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Article

Microfluidic Fabrication of Click Chemistry-Mediated Hyaluronic Acid Microgels: A Bottom-Up Material Guide to Tailor a Microgel’s Physicochemical and Mechanical Properties

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Institute of Physical Chemistry and Polymer Physics, Leibniz-Institut für Polymerforschung Dresden e. V., 01069 Dresden, Germany
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Center for Innovation Competence: Humoral Immune Reactions in Cardiovascular Disorders, University of Greifswald, Fleischmannstr. 42, 17489 Greifswald, Germany
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German Center for Cardiovascular Research e. V., University Medicine Greifswald, Fleischmannstr. 42, 17489 Greifswald, Germany
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Clinic for Internal Medicine B, University Medicine Greifswald, Fleischmannstr. 8, 17475 Greifswald, Germany
*
Author to whom correspondence should be addressed.
Polymers 2020, 12(8), 1760; https://doi.org/10.3390/polym12081760
Received: 17 July 2020 / Revised: 29 July 2020 / Accepted: 29 July 2020 / Published: 6 August 2020
(This article belongs to the Special Issue Polymer Material Design by Microfluidics)
The demand for tailored, micrometer-scaled biomaterials in cell biology and (cell-free) biotechnology has led to the development of tunable microgel systems based on natural polymers, such as hyaluronic acid (HA). To precisely tailor their physicochemical and mechanical properties and thus to address the need for well-defined microgel systems, in this study, a bottom-up material guide is presented that highlights the synergy between highly selective bio-orthogonal click chemistry strategies and the versatility of a droplet microfluidics (MF)-assisted microgel design. By employing MF, microgels based on modified HA-derivates and homobifunctional poly(ethylene glycol) (PEG)-crosslinkers are prepared via three different types of click reaction: Diels–Alder [4 + 2] cycloaddition, strain-promoted azide-alkyne cycloaddition (SPAAC), and UV-initiated thiol–ene reaction. First, chemical modification strategies of HA are screened in-depth. Beyond the microfluidic processing of HA-derivates yielding monodisperse microgels, in an analytical study, we show that their physicochemical and mechanical properties—e.g., permeability, (thermo)stability, and elasticity—can be systematically adapted with respect to the type of click reaction and PEG-crosslinker concentration. In addition, we highlight the versatility of our HA-microgel design by preparing non-spherical microgels and introduce, for the first time, a selective, hetero-trifunctional HA-based microgel system with multiple binding sites. As a result, a holistic material guide is provided to tailor fundamental properties of HA-microgels for their potential application in cell biology and (cell-free) biotechnology. View Full-Text
Keywords: hyaluronic acid microgels; bio-orthogonal click chemistry; droplet microfluidics; trifunctionality hyaluronic acid microgels; bio-orthogonal click chemistry; droplet microfluidics; trifunctionality
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MDPI and ACS Style

Heida, T.; Otto, O.; Biedenweg, D.; Hauck, N.; Thiele, J. Microfluidic Fabrication of Click Chemistry-Mediated Hyaluronic Acid Microgels: A Bottom-Up Material Guide to Tailor a Microgel’s Physicochemical and Mechanical Properties. Polymers 2020, 12, 1760. https://doi.org/10.3390/polym12081760

AMA Style

Heida T, Otto O, Biedenweg D, Hauck N, Thiele J. Microfluidic Fabrication of Click Chemistry-Mediated Hyaluronic Acid Microgels: A Bottom-Up Material Guide to Tailor a Microgel’s Physicochemical and Mechanical Properties. Polymers. 2020; 12(8):1760. https://doi.org/10.3390/polym12081760

Chicago/Turabian Style

Heida, Thomas, Oliver Otto, Doreen Biedenweg, Nicolas Hauck, and Julian Thiele. 2020. "Microfluidic Fabrication of Click Chemistry-Mediated Hyaluronic Acid Microgels: A Bottom-Up Material Guide to Tailor a Microgel’s Physicochemical and Mechanical Properties" Polymers 12, no. 8: 1760. https://doi.org/10.3390/polym12081760

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