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"APPLICATION OF LOCAL INSULIN AGENTS TO ACCELERATE OSSEOUS HEALING"

by
David Naisby Paglia
Biomedical Engineering Program
B.S. 2006, Manhattan College, Riverdale, N.Y.
M.S. 2008, NJIT, Newark, N.J.



Thesis Advisor: Sheldon Lin, M.D.
Associate Professor
Department of Orthopaedics

Wednesday, June 15, 2011
ACC D-1635, 2:00 P.M.


Abstract

Appropriate osseous fracture healing is a complex process that may be compromised by environmental factors, certain pharmaceuticals, steroid use, smoking, advanced age, pregnancy, and metabolic diseases like diabetes. To treat these individuals, as well as the normal population, clinicians must weigh the efficacy and potential side effects of available treatments. In recent years, both external stimulation systems, and biological agents have been applied to the clinical arena to treat those with risk of compromised healing. These treatment modalities are limited by risks and are dependent on patient compliance.
Orthopedic care relies on the timely principles of restoration of anatomy, appropriate osseous stabilization, and subsequent restoration of bone function. Clearly, application of an osseous agent with few potential side effects, should significantly decrease risk of delayed union and non-union.
Previous studies have indicated that local insulin administered to diabetic animals following a fracture, ameliorates the compromised mechanical and histological properties of diabetic bone. However, delivery of insulin is limited by release kinetics, potential protein degradation, and risk of hypoglycemic seizures. As such, alternative insulin agents have been investigated as options to accelerate fracture healing.
The hypothesis that locally delivered insulin or an alternative insulin agent accelerates femur fracture healing in a non-diabetic BB Wistar rat model, were investigated. Prolonged release of each adjunct at the fracture site was critical to accelerating angiogenesis, chondrogenesis, and enhancing the mechanical strength of healing bones. Application of carriers and novel coating techniques resulted in improved release kinetics and lower dosages necessary to achieve enhanced mechanical strength. Results suggest that either insulin or the proposed insulin agents discussed in this dissertation have the potential to become the new clinical “gold standard” for treating fractures in non-diabetics and those with risk factors for non-union.


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