pH-Ionizable <i>in Situ</i> Gelling Poly(oligo ethylene glycol methacrylate)-Based Hydrogels: The Role of Internal Network Structures in Controlling Macroscopic Properties

The incorporation of charge within <i>in situ</i> covalently gelling poly­(oligo ethylene glycol methacrylate) (POEGMA) precursor polymers enables the fabrication of hydrogels that exhibit both pH-responsive swelling and tunable network structures due to multimechanism cross-linking interactions. The gelation times, swelling responses, degradation kinetics, and mechanics of the resulting gels were strongly influenced by both the type of charge(s) incorporated and pH, with both amphoteric gels and anionic gels showing clear evidence of dual network formation. While the amphoteric dual network was anticipated due to charge interactions, the mechanism of the 5-fold enhancement in mechanical properties observed with the anionic gel relative to the neutral gel was revealed by isothermal titration calorimetry and small-angle neutron scattering to relate to the formation of a zippered chain structure based on dipole–dipole interactions. Consequently, rational design of the chemistry and the microscopic network structure results in controllable macroscopic properties amenable to potential biomedical applications

Injectable and Degradable Poly(Oligoethylene glycol methacrylate) Hydrogels with Tunable Charge Densities as Adhesive Peptide-Free Cell Scaffolds

Injectable, dual-responsive, and degradable poly­(oligo ethylene glycol methacrylate) (POEGMA) hydrogels are demonstrated to offer potential for cell delivery. Charged groups were incorporated into hydrazide and aldehyde-functionalized thermoresponsive POEGMA gel precursor polymers via the copolymerization of N,<i>N</i>′-dimethylaminoethyl methacrylate (DMAEMA) or acrylic acid (AA) to create dual-temperature/pH-responsive in situ gelling hydrogels that can be injected via narrow gauge needles. The incorporation of charge significantly broadens the swelling, degradation, and rheological profiles achievable with injectable POEGMA hydrogels without significantly increasing nonspecific protein adsorption or chronic inflammatory responses following in vivo subcutaneous injection. However, significantly different cell responses are observed upon charge incorporation, with charged gels significantly improving 3T3 mouse fibroblast cell adhesion in 2D and successfully delivering viable and proliferating ARPE-19 human retinal epithelial cells via an “all-synthetic” matrix that does not require the incorporation of cell-adhesive peptides