Synthesis and Characterization of Shear-thinning Hydrogel using Tetronic-adamantane conjugate(Tet-Ada) and Poly(β-cyclodextrin) for Injectable Biomaterials
Injectable biomaterials have been widely utilized for biomedical applications because their implantation into the human body is minimally invasive and the therapeutic agents can be delivered locally. Shear-thinning hydrogels are notable because of their unique property, whereby the viscosity decreases (solution) under a shear stress and recovers (gel) after the removal of the shear stress. However, as most shear-thinning hydrogels are formed by physical crosslinking, their mechanical properties are often poor. To overcome this issue, additional secondary cross-linkages, via UV-crosslinking, thiol-ene reaction, and oxidative crosslinking, are created. In this study, we developed a new shear-thinning hydrogel through host-guest interactions and thermo-gelling at 37℃ to improve the mechanical strength of shear-thinning hydrogels. Tetronic-Adamantane (Tet-Ada) and β-cyclodextrin polymers (poly(β-CD)) which can dissolve in aqueous environments were successfully synthesized. The chemical structures of the synthesized polymers were confirmed by proton nuclear magnetic resonance (1H-NMR) spectroscopy. The hydrogels rapidly started to form via host-guest interactions between the Ada and β-CD and self-assembly of the Tet micelles at 37℃. The elastic modulus of the hydrogels was assessed by varying both, the concentrations of the polymers and the temperature. Importantly, the Tet-Ada/poly(β-CD) hydrogels showed shear-thinning behaviors and rapid recovery properties. They also exhibited the pH-responsive and long-term release of hydrophobic drug, doxorubicin (DOX). In addition, we demonstrated the biocompatibility of the hydrogels and the anticancer effect of the DOX released from the hydrogels. In conclusion, we suggest the potential usage of the Tet-Ada/poly(β-CD) hydrogels as injectable materials for various biomedical applications, including drug delivery systems.
