4D Bioprinting


With the planned ZIM innovation network, EurA AG, together with partners from industry and science, will support concrete innovative products and new services in the field of bioprinting for applications in biology, pharmacy, and medicine. Thus, the network promotes the commercialization of the innovative technologies of the network partners by market-oriented R&D projects and establishment of new value chains for biopharmaceuticals and medicine.


The aim of the network is the initiation, concept development and application for funding for research and development projects of the network partners in the fields of sensors/automation, innovative bio-inks and the inclusion of time as a fourth dimension that enables innovative applications and end products. This results in an economically relevant contribution to a sustainable and personalized medicine. The network is designed and implemented jointly with partners from France and Great Britain as an international network.


Currently, 3D bioprinting is used for a wide range of applications in the bi-pharmaceutical and biomedical sectors. However, the printed end products, physiologically seen, are static and not alive, i.e. inanimate, three-dimensional objects that do not change over time. 4D-bioprinting involves time as a fourth dimension, whereby the functionality and shape of the printed objects evolve over time and, as living cells are processed into living structures, a change in time takes place.


Bioprinting processes are currently in basic research and still far from commercial applications. The development of reliable devices, storable equipment materials, cultivable and storable bio inks and reproducible control and automation that meet the application-specific approval regulations would enable the market entry of many application ideas.


The current discussion on organ donation is evidence of the urgent but unmet need for human organs. Custom-made organs, produced with human cells in an additive printing process, would be an optimal solution. Rejection reactions could be reduced if the patient's own cells rather than donor organs were used. Tissues produced with human cells in a 3D printing process, which are viable and capable of complete metabolism, would also be used in drug research. Such tissues would be closer to human metabolism than experimental animals and would therefore have the potential to achieve results that could be transferred to humans more quickly.


The social relevance and economic benefit of the network topic can therefore be expected in two applications: additively printed organs for transplantation medicine and tissues produced from human cells for drug research. Unlike the use of "dead" materials such as polymers or metals in 3D printing, time is added as a fourth dimension when using living cells, hence 4D Bioprinting. A change in the cells as a function of time, biochemical environment, temperature, light irradiation and other parameters leads to fundamentally new technical challenges.


Current 3D printing processes are concerned with the order of deposition of biotin in which human cells are dissolved. However, tissues and organs consist of interacting building blocks that interact and develop over time. Controlled growth conditions that change over hours and days during printing must be maintained. The aim is to develop tissue- or organ-specific printing processes: the network will develop and evaluate 4D printing processes that are adapted to the structure, properties and application of the printed tissues. 


Another line of development concerns intelligent cell carriers for scaffolding materials on which cells can grow in a controlled manner. The challenge for these scaffold materials is to support pressure and growth over several days or weeks, to control the controlled release of active ingredients and to be biocompatible and biodegradable. In research, scaffolding materials made of nanocellulose are being developed which may possibly meet these requirements.


A third line of development are bio inks. These inks are highly complex suspensions of different cells in aqueous solution and contain cross-linkable substances such as gelatine, hepatine or hyular acid, as well as nutrient medium and growth factors. A particular challenge is to change the composition of the bio-ink in a controlled manner during the printing process in order to fulfil the different structures and functions of the printed tissue.


The fourth line of development concerns the control, industrialisation, and automation of the process. A particular challenge is that processes involving living biologic materials are only reproducible to a limited extent. Biological inks can also change very briefly; environmental conditions such as temperature, humidity and light have a major influence. Processes must be developed to obtain reproducible results even under changing initial conditions.


The following basic technical risks exist in the development of 4D printing processes, bio inks and process control: when printing small structures, e.g. the blood capillary network in tissue, high shear forces in the pressure nozzles are unavoidable. There is a risk that cells are so heavily loaded due to these shear forces that the physiological functions of the cell are disturbed. A further technical challenge is the need for rapid replacement of bio-inks: there are more than 300 different cell types in the human body. Tissues with typically 4-8 different cell types are interesting for the intended applications. A printing process must therefore allow parallel and/or sequential printing of these cell types, which must be fed into the print head one after the other. There is a risk that the resulting lengths and curvatures of the supply lines make reliable printing of the bio inks impossible.



Our network partners are small and medium-sized companies and research institutions from all over Europe.


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