A team of investigators from the Massachusetts General Hospital, MGH has made the first steps towards development of bioartificial replacement limbs. Scientists report that they have created an bioartificial biological rat paw that has a functioning muscle and vascular systems. The results published in the journal Biomaterials.
The authors note that more than half of a million people in the US have become disabled due to loss of limbs. And while technology of prosthetics developed enough in our time, mechanical prostheses have many restrictions in terms of functionality and appearance.
Over the past two decades, a plurality of persons with disabilities transplanted donor hands. This has greatly improved the quality of life, but patients have to receive a lifetime immunosuppressive therapy.
A new method, based on the filling the matrix frame with progenitor cells, has no such disadvantages as in the procedure used patient’s own cells. The method, which uses Dr. Harald Ott, lead author of the study, based on decellularization technique (getting rid of cells) of the donor with a special solution. Then, the resulting frame is filled with progenitor cells, for the relevant organ of the body.
The team of Dr. Ott uses this technique to grow at decellularization frameworks such organs as the liver, kidneys, heart and lungs of animals. But a new technique for obtaining an bioartificial limb is much more complicated and it used for the first time.
The researchers used a front paw rat from a deceased donor. All cells of limbs were decellularizated, leaving only the matrix of blood vessels and nerve network. The process took a week. The cells, which are filled the resulting cell-free frame, previously grown in culture.
Next foot matrix cultivated in a bioreactor, while scientists are injected human endothelial cells in limb artery to restore the veins and arteries. Muscle progenitor cells (myoblasts) were injected directly into the matrix shell that determines the position of each muscle.
After five days in culture, electrical stimulation was applied to the potential limb graft to further promote muscle formation, and after two weeks, the grafts were removed from the bioreactor. Analysis of the bioartificial limbs confirmed the presence of vascular cells along blood vessel walls and muscle cells aligned into appropriate fibers throughout the muscle matrix.
Functional testing of grown limb showed that electrical stimulation causes muscle bend with strength in 80% of the strength of the newborn animal.
After transplantation of bioengineered foot recipient rats grown vessels rapidly filled with blood, which began to circulate, and with the help of electrical stimulation bent wrist and finger joints of transplants.
The research team also successfully decellularized baboon forearms to confirm the feasibility of using this approach on the scale that would be required for human patients.
Currently, scientists fill the resulting framework by endothelial cells of human. Then planned to put human myoblasts for growing muscles.
Dr. Ott believes that the first clinical trials of the technology on humans held not earlier than 10 years. In the future, perhaps, anyone can donate an arm or leg to create a bioengineered limbs for the disabled.
Researchers still have a lot of work: necessary to learn how to grow bone, cartilage and other tissue types. Also, should learn whether it is possible full innervation of a whole transplant limb, as well as it happens with successfully transplanted hands.
Limb of baboon (B J Jank, Ott Laboratory)