Gradient biomaterials have shown enormous potential in high-throughput screening of biomaterials and material-induced cell migration. To make the screening process more rapid and precise, improving the regularity of morphological structure and chemical modification on gradient biomaterials have attracted much attention. In this paper, we present a novel fabrication strategy to introduce ordered nanopattern arrays into gradient biomaterials, through combining surface-initiated atom transfer radical polymerization and inclined reactive-ion etching based on colloidal lithography. Graded protein/poly(ethylene glycol) (PEG) nanopattern arrays on a quartz substrate were fabricated and applied to affect the behaviors of cells. Owing to the continuously changed ratio of two different components, the corresponding cell adhesion density along the substrate showed obvious graded distribution after culturing for 24 h. Meanwhile, the cytoskeleton showed obvious polarization after culturing for 7 days, which is parallel with the direction of gradient. Additionally, oriented migration was generated when mouse MC3T3-E1 cells were cultured on the graded protein/PEG nanopattern arrays. On the basis of the ordered and well-defined nanopatterns, the correlation between the extracellular matrix and corresponding expressions generated by different stimuli can be investigated.
Keywords: colloidal lithography; gradient biomaterials; inducing cellular behavior; multifunctional substrate; well-defined ECM.