Integrative Clinical Lipid Metabolomics Analysis of Metabolic Characteristics Underlying Hypertrophic Scar Formation After Plastic Surgery

Objective Hypertrophic scar (HS) is a common plastic surgery complication marked by fibroblast overactivation and excessive extracellular matrix deposition. Existing studies fail to clarify the regulatory mechanism of lipid metabolic reprogramming in scar fibroblasts. This study aimed to identify differential lipid biomarkers and reveal how lipid disturbance drives scar hyperplasia for novel intervention targets.

Methods A prospective case-control design was adopted. Scar tissues, paired normal skin and serial serum samples were subjected to untargeted lipidomics via UPLC-HRMS. Lipid-transcriptome joint analysis built lipid-gene networks, and in vitro human scar fibroblast models verified the roles of ACC, FASN and CD36.

Results Scar tissues exhibited obvious lipid profile remodeling: saturated fatty acids, phosphatidylcholine and ceramides were elevated, whereas polyunsaturated fatty acids and lysophospholipids declined. Altered lipids concentrated in glycerophospholipid, sphingolipid and fatty acid synthesis pathways, correlating positively with scar severity and angiogenesis. Overexpressed ACC/FASN induced lipotoxicity, activating NF-κB/NLRP3 inflammasome to secrete pro-inflammatory factors and boost collagen synthesis. CD36 exacerbated mitochondrial oxidative stress, forming a lipid accumulation-inflammation-fibrosis vicious cycle.

Conclusion Lipid metabolism disorder serves as a core driver of hypertrophic scar formation. The screened lipid molecules can act as non-invasive diagnostic biomarkers. Targeting lipid metabolic pathways represents a promising therapeutic strategy for HS prevention and treatment.