Researchers have developed a unique approach to fabricate bone models that precisely replicate human bone tissue. They are using the model to explore fundamental disease processes, such as the origin of metastatic tumors in bone, and as a treatment for large bone injuries.
"Essentially it is a miniaturized bone in a dish that we can produce in a matter of 72 hours or less," says senior author Luiz Bertassoni, D.D.S., Ph.D., a biomedical engineer at Oregon Health & Science University.
Like real bone, the material has a 3D mineral structure populated with bone cells, nerve cells, and endothelial cells that self-organize into functioning blood vessels. And that's what makes the new material promising as a model to study bone function, diseases, and bone regeneration. "With this model system, you can start asking questions about how bone cells attract different types of cancers, how cancer cells move into bone, how bone takes part in the regulation of marrow function," says Bertassoni.
According to the paper published in Nature Communications today, the process starts by mixing human stem cells into a solution loaded with collagen. The collagen proteins link together, forming a gel embedded with the stem cells. The researchers then flood the gel with a mixture of dissolved calcium and phosphate. They then add the protein osteopontin to keep the minerals from forming crystals too quickly. This additive, which clings to calcium and phosphate, also minimizes the minerals' toxicity to cells. The mixture diffuses through a network of channels about the width of a strand of DNA in the spongey collagen, and the dissolved minerals precipitate into orderly layers of crystals.
In this calcified environment, stem cells develop into functioning bone cells, osteoblasts, and osteocytes without the addition of any other molecules. Within days, the growing cells squeeze slender protrusions through spaces in their mineralized surroundings to connect and communicate with neighboring cells. The bone-like engineered structure creates a microenvironment that is sufficient to cue stem cells that it's time to mature into bone cells.