Grants We Funded
In 2019, The Plastic Surgery Foundation (The PSF) awarded 33 investigator-initiated projects and allocated $891,274 to support the newest, clinically relevant research in plastic surgery.
The American Society of Plastic Surgeons/PSF leadership is committed to continuing to provide high levels of investigator-initiated research support to ensure that plastic surgeons have the needed research resources to be pioneers and innovators in advancing the practice of medicine.
Search The PSF database to have easy access to full-text grant abstracts from past PSF-funded research projects 2003 to present. All abstracts are the work of the Principal Investigators and were retrieved from their PSF grant applications. Several different filters may be applied to locate abstracts specific to a particular focus area, or PSF funding mechanism.
Sustained Local Anti-TNF-alpha Delivery for Hypertrophic Scars
David Brown MD, PhD
Pilot Research Grant
Tissue Engineering, Wounds / Scar
Hypertrophic scars are the most common complication of burn injury, which occur in over 40% of survivors of severe burns. Severe burns lead to long-term sequelae such as joint contractures, chronic pain, pruritus, and an inability to sweat12,3. Surgical reconstruction remains the mainstay of treatment as an effective noninvasive treatment has not yet been developed4. Molecular studies of hypertrophic scars have demonstrated that the pro-inflammatory cytokine TNF-a contributes to over-activation of immune cells and excessive collagen synthesis during wound healing5. Recent experiments from our laboratory have demonstrated that a monoclonal antibody against TNF-a reduces inflammation and secondary necrosis in a mouse burn model6. By conjugating the anti-TNF-a immunoglobulin to hyaluronic acid (HA), a sustained local delivery of anti-TNF-a was achieved, allowing a more prolonged exposure of the antibody to tissue than could be achieved with topical application. We have extensively described the biologic activity of the HA-anti-TNF-a conjugate7,8, though the delivery and binding kinetics in tissue are yet unknown. The goal of this project is to develop a novel wound care dressing that will allow sustained local delivery of TNF-a and ultimately reduce hypertrophic scarring in burn-injured patients. The objective of this study is to measure the delivery of TNF-a from the HA platform and assess the resultant inflammatory response over time in an established rabbit hypertrophic scar model. We intend to test the hypothesis that HA-anti-TNF-a allows a sustained level of TNF-a blockade at the wound healing site, which consequently reduces inflammation and scar formation in comparison to controls. This study will investigate the role of TNF-a in scar formation and suggest whether or not sustained antibody blockade of TNF-a from a degradable delivery platform represents a promising strategy for reduction of hypertrophic scarring. The following specific aim is proposed: Measure local blockade of TNF-a by immunostaining for the mouse anti-TNF-a immunoglobulin and for the rabbit TNF-a receptor over time as delivered by varying formulations of the HA-anti-TNF-a conjugate. The local inflammatory response will also be measured by measurement of tissue IL-1ß levels, quantitative immunostaining for activated macrophages (CCR7 and CD68), histologic staining with Masson's trichrome, and quantitative measurement of scar contraction. At the conclusion of this study, we will gain a mechanistic understanding of the effects of sustained TNF-a blockade on inflammation, as well as its role in hypertrophic scarring. This work will provide pre-clinical evidence that TNF-a blockade represents an approach to treat hypertrophic scarring.
David A. Brown, M.D., Ph.D., is a plastic and reconstructive surgeon at Duke University Hospital in Durham, North Carolina. Dr. Brown graduated from the University of California, Irvine School of Medicine and subsequently completed General Surgery residency at University of Washington Medical Center, followed by Plastic and Reconstructive Surgery residency at Duke University Medical Center. He holds a Ph.D. in biomedical engineering and has been active in both basic and clinical research throughout his career. Dr. Brown’s clinical and research interests revolve around wound healing and clinical wound care. He is involved in several hospital committees concerning the care of patients with chronic wounds, and he is part of an active research laboratory investigating novel therapies for wound healing. Dr. Brown currently has 40% protected time to pursue clinical and basic science research. His work is funded in part by the Department of Defense and Duke Department of Surgery.