Bioprinting a Multifunctional Bioink to Engineer Clickable 3D Cellular Niches with Tunable Matrix Microenvironmental Cues

• Published in: Advanced healthcare materials 2021-01, Vol.10 (2), p.e2001176-n/a
• Main Authors: Pereira, Rúben F., Lourenço, Bianca N., Bártolo, Paulo J., Granja, Pedro L.
• Format: Article
• Language: English
• Subjects: Barium; Bioengineering; biofabrication; bioinks; Biomimetics; Bioprinting; Calcium; Cell adhesion; Cell culture; Cell fate; Cell proliferation; Cell spreading; click chemistry; Cues; Extracellular matrix; Extrusion; Hydrogels; Printing, Three-Dimensional; Properties (attributes); Rheological properties; Rheology; Stability; Stiffness; Three dimensional printing; Tissue Engineering; Tissue Scaffolds
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202001176

The properties of the surrounding cell environment are major determinants of cell response in 3D. However, the ability to unravel how these cues dictate the biological function in bioprinted constructs is limited by the lack of extracellular matrix (ECM)‐mimetic bioinks with fully controllable properties. In this study, a multifunctional bioink that uniquely combines the independent control over the biochemical and biophysical cues that regulate cell fate with the bioorthogonal nature of thiol–norbornene photoclick chemistry is designed for the extrusion bioprinting of bioinspired 3D cellular niches with tunable properties. The bioink rheology is controlled by ionic gelation, being dependent on both the type and content of divalent ions (calcium and barium), while the mechanical and biochemical properties of hydrogels are tailored via a post printing thiol–ene reaction. Bioprinted cell‐adhesive and protease‐degradable hydrogels modulate cell proliferation and ECM deposition in a matrix‐stiffness dependent manner over 14 days of culture regardless of cell spreading, demonstrating the ability to probe the effect of matrix cues on cell response. This bioink can be used as a versatile platform where building blocks can be rationally combined for the bioprinting of functional cell‐ and tissue‐specific constructs with controlled cellular behavior. A multifunctional bioink is engineered for the bioprinting of bioinspired 3D hydrogels with tunable and independently controllable rheological, biophysical, and biochemical cues. The combination of ionic gelation and step‐growth thiol–ene chemistry enables the bioprinting of 3D cellular niches with cell‐ and tissue‐specific properties toward identifying how matrix microenvironmental cues dictate the biological function in bioprinted constructs.