Award Title: In vivo assessment of PEP-GAG hydrogels for spinal disc repair
Funder: Versus Arthritis

Abstract: We propose to examine the in vivo safety and efficacy of a novel hybrid hydrogel as a treatment for low back pain (Figure 1). 

There are over 10 million people in the UK who have persistent back pain. Low back pain is strongly associated with degeneration of the intervertebral discs, the soft tissues between the vertebrae that enable articulation. During the degeneration process, there is a loss of glycosaminoglycans (GAGs) from the proteoglycan-rich gel in the nucleus of the disc, which reduces its swelling pressure and adversely alters biomechanical performance [1]. Current surgical treatments for disc degeneration are highly invasive and have low long-term success rates. One promising alternative is ‘nucleus augmentation’, that is, the injection of a biomaterial into the nucleus to restore its height and function. Although some materials have been proposed for this purpose, there has not yet been widespread clinical uptake of this technology, partly due to reported complications such as implant extrusion [2], as well as the documented risk that large-bore needle puncture causes further damage and reduction in biomechanical performance of the disc [3].

A new versatile family of self-assembling peptides has been de novo designed at the University of Leeds to self-assemble into nanostructured networks in consistent and reproducible manners [4]. Previous work in our group has found that a peptide-glycosaminoglycan (PEP-GAG) hybrid hydrogel could have potential as a nucleus augmentation material, with the ability to form a gel in situ, allowing injection as a liquid through very fine gauge needles [5]. Formulations of the PEP-GAG hydrogel have been tested and optimised using novel in vitro methods developed by our group [6]. The outcomes of these studies have demonstrated that the PEP-GAG hydrogels can mimic the behaviour of the heathy nucleus pulposus, both in terms of its mechanical properties and its ability to draw in water, which is essential to restore healthy disc biomechanics [7].

Through work with an external consultant and a roadmapping exercise, a clear market for the technology has been identified, however it was concluded that further evidence from in vivo studies was necessary before any commercial parties would consider a licence deal.

We propose to use this funding to conduct an in vivo study to demonstrate safety and efficacy of the hydrogels. We will use an aging sheep model that naturally exhibits disc degeneration [8,9] and utilise the novel activity monitoring facilities available at the University of Cambridge [10] to provide functional outcome measures alongside post-mortem measures of biological and biomechanical performance. In parallel, we also propose work to increase the translation potential through further engagement with commercial partners, clinical key opinion leaders and patients.  If successful, this study will progress the technology to a readiness level for commercial investment and provide support for the use of the hydrogel in clinical trials.


Research Activity Codes: 5.3 MEDICAL DEVICES
Health Categories: MUSCULOSKELETAL