title: Synthetically tractable click hydrogels for three-dimensional cell culture formed using tetrazine-norbornene chemistry.
abstract: The implementation of bio-orthogonal click chemistries is a topic of growing importance in the field of biomaterials, as it is enabling the development of increasingly complex hydrogel materials capable of providing dynamic, cell-instructive microenvironments. Here, we introduce the tetrazine-norbornene inverse electron demand Diels-Alder reaction as a new cross-linking chemistry for the formation of cell laden hydrogels. The fast reaction rate and irreversible nature of this click reaction allowed for hydrogel formation within minutes when a multifunctional PEG-tetrazine macromer was reacted with a dinorbornene peptide. In addition, the cytocompatibility of the polymerization led to high postencapsulation viability of human mesenchymal stem cells, and the specificity of the tetrazine-norbornene reaction was exploited for sequential modification of the network via thiol-ene photochemistry. These advantages, combined with the synthetic accessibility of the tetrazine molecule compared to other bio-orthogonal click reagents, make this cross-linking chemistry an interesting and powerful new tool for the development of cell-instructive hydrogels for tissue engineering applications.
authors: Department of Chemical and Biological Engineering, the BioFrontiers Institute, and the Howard Hughes Medical Institute, University of Colorado at Boulder, Boulder, Colorado 80309, USA.
authors: Daniel L
authors: DL
authors: Alge
authors: Malar A
authors: MA
authors: Azagarsamy
authors: Dillon F
authors: DF
authors: Donohue
authors: Kristi S
authors: KS
authors: Anseth
mesh_terms: D001672:Biocompatible Materials; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D057930:Click Chemistry / Q000379:methods*; D003432:Cross-Linking Reagents / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009636:Norbornanes / Q000737:chemistry*; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D020100:Hydrogels; D009636:Norbornanes