Cellular responses to degradable cyclic acetal modified PEG hydrogels

In this study, high viability of bone marrow stromal stem cells (BMSCs) encapsulated in a synthetic, poly[poly(ethylene glycol)-co-cyclic acetal] (PECA) hydrogel has been reported. This novel degradable hydrogel, which contains cyclic acetal as degradable segments and poly(ethylene glycol) (PEG) as hydrophilic segments, has been designed to limit the release of acidic products during hydrolytic degradation. PECAs with three different molecular weights (PECA 600, 1000, and 2000) were prepared to evaluate the effect of polymer main chain molecular weight on the viability and morphology of BMSCs embedded in PECA hydrogels as well as the viability of BMSCs exposed to PECA degradation products. Results demonstrated high BMSC viability when incubated in control media with PECA, while a significant decrease in viability was noted after 4 days when incubated in media augmented with PEG diacrylate. There was no effect of PECA molecular weight on the differentiation and cytotoxicity of degradation products up to 4 days, indicating that the degradation products' terminal carbonyl groups do not significantly affect cell viability and differentiation. BMSC viability when embedded on PECA hydrogels was evaluated by a LIVE/DEAD assay, and confirmed high viability up to 14 days. Gene expression analysis confirmed that BMSCs embedded in PECA hydrogels undergo osteogenic differentiation. Histological analysis also showed that cell morphology was significantly influenced by hydrogel swelling degree, which is itself controllable by the molecular weights of PECA main chains. These results indicate that PECA hydrogels may be utilized as scaffolds for regeneration of bone-like tissues.