A team led by researchers at Massachusetts General Hospital (MGH) in Boston has engineered an artificial ear from animal structural tissue and cells. It looks and flexes like a human one and distorts only minimally during growth, thanks to the incorporation of a thin wire frame.
The researchers hope their techniques, once fine-tuned and adapted to use patients' own cells, could one day help people with missing or deformed outer ears.
They write about their work in a July 31st online issue of the Journal of the Royal Society Interface. Lead author Dr. Thomas Cervantes of the Department of Surgery at MGH told the press:
"This is the first demonstration of a full-size human ear that maintains shape and flexibility after 3 months."
Previously, the team had engineered an ear on a smaller scale, the size of a baby's, implanted on the back of a mouse.
This time they grew a full-sized adult ear, and they showed that it developed with minimal distortion when implanted on a rat.
How the ear was made
The full-sized artificial ear contains a titanium wire frame to hold its shape, as did the earlier small one.
Appearance of the engineered ear with embedded wire framework implanted in a rat for 12 weeks (a) Before explant. (b) After explant. (c) Image of explanted engineered ear without an embedded wire framework. (d) The explanted engineered ear with wire framework maintained its shape and could be elastically deformed. Photo credit: Royal Society Publishing
The team used collagen from cows to make a 3D tissue scaffold, held in shape with the wire frame, to "maintain the gross dimensions of the engineered ear after implantation," and populated it with ear cartilage cells from sheep.
The combination of the wire frame and collagen scaffold was able to resist the forces that would otherwise deform the structure during the reconstruction processes of making new cartilage tissue and wound healing, note the authors.
An improvement on the earlier model was that they also redesigned the ear geometry to achieve "a more accurate aesthetic" shape.
After three months embedded in the backs of nude male rats, the ears containing the titanium wire support showed much less distortion of the initial ear shape than ears without the wire frame.
All the implants were well tolerated over the 12 weeks in the live rats and showed no exposure or extrusions.
But when they removed the artificial ears, the researchers found the ones without the titanium frame were flattened and lost their shape, whereas the ones containing the wire framework held their shape and also showed similar flexibility to the human ear.
To assess changes to shape over the 12 weeks, the team took CT scans of the titanium framework before and after implantation. They analyzed several measures, including overall length, width and depth, and curvature values for each section within the framework.
Using such measures, they were able to work out changes to the various dimensions and better understand the bending forces experienced by the framework.
"These quantitative shape analysis results have identified opportunities to improve shape fidelity of engineered ear constructs," they conclude.
How engineered tissue can help in future
Cervantes explains that:
"Shape and flexibility are key; tissue engineered constructs tend to distort in shape during growth, which is obviously a problem for the ear, because we are aiming to recreate a very specific shape."
He told BBC News that their study is a "significant step forward in preparing the tissue-engineered ear for human clinical trials," which he anticipates could start in about 5 years.
The study follows a succession of breakthroughs in engineered tissue.
Earlier this year, we heard how a two-year-old girl born without a windpipe received an artificial trachea grown from her own stem cells.
Written by Catharine Paddock PhD