Hydrogel Synthesis and Stabilization via Tetrazine Click-Induced Secondary Interactions. Academic Article uri icon


  • The discovery of tetrazine click-induced secondary interactions is reported as a promising new tool for polymeric biomaterial synthesis. This phenomenon is first demonstrated as a tool for poly(ethylene glycol) (PEG) hydrogel assembly via purely non-covalent interactions and is shown to yield robust gels with storage moduli one to two orders of magnitude higher than other non-covalent crosslinking methods. In addition, tetrazine click-induced secondary interactions also enhance the properties of covalently crosslinked hydrogels. A head-to-head comparison of PEG hydrogels crosslinked with tetrazine-norbornene and thiol-norbornene click chemistry reveals an approximately sixfold increase in storage modulus and unprecedented resistance to hydrolytic degradation in tetrazine click-crosslinked gels without substantial differences in gel fraction. Molecular dynamic simulations attribute these differences to the presence of secondary interactions between the tetrazine-norbornene cycloaddition products, which are absent in the thiol-norbornene crosslinked gels.

published proceedings

  • Macromol Rapid Commun

author list (cited authors)

  • Holt, S. E., Rakoski, A., Jivan, F., Prez, L. M., & Alge, D. L.

citation count

  • 7

complete list of authors

  • Holt, Samantha E||Rakoski, Amanda||Jivan, Faraz||PĂ©rez, Lisa M||Alge, Daniel L

publication date

  • July 2020