Embedded bioprinting is an emerging technology for precise deposition of cell-laden or cell-only bioinks to construct tissue like structures. Bioink is extruded or transferred into a yield stress hydrogel or a microgel support bath allowing print needle motion during printing and providing temporal support for the printed construct. Although this technology has enabled creation of complex tissue structures, it remains a challenge to develop a support bath with user-defined extracellular mimetic cues and their spatial and temporal control. This is crucial to mimic the dynamic nature of the native tissue to better regenerate tissues and organs. To address this, we present a bioprinting approach involving printing of a photocurable viscous support layer and bioprinting of a cell-only or cell-laden bioink within this viscous layer followed by brief exposure to light to partially crosslink the support layer. This approach does not require shear thinning behavior and is suitable for a wide range of photocurable hydrogels to be used as a support. It enables multi-material printing to spatially control support hydrogel heterogeneity including temporal delivery of bioactive cues (e.g. growth factors), and precise patterning of dense multi-cellular structures within these hydrogel supports. Here, dense stem cell aggregates are printed within methacrylated hyaluronic acid-based hydrogels with patterned heterogeneity to spatially modulate human mesenchymal stem cell osteogenesis. This study has significant impactions on creating tissue interfaces (e.g. osteochondral tissue) in which spatial control of extracellular matrix properties for patterned stem cell differentiation is crucial.
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.
more » « less- PAR ID:
- 10442016
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Materials
- Volume:
- 35
- Issue:
- 36
- ISSN:
- 0935-9648
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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