From Nano to Micro: Nanostructured Titania/PLGA Orthopedic Tissue Engineering Scaffolds Assembled by Three-Dimensional Printing

A successful synthetic tissue engineering scaffold requires a hierarchical internal structure with interconnecting pores for nutrition transportation, cell infiltration and vascularization as well as nanoscale surface features favorable for cell attachment and long-term functions. However, traditionally, fabricating macro-scale scaffolds in a defined manner from nano-scale constituents has proved problematic. For example, the traditional porogen leaching techniques cannot precisely control the shape, size, location and interconnectivity of pores. In contrast, the use of three-dimensional (3D) printing, a rapid prototyping technique, can precisely produce pre-defined complex three-dimensional structures layer-by-layer based on patient medical information from computed tomography (CT) and/or magnetic resonance imaging (MRI). Previous in vitro studies demonstrated that two-dimensional PLGA (poly lactide-co-glycolide) scaffolds with well-dispersed titania nanoparticles enhanced osteoblast (boneforming cell) adhesion and subsequent functions (such as calcium deposition). In this study, threedimensional nanophase titania/PLGA scaffolds were fabricated via a novel 3D printing technique. Scanning electron microscopy (SEM) was used to characterize the structure and surface features of these 3D scaffolds. The SEM results demonstrated that the printed nano 3D scaffolds have a well-controlled, repeatable inner structure and, moreover, possessed uniformly dispersed titania nanoparticles which provided for nano-scale surface features throughout the PLGA matrix. The objective of the present in vitro study was to investigate osteoblast attachment and infiltration into such 3D composite scaffolds. Confocal microscopy was used to evaluate osteoblast attachment on the surface and infiltration into the porous structures. The results demonstrated that osteoblasts preferred the nano-scale roughness of the pore walls over that of the outer surface of the 3D nano scaffolds. Thus, this study suggests that these novel nano 3D scaffolds consisting of nanophase titania/PLGA composites created via the 3D printing technique may be promising for more effective orthopedic tissue engineering applications.