A Gal-MµS Device to Evaluate Cell Migratory Response to Combined Galvano-Chemotactic Fields

Abstract

Electric fields have been studied extensively in biomedical engineering (BME) for numerous regenerative therapies. Recent studies have begun to examine the biological effects of electric fields in combination with other environmental cues, such as tissue-engineered extracellular matrices (ECM), chemical gradient profiles, and time-dependent temperature gradients. In the nervous system, cell migration driven by electrical fields, or galvanotaxis, has been most recently studied in transcranial direct stimulation (TCDS), spinal cord repair and tumor treating fields (TTF). The cell migratory response to galvano-combinatory fields, such as magnetic fields, chemical gradients, or heat shock, has only recently been explored. In the visual system, restoration of vision via cellular replacement therapies has been limited by low numbers of motile cells post-transplantation. Here, the combinatory application of electrical fields with other stimuli to direct cells within transplantable biomaterials and/or host tissues has been understudied. In this work, we developed the Gal-MµS device, a novel microfluidics device capable of examining cell migratory behavior in response to single and combinatory stimuli of electrical and chemical fields. The formation of steady-state, chemical concentration gradients and electrical fields within the Gal-MµS were modeled computationally and verified experimentally within devices fabricated via soft lithography. Further, we utilized real-time imaging within the device to capture cell trajectories in response to electric fields and chemical gradients, individually, as well as in combinatory fields of both. Our data demonstrated that neural cells migrated longer distances and with higher velocities in response to combined galvanic and chemical stimuli than to either field individually, implicating cooperative behavior. These results reveal a biological response to galvano-chemotactic fields that is only partially understood, as well as point towards novel migration-targeted treatments to improve cell-based regenerative therapies.

A Milled Microdevice to Advance Glia-Mediated Therapies in the Adult Nervous System

“…Microsystems used for the quantitative scrutiny of neuroglia by creating chemical, electrical, and physical stimulation are underexplored. Microfluidic systems used for neuroglia applications remain surprisingly scarce despite their ability to facilitate characterization of glia responses to customized biomaterials [29], pharmacological compounds [30], and electro-chemical fields currently being explored to aid neurorepair [31]. While a slower adaptation of microsystems may be attributed to the high costs associated with clean room facilities [32] and/or the perceived need for engineering expertise to design and troubleshoot complex systems [33], the rising availability of fabrication techniques such as 3D printing/rapid prototyping [34], paper microfluidics [35,36], and toner or inkjet printing [37,38] have greatly reduced the barriers to entry in the usage of larger microscale tools (reviewed in [39]).…”

Microfluidic and Microscale Assays to Examine Regenerative Strategies in the Neuro Retina

“…The results illustrated that electric fields stimulated slightly larger migration distances than chemical fields, but with approximately the same directionality. However, stimulation from concurrent electric and chemical fields of SDF-1 resulted in five-fold increases in progenitor migratory distances and directionality of movement towards increasing gradients in the device [223], as per Figure 6. These novel results provided the first indication that combined fields can direct retinal progenitor migration very precisely, and have led the group to examine the combined use of these therapeutic fields in ex vivo models of inoculated eye [224].…”

Use Microfluidic Chips to Study the Phototaxis of Lung Cancer Cells

“…Cells cultured underneath this perfect-gradient region were observed to ensure optimal light gradient. The H-shaped microfluidic chips were commonly used in chemotaxis experiments [25,26]. Figure 1d shows the COMSOL simulation of Brilliant Blue FCF concentration inside an H-shaped chip with the same parameters and settings.…”