Comparative Characterization of Injectable Dermal Fillers: Physicochemical Properties, Cytotoxicity, Collagen-Stimulating Activity, and Macrophage Cytokine Profiles

Injectable dermal fillers are widely used in aesthetic medicine for soft-tissue augmentation and facial rejuvenation; however, systematic comparative data on their physicochemical properties and biological activities remain limited. This study aimed to characterise five commercially available dermal filler products—Facetem®, cCaHA, PDLLA, PLLA, and PCL—with respect to particle morphology and size distribution, in vitro cytotoxicity, collagen-stimulating gene expression, and macrophage cytokine secretion profiles. Particle size and distribution were determined by laser diffraction. Cytotoxicity was assessed in L929 mouse fibroblasts using the CCK-8 assay at concentrations of 0.1–5 mg/mL. Collagen-stimulating activity was evaluated by measuring COL1A1 and COL3A2 mRNA expression in primary human fibroblasts via quantitative RT-PCR. Macrophage immune responses were profiled by a multiplexed cytokine array (40 analytes) in lipopolysaccharide/interferon-γ-polarised M1 and interleukin-4/interleukin-13-polarised M2 macrophages. Scanning electron microscopy revealed distinct morphological differences among the five products. PDLLA exhibited the smallest median particle size (d(0.5) = 24.9 μm) and highest specific surface area (701.4 m2/kg), while PLLA showed the broadest size distribution (Span = 1.617). All products maintained cell viability above 85% at all tested concentrations, indicating acceptable biocompatibility. Facetem®, PDLLA, and PLLA significantly upregulated COL1A1 expression in human fibroblasts; PDLLA and Facetem® also significantly increased COL3A2 expression. Cytokine profiling demonstrated that the products did not substantially alter pro-inflammatory cytokine secretion in M1 macrophages, whereas selected products at high concentrations modulated several mediators in M2 macrophages, suggesting a tissue-remodelling rather than inflammatory response. These findings demonstrate product-specific physicochemical and biological profiles that may guide clinician selection and formulation development of injectable dermal fillers. Facetem® exhibited a favourable combination of biocompatibility, collagen-stimulating activity, and immune-modulatory properties comparable or superior to established reference products.