Grants Funded

Abstract
Skin wounds are an increasing threat to public health and the economy. These include acute and chronic wounds, burns, pressure ulcers, venous ulcers and diabetic ulcers. Novel approaches for the treatment and reconstruction of full thickness skin defects are required. Current treatments result in deforming contractures, unstable scar, suboptimal function, and poor aesthetics. Existing dermal templates lack epithelium and require at least three weeks for host incorporation; during which the template undergoes degeneration and cicatrization, risking infection and resulting in replacement of the template with a layer of scar.
The goal of this work is to utilize perfusion decellularization technology and recellularization techniques on a porcine-based skin flap in order to generate a full thickness skin substitute that can be implanted into a skin defect. In the long term, we hope to re-populate these flaps with induced pluripotent stem cells, which would permit regeneration of full thickness skin with the recipient's own cells. Given the immense economic and social impact of wounds, burns, and scarring in our society, the creation of an autologous full thickness skin analogue remains of paramount importance, has the potential to eliminate the need for donor sites, reduce morbidity from scarring and contracture, and would result in a paradigm shift in the management of wounds and skin loss from multiple causes.
Aim 1: Optimization and characterization of a perfusion decellularized fasciocutaneous porcine flap. Current methods for obtaining acellular dermal matrices involve decellularizing native tissue through physical disruption or enzymatic treatment; however, these techniques compromise the composition and structural integrity of the resultant scaffold. Alternatively, pressure-controlled perfusion decellularization is a technique that utilizes the existing vascular network to generate acellular scaffolds with preserved extracellular matrix content and architecture.
Aim 2: Recellularization of a perfusion decellularized flap with endothelial cells (pre-vascularize) and keratinocytes (pre-epithelialize), and implantation of the flap into a porcine host. Such scaffolds have previously demonstrated the support of selected cell types and the regeneration of functional, organ-specific tissue types including heart, lung, and kidney. We seek to apply these techniques to a decellularized skin flap, thereby creating a full thickness skin equivalent.

Biography
After obtaining my Medical Degree, I spent 9 years obtaining specializations that would allow me to provide the highest quality burn care to my patients - from the moment of injury, to discharge from the hospital, and then re-entry into the community. After a five year residency in General Surgery, I received additional training in burn surgery, surgical critical care, and plastic surgery. This has afforded me the unique privilege of treating patients with burns throughout their recovery. As part of the multidisciplinary team of burn care providers at the Sumner Redstone Burn Center and the Fraser Outpatient Burn Center at Massachusetts General Hospital, we treat the most complex burn injuries. In addition to my clinical responsibilities, I am the director of the Acute and Reconstructive Burn Fellowship; I have authored numerous burn-related clinical research protocols, journal publications, and book chapters; and I am the site principle investigator for two multicenter, randomized, controlled trials.