Applications of Spatially-Resolved Hybrid Hydrogels

Low-molecular-weight gelators (LMWGs) form gel networks through non-covalent interactions. Materials formed from these small molecules are often responsive to external stimuli, making them attractive for high-tech applications. This responsiveness often comes at the expense of durability. In contrast, polymer gelators form crosslinked networks which are often robust, but unresponsive. To harness the desirable properties of both classes of material, a robust hybrid hydrogel comprising LMWG 1,3:2,4-dibenzylidene-D-sorbitol diacylhydrazide (DBS-CONHNH2) and photo-inducible PG (poly(ethylene glycol)dimethacrylate), PEGDM) was developed. PEGDM was crosslinked within a supporting DBS-CONHNH2 gel matrix by photoirradiation. Spectroscopic studies indicated that non-covalent interactions between the LMWG and PG networks subtly modified the material properties (e.g. gel stiffness). The use of a printed mask during photoirradiation enabled spatial control of PEGDM crosslinking. We demonstrated the application of these hybrid gels as active drug release matrices. Specific interactions between naproxen (NPX) and the DBS-CONHNH2 nanofibres mediated pH-dependent release. DBS-CONHNH2 was found to largely retain its responsiveness within the hybrid gel, which demonstrated a good degree of pH-dependent NPX release. A photo-patterned hybrid gel preferentially delivered NPX into a compartment at pH 7 compared to one at pH 2.8, illustrating potential for targeted drug release. The applications of photo-patterned hybrid gels as enzyme bioreactors were explored next. Alkaline phosphatase retained its activity within hybrid gels which behaved as a semi-permeable membrane - entrapping the enzyme but allowing diffusion of reactants and products. First generation reactors showed good reaction conversion over relatively short timescales. Cytocompatibility studies indicated that hybrid hydrogels were compatible with mesenchymal stem cells, supporting cell growth over one month. Gel matrix-regulated stem cell differentiation was apparent on the stiffest hybrid gels tested. Cells cultured on these materials exhibited elevated alkaline phosphatase content and calcium deposition, indicators of osteoblast formation. Preliminary studies suggest that spatially-resolved hybrid gels induce spatially-resolved stem cell morphology.