Building better organ models, one collagen sphere at a time

Recreating the hollow structures of the heart, stomach, and other vital organs is crucial for accurately modeling disease, but current approaches depend on self-organizing cells and offer little control over the final shape. This constraint becomes especially problematic when studying conditions where key developmental genes are disrupted because the model architecture fails altogether.

Abeta et al. developed a process using a hollow collagen sphere loaded with a liquid suspension of cells that removes the reliance on self-organizing cells, allowing for better control of hollow organ fabrication.

Since collagen is already found in the body, the cells naturally attached to the inner wall and formed a hollow tissue. The researchers generated 30 spheres per minute with just 2.8% variation, indicating strong reproducibility and uniformity.

“Because the hollow geometry is defined by the fabrication process rather than by the cells, it is robust, reproducible, and independent of the cells’ intrinsic self-organization capacity,” author Hiroaki Onoe said.

The team created the beads by using a microfluidic nozzle to form droplets with a cell-containing core and an alginate–collagen shell. The alginate provided temporary structural support while the collagen solidified at 37 °C. Once set, they enzymatically removed the alginate, leaving a collagen shell surrounding the cell-laden core. The researchers imaged the bead morphology with microscopy and used staining to determine cell viability, which reached 90 percent after one week of culture.

The researchers plan to improve the sphericity of their beads, since the cells within the beads prevent the sphere from forming uniformly. The team then hopes to apply the method to study early-stage heart tissue.

Source: “Fabrication of cell-encapsulating hollow collagen microgel beads for engineered hollow tissues,” by Satona Abeta, Aiki Hioki, Akari Masuda, Fabio Pizzeti, Filippo Rossi, Kayoko Hirayama-Shoji, Hiroaki Onoe, Biomicrofluidics (2026). The article can be accessed at https://doi.org/10.1063/5.0328551 .