title: Process engineering of high voltage alginate encapsulation of mesenchymal stem cells.
abstract: Encapsulation of stem cells in alginate beads is promising as a sophisticated drug delivery system in treatment of a wide range of acute and chronic diseases. However, common use of air flow encapsulation of cells in alginate beads fails to produce beads with narrow size distribution, intact spherical structure and controllable sizes that can be scaled up. Here we show that high voltage encapsulation (≥ 15 kV) can be used to reproducibly generate spherical alginate beads (200-400 μm) with narrow size distribution (± 5-7%) in a controlled manner under optimized process parameters. Flow rate of alginate solution ranged from 0.5 to 10 ml/h allowed producing alginate beads with a size of 320 and 350 μm respectively, suggesting that this approach can be scaled up. Moreover, we found that applied voltages (15-25 kV) did not alter the viability and proliferation of encapsulated mesenchymal stem cells post-encapsulation and cryopreservation as compared to air flow. We are the first who employed a comparative analysis of electro-spraying and air flow encapsulation to study the effect of high voltage on alginate encapsulated cells. This report provides background in application of high voltage to encapsulate living cells for further medical purposes. Long-term comparison and work on alginate-cell interaction within these structures will be forthcoming.
authors.affiliation: Institute for Multiphase Processes, Leibniz University Hannover, D-30167 Hannover, Germany. Electronic address: gryshkov@imp.uni-hannover.de.
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Gryshkov
authors.affiliation: Institute for Multiphase Processes, Leibniz University Hannover, D-30167 Hannover, Germany. Electronic address: pogozhykh@imp.uni-hannover.de.
authors.forename: Denys
authors.initials: D
authors.lastname: Pogozhykh
authors.affiliation: Institute for Multiphase Processes, Leibniz University Hannover, D-30167 Hannover, Germany. Electronic address: zernetsch@imp.uni-hannover.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Zernetsch
authors.affiliation: Institute for Multiphase Processes, Leibniz University Hannover, D-30167 Hannover, Germany. Electronic address: hofmann@imp.uni-hannover.de.
authors.forename: Nicola
authors.initials: N
authors.lastname: Hofmann
authors.affiliation: Institute for Transfusion Medicine, Medical School Hannover, D-30625 Hannover, Germany. Electronic address: mueller.thomas@mh-hannover.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mueller
authors.affiliation: Institute for Multiphase Processes, Leibniz University Hannover, D-30167 Hannover, Germany. Electronic address: glasmacher@imp.uni-hannover.de.
authors.forename: Birgit
authors.initials: B
authors.lastname: Glasmacher
mesh_terms: D000464:Alginates / Q000494:pharmacology*; D000818:Animals; D002144:Callithrix; D018929:Cell Culture Techniques / Q000379:methods*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018914:Cells, Immobilized / Q000166:cytology / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000737:chemistry; D015925:Cryopreservation; D004560:Electricity; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008863:Microspheres; D010316:Particle Size; D012212:Rheology / Q000187:drug effects; D012996:Solutions
chemical_list: D000464:Alginates; D003432:Cross-Linking Reagents; D006603:Hexuronic Acids; D012996:Solutions; D020723:Glucuronic Acid
keywords: AF; Alginate encapsulation; ES; Electro-spraying; High voltage; MSCs; Mesenchymal stem cells; RGD; SPM; Scaling up; Spherical beads; WS; air-flow; arginylglycylaspartic acid; electro-spraying; mesenchymal stem cells; semi-permeable membrane; washing solution