Grants Funded

Abstract

Impact Statement: The proposed research offers the prospect of a paradigm shift in microvascular reconstruction. Wounds with exposed critical structures such as tendon, bone, and hardware, can be a challenge to heal. Currently, the most reliable method of reconstructing these wounds is transplanting flaps of skin or muscle with its own blood supply, which causes additional pain, scarring and loss of function. Achieving of the goal of this research to successfully decellularize and recellularize a vascularized composite tissue could lead to a paradigm shift in the management of complex wounds with exposed critical structures. Bioengineered scaffolds could obviate the need for flap donor sites and their associated morbidity with incorporation of perfusion approaches into the microsurgical filed.

Project Summary: Soft tissue injuries may result in complex wounds with exposed critical structures such as bone, tendon, blood vessels, nerve, and hardware. The gold standard in these scenarios is reconstruction with flaps, which entails moving skin/muscle/fat with an intact blood supply into the wound. These procedures are expensive and lengthy operations that result in additional scarring and functional loss. Engineered vascularized tissue flaps that contain multiple types of tissues offer an ideal and clinically viable alternative. Successful usage of a such constructs requires a thorough removal of immune response-eliciting cells while preserving the internal structure of the tissues. We propose a technology that addresses the shortcomings of the current clinical practice while matching the reliability of the standard of care by bioengineering an off-the-shelf composite, bioengineered reconstructive material through decellularization and recellularization using endothelial cells. Different methods of recellularization have been described in the literature ranging from simple seeding with cells to perfusion recellularization. Perfusion decellularization and recellularization approaches have shown exceptional promise in whole organ engineering but have seen minimal crossover into the microsurgical field. Endothelial cells as the cell source to reline the vascular endothelium have demonstrated efficacy in this field with the benefit of ease on collecting the cells. In this proposal, we aim to leverage the benefits of endothelial cells to compare different methods of recellularization and identify an optimal protocol that provides a viable vascular network within the decellularized scaffold. Our central goal is to successfully bioengineer a flap that can be connected to any recipient vessel allowing a paradigm shift in the management of complex soft tissue wounds with exposed critical structures by avoiding the risks and complications associated with alternative methods. This will set the foundation for scale-up efforts toward clinically relevant flap sizes using tissue engineering protocols defined within the scope of this funding opportunity as well as experience harvesting cadaveric tissue flaps, which we anticipate using in the to-scale version of these efforts. Our proposal seeks to provide groundwork for the inaugural technology and provide a foundation on which the field of regenerative medicine can build and refine future bioengineered technologies of this type.

Biography
Fuat Baris Bengur, MD is a Postdoctoral Research Fellow in the University of Pittsburgh, Department of Plastic Surgery Research Laboratory and the Vascularized Composite Allotransplantation and Microsurgery Laboratory. He graduated from medical school in Istanbul, Turkey with a distinguished award that is given to only one graduate each year for their professionalism and clinical competency. After graduation, Dr. Bengur joined his current institution as a Postdoctoral Research Fellow. His research is primarily focused on the intersection of plastic/reconstructive surgery and cell/tissue engineering, though he has also published research in other, related fields. He has authored over 45 abstracts and 25 peer-reviewed articles. Dr. Bengur is currently involved in projects related to peripheral nerve repair with novel nerve conduits, reconstruction of complex soft tissue defects with tissue engineered vascularized composite tissues and ex vivo machine perfusion of vascularized composite tissues. The primary goal of his research is to improve surgical outcomes in reconstructive surgery, while minimizing the morbidity to the patients. He plans to continue pursuing a career in academic plastic surgery as a surgeon/scientist, where he can dedicate his life to the care of the injured, combine research with the practice of plastic surgery to advance the field and allow for treatment of patients across the globe as an established leader.