TLR4/NF-κB Immune Inflammatory Pathway Regulates Local Tissue Repair After Fat Grafting: A Clinical Study

BACKGROUND: Autologous fat grafting is widely used in reconstructive and aesthetic surgery; however, unpredictable graft retention remains a major limitation. Early inflammatory responses and subsequent tissue repair are crucial determinants of graft survival. This study investigated the clinical relevance of the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway in local tissue repair after autologous fat grafting. METHODS: This prospective observational study enrolled 60 patients undergoing facial autologous fat grafting between January 2023 and December 2024. Stromal vascular fraction (SVF)-enriched fat samples and perigraft tissue fluid were collected at baseline and postoperative days 3, 7, and 30. Patients were divided into high- and low-retention groups based on 6-month volumetric retention measured using 3-dimensional facial imaging. Expression of TLR4, phosphorylated NF-κB p65 (p-p65), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), and transforming growth factor-β 1 (TGF-β1) was assessed using quantitative reverse-transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry. RESULTS: Fifty-six patients completed 6-month follow-up. The mean fat retention was 56.8%±12.4%. TLR4 and p-p65 levels peaked on postoperative day 3 and declined thereafter. The high-retention group showed moderate early activation of TLR4/NF-κB signaling, lower peak concentrations of TNF-α and IL-6, and higher levels of VEGF and TGF-β1 than the low-retention group. TLR4 and p-p65 expression were negatively correlated with 6-month graft retention when exceeding the cohort median, whereas VEGF expression was positively correlated with retention. Multivariate linear regression identified early p-p65 level, VEGF concentration, graft volume, and smoking status as independent predictors of fat retention. CONCLUSIONS: Controlled activation of the TLR4/NF-κB pathway may promote early angiogenesis and tissue repair after fat grafting, whereas excessive or prolonged inflammatory activation is associated with reduced graft retention. Modulation of local immune-inflammatory responses may represent a therapeutic strategy to improve clinical outcomes after autologous fat transplantation.