No abstract

Angiogenesis promotes rejuvenation in multiple organs, including the skin. Heat shock protein 90 (HSP90), hypoxia-inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF) are proangiogenic factors that stimulate the activities of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and extracellular signal-regulated kinase 1/2 (ERK1/2). Poly-D,L-lactic acid (PDLLA), polynucleotide (PN), and calcium hydroxyapatite (CaHA) are dermal fillers that stimulate the synthesis of dermal collagen. However, it is not yet known whether these compounds promote angiogenesis, which leads to skin rejuvenation. Here, we evaluated whether PDLLA, PN, and CaHA stimulate angiogenesis and skin rejuvenation using H2O2-treated senescent macrophages and endothelial cells as an in vitro model for skin aging, and we used young and aged C57BL/6 mice as an in vivo model. Angiogenesis was evaluated via endothelial cell migration length, proliferation, and tube formation after conditioned media (CM) from senescent macrophages was treated with PDLLA, PN, or CaHA. Western blot showed decreased expression levels of HSP90, HIF-1α, and VEGF in senescent macrophages, but higher expression levels of these factors were found after treatment with PDLLA, PN, or CaHA. In addition, after exposure to CM from senescent macrophages treated with PDLLA, PN, or CaHA, senescent endothelial cells expressed higher levels of VEGF receptor 2 (VEGFR2), PI3K, phosphorylated AKT (pAKT), and phosphorylated ERK1/2 (pERK1/2) and demonstrated greater capacities for cell migration, cell proliferation, and tube formation. Based on the levels of 4-hydroxy-2-nonenal, the oxidative stress level was lower in the skin of aged mice injected with PDLLA, PN, or CaHA, while the tumor growth factor (TGF)-β1, TGF-β2, and TGF-β3 expression levels; the density of collagen fibers; and the skin elasticity were higher in the skin of aged mice injected with PDLLA, PN, or CaHA. These effects were greater in PDLLA than in PN or CaHA. In conclusion, our results are consistent with the hypothesis that PDLLA stimulates angiogenesis, leading to the rejuvenation of aged skin. Our study is the first to show that PDLLA, PN, or CaHA can result in angiogenesis in the aged skin, possibly by increasing the levels of HSP90, HIF-1α, and VEGF and increasing collagen synthesis.

BACKGROUND Treatment with filler injections using a microneedle fractional radiofrequency (MFRF) device is a promising modality with proven efficacy for acne scar treatment. OBJECTIVE To investigate the efficacy and histologic differences of intradermal injection of a filler (poly-d, l-lactic acid, PDLA) using an MFRF device for the treatment of acne scars. METHODS Patients with acne scars on both cheeks were included. Poly-d, l-lactic acid was injected via the MFRF device every 4 weeks for a total of 4 sessions. Patients were evaluated using the grading system for acne scars before each session, as well as personal satisfaction. For histologic evaluation, 2 patients (who consented) underwent a skin biopsy from the upper arm before and after the same single session. RESULTS After the final session, the acne scar grading (échelle d'évaluation clinique des cicatrices d'acné) scale and visual analog scale for evaluation of satisfaction showed improvement compared with initial assessment (36.99% and 79.65% respectively [p < .001, respectively]). For histologic evaluation, biodegradation of PDLA materials and increase in collagen and elastic fibers were observed after 5 months of treatment. CONCLUSION Intradermal injection of PDLA using the MFRF device could be used as an effective treatment with fewer side effects in acne scar patients with Fitzpatrick skin type III-IV.

Poly-D,L-lactic acid (PDLLA) filler corrects soft tissue volume loss by increasing collagen synthesis in the dermis; however, the mechanism is not fully understood. Adipose-derived stem cells (ASCs) are known to attenuate the decrease in fibroblast collagen synthesis that occurs during aging, and nuclear factor (erythroid-derived 2)-like-2 factor (NRF2) increases ASCs survival by inducing M2 macrophage polarization and IL-10 expression. We evaluated the ability of PDLLA to induce collagen synthesis in fibroblasts by modulating macrophages and ASCs in a H2O2-induced cellular senescence model and aged animal skin. PDLLA increased M2 polarization and NRF2 and IL-10 expression in senescence-induced macrophages. Conditioned media from senescent macrophages treated with PDLLA (PDLLA-CMMΦ) reduced senescence and increased proliferation and expression of transforming growth factor-β (TGF-β) and fibroblast growth factor (FGF) 2 in senescence-induced ASCs. Conditioned media from senescent ASCs treated with PDLLA-CMMΦ (PDLLA-CMASCs) increased the expression of collagen 1a1 and collagen 3a1 and reduced the expression of NF-κB and MMP2/3/9 in senescence-induced fibroblasts. Injection of PDLLA in aged animal skin resulted in increased expression of NRF2, IL-10, collagen 1a1, and collagen 3a1 and increased ASCs proliferation in aged animal skin. These results suggest that PDLLA increases collagen synthesis by modulating macrophages to increase NRF2 expression, which stimulates ASCs proliferation and secretion of TGF-β and FGF2. This leads to increased collagen synthesis, which can attenuate aging-induced soft tissue volume loss.

Background and ObjectivesFractional radiofrequency micro-needle (FRM) has revolutionized the way we treat a variety of cutaneous conditions using radiofrequency technology. A comprehensive guide is required for clinicians using this technology in treatment of a variety of skin conditions in various skin types. Materials and MethodsThe guidelines were made from a recent round table discussion among experienced clinicians and a review of recent medical literature. ResultsWe concluded that FRM is a safe and effective modality for treatment of conditions commonly encountered in dermatology, and recommended guidelines for optimal treatment of several skin conditions on and off the face using FRM. ConclusionWe developed reproducible guidelines for most effective treatment of a variety of skin conditions using FRM. Conduct of large, multicenter trials will be needed for further optimization of treatment parameters.