title: Enzymatic Crosslinking of Polymer Conjugates is Superior over Ionic or UV Crosslinking for the On-Chip Production of Cell-Laden Microgels.
abstract: Cell-laden micrometer-sized hydrogels (microgels) hold great promise for improving high throughput ex-vivo drug screening and engineering biomimetic tissues. Microfluidics is a powerful tool to produce microgels. However, only a limited amount of biomaterials have been reported to be compatible with on-chip microgel formation. Moreover, these biomaterials are often associated with mechanical instability, cytotoxicity, and cellular senescence. To resolve this challenge, dextran-tyramine has been explored as a novel biomaterial for on-chip microgel formation. In particular, dextran-tyramine is compared with two commonly used biomaterials, namely, polyethylene-glycol diacrylate (PEGDA) and alginate, which crosslink through enzymatic reaction, UV polymerization, and ionic interaction, respectively. Human mesenchymal stem cells (hMSCs) encapsulated in dextran-tyramine microgels demonstrate significantly higher (95%) survival as compared to alginate (81%) and PEGDA (69%). Long-term cell cultures demonstrate that hMSCs in PEGDA microgels become senescent after 7 d. Alginate microgels dissolve within 7 d due to Ca2+loss. In contrast, dextran-tyramine based microgels remain stable, sustain hMSCs metabolic activity, and permit for single-cell level analysis for at least 28 d of culture. In conclusion, enzymatically crosslinking dextran-tyramine conjugates represent a novel biomaterial class for the on-chip production of cell-laden microgels, which possesses unique advantages as compared to the commonly used UV and ionic crosslinking biomaterials.
authors.affiliation: Department of Developmental BioEngineering, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, P.O. Box 217, 7500AE, Enschede, The Netherlands.
authors.forename: Sieger
authors.initials: S
authors.lastname: Henke
authors.affiliation: Department of Developmental BioEngineering, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, P.O. Box 217, 7500AE, Enschede, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Leijten
authors.affiliation: BIOS Lab on a Chip group, MESA + Institute for Nanotechnology, University of Twente, P.O. Box 217, 7500AE, Enschede, The Netherlands.
authors.forename: Evelien
authors.initials: E
authors.lastname: Kemna
authors.affiliation: Department of Physical Chemistry II, University of Bayreuth, Universitätsstrasse 30, 95447, Bayreuth, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Neubauer
authors.affiliation: Leibniz Institut für Polymerforschung Dresden e.V. (Leibniz Institute of Polymer Research Dresden), Institute of Physical Chemistry and Polymer Physics, Hohe Str. 6, 1079, Dresden, Germany.|Chair of Physical Chemistry of Polymeric Materials, Technische Universität Dresden, 1079, Dresden, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fery
authors.affiliation: BIOS Lab on a Chip group, MESA + Institute for Nanotechnology, University of Twente, P.O. Box 217, 7500AE, Enschede, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: van den Berg
authors.affiliation: Department of Developmental BioEngineering, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, P.O. Box 217, 7500AE, Enschede, The Netherlands.
authors.forename: Aart
authors.initials: A
authors.lastname: van Apeldoorn
authors.affiliation: Department of Developmental BioEngineering, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, P.O. Box 217, 7500AE, Enschede, The Netherlands. h.b.j.karperien@utwente.nl.
authors.forename: Marcel
authors.initials: M
authors.lastname: Karperien
mesh_terms: D000464:Alginates / Q000737:chemistry*; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D018914:Cells, Immobilized / Q000166:cytology / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000737:chemistry*; D005782:Gels; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D056656:Lab-On-A-Chip Devices; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013997:Time Factors
chemical_list: D000464:Alginates; D003432:Cross-Linking Reagents; D005782:Gels; D006603:Hexuronic Acids; D011092:Polyethylene Glycols; D020723:Glucuronic Acid
keywords: biomaterials; enzymatic; hydrogel; microfluidic; microgels