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.

Our study revealed a vigorous wound healing response is initiated post-treatment, with progressive increase in inflammatory cell infiltration from day 2 through 10 weeks. An active dermal remodeling process driven by the collagen chaperone HSP47 led to complete replacement of RFTZs with new collagen by 10 weeks post-treatment. Furthermore, using both immunohistochemical and PCR studies, we successfully demonstrated for the first time evidence of profound neoelastogenesis following RF treatment of human skin. The combination of neoelastogenesis and neocollagenesis induced by treatment with the FRF system may provide a reliable treatment option for skin laxity and/or rhytids.

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

Control of energy metabolism by increases of mito

Background and Objectives: Noninvasive bipolar and monopolar radiofrequency (RF) deep dermal heating devices have previously been described. A novel minimally invasive RF device employing a bipolar microneedle electrode system is introduced and its resultant thermal effects on human skin in vivo were characterized for the first time. Study Design/Materials and Methods: An investigational 35 W RF device was configured to operate in bipolar mode delivering energy directly within the dermis using 5 microneedle electrode pairs with real-time feedback of tissue temperature for treatment control. Superficial cooling was achieved using a Peltier device. A range of pulse durations between 1 and 25 seconds, and lesion temperatures between 60 and 80 C were tested in vivo on 15 human subjects. Thermal effects were assessed histologically using either hematoxylin & eosin (H&E) or nitroblue-tetrazoliumchloride (NBTC) staining. Treatment effects and adverse events were also monitored clinically. Results: The investigational bipolar RF device delivered controlled heating within dermal tissue. Histological staining with H&E revealed the presence of zones of denatured collagen within the reticular dermis. Lesions were generated at preselected temperatures between 60 and 80 C. Fractional lesions separated by zones of sparing as well as contiguous lesion patterns were demonstrated. Histological staining with H&E and NBTC revealed sparing of adnexal structures and adipose tissue. No major adverse events were observed. Conclusions: A novel fractional RF device utilizing a minimally invasive bipolar microneedle delivery system for the treatment of human tissue was developed. Treatment of 15 human subjects illustrated the controlled creation of dermally located thermal coagulation zones, herein known as radiofrequency thermal zones. We discovered that varying the pulse length allowed for fractional sparing of dermal tissue. To our knowledge, this is the first report to describe use of a direct real-time temperature and impedance feedback system to control energy delivery during deep dermal heating. Lasers Surg. Med. 41:87--95, 2009.

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.

No abstract

The ubiquity of increased sun exposure, oral contraceptives, and phototoxic drugs has led to an increased prevalence of conditions such as dyschromia, melasma, rhytides, and other signs of photoaging over the past few decades. Through the application of selective photothermolysis, laser surgery has attempted to create therapeutic options for these medically recalcitrant conditions. To date, however, this technology has been met with limited success, due to a high incidence of posttreatment side effects, inability to treat off the face, and a safety profile tailored to Fitzpatrick skin types I to III. More recently, a novel approach coined "fractional photothermolysis" was developed in an attempt to overcome these limitations. This new laser treatment modality has allowed for effective treatment of a diverse array of dermatologic conditions on and off the face with a wider therapeutic index and improved safety profile independent of Fitzpatrick skin type. This review sheds light on the technical aspects, biologic mechanisms, and clinical effects of fractional photothermolysis that help set it apart from previous modes of laser surgery.