Biodegradable hybrid screws for ligament-bone interface regeneration

Lead Research Organisation: Imperial College London
Department Name: Materials

Abstract

Anterior Cruciate Ligament injuries are often in the news as they are potentially career ending for footballers and athletes. One of the well-known incidents was seen during 2006 World Cup match between England and Sweden, where Michael Owen ruptured his ACL. This is not just a problem for elite athletes. Approximately 20,000 people in the UK need ACL repair every year and the National Health Service (NHS) performs about 11,000 ACL reconstruction surgeries per year.

Reconstructive surgery of the ACL usually involves harvesting replacement ACL graft from the patient's own hamstring tendons. The damaged ACL is removed through arthroscopy (keyhole surgery), then tunnels are drilled in femur (thigh bone) and tibia (shin bone) in the knee joint area. The replacement graft is aligned/positioned through the tunnels, and opposite ends are fixated in the tibial bone tunnel by interference screws.
Our clinicians and our medical device partner Xiros have identified an unmet clinical need for new screws and ACL reconstruction devices. Current metallic screws will be eventually rejected by the body as they are bioinert and will undergo fibrous encapsulation, but they can also tear the graft. The aim here is to develop an ideal screw that would be bioactive, to stimulate bonding to bone and regeneration of the connective tissue/ bone interface and biodegradable integrating the graft into the bone. The screw must also be strong, tough and a certain stiffness. Biodegradable polymer/bioactive ceramic composite screws exist, but they often fail and need replacing. This is because the bioactive component is buried in the polymer and the degradation rate of the polymer is uncontrolled and can be catastrophic or cause cysts. Our hybrid screws will overcome those problems, giving strength and a specifically designed biodegradation rate to match the rate of restoration of the bone/connective tissue interface. In some cases, it is not the screw that fails, but the tendon graft, therefore we will also develop a new totally synthetic device that eliminates the need for harvesting from the hamstring and provides more reliable long term performance, while integrating with the host bone.

Planned Impact

The Partnership will accelerate the delivery of a new innovative medical device that can revolutionise ACL reconstruction, which costs the NHS about £3000 and £6000 privately, with costs of rehabilitation for return to work are higher. Failure rates are high at 25%, mainly from loss of ACL graft fixation at the tibia end, but also by tearing or rupture of the graft. Failure requires revision operations and longer term rehabilitation, which leads to more costly procedures.

Our partnership will produce new biodegradable screws that can bond with bone and be replaced by regenerating bone to allow biological fixation of the graft into the bone, which will improve the lifetime of the graft and allow revision surgery. For cases where harvesting of the hamstring/patellar is not appropriate, the same technology will be used to adapted and improve existing synthetic ACL grafts.
This partnership will benefit: patients, orthopaedic surgeons, and health services (e.g. the NHS) in a 5-15 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 ACL injury, which is performed approximately 3 million times annually worldwide, often in young patients
2. Increased quality and longevity of ACL repair. Current best practice has up to 25% failure
3. 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 for patients to return to work
4. ACL injury often leads to early onset osteoarthritis, which results in 180 000 hip and knee replacements performed annually by the NHS ( >1M worldwide), costing the NHS approximately £10,000 each, neglecting the economic cost of lost working days
5. Commercial opportunity for ACL repair devices is a huge growth market. The UK has a strong orthopaedic industry base, and is well placed to e this opportunity for economic benefit to UK plc.

This project addresses at least two of the government's Industrial Strategy (Advanced Materials and Regenerative Medicine) and will contribute to Manufacturing the Future through RAFT upscaling and extrusion moulding of hybrid materials. Our proposal will accelerate the EPSRC's Grand Challenge f Delivery of Innovative Medical Devices. Translation will be achieved through our partnership with leading clinicians and our business partners. The patent application on one of our hybrid materials is at PCT stage. Further IP will be secured based on this project. Imperial Innovations manages the commercialisation of Imperial's IP and is highly experienced direct licensing of technologies.

Long-term impact will be judged on whether devices reach the clinic. Beyond 15 years, successful hybrid compositions would be used in scaffolds for segmental bone regeneration and as anchors in rotator cuff repair. 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.
Outreach to the general public will be achieved using our media contacts. Jones is a regular speaker for a "Pint of Science" and his materials have featured on CBBC's Operation Ouch, ITV's This Morning, BBC Radio 4, and in the Press (e.g. Daily Express, Daily Mail). Our Bioglass scaffolds feature in the permanent exhibition of ceramics in The Victoria and Albert Museum and in the Materials Library at the Institute of Making.

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