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Related Experiment Video

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Printing and Rerouting of Elastic and Protease Responsive Shape Memory Hydrogel Filaments.

Philip Lifwergren1, Viktoria Schoen1, Sajjad Naeimipour1

  • 1Laboratory of Molecular Materials, Division of Biophysics and Bioengineering, Department of Physics, Chemistry, and Biology, Linköping University, Linköping, 583 81, Sweden.

Advanced Healthcare Materials
|June 20, 2025
PubMed
Summary

A new biofabrication strategy, REFRESH, creates robust, reconfigurable hydrogel filaments for advanced 3D constructs. This method overcomes limitations of traditional techniques, enabling complex tissue engineering applications.

Keywords:
3D bioprintingREFRESHfilamenthydrogeltubular structures

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Area of Science:

  • Biomaterials Engineering
  • Tissue Engineering
  • Biofabrication

Background:

  • Fabricating mechanically robust and reconfigurable hydrogel filaments is crucial for perfusable architectures and dynamic tissue models.
  • Conventional extrusion bioprinting yields fragile filaments, limiting scalability and post-processing options.

Purpose of the Study:

  • To introduce a novel biofabrication strategy, Rerouting of Free-Floating Suspended Hydrogel Filaments (REFRESH), to overcome limitations in hydrogel filament fabrication.
  • To enable the creation of mechanically robust, reconfigurable, and cell-compatible hydrogel filaments for advanced biofabrication.

Main Methods:

  • Developed REFRESH strategy integrating an aqueous two-phase system (ATPS)-compatible bioink with flexible printing and post-processing.
  • Utilized strain-promoted azide-alkyne cycloaddition (SPAAC) for cross-linking bicyclo[6.1.0]non-4-yne-functionalized hyaluronan, achieving high elasticity (>100% strain at break).
  • Employed textile-inspired techniques (knotting, braiding) for 3D architecture reconfiguration and incorporated shape memory for programmed actuation.

Main Results:

  • Generated highly elastic hydrogel filaments with mechanical integrity for manual handling and post-processing.
  • Demonstrated successful reconfiguration into complex 3D architectures using knotting and braiding.
  • Achieved high cell viability across multiple cell types and enabled spatially defined multicellular constructs.
  • Utilized protease-degradable cross-linkers for sacrificial templating of perfusable tubular structures.

Conclusions:

  • The REFRESH strategy provides a versatile platform for fabricating mechanically robust and reconfigurable hydrogel filaments.
  • This approach significantly expands the design space for biofabrication, enabling new possibilities in vascularized tissue engineering and complex hydrogel architectures.
  • REFRESH overcomes key challenges in current biofabrication, paving the way for more advanced tissue models and constructs.