Date of Award

January 2020

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Francis Y. Lee

Abstract

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

tomography:

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.

Comments

This is an Open Access Thesis.

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