Skin Physiology Research Articles

In vitro and In vivo Evaluation of Sunscreen Formulations Containing Nanolipid Carriers

Abstract: The majority of sunscreen cosmetics are emulsions or creams. However, formulations that use lipid nanoparticles as the delivery vehicle for sunscreen chemicals may offer benefits in terms of skin retention, enhancement of penetration through the epidermal layer, and Ultraviolet (UV) absorption and scattering. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been investigated to create sunscreen products with low or medium UV protection. SLN and NLC have a wide range of characteristics and have been proven to effectively control the entry of actives showing UV protection activity through the skin. They have no hazardous effects; therefore, they can be employed safely in dermatological and cosmetic preparations to obtain different traits. When utilized as vehicles for molecular sunscreens, lipid nanoparticles showed a synergistic impact of UV scattering. The ability to minimize the concentration of the molecular sunscreen, its potential adverse effects, and the expenses of formulating pricey sunscreens are all advantages derived from these studies. The review discusses some research on how lipid nanoparticles have been encapsulating sunscreen agents. Exposure to sunlight is a key element in the aetiology of the gradual undesired changes in the skin look and physiology caused by UV rays present in the sunshine; hence evaluating sunscreen activity is an essential aspect of the cosmetic business. The author will also address some of the in vitro and in vivo assessments of sunscreens.

A scientific approach to skin radiotherapy nursing Article 4 – How nurses can predict, explain, and care for the acute side effects that may arise during a course of skin radiotherapy

Nurses play an important role in the care of patients treated with radiotherapy (RT) for skin conditions, such as skin cancers. This is the final article in a four-part series that aims to supplement general oncology nurse training by providing a scientific basis to better understand a) the use of RT in skin and its diseases; and b) the management of acute skin RT reactions to achieve best patient outcomes. The first article focused on the role of the nurse within the radiation oncology department and the initial patient assessment. The second article revised the anatomy, physiology, pathologies and radiobiology of skin. The third described the skin RT prescription and plan, especially in relation to volume and dose. The aim of this fourth article is to assist the nurse, by applying the knowledge from the previous articles, to predict, explain and care for the acute side effects that may arise during a course of skin radiotherapy.

Effect of vibroacoustic stimulation on athletes recovering from exercise.

In sports requiring multiple short bouts of high-intensity exertion, recovery while off the field is an important part of being an effective competitive athlete. This study investigated the potential of vibroacoustic stimulation to aid recovery from athletic stress. University of Pittsburgh club and varsity athletes (n = 22) pedaled on a stationary bike strenuously, followed by a period of recovery accompanied by vibration using a wearable transducer. Subjective and physiological (skin conductance responses and cardiac measures) were used to determine the extent of recovery with frontal electroencephalographic (alpha/theta) measures indexing brain reactivity. Vibrations rated as the most calming by each participant were associated with increased high-frequency heart-rate variability, representing parasympathetic tone, particularly in athletes most affected by pedaling. Yet, EEG markers, while related to subjective recovery, were not associated with physiological change. This work provides support for the idea that vibration, which is subjectively rated as calming, could affect physiological recovery from physical stressors, at least for those individuals whose physiology is affected by exertion. This is likely through direct effects on physiology rather than "top down" effects on the brain.

Pgc-1α controls epidermal stem cell fate and skin repair by sustaining NAD+ homeostasis during aging

ObjectiveThe epidermal barrier is renewed by the activation, proliferation, and differentiation of keratinocyte stem cells after injury and aging impedes this repair process through undefined mechanisms. We previously identified a gene signature of metabolic dysfunction in aged murine epidermis, but the precise regulators of epidermal repair and age-related growth defects are not well established. Aged mouse models as well as mice with conditional epidermal loss of the metabolic regulator peroxisome proliferator-activated receptor gamma coactivator-1 alpha (Pgc-1α) were used to explore the cellular pathways which control skin repair after injury and stress. MethodsAged mice or those with epidermal Pgc-1α deletion (epiPgc-1α KO) and young or Pgc1afl/fl controls were subjected to wound injury, UVB exposure or the inflammatory agent TPA. In vivo and ex vivo analyses of wound closure, skin structure, cell growth and stem cell differentiation were used to understand changes in epidermal re-growth and repair resulting from aging or Pgc-1α loss. ResultsAging impairs epidermal re-growth during wound healing and results in lower expression of Pgc-1α. Mice with conditional deletion of epidermal Pgc-1α exhibit greater inflammation- and UVB-induced cell differentiation, reduced proliferation, and slower wound healing. epiPgc-1α KO mice also displayed reduced keratinocyte NAD+ levels, shorter telomeres, and greater poly ADP-ribosylation, resulting in enhanced stress-stimulated p53 and p21 signaling. When NAD+ was reduced by Pgc-1α loss or pharmacologic inhibition of NAD+ synthesis, there was reduced stress-induced proliferation, increased differentiation, and protection against DNA damage via enhanced epidermal shedding. Similarly, aged mice exhibit disrupted epidermal NAD+ homeostasis and enhanced p53 activation, resulting in p21 growth arrest after wounding. NAD+ precursor treatment restores epidermal growth from old skin to that of young. ConclusionsOur studies identify a novel role for epidermal Pgc-1α in controlling epidermal repair via its regulation of cellular NAD+ and downstream effects on p53-driven growth arrest. We also establish that parallel mechanisms are evident in aged epidermis, showing that NAD+ signaling is an important controller of physiologic skin repair and that dysfunction of this pathway contributes to age-related wound repair defects.

Mechanistic Modeling of In Vitro Skin Permeation and Extrapolation to In Vivo for Topically Applied Metronidazole Drug Products Using a Physiologically Based Pharmacokinetic Model.

Physiologically based pharmacokinetic (PBPK) modeling has increasingly been employed in dermal drug development and regulatory assessment, providing a framework to integrate relevant information including drug and drug product attributes, skin physiology parameters, and population variability. The current study aimed to develop a stepwise modeling workflow with knowledge gained from modeling in vitro skin permeation testing (IVPT) to describe in vivo exposure of metronidazole locally in the stratum corneum following topical application of complex semisolid drug products. The initial PBPK model of metronidazole in vitro skin permeation was developed using infinite and finite dose aqueous metronidazole solution. Parameters such as stratum corneum lipid-water partition coefficient (Ksclip/water) and stratum corneum lipid diffusion coefficient (Dsclip) of metronidazole were optimized using IVPT data from simple aqueous solutions (infinite) and MetroGel (10 mg/cm2 dose application), respectively. The optimized model, when parameterized with physical and structural characteristics of the drug products, was able to accurately predict the mean cumulative amount permeated (cm2/h) and flux (μg/cm2/h) profiles of metronidazole following application of different doses of MetroGel and MetroCream. Thus, the model was able to capture the impact of differences in drug product microstructure and metamorphosis of the dosage form on in vitro metronidazole permeation. The PBPK model informed by IVPT study data was able to predict the metronidazole amount in the stratum corneum as reported in clinical studies. In summary, the proposed model provides an enhanced understanding of the potential impact of drug product attributes in influencing in vitro skin permeation of metronidazole. Key kinetic parameters derived from modeling the metronidazole IVPT data improved the predictions of the developed PBPK model of in vivo local metronidazole concentrations in the stratum corneum. Overall, this work improves our confidence in the proposed workflow that accounts for drug product attributes and utilizes IVPT data toward improving predictions from advanced modeling and simulation tools.

Targeting the Hippo/YAP/TAZ signalling pathway: Novel opportunities for therapeutic interventions into skin cancers.

Skin cancers are by far the most frequently diagnosed human cancers. The closely related transcriptional co-regulator proteins YAP and TAZ (WWTR1) have emerged as important drivers of tumour initiation, progression and metastasis in melanoma and non-melanoma skin cancers. YAP/TAZ serve as an essential signalling hub by integrating signals from multiple upstream pathways. In this review, we summarize the roles of YAP/TAZ in skin physiology and tumorigenesis and discuss recent efforts of therapeutic interventions that target YAP/TAZ in in both preclinical and clinical settings, as well as their prospects for use as skin cancer treatments.

Effects of Obesity on Infections with Emphasis on Skin Infections and Wound Healing.

Obesity represents a serious health problem as it is rapidly increasing worldwide. Obesity is associated with reduced health span and life span, decreased responses to infections and vaccination and increased frequency of inflammatory conditions. In this review, we summarize published data showing that obesity increases the risk of different types of infections, with a special focus on skin infections. Obesity also induces skin changes and conditions (inflammation-based and hypertrophic) which are often associated with fungi or bacteria overgrowth. The association of obesity with the skin microbiome has been established in both mice and humans. Balance of commensal microbes controls skin homeostasis and the host immune response, while changes in normal physiologic skin microbiome composition and pathologic bacteria contribute to skin diseases. We also summarize the major steps in wound healing and how obesity affects each of them. The role that immune cells have in this process is also described. Although the studies summarized in this review clearly demonstrate the deleterious effects of obesity on wound healing, additional studies are needed to better characterize the cellular and molecular mechanisms involved and identify specific targets of intervention.

Composition and Performance of Autologous Engineered Skin Substitutes for Repair or Regeneration of Excised, Full-Thickness Burns.

Prompt and permanent wound closure after burn injuries remains a requirement for patient recovery. Historically, split-thickness skin autograft (STAG) has served as the prevailing standard of care for closure of extensive, deep burns. Because STAG availability may be insufficient in life-threatening burns, alternatives have been evaluated for safety and efficacy of wound closure. Since the 1970s, alternatives consisting of cultured epidermal keratinocytes, and/or acellular dermal substitutes were studied and translated into services and devices that facilitated wound closure, survival, and recovery after major burns. Cultured epithelial autografts (CEA) promoted epidermal closure of wounds but were not stable during long-term recovery. An acellular dermal substitute consisting of collagen and glycosaminoglycans (C-GAG) provided more uniform dermal repair, and reduced needs for epidermal harvesting but was subject to loss from microbial contamination. More recently, an autologous engineered skin substitute (ESS) has been reported and includes a C-GAG polymer populated with fibroblasts and keratinocytes which form basement membrane. ESS can be applied clinically over a vascularized dermal substitute and generates stable wound closure that is smooth, soft, and strong. Despite these advances, no current alternatives for permanent wound closure restore the anatomy and physiology of uninjured skin. Current alternatives act by mechanisms of wound healing, not by developmental biology by which skin forms in utero with pigment, hair, sweat and sebaceous glands, microvasculature, and nerve. Until full-thickness burns are restored with all of the normal structures and functions of uninjured skin, regenerative medicine of skin will remain an ambitious aspiration for future researchers and engineers to achieve.

Differential Diagnosis of Rosacea Using Machine Learning and Dermoscopy.

IntroductionRosacea is a common chronic inflammatory disease occurring on the face, whose diagnosis is mainly based on symptoms and physical signs. Due to some overlap in symptoms and signs with other inflammatory skin diseases, young and inexperienced doctors often make misdiagnoses and missed diagnoses in clinical practices. We analyze the results of skin physiology and dermatoscopy using machine learning method and identify the characteristics of acne rosacea, which differentiate it from other common facial inflammatory skin diseases so as to improve the accuracy of clinical and differential diagnosis of rosacea.MethodsA total of 495 patients who were jointly diagnosed by two experienced doctors were included. Basic data, clinical symptoms, physiological skin detection, and dermatoscopy results were collected, and the clinical characteristics of rosacea and other common facial inflammatory diseases were summarized according to the descriptive analysis results. The model was established using a machine learning method and compared with the judgment results of young and inexperienced doctors to verify whether the model can improve the accuracy of clinical diagnosis and differential diagnosis of rosacea.ResultsThe proportion of yellow and red halos, vascular polygons, as well as follicular pustules, showed by dermatoscopy, and the melanin index in physiological skin detection revealed statistical significance in differentiating rosacea and other common facial inflammatory diseases (all P < 0.01). After adopting the machine learning, we found that GBM (Gradient Boosting Machine) algorithm was the best, and the error rate of this model in the validation set was 5.48%. In the final man-machine comparison, the accuracy of the GBM algorithm model for the classification of skin disease was significantly higher than that of young and inexperienced doctors.ConclusionDermatoscopy combined with machine learning can effectively improve the diagnosis and differential diagnosis accuracy of rosacea and other facial inflammatory skin diseases.

Acidic Skin Care Promotes Cutaneous Microbiome Recovery and Skin Physiology in an Acute Stratum Corneum Stress Model

Introduction: Skin microbiome and skin physiology are important indicators of the epidermal homeostasis status. Stress models can reveal pathological conditions and modulating effects. Here we investigated the cutaneous microbiome in relation to skin physiology after mild tape stripping (TS) without treatment compared to two cosmetic leave-on lotions (pH 5.5 vs. pH 9.3) in 25 healthy volunteers. Methods: The microbiome was analyzed by 16S-rRNA-gene amplicon sequencing and put in relation to the following skin physiology parameter: epidermal barrier function (TEWA-Meter TM300), stratum corneum hydration (Corneometer CM 825), surface pH (pH-Meter), and skin erythema (Mexameter). Results: TS reduced the alpha diversity with a recovery over 7 days without treatment. Both lotions significantly accelerated the recovery of the alpha diversity already after 2 days with a slightly higher rate for the acidic lotion. After TS, the relative abundance of Proteobacteria was increased, whereas Actinobacteria were reduced. The relative abundances of typical skin-associated genera were reduced after TS. Taxa compositions returned to normal levels after 7 days in all treatment groups. An accelerated normalization could be observed with both lotions already after 2 days. A significant difference in skin pH was observed on day 2 and day 7 with an increased pH for the alkaline lotion. Both lotions induced an increase in stratum corneum hydration. Conclusion: The study proved the suitability of an experimental stress model in the assessment of skin surface microbiome in relation to skin physiology. Stratum corneum hydration increased significantly with both lotions already at day 2. Microbiome parameters (alpha diversity, mean relative taxa, abundance of selected genera) normalized over 2–7 days. The following mechanisms could be responsible for the accelerated normalization of the microbiome: (a) optimized hydration during the recovery phase, (b) the composition of the lotion, (c) the induced repair mechanism. Thus, the formulation has a positive effect on the stratum corneum hydration and subsequently on cutaneous microbiome and skin physiology. Furthermore, this eventually has implications on the modulation of exogenous stress-induced epidermal alterations.

Effect of Solar Radiation on Skin Microbiome: Study of Two Populations.

Here, we examined the skin microbiome of two groups of healthy volunteers living on the Mediterranean coast with different exposures to sun radiation. One group, exposed to the sun in the summer, was compared with a group covered with clothing throughout the year. The seasonal effects on the skin microbiome of three body sites were determined before and after summer. Surprisingly, at the phyla level, there were no significant differences in microbiome diversity between the groups. Furthermore, within each group, there were no significant seasonal differences in high-abundance species at any of the sampling sites. These results suggest that the skin microbiome, developed over years, remains stable even after several months of exposure to summer weather, direct sunlight and humidity. However, in the group exposed to the sun during the summer months, there were significant differences in low-abundance species in sun-exposed areas of the skin (the inner and outer arm). These subtle changes in low-abundance species are interesting, and their effect on skin physiology should be studied further.

Novel human skin surface antimicrobial peptide quantification method using a skin patch test chamber: A pilot study.

Antimicrobial peptides (AMPs) on the skin surface are related to the innate immunity of the skin in preventing external infection. Skin rinsing and tape stripping (TS) are acceptable methods for analyzing AMPs on the skin surface but have limitations, such as causing skin damage. In this study, we proposed a noninvasive method to measure AMPs on the skin surface with minimal skin damage. Using the patch test assay, we aimed to analyze the skin surface human β-defensin (hBDs) levels without damaging the skin barrier. The concentrations of hBDs on the skin surface were evaluated through the skin patch testing of 13 healthy subjects, and hBD-1 concentrations were compared with those obtained using the TS method in this proof-of-concept study. In addition, changes in skin physiology and concentration of hBDs under 1% sodium lauryl sulfate stimulation were monitored in 14 healthy subjects (8 young and 6 elderly subjects) for 150 h. The correlation between the two methods had a Pearson's coefficient of 0.640, and skin patch analysis led to a relatively less impaired barrier with no significant increase in transepidermal water loss after analysis. Age-specific comparisons suggested that higher skin surface hBD-2 concentrations were present in the young group as compared with the elderly group. Skin surface expression of hBD-2 after skin barrier disruption was also higher in the young group. Our findings show that skin patch analysis is a convenient method to analyze hBDs on the skin surface. hBDs are factors of innate immunity that can be used as an index to predict a decreased chemical immune response of skin due to aging.

IL-38 orchestrates proliferation and differentiation in human keratinocytes.

Interleukin (IL)-38 is a member of the IL-1 cytokine family with reported anti-inflammatory activity. The highest constitutive IL-38 expression is detected in the skin, where it is mainly produced by differentiating keratinocytes. However, little data are available regarding its biological functions. In this study, we investigated the role of IL-38 in skin physiology. We demonstrate here that dermal fibroblasts and epithelial cells of skin appendages, such as eccrine sweat glands and sebaceous glands, also express IL-38. Next, using two- and three-dimensional cell cultures, we show that endogenous expression of IL-38 correlates with keratinocyte differentiation and its ectopic overexpression inhibits keratinocyte proliferation and enhances differentiation. Accordingly, immunohistochemical analysis revealed downregulation of IL-38 in skin pathologies characterized by keratinocyte hyperproliferation, such as psoriasis and basal or squamous cell carcinoma. Finally, intracellular IL-38 can shuttle between the nucleus and the cytoplasm and its overexpression modulates the activity of the transcription regulators YAP and ID1. Our results indicate that IL-38 can act independently from immune system activation and suggest that it may affect the epidermis directly by decreasing proliferation and promoting differentiation of keratinocytes. These data suggest an important role of keratinocyte-derived IL-38 in skin homeostasis and pathologies characterized by epidermal alterations.

A scientific approach to skin radiotherapy nursing Article 3 - The skin RT prescription and plan especially in relation to volume and dose

Nurses play an important role in the RT of skin and its diseases. This is the third of four articles that attempts to provide a scientific basis for nurses to better understand skin RT patients, skin and its diseases, and acute RT skin reactions and how to care for them to achieve the best outcomes from RT treatments. The first paper outlined the role of the nurse as an integral part of the radiation oncology team and how to conduct an effective patient assessment to ensure the patient’s optimal journey to treatment completion. The second article described the anatomy, physiology, pathology and radiobiology of skin and its diseases. This third article describes the skin RT prescription and plan, especially in relation to volume and dose. The fourth paper will show how the nurse, by applying the knowledge from the previous articles, can predict, explain and care for any side effects that may arise. This knowledge is important for establishing patient expectations, preparing the patient for side effects, and giving scientifically based reasons for complying with care protocols. Hopefully, these articles will help support the nurse to deliver best care to skin RT patients. More prospective research is needed to elucidate the many remaining facets of nursing care for skin RT patients.

A scientific approach to skin radiotherapy nursing Article 2 - The anatomy, physiology, pathology and radiobiology of skin and its diseases

Nurses play an important role in the care of patients treated with radiotherapy (RT) for skin conditions such as skin cancers. A series of four articles will aim to supplement general oncology nurse training by providing a scientific basis to better understand the skin and its diseases, the use of RT in skin, and the management of necessary acute skin RT reactions to achieve best patient outcomes. The first article focused on the role of the nurse within the radiation oncology department and the initial patient assessment. This second article describes the anatomy, physiology, pathology and radiobiology of skin and its diseases. These concepts are fundamental to the understanding of how acute effects develop during treatment and how to best care for them. The transition time of normal keratinocytes in the epidermis from creation to demise (10-14 days) is discussed as essential to understanding the timing of acute RT effects. The effect of RT on DNA, and the different effects of RT on normal cells versus tumour cells, which underscore fractionation and normal tissue conservation, are also discussed. Finally, this article addresses the late effects of RT in normal skin, accelerated repopulation, types of skin cancers and their relative radiosensitivities, and the effects of RT on benign skin diseases. The third article will describe the skin RT prescription and plan, especially in relation to volume and dose; and the fourth will show how the nurse, by applying the knowledge from the previous articles, can predict, explain and care for the acute side effects that may arise during a course of skin radiotherapy.

Thermoregulatory Response of Blackbelly Adult Ewes and Female Lambs during the Summer under Tropical Conditions in Southern Mexico.

Simple SummaryClimate change has intensified high environmental temperatures, subjecting farm animals to heat stress conditions. In this study, the thermoregulatory responses of Blackbelly adult ewes and female lambs, during the summer under tropical conditions, in southern Mexico were analyzed. The combination of temperature and relative humidity in summer in tropical conditions causes heat stress in hair ewes, resulting in thermoregulatory problems. To counteract these effects, females modify their physiological constants to avoid reproductive and productive problems under these production conditions.High environmental temperatures cause heat stress in ewes, resulting in thermoregulatory problems. In this study, the thermoregulatory responses of Blackbelly adult ewes (G1, n = 14) and female lambs (G2, n = 7), during the summer under tropical conditions, in southern Mexico were analyzed. Different physiological variables and skin temperatures (ST) of the ewes were recorded. Breathing frequency (BF) values were similar between groups at 116.73 ± 33.598 bpm (G1) and 113.661 ± 34.515 bpm (G2) (p > 0.05). In the case of skin elasticity (SE), there were no significant differences between the time of day and the age of the ewes (p > 0.05). Significant differences were observed between groups for BF, rectal temperature (RT), and heart rate (HR) values (p < 0.05). All ST values, for both groups, were significantly higher during the afternoon (p < 0.001). In general, all Blackbelly adult ewes and female lambs during the summer present severe heat stress conditions as a result of an increase in physiological constants and ST. It is concluded that all ewes thermoregulate body temperature by modifying different physiological variables to counteract the effect of heat stress.

765 A new vascularized skin substitute to study angiogenesis

Vasculature plays an essential role in skin physiology and its architecture and function are altered in aged and diseased skin. There is thus a need to develop innovative 3D in vitro models with adjustable vasculature. Several in vitro skin models co-seeding endothelial cells with fibroblasts and keratinocytes have been proposed using scaffolds or bioprinting. However, these models fail in reproducing native skin microenvironment and do not demonstrate a functional vascular network. The aim of this work was to develop a vascularized skin substitute and to demonstrate its functionality in response to angiogenic molecules.

743 Hair follicles can “taste”: Stevioside stimulation of the bitter taste receptor, TAS2R4, inhibits human hair growth ex vivo

Besides taste buds, many other tissues express taste receptors (TR), where they exert various, often ill-explored non-gustatory functions, e.g. in immunity and metabolism. These evolutionary ancient functions of human TRs can be optimally interrogated in human skin, whose keratinocytes express selected TRs, and its dominant appendage, the hair follicle (HF). However, the role of TRs in human skin physiology is unknown. Therefore, we have asked whether TRs are expressed in human scalp HFs and if their specific stimulation or silencing affects hair growth. Here, we show that human scalp HF keratinocytes prominently and hair cycle-dependently express the bitter taste receptor, TAS2R4 (mRNA, protein). When TAS2R4 was stimulated in organ-cultured anagen scalp HFs by the sweet-tasting steviol-glycoside TAS2R4 agonist, rebaudioside A (Reb A), this significantly inhibited hair matrix keratinocyte proliferation and induced premature catagen development ex vivo. These RebA effects could be reversed by TAS2R4 knockdown ex vivo. Mechanistically, these HF effects are mainly caused by TAS2R4-mediated enhanced expression/ secretion of the key catagen-promoting growth factor, TGFβ2, since TGFß-neutralization counteracted RebA-induced catagen induction and since RNAseq analysis showed upregulation of TGFß-related signaling pathways. Thus, we introduce here TRs as important, ancestral chemosensory regulators of human skin physiology, human (mini-)organ remodeling (=HF cycling), and growth factor production (TGFß). We also identify a novel, drug-free, “gustatory” strategy for the therapeutic inhibition of unwanted hair growth (hirsutism, hypertrichosis) with a natural sweetener.

842 Novel human skin organ culture models for the identification and characterization of anti-aging actives ex vivo

Research of chronological (intrinsic) aging in human skin and the development of potent anti-aging and rejuvenating agents are impeded by the limited availability of clinically relevant models. As current cell culture approaches cannot satisfactorily recapitulate normal human skin physiology and aging, even under 3D conditions, human full-thickness skin organ culture (hSOC) remains an excellent, but under-used alternative for pre-clinical aging research and the testing of candidate senolytics. Here, we present three distinct, complementary novel hSOC approaches to interrogating intrinsic, UV-free human skin aging.

832 3D Bioprinted vascularized human skin models can be used to screen modulators of angiogenesis for medical and dermo-cosmetic applications

Lack of skin vascularization or in contrast its hypervascularization are aggravating factors of some medical pathologies (ulcers and cancers) and dermo-cosmetics troubles (rosacea and dark circles). Thus, developing a suitable in vitro model to screen pharmaceutical and cosmetics ingredients able to stimulate or mitigate the angiogenesis process without changing the normal skin physiology are not easy and hampered by the existence of unreliable in vitro models. Traditional models of skin angiogenesis concentrate on analyzing the co-culture growth of endothelial cells with or without added fibroblasts or keratinocytes. However, these models do not work for topical applications and top-down layering analysis required for complex studies and do not translate well to clinical analysis. Here we describe the creation of a 3D bioprinted vascularized skin model, designed for screening those type of molecules. Human Dermal Microvascular Endothelial Cells, dermal fibroblasts and epidermal keratinocytes were harvested and expanded from juvenile foreskins. Cells were selected for optimal growth and mixed with a bioink into which adhesion proteins were added and cartridged into a CELLINK pneumatic 3D bioprinting system allowing the generation of 3D vascularized printed full thickness skins. Resulting skin models had a vascularization bed created in the lower quadrant of the dermal structure, which was confocal microscopy imaged with anti-CD31 fluorescent labelling. Reduction of epidermal growth factor and pituitary supplement resulted in the sequential reduction and cell death of the vascular bed over 14 days, whilst continual supplementation maintains the model and cellular interconnections. With 3D Bioprinting we can produce hundreds of models in one afternoon giving the potential to screen many combinations of molecules before moving to more expensive clinical experimentations.