PPARG, VEGFA, BGLAP, and IL6 are key molecular regulators in skin regeneration.

Collagen-stimulating fillers, such as calcium hydroxyapatite (CaHA), poly-l-lactic acid (PLLA), and polycaprolactone (PCL), are widely used in regenerative medicine for skin rejuvenation. However, their precise molecular mechanisms are still poorly understood. Therefore, this study aimed to investigate the gene expression profiles and molecular interactions associated with CaHA, PLLA, and PCL, focusing on the key regulators: PPARG, VEGFA, BGLAP, and IL6. To this end, a systematic search was performed to identify genes related to the fillers. Scratch assays were conducted to assess cell migration, while RT-PCR of 14 genes and molecular docking analyses examined changes in gene expression and protein-ligand interactions. The results showed that CaHA interacted with PPARG and VEGFA, suggesting roles in metabolic and inflammatory regulation. PLLA significantly increased VEGFA expression in fibroblasts, while PCL modulated IL6 expression, impacting immunological pathways. Scratch assays revealed that PCL significantly increased fibroblast and epithelial cell migration, while PLLA inhibited this migration in both cell lines, increasing the wound area. In conclusion, each filler presents distinct molecular responses, allowing targeted applications in aesthetic and regenerative medicine. Understanding these mechanisms allows for optimized treatment strategies. Further research into their molecular pathways will increase their efficacy and safety.