Dieter Manstein

Selective cryolysis: a novel method of non-invasive fat removal.

Excess fat poses a host of local and systemic problems. Various energy sources, for example, laser, ultrasound, and radiofrequency electric current have been studied as potential non‐invasive treatments aimed at local destruction of subcutaneous fat. Cryosurgery at very low temperatures is routinely used for non‐specific tissue destruction, however the potential for tissue‐specific cold injury has not been investigated. This study describes non‐invasive cold‐induced selective destruction of subcutaneous fat.

Cryolipolysis for noninvasive fat cell destruction: initial results from a pig model.

BACKGROUND Liposuction is one of the most frequently performed cosmetic procedures in the United States, but its cost and downtime has led to the development of noninvasive approaches for adipose tissue reduction. OBJECTIVE To determine whether noninvasive controlled and selective destruction of fat cells (Cryolipolysis) can selectively damage subcutaneous fat without causing damage to the overlying skin or rise in lipid levels. METHODS Three Yucatan pigs underwent Cryolipolysis at 22 sites: 20 at cooling intensity factor (CIF) index 24.5 (−43.8 mW/cm2), one at CIF 24.9 (−44.7 mW/cm2), and one at CIF 25.4 (−45.6 mW/cm2). Treated areas were evaluated using photography, ultrasound, and gross and microscopic pathology. Lipids were at various times points. One additional pig underwent Cryolipolysis at various days before euthanasia. RESULTS The treatments resulted in a significant reduction in the superficial fat layer without damage to the overlying skin. An inflammatory response triggered by cold‐induced apoptosis of adipocytes preceded the reduction in the fat layer. Evaluation of lipids over a 3‐month period following treatment demonstrated that cholesterol and triglyceride values remained normal. CONCLUSIONS Cryolipolysis is worthy of further study because it has been shown to significantly decrease subcutaneous fat and change body contour without causing damage to the overlying skin and surrounding structures or deleterious changes in blood lipids.

Intense Focused Ultrasound: Evaluation of a New Treatment Modality for Precise Microcoagulation within the Skin

BACKGROUND AND OBJECTIVE Focused ultrasound can produce thermal and/or mechanical effects deep within tissue. We investigated the capability of intense focused ultrasound to induce precise and predictable subepidermal thermal damage in human skin. MATERIALS AND METHODS Postmortem human skin samples were exposed to a range of focused ultrasound pulses, using a prototype device (Ulthera Inc.) emitting up to 45 W at 7.5 MHz with a nominal focal distance of 4.2 mm from the transducer membrane. Exposure pulse duration ranged from 50 to 200 ms. Thermal damage was confirmed by light microscopy using a nitroblue tetrazolium chloride assay, as well as by loss of collagen birefringence in frozen sections. Results were compared with a computational model of intense ultrasound propagation and heating in tissue. RESULTS Depth and extent of thermal damage were determined by treatment exposure parameters (source power, exposure time, and focal depth). It was possible to create individual and highly confined lesions or thermal damage up to a depth of 4 mm within the dermis. Thermal lesions typically had an inverted cone shape. A precise pattern of individual lesions was achieved in the deep dermis by applying the probe sequentially at different exposure locations. DISCUSSION AND CONCLUSION Intense focused ultrasound can be used as a noninvasive method for spatially confined heating and coagulation within the skin or its underlying structures. These findings have a significant potential for the development of novel, noninvasive treatment devices in dermatology.

Facilitation of transcutaneous drug delivery and vaccine immunization by a safe laser technology

Full-surface laser ablation has been shown to efficiently disrupt stratum corneum and facilitate transcutaneous drug delivery, but it is frequently associated with skin damage that hampers its clinic use. We show here that a safer ablative fractional laser (AFL) can sufficiently facilitate delivery of not only patch-coated hydrophilic drugs but also protein vaccines. AFL treatment generated an array of self renewable microchannels (MCs) in the skin, providing free paths for drug and vaccine delivery into the dermis while maintaining integrity of the skin by quick healing of the MCs. AFL was superior to tape stripping in transcutaneous drug and vaccine delivery as a much higher amount of sulforhodamine B (SRB), methylene blue (MB) or a model vaccine ovalbumin (OVA) was recovered from AFL-treated skin than tape-stripped skin or control skin after patch application. Following entry into the MCs, the drugs or OVA diffused quickly to the entire dermal tissue via the lateral surface of conical-shaped MCs. In contrast, a majority of the drugs and OVA remained on the skin surface, unable to penetrate into the dermal tissue in untreated control skin or tape stripping-treated skin. Strikingly, OVA delivered through the MCs was efficiently taken up by epidermal Langerhans cells and dermal dendritic cells in the vicinity of the MCs or transported to the draining lymph nodes, leading to a robust immune response, in sharp contrast to a weak, though significant, immune response elicited in tape stripping group or a basal immune response in control groups. These data support strongly that AFL is safe and sufficient for transcutaneous delivery of drugs and vaccines.

Omega-6 docosapentaenoic acid-derived resolvins and 17-hydroxydocosahexaenoic acid modulate macrophage function and alleviate experimental colitis

ObjectiveEnzymatically oxygenated lipid products derived from omega-3 and omega-6 fatty acids play an important role in inflammation dampening. This study examined the anti-inflammatory effects of n-6 docosapentaenoic acid-derived (17S)-hydroxy-docosapentaenoic acid (17-HDPAn-6) and (10,17S)-dihydroxy-docosapentaenoic acid (10,17-HDPAn-6) as well as n-3 docosahexaenoic acid-derived 17(R/S)-hydroxy-docosahexaenoic acid (17-HDHA).Materials and methodsThe effects of 17-HDPAn-6, 10,17-HDPAn-6 or 17-HDHA on activity and M1/M2 polarization of murine macrophage cell line RAW 264.7 were examined by phagocytosis assay and real-time PCR. To assess anti-inflammatory effects in vivo, dextran sodium sulfate (DSS) colitis was induced in mice treated with 17-HDPAn-6, 10,17-HDPAn-6, 17-HDHA or NaCl.ResultsOur results show that 17-HDPAn-6, 10,17-HDPAn-6 and 17-HDHA increase phagocytosis in macrophages in vitro and promote polarization towards the anti-inflammatory M2 phenotype with decreased gene expression of TNF-α and inducible Nitric oxide synthase and increased expression of the chemokine IL-1 receptor antagonist and the Scavenger receptor Type A. Intraperitoneal treatment with 17-HDPAn-6, 10,17-HDPAn-6, or 17-HDHA alleviated DSS-colitis and significantly improved body weight loss, colon epithelial damage, and macrophage infiltration.ConclusionThese results suggest that DPAn-6-derived 17-HDPAn-6 and 10,17-HDPAn-6 as well as the DHA-derived 17-HDHA have inflammation-dampening and resolution-promoting effects that could be used to treat inflammatory conditions such as inflammatory bowel disease.

Effects of non-invasive, 1,210 nm laser exposure on adipose tissue: results of a human pilot study.

Laser radiation (1,210 nm) has been previously shown to be capable of selective photothermolysis of adipose tissue in vitro when applied non‐invasively. The objective of this pilot study was to evaluate the in vivo effects of this laser in human subjects.

Effects of non-invasive, 1,210 nm laser exposure on adipose tissue

Laser radiation (1,210 nm) has been previously shown to be capable of selective photothermolysis of adipose tissue in vitro when applied non‐invasively. The objective of this pilot study was to evaluate the in vivo effects of this laser in human subjects.

Micro-fractional epidermal powder delivery for improved skin vaccination

Skin vaccination has gained increasing attention in the last two decades due to its improved potency compared to intramuscular vaccination. Yet, the technical difficulty and frequent local reactions hamper its broad application in the clinic. In the current study, micro-fractional epidermal powder delivery (EPD) is developed to facilitate skin vaccination and minimize local adverse effects. EPD is based on ablative fractional laser or microneedle treatment of the skin to generate microchannel (MC) arrays in the epidermis followed by topical application of powder drug/vaccine-coated array patches to deliver drug/vaccine into the skin. The novel EPD delivered more than 80% sulforhodamine b (SRB) and model antigen ovalbumin (OVA) into murine, swine, and human skin within 1h. EPD of OVA induced anti-OVA antibody titer at a level comparable to intradermal (ID) injection and was much more efficient than tape stripping in both delivery efficiency and immune responses. Strikingly, the micro-fractional delivery significantly reduced local side effects of LPS/CpG adjuvant and BCG vaccine, leading to complete skin recovery. In contrast, ID injection induced severe local reactions that persisted for weeks. While reducing local reactogenicity, EPD of OVA/LPS/CpG and BCG vaccine generated a comparable humoral immune response to ID injection. EPD of vaccinia virus encoding OVA induced significantly higher and long-lasting interferon γ-secreting CD8+ T cells than ID injection. In conclusion, EPD represents a promising technology for needle-free, painless skin vaccination with reduced local reactogenicity and at least sustained immunogenicity.

Photosensitizer fluorescence and singlet oxygen luminescence as dosimetric predictors of topical 5-aminolevulinic acid photodynamic therapy induced clinical erythema

Abstract. The need for patient-specific photodynamic therapy (PDT) in dermatologic and oncologic applications has triggered several studies that explore the utility of surrogate parameters as predictive reporters of treatment outcome. Although photosensitizer (PS) fluorescence, a widely used parameter, can be viewed as emission from several fluorescent states of the PS (e.g., minimally aggregated and monomeric), we suggest that singlet oxygen luminescence (SOL) indicates only the active PS component responsible for the PDT. Here, the ability of discrete PS fluorescence-based metrics (absolute and percent PS photobleaching and PS re-accumulation post-PDT) to predict the clinical phototoxic response (erythema) resulting from 5-aminolevulinic acid PDT was compared with discrete SOL (DSOL)-based metrics (DSOL counts pre-PDT and change in DSOL counts pre/post-PDT) in healthy human skin. Receiver operating characteristic curve (ROC) analyses demonstrated that absolute fluorescence photobleaching metric (AFPM) exhibited the highest area under the curve (AUC) of all tested parameters, including DSOL based metrics. The combination of dose-metrics did not yield better AUC than AFPM alone. Although sophisticated real-time SOL measurements may improve the clinical utility of SOL-based dosimetry, discrete PS fluorescence-based metrics are easy to implement, and our results suggest that AFPM may sufficiently predict the PDT outcomes and identify treatment nonresponders with high specificity in clinical contexts.

Histological comparison of two different fractional photothermolysis devices operating at 1,550 nm

There are a wide variety of fractional resurfacing devices that are available and it is important to understand the tissue effect of different devices at different parameters to ensure a well‐controlled treatment. Thus, we have chosen to characterize and compare two different fractional laser devices, the Fraxel SR750 and SR1500 (re:store™) (Solta Medical, Hayward, CA). While the SR750 has a fixed focus spot diameter, the SR1500 features an internally controlled zoom optic allowing for an adjustable spot size.