Clinical and histologic evaluation of a fractional radiofrequency treatment of wrinkles and skin texture with novel 1-mm long ultra-thin electrode pins.

BACKGROUND: Fractional radiofrequency (RF) microneedling technologies have shown effectiveness in treating skin laxity and wrinkles. We report the first experience using a novel device with 1-mm long ultrathin electrodes that utilizes a smooth RF-assisted ablation mode. OBJECTIVE: To evaluate the safety and effectiveness of treatment with a fractional RF device using 1.0-mm long × 0.15-mm diameter ultrathin electrode tips for improvement of facial skin texture and wrinkles. METHODS AND MATERIALS: This was a prospective, open-label, intraindividual-controlled trial. Nine participants (mean age: 47.6, Fitzpatrick skin type II-IV, Fitzpatrick Elastosis Wrinkle Scale [FEWS] score: 3-6) underwent six treatment sessions with a fractional RF technology utilizing an array of 6 × 6 1-mm long ultrathin electrodes. Treatment effectiveness was assessed by FEWS and the Global Aesthetic Improvement Scale (GAIS). Safety and tolerance were evaluated. RESULTS: Three months after the sixth treatment session, blinded, investigator-assessed FEWS decreased from baseline 4.33 ± 0.67-3.33 ± 0.67 (p < 0.005); 88.9% of participants showed overall skin improvement using the physician-assessed GAIS, and all of the participants reported improvement in skin texture and wrinkles. Treatment was well tolerated, with no adverse events and no downtime. Histological analysis in a porcine model showed a fractional pattern of epidermal ablation and dermal coagulation with intervening zones of normal healthy tissue. These changes were followed by progressive epithelialization over a period of 13 days. CONCLUSION: The fractional RF technology with the novel 1.0 long × 0.15 mm ultrathin electrodes tips was effective in improving skin texture and wrinkles without impacting the participants' daily activities.

VoluDerm microneedle technology for skin treatments-in vivo histological evidence.

INTRODUCTION: The growing demand for skin rejuvenation procedures with minimal down time and low risk has led to the development of fractional radiofrequency (RF) systems. The new VoluDerm™ RF microneedle technology creates minute columns of tissue thermal microablation. Treatment triggers natural fractional healing, resulting in dermal volumizing and skin renewal. This preclinical research assessed the safety and efficacy of the VoluDerm through histological evaluation of morphological changes in the target tissue. METHODS: Following approval of protocol by ethical committee, treatments were conducted on two domestic pigs using VoluDerm disposable tips. Histological samples of 14, 7, 4 days and immediately after treatment with various energy settings were analyzed. RESULTS: Immediate VoluDerm epidermal and dermal effects, and progress of healing process, as function of time following treatment (days 4 and 7), were demonstrated. Histology analysis of samples of 14 days demonstrated complete healing for all energy levels. SUMMARY: This in vivo histology confirmed the safe and effective performance of the VoluDerm treatment. A fractional pattern of affected areas, surrounded by healthy tissue, was demonstrated. Healing process proved natural dermal renewal and epidermal complete regeneration. Histology supports clinical advantages of the VoluDerm natural-looking skin enhancement, with none to minimal pain and no downtime.

Cutaneous gene expression of plasmid DNA in excised human skin following delivery via microchannels created by radio frequency ablation.

The skin is a valuable organ for the development and exploitation of gene medicines. Delivering genes to skin is restricted however by the physico-chemical properties of DNA and the stratum corneum (SC) barrier. In this study, we demonstrate the utility of an innovative technology that creates transient microconduits in human skin, allowing DNA delivery and resultant gene expression within the epidermis and dermis layers. The radio frequency (RF)-generated microchannels were of sufficient morphology and depth to permit the epidermal delivery of 100 nm diameter nanoparticles. Model fluorescent nanoparticles were used to confirm the capacity of the channels for augmenting diffusion of macromolecules through the SC. An ex vivo human organ culture model was used to establish the gene expression efficiency of a beta-galactosidase reporter plasmid DNA applied to ViaDerm treated skin. Skin treated with ViaDerm using 50 microm electrode arrays promoted intense levels of gene expression in the viable epidermis. The intensity and extent of gene expression was superior when ViaDerm was used following a prior surface application of the DNA formulation. In conclusion, the RF-microchannel generator (ViaDerm) creates microchannels amenable for delivery of nanoparticles and gene therapy vectors to the viable region of skin.

Transdermal delivery of human growth hormone through RF-microchannels.

PURPOSE: To evaluate the bioavailability and bioactivity of human growth hormone (hGH) delivered transdermally through microchannels (MCs) in the skin created by radio-frequency (RF) ablation. METHODS: The creation of MCs was observed in magnified rat and guinea pig skin after staining by methylene blue. Various doses of hGH in a dry form were applied on rat or guinea pig (GP) skin after the formation of MCs. The pharmacokinetic profile of systemic hGH in both animal models was monitored for 15 h post patch application. Bioactivity of the transdermally delivered hGH was verified by measuring IGF-I levels in hypophysectomized rats. RESULTS: The ordered array of MCs was clearly visible in the magnified rat and guinea pig skin. The MCs were very uniform in diameter and of equal separation. Creation of MCs in the outer layers of the skin enabled efficient delivery of hGH, with a bioavailability of 75% (rats) or 33% (GPs) relative to subcutaneous (s.c.) injection with plasma profiles resembling that of s.c. injection. Elevated levels of systemic insulin-like growth factor-1 (IGF-I) were observed after transdermal delivery of hGH to hypophysectomized rats indicative of the bioactivity of the transdermally delivered hGH in vivo. CONCLUSIONS: Formation of RF-microchannels is a well-controlled process. These MCs permitted the transdermal delivery of bioactive hGH in rats and GPs with high bioavailability.

Development of a scaled up liver device incorporating cryo-preserved pig liver micro-organs.

BACKGROUND/AIMS: Currently there is no effective therapy for most patients with fulminant or end stage liver disease. METHODS: Pig liver micro-organs (LMOs), which preserve liver micro-architecture and ensure a maximal 150-200mum distance from a source of nutrients and gases have been prepared and a method to cryo-preserve them has been developed. A new scaled-up extra-corporeal liver device termed aLIVE-H in which LMOs are exposed to liver-like hemodynamic conditions has also been developed. The purpose of this work is to test the safety and function of cryo-preserved LMOs and how the hemodynamic properties of the scaled up aLIVE device affect their function. RESULTS: Pig LMOs in aLIVE-H, transcribe albumin and Factor V at similar levels, irrespective of their position within the bioreactor, indicating that the hemodynamic features of the aLIVE-H device allow for homogeneous plasma distribution and proper function at different locations. Cryo-preserved LMOs transcribe albumin and Factor V at levels comparable to those transcribed by a normal pig liver. Connecting the aLIVE-H bioreactor to normal pigs did not affect key blood components and biochemical parameters. CONCLUSIONS: An extra-corporeal liver device aLIVE-H which imitates the hemodynamic and functional properties of the normal liver and incorporates cryo-preserved LMOs has been developed and characterized. aLIVE-H was found to perform key synthetic liver functions.