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.
Mechanisms involved in Diabetic Fracture Healing
Ruth Tevlin MD
Pilot Research Grant
Diabetes mellitus is an emerging epidemic that has consequences for musculoskeletal growth and
development. It is projected that the number of individuals diagnosed with diabetes in the United States will
increase by 198% from 16.2 million in 2005 to 48.3 million in 2050. Diabetic fracture healing is well known to
be problematic in diabetic patients. The biological effect of diabetes mellitus on bone fracture healing
remains to be elucidated.
We have found from preliminary investigation that diabetic fracture healing is impaired compared to wild-type
control in mice. We hypothesize that the impairment of fracture healing capacity of diabetic bone is likely due
to, both, cell-intrinsic and extrinsic factors. Identification of genetic mechanisms underlying these changes
will allow for manipulation of these pathways and improved diabetic fracture healing in patients requiring
plastic surgical care. We will employ a murine model of long-bone fracture to achieve our aims, in
combination with advanced scientific techniques.
In our preliminary study, we noted that bone marrow from diabetic mice formed larger osteoclasts in vitro
compared to wild type mice (*p<0.05). In addition, osteoclasts isolated from diabetic mice exhibited
increased resorptive function on osteoassay plates (*p <0.01). In vivo, closed, bi-cortical femoral fractures
were created in age- and gender-matched diabetic (db/db) and wild type mice. Interestingly, diabetic mice
showed delayed, and exaggerated, callus development on radiographic assessment. The diabetic fracture
group was also weaker on 3-point bending than its wild-type control (*p<0.05).
In this proposal, we describe our aim to study the mechanisms that are responsible for poor diabetic fracture
healing. Our specific aims include (i) determination of the cell intrinsic and extrinsic factors leading to
impaired fracture healing in diabetes and (ii) identification of the genes and genetic mechanisms that are
differentially expressed in cells involved in bone healing in diabetic versus wild-type mice. We will employ
advanced scientific techniques including surgical parabiosis to examine systemic factors involved in fracture
repair, microarray analysis of callus samples of wild-type and diabetic bone samples at different time-points
in the healing cascade and Raman laser confocal micro-spectroscopy to analyze bone mineral content and
effect of diabetes on collagen-crosslinking in fracture healing and thus, ultimate bone remodeling.
Dr. Ruth Tevlin is a postdoctoral research fellow in the Hagey Laboratory for Pediatric Regenerative Medicine at Stanford University School of Medicine under the mentorship of Dr. Michael Longaker. Dr. Tevlin is a surgical trainee from Ireland, who completed her medical education in University College Dublin. She commenced surgical training with the Royal College of Surgeons in Ireland in 2011 and was awarded Membership of the Royal College or Surgeons in Ireland in 2013. Since joining the Longaker laboratory, Dr. Tevlin has been investigating cellular and molecular mechanisms of osseous fracture healing, with a particular focus on the role of stem and progenitor cells in bone tissue regeneration following injury.