Gelation characteristics and osteogenic differentiation of stromal cells in inert hydrolytically degradable micellar polyethylene glycol hydrogels.

摘要

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 &