ECM-mimicking nanofibrous matrix coaxes macrophages toward an anti-inflammatory phenotype: Cellular behaviors and transcriptome analysis.

An in-depth understanding of biomaterial cues to selectively polarize macrophages is beneficial in the design of "immuno-informed" biomaterials that positively interact with the immune system to dictate a favorable macrophage response following implantation. Given the promising future of ECM-mimicking nanofibrous biomaterials in biomedical application, it is essential to elucidate how their intrinsic cues, especially the nanofibrous architecture, affect macrophages. In the present study, we evaluated how the nanofibrous architecture of a gelatin matrix modulated macrophage responses from the perspectives of cellular behaviors and a transcriptome analysis. In our results, the nanofibrous surface attenuated M1 polarization and down-regulated the inflammatory responses of macrophages compared with a smooth surface. Besides, the cell-material interaction was up-regulated and the adhered macrophages tended to maintain an original, non-polarized state on the nanofibrous matrix. Accordingly, whole transcriptome analysis revealed that nanofibrous architecture up-regulated the pathways related to ECM-receptor interaction and down-regulated pathways related to pro-inflammation. This study provides a panoramic view of the interaction between macrophages and nanofibers, and offers valuable information for the design of immunomodulatory ECM-mimicking biomaterials for tissue regeneration.