Alginate/Gelatin Hydrogels Reinforced with TiO2 and β-TCP Fabricated by Microextrusion-based Printing for Tissue Regeneration

Abstract

Three-dimensional (3D) printing technologies have become an attractive manufacturing process to fabricate scaffolds in tissue engineering. Recent research has focused on the fabrication of alginate complex shaped structures that closely mimic biological organs or tissues. Alginates can be effectively manufactured into porous three-dimensional networks for tissue engineering applications. However, the structure, mechanical properties, and shape fidelity of 3D-printed alginate hydrogels used for preparing tissue-engineered scaffolds is difficult to control. In this work, the use of alginate/gelatin hydrogels reinforced with TiO2 and β-tricalcium phosphate was studied to tailor the mechanical properties of 3D-printed hydrogels. The hydrogels reinforced with TiO2 and β-TCP showed enhanced mechanical properties up to 20 MPa of elastic modulus. Furthermore, the pores of the crosslinked printed structures were measured with an average pore size of 200 μm. Additionally, it was found that as more layers of the design were printed, 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 freeze dried was also measured and found to be up to 27% from the printed design. Overall, the proposed approach enabled fabrication of 3D-printed alginate scaffolds with adequate physical properties for tissue engineering applications.

Recent Advances in Natural Gum-Based Biomaterials for Tissue Engineering and Regenerative Medicine: A Review

“…Concentrated alginate/gelatin scaffolds with homogeneous nano-apatite coating were fabricated by 3D printing followed by in situ mineralization for application in bone tissue engineering [112]. In addition, alginate/gelatin constructs reinforced with TiO 2 and β-tricalcium phosphate fabricated by micro-extrusion-based printing showed enhanced mechanical properties up to 20 MPa of elastic modulus [113].…”

Engineered 3D Polymer and Hydrogel Microenvironments for Cell Culture Applications

“…In addition, to improve mechanical stability, multi-nozzle systems have been used to simultaneously print a support structure made of PCL alongside alginate hydrogel structures [250,251]. Other ways to improve the mechanical stability after print are by formulation of alginate ink mixed with PVA powder (printability decreased and compressive modulus decreased from 56 to 13 kPa with increasing PVA content from 0 to 30% v/v [252]), or TiO 2 (Young's modulus of 13 MPa compared with control of 9 MPa), or β-TCP (Young's modulus of 8 MPa) [253]. For light-assisted fabrication, methacrylated alginate hydrogels have been photopolymerized with UV light allowing tunable swelling and mechanical properties [254].…”

“…Inclusion of NiCu [237], e-polylysine [238], carrageenan [239], gelatin [240][241][242], cellulose [243,244], PVA [252], TiO 2 [253], β-TCP [253]; Feature size 150 µm, E: 280 kPa [240] Myoblasts [242]; endothelial cells [259]; E.coli [260], growth factor [250], human adipose stem cells [248]; human induced pluripotent stem cells [261]; chondrocytes [243,244,251]; Schwann cells [265] Cellulose (4.3.4) Mixed with alginate [244,[266][267][268][269][270][271][272]; As reinforcement material, E: 2.5-22.5 kPa [281] Feature size 500 µm [280]; Tensile E: 0.67-0.63 GPa [282] Chondrocytes for cartilage tissue engineering [244,269,271]; human induced pluripotent stem cells, bone-marrow hMSCs [272]; pancreatic cancer cells [268]; fibroblast and hepatoma cells [270]; NIH 3T3 cells [274] Collagen (4.4.1)…”

Use of Titanium Dioxide (TiO2) Nanoparticles as Reinforcement Agent of Polysaccharide-Based Materials

“…These synthetic routes are effective to fabricate polysaccharide-hybrid structures with enhanced technological properties and applications [3]. Currently, there is a special interest in combining organic compounds such as polysaccharides with inorganic compounds like titanium dioxide (TiO 2 ) to obtain hybrid materials with enhanced stability and new functionalities [4][5][6][7].…”

“…In the last decade, the use of TiO 2 as a reinforcement agent of polysaccharide-based materials has been explored [5,11,20]. Teymourpour et al [6] reported that the soybean polysaccharide biocomposite reinforced with TiO 2 showed good antimicrobial activity against Escherichia coli and Staphylococcus aureus.…”