Transport Analysis of Engineered Liver Tissue Fabricated Using a Capsule-Based, Modular Approach

Area of Science:

• Bioengineering
• Tissue Engineering
• Regenerative Medicine

Background:

• Microscale tissue engineering offers a scaffold-free alternative for complex organ fabrication.
• Previous work demonstrated a prototype engineered liver tissue using fused hepatocyte-containing capsules.

Purpose of the Study:

• To analyze system parameters influencing modular tissue performance in high cell density perfusion cultures.
• To predict operating limits for engineered tissues based on mass transfer and fluid dynamics.

Main Methods:

• Mathematical modeling of mass transfer and shear stress within packed capsule beds.
• Experimental validation using packed bed perfusion cultures with primary hepatocytes.
• Analysis of flow-induced bed compaction and oxygen transfer effectiveness.

Main Results:

• Capsule diameter and construct height are limited by mass transfer requirements.
• Shear stress and pressure drop depend on capsule diameter and flow rates.
• Predicted optimal capsule radius of 200 µm supports liver-specific cell densities.
• Oxygen transfer effectiveness factor (η) estimated at 0.72.
• Encapsulated hepatocytes maintained normal metabolism and formed spheroids over 7 days.

Conclusions:

• The microscale, modular tissue engineering approach is feasible for fabricating highly metabolic solid organs.
• Model predictions are valuable for optimizing high-density perfusion cultures.
• The technology provides a platform for engineering complex, vascularized tissues.