Peri-implantitis is a disease manifested by peri-implant inflammation include the loss of peri-implant alveolar bone, which gradually worsens with the development of inflammation, and bleeding of peri-implant soft tissue(Stefan et al., 2018). It exhibits a high incidence and is often difficult to reverse once established, which seriously affects the long-term prognosis of implants. Therefore, the success of implant therapy depends not only on good osseointegration around the implant, but also on good soft tissue barrier formation.

Hyperlipidemia is a systemic metabolic disorder characterized by elevated plasma levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), coupled with reduced levels of high-density lipoprotein cholesterol (HDL-C) (Murch et al., 2007). Owing to improved living standards, the incidence of hyperlipidemia continues to rise rapidly(Pirih et al., 2012).

Hyperlipidemia was found to be closely related to peri-implantitis. The meta-analysis of Gurgel et al. explored the relationship between dyslipidemia and peri-implant complications, indicating a strong association between dyslipidemia and peri-implantitis (OR=12.36, 95 % CI: 7.85–19.46, p < 0.00001)(Gurgel et al., 2025). Moreover, the cross-sectional biochemical analysis conducted by Blanco et al. found that total cholesterol, low-density lipoprotein (LDL) cholesterol in patients with peri-implantitis were significantly higher than those in healthy control subjects (P < 0.001). Additionally, peri-implant probing pocket depth was positively correlated with total cholesterol (r = 0.512) and LDL cholesterol (r = 0.463), suggesting an association between peri-implantitis and dyslipidemia(Blanco et al., 2021). Elevated lipid levels in hyperlipidemia promote the upregulation of various inflammatory factors, such as interleukin-6 (IL-6) and interleukin-10 (IL-10), thereby induce systemic or local inflammatory responses(Chen et al., 2013). Additionally, plasma lipoproteins bind to oxidized lipids or lysophospholipids to facilitate endotoxin clearance in the body. This process generates increased reactive oxygen species (ROS), induces oxidative stress, promotes lipid accumulation, inhibits bone formation, upregulates inflammatory factors, and ultimately leads to cell apoptosis or necrosis (Ilich et al., 2014). Hyperlipidemia can also increase the susceptibility to peri-implant inflammation through immune response disorders. For example, hyperlipidemia can also cause abnormal regulation of immune cells to wound healing, significantly increasing the susceptibility of patients to periodontitis and other inflammation(Pelton et al., 2012).

Nevertheless, there has been no study so far to explore whether the biological activities of human gingival fibroblasts (HGFs) on titanium surface will be affected by hyperlipidemia environment. Moreover, possible signaling pathways involved remains to be explored. Therefore, this study was designed to explore the biological behavior changes and of HGFs on the surface of titanium in the environment of high-lipid and possible mechanisms involved, so as to provide theoretical basis for the selection of clinical implant treatment indications, the improvement of the success rate of implantation therapy in patients with hyperlipidemia, and the prevention and treatment of peri-implant inflammation.