Manufacturing Living Tissue with a 3D Printer

At the international iGEM academic competition in the field of synthetic biology, a joint team from Munich won first place (Grand Prize) in the “Overgraduate” category. The scientists developed an innovative process which allows intact tissue to be manufactured with the use of a 3D printer. The team was consisting of researchers from the Technical University of Munich (TUM), the Ludwig Maximilian University of Munich (LMU) and Helmholtz Zentrum München.

Living Tissue
The biotINK tissue printer. Source: TUM/ A. Heddergott

The International Genetically Engineered Machine (iGEM) competition encourages students from the field of synthetic biology to implement innovative ideas and to go up against each other with these biotechnology projects. The competition, which was initiated by the Massachusetts Institute of Technology (MIT), has been organized by the iGEM Foundation since 2003, although the MIT campus in Cambridge, MA, remained the venue of the event until 2014. The 300 teams of finalists this year included twelve from Germany, including a joint team from Munich.

The 2016 iGEM project of the year was led by Professor Arne Skerra from the Chair of Biological Chemistry at TUM and sponsored by the Research Training Group GRK2062 of LMU. The work was done in cooperation with Professor Gil Gregor Westmeyer of the Institute of Biological and Medical Imaging at Helmholtz Zentrum München and PhD student Dong-Jiunn Jeffery Truong. The scientists examined the growing problem of insufficient donor organs in transplant medicine. “The participating students from TUM and LMU developed an innovative method that ultimately makes it possible to manufacture intact tissue and possibly even complete organs with the help of a 3D printer,” said Professor Skerra when speaking about his current project group. “This breakthrough was only made possible by a combination of the fields of synthetic biology, molecular biotechnology, protein design, and engineering.”

3D Plastic Printer Becomes ‘3D Bioprinter’

One question the team asked themselves was: What if the printed tissue could fulfill entirely new functions in the body, such as the production of therapeutic proteins? The printing of non-living biological material such as cartilage is already state-of-the-art. However, substantial obstacles still needed to be overcome on the path to printing complex cell structures. “And this is exactly where this year’s project began, in which living cells were printed onto a biocompatible matrix using a 3D printer,” project head Skerra explained. For this purpose, a conventional plastic 3D printer was converted into a 3D bioprinter.

Layer by layer, it creates biological tissue. In the past, hydrogels were used for such purposes — they provide a gelatinous scaffolding, and are only populated with cells retroactively. However, the students from both universities in Munich circumvented this restriction because the ‘scaffolding’ made printing more complicated, and held the cells together in an unnatural manner. Instead, they developed a special bio-ink, a type of biochemical two-component adhesive for directly printing living cells in 3D.

The main component of this system is biotin, most commonly known as vitamin H or B7, with which the surface of the cells was coated. The second component is Streptavidin, a protein that binds biotin and serves as the actual biochemical adhesive. In addition, bulky proteins were outfitted with biotin groups to serve as cross-links. “When a suspension of these cells in a concentrated solution of the protein components is ‘printed’,” Professor Skerra explained, “the desired 3D structure is then formed.” Hence, with this bio-ink, a plastic and moldable tissue made of living cells is created in the biotINK tissue printer — more or less ready for transplantation.