Orbital Floor Regeneration Using Cyclic Acetal Hydrogels through Enhanced Osteogenic Cell Signaling of Mesenchymal Stem Cells

Title of Document: ORBITAL FLOOR REGENERATION USING CYCLIC ACETAL HYDROGELS THROUGH ENHANCED OSTEOGENIC CELL SIGNALING OF MESENCHYMAL STEM CELLS Martha Wheaton Betz, Doctor of Philosophy, 2009 Directed By: Associate Professor John P. Fisher, Fischell Department of Bioengineering Orbital floor fractures are a serious consequence of craniofacial trauma and account for approximately 60-70% of all orbital fractures. Unfortunately, the body’s natural response to orbital floor defects generally does not restore proper function and facial aesthetics which is complicated by the thin bone and adjacent sinuses. We propose using a tissue engineering strategy to regenerate orbital floor bone. To this end, a functional biomaterial was investigated to enhance orbital floor regeneration. First, a bone marrow stromal cell population was isolated and differentiation assessed via coculture with chondrocytes and osteogenic media supplements. A cyclic acetal biomaterial composed of the cyclic acetal monomer 5-ethyl-5(hydroxymethyl)-β,β-dimethyl-1,3-dioxane-2-ethanol diacrylate (EHD) and poly(ethylene glycol) diacrylate (PEGDA) was then developed for cell encapsulation. The previously investigated bone marrow stromal cells were then used to determine the effects of the ammonium persulfate/N,N,N’,N’-tetramethylethylenediamine initiator system used to crosslink the EH-PEG hydrogels on cell viability, metabolic activity, and osteogenic differentiation. Next, EH-PEG hydrogels were implanted into orbital floor defects with bone morphogenetic protein-2, where tissue response and surrounding bone growth was analyzed. To improve surrounding tissue interaction and cell infiltration, macroporous EH-PEG hydrogels were created using porogen-leaching. These hydrogels were characterized using optical coherence tomography for pore size, porosity, and cell viability. In addition, these macroporous hydrogels were created with varying architecture to analyze the effects on osteogenic signaling and differentiation. This work outlines the potential application of EHPEG hydrogels for use in orbital floor repair. ORBITAL FLOOR REGENERATION USING CYCLIC ACETAL HYDROGELS THROUGH ENHANCED OSTEOGENIC CELL SIGNALING OF MESENCHYMAL STEM CELLS