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

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 manufacture, 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.

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 the economic 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.