http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-2.xsd
Hybrid Polyethylene Glycol Hydrogels for Tissue Engineering Applications
Currently, organ transplant procedures are insufficient to address the needs of the number of patients that suffer of organ failure related disease. In the United States alone, only around 19% of the patients are able to get an organ transplant surgery and 25% die while waiting for a suitable donor. Tissue engineering (TE) has emerged as an alternative to organ transplant; thus, the aim of the present study was to validate a poly(ethylene glycol) diacrylate (PEG-DA) hydrogel system as a model for material scaffolding in TE applications. This work explores the influence of scaffold material properties on cell behavior. Specifically, scaffold modulus, mesh size, and biochemical stimuli were characterized and their influence on cell response was analyzed at the biochemical, histological and microenvironmental levels. Three different TE targets were evaluated: vocal fold restoration, vascular grafts and osteochondral applications. Vocal fold fibroblast (VFF) phenotype and extracellular matrix (ECM) production were impacted by initial scaffold mesh size and modulus. The results showed increasing levels of SM-α-actin and collagen production with decreasing initial mesh size/increasing initial modulus, which indicated that VFFs were induced to take an undesirable myofibroblast-like phenotype. In addition, it was possible to preserve VFF phenotype in long-term cultured hydrogels containing high molecular weight hyaluronan (HAHMW). On the other hand, regarding vascular graft applications, smooth muscle cell (SMC) phenotype was enhanced by increasing scaffold mesh size and modulus. Finally, the effect of scaffold inorganic content (siloxane) on rat osteoblasts and mouse mesenchymal stem cells was evaluated. Interestingly, the impact of inorganic content on cell differentiation seemed to be highly dependent on the initial cell state. Specifically, mature osteoblasts underwent transdifferentiation into chondrocyte-like cells with increasing inorganic content. However, Mesenchymal stem cells appeared to be preferentially driven toward osteoblast-like cells with an associated increase in osteocalcin and collagen type I production. The electronic version of this dissertation is accessible from http://hdl.handle.net/1969.1/149213
Doctor of Philosophy Texas A & M University 2011 http://hdl.handle.net/1969.1/149213