Nanopillar Array on Black Titanium Prepared by Reactive Ion Etching Augments Cardiomyogenic Commitment of Stem Cells
A major impediment in clinical translation of stem cell therapy has been the inability to efficiently and reproducibly direct differentiation of a large population of stem cells. Thus, we aimed to engineer a substrate for culturing stem cells to efficiently induce cardiomyogenic lineage commitment. In this work, we present a nanopillar array on the surface of titanium that was prepared by mask-less reactive ion etching. Scanning electron and atomic force microscopies revealed that the surface was covered by vertically aligned nanopillars each of 1 μm with a diameter of 80 nm. The nanopillars supported the attachment and proliferation of human mesenchymal stem cells (hMSCs). Cardiomyogenic lineage commitment of the stem cells was enhanced on the nanopillars than on the smooth surface. When co-cultured with neonatal rat cardiomyocytes, the cyclic pattern of calcium transport observed in the cells differentiated on the arrays unlike in the cells on the smooth surface was functional validation of the differentiation. Use of small molecule inhibitors revealed that integrins namely, 21 and v3, are essential for cardiomyogenesis on the nanostructured surface, which is further mediated by FAK, Erk and Akt cell signaling pathways. This study demonstrates that nanopillar array efficiently promotes the cardiomyogenic lineage commitment of stem cells via integrin-mediated signaling and can potentially serve as a platform for ex vivo differentiation of stem cells toward cell therapy in cardiac tissue repair and regeneration.