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      Allometric scaling of skin thickness, elasticity, viscoelasticity to mass for micro-medical device translation: from mice, rats, rabbits, pigs to humans

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          Abstract

          Emerging micro-scale medical devices are showing promise, whether in delivering drugs or extracting diagnostic biomarkers from skin. In progressing these devices through animal models towards clinical products, understanding the mechanical properties and skin tissue structure with which they interact will be important. Here, through measurement and analytical modelling, we advanced knowledge of these properties for commonly used laboratory animals and humans (~30 g to ~150 kg). We hypothesised that skin’s stiffness is a function of the thickness of its layers through allometric scaling, which could be estimated from knowing a species’ body mass. Results suggest that skin layer thicknesses are proportional to body mass with similar composition ratios, inter- and intra-species. Experimental trends showed elastic moduli increased with body mass, except for human skin. To interpret the relationship between species, we developed a simple analytical model for the bulk elastic moduli of skin, which correlated well with experimental data. Our model suggest that layer thicknesses may be a key driver of structural stiffness, as the skin layer constituents are physically and therefore mechanically similar between species. Our findings help advance the knowledge of mammalian skin mechanical properties, providing a route towards streamlined micro-device research and development onto clinical use.

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          Microneedles for drug and vaccine delivery.

          Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990's when microfabrication technology enabled their manufacture as (i) solid microneedles for skin pretreatment to increase skin permeability, (ii) microneedles coated with drug that dissolves off in the skin, (iii) polymer microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications. Copyright © 2012 Elsevier B.V. All rights reserved.
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            The weight of nations: an estimation of adult human biomass

            Background The energy requirement of species at each trophic level in an ecological pyramid is a function of the number of organisms and their average mass. Regarding human populations, although considerable attention is given to estimating the number of people, much less is given to estimating average mass, despite evidence that average body mass is increasing. We estimate global human biomass, its distribution by region and the proportion of biomass due to overweight and obesity. Methods For each country we used data on body mass index (BMI) and height distribution to estimate average adult body mass. We calculated total biomass as the product of population size and average body mass. We estimated the percentage of the population that is overweight (BMI > 25) and obese (BMI > 30) and the biomass due to overweight and obesity. Results In 2005, global adult human biomass was approximately 287 million tonnes, of which 15 million tonnes were due to overweight (BMI > 25), a mass equivalent to that of 242 million people of average body mass (5% of global human biomass). Biomass due to obesity was 3.5 million tonnes, the mass equivalent of 56 million people of average body mass (1.2% of human biomass). North America has 6% of the world population but 34% of biomass due to obesity. Asia has 61% of the world population but 13% of biomass due to obesity. One tonne of human biomass corresponds to approximately 12 adults in North America and 17 adults in Asia. If all countries had the BMI distribution of the USA, the increase in human biomass of 58 million tonnes would be equivalent in mass to an extra 935 million people of average body mass, and have energy requirements equivalent to that of 473 million adults. Conclusions Increasing population fatness could have the same implications for world food energy demands as an extra half a billion people living on the earth.
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              Epidermal thickness at different body sites: relationship to age, gender, pigmentation, blood content, skin type and smoking habits.

              Epidermal thickness and its relationship to age, gender, skin type, pigmentation, blood content, smoking habits and body site is important in dermatologic research and was investigated in this study. Biopsies from three different body sites of 71 human volunteers were obtained, and thickness of the stratum corneum and cellular epidermis was measured microscopically using a preparation technique preventing tissue damage. Multiple regressions analysis was used to evaluate the effect of the various factors independently of each other. Mean (SD) thickness of the stratum corneum was 18.3 (4.9) microm at the dorsal aspect of the forearm, 11.0 (2.2) microm at the shoulder and 14.9 (3.4) microm at the buttock. Corresponding values for the cellular epidermis were 56.6 (11.5) microm, 70.3 (13.6) microm and 81.5 (15.7) microm, respectively. Body site largely explains the variation in epidermal thickness, but also a significant individual variation was observed. Thickness of the stratum corneum correlated positively to pigmentation (p = 0.0008) and negatively to the number of years of smoking (p < 0.0001). Thickness of the cellular epidermis correlated positively to blood content (P = 0.028) and was greater in males than in females (P < 0.0001). Epidermal thickness was not correlated to age or skin type.
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                Author and article information

                Contributors
                m.crichton@hw.ac.uk
                m.kendall@uq.edu.au
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                21 November 2017
                21 November 2017
                2017
                : 7
                : 15885
                Affiliations
                [1 ]ISNI 0000 0000 9320 7537, GRID grid.1003.2, Delivery of Drugs and Genes Group (D2G2), Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, ; St Lucia QLD, 4072 Australia
                [2 ]ISNI 0000 0000 9320 7537, GRID grid.1003.2, Martin group, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, ; St Lucia QLD, 4072 Australia
                [3 ]ISNI 0000 0000 9320 7537, GRID grid.1003.2, Nanomechanics and Nanomanufacturing Group, School of Mechanical and Mining Engineering, Faculty of Engineering, Architecture and Information Technology, The University of Queensland, ; St Lucia QLD, 4072 Australia
                [4 ]ISNI 0000000106567444, GRID grid.9531.e, Institute of Mechanical, Process and Energy Engineering, School of Engineering and Physical Sciences, Heriot-Watt University, ; Edinburgh, EH14 4AS United Kingdom
                [5 ]ISNI 0000 0000 9320 7537, GRID grid.1003.2, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, ; St Lucia QLD, 4072 Australia
                [6 ]Faculty of Medicine, The University of Queensland, Royal Brisbane and Women’s Hospital, Herston QLD, 4006 Australia
                Article
                15830
                10.1038/s41598-017-15830-7
                5698453
                29162871
                04c7ba95-9c17-4255-9abf-1946fc7873c3
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 June 2017
                : 2 November 2017
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