A 3D model is considered "advanced" when it's a bioactive system recreating a tissue's microenvironment. It's not just about three-dimensional growth; cells must both influence and be influenced by their surroundings, including architecture, diffusion gradients, and mechanical cues, to be truly representative.
The push away from animal models is a technical necessity, not just an ethical one. Advanced therapeutics like T-cell engagers and multispecific antibodies depend on human-specific biological pathways. These mechanisms are not accurately reproduced in animal models, rendering them ineffective for testing these new drug classes.
Scaling from a T-flask to a bioreactor isn't just increasing volume; it's a fundamental shift in the biological context. Changes in cell density, mass transfer, and mechanical stress rewire cell signaling. Therefore, understanding and respecting the cell's biology must be the primary design input for successful scale-up.
There's no universal bioreactor setting for 3D tissue models. Each tissue type has unique biological needs. For instance, neural cells require minimal shear stress and low oxygen, whereas liver cells need rigorous perfusion flow to maintain metabolic competence, mandating highly tailored process design for each model.