3D Bioplotter for Biological Tissue Development

Lead Research Organisation: Imperial College London
Department Name: Bioengineering

Abstract

Biological tissues in humans, animals, and even plants have evolved into highly complex three dimensional structures. Nature has devised and made use of a variety of materials, ranging from very stiff to highly elastic, resulting in the tremendous variety of living structures we see around us every day. These tissues also incorporate cells, which can actively change and remodel the surrounding tissue in response to changing needs. One example is the common observation that tennis players often have a dominant arm that is larger and more muscular than their other arm. While common sense tells us that the increased mechanical load on that arm causes it to grow bigger, there is much about these remodelling processes that we do not understand. There are also remodelling processes that are involved in disease formation. Indeed, many of the problems of modern human and animal medicine, agriculture, and the environment involve the response of tissues to external forces or harmful chemicals. In order to understand these responses, researchers need to be able to study tissue behaviour in great detail. The use of actual living tissue is limited, and sometimes involves complex and important ethical issues. We therefore turn to the possibility of constructing tissues in our laboratory to unlock nature's secrets and develop important new disease treatment strategies. So far, our abilities to faithfully reconstruct tissues have been limited. However, we can now literally "print" tissues in full 3D, incorporating the various complex materials and even living cells. We propose to purchase one of these 3D Bioplotters, and use it to address a variety of important biomedical problems. Our research experts in the Bioengineering Department at Imperial College are interested in a variety of diseases that cause most of the deaths and suffering in the UK. These include cancer, arthritis, heart disease, Alzheimer's, as well as burns and other injuries. We plan to apply this technology to construct tissues that imitate as closely as possible the body's tissues that are affected by these conditions. That will allow us to understand tissue behaviour and test revolutionary treatment strategies that can alleviate suffering and prevent deaths. There is also the possibility that we can print new tissues for implantation into the body. This area of research (called "regenerative medicine") is an exciting new area for exploration, but is still in the early days of application. We have several ideas for these implants that we will test, with the expectation that the actual human implants will be developed by companies and/or hospitals.

Technical Summary

Biological tissues are highly complex 3D structures composed of a variety of materials with highly tuned behaviours that respond and remodel to changing conditions. Recognition of this complexity is important for basic and applied research. The recent development of biologically compatible Additive Manufacturing (AM, a subset of which is 3D printing) technologies renders it possible to reconstruct tissues from the cell level up, incorporating a variety of materials and complex geometries. We propose to purchase the latest generation of biologically compatible AM technology (3D Bioplotter, Envisiontec, Germany), and incorporate it into the suite of research capabilities in Imperial's Department of Bioengineering. This printer can deploy polymers, ceramics, metals, cell suspensions, etc., and can print up to five materials in one construct. The potential applications span all areas of biology, including human+animal medicine, agriculture, and the environment. Our initial applications will be biomedical. The initial users (2 senior staff and 2 junior staff) will print tissue constructs of bone, cartilage, myocardium, neural, skin, tumours, and lymph nodes for application to basic and applied research. Broadly, these fall into two categories. First is the production of constructs that imitate basic tissue functions so that we can explore the complex, interconnected nature of natural tissue function, and then use those physiologically realistic constructs to test disease monitoring or treatment strategies. The second application will be more directly in the area of regenerative medicine (an important and growing research thrust for our department). It is envisioned that the 3D Bioplotter should be able to print constructs that could be implanted in vivo to treat a variety of disease conditions. While we do not anticipate producing implants for human use, this capability will allow us to develop tissue construct design concepts and perform pre-clinical testing.

Planned Impact

The facility that will be constructed around the 3D Bioplotter will be designed for optimum flexibility, so that a variety of research and development questions may be addressed. While our applications are biomedical in nature, the capabilities of the 3D Bioplotter go well beyond, including other areas of biology, animal physiology, agricultural issues, and the environment. We anticipate that bringing this capability into the UK will stimulate interest from all of these areas in both research centres and industry.

Because Bioengineering is naturally a collaborative and interdisciplinary area, we already have extensive contacts in related research fields such as biology, chemistry, and medicine, as well as other engineering discplines. This will rapidly expand our applications beyond those outlined in the Case for Support. Thus, we anticipate a profound impact on the research capabilities of the UK.

This capabilities of the 3D Bioplotter will also impact industry, and thus the economy of the UK. The medical device industry in the UK will be a particular focus at first, in part because it is largely composed of SMEs that would not normally have access to this kind of facility. We will also develop implantable device concepts that can be prototyped with this equipment. It is likely, given our previous successes with spinouts, that these technologies will be licensed out to industry, or new companies started as a result.

Society in general will benefit from the increase in knowledge of complex tissue functions, as well as the development of new methodologies to treat the diseases that are responsible for the majority of deaths and suffering in the UK. There will also be benefits from employment in the new companies that may be formed based on our technologies. These tend to be highly paying jobs with opportunities for significant growth, given the world-wide need for medical advances. Placing this equipment in an institute of higher learning also means that our students, technicians and other trainees will have the opportunity to learn to operate the equipment, directly impacting their own employability.

Publications

10 25 50
 
Description We have developed blood vessel network phantoms printed with living tissue for research purposes. We have also discovered the mechanical conditions that cause mechanical lysis of cells during printing, and are developing a new printing nozzle to optimise cell viability.
Exploitation Route Vessel network phantoms have been successfully produced and will be used for atherosclerosis research.
Sectors Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description Vascularised tissue constructs 
Organisation Imperial College School of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Prof. Peter Weinberg's PhD student Josefin Edquist mad a beautiful mock circulation with it that has now been incorporated into a tissue engineered construct in Anna Randi¹s lab. I believe she has been offered a PhD here as a result, but too early for publications.
Collaborator Contribution Fabricated a vascularised tissue construct on 3D Bioplotter.
Impact PhD studentship
Start Year 2016
 
Description Mentoring students at Kings Math School on a project 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Supervised small group of students doing a maths modelling project on lymphatic transport.
Year(s) Of Engagement Activity 2017,2018,2019