“…MitoQ is a modified coenzyme Q10 with a selective accumulation in mitochondria 16 . mTEM is a mitochondrial-targeting superoxide dismutase mimetic that possesses superoxide and alkyl radical scavenging properties 17, 18 . In order to evaluate the effects of each antioxidant, primary skin fibroblasts from a middle-aged normal individual and an HGPS patient were treated for 4 weeks.…”
Section: Resultsmentioning
confidence: 99%
“…These in vitro skin models consist of normal human-derived epidermal keratinocytes and fibroblasts cultured at the air-liquid interface on a semi-permeable tissue culture insert (Fig. 4B, details described in Material and Methods), which mimic human normal skin epidermis and are used as approved replacements of Draize rabbits for the in vitro skin irritation test (SIT) 18 .Figure 4MB increases tissue viability and shows no signs of irritation on the in vitro reconstructed 3D human skin. ( A ) H&E staining images showing two kinds of engineered human skin tissues (obtained from MatTek, Ashland, USA).…”
Oxidative stress is the major cause of skin aging that includes wrinkles, pigmentation, and weakened wound healing ability. Application of antioxidants in skin care is well accepted as an effective approach to delay the skin aging process. Methylene blue (MB), a traditional mitochondrial-targeting antioxidant, showed a potent ROS scavenging efficacy in cultured human skin fibroblasts derived from healthy donors and from patients with progeria, a genetic premature aging disease. In comparison with other widely used general and mitochondrial-targeting antioxidants, we found that MB was more effective in stimulating skin fibroblast proliferation and delaying cellular senescence. The skin irritation test, performed on an in vitro reconstructed 3D human skin model, indicated that MB was safe for long-term use, and did not cause irritation even at high concentrations. Application of MB to this 3D skin model further demonstrated that MB improved skin viability, promoted wound healing and increased skin hydration and dermis thickness. Gene expression analysis showed that MB treatment altered the expression of a subset of extracellular matrix proteins in the skin, including upregulation of elastin and collagen 2A1, two essential components for healthy skin. Altogether, our study suggests that MB has a great potential for skin care.
“…MitoQ is a modified coenzyme Q10 with a selective accumulation in mitochondria 16 . mTEM is a mitochondrial-targeting superoxide dismutase mimetic that possesses superoxide and alkyl radical scavenging properties 17, 18 . In order to evaluate the effects of each antioxidant, primary skin fibroblasts from a middle-aged normal individual and an HGPS patient were treated for 4 weeks.…”
Section: Resultsmentioning
confidence: 99%
“…These in vitro skin models consist of normal human-derived epidermal keratinocytes and fibroblasts cultured at the air-liquid interface on a semi-permeable tissue culture insert (Fig. 4B, details described in Material and Methods), which mimic human normal skin epidermis and are used as approved replacements of Draize rabbits for the in vitro skin irritation test (SIT) 18 .Figure 4MB increases tissue viability and shows no signs of irritation on the in vitro reconstructed 3D human skin. ( A ) H&E staining images showing two kinds of engineered human skin tissues (obtained from MatTek, Ashland, USA).…”
Oxidative stress is the major cause of skin aging that includes wrinkles, pigmentation, and weakened wound healing ability. Application of antioxidants in skin care is well accepted as an effective approach to delay the skin aging process. Methylene blue (MB), a traditional mitochondrial-targeting antioxidant, showed a potent ROS scavenging efficacy in cultured human skin fibroblasts derived from healthy donors and from patients with progeria, a genetic premature aging disease. In comparison with other widely used general and mitochondrial-targeting antioxidants, we found that MB was more effective in stimulating skin fibroblast proliferation and delaying cellular senescence. The skin irritation test, performed on an in vitro reconstructed 3D human skin model, indicated that MB was safe for long-term use, and did not cause irritation even at high concentrations. Application of MB to this 3D skin model further demonstrated that MB improved skin viability, promoted wound healing and increased skin hydration and dermis thickness. Gene expression analysis showed that MB treatment altered the expression of a subset of extracellular matrix proteins in the skin, including upregulation of elastin and collagen 2A1, two essential components for healthy skin. Altogether, our study suggests that MB has a great potential for skin care.
“…Similarly, EpiDerm™, EpiSkin™, SkinEthic™ and LabCyte™ models are considered as acceptable setups for skin irritation testing (OECD TG 439 (OECD, 2013)). A validation study addressing the skin irritation and sensitization potency of extracts from medical devices is furthermore underway (Casas et al, 2013;ISO, 2010;Coleman et al, 2015). Another example for the successful use of RhE is the phototoxicity assessment of topically applied substances and formulations, as demonstrated in the pre-validation study of the EpiDerm™ model (Liebsch et al, 1999).…”
Section: Tab 1: Models For Dermal Absorptionmentioning
SummaryModels of the outer epithelia of the human body -namely the skin, the intestine and the lung -have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.
“…This fact, along with the current requirement for bipolar extractions, 42 led the authors to believe that similar solvent systems would be mandated for alternative in vitro assays. 43 This article summarizes studies that have been performed to evaluate the ability of the SenCeeTox in vitro assay, complete with a new algorithm and scoring system in place, to identify skin sensitizers at concentrations similar to those of substances extracted from medical device polymers with bipolar solvents. Key findings from these proof-of-concept studies are presented and discussed.…”
In accordance with ISO 10993-10, the guinea pig maximization test, Buehler test, or murine local lymph node assay are used to assess the dermal sensitization potential of medical devices. The goal of our study was to determine if the in vitro SenCeeTox Ò assay could be an acceptable alternative. The SenCeeTox assay has previously been shown to accurately predict sensitization by monitoring viability, reactivity, and specific genes known to be crucial in dermal sensitization. Here, 10 known sensitizers were evaluated. Six were incorporated into medical device silicone (10% final concentration) and extracted in polar (physiological saline) and nonpolar (sesame oil) solvents in accordance with ISO 10993-12:2012. The four remaining compounds were added to extracts of plain silicone. This resulted in 20 test solutions (10 compounds in both saline and sesame oil). The assay controls were prepared directly in saline and sesame oil before exposure. EpiDermÔ tissues were exposed for 24 hours and tissue viability was assessed by LDH release. Expression of multiple genes controlled by Nrf2/ARE was assessed by qRT-PCR. The test solutions were also assessed for reactivity with glutathione. Eight of the 10 test samples (80%) were correctly identified as negative (nonsensitizers or weak sensitizers) or positive (moderate/strong/extreme sensitizers) in at least one of the two extracts, and 40% of the potencies were correctly identified. Our results indicate that the SenCeeTox assay combined with EpiDerm tissues can detect the presence of sensitizers in medical device extracts. If these findings are confirmed by further studies, then this model may be a suitable replacement for the animal methods currently used to evaluate medical device biocompatibility.
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