Date of Award
Open Access Thesis
Medical Doctor (MD)
Francis Y. Lee
Non-union is a devastating complication of fracture and can be precipitated by abnormal
inflammatory states including infection and diabetes.
This thesis focuses on four related research problems that are addressed through original
scientific investigation and literature review. In addressing these questions, this dissertation
presents evidence for the following conclusions through in vivo animal models and using methods
including bacterial cell culture and counting, histology, radiography, and micro-computed
1. Rifampin-loaded hydrogels decrease bacterial load and improve fracture healing in
a MRSA-infected open fracture model.
2. MRSA-infected nonunion is characterized by impaired chondrocyte maturation and
is associated with IL-1 and NF-KB activation.
3. Local teriparatide improves radiographic fracture healing in a type 2 diabetic mouse
model, but is inferior to systemic treatment.
4. Systemic administration of teriparatide, along with systemic antibiotics, improves
fracture healing in a diabetic, MRSA-infected mouse tibia fracture model.
This current work is not without limitation, and many aspects of this work are still in
progress. Nevertheless, the author hopes that this dissertation will serve as providing meaningful,
foundational data for future laboratory and clinical studies to improve our understanding of
inflammatory fracture healing and arrive at new therapies to advance the practice of fracture care.
Cahill, Sean Vincent, "Approaches To Fracture Healing Under Inflammatory Conditions: Infection And Diabetes" (2020). Yale Medicine Thesis Digital Library. 3887.
This Article is Open Access