Self-assembling peptide/glycosaminoglycan hydrogels for spinal therapies

Back pain affects 80% of adults at some stage during their lifetimes, with one of the most common causes being disc degeneration. Currently, early stage interventions are limited and many patients continue to suffer further. This work focuses for the first time on using self-assembling peptide gels in the treatment of disc degeneration by providing an injectable nucleus replacement that can mimic the mechanical function of the natural tissue and restore the swelling pressure of the disc. Here the behaviour of a range of designed P11 peptide blocks with systematic variations in their structure was studied and the design criteria for a suitable peptide hydrogel were established. The peptides were analysed using a series of complementary analytical techniques (proton nuclear magnetic resonance spectroscopy, Fourier transform infra-red spectroscopy, circular dichroism ultra-violet spectroscopy and transmission electron microscopy) to determine their behaviour at the molecular and nanoscale levels. Tests were also carried out on the gels to establish their behaviour both inside and outside the disc. The results have shown that the mechanical properties of the gels can be controlled by allowing up to a 10,000 fold variation in the stiffness. The peptides were further optimised by mixing with glycosaminoglycans (GAGs) that occur naturally within the disc. It was found that the presence of GAGs in the peptide gels can enhance their material properties, making them more similar to that of the natural nucleus. The GAGs also acted as a trigger to the onset of gelation and speed up the time for gelation to occur. P11-12:GAG solutions, injected in bovine caudal discs ex vivo, were evaluated under compressive loading, and they were found to partly restore the biomechanical function of degenerated discs. The results also demonstrate that the new peptide:GAG materials could have applications in other fields of regenerative medicine, e.g. as substrates for cell growth or cartilage tissue engineering