title: Engineered 3D tissue models for cell-laden microfluidic channels.
abstract: Delivery of nutrients and oxygen within three-dimensional (3D) tissue constructs is important to maintain cell viability. We built 3D cell-laden hydrogels to validate a new tissue perfusion model that takes into account nutrition consumption. The model system was analyzed by simulating theoretical nutrient diffusion into cell-laden hydrogels. We carried out a parametric study considering different microchannel sizes and inter-channel separation in the hydrogel. We hypothesized that nutrient consumption needs to be taken into account when optimizing the perfusion channel size and separation. We validated the hypothesis by experiments. We fabricated circular microchannels (r = 400 microm) in 3D cell-laden hydrogel constructs (R = 7.5 mm, volume = 5 ml). These channels were positioned either individually or in parallel within hydrogels to increase nutrient and oxygen transport as a way to improve cell viability. We quantified the spatial distribution of viable cells within 3D hydrogel scaffolds without channels and with single- and dual-perfusion microfluidic channels. We investigated quantitatively the cell viability as a function of radial distance from the channels using experimental data and mathematical modeling of diffusion profiles. Our simulations show that a large-channel radius as well as a large channel to channel distance diffuse nutrients farther through a 3D hydrogel. This is important since our results reveal that there is a close correlation between nutrient profiles and cell viability across the hydrogel.
authors.affiliation: Bio-Acoustic-MEMS in Medicine Lab, HST Center for Bioengineering, Brigham and Women's Hospital, Harvard Medical School, 65 Landsdowne Street #252, Cambridge, MA 02139, USA.
authors.forename: Young S
authors.initials: YS
authors.lastname: Song
authors.forename: Richard L
authors.initials: RL
authors.lastname: Lin
authors.forename: Grace
authors.initials: G
authors.lastname: Montesano
authors.forename: Naside G
authors.initials: NG
authors.lastname: Durmus
authors.forename: Grace
authors.initials: G
authors.lastname: Lee
authors.forename: Seung-Schik
authors.initials: SS
authors.lastname: Yoo
authors.forename: Emre
authors.initials: E
authors.lastname: Kayaalp
authors.forename: Edward
authors.initials: E
authors.lastname: Haeggström
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
authors.forename: Utkan
authors.initials: U
authors.lastname: Demirci
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002470:Cell Survival; D002477:Cells; D005502:Food; D020100:Hydrogels; D051379:Mice; D044085:Microfluidics / Q000295:instrumentation / Q000379:methods*; D010100:Oxygen; D010477:Perfusion; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D020100:Hydrogels; D010100:Oxygen