Facile synthesize of norbornene-hyaluronic acid to form hydrogel via thiol-norbornene reaction for biomedical application

Norbornene modified hyaluronic acid (NorHA) has attracted enormous attention in biological research for its ability to form hydrogels in a cell-friendly way. However, traditional routes to synthesis NorHA are involved with laboring and cumbersome steps. In this study, an alternative single-step approach to fabricate NorHA is reported. NorHA was first synthesized by conjugating carbic anhydride (CA) with hyaluronic acid (HA) directly and NorHA with various norbornene substitution degrees (SD) was obtained by adjusting the reaction pH, time, and the amounts of CA easily. Porous NorHA hydrogels were prepared via orthogonal thiol-norbornene reaction under blue light irradiation. Furthermore, the resulting gelation performances, swelling behaviors, and transmittance of NorHA hydrogels were adjusted by varying the content of crosslinker or NorHA. The cytocompatibility evaluation suggests that the obtained NorHA were suitable for cell encapsulation. Finally, we show that this approach also can be extended to other natural or synthesized biopolymers to prepare cytocompatible photo-crosslinked hydrogels.