Safety and efficacy of basic fibroblast growth factors for deep second-degree burn patients.

INTRODUCTION: Burn injuries are common afflictions; however, conservative wound care frequently leads to poor treatment compliance and physical disability in deep burn patients. Therefore, regenerative biologic materials, which are more effective for tissue repair, are required, particularly for deep second-degree burns. A novel spray formulation of basic fibroblast growth factors (bFGF) was produced by synthesizing fibroblast growth factor proteins. In this post-marketing surveillance (PMS) study, we assessed the safety and efficacy of bFGF and indirectly compared this formulation with cultured epidermal autografts (CEAs) for treating deep second-degree burns. MATERIALS AND METHODS: A total of 3173 patients treated at 15 hospitals were used for PMS of bFGF in South Korea for six years. In total, 1630 patients with deep second-degree burns were selected for assessing adverse events (AEs) of bFGF treatments. Efficacy was evaluated according to time periods until re-epithelialization, and clinical usefulness of bFGF was indirectly compared with that of CEAs. RESULTS: AEs occurred in 37 patients (2.3%) and included application site pain (1.7%) and contact dermatitis (0.6%). All AEs were mild and were evaluated as probably unrelated with bFGF. The average time for re-epithelialization was 8 days; this time span was significantly longer after major burns (9.7 days) than after minor (7.8 days) or moderate burns (7.9 days). Most treated burn wounds (99.8%) were assessed as improved. The indirect comparison included 534 patients using the same inclusion criteria for CEA patients (n = 35). The bFGF treatment demonstrated superior efficacy compared to CEAs by significantly reducing the average day to application (5.4 vs. 8.8 days) and re-epithelialization time (7.1 vs. 13.7 days). CONCLUSION: Our study demonstrated that bFGF is a compelling regenerative therapy with competitive clinical efficacy and safety for deep second-degree burns and reduced treatment time, which is expected to reduce medical costs, particularly for deep second-degree burn patients.

Real-time functional optical-resolution photoacoustic microscopy using high-speed alternating illumination at 532 and 1064 nm.

Optical-resolution photoacoustic microscopy (OR-PAM), which has been widely used and studied as a noninvasive and in vivo imaging technique, can yield high-resolution and absorption contrast images. Recently, metallic nanoparticles and dyes, such as gold nanoparticles, methylene blue, and indocyanine green, have been used as contrast agents of OR-PAM. This study demonstrates real-time functional OR-PAM images with high-speed alternating illumination at 2 wavelengths. To generate 2 wavelengths, second harmonic generation at 532 nm with an LBO crystal and a pump wavelength of 1064 nm is applied at a pulse repetition rate of 300 kHz. For alternating illumination, an electro-optical modulator is used as an optical switch. Therefore, the A-line rate for the functional image is 150 kHz, which is half of the laser repetition rate. To enable fast signal processing and real-time displays, parallel signal processing using a graphics processing unit (GPU) is performed. OR-PAM images of the distribution of blood vessels and gold nanorods in a BALB/c-nude mouse's ear can be simultaneously obtained with 500 × 500 pixels and real-time display at 0.49 fps.

Stacked Gold Nanodisks for Bimodal Photoacoustic and Optical Coherence Imaging.

Herein, we report on biological imaging nanoprobes: physically synthesized gold nanodisks that have inherent optical advantages-a wide range of resonant wavelengths, tunable ratio of light absorption-to-scattering, and responsiveness to random incident light-due to their two-dimensional circular nanostructure. Based on our proposed physical synthesis where gold is vacuum deposited onto a prepatterned polymer template and released from the substrate in the form of a nanodisk, monodisperse two-dimensional gold nanodisks were prepared with independent control of their diameter and thickness. The optical benefits of the Au nanodisk were successfully demonstrated by the measurement of light absorbance of the nanodisks and the application of stacked nanodisks, where a smaller sized Au nanodisk was laid atop a larger nanodisk, as bimodal contrast agents for photoacoustic microscopy and optical coherence tomography.

Physically-synthesized gold nanoparticles containing multiple nanopores for enhanced photothermal conversion and photoacoustic imaging.

Physically-synthesized gold nanoparticles having a narrow size distribution and containing multiple nanopores have been utilized as photothermal converters and imaging contrast agents. Nanopores within the gold nanoparticles make it possible to increase the light-absorption cross-section and consequently exhibit distinct improvements in photothermal conversion and photoacoustic imaging efficiencies.

Performance of AlGaN/GaN Nanowire Omega-Shaped-Gate Fin-Shaped Field-Effect Transistor.

The AlGaN/GaN nanowire omega-shaped-gate FinFET have been successfully fabricated demonstrating much improved performance compared to conventional AlGaN/GaN MISHFET. The AlGaN/GaN omega-shaped-gate FinFET exhibited the remarkable on-state performances, such as maximum drain current of 1.1 A/mm, low on-resistance, and low current collapse compared to that of the conventional device structure. In addition, the excellent off-state performances were measured: low off-state leakage current as low as -10(-10) mA, the theoretical SS value of -62 mV/dec, and high I(ON)/I(OFF) ratio (-10(9)). Improved dc performances were obtained for omega-shaped-gate structure due to the fully depletion of the active fin body and perfectly separation of the depleted fin from the underlying thick GaN buffer layer. Furthermore, the additional reason for the enhanced device performance of the proposed device is the improved gate controllability compared to the conventional MISHFET. The proposed nano-structure device is very promising candidate for the steep switching device applications.

Observation of vasculature alternation by intense pulsed light combined with physicochemical methods.

Intense pulsed light (IPL) with low energy insufficient to completely destroy a vasculature was applied to rabbit ears to investigate vasculature alteration. Glycerol was combined with IPL to enhance the transfer efficacy of IPL energy. Both trans-illumination and laser speckle contrast images were obtained and analyzed after treatment. The application of IPL and glycerol combination induced vasodilation and improvement in blood flow. Moreover, such phenomenon was maintained over time. IPL may be applied to treat blood circulatory diseases by inducing vasodilation and to improve blood flow.

Real-time GPU-accelerated processing and volumetric display for wide-field laser-scanning optical-resolution photoacoustic microscopy.

Fast signal processing and real-time displays are essential for practical imaging modality in various fields of applications. However, the imaging speed in optical-resolution photoacoustic microscopy (OR-PAM), in particular, depends on factors such as the pulse repetition rate of the laser, scanning method, field of view (FOV), and signal processing time. In the past, efforts to increase acquisition speed either focused on developing new scanning methods or using lasers with higher pulse repetition rates. However, high-speed signal processing is also important for real-time volumetric display in OR-PAM. In this study, we carried out parallel signal processing using a graphics processing unit (GPU) to enable fast signal processing and wide-field real-time displays in laser-scanning OR-PAM. The average total GPU processing time for a B-mode PAM image was approximately 1.35 ms at a display speed of 480 fps when the data samples were acquired with 736 (axial) × 500 (lateral) points/B-mode-frame at a pulse repetition rate of 300 kHz. In addition, we successfully displayed maximum amplitude projection images of a mouse's ear as volumetric images with an FOV of 3 mm × 3 mm (500 × 500 pixels) at 1.02 s, corresponding to 0.98 fps.

Short-Channel Tunneling Field-Effect Transistor with Drain-Overlap and Dual-Metal Gate Structure for Low-Power and High-Speed Operations.

We have investigated and proposed a highly scaled tunneling field-effect transistor (TFET) based on Ge/GaAs heterojunction with a drain overlap to suppress drain-induced barrier thinning (DIBT) and improve low-power (LP) performance. The highly scaled TFET with a drain overlap achieves lower leakage tunneling current because of the decrease in tunneling events between the source and drain, whereas a typical short-channel TFET suffers from a great deal of tunneling leakage current due to the DIBT at the off-state. However, the drain overlap inevitably increases the gate-to-drain capacitance (Cgd) because of the increase in the overlap capacitance (Cov) and inversion capacitance (Cinv). Thus, in this work, a dual-metal gate structure is additionally applied along with the drain overlap. The current performance and the total gate capacitance (Cgg) of the device with a dual-metal gate can be possibly controlled by adjusting the metal gate workfunction (φgate) and φoverlap-gate in the overlapping regions. As a result, the intrinsic delay time (τ) is greatly reduced by obtaining lower Cgg divided by the on-state current (Ion), i.e., Cgg/Ion. We have successfully demonstrated excellent LP and high-speed performance of a highly scaled TFET by adopting both drain overlap and dual-metal gate with DIBT minimization.

The effects of a minimally invasive laser needle system on complete Freund's adjuvant-induced arthritis.

The present study aimed to investigate the effects of a minimally invasive laser needle system (MILNS) on the acute progression of arthritis. Previous studies showed controversial clinical results regarding the effects of low-level laser therapy on arthritis, with the outcomes depending upon stimulation parameters such as laser wavelength and dosage. Based on the positive effects of MILNS on osteoporotic mice, we hypothesized that MILNS could potentially suppress the progression of arthritis owing to its biostimulation effects. Eight C57BL/6 mice with complete Freund's adjuvant (CFA)-induced arthritis were used as acute progression arthritis models and divided into the laser and control groups (n = 4 each). In the laser group, after minimally invasive laser stimulation, laser speckle contrast images (LSCIs) were obtained every 6 h for a total of 108 h. The LSCIs in the control group were obtained without laser stimulation. The effects of MILNS on the acute progression of arthritis were indirectly evaluated by calculating the paw area and the average laser speckle index (LSI) at the arthritis-induced area. Moreover, the macrophage population was estimated in the arthritis-induced area. Compared to the control group, the laser group showed (1) lower relative variations of the paw area, (2) lower average LSI in the arthritis-induced area, and (3) lower macrophage population in the arthritis-induced area. These results indicate that MILNS may suppress the acute progression of CFA-induced arthritis in mice and may thus be used as a potential treatment modality of arthritis in clinics.

The effects of minimally invasive laser needle system on suppression of trabecular bone loss induced by skeletal unloading.

This study was aimed to evaluate the effects of low-level laser therapy (LLLT) in the treatment of trabecular bone loss induced by skeletal unloading. Twelve mice have taken denervation operation. At 2 weeks after denervation, LLLT (wavelength, 660 nm; energy, 3 J) was applied to the right tibiae of 6 mice (LASER) for 5 days/week over 2 weeks by using a minimally invasive laser needle system (MILNS) which consists of a 100 µm optical fiber in a fine needle (diameter, 130 µm) [corrected]. Structural parameters and histograms of bone mineralization density distribution (BMDD) were obtained before LLLT and at 2 weeks after LLLT. In addition, osteocyte, osteoblast, and osteoclast populations were counted. Two weeks after LLLT, bone volume fraction, trabeculae number, and trabeculae thickness were significantly increased and trabecular separations, trabecular bone pattern factor, and structure model index were significantly decreased in LASER than SHAM (p < 0.05). BMDD in LASER was maintained while that in SHAM was shifted to lower mineralization. Osteocyte and osteoblast populations were significantly increased but osteoclast population was significantly decreased in LASER when compared with those in SHAM (p < 0.05). The results indicate that LLLT with the MILNS may enhance bone quality and bone homeostasis associated with enhancement of bone formation and suppression of bone resorption.

Low-level laser therapy using the minimally invasive laser needle system on osteoporotic bone in ovariectomized mice.

This study tested the effectiveness of low-level laser therapy (LLLT) in preventing and/or treating osteoporotic trabecular bone. Mice were ovariectomized (OVX) to induce osteoporotic bone loss. The tibiae of eight OVX mice were treated for 5 days each week for 2 weeks by LLLT (660 nm, 3 J) using a minimally invasive laser needle system (MILNS) which is designed to minimize loss of laser energy before reaching bone (LASER group). Another eight mice received a sham treatment (SHAM group). Structural parameters of trabecular bone were measured with in vivo micro-computed tomography images before and after laser treatment. After LLLT for 2 weeks, the percentage reduction (%R) was significantly lower in BV/TV (bone volume fraction) and Tb.N (trabecular number, p<0.05 and p<0.05) and significant higher in Tb.Sp (trabecular separation) and SMI (structure model index, p<0.05 and p<0.05) than in the SHAM group. The %R in BV/TV at sites directly treated by LLLT was significantly lower in the LASER group than the SHAM group (p<0.05, p<0.05). These results indicated that LLLT using MILNS may be effective for preventing and/or treating trabecular bone loss and the effect may be site-dependent in the same bone.

Real-time measurement of skin erythema variation by negative compression: pilot study.

Skin erythema has been widely used as a diagnostic parameter in dermatology. This study describes a methodology for real-time measurement of skin erythema variation induced by negative compression. This study developed an optical measurement probe, which includes a RGB color sensor that translates in the vertical direction, with the magnitude of vertical translation dependening on the amount of skin deformation. Real-time measurement of erythema variation as a function of both negative compression and time was performed in vivo on 10 measurement sites located on the back of each of 12 volunteers who participated in this study. Negative compression was sequentially applied from -30 to -80 kPa and continuously at a constant magnitude (-80 kPa) condition. The results showed that skin erythema was uniformly induced at the measurement sites and linearly increased as a function of both negative compression and time. A wide range of individual variation was noted for skin erythema, which may be due to variations in anisotropic skin properties between volunteers. This study demonstrated the clinical feasibility of a novel optical device for skin erythema measurement. Future studies are needed to investigate the clinical applications of this device.

Characterization of a new acne vulgaris treatment device combining light and thermal treatment methods.

BACKGROUND/PURPOSE: Conventional treatment methods for acne vulgaris have various side effects such as the development of bacterial resistance, phototoxicity, vertigo, gastro-intestinal problems, and drug eruptions. To minimize such side effects, light and thermal methods have been alternately suggested. This study characterized a new acne vulgaris treatment device (AVTD) that combines both light and thermal methods and evaluated its clinical efficacy. METHODS: We characterized the thermal and light properties of the AVTD itself and evaluated its thermal characteristics in ex vivo porcine skin samples. The Arrhenius equation was used to calculate the skin thermal injury coefficient to confirm the skin safety of the AVTD. Finally, the clinical efficacy of the AVDT was evaluated by analyzing cross-polarization and erythema index images, which were obtained from 13 volunteers undergoing treatment with the AVTD. RESULTS: The temperature of the AVTD itself was maintained at 49.1 °C on the tip and 39.7 °C in the porcine skin samples. The peak intensity of the light-emitting diode (LED) light was observed at 468 nm. The skin safety of the AVTD was confirmed and 84.2% of the volunteers presented positive treatment results. CONCLUSION: The treatment of acne using the AVTD resulted in a high treatment rate in a clinical study, minimizing side effects. On the basis of these results, we can be sure that the AVTD may be effectively used for the treatment of acne vulgaris.

Development of a minimally invasive laser needle system: effects on cortical bone of osteoporotic mice.

Many studies have shown the positive effects of low-level laser therapy in the treatment of bone disease. However, laser radiation is scattered in the skin surface which reduces the initial photon density for tissue penetration and consequently the therapeutic efficacy. We developed a minimally invasive laser needle system (MILNS) to avoid laser scattering in tissue and investigated its stimulatory effects in the cortical bone of osteoporotic mice. The MILNS was designed to stimulate cortical bone directly by employing fine hollow needles to guide 100 µm optical fibers. The study animals comprised 12 mice which were subjected to sciatic denervation of the right hind limb and were randomly divided into two groups, a sham group and a laser group which were treated using the MILNS for 2 weeks without and with laser irradiation, respectively. In vivo micro-CT images were taken to analyze the structural parameters and bone mineral density. After 2 weeks of treatment with the MILNS, the relative changes in mean polar moment inertia, cross-section thickness, and periosteal perimeter were significantly higher in the laser group than in the sham group. Moreover, the distribution of bone mineral density index was higher in the laser group. The MILNS was developed as a minimally invasive treatment modality for bone disease and resulted in positive therapeutic efficacy in the cortical bone of osteoporotic mice.

Evaluation of laser beam profile in soft tissue due to compression, glycerol, and micro-needling.

BACKGROUND AND OBJECTIVES: Various methods have been suggested to enhance photon density in biological tissues in an attempt to maximize the efficacy of laser therapy. In this study, the effects of tissue compression, glycerol, and micro-needling methods on the laser beam profile (LBP) were investigated by quantitatively evaluating the spatial distribution of subsurface tissue photon density. STUDY DESIGN/MATERIALS AND METHODS: The LBP in tissue was obtained by imaging the laser beam transmitted through ex vivo porcine skin samples. The independent and combinational effects of tissue compression, glycerol, and micro-needling methods on the LBP were evaluated by quantitatively analyzing the full width at half-maximum (FWHM), maximum intensity, and total intensity at FWHM. RESULTS: Experimental results indicate the enhancement of the quality of Gaussian beam profile in ex vivo porcine skin. Glycerol and tissue compression resulted in an increase of maximum and total intensity and a decrease of FWHM. Tissue compression in conjunction with glycerol was determined to be the most effective method for enhancing the LBP. The topical application of glycerol in conjunction with micro-needling reduced the time period to optically clear tissue, which resulted in a further increase of subsurface tissue photon density. CONCLUSION: Tissue compression, glycerol, and micro-needling methods might be used independently or in combination to effectively enhance the photon density delivered to target chromophores in subsurface tissue, thus improving the LBP quality.

Polarization color imaging system for on-line quantitative evaluation of facial skin lesions.

BACKGROUND: A number of studies have been performed for accurate evaluation of chromophores in skin lesions. Qualitative methods are subjective and cause user-dependent error in evaluation. Quantitative methods have limitations for widely distributed skin lesions due to poor spatial resolution, potential skin blanching, and difficulty in relocating identical sites for subsequent measurements and analysis. OBJECTIVE: The objective was to develop a new imaging modality that provides both qualitative and quantitative methods to evaluate widely distributed skin lesions. METHODS: We have developed a prototype polarization color imaging system named "DermaVision," which provides quantitative on-line image analysis of polarization color images. Herein, we describe the hardware and software of DermaVision in terms of its performance and usefulness for dermatologic applications. RESULTS: Polarization color images were successfully acquired from patients with vascular or pigmented skin lesions. The erythema and melanin index images were successfully computed and quantitatively confirmed the degree of erythema and pigmentation in the skin lesions. CONCLUSION: We believe that DermaVision can be a useful auxiliary tool in dermatology because it simultaneously provides both qualitative and quantitative images of skin lesions.