The effect of topography in 3D printed polymer scaffolds on stem cell differentiation is a significantly under-explored area. Compared to 2D biomaterials on which various well-defined topographies have been incorporated and been shown to direct an arrange of cell behaviours including adhesion, cytoskeleton organisation and differentiation, incorporating topographical features to 3D polymer scaffolds is challenging due to the difficulty of accessing the inside of a porous scaffold. Only roughened strut surface has been introduced to 3D printed porous 2 scaffolds. Here, a rapid, single-step 3D printing method to fabricate polymeric scaffolds consisting of micro-struts (ca. 60 µm) with micro-/nano-surface 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. 3D printed scaffolds with micro-/nano-porous struts enhanced chondrogenic and osteogenic differentiation of 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.

Three-dimensional (3D) printing is a powerful manufacturing tool for making 3D structures with well-defined architectures for a wide range of applications. The field of tissue engineering has also adopted this technology to fabricate scaffolds for tissue regeneration. The ability to control architecture of scaffolds, e.g. matching anatomical shapes and having defined pore size, has since been improved significantly. However, the material surface of these scaffolds is smooth and does not resemble that found in natural extracellular matrix (ECM), in particular, the nanofibrous morphology of collagen. This natural nanoscale morphology plays a critical role in cell behaviour. Here, we have developed a new approach to directly fabricate polymeric scaffolds with an ECM-like nanofibrous topography and defined architectures using extrusion-based 3D printing. 3D printed tall scaffolds with interconnected pores were created with disparate features spanning from nanometres to centimetres. Our approach removes the need for a sacrificial mould and subsequent mould removal compared to previous methods. Moreover, the nanofibrous topography of the 3D printed scaffolds significantly enhanced protein absorption, cell adhesion and differentiation of human mesenchymal stem cells when compared to those with smooth material surfaces. These 3D printed scaffolds with both defined architectures and nanoscale ECM-mimicking morphologies have potential applications in cartilage and bone regeneration.

We report a conductive and biodegradable 3D printed polymer scaffold that promotes chondrogenic differentiation of chondroprogenitor cells. The conductive material consists of tetraniline-b-polycaprolactone-b-tetraaniline and polycaprolactone.

uPA expression correlates with lymphatic invasion and metastasis in vivo and is required for CCA cell invasion in vitro, suggesting its potential as a therapeutic target.