Understanding human mesenchymal stem cell (hMSC) adhesion and differentiation in three-dimensional matrices in vitro is important for potential regenerative medicine and stem cell therapies. One of the key requirements for the use of scaffolds is that they correctly display the physicochemical properties mimicking those of the native extracellular matrix (ECM), in particular adhesive heterogeneity. Previous studies in 2D provide evidence for the effects of matrix properties such as stiffness, topography and surface chemistry. Yet, there are very few examples to date where ECM heterogeneity has been recapitulated and its effects on hMSCs investigated.

The main aim of this research was to design topologically defined three-dimensional porous scaffolds. This was achieved by exploiting the self-assembly of amphiphilic diblock copolymers confined at an interface. Two methods of scaffold fabrication were used in these studies;​ high internal phase emulsion (HIPE) templating and electrospinning. In both studies, mixtures of two amphiphilic block copolymers were used to induce phase separation between the dissimilar hydrophilic blocks thereby creating distinct copolymer domains in the nanometer length scales on the scaffold surface. In both scaffold fabrication methods the amphiphilic block copolymers used were a combination of cell inert and cell adhesive chemistries, thereby generating matrices with distinct cell binding sites. The functionality and adhesive heterogeneity of these materials were characterised using varying techniques including x-ray photoelectron spectroscopy, chemical force spectroscopy mapping and contact angle measurements. The effect of adhesive heterogeneity of such matrices on human mesenchymal progenitor adhesion and differentiation based on block copolymer domains were investigated. It was found that hMSCs adhered in a block copolymer dependent manner to scaffolds that most closely mimicked the adhesive heterogeneity in native extracellular matrix.