Facile Fabrication of Three-Dimensional Hydrogel Film with Complex Tissue Morphology

In this study, we proposed a simple and easy method for fabricating a three-dimensional (3D) structure that can recapitulate the morphology of a tissue surface and deliver biological molecules into complex-shaped target tissues. To fabricate the 3D hydrogel film structure, we utilized a direct tissue casting method that can recapitulate tissue structure in micro-/macroscale using polydimethylsiloxane (PDMS). A replica 3D negative mold was manufactured by a polyurethane acrylate (PUA)-based master mold. Then, we poured the catechol-conjugated alginate (ALG-C) solution into the mold and evaporated it to form a dried film, followed by crosslinking the film using calcium chloride. The ALG-C hydrogel film had a tensile modulus of 725.2 ± 123.4 kPa and maintained over 95% of initial weight after 1 week without significant degradation. The ALG-C film captured over 4.5 times as much macromolecule (FITC-dextran) compared to alginate film (ALG). The cardiomyoblast cells exhibited high cell viability over 95% on ALG-C film. Moreover, the ALG-C film had about 70% of surface-bound lentivirus (1% in ALG film), which finally exhibited much higher viral transfection efficiency of GFP protein to C2C12 cells on the film than ALG film. In conclusion, we demonstrated a 3D film structure of biofunctionalized hydrogel for substrate-mediated drug delivery, and this approach could be utilized to recapitulate the complex-shaped tissues.