Hierarchical scaffolds via combined macro- and micro-phase separation

Recent advances in biomaterial surface engineering have shown that surface biomechanical, spatial and topographical properties can elicit control over fundamental biological processes such as cell shape, proliferation, differentiation and apoptosis. Along these lines, we have very recently shown that the self-assembly of block copolymers into thin films can be used as an extremely labile method to precisely position cellular adhesion molecules, at nanometre lateral spacings, to effect control over cell attachment and morphology. Here, we extend our work in 2-dimensional block copolymer films into the production of 3-dimensional porous block copolymer scaffolds. The reported method combines macro-scale temperature induced phase separation and micro-phase separation of block copolymers to produce highly porous scaffolds with surfaces comprised of nano-scale self-assembled block copolymer domains, representing a significant advance in currently available scaffold engineering technologies. The phase behaviour of these polymer–solvent systems is described and potential mechanisms leading to the observed structure formation are presented. The nano-domains have thereafter been functionalised with CGRGDS peptides throughout the scaffold and shown to effect changes in cell attachment and spreading, in agreement with previous 2-dimensional studies. These multi-scale, functional scaffolds are easy to manufacture and scaleable, making them ideal candidates for tissue engineering applications.