The Delivery of Igf-1 for Skeletal Muscle Regeneration within Abdominal Wall Hernias

Title of Document: THE DELIVERY OF IGF-1 FOR SKELETAL MUSCLE REGENERATION WITHIN ABDOMINAL WALL HERNIAS Erin Elizabeth Falco, Doctor of Philosophy, 2009 Directed By: Associate Professor, Dr. John P. Fisher, Fischell Department of Bioengineering At an ever increasing pace, synthetic biomaterials are being developed with specific functionalities for tissue engineering applications. These biomaterials possess properties including biocompatibility, mechanical strength, and degradation as well as functionalities such as specific cell adhesion and directed cell migration. However, synthetic polymers are often not completely biologically inert and may non-specifically react with the surrounding in vivo environment. An example of this reactivity is the release of acidic degradation products from hydrolytically degradable polymers based upon an ester moiety. These degradation products can lower the local pH and incite an inflammatory response as well as increase scaffold degradation rate. Therefore there has been a concerted effort in the research community to develop alternatives. In order to address this concern, a novel class of biomaterials based upon a cyclic acetal unit has been developed and investigated for both soft and hard tissue repair. This work specifically looks at a cyclic acetal biomaterial based on a 5-ethyl5-(hydroxymethyl)-β,β-dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD) monomer as a scaffold for abdominal wall hernia repair. Abdominal wall hernias are a growing concern for clinicians today as they occur in approximately 10% of all patients that undergo an abdominal procedure. Despite many advances in repair techniques, both wound healing and skeletal muscle regeneration is limited in many cases. This results in both a decrease in abdominal wall tissue function as well as a hernia recurrence rate of up to 50%. To address this high recurrence rate this project aims to create a functional gene delivery scaffold from the EH monomer. Scaffolds with different architectures were fabricated and skeletal muscle myoblast cell compatibility, material properties and protein and gene delivery rates were all investigated. THE DELIVERY OF IGF-1 FOR SKELETAL MUSCLE REGENERATION WITHIN ABDOMINAL WALL HERNIAS