title: Responsive hydrogels produced via organic sol-gel chemistry for cell culture applications.
abstract: In this study, we report the synthesis of novel environmentally responsive polyurea hydrogel networks prepared via organic sol-gel chemistry and demonstrate that the networks can stabilize pH while releasing glucose both in simple aqueous media and in mammalian cell culture settings. Hydrogel formulations have been developed based on the combination of an aliphatic triisocyanate with pH-insensitive amine functional polyether and pH-sensitive poly(ethyleneimine) segments in a minimally toxic solvent suitable for the sol-gel reaction. The polyether component of the polyurea network is sufficiently hydrophilic to give rise to some level of swelling independent of environmental pH, while the poly(ethyleneimine) component contains tertiary amine groups providing pH sensitivity to the network in the form of enhanced swelling and release under acidic conditions. The reaction of these materials to form a network is rapid and requires no catalyst. The resultant material exhibits the desired pH-responsive swelling behavior and demonstrates its ability to simultaneously neutralize lactic acid and release glucose in both cell-free culture media and mammalian cell culture, with no detectable evidence of cytotoxicity or changes in cell behavior, in the case of either SA-13 human hybridomas or mouse embryonic stem cells. Furthermore, pH is observed to have a clear effect on the rate at which glucose is released from the hydrogel network. Such characteristics promise to maintain a favorable cell culture environment in the absence of human intervention.
authors.affiliation: Biomedical Engineering and Biotechnology Program, University of Massachusetts Lowell, One University Avenue, Lowell, MA 01854, USA.
authors.forename: Smruti
authors.initials: S
authors.lastname: Patil
authors.forename: Pulkit
authors.initials: P
authors.lastname: Chaudhury
authors.forename: Lisa
authors.initials: L
authors.lastname: Clarizia
authors.forename: Melisenda
authors.initials: M
authors.lastname: McDonald
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Reynaud
authors.forename: Peter
authors.initials: P
authors.lastname: Gaines
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D018929:Cell Culture Techniques / Q000379:methods*; D002460:Cell Line; D002474:Cell-Free System; D002625:Chemistry, Organic / Q000379:methods*; D003432:Cross-Linking Reagents / Q000737:chemistry; D005947:Glucose / Q000032:analysis; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051379:Mice; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000737:chemistry
chemical_list: D003432:Cross-Linking Reagents; D020100:Hydrogels; D011108:Polymers; D014867:Water; C045786:polyurea; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D005947:Glucose