title: Diffusion-mediated in situ alginate encapsulation of cell spheroids using microscale concave well and nanoporous membrane.
abstract: Here, we present a novel and simple process of spheroid formation and in situ encapsulation of the formed spheroid without intervention. A hemispherical polydimethylsiloxane (PDMS) micromold was employed for the formation of uniform sized spheroids and two types of nano-porous membrane were used for the control of the crosslinking agent. We characterized the transport properties of the membrane, and the selection of alginate hydrogel as a function of gelation time, alginate concentration, and membrane type. Using the developed process and micromold, HepG2 cell spheroids were successfully formed and encapsulated in alginate without replating. This method allows spheroid encapsulation with minimal damage to the spheroid while maintaining high cell viability. We demonstrate the feasibility of this method in developing a bio-artificial liver (BAL) chip by evaluating viability and function of encapsulated HepG2 spheroids. This method may be applied to the encapsulation of several aggregating cell types, such as β-cells for islet formation and stem cells for embryonic body preservation, or as a model for tumor cell growth and proliferation in a 3D hydrogel environment.
authors.affiliation: Department of Biomedical Engineering, College of Health Science, Korea University, Seoul, Korea.
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Da Yoon
authors.initials: da Y
authors.lastname: No
authors.forename: Su-Hwan
authors.initials: SH
authors.lastname: Kim
authors.forename: Ji Hee
authors.initials: JH
authors.lastname: Ryoo
authors.forename: Sau Fung
authors.initials: SF
authors.lastname: Wong
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000464:Alginates / Q000737:chemistry*; D004058:Diffusion; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D056945:Hep G2 Cells; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D036103:Nanotechnology; D016062:Porosity; D018874:Spheroids, Cellular
chemical_list: D000464:Alginates; D004129:Dimethylpolysiloxanes; D006603:Hexuronic Acids; D020100:Hydrogels; C013830:baysilon; D020723:Glucuronic Acid