High resolution, multi-material deposition of tissue engineering scaffolds

Lead Research Organisation: University of Cambridge
Department Name: Engineering

Abstract

The next generational change in health treatment will be the tailoring of artificial implants in combination with a patient's own cells to replace diseased or damaged tissues and organs. There will also be development in drug research through the creation of complex tissue models in vitro that mimic certain body systems. With these models we will be able to reduce the need for animal testing and provide a deeper understanding of the impact of drugs on cell function. To undertake these changes, one requires a fabrication technique that can accommodate a wider choice of biomaterials, combined with delivery of complexity in terms of feature size, structure and functionalities. This project aims to develop a new biomaterial fabrication technique which can process different material elements into a sizable scaffold in a controllable, scalable manner. The configuration will be tailored to fit the ultimate reaction kinetics of the biomaterial. This technique will exhibit (a) a sub-micron printing resolution of fibrous structures (vs. tens of micron of the existing 3-D printing), (b) ability to co-print both fibrous components and interstitial gel components, (c) suitability for scaled-up fabrication of a vast biomaterial library without needing to modify the native material chemistry. Ultimately, this new biomaterial fabrication technique will enable the reproducible, automated creation of multi-functional biomaterial scaffolds to support soft tissue regeneration. It is believed that the proposed technique will facilitate the fabrication of personalised scaffold parts, thus enabling more effective treatment available to the general public.

Planned Impact

Biomaterial-based tissue engineering has made significant impact on people's lives. Examples are as demonstrated with skin grafts for burn victims reducing scarring and improving healing, orthopaedic implants dramatically improving the mobility of patients, and tissue grafts for regenerating bladder functions. The global tissue engineering market is projected to be approximately £18 billion by 2020, which doubles the current (2014) market value of £9 billion. To improve the treatment outcome, and also to tackle difficult applications such as growing tissue organ transplants, innovation in tissue engineering has to be made. As stated in the EPSRC Healthcare grant challenges, enabling technologies for regenerative medicine, and patient specific treatment are two of the key areas where research inputs will generate significant impact. In this project, the technology developed will enable the deposition of a versatile range of biomaterials of mixed properties for personalised treatments. This capability is currently not adequately supported by existing fabrication technologies. The development of the proposed new biomaterial fabrication method will potentially open new avenues to tailored implants and the creation of more informative drug testing technologies. This will provide the next step change in current healthcare technologies.

For the ultimate implementation of the proposed instrumentation, its design concept will facilitate its use in a hospital setting. This attribute can greatly reduce the problems associated with preservation of the tissue scaffold from the manufacturing site to the point of use. The potential reduction in lead time will also add significant benefit to the treatment outcome.

In addition to its relevance to Healthcare, the proposed work will provide a new technology added to the existing repertoire of additive manufacturing methods. Currently, the global additive manufacturing market is valued at £1 billion per year. Among this, automotives accounts for the largest share of the market since end-products can be more conveniently produced. With new technologies developed, such as the one presented in this project, additive manufacturing will generate wider impacts in other industries such as electronics, pharmaceutical, cosmetic and food. This sees the potential to have improved manufacturing processes which is low-waste, energy efficient and stream-lined. This will in turn lead to improved productivity, and more environmentally friendly productions.
 
Description A low voltage electrospinning mechanism, which can be adapted to a 3D printing platform. Batch processing can be performed instead of the conventional one by one process.
Exploitation Route Various collaborations have been established to further the use of the printing platform for organ on a chip production
Sectors Agriculture

Food and Drink

Chemicals

Electronics

Energy

Healthcare

Manufacturing

including Industrial Biotechology

Pharmaceuticals and Medical Biotechnology

 
Description From capturing a person's breath to guiding biological cell movements, 3D printing of tiny, transparent conducting fibres could be used to make devices which can 'smell, hear and touch' - making it particularly useful for health monitoring, Internet of Things and biosensing applications. https://www.cam.ac.uk/research/news/3d-printed-invisible-fibres-can-sense-breath-sound-and-biological-cells
First Year Of Impact 2020
Sector Electronics,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal

Economic

 
Description UK Parliament Post on '3D Bioprinting in Medicine'
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact Panel of experts for advising a white paper for the UK Parliament Post on '3D Bioprinting in Medicine'
URL https://post.parliament.uk/research-briefings/post-pn-0620/
 
Description ERC Starting Grant (2017)
Amount € 1,480,000 (EUR)
Organisation European Research Council (ERC) 
Sector Public
Country Belgium
Start 01/2018 
End 12/2022
 
Description Isaac Newton Trust Research Grant
Amount £40,000 (GBP)
Organisation University of Cambridge 
Department Isaac Newton Trust
Sector Academic/University
Country United Kingdom
Start 03/2017 
End 02/2018
 
Description EPSRC-first grant 
Organisation University of Nottingham
Department School of Pharmacy
Country United Kingdom 
Sector Academic/University 
PI Contribution A technique, cEJW is being developed by my team to co-deposit a range of biomaterials, at a sub-micron resolution.
Collaborator Contribution My collaborator synthesizes materials with specific surface chemistry for tunable cell adhesion. My team is tuning the ink formulation of this materials to be deposited by the cEJW technique.
Impact The research is still being conducted. This research collaboration is multi-disciplinary, combining expertise in engineering and chemistry.
Start Year 2015
 
Description MSC-topography response 
Organisation University of Cambridge
Department Department of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Using the cJEW biomaterials fabrication developed by my team, we create hierarchical structures to investigate the effect of matrix topography on mesenchymal stem cell differentiation.
Collaborator Contribution My collaborator specialises in mesenchymal stem cell biology, and is responsible for the cell culturing and evaluate the stem cell's differentiation.
Impact Experiments are still in progress. This collaboration is multi-disciplinary which consists of expertise in stem cell biology and bioengineering.
Start Year 2015
 
Description Pittsburgh decellularised matrix 
Organisation University of Pittsburgh
Country United States 
Sector Academic/University 
PI Contribution A new biofabrication method, based on the continuous electrojetting mechanism, was developed by my team to construct basement membrane like structures. This method is instrumental in incorporating decellularised matrices to produce more biologically relevant, artificial basement membranes.
Collaborator Contribution My partners provides the decellularised matrices (dECM) extracted from small intestines and bladders.
Impact This work has started since Sep 2015, when the materials transfer agreements were completed and the materials were delivered. Our results successfully demonstrated that the collagen (as a model for dECM) can form a membrane structure to support endothelial layer formation. We are now working on using the dECM to demonstrate a similar membrane structure. The collaboration is multi-disciplinary, crossing fields of engineering, physics, biology and medicine.
Start Year 2015
 
Description 3D Printing Conference (Maastrict) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact New 3D fibre making technology was displayed at the conference, attracted interests from both the academic community as well as the industrial
Year(s) Of Engagement Activity 2017
URL https://www.3dbioprintingconference.com/program/
 
Description Homerton College Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Between 20-40 pupils attended for a school visit to the talk on Bioengineering, which sparked questions and discussion afterwards, and the school reported increased interest in related subject areas.
Year(s) Of Engagement Activity 2012,2013,2014
 
Description Interview with 3DMedNet 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Give opinion to the 3D bioprinting network
Year(s) Of Engagement Activity 2017
URL https://www.3dmednet.com/users/24427-freya-leask/videos/15549-video1
 
Description Summer placement schemes 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact I participate in summer placement schemes for undergraduate students every year since the start of my independent research. These are through schemes such as UROP, and IOP top 50 placements. These schemes are valuable for undergraduate students to get a first hand on experience of research experience, and to spark their interest for further research.
Year(s) Of Engagement Activity 2011,2012,2013,2014,2015,2016
 
Description Turin - Organoids workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Supporters
Results and Impact Delivered a speech at the workshop 'Enabling Technologies in 3D Cancer Organoids' as part of the 'Torino Donna just the woman I am' Day. The event was taken place between 8th-9th March 2016.
Year(s) Of Engagement Activity 2016
URL http://www.torinodonna.it/workshop/
 
Description Youtube podcast 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact A youtube channel was setup to share research videos with general audience.
Year(s) Of Engagement Activity 2010,2013,2014,2015,2016
URL https://www.youtube.com/watch?v=Kax_0Xd63cA