A team of Massachusetts General Hospital (MGH) investigators has made the first steps towards development of bioartificial replacement limbs suitable for transplantation. In their report, which has been published online in the journal Biomaterials, the researchers describe using an experimental approach previously used to build bioartificial organs to engineer rat forelimbs with functioning vascular and muscle tissue. They also provided evidence that the same approach could be applied to the limbs of primates



"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."



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Ref: Engineered composite tissue as a bioartificial limb graft. Biomaterials (2015) | DOI:10.1016/j.biomaterials.2015.04.051



Abstract

The loss of an extremity is a disastrous injury with tremendous impact on a patient's life. Current mechanical prostheses are technically highly sophisticated, but only partially replace physiologic function and aesthetic appearance. As a biologic alternative, approximately 70 patients have undergone allogeneic hand transplantation to date worldwide. While outcomes are favorable, risks and side effects of transplantation and long-term immunosuppression pose a significant ethical dilemma. An autologous, bio-artificial graft based on native extracellular matrix and patient derived cells could be produced on demand and would not require immunosuppression after transplantation. To create such a graft, we decellularized rat and primate forearms by detergent perfusion and yielded acellular scaffolds with preserved composite architecture. We then repopulated muscle and vasculature with cells of appropriate phenotypes, and matured the composite tissue in a perfusion bioreactor under electrical stimulation in vitro. After confirmation of composite tissue formation, we transplanted the resulting bio-composite grafts to confirm perfusion in vivo.

