Biomechanical evaluation of disc annular repair technology in human lumbar spine

Transcription

1 The University of Toledo The University of Toledo Digital Repository Theses and Dissertations 2014 Biomechanical evaluation of disc annular repair technology in human lumbar spine Sarath C. Koruprolu University of Toledo Follow this and additional works at: Recommended Citation Koruprolu, Sarath C., "Biomechanical evaluation of disc annular repair technology in human lumbar spine" (2014). Theses and Dissertations This Thesis is brought to you for free and open access by The University of Toledo Digital Repository. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of The University of Toledo Digital Repository. For more information, please see the repository's About page.

2 A Thesis entitled Biomechanical Evaluation of Disc Annular Repair Technology in Human Lumbar Spine by Sarath Koruprolu Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Master of Science Degree in Bioengineering Dr. Vijay Goel, Ph.D., Committee Chair Dr. Scott Molitor, Ph.D., Committee Member Dr. Brent Cameron, Ph.D., Committee Member Dr. Patricia R. Komuniecki, Dean College of Graduate Studies The University of Toledo December 2014

3 Copyright 2014, Sarath Chandra Koruprolu This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author.

4 An Abstract of Biomechanical Evaluation of Disc Annular Repair Technology in Human Lumbar Spine by Sarath C Koruprolu Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Master of Science Degree in Bioengineering The University of Toledo December 2014 The availability of pre-operative data on the biomechanical stability of an annular repair device may influence the clinical management of lumbar spine surgery. Having the knowledge of the performance of various annular repair devices can assist in the selection of better choices for treatment. Numerous studies investigated the effect of various implants such as artificial nucleus replacement, repair or annular tears, novel annulus repair devices with full or partial discectomy etc. However, the area of nucleus and annulus repair technology still needs to be further researched upon to devise an alternative disc replacement device that would reduce pain, minimize the restriction of range of motion and decrease the degenerative effects on the adjacent segments. As a first step towards achieving this goal, an implant must be tested under appropriate biomechanical protocols to study its stability during complex physiological motion that is encountered clinically. This study determined the biomechanical performance of a novel annular repair device in an in-vitro in the human cadaveric lumbar spine. The test criterion was to evaluate implant migration during complex cyclic loading, study its effects on the range iii

5 of motion of the functional spinal segment and intradiscal pressures. The overall stability of the device is studied under extreme physiological impact loading and the finite element analysis of the construct is conducted and compared to the in vitro data. Six human cadaveric lumbar functional spine unit specimens (L2-Sacrum < 70 years of age) were gathered for testing. Each cadaveric specimen (L2 - L5) was cleaned of all muscle and adipose tissue and dissected into L2-3 and L4-5 motion segments. Specimens were stored double bagged at -20 C and allowed to thaw at room temperature for 10 to 12 hours prior to any manipulation. Cadaveric vertebral samples provide a natural and appropriate geometric and material sample for study but may lead to significant variability due to natural patient variation. Thus, they were assessed with DEXA scans prior to use. Each specimen was stripped of soft tissue and disarticulated into separate functional spinal segments. Axial and lateral images of each vertebra were captured by fluoroscopy prior to any testing and quantified with digital analysis using Imaging software. Implant placement was confirmed under fluoroscopy. Specimens were cyclically loaded in load control through 250,000 cycles of ± 7.5 Nm of bending moment applied by offset superior-inferior loads at the cephalic endplate of the vertebral body potted in a rigid urethane compound mount in customized fixtures with a fixed moment arm. Loads were applied using an MTS servo hydraulic test frame. Following cyclic loading of the specimens, three dimensional motion tracking was performed on all the specimens. Fluoroscopy was obtained to establish the position of the implant using digital image analysis. Finally, specimens were impact loaded to failure in compression. Implant migration was studied using digital image analysis and finite element analysis was performed to evaluate intradiscal pressures and facet loads. iv

6 In comparison to intact data there was an increase in ROM for pre fatigue condition with annular repair device in extension (36%), flexion (46%), left bending (37%), and right bending (47%) left rotation (22%). In Post fatigue loading, the ROM was increased in extension (23%), flexion (78%), left bending (56%), right bending (77%) left rotation (72%) and right rotation (22%) compared to intact. Implant translation was 3 mm in pre fatigue condition compared to 1 mm in the posterior direction and implant rotation was 9 degrees in the pre cyclic condition compared to 13 degrees in the post fatigue condition. The PEEK annular repair device evaluated in this study along with posterior fusion exhibited stability during fatigue testing following partial unilateral discectomy and did not migrate posteriorly so as to cause a clinical failure due to impingement on the nerve roots. v

7 Take up one idea. Make that one idea your life - think of it, dream of it, and live on that idea. Let the brain, muscles, nerves, every part of your body, be full of that idea, and just leave every other idea alone. This is the way to success. -Swami Vivekananda vi

8 Acknowledgements I thank my parents Annapurna and Satheesh Babu Koruprolu for their love and support in realizing my dream to pursue graduate studies. I would like to thank my advisor Dr.Vijay Goel for being extremely supportive and patient in guiding me through these formative years of my career. I would also like to thank Drs. Scott Molitor and Brent Cameron for their kind acceptance to be a part of the thesis committee. I would like to thank Magellan Spine, Inc. for supporting my research and providing implants. I also like to thank Dr. Arunan Nadarajah and the department of bioengineering. Finally, I thank all my friends here at The University of Toledo. vii

9 Table of Contents Abstract...iii Acknowledgements... vii Table of Contents... viii List of Figures... xii List of Tables... xii 1. Basic Science Overview: Introduction: Low Back Pain: Scope and Objectives of the Present Study: Literature Review Overview: Background: Disc Degeneration: Biomechanics of Spine: Treatment of Low Back Pain: viii

10 2.6. Biological approach: Disc replacement technologies: Summary: Methods of Biomechanical testing Materials and Methods Overview: Specimen Selection: Implant Markers: Steps for testing: Pre and post Optotrak kinematics test: Complex cyclic loading: Considerations for complex cyclic loading Radiographic evaluation: Migration analysis: Impact loading: Optotrak Data Analysis: Finite Element Analysis: Geometric Modeling: Vertebra modeling: Inter Vertebral Disc Modeling: ix

11 Facet Joint modeling: Ligament modeling: Boundary conditions: Implant Models Used for Simulation: Intact model: Injured model: Instrumented model: FEA analysis: Results Overview: In vitro study: Range of motion analysis: Finite Element Analysis: L4-L5 Motion segment: Range of Motion (ROM): Intra Discal Pressure (IDP): Facet Loads: Migration Analysis: Discussion Overview: x

12 5.2. In vitro study: Implant material choice: Conclusion: References..69 xi

13 List of Tables 3.1 Specimen Demographics Implant sizes corresponding to specimen levels Material properties of the components spinemodel Material properties of the components of spine mddel Mean and SD values at 7.5 N-m in lateral bending mode Von mises stress (Mpa) of intervertebral disc (L4-L5) at 7.5 N-m Translation of tantalum markers during fatigue testing Rotation of tantalum markers during fatigue testing xii

14 List of Figures 2-1 Ligamentous structures of textures of the spine [7, 11] Disc Degeneration [12] Biomechanical regions of spine [11] Pressure on the nucleus [18] Stages of degenerative disc disease [20] Components of Intervertebral disc [21] Original Stubstadt system [28] Froning prosthesis [28] Downey process [28] Main prosthesis [28] Magellan spine annular repair device Potted caudal end of the motion segment [32] Threaded rods in the vertebral body for load application [32] Motion analysis test setup Test setup for complex cyclic loading Phase difference between compression and torsion Complex cyclic loading test setup Fluoroscopic images showing the implanted Intact L3-S1 FE model Intact L4-L5 FE model modified from L3-S1 model xiii

15 3-11 L4-L5 FSU A) Anterior view of B) lateral view showing vertebral bodies and disc and other components L4-L5 FSU A) Posterior view and B) Posterio-lateral view of showing facet joint Models of Magellan spine Annular repair device Implanted L4-5 motion segment L4-5 model following discectomy Interactions defined between the implant surfaces and the disc Mean values at 7.5 Nm for all loading modes (in degrees) Range of Motion at 7.5 N-m Range of Motion in Flexion with no preload Range of Motion in Extension with no preload Range of Motion in Flexion with 400N preload Range of Motion in Extension with 400N preload ROM in Flexion at 7.5 N-m prefatigue ROM in flexion at 7.5 N-m postfatigue ROM in Extension at 7.5 N-m at Prefatigue ROM in Extension with Preload at Postfatigue Neutral zone L4-L5 post fatigue testing Left facet loads during all loading conditions at 7.5 N-m Right facet loads during all loading conditions at 7.5 N-m Marker translation in millimeters Marker rotation in degrees xiv

16 Chapter 1 Basic Science 1.1. Overview: In this chapter, the basic spine anatomy along with indications for back pain is discussed, laying out the foundation for the necessity to undertake this experiment Introduction: Disc degeneration is one of the main causes of low back pain. Many patients may require surgery and the procedures that vary from conservative treatment, dynamic stabilization implant systems to fusion with or without supplementary devices. Dynamic stabilization devices are employed with the assumption that they will decrease the intervertebral disc loading at the treated level thereby reducing pain and limiting further degeneration, while minimizing the degenerative effects on the adjacent levels. Several design concepts ranging from loaded springs to articulating type devices to nucleus and annular repair devices have been proposed recently. 1

17 The prevalence of spine surgery has steadily been on the rise over the last two decades and this trend is expected to continue over the next one quarter century. Adding to that, the number of implanted medical devices that have been developed and the clinical indications for their use have been widening over the last ten years and this trend is continuing. Several total disc replacements (TDR), flexible stabilization systems, nucleus replacement devices, facet joint arthroplasty systems have been widely used. Overall, the percentage of the population who have undergone spine surgery is increasing.. The steady increase in the number of people or the percentage of population that has undergone spine surgery or intending to is gradually increasing the risk that these people will be involved in a traumatic incident such as a car collision or a fall. With the presence of an artificial implant in the body, these people can experience significantly large spinal loads that will be generated in such traumatic incidents and, at the treated levels, these loads are shared between the remaining natural anatomy and the spine implants which could result in implant and implant-bone interface loads that exceed the design loads of the implants. Such conditions have to be considered very carefully during the process of development of various spinal surgical alternative implants and other novel dynamic stabilization systems. However, the trend so far has suggested that these factors were not a part of the design of the implants that are out currently in the market and have very limited role in load sharing during a traumatic injury.. Recent medical case reports have documented the performance and failure of various instrumented spines after patients with spine implants from previous surgeries that underwent trauma.[1-6] A lot research has been focused on the biomechanics of spine implants including human cadaver experiments, in vivo animal studies and mathematical modeling at quasi- 2

18 static physiological loading rates. There has been published and active research on other areas with specific focus on the biomechanics of the natural spine under extreme traumatic impact loading conditions using cadaver experiments, mathematical models and in vivo animal experiments. While some research groups concentrate on evaluating the biomechanical performance of two or more implants to establish either the equivalence or superiority of one implant over the other under normal physiological loading conditions, other research groups focused on the natural biomechanics of the spine, research methods and appropriate biomechanical loading protocols that are clinically relevant. This can be broadly characterized as concentrating on problems involving orthopaedic treatment of the spine. The impact biomechanics research concentrates on topics related to injury mechanisms, injury tolerance and injury prevention. It has become increasingly relevant to perform evaluations of various spinal implants under normal physiological and traumatic loading conditions to ensure that implant-related damage to the spinal column, and adjacent anatomical structures and organ systems is minimized. The lordotic morphology of the cervical and lumbar spine helps bear the weight of the head and the body, unloading the annular fibers. In terms of range of motion, the S- shaped spine has its own advantages over a straight spinal column. Due to the ability of individual vertebrae to move relative to each other, movements in the more cranial segments can compensate for movements in the Lumbopelvic region. Absence of these compensatory mechanisms would require a significant cervical movement for a small range of caudal movement. Although a straight column is always more stable than a curved column, S-shaped spine can absorb more energy because of its greater resistance 3

19 to deformation or change. In spine, the articulation between two individual vertebrae is composed of the following components, Intervertebral disc Ligaments and joint capsule Musculature Intervertebral disc (IVD) contains three main components namely cartilaginous end plates, annulus fibrosus and nucleus pulposus. It is a major load-bearing and motion control element of the spine. It functions as a shock absorber and it deforms upon the application of compressive forces of the spine. Figure 1-0 The S-Shaped spine [7] 4

20 Intervertebral discs are characterized by their abundant extracellular matrix and low cell density, coupled with an absence of blood vessels, lymphatics, and nerves in all but the most peripheral annulus layers. In many respects, this absence leaves the disc prone to degeneration, because the cells have a large extracellular matrix to maintain without nociceptive feedback to limit and detect damage, and no source of repair through the vasculature. Intervertebral discs are not uniform in composition, but consist of two clearly distinct regions. The outer annulus fibrosus is a fibrocartilage, and contains concentric lamellae rich in collagen, whereas the inner nucleus pulposus is a less structured gelatinous substance rich in proteoglycans Low Back Pain: Lower-back pain has been regarded as one of the most common complaints. Previous studies showed that the musculoskeletal diseases have a major impact on the health care in North American and western European countries and lower-back pain accounts for a significant amount of these complaints [8]. Especially, studies showed that morbidity, disability and pain brought about by lower-back pain are considerable among the working population [9]. The specific lesion for the cause of lower-back pain cannot be identified and in many cases has been classified as lower-back syndrome. The Health Interview Survey of the US National Health Survey has found that each year more than 1% of persons in the age group years in the United States report having trouble with prolapsed IVD s [10]. There have been previous studies of the role of psychological variables in lower-back pain but there were no big breakthroughs. 5

21 Heredity is also mentioned as a possible factor in causing lower-back pain but there was no definitive evidence supporting this [21] Scope and Objectives of the Present Study: The rationale for this study was to evaluate implant migration or expulsion after repetitive cycling in flexion combined with axial rotation. This was achieved by applying a physiologically relevant complex cyclic loading protocol on the instrumented spinal motion segments before and after the fatigue testing. Our hypothesis for the migration study was that the Magellan Spine Interbody Fusion Device in the unilateral configuration with supplemental pedicle screw fixation will not shift or migrate beyond the natural limits of disc motion (2-3mm) and the device will not flip greater than 90 degrees. 6

22 Chapter 2 Literature Review 1.5. Overview: This chapter discusses lumbar spine disorders and explores the current research for various surgical options available for the treatment of disc degeneration. Various modalities of disc repair are discussed as well with an overview of the disc replacement technologies and implants invented in the past decade Background: Intervertebral disc space narrows as a result of nucleus prolapse or due to degeneration of the disc itself and as a consequence, osteophytes or bridging of bone occurs. Age is also an important factor that contributes to disc degeneration although it is not clear whether the pathologic mechanism or the ageing mechanism that causes it first. 7

23 Figure 0-1 Ligamentous structures of textures of the spine [7, 11] 1.7. Disc Degeneration: Intervertebral discs are rich in extracellular matrix and have low cellular density. Blood vessels, lymph nodes and nerves are absent and this absence leaves the disc vulnerable to degeneration. This is also a major factor for the disc cell s inability to repair itself due to the lack of vasculature. As we know, IVD s contain clearly two layers, the outer annulus is a fibro cartilage material and contain lamellae that have high collagen content. The inner layer of the disc is called nucleus pulposus and it contains proteoglycans and is rich in water content. 8

24 Figure 0-2 Disc Degeneration [12] Upon repeated application of mechanical loads, nucleus pulposus becomes a solid fibrous substance and loses its natural ability to absorb shock. As a result of this, focal defects appear in the layers of annulus and results in dehydration. Nucleus pulposus contains about 15-20% of collagen and the annulus contains about 65-70% of collagen by dry weight [13-15].Recent studies have shown that the collagen content decreases as a result of ageing and dis degeneration and also a decrease in the cell synthetic capacity [13]. Disc degeneration usually occurs as a result of structural proteins mainly collagen and proteoglycans within the extracellular matrix. Collagenases are mainly involved in the process of degrading collagen present in the intervertebral disc. 9

25 Some of the degenerative disorders of the spine that need surgical treatment include the herniation of discs, scoliosis, spinal stenosis and degenerated discs. Surgical procedures serve as a solution only to remove the problem of lower-back pain than repair it. An ideal repair technique would include the restoration of the physical and mechanical functionality of the disc. However, current research has been able to identify only two biological approaches to solve this problem. One of them is the use of injection of inhibitors during early stages of disc degeneration to stimulate metabolic activity and the other is the design and implantation of a biomatrix embedded with cells that has the ability to function as a native disc. This has also been referred to as the usage of scaffolds in disc repair. Based on the research conducted in this area, the principles of conducting such an experiment, two types of biomatrices can be envisaged as supplementation options. The first is a precultured matrix with cells embedded into it and positioned in a compound that simulated the extracellular environment and the second principle being the usage of a soluble polymer in which cells are placed and allowed to polymerize once the compound has been placed inside the body Biomechanics of Spine: It is necessary to understand the mechanism of the function of the spine for the purposes of mathematical modeling. Most biomechanical studies utilize a part of the spine called a Functional spinal unit. It is widely accepted that the behavior of the functional spinal unit grossly represents the actual behavior of spine invitro. The basic 10

26 biomechanical approach in studying the motion of these functional spinal units are obtained by holding the bottom vertebra rigidly and studying the relative motion of the adjacent vertebrae to the fixed lower vertebra. Physiological loads can be widely approximated into six main types of motion, i.e. flexion, extension, left bending, right bending, left rotation and right rotation. Although activities of human beings are quite complex in nature, it is a combination of these six basic motions. For this reason, all the other motion types are classified as coupled motion that involves two or more of the basic spinal motions. Biomechanical studies have widely researched on the basic and complex coupled motions of the spine and the data is well reported and published in the literature. Biomechanical tests of the spine involve dynamic loading of functional spine units or full cadaveric specimens or mathematical modeling of these dynamic or static loading conditions. Impact loading of the spine in compression may be performed using either propelling the spine against a surface or holding the spine specimen rigid and impacting with a rigid surface. One of the most complicated lower back injuries is the pain due to the compression of nerve roots that occurs as a result of protrusion of the disc into the posterior canal. 11

27 Figure 0-3 Biomechanical regions of spine [11] Although intervertebral discs are capable of withstanding a very high range of compressive loads, repeated application of these non-physiological loads results in decrease of the water content of the disc, thereby losing its flexibility and ability to bounce back to its normal height after the release of the loads. Repetitive occurrence of such activities may result in permanent damage of the fibers surrounding the nucleus and gradual degeneration may occur. Biomechanical studies use axial compressive loading of the spine as the most commonly accepted method of loading the spine. The compressive forces applied on a healthy disc are born by the cartilaginous end plates, adjacent vertebrae and the intervertebral disc between them. The hydration of these components is directly 12

28 proportional to the applied compressive stress. Prolonged loading of the spine results in the loss of hydration of the disc and thereby causes decrease in the disc height. [16, 17] Figure 0-4 Pressure on the nucleus [18] Facet joints serve as the constraints for the spine in lateral bending as well as axial rotation. Each vertebra contains two pairs of facet joints, i.e. superior and inferior. The joint surfaces of the facets are quite complex in nature and they are oriented at different angles at different parts of the spine. Facet joint surfaces are covered by cartilage and the degeneration of the cartilage leads to increased friction and loss of movement at the affected level. Several studies have tried to address the issue of changes in disc integrity due to application of loads. Brinckmann [19], found that the inner annulus fibers upto 1 mm in periphery results in a small localized bulging of less than 0.5 mm in that region under compressive loading. 13

29 Figure 0-5 Stages of degenerative disc disease [20] Figure 0-6 Components of Intervertebral disc [21] 14

30 1.9. Treatment of Low Back Pain: There are several ways to treat disc degeneration, however the key principles behind the disc replacement concepts are that some prostheses try to replace the viscoelastic properties of the disc and other type of implants mainly aims at the reproduction of the mechanical properties of the disc. There were attempts to combine these two principles in order to produce an artificial disc that mimics the native intervertebral disc but a lot of research is necessary before these implants can actually be implanted for clinical trials. The two main treatment types are spinal fusion and motion preservation or dynamic stabilization instrumentation systems. Spinal Fusion aims to restrict relative motion between spinal segments and thereby allow bony fusion to occur across the segments. It may be a treatment for deformity correction or as a pain relieving mechanism, or it could act as stabilization following spinal column trauma injury or pathology. In contrast, dynamic stabilization or motion-preserving spinal devices such as total disc replacements, dynamic posterior fixation systems and facet arthroplasty devices, often aim to preserve intact spine motion closer to the physiological motion and function as well as load-sharing while providing stability, relieving pain and eliminating adjacent spinal level degeneration.. Biomechanical testing protocols for dynamic stabilization devices typically include evaluation of spine kinematics and effect on adjacent segment motion. There are two widely accepted modes of testing protocols for these devices namely flexibility loading protocol or stiffness loading protocol. In the flexibility protocol, experimentally 15

31 controlled non-motion-constraining moments are applied to the specimen and the resultant motion of the spinal segments is measured. This protocol is suitable for examining the biomechanics of the treated or implanted functional spinal segment[22]. In the stiffness loading protocol, controlled rotations are applied with a fixed center of rotation and the resultant moments are measured[23]. A modified version of these approaches is the Hybrid protocol, in which pre-determined rotations are applied with pure non-motion constraining moments[24].stiffness loading or hybrid loading biomechanical testing protocols are used to examine the biomechanics of spinal segments adjacent to standard fusion or dynamic stabilization or motion restoring implants. Hybrid protocol marks a physiologically relevant range of motion with the primary assumption that a patient will try to move their spine through the same range of motion preoperatively and post-operatively. The nature of the spinal surgery performed may dictate the range of allowed motion in the patient however, if allowed the patient would normally exert physiologically routine loads on the spine. Given this pre-determined range of motion, hybrid protocol applies the obtained rotation on a spinal segment due to the application of physiologically relevant moments and re-testing the spinal segment by applying the obtained rotations exhibited altered loads at the instrumented and the adjacent levels Biological approach: Current research concentrates on multiple aspects of biological research in terms of producing a functionally capable intervertebral disc. Most prominent areas of such research include understanding the cell behavior in vivo, tissue engineering, studies of 16

32 disc nutrition, vertebral end plate functions and gene therapy or role of stem cells in disc therapy. Physiologic functioning of the cell needs a lot of co-ordination of cell structures and is influenced by their surrounding environment. This extra cellular matrix is constantly remodeled by adjacent cells and forms the core of disc function to absorb shock and provide tensile function. Assessment of the disc and its composition at different stages of ageing provides a valuable insight into disc degeneration and its patterns. Electron microscopy has been an extremely valuable tool in ascertaining these conditions. Novel technologies in tissue engineering have provided a variety of therapeutic options to treat degenerative disc disease. Tissue engineering methods based on cell functioning have been able to show that human disc cells can be modified and manipulated by gene transfer Disc replacement technologies: Nachemson et al injected a self-solidifying liquid silicone polymer in cadaveric discs and demonstrated relative restoration of motion properties but found that the implants disintegrated and lost their mechanical function significantly after 30 thousand cycles of normal physiological load [25-28]. 17

33 Figure 0-7 Original Stubstadt system [28] The Froning prosthesis is a discoid bladder implant model. It is filled with liquid by injecting process. This injection filled prosthesis is further secured rigidly by attaching its spike end to the vertebral end plates to secure it in place. The device is shown in Figure 2-8. Figure 0-8 Froning prosthesis [28] 18

34 The Downey prosthesis is a cushion shaped in the form of a flying object. It is made up of silicon or polyethylene and has an inner core with a more fluidic material. Two large screws are used to attach the prosthesis to the end plate. The threading of these screws is made opposite in direction so that the device screws in simultaneously in both directions at the same time when being implanted into the end plates. The technical skill required to implant such prosthesis is very high. Figure 0-9 Downey process [28] 19

35 Figure 0-10 Main prosthesis [28] Main prosthesis was designed to have two different parts. It is intended to replace both the disc and the vertebral body. It has two thick rigid housings and they are fixed by anchoring pins with a surrounding expandable structure that aims to restore the disc height Summary: A few disc/nucleus replacement concepts mentioned above showed the necessary direction in terms of finding an ideal prosthesis to replace the disc. However, most of these concepts were sound in terms of engineering principles but failed to replicate their success invitro due to the various biological factors involved. The choice of materials was further scrutinized by their failure to withstand repetitive physiological compressive loads resulting in the degradation of materials over time. This further emphasized the necessity 20

36 of an implant that could well behave as an incompressible viscoelastic material as well as provide sufficient mechanical strength to restore the disc height Methods of Biomechanical testing Understanding the biomechanical response of the intact and implanted lumbar spine upon the application of normal physiological loads as per defined testing protocols is necessary to understand the predominant injury mechanisms and also to determine injury tolerance of the implanted spine and device failure thresholds. Biomechanical testing protocols generally carry out experiments on human volunteers, human cadavers animals, physical human surrogates and also mathematical modeling. However, each one these different experimental designs has their own limitations and advantages. These are at length, discussed by previously published material in articles like Schmitt et al [29]. Normal physiological loads are in the range of 5-10 N-m. Typically, biomechanical studies involving lumbar spine segments are loaded these moments with varying loading rates depending on the desired outcome being evaluated. Traditional methods of these biomechanical protocols involve manual loading of weights to induce pure-moments on the spine based on customized test setups, use of servo hydraulic or electromechanical semi-automated testing machines and fully automated DC motor operated complex spine testing machines. However, one of the limitations of these methods is that they are incapable of simulating a loading condition that is caused by a severe traumatic injury within a laboratory space. Traumatic impact of the spine require considerable test setups, complex tracking mechanisms and remains cumbersome to the day.. Generally, lumbar spine is evaluated in six loading conditions namely, flexion, extension, left and right 21

37 lateral bending, left and right axial rotation [30]. Apart from these, a variety of complex coupled loading conditions can be generated by the combination of test setups driven by the desired relevant outcomes.. Although pure moments are not directly representative of the loads experienced in the spine in vivo, they are in the range of the overall load experienced by spine due to the manipulation of the trunk and bodyweight by a person. This varies significantly in the case of traumatic injuries to the spine where the loading rates are in the order of 100 ms or even lesser [31]. 22

38 Chapter 3 Materials and Methods Overview: In this chapter, specimen preparation, implant marker installation, steps for testing, methods and materials employed in the study, setup of optotrak motion analysis, range of motion collection and assessment, overview of finite element modeling is described Specimen Selection: Three human cadaveric lumbar spine specimens (L2-Sacrum < 70 years of age) were gathered for testing. Each cadaveric specimen (L2 - L5) was cleaned of all muscle and adipose tissue and dissected into L2-3 and L4-5 motion segments. For this study, either the L2-3 or L4-5 specimens were utilized. Each specimen was radiographed to determine anatomic and bone mineral integrity. Any specimen exhibiting significant degeneration, osteophytic bridging, narrowed disc space, and signs of metastatic disease was excluded from the study (or any spine surgery instrumented or none instrumented). The superior and inferior vertebral bodies were anchored in cups using polyester resin and pins so that they can be mounted to the gripping fixtures on the MTS machine and the Optotrak testing system. The specimens were wrapped in saline soaked towels to 23

39 prevent dehydration of the soft tissues. The L2-3 or L4-5 segment was designated as the instrumented level for testing purposes. All tests were performed at room temperature. Table 0-1 Specimen Demographics Specimen Label Level T-score L2-L L2-L L2-L L4-L L4-L L4-L Implant Markers: 3 Tantalum markers (0.9 mm diameter) were mounted onto the annular repair device by making small holes on the device and glue was used to fix the markers in position. 3 appropriately sized annular repair devices were unilaterally implanted into the L2-3 or L4-5 disc space. In two of the specimens (51331 L2-3 & L2-3) the devices were implanted to the left side and in one specimen (51331 L4-5) the device was implanted to the right. 24

40 1.17. Steps for testing: Figure 0-1 Magellan spine annular repair device The biomechanical testing was divided into two phases. In phase one, specimen L2-3, L4-5 and L4-5 were tested according to the following steps. In Phase 2, each of the specimens underwent the following steps: Pre fatigue kinematics Radiograph 1 Complex cyclic loading Radiograpj 2 Post fatigue kinematics Radiograph 3 Impact laoding 25

41 Each cadaveric specimen (L2 - L5) was cleaned of all muscle and adipose tissue and dissected into L2-3 and L4-5 motion segments. Each motion segment was rigidly secured in bondo by metallic screws. Figure 0-2 Potted caudal end of the motion segment [32] Following potting, four threaded metallic rods were inserted in the vertebral body of the specimen to facilitate the application of pure moments via a pulley-weight system. Figure 0-3 Threaded rods in the vertebral body for load application [32] 26

42 1.18. Pre and post Optotrak kinematics test: Analysis of range of motion was carried out using Optotrak 3020 (NDI Digital, Waterloo, Ontario, Canada). The following conditions were tested: 1) Intact 2) Injury + device pre fatigue loading 3) Injury + device post fatigue loading Only 3 specimens were used in kinematics testing. Each specimen was fixed to the apparatus at the caudal end and free to move in any plane at the proximal end. Each specimen was loaded to a maximum bending moment of 7.5 Nm in flexion, extension, lateral bending, and axial rotation. Loads were applied to the superior vertebral body in the order of 1.5, 3.0, 4.5, 6.0 and 7.5Nm. The moment value of 7.5 Nm for flexion and axial rotation is within the range of moments used in previous biomechanical studies of human lumbar spine segments. Moments were applied to generate the following 6 loading modes: flexion (Flex), extension (Ext), right and left lateral bending (RB, LB), and right and left axial rotation (RR, LR) without the application of a follower preload. Following the loading, a compressive preload of 400N was applied in flexion and extension loading modes. The motion was measured using an optoelectronic motion measurement system (Model 3020, Optotrak ). 27

43 1.19. Complex cyclic loading: Specimens were implanted with Magellan Spine Annular Repair Device and cyclically loaded using MTS Bionix 835 (MTS, Eden Prairie, MN) biaxial testing machine. Specimens were loaded to 7.5Nm in both flexion and axial rotation. Cyclical testing under coupled motions provides a loading paradigm that simulates the mechanics of human motion during daily activities. Following preconditioning, each specimen was loaded as discussed. The testing was conducted on implanted specimens only. To represent a worst case scenario of testing, the unilateral Interbody fusion (IBF) device was not surrounded with morselized bone but was placed laterally on either the left or right regions of the disc. A fusion was not simulated in this study to avoid compromising the motion segment for cyclic testing and to test under the worst case scenario for the device. Additionally, supplemental posterior fixation was placed across the segment so that each segment was implanted with one IBF and posterior pedicle screw implantation prior to migration testing. The parameters measured were the load applied and displacement measured during flexion and rotation. Load was applied in coupled flexion and axial rotation by using fixtures that can apply a lever arm at a predestined distance from the center of rotation of the specimen. A 400N compressive load was applied to the motion segment at a pre-measured lever arm to achieve a total of 7.5Nm of bending in flexion. Rotation to 7.5Nm was applied under torque control. Both flexion and rotation was coupled and applied simultaneously to each specimen at a rate of 3 Hz for 250,000 cycles. It is estimated that the human spine will cycle approximately 1 million cycles in compression over the course of 1 to 2 years and will experience 250,000 significant 28

44 bends in one year, which is 10,500 cycles per month. Using these numbers, the 250,000 cycles is equivalent to approximately 24 months of spinal bending. Complex cyclic loading was applied in two steps on all the specimens. Each specimen was tested for the first 125,000 cycles with the annular repair device instrumented unilaterally and posteriorly fused. Following the completion of 125,000 cycles, the pedicle rods were removed and the implant was fatigued for another 125,000 cycles to simulate a more rigorous scenario. Table 0-2 Implant sizes corresponding to specimen levels Specimen Label Level Implant Size (mm) Specimen L2-L3 8 Specimen L2-L3 8 Specimen L2-L3 8 Specimen L4-L5 8 Specimen L4-L5 8 Specimen L4-L5 8 29

45 Figure 0-4 Motion analysis test setup 30

46 Figure 0-5 Test setup for complex cyclic loading 31

47 Figure 0-6 Graph showing the phase difference between compression and torsion 32

48 1.20. Considerations for complex cyclic loading The center of rotation (COR) of the specimen was determined by the application of point load and inclinometer was used to make sure the specimen does not go into flexion/extension/bending. Flexion and Lateral bending (0 to7.5nm) were applied using load control while rotation (-7.5Nm to 7.5Nm) was applied under torque control. Flexion and rotation are applied at 90 o out of phase to each other. To achieve simultaneous lateral bending, along with flexion and rotation the fixture on the top frame (bondo) of the specimen was oriented at 45 degrees to the sagittal plane of the specimen so that it moves in flexion + lateral bend + axial rotation in a coupled fashion. A 566N compressive load was applied to the motion segment at a pre-measured lever arm (18.7mm) to achieve a total of 7.5Nm of in flexion. A sinusoidal compressive load (0N to 400N to 0N etc ) was applied to the motion segment to achieve bending in flexion forces. Flexion, lateral bending and rotation were coupled and applied simultaneously to each specimen at a rate of 3Hz for 125,000 cycles. The fixture was oriented in such a way that the implant was compressed during the complex cyclic loading. Between the two fatigue cyclic testing steps, each specimen was radiographically evaluated to document the position of the implant according to the tantalum markers affixed on it. The methodology for radiographic evaluation of implant migration is described below. 33

49 Figure 0-7 Complex cyclic loading test setup Radiographic evaluation: As described above, Tantalum markers were placed into specific regions of the bone and endplate margins using epoxy to mount the markers for quantifying migration of the implants after repetitive cycling. An initial fluoroscopic image was generated to document the position of the Magellan Spine IBF device relative to the tantalum markers. Fluoroscopic imaging was further document if migration has occurred and was allow the quantification of implant positioning relative to the tantalum markers during the course of cycling (at points 0, 125,000, and 250,000 cycles). After all cycling is done, a final fluoroscopic image was taken and each specimen was carefully dissected in the sagittal plane close to the vicinity of the IBF devices to 34

50 observe implant migration or repositioning within the surrounding tissue. Photographic evaluations were made initially and at this time point. All the measurements were made using the GE centricity DICOM viewer provided with the digitized radiographic images. All measurements are made in millimeters (Displacement) and degrees (angles). Angles of the markers are measured with respect to each other and they are represented by the three angles of the triangle formed by the markers. In Lateral View the anterior-most marker was labeled as marker 1, superior-most marker was marked as marker 2 and inferior-most marker was marked as marker 3. In A- P view, Superior-most marker was labeled as marker 2, middle marker was labeled as marker 1 and inferior-most marker was labeled as marker 3. The anatomical reference points were kept consistent across the specimens for an accurate measurement of the position of the three tantalum markers at different phases of testing to be able to compare within each loading step radiograph and also between the specimens. 35

51 Figure 0-8 Fluoroscopic images showing the implanted Migration analysis: Following the establishment of markers on each implant for each specimen radio graphically, two-dimensional positions were marked for each of the three markers. The same data was recorded for the implants following the cyclic testing and the positions of the markers for post fatigue conditions were compared against the pretest or intact condition. It was difficult to establish a common co-ordinate system for all the three specimens. Hence, each specimen was evaluated separately and a local co-ordinate system was established. By drawing a straight line spanning two rigid bony/metal landmarks a horizontal axis was defined and a perpendicular line to this axis at one of the 36

52 landmarks was defined as the vertical axis. The center of this co-ordinate system was called as origin (0, 0) and all measurements of the markers were documented as the positions (x, y co-ordinates) from this origin. The following steps were used in each of the specimens for the definition of anatomical/fixed landmarks to facilitate the migration analysis of the implant in in each testing condition L2-L3: lateral. In the lateral view the anatomical positions of the end plates are used to draw an axis vertically (call Y). An axis perpendicular to this passing through the line of surface of the lamina was taken as the reference X-axis L2-L3: Anterior-Posterior. Reference X-axis was taken as the axis joining the tip of the two screws inserted in to the vertebra at the cephalic end (bottom frame of the bondo) into the L3 vertebra. A vertical reference axis Y is drawn perpendicular to this axis passing through the line of the superior facet of the L3 vertebra. This reference system is maintained the same for all other images of the same specimen L4-L5: lateral. In the lateral view the anatomical position of the end plate of L4 is used to draw an axis vertically (call Y). An axis perpendicular to this touching the tip of the first and last screw on the radiographic image was taken as the reference X- axis L4-L5: Anterior-Posterior. Reference X-axis was taken as the axis joining the tip of the first and third screws inserted in to the L5 vertebra (counting left to right). A vertical reference axis Y is drawn perpendicular to this axis passing through the end plate of L4. This reference system is maintained the same for all other images of the same specimen. 37

53 51364-L4-L5: lateral. In the lateral view the edges of the end plates are used to draw an axis vertically (call Y). An axis perpendicular to this passing through the other end of the end plate of the vertebra L5 was taken as the reference X-axis L4-L5: Anterior-Posterior. Reference X-axis was taken as the axis joining the tip of the first and last screws inserted into the vertebra. A vertical reference axis Y is drawn perpendicular to this axis passing through the end plate of L4. This reference system is maintained the same for all other images of the same specimen Impact loading: Each motion segment was fixed onto the MTS tester and compressive load is applied at a defined rate (250mm/sec). Bending Moment Mb = (Fmax)*(0.0187m). In order to assess the impact force the specimen was placed into maximum flexion using a human hand force on the potted section. The MTS position required to bring the specimen to this maximum flexion point (MFP) was measured and the displacement was zeroed. Additionally, the specimen was placed into maximum rotation by attaching a tensile force to the potted fixture, rotating the segment to the maximum rotation point (MRP). (A tensile force of 19.6N was applied at both ends at a distance of 20 cm between the ends to produce a torque of 3.92N-m.) The specimen was placed at a pre-determined offset (18.7mm) from the center of specimen rotation and center of the impaction element so that the specimen is impacted under extreme flexion and rotation.. 38

54 1.24. Optotrak Data Analysis: Data obtained from 3D motion tracking camera was used to calculate the range of motion (ROM) using Microsoft Excel macro validated previously. Mean and standard deviation of ROM was computed for three specimens implanted with Magellan Spine Annular Repair Device device Finite Element Analysis: Three dimensional finite element models of each vertebra were generated using CT scans. In the finite element method a structure is divided into a number of elements which interact with each other and are joined to the adjacent elements by nodes. By defining the number of nodes and the way they interact with the adjacent nodes the shape of any structure can be modeled in the form of elements. Each element is considered as a unit structure and holds the same mechanical and geometrical properties across the entire gamut of the structure being modeled. In general, there are two approaches to model the spine and are termed as simple and detailed [12] Geometric Modeling: In this approach each functional spinal unit is modeled either as one or three elements. This functional spinal unit can be further augmented with elements of rib cage, muscles, ligaments and other structures to get a more complex model. This approach is mainly used because it proves to economical and mathematically simple. However, it grossly simplifies the naturally complex behavior of the human spine and its surrounding 39

55 structures as well as the interactions between them. In this approach, each element has two nodes and these nodes are located at vertebral body centroids. Figure 0-9 Intact L3-S1 FE model 40

56 Figure 0-10 Intact L4-L5 FE model modified from L3-S1 model Vertebra modeling: The intact L4-L5 functional spinal unit used for this study analysis was obtained from a previously validated intact L3-S1 spine model [51]. This spine model has 31,054 elements, 38,664 nodes and is modeled such that it is symmetrical about the midsagittal axis. The modeling was done from CT scan images obtained from a healthy spine with no deformities or geometrical abnormalities. ABAQUS 6.5 was used to perform the modeling from these computed tomography images. The vertebrae and the posterior aspect of the bone were defined as cancellous bone surrounded by a 0.5 mm cortical bone shell. Three-dimensional hexagonal elements (C3D8) were used in modeling the bone. Each element has eight nodes and was assigned three degrees of freedom. 41

57 Figure 0-11 L4-L5 FSU A) Anterior view of B) lateral view showing vertebral bodies and disc and other components Inter Vertebral Disc Modeling: Intervertebral disc was modeled as composite material to simulate both the annular and nuclear functions. It was set to be a solid matrix with fibers oriented around a viscoelastic nucleus material. Annulus was modeled as a structure of concentric rings around the nucleus with fibers oriented at ±30 degrees to the horizontal plane. These fibers were modeled as incompressible. Nucleus was defined as an incompressible, low stiffness material as physiologically it contains high water content Facet Joint modeling: Facet joints or aphophyseal joints are the superior and inferior structures of the vertebrae located posteriorly and articulate with the superior and inferior vertebrae. These joints are surrounded by cartilage. In the present model, facet joints were modeled as three-dimensional gap contact elements (GAPUNI) and they transfer force along one direction only when the gap is reduced between the nodes connecting them. This gap was initially set to about 0.5 mm based on the data obtained from the CT scanning images. The cartilaginous covering on these joints was defined as soft contact using ABAQUS s 42

58 softened contact parameter. The functionality of this feature in this software is that it determines the force transfer exponentially between the nodes with increasing gap between the nodes. The orientation of these joints was 72 degrees relative to the horizontal plane. Figure 0-12 L4-L5 FSU A) Posterior view and B) Posterio-lateral view of showing facet joint Ligament modeling: Seven major ligaments were used in this intact spine model. They are anterior longitudinal ligament, posterior longitudinal ligament, intertransverse ligament, ligamentum flavum, interspinous ligament, supraspinous ligament and capsular ligament. All these ligaments were defined to be three-dimensional, two nodes truss elements Boundary conditions: All the nodes of the superior L4 vertebrae were connected to a single node for the application of force and such that the force is equivalently distributed among all the nodes of the L4 superior vertebra representing a physiological load application. Moments 43

59 were applied to rigid beams attached to the superior nodes. Figure shows the boundary and loading conditions of L4-L5 model Implant Models Used for Simulation: Figure 0-13 Models of Magellan spine Annular repair device 44

60 1.33. Intact model: The simulations were run using AQAQUS for the intact L4-L5 motion segment in all loading modes and results were analyzed Injured model: The L4-L5 motion segment was modified by creating a unilateral laminectomy, followed by partial discectomy (4mm X4 mm) mimicking the destabilized in vitro condition. The simulations were run using ABAQUS for the destabilized L4-L5 motion segment in all loading modes as mentioned above and results were analyzed Instrumented model: Implant drawing files were imported with the FE model in the assembly module using ABAQUS. Implant was positioned appropriately and meshed by using tetrahedral (T3D4) elements and the geometry was preserved eliminating and sharp node point edges. The components of the implant were assigned of PEEK material properties. Table 0-3 Material properties of the components spinemodel Components Young's Modulus (Mpa) Poisson's Ratio Element Type Implant T3D4 Cylinders C3D8 45

61 Table 0-4 Material properties of the components of spine model Material Young's Modulus (Mpa) Poisson's Ratio Cortical bone 12, Cancellous bone Posterior bone 3, Annulus (Ground) Annulus (Fiber) Nucleus pulpous Anterior Longitudinal (ALL) Posterior Longitudinal (PLL) 7.8(<12%), 20.0(>12%) (<11%), 20.0(>11%) 0.3 Ligamentum Flavum (LF) 15.0(<6.2%), 19.5(>6.2%) 0.3 Transverse (TL) 10.0(<18%), 58.7(>18%) 0.3 Interspinous (ISL) 10.0(<14%), 11.6(>14%) 0.3 Supraspinous (SSL) 8.0(<20%), 15.0(>20%) 0.3 Capsular (CL) 7.5(<25%), 32.9(>25%)

62 Figure 0-14 Implanted L4-5 motion segment Figure 0-15 L4-5 model following discectomy 47

63 Figure 0-16 Interactions defined between the implant surfaces and the disc FEA analysis: The following L4-L5 models were analyzed: Intact Injury: In this model unilateral laminectomy followed by partial discectomy (4mm X 4 mm) was performed. Implanted: Spine Annular Repair Device was placed in the disc space created as a result of simulating the injury condition. All models were simulated in extension, flexion, lateral bending and axial rotation with 400N preload and 7.5 Nm of bending moment. 48

64 Chapter 4 Results Overview: Results of the study are discussed in detail in the following sections In vitro study: Range of motion obtained from cadaver testing as well as the fatigue and impact testing results obtained from the servohydraulic load frame are discussed in detail Range of motion analysis: Intact, pre fatigue and post fatigue steps were evaluated. With respect to intact ROM, there was an increase in ROM for pre fatigue condition with annular repair device in extension (36%), flexion (46%), left bending (37%), and right bending (47%) left rotation (22%). Post fatigue loading, ROM further increased in extension (23%), flexion (78%), left bending (56%), right bending (77%) left rotation (72%) and right rotation (22%). 49

65 Range of Motion (Degrees) Range of Motion (Degrees) Range of Motion-7.5 N-m- No Preload Intact Pre-fatigue Post fatigue Flexion Extension Left Bending Right Bending Left Rotation Right Rotation Figure 0-1 Mean values at 7.5 Nm for all loading modes (in degrees) 12.0 Range of Motion-7.5 N-m- 400 N Preload Post fatigue Pre-fatigue Flexion Extension Figure 0-2 Range of Motion at 7.5 N-m 50