Date of Award
Open Access Thesis
The use of polyethylene glycol (PEG) hydrogels in tissue engineering is limited by their persistence in the site of regeneration. In an attempt to produce degradable PEG-based hydrogels while preserving the unique properties of PEG, linear (LPELA) and star (SPELA) poly(ethylene glycol-co-lactide) acrylate, star (SPEDA) poly(ethylene glycol-co-dioxanone), star (SPEGA) poly(ethylene glycol-co-glycolide) acrylate as the least hydrophobic and (SPECA) poly(ethylene glycol-co-caprolactone) as the most hydrophobic macromonomers with short hydrophobic segments were synthesized. The hydrogels were characterized with respect to gelation time, modulus, water content, sol fraction, degradation, and osteogenic differentiation of encapsulated marrow stromal cells (MSCs). Chain extension of PEG with short hydrpphobic segments resulted in micelle formation for all types of macromonomers. Due to micelle formation, there was a significant decrease in gelation time of SPEXA precursor solutions with degradable hydrophobic chain extension for all types. The star SPELA hydrogel had higher modulus, lower water content, and lower sol fraction than the linear LPELA. The shear modulus of star SPELA hydrogel was 2.2 fold higher than LPELA while the sol fraction of SPELA hydrogel was 5 fold lower than LPELA. The degradation of SPELA hydrogels depended strongly on the number of lactide monomers per macromonomer (nL) and showed a biphasic behavior. For example, as nL increased from zero to 3.4, 6.4, 11.6, and 14.8, mass loss increased from 7 to 37, 80, 100%, and then deceased to 87%, respectively, after 6 weeks of incubation. SPEXA gels chain extended with the least hydrophobic glycolide showed the highest mechanical strength and completely degraded within days, lactide within weeks, p-dioxanone and ε-caprolactone degraded within months. The wide range of degradation rates observed for SPEXA gels can be explained by large differences in equilibrium water content of the micelles for different HA monomers. MSCs encapsulated in SPELA hydrogels, with or without supplementing with bone morphogenetic protein-2 (BMP2), expressed osteogenic markers Dlx5, Runx2, osteopontin, and osteocalcin and formed a mineralized matrix. The expression of osteogenic markers and extent of minerlization was significantly higher in the presence of BMP2. Results demonstrate that hydrolytically degradable PEG-based hydrogels are potentially useful as a delivery matrix for stem cells in regenerative medicine.
Barati, D.(2013). Gelation Characteristics and Osteogenic Differentiation of Stromal Cells In Inert Hydrolytically Degradable Micellar Polyethylene Glycol Hydrogels. (Master's thesis). Retrieved from http://scholarcommons.sc.edu/etd/2370