Randomized, Patient/Evaluator-Blinded, Intraindividual Comparison Study to Evaluate the Efficacy and Safety of a Novel Hyaluronic Acid Dermal Filler in the Treatment of Nasolabial Folds.

BACKGROUND: Comparative research on the characteristics of filler products is limited, especially in the preclinical analysis of hyaluronic acid (HA) fillers. OBJECTIVE: This study was performed to compare the preclinical characteristics, clinical efficacy, and safety of a new HA filler, IDHF-001, with Restylane SubQ in the treatment of nasolabial folds (NLFs). METHODS: Viscoelasticity and injection force were evaluated. Ninety-one subjects were enrolled in this randomized, patient/evaluator-blind, intraindividual clinical study. Each subject was randomized to receive injections of IDHF-001 or Restylane SubQ in their left or right NLF. At 4, 8, 16, 24, 36, and 48 weeks, all participants were evaluated through Wrinkle Severity Rating Scale (WSRS). RESULTS: The IDHF-001 showed higher viscosity (1,271 Pa·s), lower elastic modulus (G'; 611 Pa), and lower injection force (8.89 N) than Restylane SubQ (464.6 Pa·s; 674.8 Pa; 19.14 N). No significant difference in WSRS was detected between IDHF-001 side and Restylane SubQ side at 24 weeks (mean improvement in WSRS from baseline at Week 24-IDHF-001: 1.85 ± 0.61, Restylane SubQ: 1.88 ± 0.61). The noninferiority was sustained until Week 48. CONCLUSION: The novel HA filler IDHF-001 shows suitable characteristics and tolerability, widening the selection possibilities for clinicians and patients in the treatment of NLFs.

The efficacy and safety of a monophasic hyaluronic acid filler in the correction of nasolabial folds: A randomized, multicenter, single blinded, split-face study.

BACKGROUND: The different rheological properties of hyaluronic acid (HA) filler reflect their specific manufacturing processes and resultant physicochemical characteristics. However, there are few researches about the relationship between product differences and clinical outcome when HA fillers are used for nasolabial folds (NLFs). AIMS: This study sought to compare the rheological properties, efficacy and safety of a monophasic HA filler, and a well-studied biphasic HA filler, in the treatment of NLFs. PATIENTS/METHODS: A total of 72 Korean subjects with moderate to severe NLFs were randomized to receive injections with monophasic HA or biphasic HA on the left or right side of the face. Efficacy was evaluated by the change in the Wrinkle Severity Rating Scale (WSRS) at 2, 10, 18, 26, and 52 weeks. Safety was assessed on the basis of all abnormal reactions during the clinical test period. To compare the rheological characteristics of two cross-linked HA fillers, viscoelastic analysis was performed. RESULTS: At week 26, the mean WSRS was 2.26±0.56 for the monophasic HA side and 2.24±0.54 for the biphasic HA side. Both treatments were well tolerated. The adverse reactions were mild and transient. Monophasic HA filler had lower elasticity and higher viscosity than biphasic HA filler. CONCLUSION: Despite a number of different rheological properties, monophasic HA is noninferior to biphasic HA in the treatment of moderate to severe NLFs for 52 weeks. Therefore, monophasic HA provides an alternative option for NLFs correction.

Targeting of sebaceous glands to treat acne by micro-insulated needles with radio frequency in a rabbit ear model.

BACKGROUND AND OBJECTIVES: Many studies have investigated the application of micro-insulated needles with radio frequency (RF) to treat acne in humans; however, the use of a micro-insulated needle RF applicator has not yet been studied in an animal model. The purpose of this study was to evaluate the effectiveness of a micro-insulated needle RF applicator in a rabbit ear acne (REA) model. STUDY DESIGN/MATERIALS AND METHODS: In this study, we investigated the effect of selectively destroying the sebaceous glands using a micro-insulated needle RF applicator on the formation of comedones induced by application of 50% oleic acid and intradermal injection of P. acnes in the orifices of the external auditory canals of rabbits. The effects of the micro-insulated needle RF applicator treatment were evaluated using regular digital photography in addition to 3D Primos imaging evaluation, Skin Visio Meter microscopic photography, and histologic analyses. RESULTS: Use of the micro-insulated needle RF applicator resulted in successful selective destruction of the sebaceous glands and attenuated TNF-alpha release in an REA model. The mechanisms by which micro-insulated needles with RF using 1 MHz exerts its effects may involve inhibition of comedone formation, triggering of the wound healing process, and destruction of the sebaceous glands and papules. CONCLUSION: The use of micro-insulated needles with RF applicators provides a safe and effective method for improving the appearance of symptoms in an REA model. The current in vivo study confirms that the micro-insulated needle RF applicator is selectively destroying the sebaceous glands. Lasers Surg. Med. 49:395-401, 2017. © 2016 Wiley Periodicals, Inc.

Inhibitory effect of 660-nm LED on melanin synthesis in in vitro and in vivo.

BACKGROUND: Skin hyperpigmentary disorders including postinflammatory hyperpigmentation, melasma, solar lentigines, and conditions like freckles are common. The light-emitting diodes (LEDs) are the latest category of nonthermal and noninvasive phototherapy to be considered in skin pigmentation disorder treatment. PURPOSE: The purpose of this study was to investigate the effects of 660-nm LED on inhibition of melanogenesis. We investigated whether a 660-nm LED affected melanin synthesis in in vitro and in vivo models, and we explored the mechanisms involved. METHODS: The inhibitory effect of 660-nm LED on melanin synthesis was evaluated in B16F10 cells and HRM-2 melanin-possessing hairless mice were used to evaluate the antimelanogenic effects of 660-nm LED. RESULTS: Interestingly, 660-nm LED inhibited alpha-melanocyte-stimulating hormone-induced tyrosinase activity in B16F10 cells. We also found that 660-nm LED decreased MITF and tyrosinase expression and induced the activation of ERK. These findings suggest that the depigmenting effects of 660-nm LED result from downregulation of MITF and tyrosinase expression due to increased ERK activity. The 660-nm LED reduced UVB-induced melanogenesis in the skin of HRM-2 via downregulation of tyrosinase and MITF. CONCLUSION: These findings suggest 660-nm LED is a potentially depigmentation strategy.

Gain-switched 311-nm Ti:Sapphire laser might be a potential treatment modality for atopic dermatitis.

Phototherapy with 311-nm narrowband-UVB (NBUVB) is an effective adjuvant treatment modality for atopic dermatitis (AD). In this study, we evaluated the therapeutic effect of the newly developed gain-switched 311-nm Ti:Sapphire laser device using a NC/Nga mouse AD model. A total number of 50 mice were used in this study. Atopic dermatitis (AD) was induced in mice by exposure to Dermatophagoides farina. These, NC/Nga mice were then treated with conventional 311-nm NBUVB or the newly developed gain-switched 311-nm Ti:Sapphire laser. The clinical features, dermatitis severity scores, and scratching behavior were assessed. In addition, serologic analyses including inflammatory cytokines and histological analyses were performed. Gain-switched 311-nm Ti:Sapphire laser improved the AD-like skin lesions, severity, and symptoms of AD in the NC/Nga mouse model. This new laser also modulated the immune response found in the AD model, including hyper-IgE, upregulated Th2 cytokines, and the Th2-mediated allergic inflammatory reaction. Gain-switched 311-nm Ti:Sapphire laser shows therapeutic promise via an immune-modulation mechanism in an AD mouse model. These data suggest that gain-switched 311-nm Ti:Sapphire laser may be useful as a targeted phototherapy modality for AD.

Needle-free jet injection of hyaluronic acid improves skin remodeling in a mouse model.

PURPOSE: The purpose of this study was to improve methods of jet injection using a mouse model. We investigated the mechanism of action, efficacy, and safety of the pneumatic device using injection of hyaluronic acid (HA) solution into a mouse model. METHODS: We evaluated the efficacy and safety of an INNOJECTOR™ pneumatic device that pneumatically accelerates a jet of HA solution under high pressure into the dermis of mouse skin. We examined the treatment effects using skin hybrid model jet dispersion experiments, photographic images, microscopy, and histological analyses. RESULTS: Use of the INNOJECTOR™ successfully increased dermal thickness and collagen synthesis in our mouse model. Jet dispersion experiments were performed using agarose gels and a polyacrylamide gel model to understand the dependence of jet penetration on jet power. The mechanisms by which pneumatic injection using HA solution exerts its effects may involve increased dermal thickening, triggering of a wound healing process, and activation of vimentin and collagen synthesis. CONCLUSIONS: Collagen synthesis and increased dermal thickening were successfully achieved in our mouse model using the INNOJECTOR™. Pneumatic injection of HA under high pressure provides a safe and effective method for improving the appearance of mouse skin. Our findings indicate that use of the INNOJECTOR™ may induce efficient collagen remodeling with subsequent marked dermal layer thickening by targeting vimentin.

Effect of a 308-nm excimer laser on atopic dermatitis-like skin lesions in NC/Nga mice.

BACKGROUND AND OBJECTIVE: Atopic dermatitis (AD) is a common inflammatory skin disease that can affect all age groups. It has a relapsing course, which dramatically affects the quality of life of patients. A 308-nm excimer laser has been reported to be a safe and effective treatment for inflammatory skin diseases, although the range of potential application has not been fully explored. The purpose of this study was to evaluate the therapeutic effects of a 308-nm laser on AD-like skin lesions in NC/Nga mice. STUDY DESIGN/MATERIALS AND METHODS: Dermatophagoides farinae-exposed NC/Nga mice with a clinical score of 12 were treated with either a 308-nm excimer laser or narrowband-UVB (NB-UVB). The effects of the 308-nm excimer laser were evaluated by dermatitis scores, skin histology, skin barrier function, and immunological parameters, including IgE and Th2-mediated cytokines. RESULTS: The 308-nm excimer laser significantly reduced the severity of skin lesions and decreased the total serum levels of IgE and Th2-mediated cytokines. The excimer laser also significantly reduced the inflammatory cellular infiltrate into AD-induced skin lesions. Moreover, treatment with the 308-nm excimer laser led to recovery of skin barrier function in AD-induced skin lesions. CONCLUSION: The 308-nm excimer laser can be considered a valid and safe therapeutic option for the treatment of localized AD. Lasers Surg. Med. 48:629-637, 2016. © 2016 Wiley Periodicals, Inc.

Investigating skin penetration depth and shape following needle-free injection at different pressures: A cadaveric study.

BACKGROUND AND OBJECTIVES: The effectiveness of needle-free injection devices in neocollagenesis for treating extended skin planes is an area of active research. It is anticipated that needle-free injection systems will not only be used to inject vaccines or insulin, but will also greatly aid skin rejuvenation when used to inject aesthetic materials such as hyaluronic acid, botulinum toxin, and placental extracts. There has not been any specific research to date examining how materials penetrate the skin when a needle-free injection device is used. In this study, we investigated how material infiltrates the skin when it is injected into a cadaver using a needle-free device. STUDY DESIGN/MATERIALS AND METHODS: Using a needle-free injector (INNOJECTOR™; Amore Pacific, Seoul, Korea), 0.2 ml of 5% methylene blue (MB) or latex was injected into cheeks of human cadavers. The device has a nozzle diameter of 100 µm and produces a jet with velocity of 180 m/s. This jet penetrates the skin and delivers medicine intradermally via liquid propelled by compressed gasses. Materials were injected at pressures of 6 or 8.5 bars, and the injection areas were excised after the procedure. The excised areas were observed visually and with a phototrichogram to investigate the size, infiltration depth, and shape of the hole created on the skin. A small part of the area that was excised was magnified and stained with H&E (×40) for histological examination. RESULTS: We characterized the shape, size, and depth of skin infiltration following injection of 5% MB or latex into cadaver cheeks using a needle-free injection device at various pressure settings. Under visual inspection, the injection at 6 bars created semi-circle-shaped hole that penetrated half the depth of the excised tissue, while injection at 8.5 bars created a cylinder-shaped hole that spanned the entire depth of the excised tissue. More specific measurements were collected using phototrichogram imaging. The shape of the injection entry point was consistently spherical regardless of the amount of pressure used. When injecting 5% MB at 6 bars, the depth of infiltration reached 2.323 mm, while that at 8.5 bars reached 8.906 mm. The area of the hole created by the 5% MB injection was 0.797 mm(2) at 6 bars and 0.242 mm(2) at 8.5 bars. Latex injections reached a depth of 3.480 mm at 6 bars and 7.558 mm at 8.5 bars, and the areas were measured at 1.043 mm(2) (6 bars) and 0.355 mm(2) (8.5 bars). Histological examination showed that the injection penetrated as deep as the superficial musculoaponeurotic system at 6 bars and the masseter muscle at 8.5 bars. CONCLUSION: When injecting material into the skin using a pneumatic needle-free injector, higher-pressure injections result in a hole with smaller area than lower-pressure injections. The depth and shape of skin penetration vary according to the amount of pressure applied. For materials of low density and viscosity, there is a greater difference in penetration depth according to the degree of pressure. Lasers Surg. Med. 48:624-628, 2016. © 2016 Wiley Periodicals, Inc.

Conditioned medium from human bone marrow-derived mesenchymal stem cells promotes skin moisturization and effacement of wrinkles in UVB-irradiated SKH-1 hairless mice.

BACKGROUND: Mesenchymal stem cells (MSCs) are promising therapeutic agents for various diseases. AIMS: To investigate the effects of conditioned medium from human bone marrow-derived mesenchymal stem cells (MSC-CdM) on pro-collagen production and wrinkle formation, we performed in vitro and in vivo experiments. METHODS: We assessed the effects of MSC-CdM on proliferation and photo-aging in human dermal fibroblasts after UVB exposure using enzyme activity assays for collagen type I secretion and MMP-1. To determine the effect of topically applied MSC-CdM on wrinkle formation, MSC-CdM (1% and 10%) and vehicle (propylene glycol: ethanol, 7 : 3) were applied to the dorsal skin of UVB-irradiated hairless mice for 8 weeks. We examined the effects on wrinkle formation by assessing visual skin grading, replica, tape stripping, transepidermal water loss (TEWL), and skin hydration measurement. We also examined histology of the lesions using hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining. RESULTS: MSC-CdM markedly reduced UV-induced matrix metalloproteinase-1 expression and increased pro-collagen synthesis in a dose-dependent manner. Our findings suggest that MSC-CdM induces repair of dermal damage and effacement of wrinkles on UVB-irradiated hairless mice through protective effect of hydration. CONCLUSION: These results support an anti-wrinkle effect of MSC-CdM that involves increased collagen synthesis and suggest that MSC-CdM might be a potential candidate for preventing UV-induced skin damage.

Ultraviolet light-emitting-diode irradiation inhibits TNF-α and IFN-γ-induced expression of ICAM-1 and STAT1 phosphorylation in human keratinocytes.

BACKGROUND AND OBJECTIVES: Ultraviolet light-emitting diodes (UV-LEDs) are a novel light source for phototherapy. This research investigated the in vitro safety and efficacy of UV-LEDs as a phototherapeutic device for atopic dermatitis (AD). STUDY DESIGN/MATERIALS AND METHODS: Human keratinocytes and fibroblasts were irradiated by UV-LEDs with a center wavelength of 310 and 340 nm. We examined the effects of UV-LED irradiation on the suppression of TNF-α/IFN-γ-induced activation of STAT1 and ICAM-1 and on NF-κB expression; we used the following methods: cell viability assay, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and immunocytochemistry. RESULTS: We observed anti-inflammatory responses through the suppression of TNF-α/IFN-γ-induced expression of TARC and MCP-1/CCL2, IL-1beta, IL-6, and sICAM-1 via blockage of ICAM-1 activation and subsequent activation of STAT1 and NF-κB. The results suggested that UV-LED irradiation inhibited ICAM expression by suppressing TNF-α/IFN-γ-induced NF-κB activation in vitro. CONCLUSION: We concluded that novel UV-LED (310 and 340 nm) modalities were effective for the treatment of AD and may be promising for the treatment of inflammatory skin diseases.

Human placental extract exerts hair growth-promoting effects through the GSK-3ß signaling pathway in human dermal papilla cells.

Human placental extract (HPE) is widely used in Korea to relieve fatigue. However, its effects on human dermal papilla cells (hDPCs) remain unknown. In the present study, in an effort to develop novel therapies to promote hair growth, we screened HPE. We demonstrate that HPE has hair growth­promoting activities and induces ß­catenin expression through the inhibition of glycogen synthase kinase­3ß (GSK­3ß) by phosphorylation in hDPCs. Treatment with HPE significantly increased the viability of the hDPCs in a concentration­dependent manner, as shown by bromodeoxyuridine (BrdU) assay. HPE also significantly increased the alkaline phosphatase (ALP) expression levels. The increased ß­catenin levels and the inhibition of GSK­3ß (Ser9) by phosphorylation suggested that HPE promoted the hair-inductive capacity of hDPCs. We compared the effects of treatment with HPE alone and treatment with HPE in conjunction with minoxidil (MXD). We found that HPE plus MXD effectively inhibited GSK­3ß by phosphorylation (Ser9) in the hDPCs. Moreover, we demonstrated that HPE was effective in inducing root hair elongation in rat vibrissa hair follicles, and that treatment with HPE led to a delay in catagen progression. Overall, our findings suggest that HPE promotes hair growth and may thus provide the basis of a novel therapeutic strategy for the clinical treatment of hair loss.