Tunable Synthesis of Hydrogel Microfibers via Interfacial Tetrazine Ligation.

Crosslinked, degradable, and cell-adhesive hydrogel microfibers were synthesized via interfacial polymerization employing tetrazine ligation, an exceptionally fast bioorthogonal reaction between strained trans -cyclooctene (TCO) and s -tetrazine (Tz). A hydrophobic tris TCO crosslinker and homo-difunctional poly(ethylene glycol) (PEG)-based macromers with the tetrazine group conjugated to PEG via a stable carbamate (PEG- bis Tz1) bond or a labile hydrazone (PEG- bis Tz2) linkage were synthesized. After laying an ethyl acetate solution of tris TCO over an aqueous solution of bis Tz macromers, mechanically robust microfibers were continuously pulled from the oil-water interface. The resultant microfibers exhibited comparable mechanical and thermal properties but different aqueous stability. Combining PEG- bis Tz2 and PEG- bis Tz3 with a dangling arginine-glycine-aspartic acid (RGD) peptide in the aqueous phase yielded degradable fibers that supported the attachment and growth of primary vocal fold fibroblasts. The degradable and cell-adhesive hydrogel microfibers are expected to find utility in a wide array of tissue engineering applications.