title: Synthesis of Cell-Adhesive Anisotropic Multifunctional Particles by Stop Flow Lithography and Streptavidin-Biotin Interactions.
abstract: Cell-adhesive particles are of significant interest in biotechnology, the bioengineering of complex tissues, and biomedical research. Their applications range from platforms to increase the efficiency of anchorage-dependent cell culture to building blocks to loading cells in heterogeneous structures to clonal-population growth monitoring to cell sorting. Although useful, currently available cell-adhesive particles can accommodate only homogeneous cell culture. Here, we report the design of anisotropic hydrogel microparticles with tunable cell-adhesive regions as first step toward micropatterned cell cultures on particles. We employed stop flow lithography (SFL), the coupling reaction between amine and N-hydroxysuccinimide (NHS) and streptavidin-biotin chemistry to adjust the localization of conjugated collagen and poly-L-lysine on the surface of microscale particles. Using the new particles, we demonstrate the attachment and formation of tight junctions between brain endothelial cells. We also demonstrate the geometric patterning of breast cancer cells on particles with heterogeneous collagen coatings. This new approach avoids the exposure of cells to potentially toxic photoinitiators and ultraviolet light and decouples in time the microparticle synthesis and the cell culture steps to take advantage of the most recent advances in cell patterning available for traditional culture substrates.
authors.affiliation: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School , Charlestown, Massachusetts 02129, United States.|Department of Chemical and Biological Engineering, Korea University , Anam-dong, Seongbuk-gu, Seoul 136-713, Korea.
authors.forename: Ki Wan
authors.initials: KW
authors.lastname: Bong
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Jae Jung
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School , Charlestown, Massachusetts 02129, United States.
authors.forename: Hansang
authors.initials: H
authors.lastname: Cho
authors.affiliation: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School , Charlestown, Massachusetts 02129, United States.
authors.forename: Eugene
authors.initials: E
authors.lastname: Lim
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Doyle
authors.affiliation: Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School , Charlestown, Massachusetts 02129, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Irimia
mesh_terms: D016880:Anisotropy; D001710:Biotin / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D019809:Streptavidin / Q000737:chemistry*; D013388:Succinimides / Q000737:chemistry
chemical_list: D013388:Succinimides; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D001710:Biotin; D019809:Streptavidin; C001426:N-hydroxysuccinimide