Three-Dimensional Printed Scaffolds with Controlled Micro-/Nanoporous Surface Topography Direct Chondrogenic and Osteogenic Differentiation of Mesenchymal Stem Cells

The effect of topography in three-dimensional (3D) printed polymer scaffolds on stem cell differentiation is a significantly underexplored area. Compared to two-dimensional (2D) biomaterials on which various well-defined topographies have been incorporated and shown to direct a range of cell behaviors including adhesion, cytoskeleton organization, and differentiation, incorporating topographical features to 3D polymer scaffolds is challenging due to the difficulty of accessing the inside of a porous scaffold. Only the roughened strut surface has been introduced to 3D printed porous scaffolds. Here, a rapid, single-step 3D printing method to fabricate polymeric scaffolds consisting of microstruts (ca. 60 μm) with micro-/nanosurface pores (0.2-2.4 μm) has been developed based on direct ink writing of an agitated viscous polymer solution. The density, size, and alignment of these pores can be controlled by changing the degree of agitation or the speed of printing. Three-dimensional printed scaffolds with micro-/nanoporous struts enhanced chondrogenic and osteogenic differentiation of mesenchymal stem cells (MSCs) without soluble differentiation factors. The topography also selectively affected adhesion, morphology, and differentiation of MSC to chondrogenic and osteogenic lineages depending on the composition of the differentiation medium. This fabrication method can potentially be used for a wide range of polymers where desirable architecture and topography are required.