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Coumarin-Based Photodegradable Hydrogels Enable Two-Photon Subtractive Biofabrication at 300 mm s-1
Wanwan Qiu1, Christian Gehre1, Jaime Pietrantuono Nepomuceno1
1Institute for Biomechanics, ETH Zurich, Gloriastrasse 39, 8092, Zurich, Switzerland.
Angewandte Chemie (International Ed. in English)
|July 18, 2024
Summary
New coumarin-based hydrogels enable fast, high-precision tissue engineering using two-photon photodegradation. These materials significantly improve efficiency and reduce laser dosage, allowing for rapid fabrication of complex 3D structures while preserving cell viability.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Photochemistry
Background:
- Two-photon photodegradation of hydrogels is crucial for precise subtractive tissue engineering.
- Conventional photolabile hydrogels exhibit low efficiency in the near-infrared region, necessitating high laser doses that can harm cells.
- Achieving high-speed hydrogel erosion with two-photon excitation in cellular environments remains a significant challenge.
Purpose of the Study:
- To design and synthesize novel coumarin-based photodegradable hydrogels with enhanced efficiency for two-photon excitation.
- To overcome the limitations of conventional hydrogels regarding speed and laser dosage in tissue engineering applications.
- To demonstrate the utility of these new hydrogels in fabricating complex 3D structures and directing cell behavior.
Main Methods:
- Synthesis of coumarin-functionalized polyethylene glycol linkers via Passerini multicomponent reaction.
- In situ formation of semi-synthetic hydrogels through Michael addition crosslinking with thiolated hyaluronic acid.
- Evaluation of photodegradation efficiency under two-photon irradiation at 780 nm compared to nitrobenzyl-based hydrogels.
Main Results:
- Coumarin-based hydrogels demonstrated significantly higher photodegradation efficiency than nitrobenzyl counterparts.
- Fabrication of a complex microfluidic network mimicking bone microarchitecture was achieved at speeds up to 300 mm/s with low laser power (10 mW).
- Fast two-photon printing of hollow microchannels was demonstrated to guide cell migration in 3D hydrogel environments.
Conclusions:
- The developed coumarin-based hydrogels offer a highly efficient and rapid method for two-photon controlled subtractive fabrication.
- These materials enable precise tissue engineering with reduced laser dosage, preserving cell viability.
- The findings suggest potential for advancing laser-guided 3D tissue fabrication with high spatial resolution and speed.

