Modelling and measuring effects of shear stress in extrusion bioprinting of endothelial- epithelial cell co-cultures

Imagine a future where doctors can print living tissues to repair damaged organs or replace lost skin. This vision relies on a technique called bioprinting, where scientists use specialized machines to squeeze out tiny streams of liquid that contain living cells mixed with a supportive gel. The goal is to build structures that mimic the complex tissues of the human body. However, the process of squeezing this mixture through a narrow nozzle creates a powerful physical force known as shear stress. Think of this force like the pressure felt when squeezing a tube of toothpaste; the faster and harder you squeeze, the more the contents are rubbed and stretched against the walls of the tube. For living cells, which are delicate and fragile, this rubbing can be harmful, potentially killing them or damaging their ability to function once the structure is built. Understanding exactly how much force these cells can survive is essential if scientists hope to create reliable, living tissues.

A team of researchers set out to measure and predict how this squeezing force affects two different types of human cells working together: blood vessel cells and breast tissue cells. To do this, they did not simply print the cells and hope for the best. Instead, they built a complete system to watch, calculate, and test what happens inside the printer. First, they studied the thick, jelly-like substance used to hold the cells, known as gelatin methacryloyl. They tested this material at two different concentrations and temperatures to see how it flowed. They found that the way the material behaved could be described by mathematical models that predict how thick liquids move, allowing them to simulate the printing process on a computer before ever touching a real cell.

To ensure their computer simulations were accurate, the researchers used a high-speed camera to watch tiny particles moving inside the flowing gel, confirming that the digital predictions matched the real-world movement. With this reliable model in hand, they turned their attention to the cells themselves. They printed a mixture of the two cell types into the gel at different pressures and concentrations. The results revealed a complex relationship between the printing conditions and cell health. When the cells were printed into a weaker gel at a lower temperature, the immediate aftermath showed a rise in cell death. Interestingly, the stronger gel demonstrated higher shear stress levels compared to the weaker gel, yet it did not cause the same immediate spike in dying cells.

However, the story did not end the moment the printing stopped. The researchers let the printed structures sit for a day to see how the cells recovered. They discovered that even low levels of stress from the printing process had a delayed effect. As the pressure used during printing increased, the number of dying cells grew after just one day of culture. This suggests that the cells are sensitive to the physical forces of the printing process in ways that are not immediately obvious. The study provides a solid method for predicting these effects, showing that by combining computer modeling with careful observation, scientists can better understand the hidden forces that shape the future of living tissue printing.