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Abstract Patterning biomolecules in synthetic hydrogels offers routes to visualize and learn how spatially‐encoded cues modulate cell behavior (e.g., proliferation, differentiation, migration, and apoptosis). However, investigating the role of multiple, spatially defined biochemical cues within a single hydrogel matrix remains challenging because of the limited number of orthogonal bioconjugation reactions available for patterning. Herein, a method to pattern multiple oligonucleotide sequences in hydrogels using thiol‐yne photochemistry is introduced. Rapid hydrogel photopatterning of hydrogels with micron resolution DNA features (≈1.5 µm) and control over DNA density are achieved over centimeter‐scale areas using mask‐free digital photolithography. Sequence‐specific DNA interactions are then used to reversibly tether biomolecules to patterned regions, demonstrating chemical control over individual patterned domains. Last, localized cell signaling is shown using patterned protein–DNA conjugates to selectively activate cells on patterned areas. Overall, this work introduces a synthetic method to achieve multiplexed micron resolution patterns of biomolecules onto hydrogel scaffolds, providing a platform to study complex spatially‐encoded cellular signaling environments.
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Design, Synthesis, and Application of a Water‐soluble Photocage for Aqueous Cyclopentadiene‐based Diels‐Alder Photoclick Chemistry in Hydrogels
Abstract Spatiotemporally functionalized hydrogels have exciting applications in tissue engineering, but their preparation often relies on radical‐based strategies that can be deleterious in biological settings. Herein, the computationally guided design, synthesis, and application of a water‐soluble cyclopentadienone‐norbornadiene (CPD‐NBD) adduct is disclosed as a diene photocage for radical‐free Diels‐Alder photopatterning. We show that this scalable CPD‐NBD derivative is readily incorporated into hydrogel formulations, providing gels that can be patterned with dienophiles upon 365 nm uncaging of cyclopentadiene. Patterning is first visualized through conjugation of cyanine dyes, then biological utility is highlighted by patterning peptides to direct cellular adhesion. Finally, the ease of use and versatility of this CPD‐NBD derivative is demonstrated by direct incorporation into a commercial 3D printing resin to enable the photopatterning of structurally complex, printed hydrogels.
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- PAR ID:
- 10401124
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 62
- Issue:
- 16
- ISSN:
- 1433-7851
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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