Nanostructured gels for intervertebral disc load support and directed regeneration

Lower back pain is a major and growing healthcare problem in the UK. It causes morbidity and significantly reduces national productivity through employee absence. A major cause of lower back pain is degeneration of the intervertebral disc (DIVD). The most common treatment for DIVD is spinal fusion, which is a major surgical procedure with variable patient outcome. In principle, injectable gels that provide load support while allowing tissue regeneration can provide a non-surgical, cost-effective therapy for DIVD. We aim to establish an injectable synthetic copolymer gel that provides immediate load support (to alleviate pain) and then biodegrades to be replaced by regenerated tissue. A non-biodegradable injectable gel technology developed by the U. Manchester team has provided load support for degenerated IVDs. However, these gels fracture at high strain (low ductility) and do not recreate the nanometre-scale structural features of the natural extracellular matrix (ECM) within the intervertebral disc (IVD). Moreover, they were not able to support tissue regeneration. In the proposed work programme, we will design novel injectable biomimetic gels by combining new anisotropic block copolymer worm-like particles with new pH-responsive nanogel particles in order to produce the nanometre-scale features that are characteristic of the ECM within human IVDs. Such nanostructured gels should have improved ductility and provide both load support and the appropriate physical / biological cues to direct ECM synthesis and tissue growth. Furthermore, they will be designed to biodegrade and be gradually replaced by regenerated tissue. A successful outcome will establish a new family of injectable synthetic copolymer gels that should bring non-surgical therapies for DIVD closer to reality.

A successful outcome for this collaborative proposal would be to establish a high-ductility, injectable gel that provides instantaneous load support within degenerated intervertebral discs (IVDs) and also promotes the subsequent regeneration of native tissue. Such an advance would lead to a wide-spread, low cost, minimally-invasive therapy for degeneration of the IVD (DIVD). This major healthcare problem has a substantial economic cost and is a source of chronic pain that will become increasingly prevalent in our ageing population. A minimally-invasive treatment that provided load support from the point of injection and gradually restored the degenerated tissue would be of major benefit to patients suffering from DIVD. In the longer term, there is also considerable potential for developing effective therapies for both load-bearing tissue (e.g. cartilage) and non-load bearing tissue.

A minimally-invasive treatment for DIVD with faster recovery rates would benefit both patients and the NHS by reducing hospitalisation times. Because fewer spinal fusion operations may be required, clinicians would benefit from a reduction in surgical procedures, allowing limited resources to be targeted elsewhere. In the USA alone, 122,000 spinal fusion operations were performed in 2001 for DIVD. An injectable gel that provided both load support and enabled regeneration of native tissue would provide a cost-effective alternative therapy. If successful, this would delay the need for spinal fusion or even make such expensive interventions unnecessary. Beneficiaries of a minimally-invasive gel of this type would be the patients, the NHS and also UK-based medical device companies developing spinal implants (e.g., Smith & Nephew and Depuy Spine).

The above-named beneficiaries would only gain directly from this project if our research findings were to be translated into new medical devices, for which the essential first step is patent protection. Once obtained, and supported by high impact peer-reviewed journal articles, the PI and Co-I will actively pursue licensing opportunities with companies that have mutual development interests in this area. The PI and Co-Is have a strong record of collaborating with UK industry and the PI also has recent experience of the formation of a spin-out company for biomedical research (Gelexir Health). They have extensive networks with UK polymer and medical device companies that will be used to explore collaborative development of the new regenerative medicine platform that is expected to emerge from this project.

Our scientific findings will be disseminated to the wider media through joint university press releases (after peer-reviewed publication in high impact journals). The PI has found this approach to be an effective mechanism to promote the benefits of EPSRC-funded science to UK citizens and also for attracting interest from both UK and international companies.