Hydrogel-coated microfluidic channels for cardiomyocyte culture

Abstract

The research areas of tissue engineering and drug development have displayed increased interest in organ-on-a-chip studies, in which physiologically or pathologically relevant tissues can be engineered to test pharmaceutical candidates. Microfluidic technologies enable the control of the cellular microenvironment for these applications through the topography, size, and elastic properties of the microscale cell culture environment, while delivering nutrients and chemical cues to the cells through continuous media perfusion. Traditional materials used in the fabrication of microfluidic devices, such as poly(dimethylsiloxane) (PDMS), offer high fidelity and high feature resolution, but do not facilitate cell attachment. To overcome this challenge, we have developed a method for coating microfluidic channels inside a closed PDMS device with a cell-compatible hydrogel layer. We have synthesized photocrosslinkable gelatin and tropoelastin-based hydrogel solutions that were used to coat the surfaces under continuous flow inside 50 μm wide, straight microfluidic channels to generate a hydrogel layer on the channel walls. Our observation of primary cardiomyocytes seeded on these hydrogel layers showed preferred attachment as well as higher spontaneous beating rates on tropoelastin coatings compared to gelatin. In addition, cellular attachment, alignment and beating were stronger on 5 % (w/v) hydrogel-coated devices than on 10 % (w/v) gel-coated channels. Our results demonstrate that cardiomyocytes respond favorably to the elastic, soft tropoelastin culture substrates, indicating that tropoelastin-based hydrogels may be a suitable coating choice for some organ-on-a-chip applications. We anticipate that the proposed hydrogel coating method and tropoelastin as a cell culture substrate may be useful for the generation of elastic tissues, e.g. blood vessels, using microfluidic approaches.

Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels

“…The thickness of the GelMA coating could be adjusted by varying the feeding flow rate, the intensity of the UV light, and/or the concentration of the GelMA prepolymer solution. Moreover, GelMA precursor and cells can be mixed to fabricate microchannels coated with cell-laden GelMA hydrogels [60]. …”

From cardiac tissue engineering to heart-on-a-chip: beating challenges

“…4, E and F). Particularly, they found that MeTro coating of microfluidic channels significantly improved adhesion and spontaneous beating of cardiomyocytes compared to surface treatment by gelatin-based materials [150]. …”

Heart-on-a-chip based on stem cell biology

“…Heart models in microsystems presented in literature allow research on the single cells level (Kaneko et al, 2007, Ges et al, 2008, Murthy et al, 2006, Cheng et al, 2006, multicellular cultures (Nguyen et al, 2009, Nguyen et al, 2015, Pong et al, 2011, Annabi et al, 2013, Ren et al, 2013, Grosberg et al, 2011 and 3D tissue tests (Huang et al, 2007b, Horiguchi et al, 2009, Cheah et al, 2010, Chen et al, 2013 (Table 1). These microsystems are more representative experimental models of the in vivo environment, than conventional culture dishes.…”