A ball, a saddle, or a flat plate. The curvature of biomaterials inhibits or stimulates bone cells to make new tissue. This is what TU Delft engineers show in research published today in Nature Communications. This study of geometries could be an important step in research into repairing damaged tissues.
The research was supervised by Professor of Biomaterials and Tissue Biomechanics Prof. Dr. Amir Zadpoor (TU Delft) and connects with the scientific program Medical Delta Regenerative Medicine 4D: Generating complex tissues with stem cells and printing technology, of which Zadpoor is one of the Scientific Leaders.
Living cells can perceive and respond to the geometry of their environment. "Cells sense and respond to the geometry of the surfaces they are exposed to. Depending on their curvature, surfaces can either encourage cells to create new tissue or prevent them from doing so," says Zadpoor. "Stimulating curvatures made by a 3D printer are an easy and safe way to promote tissue growth. As compared to drugs, they are also much cheaper."
In petri dishes, the researchers grew bone cells surrounded by small moulds made from biomaterials with which the researchers have experience. Depending on the curvatures in the moulds, the cells tended to grow, divide, and form tissue to different extents.
Although curved shapes seem to exist in endless variations, they always fall roughly into one of these three categories: a ball that has a convex curvature, a saddle that has a concave curvature, and a plate that is flat. One of the authors, assistant professor of Biomaterials Dr. ir. Lidy Fratila-Apachitei: "Cells prefer a saddle shape. If they perceive a saddle shape nearby, growth is stimulated. The study also shows that cells prefer valleys over hills."
First author Dr. Sebastien Callens did the experiments and analysis in the study. "Cells also have a skeleton, which consists of fibres that are under tension to different degrees. How tension builds up in those fibres strongly influences the behaviour of cells. Our study shows that cells collectively align their stress fibers with the curvatures they experience to minimize their need to bend. I could see that cells prefer to align than to bend."
You can't have only saddle curves around cells. Just as the three angles of a triangle always add up to 180 degrees, the sum of all curvatures must also equal some fundamental numbers. "You always have a limited budget of saddle shapes," says Zadpoor. "If you use too much negative curvature somewhere, you must use positive curvatures somewhere else to keep the sum constant. You need to use your budget wisely to encourage maximum tissue regeneration."
The study provides guidance on the optimal geometry of biomaterials and implants to maximise tissue regeneration. The complex geometric designs required are made using high-precision 3D printing techniques to make the shapes so small that they are perceptible to cells. Callens: "We have now discovered new playing rules by which biomaterials can stimulate tissue growth. In follow-up research, we will try to apply those rules optimally."
The news item of TU Delft can be found here
The Nature Communications publication can be found here