Annular Repair

The annulus fibrosis is an integral part of the intervertebral segment, as its degeneration can have significant clinical implications.[1] Weakening of the annulus fibrosis from age-related changes is one of the most common reasons of lumbar disc herniations. While most symptoms may resolve with conservative treatment, lumbar discectomy is still one of the most commonly performed spine surgeries in the United States.[2] Despite overall good surgical success rates, recurrent symptomatic herniations have been reported in 7% to 18% of patients.[3,4] Recurrent disc herniations also remain a significant clinical dilemma because they carry the potential for greater complications and are being more technically demanding.[3]

Over the past several years, more emphasis has been placed on understanding the pathophysiology of the annulus as well as its healing potential.[5,6] Regardless of biologic or mechanical repair, the potential for annular healing could prevent patients from requiring subsequent surgeries. The focus of this review will be on the annulus anatomy and current repair techniques.

Annulus Fibrosus Anatomy and Healing Potential

The structural anatomy plays an important role in understanding how these herni - ations occur along with ways to prevent recurrence. The annulus surrounds the inner nucleus pulposis, acting as a laminate structure.[7] It is composed of mainly water but includes type 1 collagen, forming layers surrounding proteoglycans.[7] Its inner and outer layers are organized differently due to the different mechanical environments it faces.[7] For instance, cells of the outer annulus produce mainly type 1 collagen due to the compression it undergoes from axial loading.[7]

While several factors play a role in its degeneration, aging causes significant changes that alter its structure.1 With time, both proteoglycan and collagen density decrease, leading to weakening and eventually the formation of fissures or cracks within the annulus.[8] Self-healing of these tears are limited due the avascularity of the annulus.

In an animal study, Smith et al found that with only a stab incision of the annulus, the defect healed with fibrous in-growth within a 1-year period.[9] Even despite this healing potential, biomechanical studies have demonstrated mechanical consequences of this fibrous in-growth, such as loss of load absorption over time.[10] This inflammatory environment and limited healing capability can lead to reherniation and the need for subsequent surgical intervention. Several risk factors have been found when examining for recurrent herniations, including disc degeneration, age, sex, and obesity.[11-14] Miller et al found that an annular defect of greater than 6 mm was associated with a significantly higher likelihood of symptomatic recurrence.[11] This has led to the investigation of several biologic and mechanical devices to aid in annular healing.[15]

Biologic Repair

Although limited clinical data are available, several synthetic and natural biomaterials have been examined for annular repair.[16,17] The majority of these studies involve gene or cell therapy being delivered via a scaffold to provide a mechanical environment for collagen synthesis.[18-20]

In an animal study by Fuller et al, the authors created slit puncture defects within the annulus and repaired them with collagen sponges soaked with hyaluronan oligosaccharides to facilitate extracellular matrix remodeling.[15] This induced regrowth of annular lamellae around the puncture site, with reorganization of collagen and increased proteoglycan.[15] One common agreement in most of the biologic literature has been the importance of a mechanical scaffold to allow for host cells to integrate into the defect.[20]

While the data are promising, the current literature is based on animal models only, with the majority of defect size not always mimicking those seen clinically. In addition, a majority of commercially available scaffolds are comprised of type 2 collagen, resulting in a higher production compared to the native type 1 collagen.[20] Bron et al proposed several criteria for scaffolds, which included mimicking the native biomechanical properties of the disc, one that promotes native cells to survive and secrete extracellular matrix, and a scaffold that also contains the nucleus puloposus.[5] Despite several successful in-vivo biologic repairs, no ideal scaffold or biologic integration has been identified for clinical use.[21,22]

Surgical Repair

Given the limited healing capacity of the annulus, the more recent focus has been surgical repair at the time of discectomy.[23-25] With data supporting that large annular defects play a role in reherniation,[11] theoretically reducing this gap could prevent further extrusion of the disc. This was biomechanically supported by Bartlett et al, who found that disc load to failure was significantly lower in annular defects that were not repaired with suture.[26]

Bailey et al conducted a 2-year, prospectively randomized controlled trial comparing annular defect repaired with a suture anchor device (Xclose Tissue Repair; Anulex Technologies, Minnetonka, MN) to controls.[27] Although the authors found an overall reduction in reherniation at 2 years, the study did not reach statistical significance.[27] Thome et al performed a similar randomized controlled study using another suture anchor device and found the rate of symptomatic herniation was 50% lower with repair at 2 years, with a significantly lower reoperation rate.[28] While no significant increase in complication rates has been found using a suture device, its actual effectiveness remains in question.

More recently, a bone mesh anchor device (Barricaid; Intrinsic Therapeutics Inc., Woburn, MA) has been developed for larger defects. This device anchors into the vertebral body and has a mesh plug designed to fit into the sized annular defect as a mechanical plug. A recent US study presented a case series of 55 patients with 3-month follow up after bone anchor closure and found a reoperation rate of 1.8% at final follow up, with an overall significant improvement in leg pain and Oswestry Disability Index scores.[29] In a recent meta-analysis combining 15 studies and more than 2100 patients, the Barricaid annular device was found to be effective in reducing reoperation compared to a suture device.[30] While this bone closure repair provides promising results, longer term results, as well as a further cost analysis, is needed to know its true benefit.

Conclusions

Annular tears remain a significant clinical dilemma, with larger annular tears (>6 mm) being a major risk factor for reherniation. The ideal repair involves restoring the biomechanics of the annulus and healing with type 1 collagen. Current repair devices on the market have had mixed results, with suture anchors demonstrating no significant difference and moderate evidence to support the use of a bone anchor device. Longer-term data, in addition to cost analysis, are needed to support the use of any repair method for large annular defects.

References

1. Singh K, Masuda K, Thonar EJ-M, An HS, Cs-Szabo G. Age-related changes in the extracellular matrix of mucleus pulposus and annulus fibrosus of human intervertebral disc. Spine. 2008;34:10-16.

2. Gray DT, Deyo RA, Kreuter W, et al. Population-based trends in volumes and rates of ambulatory lumbar spine surgery. Spine (Phila Pa 1976). 2006;31:1957-1963.

3. McGirt MJ, Eustacchio S, Varga P, et al. A prospective cohort study of close interval computed tomography and magnetic resonance imaging after primary lumbar discectomy: factors associated with recurrent disc herniation and disc height loss. Spine (Phila Pa 1976). 2009;34:2044-2051.

4. Ambrossi GL, McGirt MJ, Sciubba DM, et al. Recurrent lumbar disc herniation after single-level lumbar discectomy: incidence and health care cost analysis. Neurosurgery. 2009;65:574–578.

5. Bron JL, Heider MN, Meisel H-J, Van Royen BJ, Smit TH. Repair, regenerative and supportive therapies of the annulus fibrosus: achievements and challenges. Eur Spine J. 2009;18:301-313.

6. Bailey A, Araghi A, Blumenthal S, Huffmon GV; Anular Repair Clinical Study Group. Prospective, multicenter, randomized, controlled study of anular repair in lumbar discectomy: two-year follow-up. Spine. 2013;38(14):1161-1169

7. Pezowicz CA, Robertson PA, Broom ND. The structural basis of interlamellar cohesion in the intervertebral disc well. J Anat. 2006;208(3):317-330.

8. Osti OL, Vernon-Roberts B, Moore R, Fraser RD. Annular tears and disc degeneration in the lumbar spine. A post-mortem study of 135 discs. J Bone Joint Surg Br. 1992;74(5):678-682.

9. Smith JW, Walmsley R. Experimental incision of the intervertebral disc. J Bone Joint Surg Br. 1951;33-B(4):612-625.

10. Fazzalari NL, Costi JJ, Hearn TC, et al. Mechanical and pathologic consequences of induced concentric anular tears in an ovine model. Spine. 2001;26(23):2572-2581.

11. Miller LE, McGirt MJ, Garfin SR, Bono CM. Association of annular defect width after lumbar discectomy with risk of symptom recurrence and reoperation: systematic review and meta-analysis of comparative studies. Spine. 2018;43(5):E308-e315.

12. Kim KT, Lee DH, Cho DC, et al. Preoperative risk factors for recurrent lumbar disk herniation in L5-S1. J Spinal Disord Tech. 2015;28:E571-E577.

13. Leven D, Passias PG, Errico TJ, et al. Risk factors for reoperation in patients treated surgically for intervertebral disc herniation: a subanalysis of eight-year SPORT data. J Bone Joint Surg Am. 2015;97:1316-1325.

14. Moliterno JA, Knopman J, Parikh K, et al. Results and risk factors for recurrence following single-level tubular lumbar microdiscectomy. J Neurosurg Spine. 2010;12:680-686.

15. Fuller ES, Shu C, Smith MM, Little CB, Melrose J. Hyaluronan oligosaccharides stimulate matrix metalloproteinase and anabolic gene expression in vitro by intervertebral disc cells and annular repair in vivo. J Tissue Eng Regen Med. 2018;12(1):e216-e226.

16. Grunert P, Borde, BH, Towne SB, et al. Riboflavin crosslinked high‐density collagen gel for the repair of annular defects in intervertebral discs: an in vivo study. Acta Biomaterialia. 2015;26:215-224.

17. McGuire R., Borem R, Mercuri J. The fabrication and characterization of a multi‐ laminate, angle‐ply collagen patch for annulus fibrosus repair. J Tissue Eng Regen Med. 2017;11(12):3488-3493.

18. Liang H, Ma SY, Feng G, Shen FH, Joshua LX. Therapeutic effects of adenovirus-mediated growth and differentiation factor-5 in a mice disc degeneration model induced by annulus needle puncture. Spine J. 2010;10:32-41.

19. Yoon ST, Park JS, Kim KS, et al. ISSLS prize winner: LMP-1 upregulates intervertebral disc cell production of proteoglycans and BMPs in vitro and in vivo. Spine. 2004;29:2603-2611.

20. Saad L, Spector M. Effects of collagen type on the behavior of adult canine annulus fibrosus cells in collagen-glycosaminoglycan scaffolds. J Biomed Mater Res A. 2004;71:233-241.

21. Sato M, Asazuma T, Ishihara M, et al. An experimental study of the regeneration of the intervertebral disc with an allograft of cultured annulus fibrosus cells using a tissue-engineering method. Spine. 2003;28(6):548-553.

22. Sato M, Kikuchi M, Ishihara M, et al. Tissue engineering of the intervertebral disc with cultured annulus fibrosus cells using atelocollagen honeycomb-shaped scaffold with a membrane seal (ACHMS scaffold). Med Bio Eng Comput. 2003;41(3):365-371.

23. Thome C, Klassen PD, Bouma GJ, et al. Annular closure in lumbar microdiscectomy for prevention of reherniation: a randomized clinical trial. Spine J. 2018;18:2278-2287.

24. Ardeshiri A, Miller LE, Thome C. Two- year real-world results of lumbar discectomy with bone-anchored annular closure in patients at high risk of reherniation. Eur Spine J. 2019;28:2572-2578.

25. Bailey A, Araghi A, Blumenthal S, Huffmon GV. Prospective, multicenter, randomized, controlled study of anular repair in lumbar discectomy two-year follow-up. Spine. 2013;38:1161-1169.

26. Bartlett A, Wales L, Houfburg R, et al. Optimizing the effectiveness of a mechanical suture-based anulus fibrosus repair construct in an acute failure laboratory simulation. J Spinal Disord Tech. 2013;26(7):393-399.

27. Bailey A, Araghi A, Blumenthal S, Huffmon GV; Anular Repair Clinical Study Group. Prospective, multicenter, randomized, controlled study of anular repair in lumbar discectomy: two-year follow-up [erratum in Spine (Phila Pa 1976). 2013;38(17):1527]. Spine (Phila Pa 1976). 2013;38(14):1161-1169.

28. Thome C, Klassen PD, Bouma GJ et al. Annular closure in lumbar miscrodiscectomy for prevention of reherniation: a randomized clinical trial. Spine J. 2018;18(12):2278-2287.

29. Nunley P, Strenge KB, Huntsman K, et al. Lumbar discectomy with barricaid device implantation in patients at high risk of reherniation: initial results from a postmark study. Cureus. 2021;13(12):e20274.

30. Wang Y, He X, Chen S, et al. Annulus fibrosus repair for lumbar disc herniation: a meta-analysis of clinical outcomes from controlled studies [published online ahead of print April 17, 2023]. Global Spine J. doi:10.1177/21925682231169963

AUTHORS

Cameron Kia, MD

Gregory Lopez, MD

From Midwest Orthopaedics at Rush in Chicago, Illinois.