Grants Funded
Grant applicants for the 2024 cycle requested a total of nearly $3 million dollars. The PSF Study Section Subcommittees of Basic & Translational Research and Clinical Research evaluated more than 100 grant applications on the following topics:
The PSF awarded research grants totaling over $650,000 dollars to support more than 20 plastic surgery research proposals.
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.
Targeted Mechanism Based Treatment of Heterotopic Ossification
Principal Investigator
Benjamin Levi MD
Benjamin Levi MD
Year
2014
2014
Institution
The Regents of the University of Michigan
The Regents of the University of Michigan
Funding Mechanism
National Endowment for Plastic Surgery Grant
National Endowment for Plastic Surgery Grant
Focus Area
General Reconstructive
General Reconstructive
Abstract
Over 60% of major burns, 65% of combat injuries and 20% of joint surgeries will cause heterotopic ossification (HO), the deposition of bone in soft tissues such as muscle, tendon or fascia. Current treatment strategies require surgical extirpation of HO; however, even after a technically successful operation, >75% of patients have restricted range of motion and pain. Studies have demonstrated the pathologic role of mesenchymal stem cells (MSCs) as the precursor cells to HO. Barriers to improved outcomes in HO patients include delayed diagnosis and a lack of treatments that target the key ectopic bone formation pathway. Through this proposal, we plan to improve early diagnosis and HO prevention strategies by targeting the bone morphogenetic protein (BMP) pathway. We aim to change the current treatment paradigm of HO management in plastic surgery from one of delayed diagnosis and excision to one of early detection and prevention. Specifically, we will use non-invasive Raman spectroscopy imaging to identify early indicators of HO formation. Once at risk patients are identified, we will deploy novel potent small molecule BMP inhibitors (LDN-193189 and LDN-221854) to prevent HO.
Aim 1: To mitigate HO precursor cell (MSC) osteogenesis from human heterotopic ossification tissue through targeted inhibition of BMP signaling. Studies have demonstrated a link between trauma induced HO and BMP signaling in MSCs, ultimately increasing ectopic bone. We demonstrate that our highly selective inhibitors of individual BMP type I receptors can down-regulate the osteogenic capacity of MSCs. Human MSC osteogenesis will be analyzed after treatment with LDN-193189 and LDN-221854 in vitro using established protocols and cell lines. Cell lines will include 1) MSCs from HO tissue; 2) Control MSCs harvested distant from the HO site and 3) Control age and gender matched patients without HO.
Aim 2: To change the chemical composition of pre-HO tissue and to prevent its progression to HO in vivo through inhibition of BMP signaling. This aim will use our mouse Achilles tenotomy-burn model in wild type and Bmpr1a knockout mice. Raman and MicroCT will be used to assess the effect of BMP inhibition on HO formation. We will demonstrate the central role of BMP with our Bmpr1a knockout mice and the ability of small molecules (LDN-193189 and LDN-221854) to block HO in vivo. These results will be critical towards clinical translation of BMP inhibition as an HO prevention strategy.
Over 60% of major burns, 65% of combat injuries and 20% of joint surgeries will cause heterotopic ossification (HO), the deposition of bone in soft tissues such as muscle, tendon or fascia. Current treatment strategies require surgical extirpation of HO; however, even after a technically successful operation, >75% of patients have restricted range of motion and pain. Studies have demonstrated the pathologic role of mesenchymal stem cells (MSCs) as the precursor cells to HO. Barriers to improved outcomes in HO patients include delayed diagnosis and a lack of treatments that target the key ectopic bone formation pathway. Through this proposal, we plan to improve early diagnosis and HO prevention strategies by targeting the bone morphogenetic protein (BMP) pathway. We aim to change the current treatment paradigm of HO management in plastic surgery from one of delayed diagnosis and excision to one of early detection and prevention. Specifically, we will use non-invasive Raman spectroscopy imaging to identify early indicators of HO formation. Once at risk patients are identified, we will deploy novel potent small molecule BMP inhibitors (LDN-193189 and LDN-221854) to prevent HO.
Aim 1: To mitigate HO precursor cell (MSC) osteogenesis from human heterotopic ossification tissue through targeted inhibition of BMP signaling. Studies have demonstrated a link between trauma induced HO and BMP signaling in MSCs, ultimately increasing ectopic bone. We demonstrate that our highly selective inhibitors of individual BMP type I receptors can down-regulate the osteogenic capacity of MSCs. Human MSC osteogenesis will be analyzed after treatment with LDN-193189 and LDN-221854 in vitro using established protocols and cell lines. Cell lines will include 1) MSCs from HO tissue; 2) Control MSCs harvested distant from the HO site and 3) Control age and gender matched patients without HO.
Aim 2: To change the chemical composition of pre-HO tissue and to prevent its progression to HO in vivo through inhibition of BMP signaling. This aim will use our mouse Achilles tenotomy-burn model in wild type and Bmpr1a knockout mice. Raman and MicroCT will be used to assess the effect of BMP inhibition on HO formation. We will demonstrate the central role of BMP with our Bmpr1a knockout mice and the ability of small molecules (LDN-193189 and LDN-221854) to block HO in vivo. These results will be critical towards clinical translation of BMP inhibition as an HO prevention strategy.
Biography
Benjamin Levi, MD has been involved in Burn research since High School when given the opportunity to work in the Burn Laboratory of Richard Gamelli MD and Luisa DiPietro DDS, PhD. Subsequently, and for three consecutive summers, he worked in the Burn and Shock Trauma laboratory of Dr. Gamelli and Dr. Luisa DiPietro with a focus on wound healing and inflammation. Dr. Levi completed his undergraduate education at Washington University where he graduated Phi Beta Kappa in Biology and Spanish. He then attended medical school at Northwestern University and subsequently completed his Plastic and Reconstructive Surgery residency at the University of Michigan. During his residency he completed a 2 year post-doctoral research fellowship at Stanford University while funded by a NIH Ruth L. Kirschstein National Research Service Award. His research focused on basic bone biology, bone development, stem cell biology and tissue engineering. After his residency and research training, he took an additional year to be the Kidder Fellow in Burn Surgery and Surgical Critical Care at Massachusetts General Hospital and Shriner’s Hospital for Children in Boston.
Dr. Levi is currently founder and director of the Burn/Wound and Regenerative Medicine Laboratory at the University of Michigan. This lab has focused on the significant clinical problem of heterotopic ossification. Specifically, Dr. Levi has developed new animal models to study this complex process and is working to improve early diagnostic and treatment modalities.
Benjamin Levi, MD has been involved in Burn research since High School when given the opportunity to work in the Burn Laboratory of Richard Gamelli MD and Luisa DiPietro DDS, PhD. Subsequently, and for three consecutive summers, he worked in the Burn and Shock Trauma laboratory of Dr. Gamelli and Dr. Luisa DiPietro with a focus on wound healing and inflammation. Dr. Levi completed his undergraduate education at Washington University where he graduated Phi Beta Kappa in Biology and Spanish. He then attended medical school at Northwestern University and subsequently completed his Plastic and Reconstructive Surgery residency at the University of Michigan. During his residency he completed a 2 year post-doctoral research fellowship at Stanford University while funded by a NIH Ruth L. Kirschstein National Research Service Award. His research focused on basic bone biology, bone development, stem cell biology and tissue engineering. After his residency and research training, he took an additional year to be the Kidder Fellow in Burn Surgery and Surgical Critical Care at Massachusetts General Hospital and Shriner’s Hospital for Children in Boston.
Dr. Levi is currently founder and director of the Burn/Wound and Regenerative Medicine Laboratory at the University of Michigan. This lab has focused on the significant clinical problem of heterotopic ossification. Specifically, Dr. Levi has developed new animal models to study this complex process and is working to improve early diagnostic and treatment modalities.