The entry of implants triggers the secretion of damage associated molecular patterns (DAMPs) that recruit dendritic cells (DCs) and results in subsequent foreign body reaction (FBR). Though several studies have illustrated that the surface accessible area (SAA) of implants plays a key role in the process of DAMPs release and absorption, the effect of SAA on the immune reaction still remains unknown. Here, a series of TiO2 plates with different SAA is fabricated to investigate the relationship between SAA and FBR. Compared with larger SAA surface, the aggregation of DC is significantly inhibited by lower SAA surface. Total internal reflection microscopy (TIRFM) and molecular dynamic (MD) simulation show that although high mobility group box 1 (HMGB1) is adsorbed more on plates with lower SAA, the exposure ratio of cysteine (CYS) residue in HMGB1 is significantly decreased in lower SAA group. The lower exposure of CYS reduces the activation of Toll-like receptors 4 (TLR4), which down-regulates the expression of myeloid differentiation factor (Myd88)-TNF receptor associated factor 6 (TRAF6) to inhibit nuclear factor kappa B (NF-κB) signaling. Generally, this study reveals the mechanism of how SAA, a nanoscale property, affects FBR from perspective of DAMPs, and provides a new direction for designing better biocompatible implants.
Keywords: DAMP; HMGB1; foreign body reaction; nanomodification; surface accessible area.
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