Engineering Biocompatible Interfaces via Combinations of Oxide Films and Organic Self-Assembled Monolayers

In this paper, we demonstrate that cell adhesion and neuron maturation can be guided by patterned oxide surfaces functionalized with organic molecular layers. It is shown that the difference in the surface potential of various oxides (SiO2, Ta2O5, TiO2, and Al2O3) can be increased by functionalization with a silane, (3-aminopropyl)-triethoxysilane (APTES), which is deposited from the gas phase on the oxide. Furthermore, it seems that only physisorbed layers (no chemical binding) can be achieved for some oxides (Ta2O5 and TiO2), whereas self-assembled monolayers (SAM) form on other oxides (SiO2 and Al2O3). This does not only alter the surface potential but also affects the neuronal cell growth. The already high cell density on SiO2 is increased further by the chemically bound APTES SAM, whereas the already low cell density on Ta2O5 is even further reduced by the physisorbed APTES layer. As a result, the cell density is ∼8 times greater on SiO2 compared to Ta2O5, both coated with APTES. Furthermore, neurons form the typical networks on SiO2, whereas they tend to cluster to form neurospheres on Ta2O5. Using lithographically patterned Ta2O5 layers on SiO2 substrates functionalized with APTES, the guided growth can be transferred to complex patterns. Cell cultures and molecular layers can easily be removed, and the cell experiment can be repeated after functionalization of the patterned oxide surface with APTES. Thus, the combination of APTES-functionalized patterned oxides might offer a promising way of achieving guided neuronal growth on robust and reusable substrates.