BACKGROUND AND OBJECTIVES:Ablative fractional lasers are widely used for skin renewal and rejuvenation. The typical diameter of beam incident on skin is in the range 100-500 μm, which has been shown to be safe and effective for skin treatment. This study presents the first in vivo analysis of a novel 3050/3200 nm Difference Frequency Generation laser, which has a beam diameter of 40 μm. The objective is to determine if treatment with such a small beam diameter-microfractional treatment-can induce skin renewal and improvement. MATERIAL AND METHODS:Experiments were performed with ex vivo mini-pig skin to determine the correlation between pulse energy and ablation depth. Laser treatment was then performed on in vivo human abdominal skin, which was planned for removal with abdominoplasty. Various pulse energies (range 3-29 mJ) and numbers of dots per cm² (range 2600-441 dost/cm2) were applied at 3 months, 1.5 months, 7 days, and 48, 24, and 2 h before surgery. Excised skin samples were analyzed using hematoxylin and eosin staining to assess tissue morphology, immunochemistry to determine expression of transforming growth factor-β (TGF-β) and inflammatory markers, and enzyme-linked immunosorbent assay (ELISA) to quantify procollagen I synthesis. RESULTS:Pulse energy (range 2-40 mJ) can be chosen to obtain desired ablation depth (150-2000 μm)-this relationship was obtained. The microfractional skin ablation allows application of a high density, that is, number of dots per cm² with subsequent healing in a scar-free manner. The main steps of the regeneration processes induced by 3-μm laser are similar to those induced by other lasers. The treatment resulted in an increased number of fibroblasts (1.7-2.7 fold change), procollagen I synthesis (1.4-3.4 fold change), and neovascularization (1.9-2.7 fold change) 3 months after treatment. We also observed changes in the TGF-β isoforms, CD68, and neutrophil elastase, with timing of the changes showing slight dependance on treatment parameters. Finally, tissue response in terms of collagen synthesis and neovascularization is correlated with tissue ablation volume. CONCLUSION:The microfractional 3050/3200 nm laser treatment enables application of a high dot number/cm2 density, resulting in scar-free healing and tissue renewal and improvement. This makes it an efficient alternative to other fractional devices, offering advantages such as ease of use, and potentially reducing the number of treatment sessions required.

Background and Objectives The use of ablative fractional lasers to enhance the delivery of topical drugs through the skin is known as laser-assisted drug delivery. Here, we compare a novel 3050/3200 nm difference frequency generation (DFG) fiber laser (spot size: 40 mu m) to a commercially used CO2 laser (spot size: 120 mu m). The objective is to determine whether differences in spot size and coagulation zone (CZ) thickness influence drug uptake.Materials and Methods Fractional ablation was performed on ex-vivo human abdominal skin with the DFG (5 mJ) and CO2 (12 mJ) lasers to generate 680 mu m deep lesions. To evaluate drug delivery, 30 kDa encapsulated fluorescent dye was topically applied to the skin and histologically analyzed at skin depths of 100, 140, 200, 400, and 600 mu m. Additionally, transcutaneous permeation of encapsulated and 350 Da nonencapsulated dye was assessed using Franz Cells.Results The DFG laser generated smaller channels (diameter: 56.5 mu m) with thinner CZs (thickness: 22.4 mu m) than the CO(2 )laser (diameter: 75.9 mu m, thickness: 66.8 mu m). The DFG laser treated group exhibited significantly higher encapsulated dye total fluorescence intensities after 3 h compared to the CO2 laser treated group across all skin depths (p < 0.001). Permeation of nonencapsulated dye was also higher in the DFG laser treated group vs the CO2 laser treated group after 48 h (p < 0.0001), while encapsulated dye was not detected in any group.Conclusion The DFG laser treated skin exhibited significantly higher total fluorescence uptake compared to the CO(2 )laser. Additionally, the smaller spot size and thinner CZ of the DFG laser could result in faster wound healing and reduced adverse effects while delivering similar or greater amount of topically applied drugs.

OBJECTIVES:Laser-based endoscopic procedures present special challenges to deliver energy for ablation or coagulation of target tissues. When optical fiber-target quasi-contact (< 0.5 mm distance) cannot be maintained or is undesirable, the creation of intervening vapor bubbles and channels provide for the necessary transmission of laser energy to the target. This work investigates the characteristics and the dynamics of vapor channels that directly affect ablation efficiency and ablation rate and are known to effect stone movement, all of which impact procedure efficiency and safety. METHODS:A simplified, experimental model for thulium fiber laser (1940 nm) lithotripsy consists of a water-filled cuvette and a vertically oriented laser fiber (200 μm core diameter) with its tip at 9 mm for "quasi-free" bubble generation and at vapor channel working distances 1-5 mm from and centered on the transparent cuvette bottom simulating a target's surface. Laser power transmission is recorded and synchronized with video frames from a high-speed camera (24,260 frames per second) to capture the induced vapor channels' and bubbles' development. RESULTS:Laser-induced channel transmission from 0% to 100% for 1, 2, and 3 mm fiber-target distances undergoes oscillations with average periods of 0.32, 0.64, and 1.0 ms, respectively, for 500 W laser output power. For fixed fiber-target distances of 0.5, 1, and 2 mm, the variation of these average oscillation frequencies across laser powers from 500 to 1000 W is much smaller, not exceeding 14%. For fiber-target distances in the range of 1-5 mm, the fraction of the 500 W laser's total pulse energy delivered to the target for 1, 2, and 3 ms pulses linearly decreases from 0.78 to less than 0.2. The channel and bubble dynamics begin with a spherical seed bubble expansion centered on the distal fiber tip that evolves into a pear shape whose surface exhibits periodic irregularities attributable to laser beam interruption by water droplets within the developing bubble. CONCLUSIONS:The study of laser-induced channel oscillations provides quantitative information relating fiber-target distance to channel oscillation frequency and energy transmission onto a target. These oscillations directly effect ablation efficiency and ablation rates that are important parameters for the optimization of a procedure's safety and duration. Insights that may lead to further reduction in retropulsion are also presented. Lasers Surg. Med. 00:00-00, 2024. © 2024 Wiley Periodicals LLC.

Background and Objectives Mid-infrared (IR) ablative fractional laser treatments are highly efficacious for improving the appearance of a variety of dermatological conditions such as photo-aged skin. However, articulated arms are necessary to transmit the mid-IR light to the skin, which restricts practicality and clinical use. Here, we have assessed and characterized a novel fiber laser-pumped difference frequency generation (DFG) system that generates ablative fractional lesions and compared it to clinically and commercially available thulium fiber, Erbium:YAG (Er:YAG), and CO2 lasers. Materials and Methods An investigational 20 W, 3050/3200 nm fiber laser pumped DFG system with a focused spot size of 91 mu m was used to generate microscopic ablation arrays in ex vivo human skin. Several pulse energies (10-70 mJ) and pulse durations (2-14 ms) were applied and lesion dimensions were assessed histologically using nitro-blue tetrazolium chloride stain. Ablation depths and coagulative thermal damage zones were analyzed across three additional laser systems. Results The investigational DFG system-generated deep (>2 mm depth) and narrow (<100 mu m diameter) ablative lesions surrounded by thermal coagulative zones of at least 20 mu m thickness compared to 13, 40, and 320 mu m by the Er:YAG, CO2, and Thulium laser, respectively. Conclusion The DFG system is a small footprint device that offers a flexible fiber delivery system for ablative fractional laser treatments, thereby overcoming the requirement of an articulated arm in current commercially available ablative lasers. The depth and width of the ablated microcolumns and the extent of surrounding coagulation can be controlled; this concept can be used to design new treatment procedures for specific indications. Clinical improvements and safety are not the subject of this study and need to be explored with in vivo clinical studies.

The pathophysiology of acne vulgaris depends on active sebaceous glands, implying that selective destruction of sebaceous glands could be an effective treatment. We hypothesized that light-absorbing microparticles could be delivered into sebaceous glands, enabling local injury by optical pulses. A suspension of topically applied gold-coated silica microparticles exhibiting plasmon resonance with strong absorption at 800 nm was delivered into human pre-auricular and swine sebaceous glands in vivo, using mechanical vibration. After exposure to 10-50 J cm(-2), 30 milliseconds, 800 nm diode laser pulses, microscopy revealed preferential thermal injury to sebaceous follicles and glands, consistent with predictions from a computational model. Inflammation was mild; gold particles were not retained in swine skin 1 month after treatment, and uptake in other organs was negligible. Two independent prospective randomized controlled clinical trials were performed for treatment of moderate-to-severe facial acne, using unblinded and blinded assessments of disease severity. Each trial showed clinically and statistically significant improvement of inflammatory acne following three treatments given 1-2 weeks apart. In Trial 2, inflammatory lesions were significantly reduced at 12 weeks (P=0.015) and 16 weeks (P=0.04) compared with sham treatments. Optical microparticles enable selective photothermolysis of sebaceous glands. This appears to be a well-tolerated, effective treatment for acne vulgaris.

Recent advances in nanotechnology have provided numerous opportunities to transform medical therapies for the treatment of diseases including cancer, atherosclerosis, and thrombosis. Here, we report, through in vitro studies and in vivo human pilot clinical studies, the use of inert, inorganic silica-gold nanoshells for the treatment of a widely prevalent and researched, yet poorly treated disease of acne. We use ~150nm silica-gold nanoshells, tuned to absorb near-IR light and near-IR laser irradiation to thermally disrupt overactive sebaceous glands in the skin which define the etiology of acne-related problems. Low-frequency ultrasound was used to facilitate deep glandular penetration of the nanoshells. Upon delivery of the nanoshells into the follicles and glands, followed by wiping of superficial nanoshells from skin surface and exposure of skin to near-infrared laser, nanoshells localized in the follicles absorb light, get heated, and induce focal thermolysis of sebaceous glands. Pilot human clinical studies confirmed the efficacy of ultrasonically-delivered silica-gold nanoshells in inducing photothermal disruption of sebaceous glands without damaging collateral skin.