3D Bioprintable Hydrogel with Tunable Stiffness for Exploring Cells Encapsulated in Matrices of Differing Stiffnesses

Area of Science:

• Biomaterials Engineering
• Tissue Engineering
• Cell Biology

Background:

• In vitro cell models are transitioning from 2D to 3D formats to better mimic native tissue environments.
• Three-dimensional (3D) bioprinting offers high-throughput, reproducible production of cell-laden structures.
• Existing bioprintable matrices have a limited range of stiffness, restricting their utility.

Purpose of the Study:

• To expand the tunable stiffness range of 3D bioprintable matrices.
• To develop a modular system for controlling matrix stiffness and incorporating biological cues.
• To validate the system's applicability in drop-on-demand bioprinting for cell behavior studies.

Main Methods:

• Utilized a four-armed polyethylene glycol (PEG) with maleimide-functionalized arms.
• Employed complementary cross-linkers: a matrix metalloprotease-degradable peptide and a four-armed thiolated polymer.
• Adjusted the ratio of cross-linkers to precisely tune matrix stiffness.
• Validated the system using MCF-7 cells in a drop-on-demand bioprinting platform.

Main Results:

• Successfully expanded the stiffness range of PEG-based matrices for 3D bioprinting.
• Demonstrated modular control over matrix stiffness and the incorporation of biological motifs.
• Validated cell viability and proliferation of MCF-7 cells within the printed 3D constructs.
• Showcased the system's potential for high-throughput screening.

Conclusions:

• The developed system provides a versatile method for creating 3D cell-laden matrices with tunable stiffness.
• This approach facilitates the investigation of how matrix stiffness and composition influence cell behavior.
• The technology holds promise for advancing high-throughput screening in drug discovery and regenerative medicine.