title: Fabrication of a live cell-containing multilayered polymer hydrogel membrane with micrometer-scale thickness to evaluate pharmaceutical activity.
abstract: We propose a spinning-assisted layer-by-layer method for simple fabrication of a multilayered polymer hydrogel membrane that contains living cells. Hydrogel formation occurred based on the spontaneous cross-linking reaction between two polymers in aqueous solution. A water-soluble 2-methacryloyloxyethyl phosphorylcholine polymer bearing phenylboronic acid groups (PMBV) and poly(vinyl alcohol) (PVA) were used as polymers for hydrogel membrane formation. Changing the number of hydrogel membrane layers, polymer concentration, spinning rate, and processing time for diffusion-dependent gelation of PMBV and PVA facilitated the regulation of the multilayered polymer hydrogel membrane thickness and morphology. We concluded that a multilayered polymer hydrogel membrane prepared using 5.0 wt% PMBV and 5.0 wt% PVA at a spinning rate of 2000 rpm was suitable for precise spatial control of cells in single layers. This multilayered polymer hydrogel membrane was used to prepare a single cell-laden layer to minimize barriers to the diffusion of bioactive compounds while preserving the three-dimensional (3-D) context. The pharmaceutical effects of one of the anticancer agents, paclitaxel, on a human cervical cancer line, HeLa cells, were evaluated in vitro, and the usability of this culture model was demonstrated.
authors.affiliation: a Department of Materials Engineering, School of Engineering , The University of Tokyo ,7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656 , Japan.
authors.forename: Botao
authors.initials: B
authors.lastname: Gao
authors.affiliation: b Department of Bioengineering, School of Engineering , The University of Tokyo ,7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656 , Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Konno
authors.affiliation: a Department of Materials Engineering, School of Engineering , The University of Tokyo ,7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656 , Japan.|b Department of Bioengineering, School of Engineering , The University of Tokyo ,7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656 , Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ishihara
mesh_terms: D000180:Acrylic Resins / Q000138:chemical synthesis* / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001897:Boronic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D004058:Diffusion; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation* / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis* / Q000737:chemistry; D008422:Materials Testing; D015394:Molecular Structure; D017239:Paclitaxel / Q000494:pharmacology; D011142:Polyvinyl Alcohol / Q000138:chemical synthesis* / Q000737:chemistry; D054457:Tissue Scaffolds / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D000180:Acrylic Resins; D000972:Antineoplastic Agents, Phytogenic; D001897:Boronic Acids; D020100:Hydrogels; C000604946:poly(2-methacyloyloxyethyl phosphorylcholine-co-n-butyl methacrylate-co-p-vinylphenylboronic acid); D014867:Water; D011142:Polyvinyl Alcohol; D017239:Paclitaxel
keywords: 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer; cell encapsulation; layer-by-layer (LbL) assembly process; multilayered polymer hydrogel; three-dimensional cell culture