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 -cyclooctene (TCO) and -tetrazine (Tz). A hydrophobic TCO crosslinker and homo-difunctional poly(ethylene glycol) (PEG)-based macromers with the tetrazine group conjugated to PEG via a stable carbamate (PEG-Tz1) bond or a labile hydrazone (PEG-Tz2) linkage were synthesized. After laying an ethyl acetate solution of TCO over an aqueous solution of 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-Tz2 and PEG-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.