An integrated manufacturing strategy to fabricate delivery system using gelatin/alginate hybrid hydrogels: 3D printing and freeze-drying

The extrusion-based 3D printing system was used to fabricate the bioscaffold with hybrid hydrogels of gelatin and alginate (G/A), with different total solid concentrations (3%, 5%, and 7%) and G/A ratios (1:2, 1:1, and 2:1). Rheological properties were related to the 3D printability and shape retention capacity of the hybrid hydrogels. For extrusion-based 3D printing using the current platform, the materials that were considered 3D printable showed shear-thinning flow behavior. Also, the printable materials demonstrated a storage modulus (Gʹ) higher than the loss modulus (Gʹʹ), with a loss factor (tan δ = Gʹʹ/Gʹ) in the range of 0.48–0.58 during the frequency sweep of 15–40 rad/s, which is the corresponding frequency that can be related to our 3D printing settings. Texture profile analysis indicated that among the optimal formulas for 3D printing, the bioscaffold fabricated with the hybrid gels of 7% 1:2 G/A had the highest hardness and adhesiveness. After freeze-drying, the hardness increased significantly (p < 0.05). The 3D printed bioscaffold was also freeze-dried to extend the shelf life and enhance the mechanical properties of the fabricated structure, moisture content, and water activity reduced significantly after freeze-drying. The scanning electron microscopy (SEM) results demonstrated that the 3D printed scaffolds had porous structures, which has the potential to encapsulate and deliver other bioactive compounds, such as enzymes, vitamins, antioxidants, and probiotics.