168. Minimally invasive hydrogel nucleoplasty in a goat model of moderate severity disc degeneration

BACKGROUND CONTEXT Intervertebral disc (IVD) degeneration (IVDD) is implicated as a cause of low back pain. The earliest degenerative changes typically occur in the central nucleus pulposus (NP), where progressive loss of proteoglycans and associated hydration compromise tissue mechanical function. PURPOSE We developed a noncrosslinked injectable hydrogel for NP replacement and augmentation together with its percutaneous delivery method and instrument assembly. We then evaluated the short- and long-term performance of this hydrogel in a goat model of moderate IVDD. Methods Six goats underwent two percutaneous procedures: one to induce degeneration in 3 lumbar IVDs via injection of 1U C-ABC and, 2 weeks later, a second procedure for the delivery of hydrogel at 2 levels with the third remaining untreated. Animals were euthanized at 6 weeks (n=2) and 12 weeks (n=1); three animals are currently enrolled for long-term survival. Disc height index (DHI) was measured from monthly lateral radiographs in the standing animal. Postmortem, motion segments were imaged using microcomputed tomography (µCT) to assess hydrogel distribution and bone volume fraction values (BV/TV) for cranial and caudal endplates. Volumetric analysis and compression testing were performed on explanted gels. Samples were dried to determine polymer and water content. Explant characteristics were compared to nonimplanted gels. Histology was performed to assess glycosaminoglycans and collagen content, cellularity, and disc morphology. Significant changes in DHI were established using Wilcoxon matched-pairs signed ranks tests and differences in histological grades were established using Kruskal-Wallis test with post-hoc Dunn's tests (p Results Animals recovered uneventfully from surgical procedures. Extrusion of hydrogel into the spinal canal during delivery occurred in two animals without major clinical repercussions. At 2 weeks after C-ABC injection, DHI was ∼80% of pre-C-ABC levels. For IVDs treated with hydrogel, DHI improved while untreated IVDs continued to degenerate. The hydrogel presents radiographically unremarkable for up to 2 years post nucleoplasty. µCT imaging demonstrated that the majority of hydrogel was localized to the central NP. BV/TV ratio of treated levels at 6-week and 12-week endpoint were similar to controls. Explant analyses showed higher elastic moduli and polymer content compared to nonimplanted gels. Treated IVDs exhibited an overall improved histological grade compared to positive controls. Conclusions The results of this work illustrate the practical utility of an injectable hydrogel being effective in normalizing the mechanical function of the degenerating IVD in a clinically relevant animal model. The implant showed successful retention without extrusion following delivery. A critical benchmark for the success of any injectable implant to treat IVDD is the normalization of mechanical properties. We demonstrate through long-term in vivo follow up studies that hydrogel injected into degenerating goat discs can preserve the spine motion segment. There is a critical need for new therapies for patients with symptomatic disc degeneration that preserve joint mobility. A minimally invasive injectable therapy mitigates anulus fibrosus trauma during nucleoplasty and may restore the biomechanics of the motion segment. Moreover, successful biomechanical restoration of the affected motion segment may slow or prevent further IVDD. Motion preservation therapies may also help mitigate adjacent level IVDD in these patient cohorts. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.