Engineered composite tissue as a bioartificial limb graft

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.

Decellularized skin/adipose tissue flap matrix for engineering vascularized composite soft tissue flaps

“…The peripheral sensory nerve structure in the flap matrix could easily bridge the host nerve growth into the flap. Indeed, we observed cellularization in the nerve structure after its end-to-side connection with the femoral nerve in the host; however, whether nerve function can fully recover in this setting requires further investigation [12, 51]. …”

“…More recently, Jank et al created decellularized limb composite tissue matrix. The recellularized limb tissue matrix–multiple cells construct showed perfusion in a re-endothelialized vascular conduit in a short-term non-survival procedure in a rat model [12]. Overall, the use of decellularized composite tissue matrix to engineer vascularized composite tissue has progressed much in recent years.…”

Codelivery of Infusion Decellularized Skeletal Muscle with Minced Muscle Autografts Improved Recovery from Volumetric Muscle Loss Injury in a Rat Model

“…Although perfusion decellularization has been performed on the entire forelimb of a rat 26 and whole organs, such as the liver, 27 heart, 28 kidneys, 29 and lungs, 30 muscle tissue lacks the easily accessible vasculature needed for perfusion, motivating a different approach whereby decellularization solution was infused into the bulk tissue using a needle. In our recently published work, it was demonstrated that DSM scaffolds produced through infusion decellularization retain the composition, mechanics, and architecture of native muscle ECM.…”

Controlling stem cell behavior with decellularized extracellular matrix scaffolds

“…However, the studies reviewed herein also suggest that ECM scaffolds have potential as cell delivery scaffolds, although this significantly increases treatment costs and has a more difficult regulatory pathway as a combination product. More long term development could result in the use of decellularized ECM for whole organ engineering [92–95]; however, this increase in complexity creates numerous more challenges that must be overcome, including creating fully functional constructs and preventing thrombosis in the vasculature [96, 97]. …”