The future of medicine is biological – and scientists hope that we will soon use biologically functional 3D printed fabric to replace irreparably damaged tissue in the body. A team of researchers from the Fraunhofer Institute for cross-functional engineering and biotechnology IGB has been collaborating for several years with the University of Stuttgart on a project for the development and optimization of adequate bioinks for the additive manufacturing. By varying the composition of the biomaterial, the researchers have already succeeded in expanding their portfolio by including bone inks and vascularization. This laid the foundation for the production of bone tissue structures with capillary networks.
3D printing is not only gaining ground in the manufacturing sector, but is becoming increasingly important in the field of regenerative medicine. Scientists now hope to use this additive manufacturing method to create scaffolds of tailor-made biocompatible fabrics that will replace irreparably damaged tissues. A team of researchers from Fraunhofer IGB in Stuttgart is also working on biobased inks for the production of biological plants in the laboratory using 3D printing techniques. To create a 3D object in the desired pre-programmed form, the team uses a layer by layer approach to print a liquid mixture comprising biopolymers such as gelatin or hyaluronic acid, aqueous medium and living cells. These bio-inks remain in a viscous state during printing and are therefore exposed to UV light to connect them in polymeric networks containing water called hydrogels.
Targeted chemical modification of biomolecules
Scientists can chemically modify the biomolecules to provide the resulting gels with different degrees of crosslinking and swellability. This allows you to mimic the texture of natural tissue – from stronger hydrogels to cartilage to softer gels to fatty tissues. Ample adjustments can also be made to the viscosity level: "At an ambient temperature of 21 degrees Celsius, the gelatin is as solid as gelatin, which is not good for printing. To prevent temperature-dependent gelation and allow us to process it independently of temperature , we "mask" the side chains of the biomolecules responsible for gelatinous gelatin, "says Achim Weber, head of the Group of particle systems and formulations, explaining one of the main challenges encountered in the process.
An additional challenge is that the gelatin must be chemically crosslinked to prevent liquefaction at temperatures of around 37 degrees. To achieve this, it is functionalized twice: in this case, the research group has opted for the integration of the methacrylyl crosslinkable groups in the biomolecules, thus replacing various parts of the non-crosslinking and masking acetyl groups, a unique approach in the field of bioprinting. "We form inks that offer adapted conditions for different cell types and tissue structures," says Dr. Kirsten Borchers, head of bioprinting projects in Stuttgart.
In collaboration with the University of Stuttgart, the team has recently succeeded in creating two different hydrogel environments: stiffer gels with mineral components to adapt to softer bone cells and gels without mineral components to allow blood vessel cells to form in capillary structures.
Bone and vascularization inks
Researchers have already succeeded in producing bone ink based on the material kit they created. Their goal is to enable the cells processed in the kit to regenerate the original tissue, in other words to form the bone tissue itself. The secret to creating ink is found in a special mixture of hydroxyapatite from bone mineral powder and biomolecules. "The best artificial environment for cells is the one that comes closest to the natural conditions of the body: this is why the role of the tissue matrix in our printed tissues is played by biomaterials that we generate from elements of the natural tissue matrix", says The scientist .
Vascularization ink forms soft gels that support the creation of capillary structures. The cells that form blood vessels are incorporated into the inks. The cells move, migrate one to the other and form systems of capillary networks consisting of small tubular structures. If this bone substitute were to be implanted, the biological implant would connect to the recipient's blood vessel system much more quickly than an implant without capillary pre-structures, as detailed in the relevant literature. "It would probably be impossible to print larger tissue structures in 3D without vascularization ink," says Weber.
The last research project of the Stuttgart team involves the development of matrices to regenerate cartilage. "Whatever type of cell we isolate from body tissue and multiply in the laboratory, we need to create a suitable environment in which they can perform their specific functions for longer periods of time," explains the team's bioengineer, Lisa Rebers.
Fraunhofer IGB continues to carry out its research work at the mass customization center of the masses in Stuttgart within the framework of a joint initiative with the Fraunhofer Institute for Manufacturing Engineering and Production. IPA automation and the University of Stuttgart. The interdisciplinary working group of Additive4Life is responsible for the creation of new technologies and printable biomaterials for bioprinting.