perfusion of nutrients as well as precise spatiotemporal control over delivery of signaling factors (such as biomolecule gradients) while maintaining the ability to image the cells in vitro [6]. Such technologies and their potential for the field of bioengineering have been reviewed in several articles [6][7][8].…”

“…However, in order to realize the full potential of 3D cellular cultures in microfluidics and ultimately foster wider adoption of this approach by biologists and clinicians, bioassay platforms must be designed to be user-friendly to lower the barrier to entry for these end users [8]. Here, we demonstrate the fabrication of microfluidic chips using desktop SLA and industrial inkjet-style 3D prototyping and integrate cell encapsulation in 3D hydrogel posts within the microfluidic channels.…”

Ex Vivo Tumor Culture Systems for Functional Drug Testing and Therapy Response Prediction

“…Recent progress in the cancer-on-chip field, specifically in hydrogel-incorporated microfluidics for long-term cell maintenance and exploitation of these culture devices for automated bioassay applications was reviewed by Lee et al . [77]. Specific microfluidics devices have been designed to study metastasis formation as well as personalized immunotherapy [78,79].…”

2.11 Polymers of Biological Origin ☆

“…150b, 151 Important advances have occurred on microfluidic bioassays, which incorporate hydrogel scaffolds into surfaceaccessible microchambers, driven by the strong demand for the application of spatiotemporally defined biochemical stimuli to construct in vivo-like conditions and perform real-time imaging of cell-matrix interactions. 152 One emerging use of microfluidic systems is the generation of shape-controlled hydrogels (i.e., microfibers, microparticles, and hydrogel building blocks) for various biological applications. 153 The diameters of the hollow and solid fibers can be manipulated by the flow rates.…”