Background and Objectives: A novel carbon dioxide (CO 2 ) laser device employing ablative fractional resurfacing was tested on human skin in vivo for the first time. Study Design/Materials and Methods: An investigational 30 W, 10.6 mm CO 2 laser system was focused to a 1/e 2 spot size of 120 mm to generate an array of microscopic treatment zones (MTZ) in human forearm skin. A range of pulse energies between 5 and 40 mJ was tested and lesion dimensions were assessed histologically using hematoxylin & eosin. Wound healing of the MTZ's was assessed immediately-, 2-day, 7-day, 1-month, and 3-month post treatment. The role of heat shock proteins was examined by immunohistochemistry. Results: The investigational CO 2 laser system created a microscopic pattern of ablative and thermal injury in human skin. The epidermis and part of the dermis demonstrated columns of thermal coagulation that surrounded tapering ablative zones lined by a thin eschar layer. Changing the pulse energy from 5 to 30 mJ resulted in a greater than threefold increase in lesion depth and twofold increase in width. Expression of heat shock protein (hsp)72 was detected as early as 2 days post-treatment and diminished significantly by 3 months. In contrast, increased expression of hsp47 was first detected at 7 days and persisted at 3 months post-treatment. Conclusion: The thermal effects of a novel investigational ablative CO 2 laser system utilizing fractional resurfacing were characterized in human forearm skin. We confirmed our previous ex vivo findings and show for the first time invivo, that a controlled array of microscopic treatment zones of ablation and coagulation could be deposited in human skin by varying treatment pulse energy. Immunohistochemical studies of heat shock proteins revealed a persistent collagen remodeling response lasting at least 3 months. We successfully demonstrated the first in-vivo use of ablative fractional resurfacing (AFR TM ) treatment on human skin.

Background and Objectives: We introduce a novel CO 2 laser device that utilizes ablative fractional resurfacing for deep dermal tissue removal and characterize the resultant thermal effects in skin. Study Design/Materials and Methods: A prototype 30 W, 10.6 mm CO 2 laser was focused to a 1/e 2 spot size of 120 mm and pulse duration up to 0.7 milliseconds to achieve a microarray pattern in ex vivo human skin. Lesion depth and width were assessed histologically using either hematoxylin & eosin (H&E) or lactate dehyrdogenase (LDH) stain. Pulse energies were varied to determine their effect on lesion dimensions. Results: Microarrays of ablative and thermal injury were created in fresh ex vivo human skin irradiated with the prototype CO 2 laser device. Zones of tissue ablation were surrounded by areas of tissue coagulation spanning the epidermis and part of the dermis. A thin condensed lining on the interior wall of the lesion cavity was observed consistent with eschar formation. At 23.3 mJ, the lesion width was approximately 350 mm and depth 1 mm. In this configuration, the cavities were spaced approximately 500 mm apart and interlesional epidermis and dermis demonstrated viable tissue by LDH staining. Conclusion: A novel prototype ablative CO 2 laser device operating in a fractional mode was developed and its resultant thermal effects in human abdominal tissue were characterized. We discovered that controlled microarray patterns could be deposited in skin with variable depths of dermal tissue ablation depending on the treatment pulse energy. This is the first report to characterize the successful use of ablative fractional resurfacing as a potential approach to dermatological treatment. Lasers Surg. Med. 39:87-95, 2007. ß

The wound healing process in skin is studied in human subjects treated with fractional photothermolysis. In-vivo histological evaluation of vacuoles formed over microthermal zones (MTZs) and their content is undertaken. A 30-W, 1550-nm single-mode fiber laser system delivers an array of 60 microm or 140 microm 1e2 incidence microbeam spot size at variable pulse energy and density. Treatments span from 6 to 20 mJ with skin excisions performed 1-day post-treatment. Staining with hematoxylin and eosin demonstrates an intact stratum corneum with vacuolar formation within the epidermis. The re-epithelialization process with repopulation of melanocytes and keratinocytes at the basal layer is apparent by 1-day post-treatment. The dermal-epidermal (DE) junction is weakened and separated just above zones of dermal coagulation. Complete loss of dermal cell viability is noted within the confines of the MTZs 1-day post-treatment, as assessed by lactate dehydrogenase. All cells falling outside the irradiation field remain viable. Content within the epidermal vacuoles stain positively with Gomori trichrome, suggesting a dermal origin. However, the positive staining could be due to loss of specificity after thermal alteration. Nevertheless, this dermal extrusion hypothesis is supported by very specific positive staining with an antihuman elastin antibody. Fractional photothermolysis creates microthermal lesions that allow transport and extrusion of dermal content through a compromised DE junction. Some dermal material is incorporated into the microepidermal necrotic debris and shuttled up the epidermis to eventually be exfoliated through the stratum corneum. This is the first report of a nonablative laser-induced transport mechanism by which dermal content can be predictably extruded biologically through the epidermis. Thus, treatment with the 1550-nm fiber laser may provide the first therapeutic option for clinical indications, including pigmentary disorders such as medically recalcitrant melasma, solar elastosis, as well as depositional diseases such as mucinosis and amyloidosis.

Background and Objective Due to the significant risk profile associated with traditional ablative resurfacing, a safer and less invasive treatment approach known as fractional deep dermal ablation (FDDA™) was recently developed. We report the results of the first clinical investigation of this modality for treatment of photodamaged skin. Study Design/Materials and Methods Twenty‐four subjects received treatments on the inner forearm with a prototype fractional CO2 laser device (Reliant Technologies Inc., Mountain View, CA) at settings of 5–40 mJ/MTZ and 400 MTZ/cm2. Clinical and histological effects were assessed by study investigators 1 week, 1 month, and 3 months following treatment. Thirty subjects were then enrolled in a multi‐center study for treatment of photodamage using the same device. Subjects received 1–2 treatments on the face and neck, with energies ranging from 10 to 40 mJ/MTZ and densities ranging from 400 to 1,200 MTZ/cm2. Study investigators assessed severity of post‐treatment responses during follow‐up visits 48 hours, 1 week, 1 month, and 3 months following treatment. Using a standard quartile improvement scale (0–4), subjects and investigators assessed improvement in rhytides, pigmentation, texture, laxity and overall appearance 1 and 3 months post‐treatment. Results Clinical and histologic results demonstrated that fractional delivery of a 10,600 nm CO2 laser source offers an improved safety profile with respect to traditional ablative resurfacing, while still effectively resurfacing epidermal and dermal tissue. Forearm and facial treatments were well‐tolerated with no serious adverse events observed. Eighty‐three percent of subjects exhibited moderate or better overall improvement (50–100%), according to study investigator quartile scoring. Conclusions FDDA™ treatment is a safe and promising new approach for resurfacing of epidermal and deep dermal tissue targets. Lasers Surg. Med. 41:78–86, 2009. © 2009 Wiley‐Liss, Inc.

Background and Objectives:We examined the effects of pulse energy variations on the dimensions of microscopic thermal injury zones (MTZs) created on human skin ex vivo and in vivo using nonablative fractional resurfacing. Materials and Methods: A Fraxel 1 SR laser system emitting at 1,550 nm provided an array of microscopic spots at variable densities. Pulse energies ranging from 4.5 to 40 mJ were tested on human abdominal skin ex vivo and in vivo. Tissue sections were stained with hematoxylin and eosin (H&E) or nitro blue tetrazolium chloride (NBTC) and MTZ dimensions were determined. Ex vivo and in vivo results were compared. Dosimetry analyses were made for the surface treatment coverage calculation as a function of pulse energy and collagen coagulation based on H&E stain or cell necrotic zone based on NBTC stain. Results: Each MTZ was identified by histological detection of a distinct region of loss of tissue birefringence and hyalinization, representing collagen denaturation and cell necrosis within the irradiated field immediately, 1, 3, and 7 days after treatment. At high pulse energies, the MTZ depth could exceed 1 mm and width approached 200 mm as assessed by H&E. NBTC staining revealed viable interlesional tissue. In general, no statistically significant difference was found between in vivo and ex vivo depth and width measurements. Conclusions: The Fraxel 1 SR laser system delivers pulses across a wide range of density and energy levels. We determined that increases in pulse energy led to increases in MTZ depth and width without compromising the structure or viability of interlesional tissue. Lasers Surg.