Poly-D,L-Lactic Acid Fillers Increase Subcutaneous Adipose Tissue Volume by Promoting Adipogenesis in Aged Animal Skin

During aging, subcutaneous white adipose tissue (sWAT) thickness and the adipogenic potential of adipose-derived stem cells (ASCs) decline. Poly-D,L-lactic acid (PDLLA) fillers are commonly used to restore diminished facial volume. Piezo1 increases polarizing macrophages towards the M2 phenotype, which promotes the secretion of fibroblast growth factor 2 (FGF2), thereby increasing ASC survival. This study evaluated whether PDLLA enhances adipogenesis in ASCs by modulating M2 polarization in an in vitro senescence model and in aged animals. Lipopolysaccharide (LPS)-induced senescent macrophages showed decreased Piezo1, which was upregulated by PDLLA. CD163 (an M2 marker) and FGF2 were downregulated in senescent macrophages but were upregulated by PDLLA. We evaluated whether reduced FGF2 secretion from senescent macrophages affects ASCs by applying conditioned media (CM) from macrophage cultures to ASCs. CM from senescent macrophages decreased ERK1/2 and proliferation in ASCs, both of which were restored by CM from PDLLA-stimulated senescent macrophages. Adipogenesis inducers (PPAR-γ and C/EBP-α) were downregulated by CM from senescent macrophages but upregulated by CM from PDLLA-stimulated senescent macrophages in ASCs. Similar patterns were observed in aged animal adipose tissue. PDLLA increased Piezo1 activity, M2 polarization, and FGF2 levels. PDLLA also enhanced ERK1/2, cell proliferation, PPAR-γ, and C/EBP-α expression, leading to increased adipose tissue thickness. In conclusion, our study showed that PDLLA increased adipose tissue thickness by modulating adipogenesis.