Tissue engineering can produce tendons, cartilage, and even bladders. But only now have researchers managed to make different tissues blend into one another, as they do naturally in the body.
Such gradients are necessary for some structures and organs to function properly, says bioengineer Andrés García, who with colleagues at the Georgia Institute of Technology demonstrated a way to grow tendons that gradually "fade" to bone at one end.
In the body, gradients like this strengthen the ends of tendons that attach to bones. Currently, lab-grown tendons put into the body often fail at the attachment end because they lack this property, says García.
His new technique should lead to more lifelike artificially-grown tendons, and better treatments for injuries like ruptured Achilles tendons. The technique could also be applicable to other tissues, such as blood vessels.
At the heart of the new technique is a gene that triggers the fibroblast cells that make up tendons to start forming bone. The team used viruses carrying that gene to transform a tendon made from normal fibroblasts into one with a gradient of bony properties.
They began with a protein scaffold covered in a graded coat of a polymer called PLL. A thick coat at one end faded away to a very thin layer at the other.
The scaffold was then dipped into a liquid containing the virus. Particles of virus stuck onto the graded PLL coat, creating a gradient of virus particles.
Fibroblast cells were then grown over the scaffold. In places with many virus particles, a high density of fibroblasts were infected with the gene, and started to secrete bone. In places with few virus particles, few fibroblasts were infected.
The end result was a steady gradient of bone secretion along the length of the tendon, which significantly enhanced its strength.
So far, the researchers have shown that tendons made this way are stable when implanted under the skin of rats. The next step is to graft a tendon to connect bone and muscle in a rat and see if it really does perform better.
The same technique could be used to make better ligaments, which connect bones together, says García.
"I think it's very interesting as a next horizon for tissue engineering in general," says Jennifer Elisseeff, a biomedical engineer at Johns Hopkins University in Baltimore, Maryland.
"It's often [the case] that interfaces [between tissues] are the issue. Getting that transition is going to be critical in clinical application of these technologies."