Development of engineered fasciocutaneous skin flaps

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ABSTRACT Deformities created by birth defects, trauma, inflammation, and medical conditions including cancer constitute a significant global health burden accounting for 11% of worldwide disability-adjusted life years and can be corrected by reconstructive surgery. Standard reconstructive techniques include autologous, pedicled or vascularized tissue flaps to replace moderate to severe composite tissue defects. Limitation of these methods include donor-site morbidity and difficulty in shaping the graft to restore complex three-dimensional anatomy. In the case of fasciocutaneous flaps, both factors are limiting – and a significant portion of such defects cannot be treated with current techniques. In the longer term, Vascularized composite allografts (VCAs) have potential to revolutionize the treatment of complex soft tissue absence by providing an anatomically exact tissue unit enabling like-for-like restoration, but is impractical as long as the recipient requires toxic immunosuppression which limited the number of VCA transplants to about 150 over the last 2 decades. Our long-term goal is to engineer vascular composite allografts using patient specific cells for repairing composite tissue defects. The goal of this project is to develop a novel protocol for creating fasciocutaneous flaps (FCF) that are vascularized and blood compatible, which would provide a straightforward path to treating some currently unfixable defects clinically in the short-term, while laying the groundwork for building more complex tissues in the long term. The rationale of the study is that while most past biomaterials research has focused on producing the ideal scaffold from the ground up using synthetic materials, the native extracellular matrix (ECM), de facto contains much of necessary architecture and environmental cues absent from synthetic matrices, and hence presents a promising, more realistic alternative approach for producing engineered tissue substitutes, which can vertically advance the field of tissue engineering.