Annular Repair Using High-density Collagen Gel with Riboflavin Crosslinkage: Preliminary Data from an in vivo Ovine Model
Authors: Pennicooke Brenton , Härtl Roger , Moriguchi Yu , Bonassar Lawrence , Borde Brandon 
Published: April 2016

Introduction Discectomy of herniated intervertebral discs (IVDs) successfully alleviates neurological symptoms but fails to repair the iatrogenic annulotomy. This persistent annular defect post-discectomy is associated with increased risk of reherniation, progressive IVD degeneration, and chronic low back pain. Previously we demonstrated the ability of high-density collagen (HDC) gels to facilitate annular repair in a rodent model.1,3 This study aims to use HDC gel in an ovine model which has previously been used as a surrogate for the human spine.2 The goal of this study is create an effective ovine model for a herniated nucleus pulposus through a generated annular defect and to show that our HDC helps induce annular repair reduces the degenerative changes. Methods Sheep have had intervertebral discs violated to create an annular defect and induce a herniated nucleus pulposus. These sheep were laid in a lateral position with their right-side up. A longitudinal incision was made from their most caudal rib to their iliac crest 1-cm ventral to their transverse processes. Using a lateral approach, the soft tissue and muscle were dissected of their transverse processes to expose their vertebral bodies. The annular fibrosis (AF) defect was created with a 3.2 mm drill inserted to a 9–11 mm depth and then an 18-gauge needle was inserted to a maximum depth of 9–10 mm to injure the nucleus pulposus (NP) and induce a herniation through the annular defect. The violated IVDs were then randomized to either treatment with riboflavin-crosslinked HDC gel or no treatment. Thus far 4 IVDs were randomized to the control group and 4 IVDs to the treatment group. An in vivo MRI and post-mortem MRI were performed 6 weeks after the surgery to assess the degree of herniation of the nucleus pulposus. A post-mortem X-Ray was also obtained 6 weeks after the surgery to assess for any changes in disc height, which is a surrogate for degenerative disc changes. Results Of the 8 intervertebral disc which we induced an annular defect, we were able to induce nucleus pulposus herniation through the annulotomy in all levels as in the example in Fig. 1 . Our preliminary data so far shows no difference in the disc height index of the intervertebral discs that received HDC versus those that received no treatment at 6 weeks after the surgery. The average disc height index of the treated intervertebral discs was 0.78 ± 0.005, 0.77 ± 0.004 for the untreated, puncture-only intervertebral discs, and 0.82 ± 0.006 for the healthy discs. Conclusion Lumbar discectomy to treat disc herniation is one of the most commonly performed spinal procedures,1 with an estimated 300,000 cases per year in the United States.2 A ~5% to 15% of discectomy cases result in a reherniation of their nucleus pulposus3 through the annulotomy and is associated with compromised patients outcomes and increased health care costs.4 Our preliminary data show that we are able to effectively use an ovine model to simulate a herniated nucleus pulposus via a lateral approach to the lumbar vertebral. Experiments are ongoing to analyze the disc levels using T2 mapping on MRI to assess changes in the NP hydration and overall area as our group has done previously in the rat-tail model.5 If HDC is found to be efficacious in inducing annular repair in a large mammal model, the next step would be to progress to clinical trials in humans. [Figure: see text] References Laus M, Bertoni F, Bacchini P, Alfonso C, Giunti A. Recurrent lumbar disc herniation: what recurs? (A morphological study of recurrent disc herniation). Chir Organi Mov 1993;78(3):147–154 Carragee EJ, Han MY, Suen PW, Kim D. Clinical outcomes after lumbar discectomy for sciatica: the effects of fragment type and anular competence. J Bone Joint Surg Am 2003;85-A(1):102–108 Swartz KR, Trost GR. Recurrent lumbar disc herniation. Neurosurg Focus 2003;15(3):E10 Ambrossi GLG, McGirt MJ, Sciubba DM, et al. Recurrent lumbar disc herniation after single-level lumbar discectomy: incidence and health care cost analysis. Neurosurgery 2009;65(3):574–578, discussion 578 Grunert P, Hudson KD, Macielak MR, et al. Assessment of intervertebral disc degeneration based on quantitative magnetic resonance imaging analysis: an in vivo study. Spine 2014;39(6):E369–E378