Manipulation of Serum Protein Adsorption by Nanoengineered Biomaterials Influences Subsequent Immune Responses

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