Decoupled pH- and Thermo-Responsive Injectable Chitosan/PNIPAM Hydrogel via Thiol-Ene Click Chemistry for Potential Applications in Tissue Engineering.

Stimuli-responsive chitosan (CS) hydrogels exhibit great potential for drug delivery and tissue engineering; however, the structure of these stimuli-responsive CS hydrogels, such as dual pH- and thermo-responsive hydrogels, is difficult to control or needs additional crosslinking agents. Here, a new dual pH- and thermo-responsive hydrogel system is developed by combining pH-responsive C6 -OH allyl-modified CS (OAL-CS) with thermo-responsive poly(N-isopropylacrylamide) (PNIPAM). The thiol groups in PNIPAM and the allyl groups in OAL-CS can rapidly form crosslinking hydrogel network by "thiol-ene" click chemistry under UV irradiation. As expected, the swelling ratio of the OAL-CS/PNIPAM hydrogel can be controlled by changing pH and temperature. Moreover, the hydrogel displays non-cytotoxic nature toward human bone marrow mesenchymal stem cells, and the histological analyses reveal the subcutaneous tissue with no signs of inflammation after 5 days of injection in vivo. The results indicate that the new OAL-CS/PNIPAM hydrogel has potential to serve as a smart injectable platform for application in drug delivery and tissue engineering.