Lab-Grown Bone Scaffolds Reveal How Cells React to Mechanical Stress

Bone may look solid, but at the scale of the cells that live inside it, it behaves more like a sponge. Every step, jump, or stretch compresses bone's porous structure, pushing fluid through microscopic channels and bathing embedded cells in a complex mix of mechanical strain and flowing liquid. For decades, mechanobiologists have known this environment exists, but they haven't had a way to recreate it in the lab.

Now, Ottman Tertuliano, AMA Family Assistant Professor in Mechanical Engineering and Applied Mechanics, and his lab at Penn's School of Engineering and Applied Science, have built a platform that does exactly that. In a study published in Biophysical Journal and led by postdoctoral fellow Kailin Chen and graduate students Alexander Bolanos Campos and Mistica Lozano Perez, the team has introduced a nanoengineered, 3D-printed scaffold that allows scientists to simultaneously control and observe solid deformation and fluid flow around living cells.

Using nanoscale 3D printing, the Tertuliano Lab fabricated porous, architected scaffolds with features comparable in size to the bone cells themselves. These structures aren't just placeholders, they are carefully designed environments that mimic the physical geometry and mechanical behavior of bone.

Cells seeded into these scaffolds don't float or spread randomly. Instead, they template themselves onto the architecture, wrapping around struts, aligning their cytoskeletons and forming focal adhesions that mirror the underlying structure. Even without mechanical loading, this behavior was striking.

"Within a couple of days these cells organized their internal skeleton in 3D to mimic that of the architectured scaffolds, a single biological cell mimicking a structural unit cell," says Tertuliano. To quantify what was happening, the researchers combined experiments with simulations of fluid-structure interactions. They also collaborated with Arnold Mathijssen, assistant professor in biophysics at the School of Arts & Sciences, to directly measure fluid flow at microscopic scales, validating that the engineered system behaved as predicted.

"By putting tiny particles in the 3D-printed microstructures, you can measure the streamlines and flow speeds inside," says Mathijssen. "Our lab works on fluid dynamics of biological systems, so this collaboration was a perfect fit to leverage our skills."

What they observed surprised them. Under cyclic loading, the previously ordered cellular architecture fell apart. Actin fibers became disorganized. Focal adhesions lost their elongated shape. Cells no longer aligned cleanly with the scaffold geometry.

Read more at Penn Engineering.