Journal articles on the topic '3D skin infection model'

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1

Barua, Nilakshi, Ying Yang, Lin Huang, and Margaret Ip. "VraSR Regulatory System Contributes to the Virulence of Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) in a 3D-Skin Model and Skin Infection of Humanized Mouse Model." Biomedicines 10, no. 1 (December 24, 2021): 35. http://dx.doi.org/10.3390/biomedicines10010035.

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The vancomycin-resistance associated sensor/regulator, VraSR two-component regulatory-system (VraSR), regulates virulence and the response of Staphylococcus aureus (SA) to environmental stress. To investigate the role of VraSR in SA skin and soft tissue infections (SSTI), we inactivated the VraSR of a clinical CA-MRSA ST30 strain by insertional mutation in vraR gene using the TargeTron-Gene Knockout System. We constructed an organotypic keratinocyte fibroblast co-culture (3D-skin model) and a humanized mouse as SSTI infection models. In the 3D-skin model, inactivation of VraSR in the strains ST30 and USA300 showed 1-log reduction in adhesion and internalization (p < 0.001) compared to the respective wildtype. The mutant strains of ST30 (p < 0.05) and USA300-LAC (p < 0.001) also exhibited reduced apoptosis. The wildtype ST30 infection in the humanized mouse model demonstrated increased skin lesion size and bacterial burden compared to BALB/c mice (p < 0.01). The response of the humanized mouse towards the MRSA infection exhibited human similarity indicating that the humanized mouse SSTI model is more suitable for evaluating the role of virulence determinants. Inactivation of VraSR in ST30 strain resulted in decreased skin lesion size in the humanized mouse SSTI model (p < 0.05) and reduction in apoptotic index (p < 0.01) when compared with the wildtype. Our results reveal that inactivating the VraSR system may be a potent anti-virulence approach to control MRSA infection.
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Barua, Nilakshi, Lin Huang, Carmen Li, Ying Yang, Mingjing Luo, Wan In Wei, Kam Tak Wong, Norman Wai Sing Lo, Kin On Kwok, and Margaret Ip. "Comparative Study of Two-Dimensional (2D) vs. Three-Dimensional (3D) Organotypic Kertatinocyte-Fibroblast Skin Models for Staphylococcus aureus (MRSA) Infection." International Journal of Molecular Sciences 23, no. 1 (December 28, 2021): 299. http://dx.doi.org/10.3390/ijms23010299.

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The invasion of skin tissue by Staphylococcus aureus is mediated by mechanisms that involve sequential breaching of the different stratified layers of the epidermis. Induction of cell death in keratinocytes is a measure of virulence and plays a crucial role in the infection progression. We established a 3D-organotypic keratinocyte-fibroblast co-culture model to evaluate whether a 3D-skin model is more effective in elucidating the differences in the induction of cell death by Methicillin-resistant Staphylococcus aureus (MRSA) than in comparison to 2D-HaCaT monolayers. We investigated the difference in adhesion, internalization, and the apoptotic index in HaCaT monolayers and our 3D-skin model using six strains of MRSA representing different clonal types, namely, ST8, ST30, ST59, ST22, ST45 and ST239. All the six strains exhibited internalization in HaCaT cells. Due to cell detachment, the invasion study was limited up to two and a half hours. TUNEL assay showed no significant difference in the cell death induced by the six MRSA strains in the HaCaT cells. Our 3D-skin model provided a better insight into the interactions between the MRSA strains and the human skin during the infection establishment as we could study the infection of MRSA in our skin model up to 48 h. Immunohistochemical staining together with TUNEL assay in the 3D-skin model showed co-localization of the bacteria with the apoptotic cells demonstrating the induction of apoptosis by the bacteria and revealed the variation in bacterial transmigration among the MRSA strains. The strain representing ST59 showed maximum internalization in HaCaT cells and the maximum cell death as measured by Apoptotic index in the 3D-skin model. Our results show that 3D-skin model might be more likely to imitate the physiological response of skin to MRSA infection than 2D-HaCaT monolayer keratinocyte cultures and will enhance our understanding of the difference in pathogenesis among different MRSA strains.
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3

Shim, Dong Wook, Soo Kwang An, Ha Lim Lee, Jae Yong Lee, Byung Ryul Lee, and Gi Young Yang. "Pressure Changes During Layer Cupping in a Skin Model." Journal of Acupuncture Research 38, no. 2 (May 31, 2021): 159–64. http://dx.doi.org/10.13045/jar.2020.00031.

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Background: Cupping is widely used in Korean medicine, but there is a risk of bacterial infection if the suction pump (used for inducing negative pressure) and the patients’ skin are not separated. This study aimed to investigate the effect of layer cupping by comparing the pressure changes between layer cupping and conventional cupping.Methods: To evaluate pressure changes the study was designed with 3 types of conditions applied to a skin model: (1) a Dongbang cup with a manual or motor suction pump (conventional cupping); (2) layer cupping with 2 Dongbang cups; and (3) layer cupping with a cup made by 3D printing and a Dongbang cup.Results: When a manual suction pump was used (conventional cupping), the pressure did not decrease steadily, and in 1 section there was an increase in pressure. When layer cupping was used, the pressure in the lower cup (which would be directly applied to the patient’s skin), decreased steadily.Conclusion: In the pressure change graph for layer cupping in this skin model, the pressure in the lower cup (which would be placed on the patient’s skin) steadily decreased, and reached equilibrium. Therefore, the layer cupping model may help to reduce the risks of bacterial infection.
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Merk, Helena, Tehila Amran-Gealia, Doris Finkelmeier, Christina Kohl, Isabelle Pichota, Noa Stern, Steffen Rupp, Amiram Goldblum, and Anke Burger-Kentischer. "Human-Based Immune Responsive In Vitro Infection Models for Validation of Novel TLR4 Antagonists Identified by Computational Discovery." Microorganisms 10, no. 2 (January 22, 2022): 243. http://dx.doi.org/10.3390/microorganisms10020243.

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Infectious diseases are still a major problem worldwide. This includes microbial infections, with a constant increase in resistance to the current anti-infectives employed. Toll-like receptors (TLRs) perform a fundamental role in pathogen recognition and activation of the innate immune response. Promising new approaches to combat infections and inflammatory diseases involve modulation of the host immune system via TLR4. TLR4 and its co-receptors MD2 and CD14 are required for immune response to fungal and bacterial infection by recognition of microbial cell wall components, making it a prime target for drug development. To evaluate the efficacy of anti-infective compounds early on, we have developed a series of human-based immune responsive infection models, including immune responsive 3D-skin infection models for modeling fungal infections. By using computational methods: pharmacophore modeling and molecular docking, we identified a set of 46 potential modulators of TLR4, which were screened in several tests systems of increasing complexity, including immune responsive 3D-skin infection models. We could show a strong suppression of cytokine and chemokine response induced by lipopolysacharide (LPS) and Candida albicans for individual compounds. The development of human-based immune responsive assays provides a more accurate and reliable basis for development of new anti-inflammatory or immune-modulating drugs.
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5

Xian, Dehai, Xia Xiong, Jixiang Xu, Li Xian, Qirong Lei, Jing Song, and Jianqiao Zhong. "Nrf2 Overexpression for the Protective Effect of Skin-Derived Precursors against UV-Induced Damage: Evidence from a Three-Dimensional Skin Model." Oxidative Medicine and Cellular Longevity 2019 (October 14, 2019): 1–13. http://dx.doi.org/10.1155/2019/7021428.

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Background. Skin photodamage is associated with ultraviolet- (UV-) induced reactive oxygen species (ROS) overproduction and nuclear factor erythroid 2-related factor 2 (Nrf2) inactivation. In our previous study, skin-derived precursors (SKPs) were shown to ameliorate a UV-induced damage in mice, probably through Nrf2 activation and ROS scavenging. Objective. To clarify the mechanism underlying the photoprotective effect of SKPs against UV-induced damage in a three-dimensional (3D) skin model. Methods. The Nrf2 gene in SKPs was modified using lentiviral infection, and 3D skin models were reconstructed with keratinocytes and fibroblasts on the basis of type I collagen. Subsequently, these models were divided into the following six groups: normal, model, overexpressed, control, silenced, and negative control groups. Prior to irradiation, respective SKPs were injected into the last four groups. Next, all groups except the normal group were exposed to UVA+UVB. Lastly, the pathological and molecular-biological techniques were employed to determine the parameters. Additionally, LY294002, a PI3K inhibitor, was used to investigate the roles of PI3K/Akt and Nrf2/hemeoxygenase-1 (HO-1) in SKP photoprotection. Results. Normal 3D skin models appeared as milky-white analogs with a clear, well-arranged histological structure. After the skin was exposed to irradiation, it exhibited cell swelling and a disorganized structure and developed nuclear condensation with numerous apoptotic cells. The expressions of cellular protective genes and Nrf2/HO-1/PI3K/Akt proteins remarkably decreased, which were accompanied by increased oxidative stress and decreased antioxidants (P<0.05). However, these phenomena were reversed by nrf2-overexpressing SKPs. The 3D skin in the overexpressed group showed mild swelling, neatly arranged cells, and few apoptotic cells. Cellular protective genes and Nrf2/HO-1/PI3K/Akt proteins were highly expressed, and the oxidative biomarkers were remarkably ameliorated (P<0.05). Nevertheless, the expression of these proteins decreased after LY294002 pretreatment regardless of SKP treatment or not. Meanwhile, there were increases in both UV-induced apoptotic cells and ROS level accompanied with SOD and GPX decrease in the presence of LY294002. Conclusions. Evidence from the 3D skin model demonstrates that the protection of SKPs against UV-mediated damage is primarily via the PI3K/Akt-mediated activation of the Nrf2/HO-1 pathway, indicating that SKPs may be a promising candidate for the treatment of photodermatoses.
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Ramsauer, Anna Sophie, Garrett Louis Wachoski-Dark, Cornel Fraefel, Mathias Ackermann, Sabine Brandt, Paula Grest, Cameron Greig Knight, Claude Favrot, and Kurt Tobler. "Establishment of a Three-Dimensional In Vitro Model of Equine Papillomavirus Type 2 Infection." Viruses 13, no. 7 (July 19, 2021): 1404. http://dx.doi.org/10.3390/v13071404.

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There is growing evidence that equine papillomavirus type 2 (EcPV2) infection is etiologically associated with the development of genital squamous cell carcinoma (SCC) and precursor lesions in equids. However, the precise mechanisms underlying neoplastic progression remain unknown. To allow the study of EcPV2-induced carcinogenesis, we aimed to establish a primary equine cell culture model of EcPV2 infection. Three-dimensional (3D) raft cultures were generated from equine penile perilesional skin, plaques and SCCs. Using histological, molecular biological and immunohistochemical methods, rafts versus corresponding natural tissue sections were compared with regard to morphology, presence of EcPV2 DNA, presence and location of EcPV2 gene transcripts and expression of epithelial, mesenchymal and tumor/proliferation markers. Raft cultures from perilesional skin harboring only a few EcPV2-positive (EcPV2+) cells accurately recapitulated the differentiation process of normal skin, whilst rafts from EcPV2+ penile plaques were structurally organized but showed early hyperplasia. Rafts from EcPV2+ SCCs exhibited pronounced hyperplasia and marked dysplasia. Raft levels of EcPV2 oncogene transcription (E6/E7) and expression of tumor/proliferation markers p53, Ki67 and MCM7 expression positively correlated with neoplastic progression, again reflecting the natural situation. Three-dimensional raft cultures accurately reflected major features of corresponding ex vivo material, thus constituting a valuable new research model to study EcPV2-induced carcinogenesis.
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7

Fu, Tse-Kai, Ping-Hsueh Kuo, Yen-Chang Lu, Hsing-Ni Lin, Lily Hui-Ching Wang, Yu-Chun Lin, Yu-Chen Kao, Huey-Min Lai, and Margaret Dah-Tsyr Chang. "Cell Penetrating Peptide as a High Safety Anti-Inflammation Ingredient for Cosmetic Applications." Biomolecules 10, no. 1 (January 7, 2020): 101. http://dx.doi.org/10.3390/biom10010101.

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Cosmeceutical peptides have become an important topic in recent decades in both academic and industrial fields. Many natural or synthetic peptides with different biological functions including anti-ageing, anti-oxidation, anti-infection and anti-pigmentation have been developed and commercialized. Current cosmeceutical peptides have already satisfied most market demand, remaining: “cargos carrying skin penetrating peptide with high safety” still an un-met need. To this aim, a cell-penetrating peptide, CPPAIF, which efficiently transported cargos into epithelial cells was exanimated. CPPAIF was evaluated with cell model and 3D skin model following OECD guidelines without using animal models. As a highly stable peptide, CPPAIF neither irritated nor sensitized skin, also did not disrupt skin barrier. In addition, such high safety peptide had anti-inflammation activity without allergic effect. Moreover, cargo carrying activity of CPPAIF was assayed using HaCaT cell model and rapid CPPAIF penetration was observed within 30 min. Finally, CPPAIF possessed transepidermal activity in water in oil formulation without disruption of skin barrier. All evidences indicated that CPPAIF was an ideal choice for skin penetrating and its anti-inflammatory activity could improve skin condition, which made CPPAIF suitable and attractive for novel cosmeceutical product development.
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8

de Breij, Anna, Elisabeth M. Haisma, Marion Rietveld, Abdelouahab El Ghalbzouri, Peterhans J. van den Broek, Lenie Dijkshoorn, and Peter H. Nibbering. "Three-Dimensional Human Skin Equivalent as a Tool To Study Acinetobacter baumannii Colonization." Antimicrobial Agents and Chemotherapy 56, no. 5 (January 30, 2012): 2459–64. http://dx.doi.org/10.1128/aac.05975-11.

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ABSTRACTAcinetobacter baumanniican colonize body surfaces of hospitalized patients. From these sites, invasion into the host and spread to other patients and the hospital environment may occur. The eradication of the organism from the patient's skin is an important infection control strategy during epidemic and endemic episodes. In this study, a three-dimensional (3D), air-exposed human epidermal skin equivalent was exploited to studyAcinetobacterskin colonization. We characterized the adherence ofA. baumanniiATCC 19606TandAcinetobacter juniiRUH2228Tto and biofilm formation on the skin equivalent and the responses to these bacteria. Furthermore, we assessed the ability of the disinfectant chlorhexidine to decolonize the skin equivalents. The results revealed that both strains replicated on the stratum corneum for up to 72 h but did not invade the epidermis.A. baumannii, in contrast toA. junii, formed large biofilms on the stratum corneum. Bacterial colonization did not affect keratinocyte activation, proliferation, or differentiation, nor did it induce a strong inflammatory response. Disinfection with chlorhexidine solution resulted in complete eradication ofA. baumanniifrom the skin, without detrimental effects. This 3D model is a promising tool to study skin colonization and to evaluate the effects of novel disinfectant and antimicrobial strategies.
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Jahanshahi, Maryam, David Hamdi, Brent Godau, Ehsan Samiei, Carla Sanchez-Lafuente, Katie Neale, Zhina Hadisi, et al. "An Engineered Infected Epidermis Model for In Vitro Study of the Skin’s Pro-Inflammatory Response." Micromachines 11, no. 2 (February 23, 2020): 227. http://dx.doi.org/10.3390/mi11020227.

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Wound infection is a major clinical challenge that can significantly delay the healing process, can create pain, and requires prolonged hospital stays. Pre-clinical research to evaluate new drugs normally involves animals. However, ethical concerns, cost, and the challenges associated with interspecies variation remain major obstacles. Tissue engineering enables the development of in vitro human skin models for drug testing. However, existing engineered skin models are representative of healthy human skin and its normal functions. This paper presents a functional infected epidermis model that consists of a multilayer epidermis structure formed at an air-liquid interface on a hydrogel matrix and a three-dimensionally (3D) printed vascular-like network. The function of the engineered epidermis is evaluated by the expression of the terminal differentiation marker, filaggrin, and the barrier function of the epidermis model using the electrical resistance and permeability across the epidermal layer. The results showed that the multilayer structure enhances the electrical resistance by 40% and decreased the drug permeation by 16.9% in the epidermis model compared to the monolayer cell culture on gelatin. We infect the model with Escherichia coli to study the inflammatory response of keratinocytes by measuring the expression level of pro-inflammatory cytokines (interleukin 1 beta and tumor necrosis factor alpha). After 24 h of exposure to Escherichia coli, the level of IL-1β and TNF-α in control samples were 125 ± 78 and 920 ± 187 pg/mL respectively, while in infected samples, they were 1429 ± 101 and 2155.5 ± 279 pg/mL respectively. However, in ciprofloxacin-treated samples the levels of IL-1β and TNF-α without significant difference with respect to the control reached to 246 ± 87 and 1141.5 ± 97 pg/mL respectively. The robust fabrication procedure and functionality of this model suggest that the model has great potential for modeling wound infections and drug testing.
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Schollemann, Franziska, Carina Barbosa Pereira, Stefanie Rosenhain, Andreas Follmann, Felix Gremse, Fabian Kiessling, Michael Czaplik, and Mauren Abreu de Souza. "An Anatomical Thermal 3D Model in Preclinical Research: Combining CT and Thermal Images." Sensors 21, no. 4 (February 9, 2021): 1200. http://dx.doi.org/10.3390/s21041200.

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Even though animal trials are a controversial topic, they provide knowledge about diseases and the course of infections in a medical context. To refine the detection of abnormalities that can cause pain and stress to the animal as early as possible, new processes must be developed. Due to its noninvasive nature, thermal imaging is increasingly used for severity assessment in animal-based research. Within a multimodal approach, thermal images combined with anatomical information could be used to simulate the inner temperature profile, thereby allowing the detection of deep-seated infections. This paper presents the generation of anatomical thermal 3D models, forming the underlying multimodal model in this simulation. These models combine anatomical 3D information based on computed tomography (CT) data with a registered thermal shell measured with infrared thermography. The process of generating these models consists of data acquisition (both thermal images and CT), camera calibration, image processing methods, and structure from motion (SfM), among others. Anatomical thermal 3D models were successfully generated using three anesthetized mice. Due to the image processing improvement, the process was also realized for areas with few features, which increases the transferability of the process. The result of this multimodal registration in 3D space can be viewed and analyzed within a visualization tool. Individual CT slices can be analyzed axially, sagittally, and coronally with the corresponding superficial skin temperature distribution. This is an important and successfully implemented milestone on the way to simulating the internal temperature profile. Using this temperature profile, deep-seated infections and inflammation can be detected in order to reduce animal suffering.
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Loke, Amanda S. W., B. Jack Longley, Paul F. Lambert, and Megan E. Spurgeon. "A Novel In Vitro Culture Model System to Study Merkel Cell Polyomavirus–Associated MCC Using Three-Dimensional Organotypic Raft Equivalents of Human Skin." Viruses 13, no. 1 (January 19, 2021): 138. http://dx.doi.org/10.3390/v13010138.

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Merkel cell polyomavirus (MCPyV) is a human polyomavirus causally linked to the development of Merkel cell carcinoma (MCC), an aggressive malignancy that largely arises within the dermis of the skin. In this study, we recapitulate the histopathology of human MCC tumors in vitro using an organotypic (raft) culture system that is traditionally used to recapitulate the dermal and epidermal equivalents of skin in three dimensions (3D). In the optimal culture condition, MCPyV+ MCC cells were embedded in collagen between the epidermal equivalent comprising human keratinocytes and a dermal equivalent containing fibroblasts, resulting in MCC-like lesions arising within the dermal equivalent. The presence and organization of MCC cells within these dermal lesions were characterized through biomarker analyses. Interestingly, co-culture of MCPyV+ MCC together with keratinocytes specifically within the epidermal equivalent of the raft did not reproduce human MCC morphology, nor were any keratinocytes necessary for MCC-like lesions to develop in the dermal equivalent. This 3D tissue culture system provides a novel in vitro platform for studying the role of MCPyV T antigens in MCC oncogenesis, identifying additional factors involved in this process, and for screening potential MCPyV+ MCC therapeutic strategies.
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Zahia, Sofia, Begonya Garcia-Zapirain, and Adel Elmaghraby. "Integrating 3D Model Representation for an Accurate Non-Invasive Assessment of Pressure Injuries with Deep Learning." Sensors 20, no. 10 (May 21, 2020): 2933. http://dx.doi.org/10.3390/s20102933.

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Pressure injuries represent a major concern in many nations. These wounds result from prolonged pressure on the skin, which mainly occur among elderly and disabled patients. If retrieving quantitative information using invasive methods is the most used method, it causes significant pain and discomfort to the patients and may also increase the risk of infections. Hence, developing non-intrusive methods for the assessment of pressure injuries would represent a highly useful tool for caregivers and a relief for patients. Traditional methods rely on findings retrieved solely from 2D images. Thus, bypassing the 3D information deriving from the deep and irregular shape of this type of wounds leads to biased measurements. In this paper, we propose an end-to-end system which uses a single 2D image and a 3D mesh of the pressure injury, acquired using the Structure Sensor, and outputs all the necessary findings such as: external segmentation of the wound as well as its real-world measurements (depth, area, volume, major axis and minor axis). More specifically, a first block composed of a Mask RCNN model uses the 2D image to output the segmentation of the external boundaries of the wound. Then, a second block matches the 2D and 3D views to segment the wound in the 3D mesh using the segmentation output and generates the aforementioned real-world measurements. Experimental results showed that the proposed framework can not only output refined segmentation with 87% precision, but also retrieves reliable measurements, which can be used for medical assessment and healing evaluation of pressure injuries.
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Ivanova, Aleksandra, Kristina Ivanova, Luisa Fiandra, Paride Mantecca, Tiziano Catelani, Michal Natan, Ehud Banin, Gila Jacobi, and Tzanko Tzanov. "Antibacterial, Antibiofilm, and Antiviral Farnesol-Containing Nanoparticles Prevent Staphylococcus aureus from Drug Resistance Development." International Journal of Molecular Sciences 23, no. 14 (July 7, 2022): 7527. http://dx.doi.org/10.3390/ijms23147527.

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Multidrug antimicrobial resistance is a constantly growing health care issue associated with increased mortality and morbidity, and huge financial burden. Bacteria frequently form biofilm communities responsible for numerous persistent infections resistant to conventional antibiotics. Herein, novel nanoparticles (NPs) loaded with the natural bactericide farnesol (FSL NPs) are generated using high-intensity ultrasound. The nanoformulation of farnesol improved its antibacterial properties and demonstrated complete eradication of Staphylococcus aureus within less than 3 h, without inducing resistance development, and was able to 100% inhibit the establishment of a drug-resistant S. aureus biofilm. These antibiotic-free nano-antimicrobials also reduced the mature biofilm at a very low concentration of the active agent. In addition to the outstanding antibacterial properties, the engineered nano-entities demonstrated strong antiviral properties and inhibited the spike proteins of SARS-CoV-2 by up to 83%. The novel FSL NPs did not cause skin tissue irritation and did not induce the secretion of anti-inflammatory cytokines in a 3D skin tissue model. These results support the potential of these bio-based nano-actives to replace the existing antibiotics and they may be used for the development of topical pharmaceutic products for controlling microbial skin infections, without inducing resistance development.
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Martin H., Christian, Roberto Ibáñez, Louis-Félix Nothias, Andrés Mauricio Caraballo-Rodríguez, Pieter C. Dorrestein, and Marcelino Gutiérrez. "Metabolites from Microbes Isolated from the Skin of the Panamanian Rocket Frog Colostethus panamansis (Anura: Dendrobatidae)." Metabolites 10, no. 10 (October 13, 2020): 406. http://dx.doi.org/10.3390/metabo10100406.

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The Panamanian rocket frog Colostethus panamansis (family Dendrobatidae) has been affected by chytridiomycosis, a deadly disease caused by the fungus Batrachochytrium dendrobatidis (Bd). While there are still uninfected frogs, we set out to isolate microbes from anatomically distinct regions in an effort to create a cultivable resource within Panama for potential drug/agricultural/ecological applications that perhaps could also be used as part of a strategy to protect frogs from infections. To understand if there are specific anatomies that should be explored in future applications of this resource, we mapped skin-associated bacteria of C. panamansis and their metabolite production potential by mass spectrometry on a 3D model. Our results indicate that five bacterial families (Enterobacteriaceae, Comamonadaceae, Aeromonadaceae, Staphylococcaceae and Pseudomonadaceae) dominate the cultivable microbes from the skin of C. panamansis. The combination of microbial classification and molecular analysis in relation to the anti-Bd inhibitory databases reveals the resource has future potential for amphibian conservation.
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Mohammadi, Farnoush, Abbas Azari, Nariman Nikparto, and Heliya Ziaei. "Reconstruction of the Occipital and Parietal Congenital Defect with 3D Custom-Made Titanium Prosthesis: A Case Report with Four and a Half Years of Follow-Up and a Brief Review of Literature." Case Reports in Dentistry 2021 (October 20, 2021): 1–6. http://dx.doi.org/10.1155/2021/7027701.

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Management of patients with congenital skull defects requires a multidisciplinary approach. Considering the defect’s location and size, brain protection, and the cosmetic outcome makes such reconstructions challenging. Due to limited resemblance to skull contour and donor site morbidity of autogenous bone grafts, alloplastic materials are widely used for skull reconstructions. Titanium alloys have proper strength values, low infection rates, favorable osseointegration property, and excellent marginal adaptability when manufactured by computer-aided design (CAD) and computer-aided manufacturing (CAM). A 13-year-old female patient presented with congenital defects at the superior third of occipital bone and posterior thirds of the bilateral parietal bones. On CT scan, the exact size and shape of the defect were determined. Using CAD/CAM, a 3D virtual model of the prosthesis was designed and then printed with titanium alloy (TiAl6V4) via additive manufacturing method. The prosthesis was placed on the defect in a total surgery time of only 90 minutes. On 4.5 years of follow-up, the contour of the skull was ideal and the skin over the defect and neurologic status was intact. Due to their biocompatibility and rigidity, custom-made titanium prostheses are promising options for reconstructing complex skull defects.
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van Gent, Miriam E., Tom van Baaren, Sylvia N. Kłodzińska, Muhanad Ali, Natasja Dolezal, Bjorn R. van Doodewaerd, Erik Bos, et al. "Encapsulation of SAAP-148 in Octenyl Succinic Anhydride-Modified Hyaluronic Acid Nanogels for Treatment of Skin Wound Infections." Pharmaceutics 15, no. 2 (January 28, 2023): 429. http://dx.doi.org/10.3390/pharmaceutics15020429.

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Chronic wound infections colonized by bacteria are becoming more difficult to treat with current antibiotics due to the development of antimicrobial resistance (AMR) as well as biofilm and persister cell formation. Synthetic antibacterial and antibiofilm peptide (SAAP)-148 is an excellent alternative for treatment of such infections but suffers from limitations related to its cationic peptidic nature and thus instability and possible cytotoxicity, resulting in a narrow therapeutic window. Here, we evaluated SAAP-148 encapsulation in nanogels composed of octenyl succinic anhydride (OSA)-modified hyaluronic acid (HA) to circumvent these limitations. SAAP-148 was efficiently (>98%) encapsulated with high drug loading (23%), resulting in monodispersed anionic OSA-HA nanogels with sizes ranging 204–253 nm. Nanogel lyophilization in presence of polyvinyl alcohol maintained their sizes and morphology. SAAP-148 was sustainedly released from lyophilized nanogels (37–41% in 72 h) upon reconstitution. Lyophilized SAAP-148-loaded nanogels showed similar antimicrobial activity as SAAP-148 against planktonic and biofilm-residing AMR Staphylococcus aureus and Acinetobacter baumannii. Importantly, formulated SAAP-148 showed reduced cytotoxicity against human erythrocytes, primary human skin fibroblasts and human keratinocytes. Additionally, lyophilized SAAP-148-loaded nanogels eradicated AMR S. aureus and A. baumannii colonizing a 3D human epidermal model, without inducing any cytotoxicity in contrast to SAAP-148. These findings indicate that OSA-HA nanogels increase SAAP-148′s therapeutic potential for treatment of skin wound infections.
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Ali, Muhanad, Miriam E. van Gent, Amy M. de Waal, Bjorn R. van Doodewaerd, Erik Bos, Roman I. Koning, Robert A. Cordfunke, Jan Wouter Drijfhout, and Peter H. Nibbering. "Physical and Functional Characterization of PLGA Nanoparticles Containing the Antimicrobial Peptide SAAP-148." International Journal of Molecular Sciences 24, no. 3 (February 2, 2023): 2867. http://dx.doi.org/10.3390/ijms24032867.

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Synthetic antimicrobial and antibiofilm peptide (SAAP-148) commits significant antimicrobial activities against antimicrobial resistant (AMR) planktonic bacteria and biofilms. However, SAAP-148 is limited by its low selectivity index, i.e., ratio between cytotoxicity and antimicrobial activity, as well as its bioavailability at infection sites. We hypothesized that formulation of SAAP-148 in PLGA nanoparticles (SAAP-148 NPs) improves the selectivity index due to the sustained local release of the peptide. The aim of this study was to investigate the physical and functional characteristics of SAAP-148 NPs and to compare the selectivity index of the formulated peptide with that of the peptide in solution. SAAP-148 NPs displayed favorable physiochemical properties [size = 94.1 ± 23 nm, polydispersity index (PDI) = 0.08 ± 0.1, surface charge = 1.65 ± 0.1 mV, and encapsulation efficiency (EE) = 86.7 ± 0.3%] and sustained release of peptide for up to 21 days in PBS at 37 °C. The antibacterial and cytotoxicity studies showed that the selectivity index for SAAP-148 NPs was drastically increased, by 10-fold, regarding AMR Staphylococcus aureus and 20-fold regarding AMR Acinetobacter baumannii after 4 h. Interestingly, the antibiofilm activity of SAAP-148 NPs against AMR S. aureus and A. baumannii gradually increased overtime, suggesting a dose–effect relationship based on the peptide’s in vitro release profile. Using 3D human skin equivalents (HSEs), dual drug SAAP-148 NPs and the novel antibiotic halicin NPs provided a stronger antibacterial response against planktonic and cell-associated bacteria than SAAP-148 NPs but not halicin NPs after 24 h. Confocal laser scanning microscopy revealed the presence of SAAP-148 NPs on the top layers of the skin models in close proximity to AMR S. aureus at 24 h. Overall, SAAP-148 NPs present a promising yet challenging approach for further development as treatment against bacterial infections.
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Pozuelos, Giovanna L., Matine Rubin, Samantha Vargas, Erik Ramirez, Dhiresh Bandaru, Jihui Sha, James Wohlschlegel, and Prue Talbot. "Nicotine Affects Multiple Biological Processes in EpiDermTM Organotypic Tissues and Keratinocyte Monolayers." Atmosphere 13, no. 5 (May 16, 2022): 810. http://dx.doi.org/10.3390/atmos13050810.

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Dermal exposure to nicotine is common due to the widespread use of tobacco products. Here, we assessed the effects of nicotine at concentrations found in thirdhand smoke (THS) contaminated environments and electronic cigarette (EC) spills or leaks on a 3D human skin model (EpiDermTM) and on submerged keratinocyte cultures. Air liquid interface treatment of EpiDermTM with 10 or 400 μg/mL of nicotine for 24 h followed by proteomics analysis showed altered pathways related to inflammation, protein synthesis, cell–cell adhesion, apoptosis, and mitochondrial function. Submerged cultured keratinocytes were used to validate the proteomics data and further characterize the response of skin cells to nicotine. Mitochondrial phenotype changed from networked to punctate in keratinocytes treated with 10 or 400 μg/mL of nicotine for 48 h and 24 h, respectively. After 72 h, all concentrations of nicotine caused a significant decrease in the networked phenotype. In Western blots, keratinocytes exposed to 400 μg/mL of nicotine had a significant decrease in mitofusin 2, while mitofusin 1 decreased after 72 h. The shift from networked to punctate mitochondria correlated with a decrease in mitofusin 1/2, a protein needed to establish and maintain the networked phenotype. Mitochondrial changes were reversible after a 24 h recovery period. Peroxisomes exposed to 400 μg/mL of nicotine for 24 h became enlarged and were fewer in number. Nicotine concentrations in THS and EC spills altered the proteome profile in EpiDermTM and damaged organelles including mitochondria and peroxisomes, which are involved in ROS homeostasis. These changes may exacerbate skin infections, inhibit wound healing, and cause oxidative damage to cells in the skin.
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Rehman, Abdur, Xiukang Wang, Sajjad Ahmad, Farah Shahid, Sidra Aslam, Usman Ali Ashfaq, Faris Alrumaihi, et al. "In Silico Core Proteomics and Molecular Docking Approaches for the Identification of Novel Inhibitors against Streptococcus pyogenes." International Journal of Environmental Research and Public Health 18, no. 21 (October 28, 2021): 11355. http://dx.doi.org/10.3390/ijerph182111355.

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Streptococcus pyogenes is a significant pathogen that causes skin and upper respiratory tract infections and non-suppurative complications, such as acute rheumatic fever and post-strep glomerulonephritis. Multidrug resistance has emerged in S. pyogenes strains, making them more dangerous and pathogenic. Hence, it is necessary to identify and develop therapeutic methods that would present novel approaches to S. pyogenes infections. In the current study, a subtractive proteomics approach was employed to core proteomes of four strains of S. pyogenes using several bioinformatic software tools and servers. The core proteome consists of 1324 proteins, and 302 essential proteins were predicted from them. These essential proteins were analyzed using BLASTp against human proteome, and the number of potential targets was reduced to 145. Based on subcellular localization prediction, 46 proteins with cytoplasmic localization were chosen for metabolic pathway analysis. Only two cytoplasmic proteins, i.e., chromosomal replication initiator protein DnaA and two-component response regulator (TCR), were discovered to have the potential to be novel drug target candidates. Three-dimensional (3D) structure prediction of target proteins was carried out via the Swiss Model server. Molecular docking approach was employed to screen the library of 1000 phytochemicals against the interacting residues of the target proteins through the MOE software. Further, the docking studies were validated by running molecular dynamics simulation and highly popular binding free energy approaches of MM-GBSA and MM-PBSA. The findings revealed a promising candidate as a novel target against S. pyogenes infections.
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Santacruz, Laura L. Mendez, Xavier S. Bittman-Soto, Keishla M. Rodriguez-Martir, Jesus M. Padilla Escalona, Esther Peterson, and Carmen Maldonado-Vlaar. "Abstract 5673: The role of NMDA receptors subunits in the progression of inflammatory breast cancer (IBC)." Cancer Research 82, no. 12_Supplement (June 15, 2022): 5673. http://dx.doi.org/10.1158/1538-7445.am2022-5673.

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Abstract Inflammatory Breast Cancer (IBC) has a 73% incidence of metastasis to the brain as compared to other cancer types like breast, lung, and bone cancer. Previous research showed that tumor cells from different breast cancer subtypes (-HR/-HER2) and (-HR/+ HER2) have a high incidence of crossing the blood-brain barrier and inducing increased expression of glutamate receptors NMDA subunits (NMDAR1 and NMDR2) in the brain. IBC is the most aggressive and rare type of breast cancer. The absence of a solid tumor is replaced by swelling, redness, and skin changes, resulting in many cases in misdiagnosis of an infection in the invasion and migration phase; this type of cancer blocks blood and lymphatic vessels in the breast's skin, causing local inflammation and rapid metastasis. However, little is known of the role that these glutamatergic receptors have in the development and/or progression of IBC. The present work provides a new understanding of the cellular and molecular effects NMDA receptors (NMDAR) have on oncogenic phenotypes in IBC. The detection and quantification of the NMDAR were evaluated by RT-qPCR, Western blot, and immunofluorescence (IF) techniques in deferments breast cancer cell lines (MCF7, MDA-MB-231) and IBC cell lines (SUM149, and SUM190). Also, NMDAR antagonists (memantine and dizocilpine "MK-801") were used in 2D and 3D cell cultures to see the pro-oncogenic effects of migration and proliferation in cell models. In addition to this, the autocrine regulation of Glutamate in IBC cell lines is verified. Results showed a significant increase in the expression of NMDARs in IBC cell lines. In the functional cell culture assays with NMDAR antagonists, a decrease in migration and proliferation in IBC cell lines was found. These findings may be related to the high aggressiveness and the high rate of metastasis by IBC within the brain. Our results have high clinical relevance since having extensive knowledge of the role of NMDARs in IBC progression could complement therapeutic approaches for patients with IBC. Citation Format: Laura L. Mendez Santacruz, Xavier S. Bittman-Soto, Keishla M. Rodriguez-Martir, Jesus M. Padilla Escalona, Esther Peterson, Carmen Maldonado-Vlaar. The role of NMDA receptors subunits in the progression of inflammatory breast cancer (IBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5673.
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Cadau, Sebastien, Sabrina Leoty-Okombi, Schinichi Nakajima, and Valerie Andre-Frei. "Endothelialized and innervated 3D skin glycated model." Journal of Dermatological Science 84, no. 1 (October 2016): e147. http://dx.doi.org/10.1016/j.jdermsci.2016.08.439.

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22

Kaluzhny, Yulia, Patrick Hayden, Victor Karetsky, Mitchell Klausner, and John Sheasgreen. "Skin specific micronucleus assay in the EpiDerm™ human 3D skin model." Toxicology Letters 172 (October 2007): S171. http://dx.doi.org/10.1016/j.toxlet.2007.05.438.

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23

Yusufu, Dilidaer, Erin Magee, Brendan Gilmore, and Andrew Mills. "Non-invasive, 3D printed, colourimetric, early wound-infection indicator." Chemical Communications 58, no. 3 (2022): 439–42. http://dx.doi.org/10.1039/d1cc06147j.

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CO2 indicator (blue to yellow) flags up rapid microbial growth and colonisation (green dots), due to microbial respiration, on damaged pig skin (red on pink), covered with a lint dressing (grey) as a precursor to infection.
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Kwak, Bong Shin, Wonho Choi, Joong-won Jeon, Jong-In Won, Gun Yong Sung, Bumsang Kim, and Jong Hwan Sung. "In vitro 3D skin model using gelatin methacrylate hydrogel." Journal of Industrial and Engineering Chemistry 66 (October 2018): 254–61. http://dx.doi.org/10.1016/j.jiec.2018.05.037.

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25

Park, Gyeong-Mi, and Young-Bong Kim. "Integrated 3D Skin Color Model for Robust Skin Color Detection of Various Races." Journal of the Korea Contents Association 9, no. 5 (May 28, 2009): 1–12. http://dx.doi.org/10.5392/jkca.2009.9.5.001.

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Wang, Jiahui, Hideo Saito, Shinji Ozawa, Tomohiro Kuwahara, Toyonobu Yamashita, and Motoji Takahashi. "Surface Extraction of Skin Inner Tissue Interface from 3D Volumetric Images of Human Skin via 3D Active Contour Model." IEEJ Transactions on Electronics, Information and Systems 125, no. 5 (2005): 756–64. http://dx.doi.org/10.1541/ieejeiss.125.756.

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Choi, Jonghye, Hyejin Kim, Jinhee Choi, Seung Min Oh, Jeonggue Park, and Kwangsik Park. "Skin corrosion and irritation test of sunscreen nanoparticles using reconstructed 3D human skin model." Environmental Health and Toxicology 29 (July 21, 2014): e2014004. http://dx.doi.org/10.5620/eht.2014.29.e2014004.

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28

Chau, David Y. S., Claire Johnson, Sheila MacNeil, John W. Haycock, and Amir M. Ghaemmaghami. "The development of a 3D immunocompetent model of human skin." Biofabrication 5, no. 3 (July 23, 2013): 035011. http://dx.doi.org/10.1088/1758-5082/5/3/035011.

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29

Boonnak, Kobporn, and Mary A. Marovich. "Model for local skin defense against Dengue virus infection." Future Virology 4, no. 3 (May 2009): 225–29. http://dx.doi.org/10.2217/fvl.09.6.

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30

Pratt, Lisa F., Matthew J. Troese, Horst W. Fuchs, Oliver Engelking, and George L. DeGeorge. "The highly differentiated 3D epidermal skin model (epiCS®) to characterize skin sensitizers in mixtures." Toxicology Letters 229 (September 2014): S141. http://dx.doi.org/10.1016/j.toxlet.2014.06.497.

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31

Nakatani, Hajime, and Katsutoshi Hori. "Establishing a Percutaneous Infection Model Using Zebrafish and a Salmon Pathogen." Biology 10, no. 2 (February 22, 2021): 166. http://dx.doi.org/10.3390/biology10020166.

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To uncover the relationship between skin bacterial flora and pathogen infection, we developed a percutaneous infection model using zebrafish and Yersinia ruckeri, a pathogen causing enteric redmouth disease in salmon and in trout. Pathogen challenge, either alone or together with pricking by a small needle, did not cause infection of the fish. However, cold stress given by water temperature shift from the optimum 28 °C for zebrafish to 20 °C caused fatal infection of injured fish following pathogen challenge. We investigated the effects of cold stress, injury, and pathogen challenge, alone and in combination, on fish skin bacterial flora using 16S rDNA metagenomics. We found that cold stress drastically altered the skin bacterial flora, which was dominated by Y. ruckeri on infected fish. In addition, fish whose intrinsic skin bacterial flora was disrupted by antibiotics had their skin occupied by Y. ruckeri following a challenge with this pathogen, although the fish survived without injury to create a route for invasion into the fish body. Our results suggest that the intrinsic skin bacterial flora of fish protects them from pathogen colonization, and that its disruption by stress allows pathogens to colonize and dominate their skin.
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Pachera, E., G. Kania, A. Juengel, M. Calcagni, and O. Distler. "OP0248 DEVELOPMENT OF A 3D SKIN MICROTISSUE MODEL FOR FIBROTIC DISEASES." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 151.2–152. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3306.

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Background:Traditional preclinical approaches, such as two-dimensional cell culture and animal models, are often inadequate to mimic the pathophysiological features of complex diseases such as systemic sclerosis (SSc). Human specific targets, such as the recently described pro-fibrotic long non coding RNA (lncRNA) H19X1, are becoming increasingly relevant in preclinical research, creating the need of new strategies and tools in translational medicine. The employment of novel three-dimensional (3D) culture systems, where multiple cell types are included, is filling an important gap left by the traditional preclinical methods.Objectives:To develop an easy to produce 3D fibrotic skin microtissues model for translational proof of concept studies.Methods:Two thousand five hundred dermal fibroblasts isolated from skin of SSc patients were seeded in ultra-low attachment 96-well plates. Fibroblast were let to aggregate into spheres for 48h. Two thousand five hundred primary normal human keratinocytes were added to the culture and let to layer onto the fibroblast spheres for 72h. H19X silencing experiments were used as proof of concept studies. H19X silencing with antisense oligonucleotides or transfections with a scrambled control were performed in fibroblasts prior to the sphere formation for 24h. TGFβ (10 ng/ml) was added to microtissue to exacerbate the fibrotic phenotype. Haematoxylin eosin staining as well as immunohistochemistry staining for vimentin and cytokeratin 10 was performed. Skin microtissues were processed for RNA and protein isolation. Pro-collagen Iα1 and fibronectin were quantified in the supernatants with ELISA.Results:The microtissues presented a core of SSc fibroblast as revealed by vimentin staining and an external layer of keratinocytes as revealed by cytokeratin 10 staining, mimicking the human skin architecture. Gene expression analysis following TGFβ stimulation displayed induced expression of extracellular matrix gene COL1A1 (p=0.044) and the myofibroblast marker ACTA2 (p=0.018), indicating that the microtissues were able to develop a fibrotic response. Microtissues, where H19X was silenced, displayed reduced gene expression of COL1A1 and ACTA2 after TGFβ stimulation (COL1A1 p=0.007, ACTA2 p=0.045). Additionally, H19X silencing led to lower levels of αSMA protein expression (p=0.009) and pro-collagen1α1 secretion (p=0.039) in the supernatant of the microtissue cultures as revealed by Western Blot and ELISA, respectively. FN1 expression and fibronectin protein levels were not significantly reduced in the microtissues after H19X silencing.Conclusion:We were able to produce a 3D microtissue resembling skin architecture that can respond to fibrotic stimuli. Knockdown experiments of pro-fibrotic lncRNA H19X confirmed the potential of the model as screening platform for novel pro-fibrotic effectors. A future aim will be to optimize the model for high-throughput automated screening platforms.References:[1]Pachera, E., et al. (2020). “Long noncoding RNA H19X is a key mediator of TGF-β–driven fibrosis.” The Journal of Clinical Investigation 130(9): 4888-4905.Disclosure of Interests:Elena Pachera: None declared, Gabriela Kania: None declared, Astrid Juengel: None declared, Maurizio Calcagni Speakers bureau: Arthrex, Consultant of: Medartis, Arthrex, SilkBiomaterials, Grant/research support from: Medartis, Oliver Distler Speakers bureau: Actelion, Bayer, Boehringer Ingelheim, Medscape, Novartis, Roche, Consultant of: Abbvie, Actelion, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, ChemomAb, Corpuspharma, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, -Kymera, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi, UCB, Grant/research support from: Abbvie, Actelion, Bayer, Boehringer Ingelheim, Kymera Therapeutics, Mitsubishi Tanabe
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De Oliveira Vilaca, Luis Miguel, Michel C. Milinkovitch, and Ricardo Ruiz-Baier. "Numerical approximation of a 3D mechanochemical interface model for skin patterning." Journal of Computational Physics 384 (May 2019): 383–404. http://dx.doi.org/10.1016/j.jcp.2019.01.023.

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34

Chaib, Y., S. Larochelle, C. Mainzer, B. Closs, C. Gilbert, and V. Moulin. "902 A new 3D immunocompetent skin model reconstructed by tissue engineering." Journal of Investigative Dermatology 139, no. 5 (May 2019): S156. http://dx.doi.org/10.1016/j.jid.2019.03.978.

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35

Kovalovs, Andrejs, Evgeny Barkanov, and Sergejs Gluhihs. "ACTIVE TWIST OF MODEL ROTOR BLADES WITH D-SPAR DESIGN." TRANSPORT 22, no. 1 (March 31, 2007): 38–44. http://dx.doi.org/10.3846/16484142.2007.9638094.

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The design methodology based on the planning of experiments and response surface technique has been developed for an optimum placement of Macro Fiber Composite (MFC) actuators in the helicopter rotor blades. The baseline helicopter rotor blade consists of D‐spar made of UD GFRP, skin made of +450/‐450 GFRP, foam core, MFC actuators placement on the skin and balance weight. 3D finite element model of the rotor blade has been built by ANSYS, where the rotor blade skin and spar “moustaches” are modeled by the linear layered structural shell elements SHELL99, and the spar and foam ‐ by 3D 20‐node structural solid elements SOLID 186. The thermal analyses of 3D finite element model have been developed to investigate an active twist of the helicopter rotor blade. Strain analogy between piezoelectric strains and thermally induced strains is used to model piezoelectric effects. The optimisation results have been obtained for design solutions, connected with the application of active materials, and checked by the finite element calculations.
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36

Prabhakara, Ranjani, Oded Foreman, Roberto De Pascalis, Gloria M. Lee, Roger D. Plaut, Stanley Y. Kim, Scott Stibitz, Karen L. Elkins, and Tod J. Merkel. "Epicutaneous Model of Community-Acquired Staphylococcus aureus Skin Infections." Infection and Immunity 81, no. 4 (February 4, 2013): 1306–15. http://dx.doi.org/10.1128/iai.01304-12.

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ABSTRACTStaphylococcus aureusis one of the most common etiological agents of community-acquired skin and soft tissue infection (SSTI). Although the majority ofS. aureuscommunity-acquired SSTIs are uncomplicated and self-clearing in nature, some percentage of these cases progress into life-threatening invasive infections. Current animal models ofS. aureusSSTI suffer from two drawbacks: these models are a better representation of hospital-acquired SSTI than community-acquired SSTI, and they involve methods that are difficult to replicate. For these reasons, we sought to develop a murine model of community-acquired methicillin-resistantS. aureusSSTI (CA-MRSA SSTI) that can be consistently reproduced with a high degree of precision. We utilized this model to begin to characterize the host immune response to this type of infection. We infected mice via epicutaneous challenge of the skin on the outer ear pinna using Morrow-Brown allergy test needles coated inS. aureusUSA300. When mice were challenged in this model, they developed small, purulent, self-clearing lesions with predictable areas of inflammation that mimicked a human infection. CFU in the ear pinna peaked at day 7 before dropping by day 14. The Th1 and Th17 cytokines gamma interferon (IFN-γ), interleukin-12 (IL-12) p70, tumor necrosis factor alpha (TNF-α), IL-17A, IL-6, and IL-21 were all significantly increased in the draining lymph node of infected mice, and there was neutrophil recruitment to the infection site.In vivoneutrophil depletion demonstrated that neutrophils play a protective role in preventing bacterial dissemination and fatal invasive infection.
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Chung, Eunkyung, Hyeongwon Choi, Ji Eun Lim, and Youngsook Son. "Development of skin inflammation test model by co-culture of reconstituted 3D skin and RAW264.7 cells." Tissue Engineering and Regenerative Medicine 11, no. 1 (January 25, 2014): 87–92. http://dx.doi.org/10.1007/s13770-013-1113-x.

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38

Dimitrov, Sabcho D., Lawrence K. Low, Grace Y. Patlewicz, Petra S. Kern, Gergana D. Dimitrova, Mike H. I. Comber, Richard D. Phillips, Jay Niemela, Paul T. Bailey, and Ovanes G. Mekenyan. "Skin Sensitization: Modeling Based on Skin Metabolism Simulation and Formation of Protein Conjugates." International Journal of Toxicology 24, no. 4 (July 2005): 189–204. http://dx.doi.org/10.1080/10915810591000631.

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A quantitative structure-activity relationship (QSAR) system for estimating skin sensitization potency has been developed that incorporates skin metabolism and considers the potential of parent chemicals and/or their activated metabolites to react with skin proteins. A training set of diverse chemicals was compiled and their skin sensitization potency assigned to one of three classes. These three classes were, significant, weak, or nonsensitizing. Because skin sensitization potential depends upon the ability of chemicals to react with skin proteins either directly or after appropriate metabolism, a metabolic simulator was constructed to mimic the enzyme activation of chemicals in the skin. This simulator contains 203 hierarchically ordered spontaneous and enzyme controlled reactions. Phase I and phase II metabolism were simulated by using 102 and 9 principal transformations, respectively. The covalent interactions of chemicals and their metabolites with skin proteins were described by 83 reactions that fall within 39 alerting groups. The SAR/QSAR system developed was able to correctly classify about 80% of the chemicals with significant sensitizing effect and 72% of nonsensitizing chemicals. For some alerting groups, three-dimensional (3D)-QSARs were developed to describe the multiplicity of physicochemical, steric, and electronic parameters. These 3D-QSARs, so-called pattern recognition-type models, were applied each time a latent alerting group was identified in a parent chemical or its generated metabolite(s). The concept of the mutual influence amongst atoms in a molecule was used to define the structural domain of the skin sensitization model. The utility of the structural model domain and the predictability of the model were evaluated using sensitization potency data for 96 chemicals not used in the model building. The TIssue MEtabolism Simulator (TIMES) software was used to integrate a skin metabolism simulator and 3D-QSARs to evaluate the reactivity of chemicals thus predicting their likely skin sensitization potency.
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Jang, Kwang-Sik, Soon-Jung Park, Jong-Jin Choi, Ha-Na Kim, Kyung-Mi Shim, Mi-Jeong Kim, Il-Ho Jang, et al. "Therapeutic Efficacy of Artificial Skin Produced by 3D Bioprinting." Materials 14, no. 18 (September 9, 2021): 5177. http://dx.doi.org/10.3390/ma14185177.

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The skin protects the body from external barriers. Certain limitations exist in the development of technologies to rapidly prepare skin substitutes that are therapeutically effective in surgeries involving extensive burns and skin transplantation. Herein, we fabricated a structure similar to the skin layer by using skin-derived decellularized extracellular matrix (dECM) with bioink, keratinocytes, and fibroblasts using 3D-printing technology. The therapeutic effects of the produced skin were analyzed using a chimney model that mimicked the human wound-healing process. The 3D-printed skin substitutes exhibited rapid re-epithelialization and superior tissue regeneration effects compared to the control group. These results are expected to aid the development of technologies that can provide customized skin-replacement tissues produced easily and quickly via 3D-printing technology to patients.
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Wan, Wenbing, Feng Cai, Jiayu Huang, Shixuan Chen, and Qi Liao. "A skin-inspired 3D bilayer scaffold enhances granulation tissue formation and anti-infection for diabetic wound healing." Journal of Materials Chemistry B 7, no. 18 (2019): 2954–61. http://dx.doi.org/10.1039/c8tb03341b.

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We design and fabricate a bilayer 3D scaffold inspired by the structure of skin. The top layer is made of silver loaded GelMA cryogel to prevent infection. The bottom layer is made of a PDGF-BB loaded 3D printed scaffold to promotes angiogenesis and collagen deposition to accelerate granulation tissue formation.
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Wang, Jiahui, Hideo Saito, Shinji Ozawa, Tomohiro Kuwahara, Toyonobu Yamashita, and Motoji Takahashi. "Extraction of Dermo-Epidermal Surface from 3D Volumetric Images of Human Skin." International Journal of Image and Graphics 03, no. 04 (October 2003): 589–608. http://dx.doi.org/10.1142/s0219467803001202.

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Analysis of the dermo-epidermal surface in three-dimensions has great value in evaluating cosmetics. One approach is based on the active contour model, which is used extensively in computer vision and image processing applications, particularly for local object boundaries with closed curve form. The dermo-epidermal surface, however, is a plane with open form. We have developed a method of automatically extracting the dermo-epidermal surface from volumetric confocal microscopic images, as well as constructing a 3D visual model of the surface by using the geometric information contained in the control points. Our method is a 3D extension of the active contour model, so we call it the active open surface model (AOSM). The initial surface for AOSM is an open curve plane, guided by a 3D internal force, a 3D external constraint force, and a 3D image force, which pull it towards the objective surface. The proposed tecnique has been applied to extract actual dermo-epidermal surface in the given volumetric confocal microscopic images.
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Kang, Min, Kyohee Cho, Jae Lee, Lalita Subedi, Silvia Yumnam, and Sun Kim. "Effect of Resveratrol-Enriched Rice on Skin Inflammation and Pruritus in the NC/Nga Mouse Model of Atopic Dermatitis." International Journal of Molecular Sciences 20, no. 6 (March 21, 2019): 1428. http://dx.doi.org/10.3390/ijms20061428.

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Resveratrol-enriched rice (RR) was developed using genetic engineering to combine the properties of resveratrol and rice. To evaluate the effect of RR on pruritic skin inflammation in atopic dermatitis (AD)-like skin lesions, we used dinitrochlorobenzene (DNCB)-induced NC/Nga mice and an in vitro 3D skin model. Normal rice (NR), resveratrol, and RR were topically applied to mice dorsal skin, following which the dermatitis index and scratching frequency were calculated. Histological examination was performed by hematoxylin and eosin and immunohistochemistry staining of IL-31 level. The level of immunoglobulin E (IgE) and IL-31 in the serum was determined by enzyme-linked immunosorbent assay (ELISA). The cytotoxicity of RR and the expression levels of pro-inflammatory cytokines were also determined in cultured human keratinocytes and a 3D skin model. RR significantly reduced scratching frequency, decreased the dermatitis severity and trans-epidermal water loss (TEWL) and improved skin hydration in DNCB-induced NC/Nga mice. RR also significantly decreased serum IL-31 and IgE levels and suppressed the production of IL-6 in human keratinocytes and the 3D skin model. Our study indicates that the synergistic effect of rice and resveratrol manifested by the topical application of RR can serve as a potential alternative therapy for chronic skin inflammatory diseases such as AD.
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43

Kozhina, K. V., E. N. Volkova, I. N. Saburina, Sergey G. Morozov, I. M. Zurina, N. V. Kosheleva, A. A. Gorkun, and A. A. Grigorieva. "The influence of peptide bioregulators on skin aging in 3D culture model." Russian Journal of Skin and Venereal Diseases 19, no. 1 (February 15, 2016): 58–63. http://dx.doi.org/10.18821/1560-9588-2016-19-1-58-63.

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He effect of mesotherapy injection (Meso-Wharton R199TM) on the dermal fibroblasts culture, simulating condition of (mature) aging skin cells are studied. Material and methods. The culture of 4th passage fibroblasts (P4), that corresponds to young skin fibroblasts (control) and the culture of 18th passage fibroblasts (P18), that has all the signs of aging dermal fibroblasts (predominance of large cells, slow cell division) were used. Bioactivity was assessed by cell morphology, epithelium-mesenchyme plasticity and expression of fibroblasts markers: cytokeratin 19, elastin, a-smooth muscle actin (aSMA), PCNA (proliferation marker), collagen types I, III, IV and fibronectin. The formation of spheroids occur when fibroblasts P18 are cultivating with the injection medication, on terms comparable to the formation of spheroids from P4 young fibroblasts. From culture of fibroblasts P18, that was cultured without medication, does not form the full spheroid, but aggregation of cells and their gradual destruction with necrotic masses within the unit are observed. The presence of the medication stimulates the “rejuvenation” of cells and subsequent recovery of the mesenchyme-epithelial plasticity of cultured fibroblasts due to the reduced ability to synthesize sufficient to establish the amount of intercellular contacts the extracellular matrix components (fibronectin and collagen), which affects the ability to form spheroids. Culturing spheroids formed with the medication stimulates expression of elastin, collagen type IV, fibronectin extracellular matrix protein that supports the skin elasticity and superficial cells actively express cytokeratin 19. The study results clearly demonstrate the effectiveness of mesotherapeutic treatment for skin rejuvenation.
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44

Nagayama, Katsuya, Takahiro Uehara, Yasuko Amano, and Masanori Tanahashi. "3D Numerical Simulation of Epidermal Skin Turnover Process Using a Particle Model." Journal of Biosciences and Medicines 03, no. 03 (2015): 45–49. http://dx.doi.org/10.4236/jbm.2015.33007.

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45

S.P, Maniraj, and P. Sardar Maran. "3D-WAVELET TRANSFORM BASED SKIN CANCER CLASSIFICATION OF VGG-16 NETWORK MODEL." Indian Journal of Computer Science and Engineering 12, no. 5 (October 20, 2021): 1510–18. http://dx.doi.org/10.21817/indjcse/2021/v12i5/211205117.

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46

Ratovoson, Domoina, Vincent Huon, and Franck Jourdan. "A 3D finite element model for hyperthermia injury of blood-perfused skin." Computer Methods in Biomechanics and Biomedical Engineering 18, no. 3 (June 14, 2013): 233–42. http://dx.doi.org/10.1080/10255842.2013.790963.

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47

Van Gele, Mireille, Barbara Geusens, Reinhart Speeckaert, Peter Dynoodt, Barbara Vanhoecke, Karolien Van Den Bossche, and Jo Lambert. "Development of a 3D pigmented skin model to evaluate RNAi-induced depigmentation." Experimental Dermatology 20, no. 9 (June 24, 2011): 773–75. http://dx.doi.org/10.1111/j.1600-0625.2011.01319.x.

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48

Hill, David S., Neil D. P. Robinson, Matthew P. Caley, Mei Chen, Edel A. O'Toole, Jane L. Armstrong, Stefan Przyborski, and Penny E. Lovat. "A Novel Fully Humanized 3D Skin Equivalent to Model Early Melanoma Invasion." Molecular Cancer Therapeutics 14, no. 11 (September 1, 2015): 2665–73. http://dx.doi.org/10.1158/1535-7163.mct-15-0394.

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49

Ozdogan, Candan Yilmaz, Halime Kenar, Kivanc Emre Davun, Deniz Yucel, Emek Doger, and Sahin Alagoz. "An in vitro 3D diabetic human skin model from diabetic primary cells." Biomedical Materials 16, no. 1 (December 17, 2020): 015027. http://dx.doi.org/10.1088/1748-605x/abc1b1.

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50

CHANDA, ARNAB, and VINU UNNIKRISHNAN. "A REALISTIC 3D COMPUTATIONAL MODEL OF THE CLOSURE OF SKIN WOUND WITH INTERRUPTED SUTURES." Journal of Mechanics in Medicine and Biology 17, no. 01 (February 2017): 1750025. http://dx.doi.org/10.1142/s0219519417500257.

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Wounds or cuts are the most common form of skin injuries. While a shallow wound may heal over time, deep wounds often require clinical interventions such as suturing to ensure the wound closure and timely healing. To date, suturing practices are based on a surgeon's experience and there is no benchmark to what is right or wrong. In the literature, there have been few attempts to characterize wound closure and suture mechanics using simple 2D computational models. In our current work, for the first time, a realistic three-dimensional (3D) computational model of the skin with the two layers, namely the epidermis and dermis, have been developed. A 3D diamond shaped wound with a varying cross-section has been modeled, and interrupted sutures have been placed numerically in multiple steps to close the wound. Nonlinear hyperelastic material properties have been adopted for the skin and a skin pre-stress was applied bi-axially. The force requirements for each suture were estimated numerically using a novel suture pulling technique. The suture forces were found to lie in the range of 0–5 N with a maximum value at the center. Also, the center suture was observed to require an approximately four times pull force compared to the first end suture. All these findings provide important guidelines for suturing. Additionally, the suture force can be approximated as a polynomial function of the displacement. Given a wound geometry, wound depth, skin material properties, skin pre-stress, suture wire material and cross-sectional area, using our computational model, such a relationship can be used to estimate and characterize the suture force requirements accurately. To our knowledge, such a 3D computational model of skin wound closure with interrupted sutures have not been developed till date, and would be indispensable for planning robotic surgeries and improving clinical suturing practices in the future.
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