Scientists have long been working to improve methods and procedures for artificially producing tissue. In the current work, researchers at Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB) in Stuttgart, Germany, developed a suitable bio-ink for 3D printing that consist of gelatin-based components from natural tissue matrix and living cells. Gelatin is a well-known biological material derived from collagen that serves as the main constituent of native tissue.
The IGB researchers were able to chemically modify the gelling behavior of the gelatin to adapt the biological molecules for printing. This allowed the bio-ink to remain fluid during printing, instead of gelling like unmodified gelatin. Once the bio-inks are irradiated with UV light, they crosslink and cure to form hydrogels – polymers containing a large amount of water (just like native tissue), but which are stable in aqueous environments and when heated to 98.6 degree Fahrenheit – the average temperature of the human body.
The chemical modification of these biological molecules can be controlled so that the resulting gels have differing strengths and swelling characteristics, allowing researchers to imitate various properties of natural tissue – from solid cartilage to soft adipose tissue.
The IGB research facility also prints synthetic raw materials that can serve as substitutes for the extracellular matrix, such as systems that cure to a hydrogel devoid of by-products, which can immediately be populated with genuine cells.
“We are concentrating at the moment on the ‘natural’ variant. That way we remain very close to the original material. Even if the potential for synthetic hydrogels is big, we still need to learn a fair amount about the interactions between the artificial substances and cells or natural tissue. Our biomolecule-based variants provide the cells with a natural environment instead, and therefore can promote the self-organizing behavior of the printed cells to form a functional tissue model,” said Dr. Kirsten Borchers in describing the approach at IGB.
The printers at IGB’s labs in Stuttgart have a lot in common with conventional office printers – the ink reservoirs and jets are all the same. The differences are only observable upon close inspection, such as the heater on the ink container with which the right temperature is set for the bio-inks. The number of jets and tanks is also smaller than those in the office counterpart.
“We would like to increase the number of these in cooperation with industry and other Fraunhofer Institutes in order to simultaneously print using various inks with different cells and matrices. This way we can come closer to replicating complex structures and different types of tissue,” said Borchers.
The researchers said their current challenge is to produce vascularized tissue that has its own system of blood vessels through which the tissue can be provided with nutrients. To reach this goal, IGB is collaborating with partners under the EU-supported Project ArtiVasc 3D, which seeks to develop a technology platform to generate fine blood vessels from synthetic materials to create artificial skin with subcutaneous adipose tissue.
“This step is very important for printing tissue or entire organs in the future. Only once we are successful in producing tissue that can be nourished through a system of blood vessels can printing larger tissue structures become feasible,” said Borchers.
The development of suitable bio-inks represents an important step towards 3D printing of tissues and organs, for which demand is expected to soar in the coming years due to an aging population and advancements in the field of transplantation medicine.