Composite Tissue Regeneration

Engineering composite tissue – A potential future treatment for soft tissue loss.

The composite tissue project aims at engineering complex soft tissue grafts, such as a whole forearm, for the treatment of devastating injuries.

The loss of an extremity, as one of the most severe forms of soft tissue loss, is a devastating injury with a tremendous impact on a patient’s functional abilities and quality of life. Such amputations affect approximately 10 million people worldwide. Although current arm prostheses are highly sophisticated devices, they can only replace a small portion of physiologic functions and aesthetics. As an alternative approach, approximately 70 patients worldwide have received hand transplants since 1998. However, side effects of long-term immunosuppression pose a significant ethical dilemma. Bioengineered grafts derived from cadaveric matrix and autologous cells could be a theoretical alternative.

To investigate the feasibility of this approach, we decellularized whole rat extremities and tested them for their biomechanical properties. Our decellularization protocol generates a complex composite tissue graft with a perfusable vascular tree, preserved mechanical characteristics of bones and the joint apparatus and an intact three-dimensional matrix that can be reseeded with cells of appropriate phenotype. We reseeded acellular grafts with a mixture of myoblasts and fibroblasts to regenerate muscle tissue and endothelial cells to regenerate the vascular system. We could achieve formation of functional muscle tissue within our composite tissue graft after 16 days of in-vitro culture. After maturation of the engineered tissue in the bioreactor, we tested the engineered limb graft for its passive mechanical function in vivo.

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