Biomaterial Surface Nanotopography Induced IgG Unfolding Modulates Macrophage Innate Immune Responses

Implantable devices often encounter challenges related to adverse immune reactions and rejection due to poor host responses. Biomaterial surface nanotopography is known to modulate the host immune responses at cellular and molecular levels. In this study, we investigate how nanoscale modifications of surface topography influence the adsorption of Immunoglobulin G, the resultant attachment of innate immune cells, and inflammatory responses. We engineered model surfaces with well-defined nanoscale features of 16, 38, and 68 nm and ensured uniform surface chemistry. We demonstrated that nanoscale dimensions significantly impact IgG adsorption, leading to conformational changes. IgG adsorption and unfolding promoted macrophage attachment, migration, and activation. Although IgG adsorption led to an increase in both pro- and anti-inflammatory markers, surfaces with preadsorbed IgG promoted a net anti-inflammatory response, favoring the M2 macrophage phenotype, demonstrating the importance of surface topography in modulating IgG adsorption and conformational changes in shaping the behavior of immune cells. These findings pave the way for designing implantable medical devices that enable targeted modulation of immune responses, leading to improved patient outcomes.