61. MODULATION OF CELL-CELL AND CELL-SUBSTRATE INTERACTIONS TO CONTROL THE MORPHOLOGY OF PERFUSED 3D MULTICELLULAR CULTURES

Department: Bioengineering
Faculty Advisor(s): Shyni Varghese

Primary Student
Name: Nailah Makini Seale
Email: nseale@ucsd.edu
Phone: 858-822-7986
Grad Year: 2019

Student Collaborators
Lynn Theprungsirikul, lynn.thep@gmail.com

Abstract
The ability to control the composition of cells and their spatial organization in three-dimensions in vitro holds great promise in achieving more physiologically relevant tissues that can be used for disease modeling and drug testing. The combination of micro-photopatterning of photopolymerizable hydrogels and microfluidic technology allows us the ability to control the ?on-chip? suspension culture formation of perfusable multicellular spheroids. Utilizing these tools and manipulating the composition of biomaterials, we have demonstrated that the configuration of the cells can be controlled to achieve a desired morphology. Briefly, cocultures of human fibroblasts (HF) and HepG2 cells are combined in a prepolymer gelatin methacrylate (GelMA) and poly(ethylene glycol) diacrylate (PEGDA) solution (20 million cells/mL) and infused into a microfluidic device where photopatterning is used to trap the cells within a ring-like structure. By varying the ratio of GelMa: PEGDA in the prepolymer solution, as well as the seeding density of the cells we studied their impact on 3D culture morphology. Our results showed that a 1:1 ratio of GelMA:PEGDA (10% solution) facilitates HF movement (towards) and adhesion on the interior of the ring, while, the HepG2 cells form and grow as a spheroid in the center of the ring. Over time, a compartmentalized multicellular microtissue is formed with HF cells, which can function as an endothelial barrier, encasing the hepG2 spheroid. By comparing the spheroids formation from each hydrogel and cell density variation, our microstructure model could be useful for creating complex, yet convenient, microtissues within microfluidic devices.

Industry Application Area(s)
Life Sciences/Medical Devices & Instruments

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