Team develops transplantable bioengineered forelimb in an animal model

A team of Massachusetts General Hospital (MGH) investigators has made the first steps towards development of bioartificial replacement limbs suitable for transplantation.

"The composite nature of our limbs makes building a functional biological replacement particularly challenging," explains Harald Ott, MD, of the MGH Department of Surgery and the Center for Regenerative Medicine, senior author of the paper. "Limbs contain muscles, bone, cartilage, blood vessels, tendons, ligaments and nerves - each of which has to be rebuilt and requires a specific supporting structure called the matrix.

We have shown that we can maintain the matrix of all of these tissues in their natural relationships to each other, that we can culture the entire construct over prolonged periods of time, and that we can repopulate the vascular system and musculature."

The authors note that more than 1.5 million individuals in the U.S. have lost a limb, and although prosthetic technology has greatly advanced, the devices still have many limitations in terms of both function and appearance.

Over the past two decades a number of patients have received donor hand transplants, and while such procedures can significantly improve quality of life, they also expose recipients to the risks of life-long immunosuppressive therapy.

The current study uses technology Ott discovered as a research fellow at the University of Minnesota, in which living cells are stripped from a donor organ with a detergent solution and the remaining matrix is then repopulated with progenitor cells appropriate to the specific organ. His team and others at MGH and elsewhere have used this decellularization technique to regenerate kidneys, livers, hearts and lungs from animal models, but this is the first reported use to engineer the more complex tissues of a bioartificial limb.