Additive manufacturing of advanced medical devices for cartilage regeneration: minimally invasive early intervention

Lead Research Organisation: Imperial College London
Department Name: Materials

Abstract

No current surgical technique can regenerate articular cartilage and no current device can mimic the properties of cartilage. This Partnership will accelerate delivery of an innovative medical device for healing cartilage that will cross a frontier in orthopaedic surgery, allowing regeneration of articular cartilage rather than replacement. The device will restore cartilage to its healthy state. The surgical technique will be optimised through a new precise and minimally invasive keyhole technique. Patients will be able to use their knee immediately after the operation and recovery time will be rapid.

Osteoarthritis affects 1 in 4 people, is debilitating and costs >£3bn in UK lost economic productivity, >£2.4bn in out-of-work benefits and contributes to the NHS's £5.4bn annual spend on musculoskeletal disorders. Current treatment for severe osteoarthritis is total joint replacement and current best practice for cartilage impact damage is microfracture, which involves drilling into bone to liberate the marrow, which can form weak fibrous cartilage over the defect. Early intervention is important as complete degeneration results in total joint replacement. The problem is that the cartilage only lasts 2-5 years before the procedure must be repeated and total joint replacements are major operations, which involve removing a lot of tissue, and last 15-25 years.

Previous EPSRC research grants by Jones led to the invention of a new type of material that produced unique properties in terms of strength, flexibility and biodegradation. In fact, the mechanical properties can be precisely selected to match cartilage or bone. The material can also self heal. When 3-D printed, the material is able to instruct cartilage cells to produce articular cartilage rather than fibrous cartilage. Imperial Innovations submitted a patent, providing a strong IP position.

Our Healthcare Impact Partnership will bring expertise in biomechanics, precision surgery, medical device manuface, technology transfer and regulatory procedures and product delivery. The team will evaluate the device and develop manufacturing capability, producing cost-effective, reliable and effective medical devices. Surgery will be tested in cadaver knees for how they fit and ensure they can provide an immediate articular surface. Then, biological testing will determine whether our hypothesis that the device can guide the regeneration of the cartilage under joint loading.

Eventually, surgeons will be able to send implant design specifications to the medical device company and receive a bespoke, patient specific device within a few days.

Planned Impact

The Partnership will accelerate the delivery of a new innovative medical device that can regenerate hyaline cartilage and restore the articular surface through minimally invasive early intervention, by beginning the translation of advanced materials that have unprecedented properties.
This partnership will benefit: patients, orthopaedic surgeons, and health services (e.g. the NHS) in a 5-20 year timeframe. This is important as it is expected that a third of workers will be over 50 by 2020. Specific impact targets are:

1. A new option for surgeons to treat chondral injury. This is often observed during anterior cruciate ligament repair surgery, which is performed approximately 3 million times annually worldwide;
2. Increased quality and longevity of chondral repair. Current best practice generates fibrocartilage with inferior mechanical properties to the desired hyaline cartilage. Hyaline cartilage repair will withstand joint loading better.
3. Reduced osteoarthritis (OA) progression. Early correction of the cartilage damage will restore the natural biomechanical loading of the joint. Changes in joint loading contribute to the degenerative process.
4. The population will be active for longer. Patients will benefit from improved healing and accelerated recovery, which will benefit the UK economy by reducing operation and hospital stay costs and the time it takes for patients to return to work.

Early interventional joint preserving surgery is a growing sector in the orthopaedic market and achieving points 1-4 above will increase the uptake of this surgery. If this is achieved, further impact will be:

- Delay in need for joint replacement. OA results in 180 000 hip and knee replacements performed annually by the NHS( >1M worldwide). They only last 15-25 years and as life expectancy increases, more are revised. The cost to the NHS of a hip or knee replacement (including surgery, implant, hospital stay and rehabilitation) is approximately £10,000, neglecting theeconomic cost of lost working days. By making a small repair, before the joint is irreparably damaged, joint preserving techniques allow a far less invasive and traumatic surgery, less rehabilitation and if patients can be discharged the same day, could be performed at a fraction of the cos.
- Commercial opportunity for chondral repair device which would be a huge growth market. The UK has a strong orthopaedic industry base, and is well placed to take this opportunity for economic benefit to UK plc.

The research is also structured to plan for secondary, lower risk, impact. By proving that matching stiffness of a device improves osteochondral repair and fixation, we will have developed a method for manufacturing conventional joint replacement implants that will enable joint replacements with lower profile fixation features. This reduce bone removal and give a better physiological load transfer to bone. Patients would benefit by:

- Improved proprioception and activity levels for patients after total joint replacement
- Reduced pain after joint replacement - this is currently the second most common cause of revision.
- New opportunities in joint replacement implant design.

The long-term impact will be judged on whether devices reach the clinic. We will develop a translation pathway to map progress through technology readiness (TR) levels from 1 to 10, where 10 is a clinical product. The pathway will include: proving efficacy; sourcing raw materials, manufacturing to GMP standards; risk analysis; biological risk assessment and testing; clinical trials; distribution etc. By the end of the grant we expect to have taken the device from TR level 2 to 4. A key aspect is longevity of the Partnership beyond the 3 years. The engagement partners will invest more resources once we are at TR4 and more partners will be recruited where needed.

Publications

10 25 50
 
Description New device for testing tribology of our implants against cartilage. PCL/Silica hybrids can be 3D printed into scaffolds suitable for knee cartilage regeneration, including matching the tribology to native cartilage. A 3D scaffold can be 3D printed into the back of the bearing surface to produce an osteochondral device.

Our scaffolds work well in vitro to stimulate cartilage growth. The first generation devices were implanted in in vivo studies. The pilot study showed good cartilage ingrowth into the device. A full study has been carried out but analysis is ongoing

Silica/polymer hybrids can be made into intervertebral disc replacements with stiffness gradients or moulded into the shape of a meniscus and have been integrated with porous Ti metal plugs
Exploitation Route We have a Healthcare Impact Partnership of Surgeons, academics and industry working on technology transfer
Sectors Healthcare,Manufacturing, including Industrial Biotechology

 
Description With industrial partners we are beginning the process of technology transfer of our hybrid materials. New industrial collaborators, including Orthonika and Smith and Nephew Clinical partners are beginning handling trials and giving input.
First Year Of Impact 2017
Sector Healthcare,Manufacturing, including Industrial Biotechology
Impact Types Economic

 
Description Biodegradable hybrid screws for ligament-bone interface regeneration
Amount £1,119,981 (GBP)
Funding ID EP/S025782/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 05/2019 
End 05/2022
 
Description NIHR Global Health Research Global Health Research Group on POsT Conflict Trauma; PrOTeCT
Amount £1,880,000 (GBP)
Funding ID 1613745 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 11/2017 
End 10/2020
 
Title Tribology of hybrids against cartilage 
Description A tribology testing rig that allows testing of our materials and devices for wear resistance in a model of a joint, including against natural (bovine) cartilage in fluid. 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2018 
Provided To Others? No  
Impact ability to test osteochondral regeneration devices in an accurate model of the human joint. reduction in the need for animal testing 
 
Description Meniscus replacement 
Organisation Orthonika Limited
Country United Kingdom 
Sector Private 
PI Contribution Orthonika have IP on a method for anchoring a replacement meniscus device to host bone and are looking for a next generation material for the meniscus. we have been working on shaping our hybrid materials to the shape of a meniscus and incorporation of their device.
Collaborator Contribution Orthonika have supplied their materials and are testing the new device, e.g. the surface tribology.
Impact Orthonika have IP on a method for anchoring a replacement meniscus device to host bone and are looking for a next generation material for the meniscus. we have been working on shaping our hybrid materials to the shape of a meniscus, on the surface tribology and incorporation of their device.
Start Year 2017
 
Title Hybrid materials and process for production thereof 
Description An inorganic/organic hybrid composition and synthesis process that yeilded a material with self healing properties and excellent mechanical properties, that could be 3D printed 
IP Reference GB1605446.2 
Protection Patent application published
Year Protection Granted 2016
Licensed No
Impact Healthcare Impact Partnership grant from the EPSRC and partnership with surgeons and industry to begin technology transfer
 
Description Children's BBC Operation Ouch! episode 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact CBBC Operation Ouch! Hospital Takeover Series 5, Episode 9
A child was featured in the programme who had had an operation involving a bone graft. The presenter came to my lab to film the making of bioglass and to film an interview explaining how it works and our future developments in the area, such as 3D printing
Year(s) Of Engagement Activity 2016,2017
 
Description Chris Xand and Drake Award Pilot in Primary Schools 
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 The Chris Xand and Drake Award raises awareness of STEM subjects in schools, including Materials Science. I arranged mentors for two primary schools for the scheme
Year(s) Of Engagement Activity 2018
URL http://www.chrisxanddrake.com
 
Description Daily Mail article featuring our work on hybrid biomaterials 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Daily Mail article featuring our work on hybrid biomaterials
Year(s) Of Engagement Activity 2016
 
Description Exhibition for future materials Jaguar Land Rover 
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 Supplied bioactive glass scaffolds for an Exhibition for future materials set up by Jaguar Land Rover
Year(s) Of Engagement Activity 2018
URL http://www.jaguarlandrover.com
 
Description Pint of Science science festival talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Pint of Science science festival talk
Year(s) Of Engagement Activity 2018
URL https://pintofscience.co.uk/event/fixing-our-body
 
Description Radio Programme on BBC Radio 4 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Appearance on BBC Radio 4's In their Element, talking about the role of Lithium in glass with Prof Sophie Scott
Year(s) Of Engagement Activity 2017
URL http://www.bbc.co.uk/programmes/b08pdzxq
 
Description Segment on BBC Radio 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact BBC Radio 4's In Business, talking about 3D printing of biomaterials with presenter Peter Day.
Year(s) Of Engagement Activity 2016