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Production of hyaluronic‐acid‐based cell‐enclosing microparticles and microcapsules via enzymatic reaction using a microfluidic system
Authors:Mehdi Khanmohammadi  Shinji Sakai  Tomoaki Ashida  Masahito Taya
Abstract:This article describes the preparation of cell‐enclosing hyaluronic acid (HA) microparticles with solid core and microcapsules with liquid core through cell‐friendly horseradish peroxidase (HRP)‐catalyzed hydrogelation. The spherical vehicles were made from HA derivative possessing phenolic hydroxyl moieties (HA‐Ph) cross‐linkable through the enzymatic reaction by extruding cell‐suspending HA‐Ph aqueous solution containing HRP from a needle of 180 μm in inner diameter into the ambient coaxial flow of liquid paraffin containing H2O2 in a microtubule of 600 μm in diameter. By altering the flow rate of liquid paraffin, the diameters of gelatin and HA‐Ph microparticles were varied in the range of 120–220 μm and 100–300 μm, respectively. The viability of the enclosed human hepatoma HepG2 cells in the HA‐Ph microparticles of 180 μm in diameter was 94.2 ± 2.3%. The growth of the enclosed HepG2 cells was enhanced by decreasing the HRP concentration. The microcapsules of 200 μm in diameter were obtained by extruding HA‐Ph aqueous solution containing thermally liquefiable cell‐enclosing gelatin microparticles of 150 μm in diameter using the same microfluidic system. The enclosed cells grew and filled the cavity within 10 days. Spherical tissues covered with a heterogeneous cell layer were obtained by degrading the microcapsule membrane using hyaluronidase after covering the surface with a heterogeneous cell layer. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43107.
Keywords:biocompatibility  biodegradable  biomedical applications  cross‐linking
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