Mechanically tunable, human mesenchymal stem cell viable poly(ethylene glycol)–oxime hydrogels with invariant precursor composition, concentration, and stoichiometry

Hydrogels are used widely for exploratory tissue engineering studies. However, currently, no hydrogel systems have been reported which exhibit a wide range of elastic modulus without changing precursor concentration, identity, or stoichiometry. Herein, ester- and amide-based poly(ethylene glycol) (PEG)–oxime hydrogels with tunable moduli (∼5–30 kPa) were synthesized with identical precursor mass fraction, stoichiometry, and concentration by varying the pH and buffer concentration of the gelation solution, exploiting the kinetics of oxime bond formation. The observed modulus range can be attributed to increasing amounts of network defects in slower forming gels, as confirmed by equilibrium swelling and small-angle neutron scattering (SANS) experiments. Finally, human mesenchymal stem cell (hMSC) viability was confirmed in these materials in a 24-h assay. While this was only an initial demonstration of the potential utility, the controlled variation in defect density and modulus is an important step forward in isolating system variables for hypothesis-driven biological investigations.