Chang, Chun-YiNguyen, HanFrahm, EllenKolaczyk, KeithLin, Chien-Chi2024-09-162024-09-162024-03-28Chang CY, Nguyen H, Frahm E, Kolaczyk K, Lin CC. Triple click chemistry for crosslinking, stiffening, and annealing of gelatin-based microgels. RSC Appl Polym. 2024;2(4):656-669. Published 2024 Mar 28. doi:10.1039/d3lp00249ghttps://hdl.handle.net/1805/43313Microgels are spherical hydrogels with physicochemical properties ideal for many biomedical applications. For example, microgels can be used as individual carriers for suspension cell culture or jammed/annealed into granular hydrogels with micron-scale pores highly permissive to molecular transport and cell proliferation/migration. Conventionally, laborious optimization processes are often needed to create microgels with different moduli, sizes, and compositions. This work presents a new microgel and granular hydrogel preparation workflow using gelatin-norbornene-carbohydrazide (GelNB-CH). As a gelatin-derived macromer, GelNB-CH presents cell adhesive and degradable motifs while being amenable to three orthogonal click chemistries, namely the thiol-norbornene photo-click reaction, hydrazone bonding, and the inverse electron demand Diels-Alder (iEDDA) click reaction. The thiol-norbornene photo-click reaction (with thiol-bearing crosslinkers) and hydrazone bonding (with aldehyde-bearing crosslinkers) were used to crosslink the microgels and to realize on-demand microgel stiffening, respectively. The tetrazine-norbornene iEDDA click reaction (with tetrazine-bearing crosslinkers) was used to anneal microgels into granular hydrogels. In addition to materials development, we demonstrated the value of the triple-click chemistry granular hydrogels via culturing human mesenchymal stem cells and pancreatic cancer cells.en-USPublisher PolicyMicrogelsBiomedical researchGranular hydrogelsArticle