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

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.

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.

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.

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.