Programmable Relaxation Dynamics in Bioinspired Coacervates for 3D Printing Cell Scaffolds

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Polymer Chemistry

Background:

• Intracellular biomolecular condensates inspire tunable biomaterials.
• Chitosan and hyaluronic acid coacervates offer potential for advanced scaffolds.

Purpose of the Study:

• To develop and characterize chitosan-hyaluronic acid coacervates for 3D bioprinting.
• To investigate the role of relaxation dynamics in scaffold structural organization and processability.
• To establish a multi-parameter framework for tuning coacervate properties.

Main Methods:

• Liquid-liquid phase separation to form coacervates.
• Multiscale analysis to study structural organization and relaxation dynamics.
• Time-salt-molecular weight-pH superposition principles to tune relaxation times.
• Quantitative extrusion force measurements.
• Cell culture studies with L929 fibroblasts and adipose-derived stem cells.

Main Results:

• Relaxation times were tuned over seven orders of magnitude (10^-3 to 10^4 s) by modulating pH, ionic strength, and molecular weight.
• Programmable solid-gel-liquid transitions were achieved via electrostatic, hydrophobic, and hydration interactions.
• A relaxation time threshold (>0.5 s) ensured structural integrity during 3D printing.
• Printed scaffolds exhibited excellent mechanical properties, reprocessability, and supported cell adhesion, spreading, and proliferation.
• Coacervate extrudability was enhanced by salt, while stability was improved by higher molecular weight and pH.

Conclusions:

• Relaxation dynamics provide a framework for simultaneously achieving extrudability and stability in natural polyelectrolyte coacervates.
• The developed coacervates are biocompatible and functional for 3D bioprinting of cell scaffolds.
• This study advances the application of coacervates in tissue engineering and regenerative medicine.