Bioprinted high cell density liver model with improved hepatic metabolic functions

Area of Science:

• Biomedical Engineering
• Tissue Engineering
• Regenerative Medicine

Background:

• In vitro liver models are crucial for drug development and disease research.
• Current 3D bioprinting faces challenges in achieving high cell density (HCD) and long-term viability in liver tissues.
• HCD is essential for mimicking liver functions but increases light scattering in bioprinting.

Purpose of the Study:

• To develop a 3D bioprinting strategy for fabricating high cell density (HCD) hepatic tissue constructs.
• To overcome light scattering issues in HCD bioinks for improved bioprinting resolution and viability.
• To create a more physiologically relevant in vitro liver model for drug screening and toxicity assessment.

Main Methods:

• Incorporation of iodixanol into bioink to reduce light scattering.
• Fabrication of hepatic tissue constructs using light-based 3D bioprinting at HCD (8 × 10^7 cells/mL).
• Assessment of cell viability, cell-cell interactions (E-cadherin, ZO-1), liver functions (albumin, urea, P450), and drug response.

Main Results:

• Successfully fabricated HCD hepatic tissue constructs with high cell viability (∼80%).
• Demonstrated enhanced cell-cell interactions and preserved key hepatocyte functions (albumin secretion, urea production, P450 activity).
• Showed that HCD models exhibit greater sensitivity to drug treatments, reflecting physiological responses.

Conclusions:

• The iodixanol-based bioink effectively enables 3D bioprinting of HCD liver tissue, overcoming light scattering limitations.
• The developed HCD hepatic tissue model offers improved cell-cell interactions and functional mimicry of native liver.
• This advanced in vitro model provides a more accurate platform for drug screening and toxicity evaluation.