The purpose of this study was to develop a novel, minimally invasive therapy for nucleus pulposus augmentation without the need for major surgical incision. Two optimum patented self-assembling peptides based on natural amino acids were mixed with glycosaminoglycans (GAGs) to form reversible, tunable hydrogels that mimic the vital biological osmotic pumping action and aid in swelling pressure of the intervertebral disc (IVD). Separate peptide and GAG solutions can be switched from fluid to gel upon mixing inside the body. The gels were analysed using a series of complementary techniques (FTIR, TEM & rheometry) to determine their cross-length scale structure and properties. Approaches to developing a clinical product were then developed including the incorporation of a fluorescent probe and a CT contrast agents to aid visualization of the gels, and a semi-automatic syringe driver rig, incorporating a pressure sensor, for the delivery of the solutions into the intervertebral discs. The efficacy of the procedure in restoring disc height and biomechanics was examined using chemically degenerated bovine caudal samples. It was found the presence of the GAGs stabilized the peptides forming stiffer gels, even upon injection through a long (∼10cm) small gauge needle. The injected gels were easily visualized post injection by microCT and by eye during dissection under visible and UV light. It was also noted that following injection, the disc height of the degenerated samples was restored to a similar level of that observed for native discs. A hydrogel has been developed that is injected through a narrow bore needle using a semi-automatic delivery rig and forms a self-assembled gel in situ which has shown to restore the disc height. Further tests are now underway to examine their biomechanical performance across more physiological time periods.
Intervertebral disc (IVD) degeneration is one of the major causes of back pain. A number of emerging treatments for the condition have failed during clinical trial due to the lack of robust biomechanical testing during product development. The aim of this work was to develop improved in-vitro testing methods to enable new therapeutic approaches to be examined pre-clinically. It forms part of a wider programme of research to develop a minimally invasive nucleus augmentation procedure using self-assembling hydrogels. Previous static testing on extracted IVDs have shown large inter-specimen variation in the measured stiffness when specimen hydration and fluid flow were not well controlled. In this work, a method of normalising the hydration state of IVDs prior-to and during compressive testing was developed. Excised adult bovine IVDs underwent water-pik treatment and a 24-hour agitated bath in monosodium citrate solution to maximise fluid mobility. Specimens were submerged in a saline bath and held under constant pressure for 24 hours, after which the rate of change of displacement was low. Specimens were then cyclically loaded, from which the normalised specimen stiffness was determined. A degenerate disc model was developed with the use of enzymatic degeneration, allowing specimens to be tested sequentially in a healthy, degenerate, and then treated state. Self-assembling peptide-GAG hydrogels were tested using the developed method and the effect of treatment on stiffness and disc height were assessed. Compared to previous static tests, the improved method reduced the variation in the normalised specimen stiffness. In addition, statistically significant differences were seen before and after enzymatic degradation to simulate degeneration, thus providing controls against which to evaluate treatments. The augmentation of the nucleus with the hydrogel intervention reduces the stiffness of the degenerate disc towards that of the healthy disc. This method is now being used to further investigate nucleus augmentation devices.
