Abstract
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.
Highlights
Substrate-mediated drug delivery has been a promising approach for treating a wide spectrum of human diseases [1,2]
The alginate film (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 PDMS-based negative mold of the cardiac structure was produced after removing cardiac tissue
Summary
Substrate-mediated drug delivery has been a promising approach for treating a wide spectrum of human diseases [1,2]. In the field of cardiac tissue engineering, substrate-mediated approaches of biocompatible polymers have been widely applicable for ease of drug loading and delivery [5,6]. The big challenges in designing the substrate for in vivo delivery of drugs have been addressed in terms of the heterogeneous tissue surface, such as cardiac structure. Conventional substrates such as 2D flat cell sheet or nanofiber scaffold have inappropriate structures to adhere stably on the rough surface of cardiac tissue [11]. Even though a two-dimensional scaffold can be stretchable or flexible, it might be readily dislocated or detached from the cardiac surface owing to the active contraction of cardiomyocytes
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