Vat 3D printing of full-alginate hydrogels via thiol–ene reactions towards tissue engineering applications

The rise of 3D printing has given an important impulse to the medical field, envisaging the possibility of creating artificially engineered tissues/organs perfectly suiting the tissue defects of patients using their own cells; this approach could in the future overcome the lack of tissue donors and decrease the possible dangerous tissue rejection. Different 3D printing technologies can be considered for the building of scaffolds; despite these promises, very few inks for light-induced 3D printing are nowadays available on the market. Herein, for the first time, the alginate backbone is completely functionalized with thiol and alkene groups (separately) to create an innovative full-alginate ink for digital light processing (DLP) printers. The alginate hydrogel is produced with the more biocompatible thiol-ene reaction instead of the most commonly used radical photopolymerization based on (meth)acrylates and without any addition of small crosslinkers to the printable formulation. Simple synthetic "two-reactions" or "one-pot" strategies are explored to functionalize alginate with thiol/alkene groups that are able to undergo click reactions. High levels of reproducibility of the modification strategy are obtained. The hydrogels are characterized by studying their formulation reactivity, mechanical properties, swelling kinetics and morphological appearance, placing the resulting hydrogel into the stiffer scaffold category. The selected hydrogel formulation, tested as the ink for DLP 3D printing, demonstrates good processability and geometry fidelity with the possibility of forming 3D suspended structures. In the end, cell attachment and proliferation are evaluated on the hydrogel, certifying the possible use of the ink for the creation of tissue/organ substitutes (e.g., intestines or tendons) in tissue engineering applications.