(190a) Novel Thermally Responsive Macromers for the Fabrication of Injectable, in Situ Crosslinkable Hydrogels

Injectable hydrogels have demonstrated great potential for use as cell carriers in applications to engineer and regenerate human tissues. The main advantages of these systems are the ability to minimally invasively fill defects of complex shapes and the potential to encapsulate cells as well as growth factors during injection. However, hydrogels made from exclusively hydrophilic polymers often suffer from limited mechanical stability restricting their use in orthopedic applications. Ultimately, this project aims at developing injectable hydrogels of improved and controllable mechanical properties. In this study, we present the synthesis and characterization of novel injectable macromers that contain hydrophobic domains for mechanical reinforcement and functionalities for chemical crosslinking in situ. Macromers are synthesized from pentaerythritol diacrylate monostearate and N-isopropylacrylamide by radical polymerization. The physicochemical properties of the macromers, especially the phase transition temperature, and the density of hydroxyl groups available for chemical modification were controlled by copolymerization with acrylamide (AAm) and 2-hydroxyethyl acrylate (HEA), respectively. Macromer composition was verified by NMR spectroscopy and molecular weight was determined by GPC. Oscillating rheology was employed to characterize the thermally induced phase transition and the resulting gels. It was found that copolymerization with hydrophilic AAm increased the transition temperature and enhanced the stability of thermogels at 37°C. The integration of HEA with the macromers had opposed effects on hydrogel properties. Functional groups for in situ crosslinking were introduced by (meth)acrylation of the hydroxyl groups available along the thermogelling macromers. Acrylated macromers were analyzed by NMR and rheology. Crosslinked hydrogels were fabricated by heating a viscous solution of the acrylated macromers containing thermal initiators to 37°C. Initial experiments towards the encapsulation of cells are presented.