3D Printing of Hydrophobic API-Infused Alginate–Gelatin Porous Scaffolds Reinforced with TiO ₂ and β-TCP for Tissue Regeneration and Drug Delivery

Scaffolds in tissue engineering and regenerative medicine have demonstrated improved functionality when loaded with pharmaceutical active ingredients (APIs). However, few systematic and energy-efficient methodologies allow controllable drug loading, particularly for hydrophobic compounds. This study presents a novel and controllable approach for loading 3D-printed alginate/gelatin hydrogel scaffolds with hydrophobic ibuprofen. The scaffold, composed mainly of alginate biopolymer, is nontoxic, biocompatible, and highly porous, allowing APIs to be easily incorporated within its structure. Owing to the ease of alginate gelation, microextrusion 3D printing was used to fabricate these hydrogel-based scaffolds. Reinforcing agents, including TiO₂ nanoparticles and β-tricalcium phosphate (β-TCP), were added to enhance mechanical strength and bioactivity. Rheological profiles of the emulsion-laden precursor solutions were evaluated to determine the optimal viscosity for extrusion. Physicochemical characterization using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermal analysis, and electron microscopy was performed to assess porosity and ibuprofen crystal morphology. The mechanical properties of the hydrogels were compared with those of a reference alginate/gelatin system, and drug release profiles were analyzed to evaluate diffusion mechanisms. The results showed that the loaded composite hydrogels could be successfully manufactured via 3D printing. The resulting cross-linked structures exhibited porosities ranging from 25 to 50 μm, with ibuprofen crystals (7-18 μm) formed within those pores. Furthermore, the 3D-printed composite hydrogels demonstrated enhanced mechanical properties, achieving elastic moduli up to 65 MPa, while drug release followed a biphasic, non-Fickian profile influenced by crystal size and pore structure. Overall, this approach demonstrates the feasibility of manufacturing printable alginate-based hydrogels with tunable drug-loading capacity, improved mechanical performance, and controlled release behavior, showing promising potential for bone and soft-tissue regeneration applications.