Injectable and Degradable pH-Responsive Hydrogels via Spontaneous Amino–Yne Click Reaction

Injectable hydrogels have attracted increasing attention in tissue regeneration and local drug delivery applications. Current click reactions for preparing injectable hydrogels often require a photoinitiator or catalyst, which may be toxic and may involve complex synthesis of precursors. Here, we report a facile and inexpensive method to prepare injectable and degradable hydrogels via spontaneous amino-yne click reaction without using any initiator or catalyst under physiological conditions based on telechelic electron-deficient dipropiolate ester of polyethylene glycol and water-soluble commercially available carboxymethyl chitosan (CMC). The gelation time, mechanical property, and degradation rate of the hydrogels could be adjusted by varying CMC concentrations and stoichiometric ratios. The reversible pH-induced sol-gel transitions of the hydrogel are presented and the pH-controlled drug release behaviors are demonstrated, of which the mechanism is discussed. In vitro cytotoxicity assays and in vivo in situ injection study of the CMC-based hydrogels showed favorable gel formation, nontoxicity, and good tissue biocompatibility. Therefore, these biodegradable and injectable hydrogels prepared by spontaneous amino-yne click reaction hold potential for tissue engineering and other biomedical applications.