Skin and bones from the 3D bio-printer

Spare parts for human beings

 

OHB Redaktionsteam
Published on
by OHB Redaktionsteam, OHB SE

What is the most complex organ in the human body? If you think about this question, you will probably instinctively come up with the very organ that you are using to answer this question, namely the brain. The brain is unimaginably complex, yet the other organs inside the human body are not lagging far behind. Humans move, grow, exchange substances with their environment, reproduce and interact with their environment. In brief, they are alive. And for that, they need specialized organs. In the course of evolution, these organs have developed a high degree of efficiency and adaptability, thus ensuring the survival of the human species. Their functionality is closely linked to the specific environmental conditions prevailing on the Earth. Humans are living beings that have adapted to the living conditions on planet Earth in the course of evolution. All the extraterrestrial destinations currently within reach, including the Moon, Mars and the ISS, are subject to different conditions that pose special challenges for the human organism.

Life on Earth has been shaped by gravity

The Earth, the Moon and Mars are natural celestial bodies that have a gravitational force corresponding to their mass. The ISS, on the other hand, is an artificial satellite orbiting the Earth in a state of permanent free fall. For this reason, there is no gravity on board the space station.

The Earth’s gravity has been a constant and decisive design factor for life on our planet since its origin about 3.8 billion years ago. For this reason, health is impaired after only a short time when gravity changes and, in particular, when there is no gravity at all.

One factor here is the changed load on the bones and muscles. Since it has proved to be an advantage in the course of evolution to use the available resources sparingly, the body quickly starts degenerating structures that are not exposed to any strain. In gravity-free conditions, muscle atrophy occurs and bone density declines after only a short time.

Moreover, the cardiovascular system is designed to pump the blood from the legs back to the heart against the pull of gravity. If there is no gravity, this mechanism causes the blood to collect in the head, causing the head and face to swell.

A similar effect occurs in the brain: Where there is no gravity, the cerebrospinal fluid cannot drain unhindered. This puts pressure on the brain, leading to headaches, visual impairment and reduced cognitive abilities.

In addition, a change in gravity also has effects on the sense of equilibrium. In gravity-free conditions, it is no longer possible to distinguish between top and bottom and this leads to astronauts losing their ability to stand upright after some time. In addition, the lack of situational information often causes temporary nausea and coordination problems. Coordination disorders also occur in reduced gravity. Astronauts often tumbled during the Apollo missions due to the lack of traction on the Moon.

Another problem is “space fever”, an increase in body temperature in weightless conditions due to a lack of evaporative cooling: Sweat remains on the surface of the skin and forms very large drops, which are slow to evaporate due to the unfavorable surface-to-volume ratio. This means that the body temperature of astronauts can easily rise to over 40 °C during physical exertion.

The effects of a combination of a lack of gravity and increased radiation exposure on the immune system and the ability for wounds to heal also have serious consequences. Astronauts are susceptible to infections and suffer from wound healing disorders. At the same time, protracted stays in space reduce the variety of microorganisms to which astronauts are exposed. The immune system adapts to the lower risk of infection, leading to a significant increase in susceptibility to infections when the astronauts return to Earth.

In brief, spending time in space makes you sick. And this effect grows in significance, the longer the duration of the mission. This means that the health risks of space travel must be taken into account and are critical for the success of the mission when voyages to Mars or even projects to settle other planets are planned.

There’s no rescue service in space

The Earth can be reached in just a few hours from the ISS. A return flight from the Moon takes several days, while a trip to Mars and back again will take around three years with the propulsion technology currently available. There is also a lag in the communications between the Earth and Mars on account of the distance: Messages take about 20 minutes to reach the recipient in either direction. This means that in the event of medical emergencies on the Moon or Mars, no immediate assistance can be provided from the surface of the Earth.

To date, all astronauts have undergone only basic medical training. This includes the diagnosis of common diseases and the initial treatment of wounds, but is not sufficient to address more serious injuries. Because of space and budget restrictions, only limited equipment can be carried on board, rendering it virtually impossible to prepare for all eventualities. For this reason, the medical equipment currently available in space tends to be rather rudimentary.

Structural components and implants from the 3D printer

Additive manufacturing could remedy this problem. Also referred to as 3D printing, this method can be used in various manufacturing processes to produce components from a wide variety of materials at the touch of a button if required. All you need is a suitable 3D printer, the raw material and a corresponding digital sketch. This means that even components with complex shapes can be produced with high precision and minimum material consumption.

While at first glance it would seem obvious to use conventional materials such as plastic, metal or ceramics for this new kind of production method, the idea of printing living material and pulling entire organs out of the 3D printer sounds far-fetched at first. Yet, various groups of researchers have found ways of doing precisely that.

However, the complex structure of most organs with their many different cell types poses a challenge. In addition, the cells in functional tissues constantly communicate with each other, are connected to other organs via nerve fibers and are supplied with blood through a finely branched capillary system. Tissues that consist of only a few cell types and have a relatively homogeneous structure are easier to print. Examples include cartilage, skin and certain bone types. While there is still a long way to go before we see the first fully functional 3D-printed heart, cartilage, skin and bone can already be produced in transplantable quality.

3D bio-printing at OHB

OHB’s Life Science department has been working on this task since 2018 in a project entitled “3D printing of living tissue for space research”. Funded by ESA’s “Discovery and Preparation” program, processes have been developed in cooperation with the Technical University of Dresden and OHB subsidiary Blue Horizon to print skin and bones under space conditions.

Minute tissue samples from which the appropriate cells are then obtained are used as the input material for the production of printable living material. For example, cells from the dermis are used as starting material for printing skin. Blood plasma is used as the liquid basis for the production of the “bio ink” required for printing. However, as the consistency is too liquid for printing under changed gravitational conditions, methyl cellulose (cellulose derivative) and alginate (structural element of the cell walls of brown algae) are added to increase viscosity. The skin tissue can then be built up layer for layer using this nutrient-rich mixture. So far, pieces of skin up to the size of a DIN A4 sheet can be printed in this way. Fresh from the printer, they still need an incubation phase of a few hours to mature and to build up intracellular connections. Once this phase has been completed, the skin is ready for transplantation. The time required for this is so short that even a patient with fresh injuries can be treated with skin made from his own cells.

One advantage of using printed skin compared to autologous transplants, i.e. transplants taken from the patient’s healthy skin, is that no further wounds are inflicted on the patient. This is particularly important in space conditions where the healing process takes longer. Because the graft is generated from the body’s own cells, the risk of rejection is low.

Blood plasma is also used as a nutrient and a carrier medium for printing bones and is enriched with mesenchymal stem cells harvested from fatty tissue for example. These are multipotent cells, which can develop into different tissue types. Calcium phosphate bone cement is used as a structuring element. The living cells are imprinted into the bone cement grid and gradually convert it into vital bone tissue. The process corresponds to the permanent process of bone tissue modelling that also occurs in healthy bone material. Functional metacarpal bone has already been printed using this method. One of the advantages of the method is that data harvested from imaging procedures, such as CT or MRI, can be included in the creation of the 3D models, thus allowing implants tailored to the individual patient to be manufactured.

 

In order to demonstrate that the 3D bio-printing methods that have been developed are suitable for use in space, both the skin and bone samples have been printed upside down. This test proves that implants can also be printed under changed gravitational conditions and can theoretically therefore also be used on board spaceships or on other planets.

This would permit a flexible response in medical emergencies, particularly on long-term missions. Blood plasma and living cells can be gained from the patient if necessary or harvested in advance and stored. As it is, it is crucial for biological material to be taken on long-term missions as a basis for producing renewable resources. Accordingly, the additives required for creating the bio inks could also be gained in space. At this point in time, it is already possible for 3D bio-printers to be built in a handy format, meaning that they are also viable in the cramped conditions of a space mission.

3D bio-printing as a variant of regenerative medicine thus represents a technology offering great potential both for missions to explore other planets and for use on Earth. The technology still has a few years in which to continue maturing before humankind sets off to Mars. Klaus Slenzka, Head of the Life Science department at OHB, is convinced that in the not too distant future it will be also possible to print more complex organs such as a liver, kidney or heart.

And what about the human brain? Klaus Slenzka is a little more cautious: “The human brain is an extremely complex structure based on extremely complex nerve cells. Nerve cells differentiate, grow contacts to other cells, release these again and then establish contact to another neighboring cell. In addition, the brain has a special protective mechanism, the blood-brain barrier, which at the same time ensures the supply of nutrients to the brain cells. To print ONE brain sometime in the future, yes, that will probably work. But how do the cells interconnect and what happens then? There is no answer to this question. And what use is a printed brain that behaves unpredictably after printing?”

To print a brain sometime in the future, yes, that will probably work. But how do the cells interconnect and what happens then? There is no answer to this question.

Klaus Slenzka, Head of the Life Science department at OHB