Novel implant design and manufacture with embedded therapeutics

Lead Research Organisation: University of Birmingham
Department Name: Chemical Engineering

Abstract

The development of implantable prosthetics has revolutionised medicine. Where joint injury or destruction would once have once significantly reduced quality of life, to the detriment of a patient's fitness and health, we can now almost fully restore function. The manufacturing methods used for the production of prosthetics are quite crude and often require the casting of metal into a mould before finishing by hand. As a consequence they are usually made to only a few different sizes and the resulting structures must be made to fit by the surgeon. This is acceptable for the majority of patients who require joint replacement, but there are some medical conditions that require very irregularly shaped (customised) structures to enable an adequate repair. For example, bone cancers often require extensive cutting away of the bone and this can leave a very large and irregular defect. Similarly the bone structure of the face and skull is very specific to an individual and when bone must be removed, again due to cancer or following physical damage. To restore physical appearance, it would be best if a clinician were able to generate a plate that could allow them to replace like for like.
In this project, we will refine an Additive Layer Manufacturing (ALM) technology called selective laser meeting (SLM) to allow us to produce implants that are individual to a patient. These technologies use lasers to fuse powder and create a three dimensional object in a layer by layer fashion. By taking three dimensional images (MRI and CT) from a patient, operators can design structures that will be able to directly replace tissue with the optimum shaped implant. In this project, we will work with doctors from the Royal Orthopaedic Hospital, Queen Elizabeth Hospital and the Royal Centre for Defence Medicine to develop a process that we hope will eventually allow these clinicians to produce implants in their own hospitals or even on the front-line of a conflict and enable better treatment for their patients.
As well as allowing the production of complex-shaped parts, ALM has another significant advantage over casting in that it allows the production of very complex porous structures within a material. This means that we can modify the physical properties of the material by incorporating holes or structured porosity into the structure. These holes can be sealed from the surface of the prosthesis, or can be linked to the surface using a network of even narrower holes. We would like to explore the use of this added manufacturing capability to make prosthetics with a very closely defined internal structure that is completely interconnected. A second, cement like, material can then be injected into the pore structure and will harden in place. This second phase can be used to modify mechanical properties or could be used as a carrier for drugs that may stop infection or help the tissue to heal. It is hoped that this modification could help us eliminate implant-based infections, which is the leading cause of failure following prosthetic implantation.

Planned Impact

The research undertaken in this project will generate impacts of academic, economic and social importance, often in a non-mutually exclusive manner. From the possible impacts outlined by the RCUK as allowable, we would deliver academic impact from:
The development and utilisation of new and innovative methodologies, equipment, techniques, technologies and cross-disciplinary approaches - the proposed work will optimise existing processes in terms of the resolution and performance of the final product. It will also bring together industrial partners from sectors who would not normally work together. Transfer of technologies across disciplines in this manner will undoubtedly advance the technology and generate impact to UK industry.
Contributing towards the health of academic disciplines - developing knowledge in new disciplines or multidisciplinary areas - ALM is now recognised as a highly disruptive technology, which is set to change the face of the manufacturing industries. Although in development since the 70's, relatively recent innovations have meant that the potential of this technology is now being realised. Application of technology in this sector will require the development of multidisciplinary researchers and knowledge that will help shape medical technology in the future.
Delivering and training highly-skilled researchers - The project will employ two postdoctoral researchers and will also attract two CASE PhD students from industry (TWI and Johnson Matthey), and at least one university-funded position. These individuals will be exposed to technologies and techniques outside their normal skill-set. As such the project will provide a high-quality multidisciplinary training environment. Prof. Grover's works across disciplines and his experience in supervising PhD students and postdoctoral researchers will help the project to deliver highly skilled, multidisciplinary individuals.
From the point of view of Economic and Social Impact, the project will deliver in the following areas:
Enhancing cultural enrichment, quality of life, health and well-being - Ultimately, the most important beneficiaries of medical technologies ought to be the patients that will benefit from better treatment. One consequence in an improvement in patient treatment, if effectiveness is enhanced is a reduction in the cost of the healthcare provision and an improvement in the way that the individual is able to contribute to society.

Shaping and enhancing the effectiveness of public services - Related to patient well-being, is an improvement in clinical practice that will be of benefit to the clinicians delivering the treatment. The clinicians that we have engaged in this project are all excited to be involved with the project since its findings are likely to assist them in delivering better care to their patients. Although initially the high cost of single parts means that use of this technology will be limited to the production of specialised prosthetics, in the longer term, ALM may be used to drive down cost by wasting less material, using less energy and eliminating the need for finishing by hand.
Contributing towards evidence-based policy making - Critical to commercialisation of a medical technology is gaining the correct regulatory approval and planning for gaining regulatory approval as early as possible. From our discussions with industry there is clear uncertainty surrounding how these prosthetics may be manufactured to comply with the regulatory framework. Furthermore, the creation of multifunctional devices causes regulatory problems that may prevent the implant industry from innovating to develop antibacterial implants - ultimately at the cost of the patient. By working with regulators from the first step, and working with those that set device standards, we may de-risk this technology for others in the sector and ultimately open up new pathways for innovation.

Publications


10 25 50
Cox SC (2016) Adding functionality with additive manufacturing: Fabrication of titanium-based antibiotic eluting implants. in Materials science & engineering. C, Materials for biological applications
Cox SC (2014) Preparation and characterisation of nanophase Sr, Mg, and Zn substituted hydroxyapatite by aqueous precipitation. in Materials science & engineering. C, Materials for biological applications
 
Description We have demonstrated that it is possible to develop hollow implants and control release from the implants by simply controlling microstructure. We have recently submitted a paper that shows that it is possible to deliver antibiotics in a sustained way, which kills pathological bacteria. This might go somewhere towards reducing the risk of implant related infections, which is currently the largest cause of failure in implants. We are now exploring whether it is possible to deliver factors that may be used to expedite healing.
Exploitation Route Our findings show that it is possible to tailor release by varying pore geometry, this is a major finding since that may be used by others to develop novel structured implants.
Sectors Construction,Healthcare,Manufacturing, including Industrial Biotechology
 
Description Our findings are in the process of being used to refine existing manufacturing processes to reduce the likelihood of infection following the production of bespoke prosthetics.
First Year Of Impact 2016
Sector Healthcare
 
Description EPSRC Healthcare Impact Partnership
Amount £1,100,000 (GBP)
Funding ID EP/P02341X/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom of Great Britain & Northern Ireland (UK)
Start 07/2017 
End 06/2020
 
Description Silver embedding on ALMd surfaces 
Organisation Accentus Medical
Country United Kingdom of Great Britain & Northern Ireland (UK) 
Sector Private 
PI Contribution We have set up a collaboration between ourselves, the University Hospital of Birmingham Maxillofacial Repair Department, the Royal Centre for Defence Medicine, Accentus Medical and Cavendish Implants. Within this collaboration, we seek to bring together process innovation in additive layer manufacturing and silver embedding to produce prescribed prosthetics with a lower chance of infection.
Collaborator Contribution Birmingham Maxillofacial Repair Departments - have allowed us to examine their processes and identify potential sources of infection. RCDM - have initiated work with us to investigate how our prosthesis modification technology can be used to reduce infection in transcutaneous prosthetics. Accentus are working with us to implement their novel silver coating process into our additive layeer manufacturing process. Cavendish implants are working in collaboration with us to provide cast alternatives for our additively manufactured implants.
Impact We have recently secured an EPSRC grant that will help us to move the collaboration forwards, hopefully to the point that it is of significant clinical value (EP/P02341X/1). The collaboration is highly multidisciplinary and involves industry (Accentus and Cavendish), medical practicioners (RCDM, UHB and Addison), materials scientists (Grover and Attalah), and Mechanical Engineers (Shepherd and Cox).
Start Year 2016
 
Description Silver embedding on ALMd surfaces 
Organisation Royal Centre for Defence Medicine (RCDM)
Country Unknown 
Sector Hospitals 
PI Contribution We have set up a collaboration between ourselves, the University Hospital of Birmingham Maxillofacial Repair Department, the Royal Centre for Defence Medicine, Accentus Medical and Cavendish Implants. Within this collaboration, we seek to bring together process innovation in additive layer manufacturing and silver embedding to produce prescribed prosthetics with a lower chance of infection.
Collaborator Contribution Birmingham Maxillofacial Repair Departments - have allowed us to examine their processes and identify potential sources of infection. RCDM - have initiated work with us to investigate how our prosthesis modification technology can be used to reduce infection in transcutaneous prosthetics. Accentus are working with us to implement their novel silver coating process into our additive layeer manufacturing process. Cavendish implants are working in collaboration with us to provide cast alternatives for our additively manufactured implants.
Impact We have recently secured an EPSRC grant that will help us to move the collaboration forwards, hopefully to the point that it is of significant clinical value (EP/P02341X/1). The collaboration is highly multidisciplinary and involves industry (Accentus and Cavendish), medical practicioners (RCDM, UHB and Addison), materials scientists (Grover and Attalah), and Mechanical Engineers (Shepherd and Cox).
Start Year 2016
 
Title A new process for manufacturing prescribed prosthetics 
Description We are working to develop processes with our clinical partners to minimise the infection caused by prosthetics that are used in maxillofacial reconstruction and complex orthopaedic reconstructions. We hope that by utilising a novel silver embedding method and by optimising manufacturing processes, we will be able to develop technologies that reduce infection in applications that typically have high levels of infection (30%) as compared with typical elective orthopaedic indications (<2%). 
Type Therapeutic Intervention - Medical Devices
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2017
Development Status Under active development/distribution
Impact The development process is still very early, however, we have demonstrated that modifying processing techniques can significantly modify levels of infection at implant surfaces. We have also shown that it is possible to create tailored porosity within prosthetics in which a drug eluting material may be placed. 
 
Description An introduction to public engagement in research 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Sophie organised a meeting on best practice in public engagement in engineering.
Year(s) Of Engagement Activity 2016
 
Description Careers workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Sophie attended this careers day to advise students on the best way to pursue a career in engineering.
Year(s) Of Engagement Activity 2015
 
Description Industrial stakeholders day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact We held a Industrial Advisory Board event at the University of Birmingham, where we had attendees from the NHS and Industry to guide us on the way forwards for the project and identify opportunities for exploitation.
Year(s) Of Engagement Activity 2015
 
Description Presentation at the British Science Festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The talk received a lot of questions from the general public.

I have since been asked to talk on the importance of multidisciplinary science at a local school. A journalist in the crowd wrote up the research that I presented as an article in the Telegraph.
Year(s) Of Engagement Activity 2014
URL http://www.britishscienceassociation.org/british-science-festival/making-body-parts
 
Description School visit - "My research journey" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Dr Sophie Cox visited Camp Hill School as part of their extracurricular science program, to engage with young people taking GCSE or A level science. Sophie discussed with the students her experiences of working in research and her route to entry.
Year(s) Of Engagement Activity 2015