Descripción del proyecto
Facial reconstruction usually involves the use of autologous grafts or composite tissue allografts, which are highly complex tissues that pose significant challenges to tissue engineering experts. Tissue engineering of independent facial elements, e.g., bone, adipose, skin and muscle tissues, has been demonstrated. However, to date, no composite soft tissues composed of multiple facial layers have been created. Composite facial tissue engineering will require proper innervation and vascularization, essential to support generation of large thick implants. However, techniques for effective innervation of engineered tissues are currently insufficient and generation of well-vascularized large and thick engineered tissues is still one of the major obstacles limiting their translation to the clinic. Our goal is to engineer thick, composite, human-scale, facial tissues (muscle-adipose-dermis composite, and bone) of a personally adaptable shape, that will be vascularized in-vitro, and innervated upon transplantation. Our concept is to create in-vitro a functional vascular network (VesselNet), composed of both large and small vessels, within engineered constructs, which will allow for the generation of thick engineered tissues under continuous flow conditions. 3D bio-printing techniques will be applied to create the engineered tissues. These tissues will serve as a model to study mechanisms involved in vessel anastomosis, and tissue organization and stabilization. The applicability of the engineered composite soft and bone tissues will be evaluated in facial, breast and abdominal wall defect reconstruction models, and in an open fracture model. Such engineered large-scale composite tissues are expected to have a major impact on reconstructive surgery and will shed light on yet unknown tissue organization mechanisms.