Expert Q&A: exploring the potential of 3D bioprinting

Left: Chuck Hull - EVP, Chief Technology Officer for Regenerative Medicine, 3D Systems
Right: Felicity Rose - Professor of Biomaterials and Tissue Engineering, University of Nottingham

In general terms what is 3D bioprinting and how does it work?

FR: Bioprinting is defined as the application of 3D printing to biomedical applications. It involves the use of materials or ‘bioinks’ that include the cells found in our body. Using these bioinks, we can print 3D structures that recreate the tissues and organs found in our body. This process involves creating a design file that can be used by the printer to create the desired shape, developing a bioink that is suitable for the cells but also compatible with the bioprinting process, and isolated and expanding the cells of interest in the laboratory. Once printed, the bioink and the shape provide the necessary biochemical cues to the cells, during incubation, to support their growth and maturation into a functional tissue or organ.

CH: 3D bioprinting is any form of 3D printing that involves living cells, sometimes printing with cells but more often printing a biomaterial scaffold that will then have cells added.

Why is it an important area of research and what are its potential applications?

FR: Globally, the demand for donor organs is greater than the supply. With an increasing and ageing population combined with  medical successes in organ and tissue transplantation, the increasing need for donor organs and tissues has resulted in a shortage in the supply. In some countries, there are national organ donor programmes to increase the number of organs available for transplantation, but such schemes are still not sufficient to provide the numbers of organs needed. Without these tissues, many people waiting for organ transplantation will die. 3D bioprinting also holds great potential to provide biomedical scientists with lab-based models of human tissue to investigate and understand disease, and to support the discovery of new drugs and medicines.

CH: There are numerous areas of research being conducted all around the world. Typical applications include biological laboratory studies; pharmaceutical drug testing; and soft and hard tissues for human regenerative medicine, including complete organs.

Outline your key areas of activity in this field?

FR: The Additive Biofabrication Laboratory is located within the Nottingham Biodiscovery Institute and is a multi-disciplinary collaboration between cell biologists and biomaterials scientists, with engineers and clinicians. The Additive Biofabrication Laboratory houses state-of-the-art 3D bioprinting equipment to allow for the printing of biologically relevant structures. An example of our work is the development of bioprinting strategies to recreate intestinal tissue, specifically the intestinal stem cell crypt, so that we can provide a future cell-based therapy or ‘living plaster’ that resembles and functions in the same way as the lining of the large intestine. We hope to use this to treat patients during the early stages of inflammatory bowel disease where the intestinal lining is lost, causing pain and diarrhoea. By replacing this lost tissue with a 3D bioprinted ‘living plaster’, we hope to support the tissue to heal and reduce the numbers of patients where the disease progresses such that they need surgery.

CH: We are specifically doing work for pharmaceutical testing, for various soft and hard tissues, and for transplantable lungs.

How do you expect the technology to develop over the next 10 years?

FR: 3D bioprinting is a rapidly developing field. Recent advances have seen the development of new 3D printing systems able to create 3D tissue structures in a single print (volumetric additive manufacturing) and systems that provide unprecedented resolution and feature size (multi-photon lithography). Further advancements are likely to focus on the scalability and increasing the speed of these systems such that we can manufacture regenerative medicine products as required. The development of bioinks that include chemistries with the required reaction kinetics for these new technologies, and that can be synthesised at scale and quality (GMP) will be needed to enable us to print the diversity of organs and tissues required. Further research will unlock the cell supply chain for new regenerative medicines and will pave the way towards personalised therapies. These technologies need to progress together, under a guiding regulatory framework, to ensure the full potential of 3D bioprinting can be realised.

CH: Our hopes and expectations are that in 10 years bioprinting will have significantly reduced animal testing for drug development and that some drugs will have been approved based on using bioprinted tissues. Additionally, we hope that regenerative medicine will have opened new and exciting treatments to significantly improve human health.

Do you believe we can ever expect to see 3D printed tissue or organs for transplantation? And what are the key technical obstacles to that vision?

FR: Yes, I do expect to see 3D printed tissues and organs available for transplantation, but I expect that it will take 50 years or more to see a fully transplantable organ manufactured using these technologies. The technical hurdles that need to be overcome include the development of new bioinks suitable for the various cell and tissue types in the body such that we can create not only the desired shapes and structures but also deliver the right biochemical cues to the cells to produce functional tissues and organs. We will need to develop the technologies available to allow for faster printing times (to support cell survival) without losing resolution of the print; these printing technologies will also need to be scaleable for manufacture. We will need to develop the bioprinting strategies to allow for the printing of larger and more complex tissues, such as a whole organ, that contains blood vessels and a nerve supply, so that the organ remains viable and is fully functional at the time of transplantation.

CH: We certainly believe this. Living cells are the key to regenerative medicine, and the purpose of 3D bioprinting is to build an environment where the cells can live and function as they should. The obstacles include having the right materials, printing with the required precision, and placing the right cells to create new tissue. Other obstacles include the significant pre-clinical and clinical work for human health applications. This includes demonstrating to the regulatory agency (the U.S. Food and Drug Administration) that the treatments are safe and effective and are produced using Good Manufacturing Practice (GMP). The timeframe for this is uncertain and it usually takes several years.