Abstract 1
Recapitulating hard-to-heal wounds on 3D skin equivalents
Kamaladasan Kalidasan
Abstract
Elevated oxidative stress has been known to disrupt cutaneous wound healing, and thus result in hard-to-heal wounds. Since the first report of oxidative stress more than 80 years ago, many studies have suggested that oxidative stress precipitates metabolic stress. The molecular mechanism(s) underlying such disease aetiologies are poorly understood. Herein, we used small molecule inhibitors to induce oxidative stress in 2D keratinocyte monolayers, and 3D De-Epidermized Dermis human skin equivalent (3D-DED HSE) models in vitro, to recapitulate the physiology and biochemistry of stress responses observed in hard-to-heal wounds in vivo. We found that inhibition of glutathione peroxidase, and quenching of glutathione in keratinocytes, activated the nuclear factor erythroid 2–related factor 2 (Nrf2) pathway. Coincidentally, we observed reduced cell migration. These data suggest that mediators of oxidative stress can be activated in primary human keratinocytes and result in modified keratinocyte function. We are evaluating responses to oxidative stress using the 3D-DED HSE in vitro model, where wound healing events after, superficial, partial thickness and full thickness injuries has been shown, previously. The reconstructed, human 3D skin technology offers a platform to interrogate the role of oxidative stress in hard-to-heal wounds.
Bio
I completed my PhD in Cell biology at NTU in 2019 where I had examined the role actin nucleators in the formation of actin rich structures called “Circular Dorsal Ruffles” and their downstream role in directed cell migration. I now look at cell proliferation and migration in the wound healing context on 3D DED HSE models. My interests lie in developing disease relevant 3D skin wound models to enable a wider range of target validation and candidate screening. Currently interested in recapitulating oxidative stress, altered pH and infection to develop target rich skin models just as one would see in hard-to-heal wounds. Outside research, I indulge in sports namely, soccer but that was before Covid!
Recapitulating hard-to-heal wounds on 3D skin equivalents
Kamaladasan Kalidasan
Abstract
Elevated oxidative stress has been known to disrupt cutaneous wound healing, and thus result in hard-to-heal wounds. Since the first report of oxidative stress more than 80 years ago, many studies have suggested that oxidative stress precipitates metabolic stress. The molecular mechanism(s) underlying such disease aetiologies are poorly understood. Herein, we used small molecule inhibitors to induce oxidative stress in 2D keratinocyte monolayers, and 3D De-Epidermized Dermis human skin equivalent (3D-DED HSE) models in vitro, to recapitulate the physiology and biochemistry of stress responses observed in hard-to-heal wounds in vivo. We found that inhibition of glutathione peroxidase, and quenching of glutathione in keratinocytes, activated the nuclear factor erythroid 2–related factor 2 (Nrf2) pathway. Coincidentally, we observed reduced cell migration. These data suggest that mediators of oxidative stress can be activated in primary human keratinocytes and result in modified keratinocyte function. We are evaluating responses to oxidative stress using the 3D-DED HSE in vitro model, where wound healing events after, superficial, partial thickness and full thickness injuries has been shown, previously. The reconstructed, human 3D skin technology offers a platform to interrogate the role of oxidative stress in hard-to-heal wounds.
Bio
I completed my PhD in Cell biology at NTU in 2019 where I had examined the role actin nucleators in the formation of actin rich structures called “Circular Dorsal Ruffles” and their downstream role in directed cell migration. I now look at cell proliferation and migration in the wound healing context on 3D DED HSE models. My interests lie in developing disease relevant 3D skin wound models to enable a wider range of target validation and candidate screening. Currently interested in recapitulating oxidative stress, altered pH and infection to develop target rich skin models just as one would see in hard-to-heal wounds. Outside research, I indulge in sports namely, soccer but that was before Covid!
Abstract 2
In-silico approach for predicting human skin penetration kinetics
Anjaiah Nalaparaju
Abstract
TBA
Bio
Anjaiah Nalaparaju is a research scientist at Institute of High Performance Computing, A*STAR Singapore. He obtained his Ph.D. from the Department of Chemical and Biomolecular Engineering at National University of Singapore. His research expertise is in multiscale simulations to combine the molecular scale computations with real scale problems. His current research is focused on employing multiscale simulation techniques to transdermal transport, in-silico skin modeling and specialty chemicals domain. In this talk, Dr Anjaiah Nalaparaju will be sharing a multiscale In-silico approach that allows formulators to simulate and visualize active ingredients’ permeation through the lipid lamellar structures at an atomistic scale and also to estimate the absorption and disposition kinetics in skin layers at larger-scale.
In-silico approach for predicting human skin penetration kinetics
Anjaiah Nalaparaju
Abstract
TBA
Bio
Anjaiah Nalaparaju is a research scientist at Institute of High Performance Computing, A*STAR Singapore. He obtained his Ph.D. from the Department of Chemical and Biomolecular Engineering at National University of Singapore. His research expertise is in multiscale simulations to combine the molecular scale computations with real scale problems. His current research is focused on employing multiscale simulation techniques to transdermal transport, in-silico skin modeling and specialty chemicals domain. In this talk, Dr Anjaiah Nalaparaju will be sharing a multiscale In-silico approach that allows formulators to simulate and visualize active ingredients’ permeation through the lipid lamellar structures at an atomistic scale and also to estimate the absorption and disposition kinetics in skin layers at larger-scale.
Abstract 3
Beyond skin deep: Using modelling and simulation to assess whole body tissue penetration of topically-applied actives
Eleanor Cheong
Abstract
TBA
Bio
Eleanor Cheong graduated from the National University of Singapore in 2020. During her postgraduate studies, her research primarily revolved around in silico physiologically based pharmacokinetic modelling in the domain of pharmaceuticals, where simulations of exposure variations in complex clinical scenarios were utilized to substantiate rational dose adjustments. Currently, as a research fellow in both SIFBI and A*SRL, she is interested to demonstrate how such virtual human models can similarly be employed to predict the whole-body kinetics of chemical and nutritional compounds. Insights gained from modelling will aid in defining levels of both safe and efficacious exposure. Within A*SRL, she has also had the opportunity to work on a project where the aim is to expand the application of the virtual human model to mechanistically understand and project the behavior of compounds in the systemic circulation after non-oral skin application. This would form the basis of the sharing at the SRSS Mini Symposium 2022.
Beyond skin deep: Using modelling and simulation to assess whole body tissue penetration of topically-applied actives
Eleanor Cheong
Abstract
TBA
Bio
Eleanor Cheong graduated from the National University of Singapore in 2020. During her postgraduate studies, her research primarily revolved around in silico physiologically based pharmacokinetic modelling in the domain of pharmaceuticals, where simulations of exposure variations in complex clinical scenarios were utilized to substantiate rational dose adjustments. Currently, as a research fellow in both SIFBI and A*SRL, she is interested to demonstrate how such virtual human models can similarly be employed to predict the whole-body kinetics of chemical and nutritional compounds. Insights gained from modelling will aid in defining levels of both safe and efficacious exposure. Within A*SRL, she has also had the opportunity to work on a project where the aim is to expand the application of the virtual human model to mechanistically understand and project the behavior of compounds in the systemic circulation after non-oral skin application. This would form the basis of the sharing at the SRSS Mini Symposium 2022.
Abstract 4
Development of Stable and Reproducible Hydrogel Scaffolds for in vitro 3D Reconstructed Skin Model
Kun Liang
Abstract
In vitro reconstructed human skin models are valuable tools in building our knowledge of skin physiology, function, skin disease pathology as well as assessing the pharmacological response of topical compounds. As Type I collagen is the most predominant component in the human dermal extracellular matrix, existing in vitro skin models are typically constructed using a dermal scaffold based on mammalian Type I collagen. However, these dermal equivalents generally have weak mechanical properties, which leads to uncontrollable contraction and poor formation of the overlying epidermal layer. To overcome this, we developed a dermal scaffold using fortified fish collagen Type I. Collagen derived from fish skin was chosen for its low cost, sustainable nature and minimal risk of zoonotic diseases transmission. When seeded with primary human fibroblasts in 3D culture, the fortified dermal scaffold demonstrated excellent biocompatibility and exhibited no visible contraction. Upon the addition of keratinocytes, the fortified collagen scaffold enabled the generation of a stable and reproducible reconstructed human skin equivalent with a healthy and differentiated epidermis. This dermal scaffold holds great potential for development of in vitro reconstructed human skin models of higher stability and consistency.
Bio
Kun is a material scientist in the model development team at A*SRL working on skin-related biomaterials research. He received his Ph.D. degree from NUS, followed by a postdoc fellowship in ETH Zürich. His research interest focuses on designing biomaterials for various healthcare applications such as drug delivery and tissue engineering. Some of his notable works have been published in top journals including Advanced Materials and Science Advances. He is also the recipient of several early-career researcher grants in related areas.
Development of Stable and Reproducible Hydrogel Scaffolds for in vitro 3D Reconstructed Skin Model
Kun Liang
Abstract
In vitro reconstructed human skin models are valuable tools in building our knowledge of skin physiology, function, skin disease pathology as well as assessing the pharmacological response of topical compounds. As Type I collagen is the most predominant component in the human dermal extracellular matrix, existing in vitro skin models are typically constructed using a dermal scaffold based on mammalian Type I collagen. However, these dermal equivalents generally have weak mechanical properties, which leads to uncontrollable contraction and poor formation of the overlying epidermal layer. To overcome this, we developed a dermal scaffold using fortified fish collagen Type I. Collagen derived from fish skin was chosen for its low cost, sustainable nature and minimal risk of zoonotic diseases transmission. When seeded with primary human fibroblasts in 3D culture, the fortified dermal scaffold demonstrated excellent biocompatibility and exhibited no visible contraction. Upon the addition of keratinocytes, the fortified collagen scaffold enabled the generation of a stable and reproducible reconstructed human skin equivalent with a healthy and differentiated epidermis. This dermal scaffold holds great potential for development of in vitro reconstructed human skin models of higher stability and consistency.
Bio
Kun is a material scientist in the model development team at A*SRL working on skin-related biomaterials research. He received his Ph.D. degree from NUS, followed by a postdoc fellowship in ETH Zürich. His research interest focuses on designing biomaterials for various healthcare applications such as drug delivery and tissue engineering. Some of his notable works have been published in top journals including Advanced Materials and Science Advances. He is also the recipient of several early-career researcher grants in related areas.
Abstract 5
Easing the friction: A study of skin surface characteristics in “Maskne” among health care workers
Madhumita Monisha
Abstract
Background: Maskne has become a challenge with universal mask-wearing being considered a critical component to limit the spread of SARS-CoV 2. Alteration of the skin microenvironment and its biophysical properties in addition to skin friction has been implicated in its pathogenesis.
Objective: To objectively measure the effects of medical masks on skin barrier integrity by measuring skin parameters such as trans-epidermal water loss (TEWL) and skin pH. Methods: A cross-sectional study consisting of 300 healthy healthcare workers were included in this study. We measured the parameters to assess skin barrier integrity (TEWL and skin pH) at baseline in the mask-covered and mask-uncovered areas of the face at baseline, 6 hours, and 12 hours of wearing masks. Results: TEWL and skin pH were significantly increased in the mask-covered areas after wearing it for 6 hrs and 12 hrs compared to baseline measurements (p< 0.05). By contrast, in the mask-uncovered areas, TEWL and pH showed no significant changes over time. Based on the analysis, the changes in skin characteristics over time were significantly different between mask covered and uncovered areas. Conclusion: Based on the alteration of skin characteristics with the prolonged use of masks/respirators, we conclude that a compromised skin barrier is key to the pathogenesis of Maskne. Thus, addressing the disruption of the skin barrier is indispensable in treating Maskne.
Bio
Monisha Madhumita is the chief dermatology resident (PGY-3) at Father Muller Medical College, Mangalore, India. She is the co-founder of Dermanalytica, a start-up working on harnessing artificial intelligence to improve dermatological health equity. She holds a masters in Global Health from Ghent University (Class of 2014). She is a writing scholar of the Harvard Graduate School of Arts (Class of 2021). Her research interests include occupational skin health, hair biology, global dermatology and AI. She loves cycling, writing and spending time with her dog, Rocky.
Easing the friction: A study of skin surface characteristics in “Maskne” among health care workers
Madhumita Monisha
Abstract
Background: Maskne has become a challenge with universal mask-wearing being considered a critical component to limit the spread of SARS-CoV 2. Alteration of the skin microenvironment and its biophysical properties in addition to skin friction has been implicated in its pathogenesis.
Objective: To objectively measure the effects of medical masks on skin barrier integrity by measuring skin parameters such as trans-epidermal water loss (TEWL) and skin pH. Methods: A cross-sectional study consisting of 300 healthy healthcare workers were included in this study. We measured the parameters to assess skin barrier integrity (TEWL and skin pH) at baseline in the mask-covered and mask-uncovered areas of the face at baseline, 6 hours, and 12 hours of wearing masks. Results: TEWL and skin pH were significantly increased in the mask-covered areas after wearing it for 6 hrs and 12 hrs compared to baseline measurements (p< 0.05). By contrast, in the mask-uncovered areas, TEWL and pH showed no significant changes over time. Based on the analysis, the changes in skin characteristics over time were significantly different between mask covered and uncovered areas. Conclusion: Based on the alteration of skin characteristics with the prolonged use of masks/respirators, we conclude that a compromised skin barrier is key to the pathogenesis of Maskne. Thus, addressing the disruption of the skin barrier is indispensable in treating Maskne.
Bio
Monisha Madhumita is the chief dermatology resident (PGY-3) at Father Muller Medical College, Mangalore, India. She is the co-founder of Dermanalytica, a start-up working on harnessing artificial intelligence to improve dermatological health equity. She holds a masters in Global Health from Ghent University (Class of 2014). She is a writing scholar of the Harvard Graduate School of Arts (Class of 2021). Her research interests include occupational skin health, hair biology, global dermatology and AI. She loves cycling, writing and spending time with her dog, Rocky.
Abstract 6
Elucidating the role of polymers in mild skin care formulation with experimental & simulation approach
Kwek Jin Wang
Abstract
TBA
Bio
Kwek Jin Wang is currently working as a scientist in the Formulated Products division in the Institute of Chemical and Engineering Sciences (ICES), A*STAR. He has a PhD (Chemical Engineering) from the National University of Singapore (NUS) in 2015. His main interests in research include evaluation of care formulations’ performances, liquid to powders transformation, characterization of powders, and modeling of bulk behaviours of powders.
Elucidating the role of polymers in mild skin care formulation with experimental & simulation approach
Kwek Jin Wang
Abstract
TBA
Bio
Kwek Jin Wang is currently working as a scientist in the Formulated Products division in the Institute of Chemical and Engineering Sciences (ICES), A*STAR. He has a PhD (Chemical Engineering) from the National University of Singapore (NUS) in 2015. His main interests in research include evaluation of care formulations’ performances, liquid to powders transformation, characterization of powders, and modeling of bulk behaviours of powders.
Abstract 7
The role of Polyketide synthase in Polyunsaturated Fatty Acid synthesis by Malassezia on human skin
Lee Shi Mun
Abstract
50% of the dandruff sufferers have Malassezia growing on their scalp. The widespread use of antifungal shampoo to eliminate Malassezia has alleviate dandruff indicating its involvement in dandruff formation. However, healthy scalps also harbour Malassezia, hence, its role in modulating the host’s responses leading to dandruff remains unclear. Metagenomics studies found Malassezia mostly localized on the oily regions of the human skin – this adaption has been hypothesized due to its inability to synthesize fatty acids essential for primary functions. Hence, these fatty acids have to be either made through other pathways or uptake mechanisms. Polyketide Synthase (PKS) also known as Polyunsaturated Fatty Acid (PUFA) Synthase, have been reported to share homology with animal Fatty acid synthase (FAS) and it is highly conserved among all Malassezia species. In other microbes, PKS is an alternative pathway for PUFA synthesis leading to the hypothesis that this is the enzyme responsible for making PUFAs in Malassezia. We have shown that knocking out PKS in Malassezia resulted in a reduced levels of Polyunsaturated Fatty Acids (PUFAs) as well as its secondary metabolites. This preliminary study have shown Malassezia PKS is involved in the synthesis of PUFAs and its secondary metabolites.
Bio
Shi Mun is a research officer in Thomas Dawson's lab and she have worked on the mechanisms involve in the antimicrobial susceptibility of Malassezia as well as the characterizing the mycovirus infecting them. Malassezia is the major fungus genus found on human skin and is known to be associated with dandruff, eczema and other skin disorders. However, little is known about the exact mechanism of how it interacts with its host. In this talk, she will share about the PKS, which is shown to involve in the synthesis of Polyunsaturated fatty acid and secondary metabolites wherein other species model are known to be involved in host-pathogen interaction.
The role of Polyketide synthase in Polyunsaturated Fatty Acid synthesis by Malassezia on human skin
Lee Shi Mun
Abstract
50% of the dandruff sufferers have Malassezia growing on their scalp. The widespread use of antifungal shampoo to eliminate Malassezia has alleviate dandruff indicating its involvement in dandruff formation. However, healthy scalps also harbour Malassezia, hence, its role in modulating the host’s responses leading to dandruff remains unclear. Metagenomics studies found Malassezia mostly localized on the oily regions of the human skin – this adaption has been hypothesized due to its inability to synthesize fatty acids essential for primary functions. Hence, these fatty acids have to be either made through other pathways or uptake mechanisms. Polyketide Synthase (PKS) also known as Polyunsaturated Fatty Acid (PUFA) Synthase, have been reported to share homology with animal Fatty acid synthase (FAS) and it is highly conserved among all Malassezia species. In other microbes, PKS is an alternative pathway for PUFA synthesis leading to the hypothesis that this is the enzyme responsible for making PUFAs in Malassezia. We have shown that knocking out PKS in Malassezia resulted in a reduced levels of Polyunsaturated Fatty Acids (PUFAs) as well as its secondary metabolites. This preliminary study have shown Malassezia PKS is involved in the synthesis of PUFAs and its secondary metabolites.
Bio
Shi Mun is a research officer in Thomas Dawson's lab and she have worked on the mechanisms involve in the antimicrobial susceptibility of Malassezia as well as the characterizing the mycovirus infecting them. Malassezia is the major fungus genus found on human skin and is known to be associated with dandruff, eczema and other skin disorders. However, little is known about the exact mechanism of how it interacts with its host. In this talk, she will share about the PKS, which is shown to involve in the synthesis of Polyunsaturated fatty acid and secondary metabolites wherein other species model are known to be involved in host-pathogen interaction.
Abstract 6
Elucidating the role of polymers in mild skin care formulation with experimental & simulation approach
Kwek Jin Wang
Abstract
TBA
Bio
Kwek Jin Wang is currently working as a scientist in the Formulated Products division in the Institute of Chemical and Engineering Sciences (ICES), A*STAR. He has a PhD (Chemical Engineering) from the National University of Singapore (NUS) in 2015. His main interests in research include evaluation of care formulations’ performances, liquid to powders transformation, characterization of powders, and modeling of bulk behaviours of powders.
Elucidating the role of polymers in mild skin care formulation with experimental & simulation approach
Kwek Jin Wang
Abstract
TBA
Bio
Kwek Jin Wang is currently working as a scientist in the Formulated Products division in the Institute of Chemical and Engineering Sciences (ICES), A*STAR. He has a PhD (Chemical Engineering) from the National University of Singapore (NUS) in 2015. His main interests in research include evaluation of care formulations’ performances, liquid to powders transformation, characterization of powders, and modeling of bulk behaviours of powders.