Bioorthogonally Cross‐Linked Hyaluronan–Laminin Hydrogels for 3D Neuronal Cell Culture and Biofabrication

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  • Michael Jury
    Laboratory of Molecular Materials Division of Biophysics and Bioengineering Department of Physics, Chemistry and Biology Linköping University Linköping 581 83 Sweden
  • Isabelle Matthiesen
    Division of Micro and Nanosystems KTH Royal Institute of Technology Stockholm 100 44 Sweden
  • Fatemeh Rasti Boroojeni
    Laboratory of Molecular Materials Division of Biophysics and Bioengineering Department of Physics, Chemistry and Biology Linköping University Linköping 581 83 Sweden
  • Saskia L. Ludwig
    Division of Micro and Nanosystems KTH Royal Institute of Technology Stockholm 100 44 Sweden
  • Livia Civitelli
    Laboratory of Molecular Materials Division of Biophysics and Bioengineering Department of Physics, Chemistry and Biology Linköping University Linköping 581 83 Sweden
  • Thomas E. Winkler
    Division of Micro and Nanosystems KTH Royal Institute of Technology Stockholm 100 44 Sweden
  • Robert Selegård
    Laboratory of Molecular Materials Division of Biophysics and Bioengineering Department of Physics, Chemistry and Biology Linköping University Linköping 581 83 Sweden
  • Anna Herland
    Division of Micro and Nanosystems KTH Royal Institute of Technology Stockholm 100 44 Sweden
  • Daniel Aili
    Laboratory of Molecular Materials Division of Biophysics and Bioengineering Department of Physics, Chemistry and Biology Linköping University Linköping 581 83 Sweden

書誌事項

公開日
2022-02-20
権利情報
  • http://creativecommons.org/licenses/by/4.0/
DOI
  • 10.1002/adhm.202102097
公開者
Wiley

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説明

<jats:title>Abstract</jats:title> <jats:p>Laminins (LNs) are key components in the extracellular matrix of neuronal tissues in the developing brain and neural stem cell niches. LN‐presenting hydrogels can provide a biologically relevant matrix for the 3D culture of neurons toward development of advanced tissue models and cell‐based therapies for the treatment of neurological disorders. Biologically derived hydrogels are rich in fragmented LN and are poorly defined concerning composition, which hampers clinical translation. Engineered hydrogels require elaborate and often cytotoxic chemistries for cross‐linking and LN conjugation and provide limited possibilities to tailor the properties of the materials. Here a modular hydrogel system for neural 3D cell cultures, based on hyaluronan and poly(ethylene glycol), that is cross‐linked and functionalized with human recombinant LN‐521 using bioorthogonal copper‐free click chemistry, is shown. Encapsulated human neuroblastoma cells demonstrate high viability and grow into spheroids. Long‐term neuroepithelial stem cells (lt‐NES) cultured in the hydrogels can undergo spontaneous differentiation to neural fate and demonstrate significantly higher viability than cells cultured without LN. The hydrogels further support the structural integrity of 3D bioprinted structures and maintain high viability of bioprinted and syringe extruded lt‐NES, which can facilitate biofabrication and development of cell‐based therapies.</jats:p>

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