It has been shown that material surface topography greatly affects cell attachment, growth, proliferation, and differentiation. However, the underlying molecular mechanisms for cell-material interactions are still not understood well. Here, two kinds of butterfly wings with different surface architectures were employed for addressing such an issue. Papilio ulysses telegonus (P.u.t.) butterfly wing surface is composed of micro/nanoconcaves, whereas Morpho menelaus (M.m.) butterfly wings are decorated with grooves. RSC96 cells grown on M.m. wings showed a regular sorting pattern along with the grooves. On the contrary, the cells seeded on P.u.t. wings exhibited random arrangement. Transcriptome sequencing and bioinformatics analysis revealed that huntingtin (Htt)-regulated lysosome activity is a potential key factor for determining cell growth behavior on M.m. butterfly wings. Gene silence further confirmed this notion. In vivo experiments showed that the silicone tubes fabricated with M.m. wings markedly facilitate rat sciatic nerve regeneration after injury. Lysosome activity and Htt expression were greatly increased in the M.m. wing-fabricated graft-bridged nerves. Collectively, our data provide a theoretical basis for employing butterfly wings to construct biomimetic nerve grafts and establish Htt lysosome as a crucial regulator for cell-material interactions.

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