It has been well studied that the surface topography affects the growth and development of neurons. However, the precise mechanism of how the surface topography leads to cellular changes remains unknown. In this study, an irregular surface was created using nanodiamonds, and this surface topography was found to accelerate the development of primary neurons from both the central and peripheral nervous systems. With the use of RNA sequencing technology, a previously uncharacterized microRNA (miR6236) was found to exhibit a significant and the most substantial decrease when neurons are cultured on this nanodiamond surface. Gain-and loss-of-function assays confirm that miR6236 is the predominant molecule responsible for converting the surface topography into biological responses. The depletion of miR6236 was also discovered to enhance neuroregeneration on an inhibitory substrate, raising its therapeutic potential for promoting nervous system regeneration.