Bioprinting has emerged as one of the most promising techonologies for fabricating artificial tissues and organs that could revolutionize the diagnosis and treatment of many different medical conditions. In a recent review article for the journal Biofabrication, researchers at Stanford University in the US discuss the current status of bioprinting research, and assess its future potential for drug screening and toxicology studies, as well as tissue and organ transplantation.
“Just as the printing press allowed massive amounts of information to be accessed at low cost for the first time in mankind’s history, so bioprinting could potentially provide a high-throughput and affordable way to assemble cells to make complex tissue constructs that are widely available to a very large number of researchers and scientists,” says team leader Utkan Demirci. “We aim to provide real solutions to many clinical problems that exist today.”
Demirci defines bioprinting as the process of using advanced additive manufacturing technologies to pattern biological materials, such as cells, biomaterials and biomolecules, for the fabrication of tissue-mimicking constructs. This novel approach requires biocompatible materials called bioinks to act as the matrices for printed cells, which can then be grown in bioreactors to further develop and become functionally mature.
Control at the cellular level
In their own research, Demirci and his colleagues exploit various micro- and nanoscale technologies, including 3D bioprinting and assembly, to create artificial tissues for biomedical applications. A key focus for their research is to control the cellular micro-environment and push the limits of cell manipulation through dedicated nano- and microscale technology platforms. Creating architectures that mimic the complexity of native tissues, as well as the functions and structures of specific cells, are expected to have important applications in precision medicine.
“Our research group aims to build complex cellular systems that mimic nature, but we also want to create systems from scratch that direct self-assembly,” explains Demirci. “Externally applied forces can actually trigger the act of complex self-assembly; these forces can be magnetic, electrical or even acoustic.”
Demirci says that a number of significant new approaches have been developed by research groups around the world since the team’s review was published in March 2016. “One example that comes to mind is an innovative label-free magnetic levitation platform that has been developed for 3D assembly of cells in complex living architectures,” he says.
Out of this world
Demirci and his team have focused their efforts on biofabrication through the self-assembly of cells, rather than growing constructs on tissue scaffolds. More recently, however, they have become interested in biomanufacturing cellular constructs in the absence of a gravitational force field – with the aim of exploring whether tissue could be engineered in space.
“All existing bioprinting methods rely on the presence of droplets (for example, in the drop-by-drop or drop-on-demand bioprinter) or on extruding materials landing on a surface, which is the one of the most affordable ways to bioprint,” comments Demirci. “We are trying out alternative approaches, such as assembling cells in 3D using a controlled magnetic field, to direct cells to form organoids.”
How do you define biofabrication today?
Demirci explains that cells in nature self-assemble at the microscale into complex functional configurations and microarchitectures, and researchers are increasingly exploiting this mechanism to assemble biomimetic systems in vitro. “However, we would ultimately like to precisely code 3D multicellular complex living materials, which is an exciting challenge given their architectural complexity and spatiotemporal heterogeneity.”
“Such techniques, which would build living materials with 3D control over geometry and organization, might be able to create model systems that mimic the physiological as well as pathological behaviour of native tissues,” he continues. “Such models might be extremely valuable in cancer for precision medicine to better care for patients.”