title: 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) than on 10% (w/v) hydrogel-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.
authors.affiliation: Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, Massachusetts 02139, USA.
authors.forename: Nasim
authors.initials: N
authors.lastname: Annabi
authors.forename: Šeila
authors.initials: Š
authors.lastname: Selimović
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Acevedo Cox
authors.forename: João
authors.initials: J
authors.lastname: Ribas
authors.forename: Mohsen
authors.initials: M
authors.lastname: Afshar Bakooshli
authors.forename: Déborah
authors.initials: D
authors.lastname: Heintze
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Weiss
authors.forename: Donald
authors.initials: D
authors.lastname: Cropek
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D004548:Elasticity; D005780:Gelatin / Q000494:pharmacology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D018613:Microscopy, Confocal; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014333:Tropoelastin / Q000494:pharmacology; D019210:Troponin I / Q000378:metabolism
chemical_list: D004129:Dimethylpolysiloxanes; D014333:Tropoelastin; D019210:Troponin I; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C013830:baysilon; D005780:Gelatin