4D Printing of Hydrophobic API-Infused Alginate-Gelatin Porous Scaffolds Reinforced with TiO2 and β-TCP for Tissue Regeneration and Drug Delivery

Although scaffolds in tissue engineering and regenerative medicine have shown enhanced properties when loaded with pharmaceutical active ingredients (API), not many systematic methodologies have been developed allowing controllable loads and a low energy input, especially hydrophobic drugs. In this work, a novel approach to load 3D printed alginate/gelatin hydrogel scaffolds with a hydrophobic antiinflammatory is presented. The scaffold, made mainly of alginate biopolymer is non-toxic, biocompatible, and highly porous. Inside its porous structure, active pharmaceutical ingredients (API) can be easily loaded. Due to the alginate ease of gelation, microextrusion 3D printing was used to produce these hydrogels-based scaffolds. In addition to the API, TiO2 and beta-tricalcium phosphate (𝛽-TCP) were incorporated in the scaffold to create reinforced composite hydrogels. Rheological profiles of the emulsion-laden solutions before crosslinking were analyzed. FTIR, XRD, thermal analysis, and electron microscopy are used to measure porosity and analyze the ibuprofen crystal size. Mechanical properties of the hydrogels were also compared and analyzed against a reference hydrogel with just alginate/gelatin. Finally, drug release curves were developed. The results showed that the loaded composite hydrogels could be manufactured by 3D printing. The resulting crosslinked structures have a porosity from 25𝜇m to 50 𝜇m, and crystals of the API were formed inside those pores. Moreover, the composite hydrogels showed enhanced mechanical properties up to 65 MPa of elastic modulus. Drug delivery curves also showed dependence on the crystal size inside the porous structure. Overall, this approach enables the synthesis of a printable composite alginate solution, loaded with an API, and with adequate physical properties for tissue regeneration.