Printing Blood Vessels

To grow viable organs in the lab, biologists are going beyond the genetics of development to study the physics and mechanics of cells in the early embryo.

Humans have distinct parts -- fingers, toes, arms, legs, organs -- thanks to a complex process of cell migration and self-assembly in the early embryo. One of the great mysteries still confronting developmental biologists is that this process is only partly driven by information stored in our genes.

Instead, much of the structure of a developing embryo, including fundamental body segments like the head, thorax, and abdomen, seems to emerge as the result of physical forces between cells and molecular signals that ripple through the embryo like waves. This biological cascade creates self-organized, complex structures "that are represented nowhere in an organism's genome

," according to Stuart Newman, a cell biologist at New York Medical College in Valhalla, NY.

But recently, biologists have begun to understand -- and even manipulate -- some of the physical and chemical factors that regulate how cells proliferate, congregate, and separate. Equations usually found in physics textbooks are turning up in tissue-engineering labs, where they're being used in a radical new process called organ printing.

Tissue engineering is a broad discipline that aims to manufacture viable replacements for damaged or missing body parts such as skin, cartilage, bone, blood vessels, muscles, and livers. One of the field's pioneers is chemical engineer Robert Langer of MIT, whose lab, in the 1980s, developed a polymer scaffolding to mold into the shape of an organ or a chunk of tissue. Such scaffolds became the most common way to try to build body parts; but over the past six years, researchers have begun to explore organ printing as an alternative to it.

Printing involves depositing layer after layer of cells into a Jello-like support called a hydrogel, a substance that is suffused with nutrients that cells digest and then use to create their own support. The hydrogel physically and chemically mimics the surroundings of embryonic cells during development and allows the cells to migrate as they would naturally. The advantage of organ printing over polymer scaffold-based tissue engineering is that tissues can be built up in days rather than months, and no polymers need to be absorbed by the body -– the hydrogel is made mainly from the same elastins and other molecules found in the extracellular matrix of biological tissue.

"Organ printing can guide the [tissue] assembly," cell biologist Newman explains. "Instead of leaving it up to the embryo, you set up the initial conditions with an organ printer." Newman's team won a $5 million dollar grant from the National Science Foundation last fall to explore the physical mechanisms that help printed organs develop.

One of the fundamental physical principles of tissue development, Newman says, is the Steinberg model, named after Malcolm Steinberg, a well-known Princeton University molecular biologist. Proposed in the 1960s, this model depicts the cells of an embryo as if they were molecules in a liquid. Just as molecules in liquid are bound by molecular forces, cells in tissue are bound by molecules called cadherins. Different tissues have different cells with different binding strengths and they can separate into layers, like oil and water. Consequently, tissue engineers don't have to worry about meticulously controlling different cell types once they're deposited, because "they will sort out like salad dressing," Newman says.