Annular Defects Research Articles

Annular Repair Using High-density Collagen Gel with Riboflavin Crosslinkage: Preliminary Data from an in vivo Ovine Model

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

Annular Repair Using Cross-Linked High Density Collagen Gel Seeded with Fibrochondrocytes: In Vivo Outcomes of a Rodent Disc Study

Introduction Despite alleviating associated neurological symptoms, discectomy of herniated intervertebral discs (IVDs) fails to repair the underlying degenerative process. Persistent annular defect post discectomy is associated with increased risk of reherniation, progressive IVD degeneration, and chronic low back pain.1–7 Although many studies have previously employed cell transplantation to regenerate the nucleus pulposus (NP), few have focused on annulus fibrosus (AF) repair. Recently, we demonstrated the ability of riboflavin crosslinked high-density collagen gels (HDC) to facilitate annular repair in vivo.8,9 In this study, we assessed the in vivo efficacy of AF fibrochondrocytes seeded in a gel scaffold at enhancing the the repair of an annular defect to prevent further degenerative changes in a post-puncture rat-tail model. Material and Methods 38 athymic rats, punctured with an 18-gauge needle in the tail disc, were divided into 3 groups: untreated ( n = 6), injected with crosslinked HDC ( n = 16), and injected with fibrochondrocyte-laden crosslinked HDC ( n = 16). At 1, 2, and 5 weeks postoperatively, a series of in vivo images with X-ray and 7T MRI were conducted to determine the disc height index and nucleus pulposus (NP) size and hydration, respectively.8,10,11 Histological assessments were performed to evaluate the viability of implanted cells, degree of annular repair and secondary disc degeneration. The study was approved by and undertaken in accordance with guidelines outlined by the Hospital for Special Surgery Institutional Animal Care and Use Committee and New York State. For the analyses of continuous outcomes in disc height index, NP size, and NP hydration, we employed linear regression models with a generalized estimating equation and robust standard errors to estimate differences in mean changes from baseline controls (discectomy) across displaced and stable implantation groups. P values < 0.05 were considered statistically significant. Results The untreated discs showed substantial NP herniation at two weeks and NP absence with signs of degeneration by five weeks, resulting in 40% loss of disc height. Both HDC gel groups, cellular and acellular, had significant retention of disc height and NP voxel count over the course of five weeks. Average NP voxel counts of cellular gels were higher than those of acellular gels at all time points and statistical significance was achieved at 1 week. Only the cellular group restored NP hydration relative to that of the adjacent healthy control. Further histological assessments indicate that while HDC gels influence the sealing of the defect, the addition of cells generates abundant tissue growth and extracellular matrices at the site of the annular defect, accelerating the reparative process. Disruption of endplate was observed in the puncture group, but not in the treated segments. Conclusion In vivo studies on the cell-based annular repair are few in number. Our preliminary findings suggest that fibrochondrocytes can potentially improve HDC gel-based annular repair. A long term study with sufficient sample size are necessary to confirm these results. References Bruske-Hohlfeld I, Merritt JL, Onofrio BM, et al. Incidence of lumbar disc surgery. A population-based study in Olmsted County, Minnesota, 1950-1979. Spine 1990;15(1):31–35 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 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 Barth M, Weiss C, Thomé C. Two-year outcome after lumbar microdiscectomy versus microscopic sequestrectomy: part 1: evaluation of clinical outcome. Spine 2008;33(3):265–272 O'Connell GD, Malhotra NR, Vresilovic EJ, Elliott DM. The effect of nucleotomy and the dependence of degeneration of human intervertebral disc strain in axial compression. Spine 2011;36(21):1765–1771 Frei H, Oxland TR, Rathonyi GC, Nolte LP. The effect of nucleotomy on lumbar spine mechanics in compression and shear loading. Spine 2001;26(19):2080–2089 DePalma MJ, Ketchum JM, Saullo TR, Laplante BL. Is the history of a surgical discectomy related to the source of chronic low back pain? Pain Physician 2012;15(1):E53–E58 Grunert P, Borde BH, Hudson KD, Macielak MR, Bonassar LJ, Härtl R. Annular repair using high-density collagen gel: a rat-tail in vivo model. Spine 2014;39(3):198–206 Borde B, Grunert P, Härtl R, Bonassar LJ. Injectable, high-density collagen gels for annulus fibrosus repair: An in vitro rat tail model. J Biomed Mater Res A 2015;103(8):2571–2581 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 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 Biomater 2015;26:215–224

Closure of the annulus fibrosus of the intervertebral disc using a novel suture application device—in vivo porcine and ex vivo biomechanical evaluation

Background ContextDefects in the annulus fibrosus (AF) remain a challenge in the surgical treatment of lumbar disc herniations with persistent defects, allowing potential re herniation of nucleus pulposus (NP) tissue. A cervical porcine model was chosen to simulate human lumbar intervertebral disc (IVD). PurposeThe aim of this study was to determine the technical feasibility of closure of the AF of the IVD using a novel minimally invasive Kerrison-shaped suture application device. Study DesignEx vivo biomechanical and in vivo porcine device evaluations were performed. MethodsEx vivo biomechanical evaluation: 15 porcine spinal units were explanted and subjected to mock discectomy. The annular defect was closed using 2-0 non-absorbable (ultra-high molecular-weight polyethylene, UHMWPE) suture and Dines knot. The knot was backed up with two, three, or four throws. The spinal unit was subject to 4000 cycles of flexion/extension with 1500 N of axial load, and assessed for knot slippage. In vivo porcine device evaluation: three pigs (53–57 kg) were anesthetized and underwent a ventral surgical approach to the cervical spine. The AF of two discs was incised, and simulated partial NP discectomy was performed. The defect was closed at one level using the AnchorKnot device to apply the suture with a Dines knot and four throws. The pigs were observed for 4 weeks before euthanasia, allowing 7T magnetic resonance imaging (MRI) and histological evaluation. ResultsA Dines knot with four throws experienced no slippage after 4000 cycles. This configuration was tested in vivo. Clinically, the neurological examination in treated pigs was normal following surgery. Histological and MRI assessment confirmed sustained defect closure at 4 weeks. There was no reaction to the suture material and no NP extrusion at any of the sutured levels. ConclusionsThis study demonstrates that it is technically feasible to perform AF defect closure in a porcine model. This novel device achieved AF defect closure that was maintained through 4 weeks in vivo.

Minimal invasive annulotomy for induction of disc degeneration and implantation of poly (lactic-co-glycolic acid) (PLGA) plugs for annular repair in a rabbit model.

BackgroundThe rabbit disc model is useful for the study of intervertebral disc (IVD) degeneration and experimental therapeutic interventions. The annulotomy-induced disc models present several drawbacks, particularly an excessive disruption of disc integrity and a rapidly disc degeneration; therefore, this study sought to establish a minimal invasive annulotomy for induction of disc degeneration model, combined to annulus repair using implantation of a PLGA (poly lactic-co-glycolic acid) plug.MethodsNew Zealand white rabbits (n = 24) received annular injuries in three discs (L3/4, L4/5 and L5/6). The experimental discs were randomly assigned to four groups: (a) annular defect with a 1.8 mm diameter mini-trephine; (b) annular puncture by 16G needle; (c) annular defect with a PLGA plug implanted by press-fit fashion; (d) uninjured L2/3 disc served as control. Postsurgical x-ray, MRI examination, and real-time PCR analysis were performed at 1, 3 and 6 months. Gross morphology and histology were evaluated at postoperative 6 months.ResultsRadiographic examinations showed a slow, progressive disc space narrowing and a significant degree of disc degeneration on MRI grade in the injured discs at 6 months in all rabbits. Histological examinations and aggrecan, Col1A1, Col2A1 and matrix metalloprotease (MMP)-3 mRNA expression confirmed the disc degeneration, supporting the imaging results. The PLGA implantation reduced the marked loss of T2-weighted signal intensity seen at MRI in the injured discs and slowly decreased the disc height index (DHI) over the follow-up period. HE/Safranin O staining showed that annular defect was replaced by regenerated connective tissue with significant loss of proteoglycan content.ConclusionsThe minimally invasive approach for the creation of annular defects by an appropriately sized mini-Trephine is a suitable option for the study of disc degeneration in a rabbit model. Implantation of a suitable PLGA plug induced a successful repair of the annulus fibrosus within the degenerated disc, and retarded the degenerative process in the annular injury model.

Preoperative Risk Factors for Recurrent Lumbar Disk Herniation in L5-S1.

Although numerous studies have reported on recurrent lumbar disk herniation (rLDH), few have reported on recurrence of L5-S1 level. We investigated whether the preoperative risk factors, such as disk degeneration, disk height, sagittal range of motion (sROM), width of L5 vertebral transverse process, and iliac crest height, have any effect on rLDH in L5-S1. A retrospective case control study. A total of 467 patients were enrolled in this study. The disk degeneration, disk height, sROM, width of L5 vertebral transverse process, and iliac crest height were calculated using magnetic resonance imaging and simple radiography. We compared the clinical parameters (age, sex, body mass index, symptom duration, diabetes, smoking, preoperative visual analogue scale, herniation type, annular defect size) and preoperative radiologic parameters [disk degeneration, disk height, sROM, relative width of L5 vertebral transverse process (RT), iliac crest height index (IHI)] of recurrent and nonrecurrent groups. Patient with rLDH had its onset 39.4±17.9 months (7-90 mo) after primary surgery. Of the 39 rLDH cases, herniation was ipsilateral to previous LDH in 29 patients and contralateral in 10. Multiple logistic regression analysis showed that moderate disk degeneration with preserved height (group B), a large sROM, a small RT, a low IHI, and being male were significant risk factors for rLDH. Moderate disk degeneration, a large sROM, a small RT, and a low IHI are biomechanical risk factors of rLDH in L5-S1. The results also suggested being male and having a large annular defect increase recurrence after discectomy, especially in cases of ipsilateral rLDH.

Mechanical restoration and failure analyses of a hydrogel and scaffold composite strategy for annulus fibrosus repair

Unrepaired defects in the annulus fibrosus of intervertebral disks are associated with degeneration and persistent back pain. A clinical need exists for a disk repair strategy that can seal annular defects, be easily delivered during surgical procedures, and restore biomechanics with low risk of herniation. Multiple annulus repair strategies were developed using poly(trimethylene carbonate) scaffolds optimized for cell delivery, polyurethane membranes designed to prevent herniation, and fibrin-genipin adhesive tuned to annulus fibrosus shear properties. This three-part study evaluated repair strategies for biomechanical restoration, herniation risk and failure mode in torsion, bending and compression at physiological and hyper-physiological loads using a bovine injury model. Fibrin-genipin hydrogel restored some torsional stiffness, bending ROM and disk height loss, with negligible herniation risk and failure was observed histologically at the fibrin-genipin mid-substance following rigorous loading. Scaffold-based repairs partially restored biomechanics, but had high herniation risk even when stabilized with sutured membranes and failure was observed histologically at the interface between scaffold and fibrin-genipin adhesive. Fibrin-genipin was the simplest annulus fibrosus repair solution evaluated that involved an easily deliverable adhesive that filled irregularly-shaped annular defects and partially restored disk biomechanics with low herniation risk, suggesting further evaluation for disk repair may be warranted. Statement of significanceLower back pain is the leading cause of global disability and commonly caused by defects and failure of intervertebral disk tissues resulting in herniation and compression of adjacent nerves. Annulus fibrosus repair materials and techniques have not been successful due to the challenging mechanical and chemical microenvironment and the needs to restore biomechanical behaviors and promote healing with negligible herniation risk while being delivered during surgical procedures. This work addressed this challenging biomaterial and clinical problem using novel materials including an adhesive hydrogel, a scaffold capable of cell delivery, and a membrane to prevent herniation. Composite repair strategies were evaluated and optimized in quantitative three-part study that rigorously evaluated disk repair and provided a framework for evaluating alternate repair techniques.

Sutureless, rapid deployment valves and stented bioprosthesis in aortic valve replacement: recommendations of an International Expert Consensus Panel.

After a panel process, recommendations on the use of sutureless and rapid deployment valves in aortic valve replacement were given with special respect as an alternative to stented valves. Thirty-one international experts in both sutureless, rapid deployment valves and stented bioprostheses constituted the panel. After a thorough literature review, evidence-based recommendations were rated in a three-step modified Delphi approach by the experts. Literature research could identify 67 clinical trials, 4 guidelines and 10 systematic reviews for detailed text analysis to obtain a total of 28 recommendations. After rating by the experts, 12 recommendations were identified and degree of consensus for each was determined. Proctoring and education are necessary for the introduction of sutureless valves on an institutional basis as well as for the individual training of surgeons. Sutureless and rapid deployment should be considered as the valve prosthesis of first choice for isolated procedures in patients with comorbidities, old age, delicate aortic wall conditions such as calcified root, porcelain aorta or prior implantation of aortic homograft and stentless valves as well as for concomitant procedures and small aortic roots to reduce cross-clamp time. Intraoperative transoesophageal echocardiography is highly recommended, and in case of right anterior thoracotomy, preoperative computer tomography is strongly recommended. Suitable annular sizes are 19-27 mm. There is a contraindication for bicuspid valves only for Type 0 and for annular abscess or destruction due to infective endocarditis. Careful but complete decalcification of the aortic root is recommended to avoid paravalvular leakage; extensive decalcification should be avoided not to create annular defects. Proximal anastomoses of concomitant coronary artery bypass grafting should be placed during a single aortic cross-clamp period or alternatively with careful side clamping. Available evidence suggests that the use of sutureless and rapid deployment valve is associated with (can translate into) reduced early complications such as prolonged ventilation, blood transfusion, atrial fibrillation, pleural effusions and renal replacement therapy, respectively, and may result in reduced intensive care unit and hospital stay in comparison with traditional valves. The international experts recommend various benefits of sutureless and rapid deployment technology, which may represent a helpful tool in aortic valve replacement for patients requiring a biological valve. However, further evidence will be needed to reaffirm the benefit of sutureless and rapid deployment valves.

Initial Two-Year Safety Data for an Annular Closure Device: Interim Results from a Multicenter, Prospective, Randomized Clinical Trial

Objective Lumbar discectomy is the most frequently performed spine surgery, generally resulting in acute relief of symptoms from herniated or bulging discs. Longer term results are less positive, with many patients suffering recurrent herniations and/or continued degeneration. Limited nucleus removal results in reduced back pain, but more frequent reherniation, particularly in patients with large annular defects. Implantation of an annular closure device (ACD) may allow for the advantages of limited nucleus removal without increased reherniation risk. We report here interim results of an ongoing randomized clinical trial (RCT) of an ACD.

Risk Factors for Early Reherniation after Lumbar Discectomy with or without Annular Closure: Results of a Multicenter Randomized Controlled Study

Aim: Reherniation (RH) after lumbar discectomy (LD) is known as a failure and reported in the literature ranging from 3 to 18%. Different risk factors for RH have been discussed such as age, sex, BMI, smoking, type and size of annular defect, amount of removed disc volume, grade of disc degeneration, disc height, etc. The aim of this study was to identify preoperative demographic, radiological, and intraoperative surgical factors associated with early RH in patients undergoing one level LD with or without annular closure within 3 months after surgery. Methods: This study is based on the analysis of data of a postmarketing, prospective, multicenter RCT in Europa including patients undergoing standard LD with or without implantation of an annular closure device (ACD) (Barricaid®, Intrinsic Therapeutics, Inc., Massachusetts, United States). Enrollment of 554 patients in 21 Centers in Europa (DE, CH, AT, BE, NL, FR) started in 2010 and was completed by October 2014. A total of 276 patients were randomized to the ACD group and 278 patients to the control group. Results: Within 3 months after surgery, 20 (3.7%) patients had a symptomatic RH. 4 (1.5%) occurred in the ACD group and 16 (5.8%) in the Control group. Reoperation was performed in 3 patients in the ACD group and 9 patients in the Control group. Regarding the risk factors for RH, there was a trend with gender in the overall population (p = 0.077) – A 5.5% rate of RH was observed in females (12/219) in comparison to 2.5% (8/326) in male patients. A larger annular defect was a significant risk factor for RH overall (p = 0.017) and in the Control Group (p = .0.01). 21 (4%) patients had a defect size > 54 mm2 and 14.3% of these patients developed a RH. In the ACD group all 4 RH were found in patients with defects ≤ 54 mm2. Disc degeneration according to the classification of Kellgren and Lawrence showed a trend as a predictor for RH overall (p = 0.077) and was a significant risk factor in the Control group (p = 0.017). In addition the Pfirrmann classification correlated significantly with RH, both overall (p = 0.004) and in the Control group (p = 0.010). Out of 400 patients who showed a Pfirrmann Grade 2, 2.5% suffered RH, while 9.5% of the 95 patients with a Pfirrmann Grade 3 reherniated. Conclusion: Risk factors for early RH after LD in our study were large annular defect and disc degeneration. The ACD significantly reduces the risk for early RH. These results suggest that implantation of an ACD can prevent early RH after LD.

Microsurgical Annular Restoration with a Z-Suture following Lumbar Microdiscectomy: A Retrospective Comparative Study on 763 Patients with a Mean Follow-up of 12.5 Years

Background: Microdiscectomy for lumbar disc herniation (LDH) is one of the most common procedures performed by spine surgeons worldwide. It usually significantly reduces pain and restores both functional disability and health-related quality of life. The incidence of a postoperative recurrence, however, is encountered in 10 to 25%. A large annular defect is known to increase the risk of recurrence. A perioperative annular restoration may thus decrease the risk of recurrence. Methods: A retrospective study was performed comparing the risk of recurrence after lumbar single-level microdiscectomy with (study group) or without (control group) annular restoration using a Z-suture. Included patients were consecutively operated between May 1990 and April 1994 (control group) and September 1998 and December 1998 (study group). Subsequent LDH recurrence was recorded analyzing the patients' records and rereferrals until a mean follow-up of 12.5 years. Results: A total of n = 763 patients were included, of which 374 patients received a Z-suture (study group) and 389 patients served as controls (control group). The study groups did not differ in age (mean: 44.8 vs. 45.1 years; p = 0.86), gender (54.8 and 51.7% males; p = 0.38), or distribution of the lumbar segments (p = 0.46). Surgical time was significantly longer in the study group (81.6 vs. 69.3 minutes, p < 0.0001). The rate of reoperation for a local LDH recurrence was significantly lower in the study group at 3 months (0 vs. 1.8%, p = 0.02) and remained to show a clear trend at 12 months postoperative (2.1 vs. 4.6%, p = 0.07). At the time of last follow-up (mean: 8.3 vs. 16.6 years, p < 0.0001), local recurrence was observed in 21 out of 374 (5.6%) in the study group compared with 36 out of 389 (9.3%) in the control group (p = 0.06). The subsequent risk reduction of reoperation for local recurrence was 100, 54.3, and 39.8% after 3 months, 12 months, and at long-term follow-up using a Z-suture. There were no complications associated with the Z-suture in this series. Conclusions: Our data indicate that a Z-suture as annular restoration is safe and prolongs the surgery by ∼12 minutes. It reduces the recurrence rate at 3 and 12 months after microdiscectomy, while its impact on the long-term follow-up has to be interpreted with caution due to the longer follow-up of our control group. Therefore, annular defect restoration should be considered as an option to reduce the local recurrence rate for patients undergoing lumbar microdiscectomy.

Riboflavin crosslinked high-density collagen gel for the repair of annular defects in intervertebral discs: An in vivo study

Open annular defects compromise the ability of the annulus fibrosus to contain nuclear tissue in the disc space, and therefore lead to disc herniation with subsequent degenerative changes to the entire intervertebral disc. This study reports the use of riboflavin crosslinked high-density collagen gel for the repair of annular defects in a needle-punctured rat-tail model. High-density collagen has increased stiffness and greater hydraulic permeability than conventional low-density gels; riboflavin crosslinking further increases these properties. This study found that treating annular defects with crosslinked high-density collagen inhibited the progression of disc degeneration over 18weeks compared to untreated control discs. Histological sections of FITC-labeled collagen gel revealed an early tight attachment to host annular tissue. The gel was subsequently infiltrated by host fibroblasts which remodeled it into a fibrous cap that bridged the outer disrupted annular fibers and partially repaired the defect. This repair tissue enhanced retention of nucleus pulposus tissue, maintained physiological disc hydration, and preserved hydraulic permeability, according to MRI, histological, and mechanical assessments. Degenerative changes were partially reversed in treated discs, as indicated by an increase in nucleus pulposus size and hydration between weeks 5 and 18. The collagen gel appeared to work as an instant sealant and by enhancing the intrinsic healing capabilities of the host tissue.

In Vivo Repair of Rat Annulus Fibrosus Defects using High-Density Collagen Gels

Introduction Although a discectomy successfully relieves the neurological symptoms of a herniated intervertebral disc (IVD), it does not treat the underlying degenerative process; the annular defect remains unrepaired. Persistent annular defect is associated with an increased risk of recurrent herniation and progressive degenerative changes to the IVD. It may also be the primary cause of chronic low back pain following discectomy. To date, there is no established method for repairing annular defects in vivo. The presented study aims to determine whether injectable high-density collagen (HDC) gels can reduce further disc herniation and inhibit degenerative changes in a needle-punctured rat-tail model, and whether riboflavin (RF) cross-linking of injected collagen influences the repair process. Materials and Methods A total of 31 athymic rats were punctured with an 18-gauge needle in C3/4 of the caudal spine. They were divided into four groups: group 1 punctured and injected with HDC cross-linked with 0.5 mM (n = 6) or 0.75 mM (n = 7) RF; group 2 punctured and injected with noncross-linked collagen (n = 6); group 3 punctured and untreated (n = 8); group 4 punctured and injected with FITC-labeled cross-linked collagen (n = 4). Degenerative changes to punctured discs, NP size, and NP hydration were analyzed using X-ray, MRI), and histology. Functionality of repaired AF tissue was measured by mechanical tests, by comparing the hydraulic permeability of treated discs to that of healthy discs. Results After 5 weeks, untreated discs showed signs of terminal degenerative changes on MRI and histological sections ( Fig. 1 ). No NP tissue remained in the disc space. In contrast, discs treated with RF cross-linked collagen gels retained 63% of NP and 80% of disc height at 5 weeks, and showed minimal degenerative changes on histological section. Interestingly, a series of in vivo imaging showed that after 5 weeks, discs treated with cross-linked HDC demonstrated consistent improvement in both volume and hydration over time, while untreated discs and discs treated with noncross-linked HDC, lost volume, and water content. Injected collagen was seen to form a zipper-like adhesion to the host AF and connective tissue after 1 week and by 5 weeks a fibrous cap that persisted until 18 weeks. NP hydration and IVD functionality of treated discs were found to be similar to those of adjacent healthy discs at 18 weeks. [Figure: see text] Conclusion Injection of high-density collagen gel cross-linked with RF can repair annular defects, prevent the degenerative cascade, and maintain the functionality of IVDs in a rat-tail spine. Further studies will be performed to confirm the ability of HDC gels to repair annular defects in a large animal model.

New Method of Posterior Scallop Augmentation for Ischemic Mitral Regurgitation

We report a new method of posterior middle scallop (P2) augmentation for ischemic mitral regurgitation to achieve deep coaptation. First, P2 was divided straight at the center and partially detached from the annulus in a reverse Tshape. A narrow pentagon-shaped section of pericardium was sutured to the divided P2 and annular defect. The tip of the pentagon was attached directly to the papillary muscle, thus creating a very large P2 scallop. A standard-sized ring was placed. We adopted this technique in 2 patients with advanced ischemic cardiomyopathy, and no mitral regurgitation was observed during a 1-year follow-up.

环形线缺陷光子晶体滤波器的设计与数值研究

环形线缺陷光子晶体滤波器的设计与数值研究

Http://www.omicsonline.org/open-access/obtaining-of-hydrogels-using-pva-and-hec-for-adipose-tissue-regeneration-2157-7552-1000152.php?aid=58212

Circumferential tears of the Annulus Fibrosus (AF) are frequently observed pathological features of degenerate lumbar discs and have been associated with vascular propagation and the generation of low back pain. In order to evaluate the potential of novel biological agents to repair annular defects and arrest disc degeneration we required an animal model that would permit injection of cells or their cryoprotectant into adjacent lumbar discs of the same animal. Three lumbar discs (L2/3, L3/4 and L4/5) of 6 sheep were subjected to a peripheral lateral annular surgical incision. The adjacent uninjured lumbar L1/2 and L5/6 discs served as uninjured controls. After three months the spines were radiographed and disc height indices (DHI) calculated and Pfirrmann disc degeneration scores determined from MRI spinal images. Isolated lumbar discs were analysed morphologically, histologically and biochemically using published procedures. Disc height index measurements of injured discs revealed an average decrease of 23.67% relative to baseline values (p<0.0001). The corresponding MRI Pfirrmann degeneration scores were significantly higher than non-injured control discs (p<0.05), as were their morphology scores (p<0.005). The sulphated - glycosaminoglycan content, of the Nucleus Pulposus (NP) and injured side of the AF of lumbar discs, were significantly lower than control discs (p<0.05 and p<0.0005) respectively. Conversely, the DNA levels of the injured side of the AF were higher than the uninjured side (p<0.05). The histological scores showed higher degenerative changes in injured than in control discs (p<0.005). For all parameters monitored in this study no statistical differences were observed between the three injured lumbar discs confirming their uniform response to injury. This study therefore confirmed the suitability of this large animal model for evaluating the potential of biologicals to reconstitute degenerate ovine lumbar discs relative to their carriers/cryoprotectant.

Limited Lumbar Discectomy with Reconstruction of the Fibrous Annulus- Initial Experience

Introduction: Microdiscesctomy is a standard and effective surgical procedure for patients with lumbar disc herniation. Despite the satisfying results in most patients, recurrence is present in 5-15% of the patients. Literature data suggests greater than a 25% loss of preoperative disc height after surgery, which has been associated with poor clinical outcomes, particularly low back pain. To avoid re-herniation and preserve disc height, in recent years the standard surgical technique has been changing searching for possibilities for reconstruction of the fibrous annulus. Aim: We present our initial experience of fibrous annulus reconstruction in patients with lumbar disc herniations (annulus closure device Barricaid, Intrinsic Therapeutics, Inc). Material and Methods: The Barricaid endoprosthesis consists of a woven-polyester mesh intended to block an annular defect and titanium bone anchor that anchors the mesh to one of the adjacent vertebral bodies. After preoperative selection based on the clinical data and imaging findings limited microdiscectomy discectomy was performed in three patients with lumbar disc herniations. We located and measured the defect of the fibrous annulus and a Barricaid endoprosthesis was inserted. Results: We observed no complications associated with the method and all patients had good immediate and short-term clinical outcome. Conclusion: Recent investigations confirm that the use of annulus closure devices reduces reherniation rate, including high-risk patients and keep the height and biomechanics of the disc. This reduces subsequent degenerative changes and the associated impaired functional outcome in the long run. Our initial experience shows no significant prolongation of operative time or technical difficulties and good results in early clinical and imaging follow-up.

High-Density Collagen Gel Can Repair Annular Defects and Restore Biomechanical Function to Needle-Punctured Intervertebral Discs

IntroductionUnrepaired annular defects potentially increase the reherniation rate after lumbar discectomies and have been shown to accelerate degenerative changes after discographies.This is the fi...

Current Status of Disc Repair and Regeneration

Introduction Repair and regeneration efforts for intervertebral discs can be directed toward the annulus fibrosus (AF) and/or the nucleus pulposus (NP). Several different mechanical and biological approaches have recently been investigated for both disc components. We present a comprehensive literature research with a focus on biomaterials tested in vivo or in clinical trials for the treatment of disc degeneration. Methods Papers available in electronic databases such as PubMed, Web of Science, and Google Scholar by May 2013 were reviewed. The primary inclusion criterion was the presence of in vivo experiments or clinical trials. The secondary inclusion criterion was the ability to be categorized into one of the following four categories: (1) therapies with growth factors/cells, (2) gene/protein therapies, (3) annulus fibrosus repair, and (4) injectable biomaterials. Results Efforts to regenerate the NP focused on replenishing lost nuclear tissue by implantation of scaffolds with and without cell load or enhancing intrinsic synthesis of nuclear matrix by injection of human growth factors. Electrospun fibers were utilized as rigid scaffolds, collagen, and fibrin hydrogels as injectable scaffolds. Mesenchymal stem cells (MSC) or juvenile chondrocytes as allografts or xenografts have been predominately used as cell load. Cell/hydrogel combinations were successfully tested in various animal degeneration models. Cells proved to maintain viable in vivo and formed an extracellular matrix with a similar composition as the native NP. Typical degenerative parameters such as reduced disc height or loss of hyperintensity on MRIs were partially reversed. The growth factors osteogenic protein-1 and growth/differentiation factor-5 have been tested in rabbit disc degeneration models in vivo and proved to increase proteoglycan synthesis and extracellular matrix production of the NP. They showed to increase disc height and reverse histological and radiological degenerative changes in the rabbit spine. Injection of BMP-13 into sheep intervertebral discs found that it can prevent neovascularization and slow degenerative changes. MSC and juvenile chondrocyte injections for the treatment of degenerative disc disease demonstrated a significant reduction of pain scores in clinical trials with a maximum follow-up of 2 years. For annular repair, simple mechanical solutions such as special suture techniques or annuloplasty devices were initially tested but did not significantly alter annular healing strength or demonstrate long-term benefits in a clinical trial. Rigid biological implants using tissue-engineered AF constructs in vitro stimulate annular fibroblasts to produce extracellular matrix. Implants made from small intestinal submucosa reduced degenerative changes after annular incision in sheep spine in vivo. Recently, to improve clinical applicability, the potential of injectable biomaterials was investigated. Injectable genipin cross-linked fibrin hydrogels were shown to integrate with sections of human AF tissue and showed promising biomechanical and cell-seeding properties in vitro. Injectable riboflavin cross-linked collagen gel-proved viable to repair annular defects in the rat tail spine by enhancing intrinsic healing capabilities. This helped to retain nuclear tissue after inducing annular defects and inhibited degenerative changes defects in the rat spine. Conclusion Implantable biomaterials have the potential to integrate with host tissue and induce a regeneration process in the NP and AF. Several biomaterials have been tested in animal experiments for disc regeneration efforts and demonstrated the ability to partially reverse degenerative changes. Most of these data still have to be corroborated in clinical trials. Cell/scaffold combinations have already been tested in clinical trials to treat degenerative disc disease. However, results from long-term randomized trials with a greater patient population are not yet available. Disclosure of Interest Consultant for Lanx Consultant for BrainLab Consultant for DePuy-Synthes

Annulus Fibrosus Repair

Intervertebral disc (IVD) herniation is a common origin of disabled spine and low back pain (LBP) which cause enormous health care toll. The annulus fibrosus (AF), which constitutes the outer part ...

Percutaneous Endoscopic Intra-annular Subligamentous Herniotomy for Large Central Disc Herniation

Technical case report. To describe the novel technique of percutaneous endoscopic herniotomy using a unilateral intra-annular subligamentous approach for the treatment of large centrally herniated discs. Open discectomy for large central disc herniations may have poor long-term prognosis due to heavy loss of intervertebral disc tissue, segmental instability, and recurrence of pain. Six consecutive patients who presented with back and leg pain, and/or weakness due to a large central disc herniation were treated using percutaneous endoscopic herniotomy with a unilateral intra-annular subligamentous approach. The patients experienced relief of symptoms and intervertebral disc spaces were well maintained. The annular defects were noted to be in the process of healing and recovery. Percutaneous endoscopic unilateral intra-annular subligamentous herniotomy was an effective and affordable minimally invasive procedure for patients with large central disc herniations, allowing preservation of nonpathological intradiscal tissue through a concentric outer-layer annular approach.