Team:LMU-TUM Munich/Description

biotINK - a synthetic biology approach to bioprinting

While the interaction of biomolecules makes up the cellular system, the three-dimensional organization of cells makes up tissues and organs. For decades now, scientists have tried to reconstitute such functional tissues by assembling the cells they are made out of - especially for the field of regenerative medicine, where the acquisition of transplants often proves difficult and may mean life or death for the patient. The prospect of creating transplants artificially - especially when grown out of the patient's cells - has since motivated groups all around the world to take part in this endeavour.

But not only could bioprinting prove fruitful in the field of personalized medicine - for pharmacological applications, three-dimensional cell culture systems often constitute the first step in testing a potential pharmacological agent. Systems that resemble the mammalian system as much as possible are hereby especially desired, as they allow a more faithful prediction of a drug's effect in vivo.

Bioprinting systems nowadays have not been able to have a distinct impact on either of these fields. Most of the current techniques here rely on a scaffold, on which cells are seeded. After a certain timespan of in vitro maturation, cells form intercellular contacts and start to grow into two-dimensional cell layers. For the reconstruction of the tissue, layers have to then be combined and the scaffold needs to be removed or degrade automatically within the recipient. The technical complexity of the printing process itself makes bioprinting as it exists now not only technically complex, but also time-consuming and expensive. Furthermore, the growth of two-dimensional cellular layers does not resemble histogenesis in vivo, and is limited to simple tissues that do not require exact positioning or multiple cell types.

Our ambitious project intends to eliminate all of these factors: We are able to create three-dimensional cellular structures easily, quickly and at low cost by immediately cross-linking cells into a protein-cell-matrix. The interactions between cells and the protein matrix are hereby mediated by the strongest non-covalent interaction found in nature - the biotin-streptavidin interaction. By using a two-component system of cells that interact with the matrix, we create a kind of molecular superglue that allow precise positioning of cells via bioprinting.

For delivery of cells, we hijacked a conventional three-dimensional 3D-printer that can be programmed to inject cells with a milimeter presition. Due to the quick nature of the polymerization of cells, we achieve a very high prevision for positioning. But that's not everything: The printing system we created can easily be adapted by any lab around the world, allowing them to print cellular structures as required with only little initial investment.

Apart from the more medically orientated aspects of regenerative medicine and pharmacology, cellular systems are also of great interest for basic and applied research. While much on the molecular interactions within cells is known, little is known about the interactions of cells with each other. Thus, by providing a tool to make research on a supercellular scale more accessible, we are convinced that our system is able to noticeably advance science in many areas.

3D bioprinting comes up with some challenges that are not being addressed in non-tissue printing: choice of cell types, assembly method, growth, differentiation and vascularization factors as well as technical difficulties concerning the sensitivity of biological material. Bioprinting is therefore a melting pot of natural sciences and thus a highly interdisciplinary field. Due to its high complexity and tremendous relevance for synthetic biology, we even recommend and advocate a future iGEM-track only for bioprinting; the imagination of new possibilities offered by overall functional and fully controllable bioprinting is sheer endless. Our self-assembled bioprinter makes further improvements by future iGEM-teams possible. To get an idea about the variety of 3D-bioprinters, the following article should reveal a short overview

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