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

Abstract 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 C 6 ‐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.