Scientists at Massachusetts General Hospital (MGH) have successfully engineered and transplanted the first fully biological artificial limb. Using an experimental approach previously utilized to build bio-artificial organs, they constructed rat forelimbs with functional muscle and blood tissue.

According to the Amputee Coalition, there are at least 2 million Americans who are living with limb loss. The various causes of limb loss include vascular disease (54%), trauma (45%) and cancer (less than 2%). Out of vascular diseases, peripheral arterial disease and diabetes are the main culprits.

In a research conducted by Massachusetts General Hospital Center for Regenerative Medicine, a team of scientists have reportedly crafted for the first time a functional rat limb by taking a dead rat limb, stripping off its living cells, leaving a framework and allowing new cells to grow. The end result was a living rat leg able to respond to stimuli.

Harald Ott, of the MGH and a senior author said that “Limbs contain muscles, tendons, bone, ligaments, cartilage, nerves and blood vessels- each of which has to be built and needs a supporting structure known as a matrix. The composite nature of our limbs makes it difficult to make a functional bio-replacement.”

Using the process of decellularization, all living cells of limbs of dead donor rats were stripped using a detergent and the primary matrix was exposed. The primary matrix supports all the living cells of the limb and gives them a structure. Simultaneously cells were cultured which would provide new muscle and blood cells on the matrix.

The limbs were then recellularized by using these cells and were injected onto the scaffolds. The scaffold was then inserted into a specially designed bioreactor and was provided with nutrients to help the cells grow. After 5 days, they were given electrical stimulation in the reactor to stimulate the cells’ growth and after two weeks the biolimb was removed from the bioreactor and tested.

Scientists tested motor response by applying electric current and recording the flexing of the limb’s fingers and muscles as well as transplanting these biolimbs onto real animals with missing limbs. It was observed that the blood vessels in the biolimb got filled with blood and it continued to circulate throughout it.

The scientists claimed that the same method could be applied to primate limbs. They decellularized baboon limbs to determine the feasibility of using this method on the scale required for human patients.

Artificial organs have been previously made using cells from a donor. Examples include windpipes, human organs for transplant and synthetic ladders. But these have been primarily simple with few cell types. A whole limb consisting of bone, blood and muscles is far more complex and harder to manufacture in such a way as to prevent tissue rejection.

Scientists hope that this could be the first steps towards regeneration of human limbs with patient’s own cells. These “biolimbs” could be the answer for people who have lost limbs to accidents or are amputees. Though there has been much advancement in the field of prosthetics, prosthetic limbs lack the finesse of real limbs. Even with transplanted limbs, patients have to take immunosuppressive drugs for the rest of their lives to prevent tissue rejection.

After vascular and muscle progenitors have been introduced into a decellularized rat limb, it is suspended in a bioreactor, which provides a nutrient solution and electrical stimulation to support and promote the growth of new tissues. (Bernhard Jank, MD, Ott Laboratory, Massachusetts General Hospital Center for Regenerative Medicine)