A Comparison of Human and Porcine Skin in Laser-Assisted Drug Delivery of Chemotherapeutics.

BACKGROUND AND OBJECTIVES: Porcine skin is a widely used model in diffusion studies, but its usefulness for laser-assisted drug delivery (LADD) has not been evaluated in comparison with human skin. This study compared porcine and human skin in ex vivo LADD diffusion studies. STUDY DESIGN/MATERIALS AND METHODS: Ex vivo ablative fractional laser (AFL) treatments (5, 20, and 80 mJ/mb) were applied to skin samples from three sources: human, normal pig (Duroc × Landrace × Yorkshire breed), and a hyperkeratotic pig phenotype. Samples were stained using hematoxylin and eosin, photo-documented, and measured digitally. Samples (20 mJ/mb) were exposed to bleomycin or 5-fluorouracil (5-FU) for 19 hours in Franz diffusion cells. Drug uptake was quantified at three skin depths (100, 500, and 1,500 µm) by high-performance liquid chromatography-mass spectrometry. Drug biodistribution and endogenous lipids were visualized by matrix-assisted laser desorption/ionization-mass spectrometry imaging. RESULTS: Epidermal and dermal thicknesses of human and normal pig skin were similar (76-87 µm and 1,668-1,886 µm, respectively; P = 0.082-0.494). Endogenous lipids were investigated, and 116 compounds were identified. Of these compounds, 100 were found in all three skin types, while six were present exclusively in human skin. Laser channel depths (20 mJ/mb) in human and normal pig skin were similar (1,081 vs. 1,126 µm; P = 0.588). Bleomycin uptake was similar in all skin types at all depths (101.4-175.6 µg/cm3 ; P = 0.132-0.699). 5-FU uptake in human and normal pig skin was similar at 100 and 500 µm (80.5 vs. 140.3 µg/cm3 and 131.2 vs. 208.1 µg/cm3 , respectively; P = 0.065-0.093). At 1500 µm, 5-FU concentrations in the porcine skin types differed from those in human skin (104.7 vs. 196.7-344.8 µg/cm3 ; P = 0.002-0.026). Drug biodistribution was similar among skin types, but differences between bleomycin and 5-FU biodistribution were observed. CONCLUSIONS: Normal porcine and human skin showed similar morphology, the composition of endogenous lipids, and AFL-assisted cutaneous uptake, and biodistribution of chemotherapeutics. Therefore, normal porcine skin, but not hyperkeratotic pig phenotype skin, is a practical and reliable model for healthy human skin in ex vivo LADD diffusion studies. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Randomized, Controlled Early Intervention of Dynamic Mode Fractional Ablative CO2 Laser on Acute Burn Injuries for Prevention of Pathological Scarring.

BACKGROUND AND OBJECTIVES: This study challenges the currently accepted treatment parameters of waiting 1 year following burn injury to treat the resultant scarring. It assesses the impact of treating burn and trauma wounds at less than 3 months of injury on scar formation, providing a new temporal paradigm to patients in the prevention and minimization of scar formation. STUDY DESIGN/MATERIALS AND METHODS: This randomized clinical trial included 19 patients with moderate-to-severe acute burn injuries less than 3 months from injury. The treatment areas underwent three fractional ablative CO2 laser treatments at 8-week intervals. The primary outcomes were improvement in the Manchester Scar Scale (MSS) and photography. Secondary outcomes were optical coherence tomography (OCT), treatment time, immediate post-treatment response, and histology. RESULTS: Upon blinded evaluation, 100% of treatment areas were correctly identified when compared with control. MSS scores before and after treatment were totaled with an averaged sum of 13.33 per scar at baseline to 8.39 after treatment, a 63% average improvement versus control (P < 0.001). Histology and OCT demonstrated a re-organization of the underlying skin structure. The average treatment time was 18 minutes. Immediate post-treatment responses were limited to mild-to-moderate erythema. CONCLUSIONS: Early intervention with ablative fractional laser on acute traumatic wounds resulted in significant decrease of scar formation compared with untreated areas on the same wounds, providing an impactful new time course to treat severe burn and trauma injuries. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Delivery of Methotrexate and Characterization of Skin Treated by Fabricated PLGA Microneedles and Fractional Ablative Laser.

PURPOSE: This study investigated in vitro transdermal delivery of methotrexate through dermatomed porcine ear and cadaver human skin treated with poly (D,L-lactide-co-glycolide) acid microneedles or fractional ablative laser. METHODS: PLGA microneedles were fabricated and characterized using scanning electron microscopy and mechanical assessment techniques. The integrity of treated skin was evaluated by rheometer, transepidermal water loss, and skin electrical resistance measurements. Successful skin microporation was demonstrated by dye binding, histology, pore uniformity, confocal laser microscopy, and DermaScan studies. In vitro permeation experiment was performed on Franz diffusion cells to determine drug delivery into and across the skin. RESULTS: Both physical treatments resulted in a considerable decrease in skin resistance and an increase in transepidermal water loss value. The laser-created microchannels were significantly larger than those formed by microneedles (p < 0.05). An effective force of 41.04 ± 18.33 N was required to achieve 100% penetration efficiency of the microneedles. For both porcine ear and human skin, laser ablation provided a significantly higher methotrexate permeability into the receptor chamber and skin layers compared to microneedle poration and untreated skin (p < 0.05). CONCLUSIONS: Both fractional ablative laser and polymeric microneedles markedly enhanced in vitro transdermal delivery of methotrexate into and across skin. Graphical Abstract ᅟ.

Significant skin-tightening by closure of fractional ablative laser holes.

BACKGROUND AND OBJECTIVE: Ablative fractional laser treatment uses thousands of very small laser beam wounds to damage a fraction of the skin, which stimulates tissue remodeling. Each open micro-wound heals without scarring, but the amount of skin tightening achieved is limited. This animal study was performed to test the hypothesis that immediate temporary closure of fractional laser wounds could increase skin tightening after fractional ablative laser treatment. MATERIALS AND METHODS: Four adult swine were used for the study; 98 square test sites (3 × 3 cm) were tattooed on the abdomen and flanks of each pig. An ablative fractional Erbium:YAG laser (Sciton Profile, Sciton Inc, Palo Alto, CA) was used to treat the test areas. A laser micro-spot fluence of 375 J/cm2 was delivered in 150-250 microseconds pulses, resulting in an array of ablation channels extending 1.5 mm deep into the skin, with a spot size of 250 µm, with 10% treatment density. Immediately following laser exposure the resulting holes were closed using a stretched elastic adhesive dressing, which, when applied, recoiled and compressed the diameter of the ablation holes. The compressive dressings were removed after 7 days. This procedure was compared to removing the same amount of skin (10%) mechanically by specially designed 19 gauge coring needles, as well as to the same laser and coring methods without compression closure. Area and shape of test sites were measured by digital photography before and 28 days after treatment. Data analysis included compensation for animal growth, as measured by increase in the area of the untreated control sites. RESULTS: All treated and control sites healed within a week, without scarring evident at 28 days. Laser treatment combined with compressive wound closure caused significant shrinkage at 28 days compared with untreated control sites. The treated skin area was reduced by 11.5% (P = 0.0001). Needle coring with wound closure produced similar, significant shrinkage (8%, P < 0.0021), whereas laser and needle coring treatment without closure did not result in significant area reduction (P = 0.1289) compared with untreated control sites. CONCLUSION: Significant skin tightening can be achieved by immediate temporary non-invasive wound closure after short pulse Er:YAG fractional ablative laser treatment, as well as after mechanically removing skin with a coring needle. This approach may improve skin tightening after ablative laser treatments. Further clinical studies are necessary to confirm successful application in humans. Lasers Surg. Med. 50:64-69, 2018. © 2017 Wiley Periodicals, Inc.

Laser-assisted topical corticosteroid delivery for the treatment of keloids.

Laser-assisted drug delivery has generated intense interest. The objectives of this study are to evaluate the clinical benefit of laser-assisted corticosteroid delivery and to compare this technique to corticosteroid intralesional injection, a standard treatment for keloids. Patients with keloids on the left shoulder after BCG vaccination were enrolled in this study. The entire lesion was first treated with an ablative fractional erbium-YAG laser. After this treatment, the lesion was divided into two halves. The first half received an intralesional injection of corticosteroid, whereas the second half received topical application of corticosteroids that were occluded for 3 hours. Four treatment sessions were conducted, with treatments occurring once every 6 weeks. Treatment outcomes were evaluated using the Vancouver Scar Scale (VSS). Pain was self-assessed by the patient during the procedure. The mean keloid VSS score before treatment was 8.59 ± 1.23 for the corticosteroid injection site and 8.31 ± 2.09 for the topical site. After treatment, the mean keloid VSS score was decreased on both sides (4.56 ± 1.09 vs 5.02 ± 0.87, respectively, P > 0.05). Patients rated their satisfaction level as "moderate" on both sides. However, the mean pain score was 1.1 out of 10 on the topical side versus 6.1 on the corticosteroid injection site. The combination of ablative fractional laser treatment and topical corticosteroid application is a promising modality for the treatment of keloids. Moreover, this procedure was not associated with any serious adverse reactions or unbearable pain.

Ultrapulsed fractional ablative carbon dioxide laser treatment of hypertrophic burn scars: evaluation of an in-patient controlled, standardized treatment approach.

In this study, we aimed to quantify the effects of fractional ablative carbon dioxide laser therapy in the treatment of widespread hypertrophic burn scars. While many different pilot studies have described the potential of the technology and expert groups and current guidelines, alike, recommend its use, the level of evidence for the efficacy of fractional CO2-laser treatment for burn scars is currently very low. Ten patients (three male, seven female) with hypertrophic burn scars were treated with a single course of fractional CO2-laser therapy in an in-patient controlled setup, using a standardized treatment paradigm. Documentation was based on modern scar scales and questionnaires, like the Vancouver Scar Scale (VSS), Patient and Observer Scar Assessment Scale (POSAS), and Dermatology Life Quality Index (DLQI), as well as state of the art clinical measurements (PRIMOS, Cutometer). Over the course of 6 months after treatment, VSS and POSAS scores showed significant improvement in the rating of scar parameters, as did the quality of life rating according to the DLQI. In the treated scars, surface relief improved significantly, as S max decreased by 1893 µm (-36.92%) (p = 0.0273) and S z by 1615 µm (-36.37%) (p = 0.0488). Scar firmness in treated scars could be reduced by 30% after one treatment session, as R 0 improved by 0.0797 mm (+30.38%) (p = 0.0212). Fractional ablative CO2-laser treatment is a safe and efficacious option for the treatment of hypertrophic burn scars. While more treatment sessions are required for satisfying results, significant improvement is already apparent after a single course of treatment.

Micro-fractional, directional skin tightening: A porcine model.

BACKGROUND AND OBJECTIVE: Skin changes are among the most visible signs of aging. Fractional ablative lasers improve skin quality by making small skin wounds that heal rapidly without scarring. While they improve skin texture and discoloration, there is minimal effect on skin laxity. This study was performed to assess skin shrinkage performed by removing multiple small full-thickness skin columns with coring needles combined with wound closure. MATERIALS AND METHODS: In 5 swine 116 squares (3 cm(2) ) were demarcated for treatment and control sites. In treatment sites 10% of the skin was removed by full-thickness skin coring needles (19 gauge) and afterwards closed and compressed with an elastic adhesive dressing. This procedure was compared to puncturing the skin with standard hypodermic needles (without tissue removal) and subsequent closure with compressive dressing. Area and shape of sites were measured before and 28 days after treatment. RESULTS: Test and control sites healed within a week without scarring. Coring with wound closure caused significant shrinkage after 28 days. The treated skin area was reduced by 9% (P < 0.0001) and the direction of shrinkage was influenced by the direction of wound closure. Coring without wound closure and puncturing the skin without tissue removal produced an insignificant 3% decrease in area. CONCLUSION: Significant minimally invasive skin tightening in a preferred direction can be achieved by removing skin with coring needles followed by wound closure. The direction of shrinkage is influenced by the direction of micro-hole closure, irrespective of the skin tension lines. This approach may allow reshaping the skin in a desired direction without scarring.

The Correction of Facial Morphea Lesions by Hyaluronic Acid: A Case Series and Literature Review.

INTRODUCTION: The aim of the study is to assess the long-term safety and efficacy of hyaluronic acid (HA) administration in correction of facial morphea lesions and to review the literature on the subject. Morphea is a chronic inflammatory disease of the connective tissue which may lead to serious deformations. The lesions located on the face particularly affect patients' quality of life and self-esteem; thus, there is a demand for safe and effective methods of treatment. CASE PRESENTATION: The paper presents three female patients aged 16, 17 and 70 with facial morphea lesions who had HA preparation Juvéderm® Voluma or Volux, Vycross® technology, Allergan, injected. One of the patients had additionally fractional ablative CO2 laser (FAL) therapy. DISCUSSION: The literature provides reports on successful use of HA, polymethylmethacrylate and poly-L-lactic acid for the correction of facial defects in localized scleroderma. HA is a natural component of the extracellular matrix and it therefore minimizes the probability of immunogenicity. The application technique also plays an important role. On the other hand, FAL therapy leads to the degradation of the abnormal collagen and the induction of normal collagen synthesis. CONCLUSIONS: HA injection and combination of HA application with FAL are minimally invasive, effective and safe therapeutic options for patients suffering from morphea.

Comparison of a novel wound dressing vs current clinical practice after laser resurfacing.

BACKGROUND: There are many postprocedure skin care options, but no consensus on the best formulation to optimize healing. Silicone gels have only been used to treat keloids and hypertrophic scars and typically applied after the wound has healed. This study compared the healing response after fractional ablative erbium laser resurfacing with a petrolatum-based ointment and a silicone gel. METHODS: A randomized, open-label, split-face study was performed. Ten subjects underwent Erbium:YAG (Sciton) fractional laser resurfacing. Patients were randomized to apply a petrolatum-based gel or a silicone gel (Stratacel® ; Stratpharma) on either the right or left side of the face. Subjects applied the products twice a day for 7 days and were evaluated in person 7, 30, and 60 days postprocedure. Subjects reported on the overall general aesthetic outcome, perceived pain, itch, and tightness via questionnaires using the Global Aesthetic Improvement Scale and the Wrinkle Severity Rating Scale (WSRS). RESULTS: All subjects healed without complications. By day 60, there was no difference in signs and symptoms of healing between the two different dressing approaches. However, patients treated with the silicone gel had less post-treatment erythema and hyperpigmentation. CONCLUSIONS: A novel silicone gel resulted in reduced signs of erythema and hyperpigmentation postprocedure, without an increase in adverse events. Additionally, the silicone gel dries to form a thin, full contact film and can be covered with sunscreen or cosmetics once dry. This new silicone gel presents a good option for postprocedure care after ablative fractional laser resurfacing.

Efficacy and safety of moisturizer containing 5% panthenol, madecassoside, and copper-zinc-manganese versus 0.02% triamcinolone acetonide cream in decreasing adverse reaction and downtime after ablative fractional carbon dioxide laser resurfacing: A split-face, double-blinded, randomized, controlled trial.

INTRODUCTION: Fractional carbon dioxide (FrCO2 ) laser is effective for atrophic acne scar treatment, but unavoidable downtime. Meanwhile, postoperative topical steroid decreases the downtime, yet still possibly increases other steroid side effects. OBJECTIVE: To evaluate the efficacy and safety of moisturizer containing 5% panthenol, madecassoside, and copper-zinc-manganese (experimental cream) versus 0.02% Triamcinolone acetonide (TA) cream in decreasing adverse effects and downtime after FrCO2 laser, with wound healing improvement and prevention of certain steroid-related side effects like postinflammatory hyperpigmentation (PIH). METHODS: We conducted a double-blinded, split face, randomized controlled trial in 20 subjects receiving FrCO2 laser on both sides of the faces and randomly treated with two posttreatment regimens on each side for 7 days. Clinical, expert panel assessment of photography, downtime, side effects, and biometric evaluation for erythema and melanin were performed on baseline, immediately after treatment, day 3, 5, 7, 14, 30 and, 60 postoperatively. RESULTS: Both experimental cream (EC) and 0.02% TA cream could significantly reduce postlaser downtime including swelling, redness, crusting, and scaling in 5-7 days, with comparable efficacies in decreasing downtime and adverse reactions, as well as wound healing improvement and lower PIH without statistically significant difference between the two treatments. The incidence of PIH was 60% in the EC treated group with minimal intensity. CONCLUSION: The moisturizer with anti-inflammatory ingredients could be a novel treatment modality for reduction of postablative laser downtime by using nonsteroidal anti-inflammatory agents to avoid adverse effects and improve wound healing process with lower PIH.

Effect of ablative laser on in vitro transungual delivery.

Topical therapy of nail psoriasis using methotrexate has not been realized due to the high molecular weight and low permeability of the compound. In this study, we used a 2940nm fractional ablative laser to disrupt the nail barrier to enhance the in vitro transungual delivery of methotrexate. Bovine hoof membrane-an in vitro model of the human nail-was treated by the laser at different energy levels and pore densities. A successful microporation was characterized by mechanical properties, scanning electron microscopy, Fourier transform infrared spectrophotometer, dye binding, histology, pore uniformity, confocal laser microscopy, nail integrity measurement, and permeation studies. No significant difference in the pore dimension was found in different treatment groups (p>0.05). Increases in pore depth corresponded with increases in the laser energy. Laser ablation was found to affect the mechanical properties of the hoof membrane. In in vitro permeation studies, laser ablation resulted in a significant increase in the drug cumulative delivery, flux, and permeability coefficient as compared to the untreated group (n=3, p<0.05). A change in the laser energy and pore density was found to alter the drug permeability. Thus, transungual methotrexate delivery was enhanced by the fractional laser ablation.