EXPERIMENT RECORD N° 9392
SKIN B
  1. 2013 • ISS Increments 35-36
  2. 2013 • ISS Increments 37-38
  3. 2014 • ISS Increments 39-40
  4. 2014 • ISS Increments 41-42
  5. 2015 • ISS Increments 43-44
  6. 2015 • ISS Increments 45-46
  7. 2016 • ISS Increments 47-48
  8. 2016 • ISS Increments 49-50
Life Sciences:
  • Biotechnology
  • Human Physiology
BIOLAB
U. Heinrich (1), H. Tronnier (1), N. Gerlach (1), T. Rodic (2), T. Sustar (2), A. Grm (2), P. Sustaric (2), J. Langus (2), M. Schweitzer (3)
(1)  
DermaTronnier GmbH & Co.KG
University of Witten-Herdecke
Alfred-Herrhausen-Strasse 44 (FEZ)
58455 Witten
GERMANY
Tel:  
+49(0)23022826300
Fax:  
+49(0)23022826326
e-mail:  
ulrike.heinrich@uni-wh.de
info@dermatronnier.de
nicole.gerlach@uni-wh.de
(2)  
C3M d.o.o.
Tehnoloski park 21
SI-1000 Ljubljana
SLOVENIA
Tel:  
+386(0)12000444
Fax:  
+386(0)12000440
e-mail:  
tomaz.rodic@c3m.si
(3)  
Kayser-Threde GmbH
Wolfratshauser Strasse 48
81379 München
GERMANY
e-mail:  
mario.schweitzer@kayser-threde.com

The Skin B experiment is the combination of 2 selected experiments:
Validation of skin physiological changes in space and skin as a model for other body systems
and
In vivo biomechanical measurements of human skin properties under accelerated aging conditions during ISS mission

The experiment will ‎complement the ‎scientific data collected during the Astrolab mission 2006 with the precursor experiment Skin Care. Compared ‎to Skin Care several technical improvements of the hardware could be ‎achieved to guarantee an even better data quality and handling comfort.

The experiment is jointly supported by the German Federal Ministry for Economics and Technology, the German Aerospace Centre DLR, and ESA.

Scientific Background
Until 2005 there were no information available concerning the long-term impact of weightlessness on living skin. A series of skin physiological measurements before, during (second half of his six-month stay on the ISS) and after a space flight were carried out on a single astronaut. The study investigated possible changes in skin parameters like hydration (via Corneometry), barrier function (via measurements of the trans epidermal water loss - TEWL) and skin topography (via SELS – Surface Evaluation of the Living Skin, VisioScan). In addition to these epidermal measurements which were regularly done on the ISS by the astronaut, before and after the mission, dermal parameters like the elasticity (by Cutometry) and the density of the skin were recorded. For the latter, a ultrasound device (DermaScan C) with a frequency of 20 MHz was used.

Results of the space experiment done during the Astrolab mission show changes in the skin as follows:
Concerning the epidermal parameters in space, an apparently slight increase of hydration could be shown; it is also a common phenomenon in aging skin. This can be interpreted in relation to the thinning of corneal layers in aging skin and the measuring principle of Corneometry by means of the condensator method. Due to the thinning, deeper parts of the epidermis with more water are measured, which leads to higher hydration values. But overall pre-flight values compared to postflight values showed a slight decrease in skin hydration. The transepidermal water loss increased during the space mission, which shows an impairment of the barrier function of the skin and implies a loss of integrity of the basal lamina. With respect to the surface structure of the skin, an increased coarsening of the skin fields has been found. This is also found in aging skin [3]. This could be due to a decreased turnover of epidermal cells from the basal layer up to the stratum corneum and would also explain why the epidermis gets thinner. An explanation of these phenomena might be the flattening of the interface between dermis and epidermis which causes less surface area for proliferative stem cells in the stratum basale [1,8]. In contrast to the epidermal effects which are reminiscent of aging effects both the biological elasticity and the elastic properties of the dermis increased. This might be due to fluid shifts in weightlessness [2]. However the far more important change observed after the mission was a severe degradation of the dermal connective tissue. This gets apparent through large amorphous low-echo zones on ultrasound images of the skin obtained two weeks after the end of the mission. This is considered not to be due to inactivity like in paraplegia, since corresponding ultrasound images would happen to look different [6].

General advantages of the skin for investigations:

  • skin is easily accessible and can be continuously examined by means of a large number of non-invasive test methods
  • the large surface area allows comparative examinations
  • due to its constitution made out of two blastodermic layers, the ectoderm and the mesoderm, the skin integrates a multitude of tasks and functions (i.e. immunological organ) and acts as a “mirror” of the physical and mental health status
  • in relation to the last mentioned point skin may be utilized as an early recognition system for pathologic changes of the body


OBJECTIVES
There are two objectives to this combined study:
a) increasing the scientific knowledge of skin physiology and skin “aging” process and
b) use those parameters in a skin mathematical model.

AIM
In the first Skin Care project we were able to show that the skin corresponds to an aging skin after a prolonged stay in weightlessness conditions. In this project our aim is to validate the previously obtained data and we expect to see an ageing skin with a thinner, more structured epidermis and a decrease of collagen and elastic fibres.

So far, there is no model for skin aging. If we can validate our previous data, we will be able to develop further therapy approaches and prevention of prematurely aged skin as well as poor wound healing.

The skin could serve as a model for connective tissues, different epithelia, vascular system, neuronal and stem cell system and may lead to further diagnostic options. Furthermore, it will help the astronauts to prepare a long stay in space and to set up space travels, e.g. journey to Mars.

The different measurements are:

Hydration-measurements
The Corneometer measures skin moisture by means of a capacitive method. The measuring head, with a diameter of 10 mm is placed on the location to be measured with constant pressure and the skin functions as a dielectric of the capacitor. With this method the water content of the stratum corneum will be measured in relative units.

Measuring the TEWL - transepidermal water loss
Tests of transepidermal water loss of the skin are necessary in order to determine the barrier function of the skin. They are used in dermatology to assess the therapeutic effects in the case of different dermatoses or when the effects of medical drugs have to be tested with regard to perspiration and transpiration. With a Tewameter the evaporation of water is measured directly on the skin surface with a special probe. For measuring, the probe is placed on the skin surface and after an adjustment time of 30 seconds the measured value (g / h x m²) is displayed and recorded digitally.

SELS - Surface evaluation of living skin
The measuring principle of the SELS-method is based upon the graphic representation of living skin. The SELS measuring device (called VisioScan) consists of a measuring head containing two special metal-halogenide lights (UV range) that illuminate the 15 x 17 mm measuring area of the skin uniformly. The spectrum and density of the lamps have been chosen in such a way that only the skin surface, without reflections of deeper layers, is monitored. A CCD-camera, built into the measuring head, records a picture of the skin, which is then transferred as a grey-value bitmap-file to the storage-device, which can be later analysed by software in respect of the skin parameters roughness, scaling, wrinkles and volume.
For measuring, the camera is placed on the skin surface without pressure and after it is sure that the head of the camera rests evenly on the skin a picture can be taken.

Microcirculation (if no existing hardware is available on board to perform such a measurement it will only be performed pre- and post-flight)
The measuring device (called O2C, “oxygen to see”) uses laser light for examining perfusion parameters in the tissue. The movement of the erythrocytes triggers a Doppler shift in the detected laser light. This Doppler shift in the frequency of the detected laser light shows the blood flow velocity. The detected laser light signal increases as the number of erythrocytes goes up. This value represents the parameter flow. Normally the probe is just set on the skin, whereas veins should be avoided, and the measurement can start. The device does also measure haemoglobin concentration and oxygen saturation.

Ultrasound (if no existing hardware is available on board to perform such a measurement it will only be performed pre- and post-flight)
For the usage of ultrasound in the field of dermatology it is necessary to have high resolution devices. Tumour diagnosis and objective measurements of the healing of wounds, skin thickness and density, chronic skin changes, scars, cellulite, and photoaging are areas of use for this technology. At least a 20 MHz transducer providing a 60 by 200 micron resolution (with 10-15 mm penetration) is mandatory in order to investigate the skin properly.

Pseudo biopsies (multiphoton tomography) pre- and post-flight only: (optional, only possible at EAC)
To get a better understanding of the degradation of the dermal connective tissue high resolution images with a multiphoton tomograph will be taken. This device non-invasively enables for three-dimensional optical in vivo biopsies and gives information about the thickness of the stratum corneum and the exact depth of the epidermal and dermal junction, intratissue cell morphology, cell-cell-distances, occurrence of melanocytes, occurrence of cavities, occurrences of macrophages or other signs of inflammation, ECM morphology of upper dermis (elastin and collagen network), autofluorescence levels, ratio free to bound NAD(P)H as well as skin age index based on ration elastin to collagen.

Skin Elasticity, pre- and post-flight only
The cutometer is a device that applies a known suction to a small portion of the skin; it then measures the displacement of the skin that relates to elasticity.

JUSTIFICATION FOR NEED OF SPACE EXPERIMENT
Since there exists no experience of skin physiology in weightlessness, the first investigations (Skin Care project) were performed [3] in order to validate changes in skin hydration, barrier function, skin surface, skin ultra structure (skin density and thickness) and skin elasticity. An increased skin aging as well as a decreased skin density was observed during flight conditions, whereas skin hydration and barrier function showed only slight changes. However data were measured only with only one test subject, so that validation of the skin physiology under conditions of weightlessness has to be confirmed.
Furthermore skin aging cannot be accelerated on Earth in a controlled way, and space is the only potential alternative where the experimental conditions are known.

It is well-known that weightlessness compromises the whole biological network for instance the osseous and muscular supporting system or the cardiovascular and vestibular system. Along with side effects in these systems, skin impairments belong to the most frequent medical events during Space Missions [5]. This suggests that also cells of the skin employ molecules and pathways dependent on gravity. By way of example, it has been shown that cyclic Guanosine MonoPhosphate (cGMP) in melanocytes, the pigment cells of the epidermis, is sensitive to gravitational forces [4].
Among other functions cGMP does not only regulate the programmed cell death (apoptosis) but also leads to activation of protein kinases which in turn trigger specific pathways in the cell. This implies global changes of the cells.
These facts should be reason enough to investigate skin in space.
Since the turnover of epidermal cells takes almost a month, long-term changes cannot be studied on parabolic flights or in drop towers. Since some alterations of the dermal connective tissue require even more time, even long-term bedrest studies up to three month are not an appropriate way to investigate thoroughly the skin under microgravity conditions.

Several points militate in favour for investigations on living skin under microgravity conditions:

  • in regard to our previous findings a time lapse model of aging is contemplated (and potentially for wound healing as well)
  • usage of the skin as a model for connective tissues, different kinds of epithelia, vascular system, neuronal system and stemcell systems in weightlessness (may be used for the development of new diagnostic possibilities)
  • all measurements are non-invasive and can be carried out easily within few minutes without any strain for the person to be examined
  • study of skin modifications in space is possible even after a space mission, caused by its long adaptation time to new environmental conditions and its inherent memory effect

related research:
Skin Care
Astrolab mission 2006

Operational Overview
The measurement will be performed on the volar (inside) part of one forearm (non dominant except if the skin has been previously damaged on that arm)

Procedure Outline
An inflight session will consist of:
- Hydration measurement with Corneometer (repeat 3 times)
- TEWL measurement with Tewameter (repeat 3 times)
- Pictures from the skin with VisioScan (2 pictures)
- And if available laser Doppler and echographic measurement (otherwise only pre and post flight measurements)

Parameters Measured
In flight and on ground:
- Hydration level (Corneometer)
- TEWL Transepidermal water loss / barrier function (Tewameter)
- SELS Surface evaluation of the living skin: from the skin pictures (VisioScan), roughness, scaling, wrinkles and volume will be analysed
- Microcirculation blood flow and velocity, Haemoglobin content and oxygen saturation (laser Doppler - if hardware available on ISS - lower priority)
- Ultrasound imaging: density and thickness (if hardware available on ISS, lower priority)

Additional measured parameters on ground
- Elasticity (Cutometer)
- Pseudo skin biopsies (Multiphoton Tomography) when possible, i.e. when pre- and part of the postflight measurements can be performed at EAC (e.g. ESA astronaut)

Test Subjects
Number of subjects desired: 5
Number of subjects required: 3 in flight but 5 on ground
Subject exclusions: Crew can be any (male or female) but without bilateral inner forearm scars, tattoos or injury. All the test subjects should have Caucasian skin. (There are big differences between Caucasian skin and Asiatic or African origin, i.e. the skin surface, the skin hydration sebum content etc. are different from the Caucasian skin. The international skin research is mostly based on Caucasian skin. Additionally the hardware/software of the VisioScan is adapted to the Caucasian skin type II by the manufacturer in order to get a very good quality (contrast) of the pictures of the skin surface.)

Inflight Session Requirements
FD 15 +/-4,
FD 30 +/-4,
FD 45 +/-5 (nice to have/reserve session),
FD 60+/-5,
FD 90 +/-5 (nice to have/reserve session),
FD 120 +/-5,
FD 150+/- 5,
and FD 180 or as late as possible before return (R-15 days is max acceptable).

If the flight is a month shorter, last measurement is to be kept at R-15 or closer to landing and the previous one can drop.

There should be a minimum of 2 weeks between each measurement.
Session (without echo and laser Doppler) duration estimated to be less than 30 min, depending on data saving and power supply design. The measurements themselves will be around 7 min when no laser Doppler or echographic measurements are performed.

Baseline Data Collection
Preflight:
2 sessions in the last 10 months before flight, the last one closer to launch, best when the crew has its last stop over in EAC while travelling to Russia for launch. There should be at least 2 months between the 2 sessions.

Postflight: R+3-10, R+30 +/-5 and R+150-180
In case the last flight data point (R-15 or later) could not be performed (by planning or off-nominal issues), the subject(s) shall have an additional reduced session at R+0-1.
Early Postflight Requirements (R+0 to R+4) justification: If some subjects are only studied pre- and post-flight or miss the very late in-flight data point then early measurement are needed to get the status of the skin before the recovery process starts so the data can be assimilated to last in flight data points of other subjects.
Both pre- and post-flight BDC sessions require 1 hour each; the reduced session at R+0-1 will require 15 min.

Crew Constraints
The following constraints apply to all measurements unless stated otherwise:

  1. No (normal level – e.g. daily prescribed Space Medicine regimen) exercise 2 hours before measurement (also means crew shall not arrive rushing to the BDC sessions), no high level exercise above 75% VO2 Max, high workloads, or long-duration exercises (e.g.1/2 marathon) 12 hours before measurements.
  2. No caffeine, hot drinks, spices, meal ideally 2 hours before measurements (1 hour minimum).
  3. After exercise the crew can/should drink room temperature or slightly cooled water or juice to rehydrate and cut thirst.
  4. Ideally, crewmember should not apply skin moisturizer (body lotion, cream, body oil etc.) more than once a day over the Skin B measurement area. 
  5. No pool or sauna on same day before measurement (ground only).
  6. Measurement to be in a place with minimal air flow, temp 20-25 Deg C (careful with air conditioning). In flight, and at each BDC facility, the location where the measurements will be done should be always the same to best “guarantee” same temperature and humidity.
  7. Measurements are to always be performed in same period of the day (either morning or afternoon), and at least 48 hours away from any skin moisturizer (body lotion, crean, body oil etc.) application to the measurement area (inner part of lower arm).
  8. Measurements are to be at least 2 hours away from washing with water, 3 hours if washing with cleaning medium.

Constraints regarding other experiments:

  1. No fluid loading (more than voluntary drinking) 24 hours prior to measurements.
  2. No exercises of 75% VO2 max or equivalent 12 hours prior to Skin B measurements.

Hypothesis and Expected Results
It is well-known that weightlessness compromises the whole biological network for instance the osseous and muscular supporting system or the cardiovascular and vestibular system. Along with side effects in these systems, skin impairments belong to the most frequent medical events during space missions [5]. This suggests that also cells of the skin employ molecules and pathways dependent on gravity. By way of example, it has been shown that cyclic Guanosine MonoPhosphate (cGMP) in melanocytes, the pigment cells of the epidermis, is sensitive to gravitational forces [4].
Among other functions cGMP does not only regulate the programmed cell death (apoptosis) but also leads to activation of protein kinases which in turn trigger specific pathways in the cell. This implies global changes of the cells. These facts should be reason enough to investigate skin in space.
Since the turnover of epidermal cells takes almost a month, long-term changes cannot be studied on parabolic flights or in drop towers. Since some alterations of the dermal connective tissue require even more time, even long-term bedrest studies up to three month are not an appropriate way to investigate thoroughly the skin under microgravity conditions.

Planned Analyses
A time kinetic per astronaut will be created and the obtained kinetic on the ISS of the individual astronauts will be compared to the measured data before and after the space mission. Thus, after data collection and analysis we will interpret the data. A coarser skin surface field, a decrease in skin elasticity, a thinning of the stratum corneum, a decline in the hydration of the skin and TEWL will be considered as an effect similar to the one observed by an aging skin. Due to the relative small amount of volunteers (n=5+1 from earlier flight) the statistical validation is limited.

RESULTS
Data from the Skin-B subjects (n = 6) contradict the results obtained in the previous pilot study SkinCare (n = 1 subject). In the present study, no deterioration of the skin was found but rather an improvement in skin hydration and skin barrier function, and no changes or improvement in the appearance of the skin surface. Furthermore, the skin density and skin thickness as well as skin elasticity values were unchanged from pre-flight values.

CONCLUSION
In conclusion, we found that spaceflight under present conditions has no negative impact on skin physiological parameters.

Self-Reported Skin Changes by a Selected Number of Astronauts after Long-Duration Mission on ISS as Part of the Skin B Project
In an extention of the SKIN-B experiment, a study on 46 U.S. and European ISS crew members who were on 6-month (average) missions was conducted. A pre-flight questionnaire was given to the astronauts asking about their terrestrial skin care habits and skin conditions/atopy before launch. In addition, they were asked to fill out a post-flight questionnaire asking about their on-orbit skin care routine and whether any special observations regarding the skin were made during flight. Skin rashes were the most self-reported event. Furthermore, among notable events, 40% were classified as skin rashes/hypersensitivities. Thus, especially skin conditions during space travel are of major clinical interest and require further research. 

RESULTS
A total of 23 skin symptoms were recorded by 8 nonatopic astronauts (mean age: 41 years) during the mission. The symptoms were peeling (21.74%), rash (17.39%), dryness (13.04%), severe dryness (8.70%), reddening (8.70%), itchiness (8.70%), bruising (4.35%), skin sensitivity (4.34%), bumps (4.35%), acne (4.35%) and slow healing of contusions and lacerations (4.35%). Especially the hands and feet were affected by skin problems. As a result of this examination, it was shown that the skin symptoms correlate with poor hygiene on orbit, whereas the factor "environment" on the ISS plays a minor role. Surprisingly, 2 astronauts even experienced positive effects on their skin.

CONCLUSION
Based on these preliminary data, it is important to pay more attention to skin hygiene and maintenance in space.
[1]  
R.M. Lavker, P.S. Zheng, G. Dong, (1987), "Aged skin: a study by light, transmission electron, and scanning electron microscopy", Journal of Investigative Dermatology, 88, 3 Suppl, pp. 44s-51s.
[2]  
K.A. Kirsch, F.J. Baartz, H.C. Gunga, L. Röcker, (1993), "Fluid shifts into and out of superficial tissues under microgravity and terrestrial conditions", Journal of Clinical Investigation, 71, 9, pp. 687-689.
[3]  
H. Tronnier, M. Wiebusch, U. Heinrich, R. Stute, (1999), "Surface evaluation of living skin", Advances in Experimental Medicine and Biology, 455, pp. 507-516.
[4]  
K. Ivanova, N.H. Zadeh, I. Block, P.K. Das, R. Gerzer, (2004), "Stimulation of cyclic GMP efflux in human melanocytes by hypergravity generated by centrifugal acceleration", Pigment Cell Research, 17, 5, pp. 471-479.
[5]  
D. Risin, (2008), "Evidence Report on: Risk of Inability to Adequately Treat an Ill or Injured Crewmember", Human Research Evidence Book 2008, Exploration Medical Capability (ExMC) Element, NASA, Johnson Space Center, Houston, Texas, http://humanresearchroadmap.nasa.gov/Evidence/reports/ExMC.pdf.
[6]  
H. Tronnier, M. Wiebusch, U. Heinrich, (2008), "Change in Skin Physiological Parameters in Space - Report on and Results of the First Study on Man", Skin Pharmacology and Physiology, 21, pp. 283-292.
[7]  
H. Tronnier, M. Wiebusch, U. Heinrich, (2008), "First Skin Physiological Tests in Weightlessness in the ISS Space Station", International Federation of the Societies of Cosmetic Chemists, 11, 3, pp. 231-238.
[8]  
S. Mine, N.O. Fortunel, H. Pageon, D. Asselineau, (2008), "Aging alters functionally human dermal papillary fibroblasts but not reticular fibroblasts: a new view of skin morphogenesis and aging", Public Library of Science ONE, 3, 12, pp. e4066.
[9]  
(2013), "Studying human skin in space - Soyuz mission takes SKIN B to the ISS", DLR Webportal, 29 March, http://www.dlr.de/dlr/en/desktopdefault.aspx/tabid-10081/151_read-6652/year-all/#gallery/9250.
[10]  
N. Braun, S. Binder, H. Grosch, C. Theek, J. √úlker, H. Tronnier, U. Heinrich, (2019), "Current Data on Effects of Long-Term Missions on the International Space Station on Skin Physiological Parameters", Skin Pharmacology and Physiology, 32, 1, DOI: 10.1159/000494688, pp. 43-51.
[11]  
N. Braun, S. Thomas, H. Tronnier, U. Heinrich, (2019), "Self-Reported Skin Changes by a Selected Number of Astronauts after Long-Duration Mission on ISS as Part of the Skin B Project", Skin Pharmacology and Physiology, 21, 1, DOI: 10.1159/000494689, pp. 52-57.
click on items to display

The set-up configuration of the several parts of the flight model of the Skin B experiment hardware as uploaded to the ISS. Photo: EAC/U. Muellerschkowski

The flight model of the Corneometer hardware. Photo: EAC/U. Muellerschkowski

The flight model of the Tewameter hardware. Photo: EAC/U. Muellerschkowski

The flight model of the VisioScan device. Photo: EAC/U. Muellerschkowski

Close-up of the VisioScan device with the UV light camera switched on. Photo: EAC/U. Muellerschkowski

Demonstration of the use of the Tewameter device. Photo: Kayser-Threde GmbH

European Space Agency astronaut Luca Parmitano, Expedition 36 flight engineer, performing the Skin-B experiment onboard the International Space Station. Credit: NASA

Looking at astronaut skin - Link to article on Tim Peake´s Principia blog: http://blogs.esa.int/tim-peake/2016/02/12/looking-at-astronaut-skin/
 
© 2019 European Space Agency