Manipulation of Serum Protein Adsorption by Nanoengineered\nBiomaterials Influences Subsequent Immune Responses

The\nadsorption of serum proteins on biomaterial surfaces is a critical\ndeterminant for the outcome of medical procedures and therapies, which\ninvolve inserting materials and devices into the body. In this study,\nwe aimed to understand how surface topography at the nanoscale influences\nthe composition of the protein corona that forms on the (bio)material\nsurface when placed in contact with serum proteins. To achieve that,\nwe developed nanoengineered model surfaces with finely tuned topography\nof 16, 40, and 70 nm, overcoated with methyl oxazoline to ensure uniform\noutermost chemistry across all surfaces. Our findings revealed that\nwithin the studied height range, surface nanotopography had no major\ninfluence on the overall quantity of adsorbed proteins. However, significant\nalterations were observed in the composition of the adsorbed protein\ncorona. For instance, clusterin adsorption decreased on all the nanotopography-modified\nsurfaces. Conversely, there was a notable increase in the adsorption\nof ApoB and IgG gamma on the 70 nm nanotopography. In comparison,\nthe adsorption of albumin was greater on surfaces that had a topography\nscale of 40 nm. Analysis of the gene enrichment data revealed a reduction\nin protein adsorption across all immune response-related biological\npathways on nanotopography-modified surfaces. This reduction became\nmore pronounced for larger surface nanoprotrusions. Macrophages were\nused as representative immune cells to assess the influence of the\nprotein corona composition on inflammatory outcomes. Gene expression\nanalysis demonstrated reduced inflammatory responses on the nanotopographically\nmodified surface, a trend further corroborated by cytokine analysis.\nThese findings underscore the potential of precisely engineered nanotopography-coated\nsurfaces for augmenting biomaterial functionality.