Main ingredients for tissue engineering
To grow the ‘mini bones’, De Wildt needed four important parts. First, she needed specialized stem cells, called parental cells. Unlike pluripotent stem cells, which are cells that can become any type of cell in the body, the parent cells can only become osteoblasts or osteoclasts. De Wildt: “These parental cells must receive the correct biochemical signals in order to change into osteoclasts and osteoblasts.”
Second, de Wildt needed a structure on which the bone cells could fuse into the ‘mini bone’. “We used silk from silkworms for this, because it is a material with favorable mechanical properties, it is biocompatible, and human cells can grow on the material in three dimensions,” says De Wildt.
Third, the cells need an environment in which to grow and thrive. “The cells are placed in an incubator that is maintained at a temperature of 37 degrees Celsius, which also contains the oxygen and CO2-content and humidity,” says De Wildt.
Finally, to mimic bone as much as possible, the bone cells are placed in a bioreactor, which is then placed in the incubator. De Wildt: “The bioreactor circulates a nutrient fluid and mimics the mechanical stress of bone in the human body. If a ‘minibot’ is to be representative of real bone, the cells must be challenged to withstand these forces.”
“Together, these are the essential prerequisites for tissue engineering, which has been used in regenerative medicine since the 1990s to grow implants for the body,” says De Wildt. “Recently, however, tissue engineering has been used to in vitro versions of human bone, which are versions of bone grown outside the human body.”