Technological development of Alginate/Gelatin composite hydrogel fabricated by microextrusion based printing for tissue regeneration

Alginate hydrogels have shown an enormous potential for tissue engineering due to its non-toxicity, biocompatibility, and structural similarity to extracellular matrices. To produce these hydrogels, different manufacturing techniques can be used, including microextrusion 3D printing. Current efforts for hydrogels in tissue engineering are centered on improving bioactivity and mechanical properties by the incorporation of a second biopolymer or bioceramics; and loading these materials with pharmaceutical drugs to promote a better healing process. In this work, the study of the synthesis process of alginate/gelatin hydrogels reinforced with TiO2 and beta-tricalcium phosphate (beta-TCP) and loaded with ibuprofen, its extrusion in a modified 3D Printer, and its material characterization were proposed. The hydrogel systems were successfully micro-extruded by tuning the concentration of the pre-crosslinking agent up to 0.20 w/v% and a rheological profile was obtained. FT-IR, XRD, and TGA were used to perform a physicochemical characterization and prove the growth of ibuprofen crystals inside the porous material. For the drug loading, stable microemulsions were obtained with polyvinyl alcohol (PVA) as emulsifier and various solvents, including dichloromethane. The pores of the crosslinked printed structures were measured using SEM and resulted in an average pore size from 160 μm to 40 μm, depending on the material composition, all with adequate porosity for tissue engineering. Furthermore, the hydrogels reinforced with TiO2 and beta-TCP showed enhanced mechanical properties up to 65 MPa of elastic modulus. Controllable drug loading was achieved up to 35 w/w% of the dry hydrogel with more than 50% of the loaded ibuprofen dissolving in less than one hour. Additionally, while the hydrogel was microextruded in the 3D printer, it was found that as more layers of the design were deposited in the built platform, there was an increase of the line width of the bottom layers due to its viscous deformation. Shrinkage of the design when the hydrogel is crosslinked and later freeze-dried was also measured and found to be up to 27% from the printed design. Overall, the approach taken enables to synthesize a printable composite alginate solution, loaded with an API, with adequate physical properties for tissue regeneration.