Abstract
In this work, we engineered highly biocompatible and fast absorbent injectable hydrogels derived from norbornene (Nb)-functionalized hyaluronic acid (HA-Nb) and a water-soluble cross-linker possessing tetrazine (Tz) functional groups on both ends of polyethylene glycol (PEG-DTz). The by-product (nitrogen gas) of the inverse electron demand Diels−Alder (IEDDA) cross-linking reaction carved porosity in the resulting hydrogels. By varying the molar ratio of HA-Nb and PEG-DTz (Nb:Tz = 10:10, 10:5, 10:2.5), we were able to formulate hydrogels with tunable porosity, gelation time, mechanical strength, and swelling ratios. The hydrogels formed quickly (gelation time < 100 s), offering a possibility to use them as an injectable drug delivery system. The experimental data showed rapid swelling and a high swelling ratio thanks to the existence of PEG chains and highly porous architectures of the hydrogels. The hydrogels were able to encapsulate a high amount of curcumin (~99%) and released the encapsulated curcumin in a temporal pattern. The PEG-DTz cross-linker, HA-Nb, and the resulting hydrogels showed no cytotoxicity in HEK-293 cells. These fast absorbent hydrogels with excellent biocompatibility fabricated from HA-Nb and the IEDDA click-able cross-linker could be promising drug carriers for injectable drug delivery applications.