Page 122 - Development of Functional Scaffolds for Bone Tissue Engineering Using 3D-Bioprinting of Cells and Biomaterials - Yasaman Zamani

GENERAL DISCUSSION
In recent years, additive manufacturing (AM) techniques, such as 3D-printing, have gained increasing attention for the fabrication of patient-specific scaffolds with defined internal structures [1-4]. 3D-bioprinting, i.e. layer-by-layer deposition of cells and biomaterials in a single construct, is rapidly becoming one of the main innovation sectors of the 3D-printing industry. While this technology is deemed to be the future of medicine, there is still significant room for improvements. Mechanical, structural, and surface properties of 3D-printed scaffolds are among the key factors influencing the performance of the scaffolds in vivo. The main goal of the studies presented in this thesis was to fine tune these properties in order to optimize them for bone tissue engineering.
The innate hydrophobicity and surface smoothness of 3D-printed polycaprolactone (PCL) scaffolds hamper cell activities [5, 6]. Different surface modifications have been used on PCL scaffolds to overcome these obstacles. We have shown that surface modification of 3D-printed PCL scaffolds with 3M sodium hydroxide (NaOH) for 24 h results in the creation of a topography on the surface consisting of oval pores, and therefore more strongly enhances the osteogenic activity of pre-osteoblasts compared with RGD immobilization on the surface, which enhances cell attachment and proliferation, but does not alter the smooth surface of PCL [7]. With increasing the NaOH treatment time from 24 to 72 h, the size of the oval pores created on the surface increases, while interestingly, cells display less osteogenic activity on these scaffolds compared with 24 h NaOH-treated scaffolds [7]. Additionally, we have shown that mechanical properties of 3D-printed PCL scaffolds can be customized based on the forces on the defect site predicted by finite element modeling [8]. This is of great importance for the integration of the scaffold with the surrounding bone. Furthermore, we evaluated the osteogenic differentiation potential of pre- osteoblasts in 3D-printed poly(lactic-co-glycolic) acid/β-tricalcium phosphate (PLGA/β-TCP) scaffolds compared with porous scaffolds fabricated by solvent casting-porogen leaching. The surface of the 3D-printed PLGA/β-TCP struts had a homogeneous roughness resulting from dispersion of β-TCP particles, while β-TCP particles were not homogeneously dispersed on the surface of the porous scaffolds, and β-TCP aggregates were observed at some locations. This inhomogeneous distribution of β-TCP particles probably contributed to increased surface roughness in the porous scaffolds compared with the 3D-printed scaffolds. Our data showed that osteogenic activity of MC3T3-E1 pre-osteoblasts was higher on the 3D-printed scaffolds compared with the porous scaffolds. These results highlight the importance of surface topography and the size of topographical surface features in the osteogenic differentiation of pre-osteoblasts attached to scaffolds. We also showed that when cells were encapsulated in alginate and printed
120