Mechanoimmunomodulation-based strategy on advancing tissue-engineered nanotopographic structures

The application of nanotopographic structures is considered a promising strategy for improving outcomes in tissue engineering. Nanotopographic structures-mediated immune responses have a more profound influence than the direct modulation of functional cell responses. However, the reported immunomodulatory effects of different nanotopographic structures are inconsistent and unpredictable. Therefore, it is necessary to further understand the general or fundamental biological mechanisms underlying nanotopographic structures-mediated immune regulation to fabricate structures with the desired immunomodulatory properties. Compared to the effects on protein absorption and physiochemical signals, the mechanical forces induced by nanotopographic structures play a more pivotal role in determining immune responses. Elucidating the mechanotransduction mechanisms by which mechanical forces from nanotopographic structures are converted into intracellular biochemical signals in immune cells is crucial. This understanding is essential for the precise regulation of immune responses mediated by nanotopographic structures and for guiding the development of nanotopographic structures with advanced immunomodulatory properties. This review elucidates the impact of nanotopographic structures on cellular mechanical forces and the subsequent activation of mechanosensors. The ensuing mechano-regulatory effects on immune responses are reviewed, and mechanoimmunomodulation is proposed as a strategy for designing nanotopographic structures to modulate immunity. This review contributes to revolutionizing the strategy for developing nanotopographic structures and promotes the application of nanotopographic structures with the mechanoimmunomodulatory property in tissue engineering.