title: Facile and rapid generation of 3D chemical gradients within hydrogels for high-throughput drug screening applications.
abstract: We propose a novel application of dielectrophoresis (DEP) to make three-dimensional (3D) methacrylated gelatin (GelMA) hydrogels with gradients of micro- and nanoparticles. DEP forces were able to manipulate micro- and nanoparticles of different sizes and materials (i.e., C2C12 myoblasts, polystyrene beads, gold microparticles, and carbon nanotubes) within GelMA hydrogels in a rapid and facile way and create 3D gradients of these particles in a microchamber. Immobilization of drugs, such as fluorescein isothiocyanate-dextran (FITC-dextran) and 6-hydroxydopamine (6-OHDA), on gold microparticles allowed us to investigate the high-throughput release of these drugs from GelMA-gold microparticle gradient systems. The latter gradient constructs were incubated with C2C12 myoblasts for 24h to examine the cell viability through the release of 6-OHDA. The drug was released from the microparticles in a gradient manner, inducing a cell viability gradient. This novel approach to create 3D chemical gradients within hydrogels is scalable to any arbitrary length scale. It is useful for making anisotropic biomimetic materials and high-throughput platforms to investigate cell-microenvironment interactions in a rapid, simple, cost-effective, and reproducible manner.
authors.affiliation: WPI-Advanced Institute for Materials Research, Tohoku University, P. O. Box 980-8577, Sendai, Japan.
authors.forename: Samad
authors.initials: S
authors.lastname: Ahadian
authors.affiliation: WPI-Advanced Institute for Materials Research, Tohoku University, P. O. Box 980-8577, Sendai, Japan. Electronic address: javier@bioinfo.che.tohoku.ac.jp.
authors.forename: Javier
authors.initials: J
authors.lastname: Ramón-Azcón
authors.affiliation: International Center for Young Scientists (ICYS), National Institute for Materials Science (NIMS), Tsukuba 305-0047, Japan.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Estili
authors.affiliation: Graduate School of Environmental Studies, Tohoku University, P. O. Box 980-8579, Sendai, Japan.
authors.forename: Raquel
authors.initials: R
authors.lastname: Obregón
authors.affiliation: Graduate School of Environmental Studies, Tohoku University, P. O. Box 980-8579, Sendai, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shiku
authors.affiliation: WPI-Advanced Institute for Materials Research, Tohoku University, P. O. Box 980-8577, Sendai, Japan; Graduate School of Environmental Studies, Tohoku University, P. O. Box 980-8579, Sendai, Japan. Electronic address: matsue@bioinfo.che.tohoku.ac.jp.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Matsue
mesh_terms: D000818:Animals; D015374:Biosensing Techniques / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004586:Electrophoresis / Q000379:methods; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000737:chemistry; D057166:High-Throughput Screening Assays / Q000379:methods*; D020100:Hydrogels / Q000737:chemistry*; D051379:Mice; D016627:Oxidopamine / Q000737:chemistry / Q000494:pharmacology; D013565:Sympatholytics / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003911:Dextrans; D020100:Hydrogels; D013565:Sympatholytics; C015219:fluorescein isothiocyanate dextran; D016627:Oxidopamine; D016650:Fluorescein-5-isothiocyanate
keywords: Chemical gradients; Dielectrophoresis; Drug release; High-throughput; Hydrogels