Biofabrication – Building Blocks for the Medicine of the Future

The future of medicine is biological. Fraunhofer IGB combines cell biology, materials science, and biotechnology to produce in-vitro tissues – from cell cultivation and optimization of the biomaterials required as scaffolds to the production of three-dimensional tissue constructs using printing processes. The printed in-vitro tissues will serve as test systems to investigate the efficacy of drug candidates, as tissue models for biomedical research, or as personalized and – in the future – biological implants that stimulate the regeneration of damaged tissue or replace it.

At Fraunhofer IGB, the research field of biofabrication encompasses the systematic production of complex biological structures, such as tissues and organs, through the targeted interaction of cells, biomaterials, and process-based manufacturing technologies. Additive processes in particular enable the creation of hierarchically structured tissues, which can be crucial for the functionality of cell structures. Biofabrication thus forms the technological basis for the targeted development, functional design, and scalable production of biological systems.

As an interdisciplinary field at the interface of cell biology and biotechnology, materials science, and process engineering, biofabrication is a key enabler for modern biomedicine – whether for the development of functional tissue models, meaningful in-vitro test systems, personalized implants, or, in the future, regenerative tissue replacement.

In vivo, cells are embedded in a natural tissue matrix, the extracellular matrix (ECM), a dynamic structural network of proteins such as collagen and carbohydrates with the consistency of a highly water-containing gel. The ECM stabilizes the tissue, giving it mechanical strength and elasticity. In addition, it is also involved in intercellular communication and ensures the supply of nutrients. These comprehensive functions cannot be easily replicated by synthetic materials.

In biofabrication, we use biomaterials as scaffolds or carrier structures for cells to create biologically active cell models, tissue constructs, or implants. As in their natural counterparts, biomaterials must also provide cells with an environment that is as physiological as possible, i.e., conditions that promote adhesion, growth, and differentiation.

Versatile applications in biomedicine and biotechnology

The institute has been researching and developing bio-based and functional biomaterials for applications in biofabrication for many years. These include natural and polymer-based carrier materials and hydrogel systems, for example made from gelatin, collagen, or hyaluronic acid, which are specifically designed for the respective application in terms of their mechanical properties, structurability, and biological functionality. Particular attention is paid to sustainable raw material concepts, precise adaptability to cellular requirements, and integration into scalable manufacturing processes.

The materials developed are used, among other things, as coatings for implants and other medical devices, but also in inks and formulations for bioprinting tissue models, biomedical test systems, and biotechnological production platforms.

The controlled cultivation of cells is a key challenge in biofabrication – particularly with regard to reproducibility, scale-up, and process stability. Fraunhofer IGB establishes suitable cell lines and production strains for this purpose, develops defined and sustainable cell culture media, co-culture models, and process-based cultivation concepts that realistically replicate physiologically relevant conditions.

This work forms the basis for robust in-vitro models and enables the transfer of biointelligent research solutions to industrial development environments. To this end, a pilot bioreactor plant is currently being set up at Fraunhofer IGB, which will enable processes to be transferred to an application-oriented scale. This represents a milestone that will directly benefit our partners and customers.

In order to build tissue in the laboratory that functions as well as its natural counterparts, in addition to the optimal biomaterial, manufacturing processes are also required that impose as few limitations as possible in terms of shaping. Additive processes offer great flexibility in this regard. With their help, three-dimensional objects that were previously designed on the computer can be built up layer by layer. In addition to the advantage of free and precise design, 3D printing also offers the possibility of faster prototype development. Another factor here is that production takes place under controlled and standardized conditions thanks to automation and digital control.

Before biomaterials can be shaped using printing processes, their flow properties must be adapted to the printing technique used. After the printing process, the structure produced is then additionally stabilized by a cell-compatible cross-linking reaction. 

Printable biomaterials enable additive manufacturing

A major focus is therefore on the development of printable bioink formulations for 2D and 3D bioprinting applications. At Fraunhofer IGB, natural polymer materials (e.g., alginates, gelatin, collagen, or hyaluronic acid) and bio-based polymer materials (e.g., chemically modified biopolymers such as GelMA, modified hyaluronic acid) are combined into application-specific bioinks that combine high cell viability, defined rheological properties, and reliable processability. For tissue engineering applications, for example, cross-linking biocompatible hydrogels are used and biomolecules are equipped with cross-linkable groups or functionalities through chemical modification to control solubility properties and viscosity.

The close integration of material design, printing process, and application enables the construction of complex cell-material constructs for research, technology development, and industry-oriented demonstrators.

The flexible shaping capabilities of additive manufacturing are also important in terms of the vision of producing printed biological implants. Modern imaging diagnostic procedures, which are already widely used in everyday medical practice today, can provide the precise digital 3D data required for the manufacture of customized implants.

TriAnkle: Faster regeneration thanks to personalized implants 

A successful example was the European research project TriAnkle, which aimed to develop innovative personalized implants for the regeneration of tendon and cartilage tissue in the ankle joint. At Fraunhofer IGB, we developed new materials from gelatin and collagen, which were shaped into artificial tissue using a special 3D printer. Animal experiments with rats and sheep have shown that this artificial tissue helps the body to regenerate better and faster. The project is also exemplary for the systemic approach of bioconvergence between materials science, biology, and medical technology.

In addition to medicine and medical technology, biofabrication also opens up new perspectives as a resource-efficient production system. In the research field of “Biofabrication,” we therefore also use the biofabrication technologies we have developed for other applications.

For example, we are currently working on animal cell culture systems for sustainable nutrition and “cell-based agriculture.” One focus here is on providing alternative protein sources such as cultured meat and fish.

Another field of application is engineered living materials (ELM), biologically active structures based on living fungal cells that grow into predefined shapes. At Fraunhofer IGB, we use fungal mycelium as a promising material for a new generation of sustainable, bio-based composites that are biodegradable and made from renewable raw materials. Our research focuses on structuring, shaping, and functionally adjusting such living materials. In ongoing projects, we are working on the development of suitable inks for 3D printing of mycelium-based materials that can be used for sustainable lightweight constructions, as biodegradable components, and in biologically active filter systems.