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WEB Microfluidic generation of UV cross-linkable Poly(2-oxazoline)-based Microgels

3D-printing of living cells with a reproducible high cell survival and high resolution is still a challenge in the biofabrication field. Due to the substantial shear forces during many high-resolution printing processes, which can negatively impact cell viability, an additional cellular protection is needed. A possible way to improve cell survival, cell viability and expand the biofabrication window towards higher resolution is the encapsulation of cells in microgels as protective coatings. This can be achieved via microfluidics of in situ cross-linking polymers, which form mechanically stable hydrogels.[1] In this study, we prepared POx-based microgels of controlled size via UV mediated thiol-ene reaction using a custom-build microfluidic setup.

Poly(2-oxazoline)s are ideal synthetic polymers for this application, because of several promising properties, such as their excellent biocompatibility and synthetic availability, while providing easy opportunities for a functionalization of their side chains and both termini to control cross-linking degree and substitution of the obtained microgels.[2] A appropriate modification of the side chains with free thiol groups allows covalent cross-linking of individual polymer chains to non-degradable hydrogel networks with adjustable mechanical stabilities. The hydrogels were formed via thiol-ene reaction between thiol functionalized POx-based polymers and others carrying reactive vinyl functions.

The two polymers were subsequently combined in a custom-designed microfluidic chip, which allowed the production of droplets of varying sizes with high uniformity. For the in situ cross-linking of the hydrogel precursor solution, low concentrations (0.05 to 0.1 %) of a UV sensitive photo initiator (Iragcure 2959) were added to the polymer solution. The prepared microgel droplets could be stably cross-linked both afterwards or directly on the microfluidic chip to avoid coalescence or complete phase separation. These microgels will be applied to encapsulate cells and after washing and jamming the microgels beads will be used as particulate bioink for extrusion-based 3D-printing. In future studies the POx-based microgels might be cross-linked with other biologically active compounds, like peptides or thiolated biopolymers, to achieve cell carriers also providing biological functions to the encapsulated cells.

[1] E. Tumarkin, et al., Chem. Soc. Rev. 2009, 38, 2161.

[2] B. Verbraeken, et al., Eur. Polym. J. 2017, 88, 451.

Ilona Paulus
University Hospital Würzburg
Additional Authors:
  • Benjamin Reineke
    Forschungszentrum Jülich GmbH
  • Johannes Herbig
  • Dr. Julia Liebscher
  • Dr. Stephan Hauschild
    Forschungszentrum Jülich GmbH
  • Dr. Jörg Teßmar
    University Hospital Würzburg
  • Prof. Dr. Stephan Förster
    Forschungszentrum Jülich GmbH
  • Prof. Dr. Jürgen Groll
    University Hospital Würzburg