Comparison of Thiol-ene and Tetrazine Click Crosslinking of Gelatin Hydrogels for Tissue Engineering

Abstract

Chemically crosslinked gelatin hydrogels are popular biomaterials applied for uses such as 3D matrices for tissue engineering applications. Gelatin hydrogels can be chemically crosslinked using various reactions that fall under the “click” chemistry paradigm. Click chemistry is an incredibly powerful tool to alter different hydrogel properties in fast, simplistic way. Here, we compare two impactful click reactions: a radical mediated, thiol-ene–norbornene reaction and an inverse electron demand Diels-Alder (IEDDA) tetrazine–norbornene reaction. The radical mediated reaction resulted in chemical crosslinks throughout the hydrogel while the IEDDA reaction resulted in not only chemical crosslinks, but physical crosslinks as well due to various secondary interactions. To truly understand how these different click reactions impact hydrogel properties, experiments were performed to characterize hydrogel modulus, swelling, degradability, and cytocompatibility. Based upon the contrasting aspects of the two gel formulations, it can be concluded that these two different chemistries have diverse applications due to their differences in modulus, swelling ratio, and degradability.