Long‐Term Pathology of Ovine Lumbar Spine Degeneration Following Injury Via Percutaneous Minimally Invasive Partial Nucleotomy

Abstract

The focus of this work is to assess the long‐term progression of degeneration in the ovine lumbar spine following a minimally invasive model injury comparable to the damage of an intervertebral disc (IVD) herniation. A partial nucleotomy was performed on 18 sheep via the percutaneous dorsolateral approach. The animals were culled at 6 and 12 months to evaluate the damaged and neighboring functional spine units (FSUs) for degenerative characteristics via μ‐CT and histology. Both quantitative μ‐CT and histology investigations demonstrated statistically significant differences between the native and damaged FSUs investigated. Qualitative analysis of μ‐CT revealed numerous pathological markers consistent with intervertebral disc degeneration (IDD), with differences in frequency and severity between the native and damaged FSUs. The annulus fibrosus reforms a pressure seal within 6 weeks, but the extent of the trauma is significant enough to initiate IVD degeneration, which is already clearly visible at 6 months and especially so 12 months post‐op. IDD pathology consistent with signs of a herniation was seen in both the 6‐ and 12‐month groups. This technique provides a useful model injury for the preclinical evaluation of IDD in large animal models, especially in regards to simulating disc herniation as well as for testing the efficacy of associated therapies in the future. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2376–2388, 2019

Long‐term pre‐clinical evaluation of an injectable chitosan nanocellulose hydrogel with encapsulated adipose‐derived stem cells in an ovine model for IVD regeneration

“…Several degenerative features were detected, such as concave curvature of the lamellae, a blurred AF‐NP boundary, condensation and concave scarring of the matrix, as well as cluster formation of chondrocytes. The histological degeneration values of degenerated and native IVDs according to Hoogendoorn scoring barely changed when comparing the samples harvested 12 months post‐op to those from a similar previous study harvested at 6 months post‐op (Schwan et al., 2019). The degeneration of the native IVDs is possibly attributable to the fact that each test animal harbored damaged, untreated discs as well as damaged, chitosan‐treated discs adjacent to the native discs.…”

“…Based on previous results, it's been demonstrated that within 6 weeks after surgery pressure‐resisant scar tissue has formed on the damaged side of the IVD, but the original tissue structure cannot be regenerated. Puncture of the IVD via a Sprotte® 21G × 120 mm cannula for injection does not lead to an effect in large animal models as shown in (Schwan et al., 2018, 2019). It is generally accepted that in cadaver experiments the stiffness of the IVD is compromised.…”

“…The damage model used here has been previously published as a model for disc herniation (Schwan et al., 2019). Our results here were comparable to the native group and damaged group in that previous work.…”

“…The segments were frozen again at −20°C and sawed into three segments (left/right/middle) parallel to the sagittal plane with the cranial end of each was notched for orientation. The segments were then postfixed over 48h in 2.5% glutaraldehyde in PBS before being embedded in Technovit 9100 (Heraeus, Kulzer, Germany) according to (Schwan et al., 2018, 2019). The samples were cut into 1.7 mm thick slices, ground down, and polished step‐wise with abrasive paper up to a final fineness of 4000 grit, resulting in an overall thickness of 0.2 mm.…”

Intervertebral Disc Regeneration Injection of a Cell-Loaded Collagen Hydrogel in a Sheep Model

“…The animal model used [29] can effectively depict traumatic situations and is suitable for conducting long-term studies of up to one year. For the examination of cell-loaded scaffolds, however, the model described in this study was modified so that discography using an X-ray contrast medium was not necessary.…”