Reconstructive and Aesthetic Surgeries on the Female Genitalia. Guideline of the DGGG, DGPRÄC, OEGGG and SGGG (S2k-Level, AWMF Registry No. 009/019, May 2022).

Aim This official guideline was coordinated and published by the German Society for Gynaecology and Obstetrics (DGGG), the German Society for Plastic, Reconstructive and Aesthetic Surgery (DGPRÄC), the Austrian Society for Gynaecology and Obstetrics (OEGGG), and the Swiss Society for Gynaecology and Obstetrics (SGGG). The guideline aims to provide a consensus-based overview of reconstructive and aesthetic surgeries on female genitalia based on an evaluation of the relevant literature. Methods This S2k-guideline was developed by representative members from different medical professions on behalf of the guidelines commission of the DGGG, DGPRÄC, OEGGG and SGGG using a structured consensus process. Recommendations Statements and recommendations on the epidemiology, aetiology, classification, symptoms, diagnosis, and treatment of acquired changes of the external genitalia are presented and special situations are discussed.

Genital Wound Repair and Scarring.

Skin wound repair has been the central focus of clinicians and scientists for almost a century. Insights into acute and chronic wound healing as well as scarring have influenced and ameliorated wound treatment. Our knowledge of normal skin notwithstanding, little is known of acute and chronic wound repair of genital skin. In contrast to extra-genital skin, hypertrophic scarring is uncommon in genital tissue. Chronic wound healing disorders of the genitals are mostly confined to mucosal tissue diseases. This article will provide insights into the differences between extra-genital and genital skin with regard to anatomy, physiology and aberrant wound repair. In light of fundamental differences between genital and normal skin, it is recommended that reconstructive and esthetic surgery should exclusively be performed by specialists with profound expertise in genital wound repair.

Homophilic and heterophilic cadherin bond rupture forces in homo- or hetero-cellular systems measured by AFM-based single-cell force spectroscopy.

Cadherins enable intercellular adherens junctions to withstand tensile forces in tissues, e.g. generated by intracellular actomyosin contraction. In-vitro single molecule force spectroscopy experiments can reveal cadherin-cadherin extracellular region binding dynamics such as bond formation and strength. However, characterization of cadherin-presenting cell homophilic and heterophilic binding in the proteins' native conformational and functional states in living cells has rarely been done. Here, we used atomic force microscopy (AFM) based single-cell force spectroscopy (SCFS) to measure rupture forces of homophilic and heterophilic bond formation of N- (neural), OB- (osteoblast) and E- (epithelial) cadherins in living fibroblast and epithelial cells in homo- and hetero-cellular arrangements, i.e., between cells and cadherins of the same and different types. In addition, we used indirect immunofluorescence labelling to study and correlate the expression of these cadherins in intercellular adherens junctions. We showed that N/N and E/E-cadherin homophilic binding events are stronger than N/OB heterophilic binding events. Disassembly of intracellular actin filaments affects the cadherin bond rupture forces suggesting a contribution of actin filaments in cadherin extracellular binding. Inactivation of myosin did not affect the cadherin rupture force in both homo- and hetero-cellular arrangements, but particularly strengthened the N/OB heterophilic bond and reinforced the other cadherins' homophilic bonds.

Injury triggers fascia fibroblast collective cell migration to drive scar formation through N-cadherin.

Scars are more severe when the subcutaneous fascia beneath the dermis is injured upon surgical or traumatic wounding. Here, we present a detailed analysis of fascia cell mobilisation by using deep tissue intravital live imaging of acute surgical wounds, fibroblast lineage-specific transgenic mice, and skin-fascia explants (scar-like tissue in a dish - SCAD). We observe that injury triggers a swarming-like collective cell migration of fascia fibroblasts that progressively contracts the skin and form scars. Swarming is exclusive to fascia fibroblasts, and requires the upregulation of N-cadherin. Both swarming and N-cadherin expression are absent from fibroblasts in the upper skin layers and the oral mucosa, tissues that repair wounds with minimal scar. Impeding N-cadherin binding inhibits swarming and skin contraction, and leads to reduced scarring in SCADs and in animals. Fibroblast swarming and N-cadherin thus provide therapeutic avenues to curtail fascia mobilisation and pathological fibrotic responses across a range of medical settings.

[Improvement in burn wound care: summary of the AWMF guideline for the treatment of thermal injuries in adults]. / Optimierung der chirurgischen Behandlung Brandverletzter: Auszüge aus der fachübergreifenden S2k-Leitlinie "Behandlung thermischer Verletzungen des Erwachsenen".

INTRODUCTION: More than half a million patients suffer from minor burns in Germany per year. In 2018, almost 2000 patients needed intensive care for their burn injuries. Despite high standards of burn care, mortality remains high. Burn injuries may lead to long-term sequelae. In order to provide up-to-date burn care, guidelines are available online with public access. METHODS AND RESULTS: This overview presents a summary of the German AWMF guideline for the treatment of thermal injuries in adults (https://www.awmf.org/leitlinien/detail/ll/044-001.html). Experts of eleven different medical organisations and specialties have contributed to this S2k guideline with their expertise. The focus of the article is on acute burn wound assessment, the indication for specialised care in burn centres, the management of the burn wound at the trauma scene and in hospitals as well as scar management and rehabilitation. CONCLUSION: This overview reports on the consensus-based treatment of acute burn wounds in adults in Germany. The article is intended to guide doctors and professional caretakers to perform state-of-the-art burn care. The current guideline aims to improve burn outcome.

[Suitability of biological acellular dermal matrices as a skin replacement]. / Eignung biologischer azellulärer dermaler Matrices als Hautersatz.

INTRODUCTION: Tissue defects are associated with loss of epidermal and dermal components of the skin. For full-thickness tissue defects, dermal equivalents are useful to enable rapid wound closure. Split-thickness skin grafts are associated with loss of tissue elasticity resulting in scar contractures that can impair joint mobility. Synthetic collagen matrices and allogeneic acellular dermal matrices (ADM) are commercially available and could serve as skin tissue replacement. The aim of this study was to investigate whether ADM of different dermal layers or bioartificial matrices can serve as cutaneous replacement. For this purpose, cellular migration, differentiation and the inflammatory reaction were studied in an established ex vivo skin organ model. MATERIALS AND METHODS: Human split-thickness skin grafts were transplanted onto ADM (Epiflex, DIZG, Berlin, Germany), de-epidermized dermis (DED) or an artificial collagen-elastin matrix (Matriderm, Dr. Suwelack, Billerbeck, Germany). Epithelial migration was studied using an established skin culture model at the air-liquid interface. In addition, the effect of tissue from different dermal compartments, e. g. papillar and reticular dermis, on epithelial migration was compared. Epithelial resurfacing and differentiation of matrices as well as the inflammatory reaction were studied using histological, immunohistochemical and biochemical analyses. RESULTS AND CONCLUSION: Significantly more epithelial outgrowth area was found on DED (2.54 mm ± 0.43 mm, mean ± SEM) compared to papillary ADM (1.32 mm ± 0.44 mm, p = 0.039), to reticular ADM (no horizontal growth, p < 0.0001) and collagen-elastin matrix (0.78 mm ± 0.11 mm, p = 0.0056) measured by fluorescence microscopy over 10 days presumably due to the presence of pro-migratory basement membrane residues on DED. Reepithelialization was significantly higher (p < 0.002) on papillary dermis compared to ADM of reticular origin. In contrast to the biological matrices, a complete horizontal penetration was found in the macroporous collagen-elastin matrix. Pro-inflammatory mediators varied depending on the human skin donor and matrix. In summary, the biochemical structure of the matrix' surface and its origin influenced the epithelial behaviour with regard to migration, differentiation and inflammatory response.

Body hair removal: Prevalence, demographics, and body experience among men and women in Germany.

BACKGROUND: Body hair removal is an increasing trend that has an impact on the individual's body image. AIMS: To characterize current body hair removal practices in Germany and the extent to which body hair removal was related to demographic characteristics, body image, and body mass index. PATIENTS/METHODS: A national survey was conducted from September to October 2016 in men and women in Germany. Body experience was measured by a standardized questionnaire. In addition to sociodemographic data, age, gender, education, marital status, monthly income, and body mass index were collected. RESULTS: A total of n = 2510 participants aged 14 to 94 years (Mage = 48.4 years (SD = 18.2), 53.4% females) were randomly selected from the general population. 69% of the questioned women removed their body hair while only 41% of men do. The gender effect is statistically significant (χ2  = 203.43; df = 1; P < .001). Income, a higher level of education, and living in an urban region were significantly associated with body hair removal in both, men and women. Furthermore, significant differences with regard to body image were found between hair removers and nonremovers which are associated with a different attitude toward the own body. CONCLUSIONS: Germans were likely to remove body hair if they were of younger age, better educated, and with high income. Hair removal is above all a women's issue. Especially, female hair removers experience their body as an esthetic entity with the need of active reshaping. There is a "shift" from ideal of a naturally hairy body to an increased hairlessness in Germany.

Lung Surfactant Accelerates Skin Wound Healing: A Translational Study with a Randomized Clinical Phase I Study.

Lung surfactants are used for reducing alveolar surface tension in preterm infants to ease breathing. Phospholipid films with surfactant proteins regulate the activity of alveolar macrophages and reduce inflammation. Aberrant skin wound healing is characterized by persistent inflammation. The aim of the study was to investigate if lung surfactant can promote wound healing. Preclinical wound models, e.g. cell scratch assays and full-thickness excisional wounds in mice, and a randomized, phase I clinical trial in healthy human volunteers using a suction blister model were used to study the effect of the commercially available bovine lung surfactant on skin wound repair. Lung surfactant increased migration of keratinocytes in a concentration-dependent manner with no effect on fibroblasts. Significantly reduced expression levels were found for pro-inflammatory and pro-fibrotic genes in murine wounds. Because of these beneficial effects in preclinical experiments, a clinical phase I study was initiated to monitor safety and tolerability of surfactant when applied topically onto human wounds and normal skin. No adverse effects were observed. Subepidermal wounds healed significantly faster with surfactant compared to control. Our study provides lung surfactant as a strong candidate for innovative treatment of chronic skin wounds and as additive for treatment of burn wounds to reduce inflammation and prevent excessive scarring.

Patch repair of deep wounds by mobilized fascia.

Mammals form scars to quickly seal wounds and ensure survival by an incompletely understood mechanism1-5. Here we show that skin scars originate from prefabricated matrix in the subcutaneous fascia. Fate mapping and live imaging revealed that fascia fibroblasts rise to the skin surface after wounding, dragging their surrounding extracellular jelly-like matrix, including embedded blood vessels, macrophages and peripheral nerves, to form the provisional matrix. Genetic ablation of fascia fibroblasts prevented matrix from homing into wounds and resulted in defective scars, whereas placing an impermeable film beneath the skin-preventing fascia fibroblasts from migrating upwards-led to chronic open wounds. Thus, fascia contains a specialized prefabricated kit of sentry fibroblasts, embedded within a movable sealant, that preassemble together diverse cell types and matrix components needed to heal wounds. Our findings suggest that chronic and excessive skin wounds may be attributed to the mobility of the fascia matrix.

Matrix Metalloproteinase-3 is Key Effector of TNF-α-Induced Collagen Degradation in Skin.

Inflammatory processes in the skin augment collagen degradation due to the up-regulation of matrix metalloproteinases (MMPs). The aim of the present project was to study the specific impact of MMP-3 on collagen loss in skin and its interplay with the collagenase MMP-13 under inflammatory conditions mimicked by the addition of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Skin explants from MMP-3 knock-out (KO) mice or from transgenic (TG) mice overexpressing MMP-3 in the skin and their respective wild-type counterparts (WT and WTT) were incubated ex vivo for eight days. The rate of collagen degradation, measured by released hydroxyproline, was reduced (p < 0.001) in KO skin explants compared to WT control skin but did not differ (p = 0.47) between TG and WTT skin. Treatment with the MMP inhibitor GM6001 reduced hydroxyproline media levels from WT, WTT and TG but not from KO skin explants. TNF-α increased collagen degradation in the WT group (p = 0.0001) only. More of the active form of MMP-13 was observed in the three MMP-3 expressing groups (co-incubation with receptor-associated protein stabilized MMP-13 subforms and enhanced detection in the media). In summary, the innate level of MMP-3 seems responsible for the accelerated loss of cutaneous collagen under inflammatory conditions, possibly via MMP-13 in mice.

Nano-mechanical mapping of interdependent cell and ECM mechanics by AFM force spectroscopy.

Extracellular matrix (ECM), as a dynamic component of the tissue, influences cell behavior and plays an important role in cell mechanics and tissue homeostasis. Reciprocally, this three-dimensional scaffold is dynamically, structurally and mechanically modified by cells. In the field of biophysics, the independent role of cell and ECM mechanics has been largely investigated; however, there is a lack of experimental data reporting the interdependent interplay between cell and ECM mechanics, measured simultaneously. Here, using Atomic Force Microscopy (AFM) we have characterized five different decellularized matrices diverse in their topography, ECM composition and stiffness and cultured them with normal and pathological fibroblasts (scar and Dupuytren's). We investigated the change in topography and elasticity of these matrices due to cell seeding, by using AFM peak force imaging and mechanical mapping, respectively. We found normal fibroblasts soften these matrices more than pathological fibroblasts, suggesting that pathological fibroblasts are profoundly influencing tissue stiffening in fibrosis. We detected different ECM composition of decellularized matrices used here influences fibroblast stiffness, thus highlighting that cell mechanics not only depends on ECM stiffness but also on their composition. We used confocal microscopy to assess fibroblasts invasion and found pathological fibroblasts were invading the matrices deeper than normal fibroblasts.

[Tattoos in Germany: prevalence, demographics, and health orientation]. / Tattoos in der deutschen Bevölkerung ­ Prävalenzen, Soziodemografie und Gesundheitsorientierung.

BACKGROUND: Tattooing has become very popular in recent years. In this context, socio-demographic information and health orientation is important. OBJECTIVES: The objective of this study was to evaluate the development of the prevalence of tattoos over the last thirteen years and the social and economic background of people with tattoos. Three national representative surveys were compared for this purpose; men and women residing in Germany were included. Additionally, the purpose of the study was to assess socio-demographic information and the health orientation of respondents with tattoos. MATERIALS AND METHODS: Three national, representative surveys were conducted on German participants (2016: n = 2510, 2009: n = 2512, 2003: n = 2043). The number of tattoos and socio-demographic information were investigated. The Health Regulatory Focus Scale (HRFS) assessing the individual's health orientation was used in 2016. RESULTS: Currently, one out of five Germans (≥14 years) has at least one tattoo. In Germany, tattoos are most prevalent among younger adults of both sexes aged 25 to 34 years. People with all levels of education have tattoos, although there were weak correlations with a lower education level and unemployment. Only men with several tattoos showed a significantly lower health orientation than non-tattooed ones. CONCLUSION: The fact that nearly one fifth of the German population has tattoos suggests that this permanent body art is becoming more and more accepted in German society. As a result, a need for better health risk information on the topic for both tattooists and the people getting tattoos appears evident because of the high prevalence of tattoos in younger generations as well as the lower health orientation in men with several tattoos.

Novel specific human and mouse stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10) antibodies for biochemical and immunohistochemical analyses.

Matrix metalloproteinases (MMP) are a family of more than 25 zinc-dependent enzymes that are centrally involved in cellular migration, tissue remodeling, cancer invasion and metastasis. Besides degrading extracellular matrix proteins, MMPs are crucial for growth factor and cytokine release and activation. At the same time, they can inactivate inflammatory mediators and enzymes themselves through protein degradation. Subclasses of MMPs include collagenases, gelatinases, stromelysins, membrane-bound MMPs, and others. With regard to the stromelysin subfamily, three members exist, e.g., stromelysin-1 (MMP-3), stromelysin-2 (MMP-10), and stromelysin-3 (MMP-11). MMP-3, and MMP-10 share extensive similarities at the amino acid level that made it difficult to develop specific antibodies distinguishing between MMP-3 and MMP-10. Scrutinizing published data on and performing different analyses with detection of both stromelysins with commercially available or lab-made antibodies showed ambiguous results with regard to specificity of antibodies used to date. We developed new specific antibodies against the most divergent parts of the active forms of both proteins. We assessed the specificity of our novel specific anti-human and anti-mouse MMP-3 and MMP-10 antibodies in cell lysates and different human and murine skin tissues. Tests analyzing specificity of the novel antibodies included Western immunoblotting, immunofluorescence, and immunohistochemistry on paraffin sections. Analyses demonstrated specific detection of respective protein for human or mouse samples except for the anti-human MMP-3 antibody. The aim of this summary was to call attention the MMP research community to distinguish clearly between both enzymes. Our new specific anti-mouse MMP-3 and both MMP-10 antibodies allow us to address this detection problem and to enable comparative studies between both stromelysins with regard to their respective location and function in the tissue.

Panta Rhei: Neovascularization, Angiogenesis and Nutritive Perfusion in Wound Healing.

BACKGROUND: In response to tissue damage, angiogenesis is an extremely dynamic process that is finely regulated by signals from cells, the surrounding extracellular matrix (ECM), and derived mediators. As the only process, angiogenesis remains of decisive importance in the context of the entire wound healing process and is subject to constant change. The dissolution of the endothelial basement membrane, the migration of endothelial cells, and the development of new capillary vessels during wound healing depend not only on the cells and cytokines present, but also on the production and organization of ECM components in the immediate wound. SUMMARY: Angiogenesis in wound healing can be divided into two main phases. During the pro-angiogenic phase at the beginning of wound healing, excessive neo-formation of blood vessels, some of which are poorly differentiated, occurs, which restore blood flow and thus nutritive perfusion as quickly as possible. This is followed by an anti-angiogenic phase in which the initially established vascular network undergoes a maturing process, which, however, is accompanied by a significant reduction in the number of vessels. Key Messages: Although many mechanisms and specific cell functions in wound healing have already been described, many underlying pathophysiological processes remain unknown. Because angiogenesis and its maturation is a very fast but also very long-lasting process, the understanding of the underlying mechanisms is of crucial importance. This article will give an overview of the current understanding and controversy in this sub-step of wound healing.

Transcriptome Study of an Exophiala dermatitidis PKS1 Mutant on an ex Vivo Skin Model: Is Melanin Important for Infection?

The black yeast Exophiala dermatitidis is a polyextremophilic human pathogen, especially known for growing in man-made extreme environments. Reported diseases caused by this fungus range from benign cutaneous to systemic infections with 40% fatality rate. While the number of cases steadily increases in both immunocompromised and immunocompetent people, detailed knowledge about infection mechanisms, virulence factors and host response are scarce. To understand the impact of the putative virulence factor melanin on the infection, we generated a polyketide synthase (PKS1) mutant using CRISPR/Cas9 resulting in a melanin deficient strain. The mutant and the wild-type fungus were inoculated onto skin explants using an ex vivo skin organ culture model to simulate in vivo cutaneous infection. The difference between the mutant and wild-type transcriptional landscapes, as assessed by whole RNA-sequencing, were small and were observed in pathways related to the copper homeostasis, cell wall genes and proteases. Seven days after inoculation the wild-type fungus completely colonized the stratum corneum, invaded the skin and infected keratinocytes while the mutant had only partially covered the skin and showed no invasiveness. Our results suggest that melanin dramatically improves the invasiveness and virulence of E. dermatitidis during the first days of the skin infection.

Body Image, Personality Traits, and Quality of Life in Botulinum Toxin A and Dermal Filler Patients.

BACKGROUND: The demand for minimally invasive cosmetic procedures has continued to rise, especially in Germany, yet few studies have examined this patient population. The literature in Germany has repeatedly voiced the speculation that users of minimally invasive, skin-rejuvenating procedures displayed a higher tendency toward dysmorphic behavior patterns or, respectively, other abnormal personality traits. OBJECTIVES: The aim of this study was to investigate body image, personality traits, quality of life, and socioeconomic parameters in users of botulinum toxin and/or facial fillers. METHODS: One hundred forty-five females presented for botulinum toxin and/or soft tissue filler injections completed demographic and standardized psychometric questionnaires such as the World-Health-Organization Quality of Life-Short Form, Big Five Inventory-10, Body Dysmorphic Disorder Questionnaire before treatment. RESULTS: Patients undergoing injectable aesthetic treatments in an urban dermatology practice were women, middle-aged, highly educated, and mostly employed. Furthermore, participants showed higher quality of life, especially health-related quality of life, and a lower body mass index than controls. Concerning personality traits, our participants scored significantly higher on extraversion, agreeableness, openness to experience, and neuroticism. CONCLUSIONS: This study helps to better understand the psychosocial factors characterizing this patient population. Patients differ from controls by having a higher level of quality of life. No signs of body dysmorphic patterns or problematic personality traits were found. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Mechanical and migratory properties of normal, scar, and Dupuytren's fibroblasts.

Mechanical properties of myofibroblasts play a key role in Dupuytren's disease. Here, we used atomic force microscopy to measure the viscoelastic properties of 3 different types of human primary fibroblasts derived from a same patient: normal and scar dermal fibroblasts and palmar fascial fibroblasts from Dupuytren's nodules. Different stiffness hydrogels (soft ~1 kPa and stiff ~ 50 kPa) were used as cell culture matrix to mimic the mechanical properties of the natural tissues, and atomic force microscopy step response force curves were used to discriminate between elastic and viscous properties of cells. Since transforming growth factor-ß1 (TGF-ß1) is known to induce expression of α-smooth muscle actin positive stress fibers in myofibroblasts, we investigated the behavior of these fibroblasts before and after applying TGF-ß1. Finally, we performed an in vitro cell motility test, the wound healing or scratch assay, to evaluate the migratory properties of these fibroblasts. We found that (1) Dupuytren's fibroblasts are stiffer than normal and scar fibroblasts, the elastic modulus E ranging from 4.4, 2.1, to 1.8 kPa, for Dupuytren's, normal and scar fibroblasts, respectively; (2) TGF-ß1 enhances the level of α-smooth muscle actin expression and thus cell stiffness in Dupuytren's fibroblasts (E, ~6.2 kPa); (3) matrix stiffness influences cell mechanical properties most prominently in Dupuytren's fibroblasts; and (4) Dupuytren's fibroblasts migrate slower than the other fibroblasts by a factor of 3. Taking together, our results showed that mechanical and migratory properties of fibroblasts might help to discriminate between different pathological conditions, helping to identify and recognize specific cell phenotypes.