Polyelectrolyte multilayers of poly (l-lysine) and hyaluronic acid on nanostructured surfaces affect stem cell response.
Laser interference lithography (LIL) and the layer-by-layer (LbL) technique are combined here for the first time to design a system with variable nanotopographies and surface viscoelasticity to regulate cell behavior. LIL is used to generate hexagonally arranged nanostructures of gold with different periodicity. In contrast, LBL is used to assemble a multilayer system of poly-l-lysine and hyaluronic acid on top of the nanostructures. Moreover, the viscoelastic properties of that system are controlled by chemical cross-linking. We show that the topography designed with LIL is still present after multilayer deposition and that the formation of the multilayer system renders the surfaces hydrophilic, which is opposite to the hydrophobic nature of pristine nanostructures. The heterogenic system is applied to study the effect on adhesion and differentiation of human adipose-derived stem cells (hADSC). We show that hADSC spreading is increasing with cross-linking degree on flat multilayers, while it is decreasing on nanostructures modified with multilayers. In addition, early effects on signal transduction processes are seen. Finally, hADSC differentiation into chondrogenic and osteogenic lineages is superior to adipogenic lineages on nanostructures modified with multilayers. Hence, the presented system offers great potential to guide stem cell differentiation on surfaces of implants and tissue engineering scaffolds.