Grants Funded
ASPS/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.
Research Abstracts
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.
Micro-mechanical Forces to Stimulate Wound Healing
Principal Investigator
Dennis Orgill MD, PhD
Dennis Orgill MD, PhD
Year
2005
2005
Institution
Brigham and Women's Hospital
Brigham and Women's Hospital
Funding Mechanism
National Endowment
National Endowment
Focus Area
Wounds / Scar
Wounds / Scar
Abstract
There are an estimated 10.8 million wounds in the United States every year, many of which are chronic and difficult to heal. Wound healing is critical to all plastic surgical interventions and novel strategies, such as micro-mechanical forces to stimulate healing, should lead to better cost-effective therapies. Mechanical forces are commonly used in plastic surgery, yet understanding the optimal application is lacking. We hypothesize that refined mechanical stretch of skin tissue in vivo, induces cell proliferation and angiogenesis as a consequence of structural deformations and hypoxic stress. The optimized mechanical input of stretch on cells, indeed, can be transformed into a chemical mitogenic output that induces protein synthesis and ultimately cell proliferation. Moreover, stretch alters blood flow and determines hypoxic areas that can act as potent inducers of VEGF/NO pathway, leading to a powerful angiogenic effects. Both cell proliferation and angiogenesis are crucial in wound healing and we believe that the study and optimization of two simple triggers will bring the-needed innovation into wound healing management. In the first set of experiments we will try to optimize the mechanical stretch Signal in order to obtain maximal proliferation effects. Using a servo-controlled tension device that allows us to apply precise loads in a predetermined wave-form, we will stretch rat ears following different protocols and study the effects on vasculature (lHC: CD31, CD34, Mecca32) and vascular-related growth factor expression (VEGF). The stretch protocols will include variations in magnitude and intervals of applied forces, as well as, waveform. In the second set of experiments we will try to demonstrate that optimized cyclical stretch determines angiogenesis also by inducing hypoxic stress. We will use the tension device on the back of different type of mice (VEGF -/-, eNOS-/-, db/db, wyld type) in the attempt to show the correlation between cyclical stretch and hypoxia, and the correlations with angiogenesis. We will study the expression of VEGFNEGF-R2 and eNOS with immunohistochemistry and elisa assays. This project aims ultimately to acquire the needed knowledge to design the next generation wound healing device to help surgeons to successfully face the increasing number of complicated wound of everyday practice.
There are an estimated 10.8 million wounds in the United States every year, many of which are chronic and difficult to heal. Wound healing is critical to all plastic surgical interventions and novel strategies, such as micro-mechanical forces to stimulate healing, should lead to better cost-effective therapies. Mechanical forces are commonly used in plastic surgery, yet understanding the optimal application is lacking. We hypothesize that refined mechanical stretch of skin tissue in vivo, induces cell proliferation and angiogenesis as a consequence of structural deformations and hypoxic stress. The optimized mechanical input of stretch on cells, indeed, can be transformed into a chemical mitogenic output that induces protein synthesis and ultimately cell proliferation. Moreover, stretch alters blood flow and determines hypoxic areas that can act as potent inducers of VEGF/NO pathway, leading to a powerful angiogenic effects. Both cell proliferation and angiogenesis are crucial in wound healing and we believe that the study and optimization of two simple triggers will bring the-needed innovation into wound healing management. In the first set of experiments we will try to optimize the mechanical stretch Signal in order to obtain maximal proliferation effects. Using a servo-controlled tension device that allows us to apply precise loads in a predetermined wave-form, we will stretch rat ears following different protocols and study the effects on vasculature (lHC: CD31, CD34, Mecca32) and vascular-related growth factor expression (VEGF). The stretch protocols will include variations in magnitude and intervals of applied forces, as well as, waveform. In the second set of experiments we will try to demonstrate that optimized cyclical stretch determines angiogenesis also by inducing hypoxic stress. We will use the tension device on the back of different type of mice (VEGF -/-, eNOS-/-, db/db, wyld type) in the attempt to show the correlation between cyclical stretch and hypoxia, and the correlations with angiogenesis. We will study the expression of VEGFNEGF-R2 and eNOS with immunohistochemistry and elisa assays. This project aims ultimately to acquire the needed knowledge to design the next generation wound healing device to help surgeons to successfully face the increasing number of complicated wound of everyday practice.
Biography
Dr. Orgill is the Vice Chairman for Quality Improvement in the Department of Surgery at Brigham and Women’s Hospital in Boston, MA and a Professor of Surgery at Harvard Medical School. He obtained his PhD at MIT while working with Dr. I.V. Yannas to develop artificial skin for burn victims. As a Plastic Surgeon, he has a major investigative interest in the area of wound healing through the development of better technologies including work with artificial skin, micromechanical forces, platelets, stem cells and fat grafting.
Dr. Orgill is the Vice Chairman for Quality Improvement in the Department of Surgery at Brigham and Women’s Hospital in Boston, MA and a Professor of Surgery at Harvard Medical School. He obtained his PhD at MIT while working with Dr. I.V. Yannas to develop artificial skin for burn victims. As a Plastic Surgeon, he has a major investigative interest in the area of wound healing through the development of better technologies including work with artificial skin, micromechanical forces, platelets, stem cells and fat grafting.