(513f) Fabrication and Characterization of Thermally Responsive, in Situ Crosslinkable Hydrogels Based On Poly(N-isopropylacrylamide)

Injectable, in situ forming hydrogels are an attractive option for cell encapsulation in tissue engineering. Physical, thermoresponsive hydrogels form in a mild and fast manner which is advantageous for the delivery of cells and bioactive molecules, but often possess insufficient stability and mechanical properties. In this study, we have developed hydrogels that gel in response to two independent, physical and chemical, mechanisms, namely lower critical solution temperature behavior and covalent crosslinking. Poly(N-isopropylacrylamide)-based macromers were functionalized with (meth)acrylate end groups which enable crosslinking upon the addition of a free radical initiator system. Rheological, macroscopic and swelling studies confirmed the increased stability and higher swelling of thermally gelled and chemically crosslinked hydrogels as compared to only thermally gelled samples. The effect of end-group functionalization on hydrogel swelling in aqueous media was evaluated as a function of temperature, crosslinking initiator concentration and time. Acrylated formulations showed higher swelling ratios than their methacrylated analogues below their lower critical solution temperatures (4°C) but this phenomenon was reversed above the LCST (37°C). Upon incubation in osteogenic cell culture medium, the hydrogels exhibited constant swelling over a period of eight weeks and increasing mineralization. These materials are further evaluated as promising candidates for cell and drug delivery in craniofacial bone tissue engineering.