Deciphering the Role of Biomaterial Surface Chemistry in Toll-Like Receptor-Mediated Immune Modulation

The inflammatory response to biomaterials plays a critical role in determining the implant performance and longevity. As key early responders, macrophages detect the implant surface and orchestrate immune reactions. Biomaterial surface properties are a key modifiable factor that significantly influences macrophage activation and local immune response. Because macrophages depend on Toll-like receptor (TLR) signaling to identify and respond to foreign materials, understanding how biomaterials influence this pathway is crucial. In this study, we aim to investigate the role of surface chemistry in TLR signaling. To achieve this, we utilized plasma polymerization to engineer biomaterial surfaces with four distinct surface chemistries. Synchrotron ATR-FTIR microspectroscopy revealed shifts in the infrared spectra, indicating changes in macromolecules in macrophages upon interaction with various surface coatings. Gene expression analysis showed that macrophages cultured on hydrocarbon-rich surfaces exhibited increased TLR2 expression and upregulated proinflammatory genes, including TNF-α, IL-1β, IL-6, and iNOS. In contrast, surfaces rich in carboxylic acid, amine, and oxazoline functionalities heightened TLR4 expression and upregulated anti-inflammatory genes, such as IL-1RA, arginase, and IL-10. These findings highlight the impact of biomaterial surface chemistry on immune signaling pathways, demonstrating that surface modifications can actively influence the polarization of macrophages. By leveraging these insights, we can refine biomaterial design to create immune-modulatory surfaces that optimize healing, reduce inflammation, and enhance success with implantable medical devices.