By HDIAC Staff
Between 2001 and 2014 nearly 1,600 U.S. service members suffered battle-injury major limb amputation. Service members who endure limb loss are challenged with a complex recovery process that evolves over weeks, months and years. Although prostheses have improved, amputees still experience other complications such as difficulties with healing, multiple limb loss, stump pain, decreased functional abilities, delayed psychological adjustment to the loss and impaired confidence in their ability to resume normal life activities.
A suspension of muscle progenitor cells is injected into the cell-free matrix of a decellularized rat limb, which provides shape and structure onto which regenerated tissue can grow. (Photo: Bernhard Jank, MD, Ott Laboratory, Massachusetts General Hospital Center for Regenerative Medicine/Released)
Medical researchers and bioengineers are working toward developing bio-artificial replacement limbs for transplantation. The early stage of medical bioengineering began with smaller, less complicated cell regeneration and grew to encompass the development of transplantable bioengineered organs. Researchers at Harvard Stem Cell Institute engineered a rat forelimb with functioning vascular and muscle tissue and are confident that the same method could be used with primates. The forearm was created using biological material from the recipient rat.
“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,” said Dr. Harald Ott, of the Massachusetts General Hospital (MGH) Department of Surgery and the Center for Regenerative Medicine.
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. (Photo: Bernhard Jank, MD, Ott Laboratory, Massachusetts General Hospital Center for Regenerative Medicine/Released)
Performance testing of the grafted limbs showed that electrical stimulation of the muscles triggered contractions “with a strength 80% of what would be seen in newborn animals. The vascular systems of bioengineered forelimbs transplanted into recipient animals quickly filled with blood which continued to circulate, and electrical stimulation of muscles within transplanted grafts flexed the wrists and digital joints of the animals’ paws.”
The use of a patient’s own genetic materials to engineer organs or limbs significantly reduces the chances of rejection and eliminates the need for patients to take life-long courses of immunosuppressant drugs. The research team at Massachusetts General Hospital also successfully decellularized baboon forearms to prove the probability of using the same approach on the scale required for human patients.
Photo: Massachusetts General Hospital Center for Regenerative Medicine (Released)
Both HSCI and MGH agree that the next step in the transplantation of bioengineered limbs is to decipher the bioelectric code would allow the grafting of nerve matrix. Ott notes that, while regrowing nerves within a limb graft and reintegrating them into a recipient’s nervous system is one of the next challenges that needs to be faced, the experience of patients who have received hand transplants is promising. “In clinical limb transplantation, nerves do grow back into the graft, enabling both motion and sensation, and we have learned that this process is largely guided by the nerve matrix within the graft. We hope in future work to show that the same will apply to bioartificial grafts. Additional next steps will be replicating our success in muscle regeneration with human cells and expanding that to other tissue types, such as bone, cartilage and connective tissue.”
Story and information provided by the Homeland Defense & Security Information Analysis Center where additional references may be found.
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