Poly-L-Lactic Acid Fillers Improved Dermal Collagen Synthesis by Modulating M2 Macrophage Polarization in Aged Animal Skin

Abstract

Poly-L-lactic acid (PLLA) fillers correct cutaneous volume loss by stimulating fibroblasts to synthesize collagen and by augmenting the volume. PLLA triggers the macrophage-induced activation of fibroblasts that secrete transforming growth factor-β (TGF-β). However, whether M2 macrophage polarization is involved in PLLA-induced collagen synthesis via fibroblast activation in aged skin is not known. Therefore, we evaluated the effect of PLLA on dermal collagen synthesis via M2 polarization in an H2O2-induced cellular senescence model and aged animal skin. H2O2-treated macrophages had increased expression levels of the M1 marker CD80 and decreased expression levels of the M2 marker CD163, which were reversed by PLLA. The expression levels of interleukin (IL)-4 and IL-13, which mediate M2 polarization, were decreased in H2O2-treated macrophages and increased upon the PLLA treatment. CD163, IL-4, and IL-13 expression levels were decreased in aged skin, but increased after the PLLA treatment. The expression levels of TGF-β, pSMAD2/SMAD2, connective tissue growth factor (CTGF), alpha-smooth muscle actin (α-SMA), collagen type 1A1 (COL1A1), and COL3A1 were also decreased in aged skin, but increased after the PLLA treatment. Moreover, PLLA upregulated phosphatidylinositol 3-kinase p85α (PI3-kinase p85α)/protein kinase B (AKT) signaling, leading to fibroblast proliferation. PLLA decreased the expression of matrix metalloproteinase (MMP) 2 and MMP3, which destroy collagen and elastin fibers in aged skin. The amount of collagen and elastin fibers in aged skin increased following the PLLA treatment. In conclusion, PLLA causes M2 polarization by increasing IL-4 and IL-13 levels and upregulating TGF-β expression and collagen synthesis in aged skin.

An evaluation of the effectiveness of ‘ULTRACOL 200′ in enhancing nasolabial fold wrinkles through cutaneous repair

“…PDO exhibits excellent flexibility and tensile strength, accompanied by biocompatibility and minimal inflammation, which has a 12‐week retention time in the body and does not interfere with the activities of macrophages and white blood cells 31,32 …”

Skin rejuvenation effect of the combined PDLLA and non cross‐linked hyaluronic acid: A preliminary study

“…PLLA, a biocompatible and biodegradable polymer, can break into lactic acid to stimulate collagen synthesis 5,12 . PLLA injection was approved for HIV‐associated facial lipoatrophy in 2004 19,20 .…”

“…However, injectable PLLA is known to induce local skin reaction and stimulate foreign body reaction, which can lead to M2 subtype macrophage polarization and recruitment of immune cells. With these reactions, PLLA‐induced collagen synthesis, soft tissue augmentation, and skin thickening can occur by secreting various cytokines in vitro, in vivo, and animal studies 5,12 . Furthermore, there are several reports of late‐onset granuloma formation after PLLA injection 21 …”

“…Poly‐L‐lactic acid (PLLA), poly‐D, and L‐lactic acid (PDLLA), belonging to the category of biodegradable collagen stimulators, have been increasingly utilized in recent years 10,11 . Because of their biodegradable and biocompatible features, these poly‐lactic acid (PLA) materials have already been used as various surgical materials, including suture threads, nails, pins, and screws 12 …”

Do PLLA and HA potentially mimic estrogen effects in skin quality?

“…Both injectable PLLA and crosslinked HA can increase fibroblast activity resulting in increase of collagen content as demonstrated by in vivo and in vitro studies. [3][4][5] The expression of TGFß1 mRNA increased progressively with PLLA applications in menopaused skin through the stimulation of IL-4 and IL-13 and consequent activation of the TGFβ signaling pathway and remodeling of the extracellular matrix. 3,6 The increase was sustained for 10 months.…”