Nucleus Arthroplasty Volume IV

8/9/2019 Nucleus Arthroplasty Volume IV

1/48

NucleusArthroplasty

Volume IV: EmergingTechnologies

Technology

in Spinal Care


2/48

Table of Contents

This monograph series is a groundbreaking project in the

rapidly emerging field of non-fusion spinal surgery. The

full range of nucleus replacement technologies is examined

with discussion on emerging technology, detailed informa-tion on each cutting-edge device technology, indications,

and patient selection criteria.

Nucleus Arthroplasty Technology in Spinal Careis

published for the medical profession by Raymedica, LLC,

Minneapolis, MN 55431.

The views expressed in this series are those of the authors

and do not necessarily represent those of Raymedica, LLC.

ACKNOWLEDGEMENT

We, Raymedica, LLC, and the authors of this volume, wish

to acknowledge our debt of gratitude for the important con-

tribution of the developmental editors, John J. Grabowski,

Rebecca S. Gorman, O. James May, and Steven J. Seme.

Their collective guidance has added a great deal to the

teaching value of this volume.

Copyright 2006 and 2007 Raymedica, LLC. All rightsreserved. Printed in the U.S.A.

1 Introduction

2 Deputy Editorial Board

C H A P T E R 2 1 3 Nucleus Arthroplasty Technology: Patient Demographics and Selection

C H A P T E R 2 2 7 Spinal Motion Preservation Technologies: Surgical Approach and Procedure

C H A P T E R 2 3 15 Nucleus Arthroplasty Design and Evaluation Challenges

C H A P T E R 2 4 25 Early Clinical Results of Nucleus Arthroplasty Technology

C H A P T E R 2 5 30 Socioeconomic Impact of Nucleus Arthroplasty Procedures

C H A P T E R 2 6 37 Biologics and Nucleus Arthroplasty Technology Applications

C H A P T E R 2 7 42 The Future of Nucleus Arthroplasty Technology

44 Closing Remarks

www.nucleusarthroplasty.com


3/48

Introduction

1

The first documented works describing the diagnosis andtreatment of the spine, spinal disorders, and spinal instabilitydate back to 1900-2500 B.C. Interestingly, the documents recom-mended against the treatment of spinal cord injury. The develop-

ment of therapeutic treatments has a long history starting withthe cane, the first load-sharing device. Today, our efforts to

improve therapies to treat spine disease persist. We continue torecognize problems, identify issues, and define variables in an

effort to better understand spinal degeneration and to develop

innovative solutions that utilize a wide array of materials andtechnologies. Our field has had a rich history of advancements,

accomplishments, and inventiveness. We owe a great debt to thepioneers who, armed with little more than a detailed knowledge

of anatomy, heralded in the era of spinal surgery. Their trials,errors, innovations, and teachings have guided our efforts to

ultimately improve clinical outcomes.

Early on, it was recognized that the disc played a vital role in overallspine health. With great effort and ingenuity, the unique anatomical,biomechanical, and physiological properties of the disc were eluci-

dated and incorporated into elegant treatment algorithms. We nowhave access to an almost overwhelming flow of information about

lumbar disc arthroplasty from countless sources. Central to the evo-lution of therapies is a better appreciation of the complexities of the

lumbar disc. By combining knowledge gleaned from anatomical dis-section, biochemical processes, and resultant physiology with a disci-plined foundation in biomechanics, we have created a fabric of

understanding never before enjoyed. Spine arthroplasty is now animportant and evolving area within the treatment of spinal disor-

ders. This sub-discipline represents the coalescence of many areas ofstudy focused on the development of new and exciting solutions to

address clinical problems.

These significant advances in our understanding of the spine rep-

resent a culmination of efforts occurring across many fronts. Ourincreased understanding of the biological factors at work in disc

disease has been a driving force in the development and emer-gence of new materials and delivery methods. The critical role

that advanced biocompatible alloys, polymers, and viscoelastichydrogels play in the innovation of disc arthroplasty technologiescannot be over emphasized.

Technological advancements have played a vital role in supporting

and expanding our knowledge of motion preserving disc technolo-gies. The latest imaging technologies allow a much more detailed

appreciation of pathological processes, such as disc degeneration,and provide the ability to monitor the results of an intervention.

Computerized finite element analysis offers a risk-free environment

in which to test hypotheses and predict clinical impact. Biochemicaladvancements yield an intimate understanding of the chemical envi-

ronment including chemical mediators and potential interventionportals. This wealth of knowledge can be used to great advantagewhen developing disc arthroplasty technologies.

Not to be overlooked, the socioeconomic challenges involved in the

development of new technologies, such as the Nucleus Arthroplastymotion preservation system, have also become more apparent.

The all important variable of proper patient selection continues to

require constant reassessment and vigilance. Increasingly, third-partypayers control access to care and treatment choice to an alarming

degree. Such considerations can no longer be ignored in the questfor ideal patient management methods.

This publication has been constructed to provide an overview of

Nucleus Arthroplasty as an emerging technology. Key elementsinclude an overview of Patient Demographics and Selection, SurgicaApproach and Procedure, Challenges of Design and Evaluation,

Clinical Experience, Socioeconomic Impact, Biological Applications,and Future Technology Applications. In addition,Volume IV of this

series will provide insight into the potential market and the currentplayers working in the forefront of Nucleus Arthroplasty technology

development activities. This is an incredibly exciting field as tech-nologies focused on the repair and replacement of the diseased discnucleus will catapult us far beyond the treatment options we have

available today.

In conclusion, we can say that the spine arthroplasty specialistof today is well prepared to deliver the most advanced solutions

to the clinical puzzle of disc disease with technologies based ona rich tradition of innovation and compassion coupled with a

tremendous wealth of physiological knowledge and assessmenttools. As spine surgery evolves from mechanical solutions totherapeutic solutions both surgeons and patients will benefit.

We hope you will find this series on Nucleus Arthroplasty

technology to be a valuable asset.

Reginald J. Davis, MD, FACSCHIEF OF NEUROSURGERY

Baltimore Neurosurgical Associates, PA

Baltimore, MD 21204

Federico P. Girardi, MDASSOCIATE PROFESSOR

OF ORTHOPEDIC SURGERY

Hospital for Special SurgeryNew York, NY 10021

Frank P. Cammisa, Jr., MD, FACSASSOCIATE PROFESSOR

OF CLINICAL SURGERY

Hospital for Special SurgeryNew York, NY 10021

Federico P. Girardi, MDReginald J. Davis, MD, FACS

Frank P. Cammisa, Jr., MD, FACS


4/48

2

R aymedica has selected Reginald J. Davis, MD, FACS, Federico P. Girardi, MD, and Frank P. Cammisa, Jr.,MD, FACS to edit this series of monographs on Nucleus Arthroplasty technology, because of theirspecial interest in this dynamic area of medicine. Drs. Davis, Girardi, and Cammisa are noted for theirexpertise in spine surgery and advanced training in minimally invasive surgical techniques. They are well

respected for their clinical work and travel widely to speak and train other physicians.

Reginald J. Davis, MD, FACS

Dr. Davis is founder of Baltimore Neurosurgical Associates, chief of Neurosurgery at the Greater Baltimore

Medical Center, and a faculty member at the Johns Hopkins School of Medicine and the University of Maryland

He is a Fellow of the American College of Surgeons and a Diplomate of the American Board of Surgery.

Dr. Davis received his medical degree from Johns Hopkins University School of Medicine, Baltimore, Maryland.

He has broad experience in advanced procedures such as spinal stabilization, intradiscal electrothermal ther-

apy, and microendoscopic discectomy and has conducted physician training programs on these procedures. His

professional affiliations include the AANS-CNS Section on Disorders of the Spine, the American Association of

Neurological Surgeons, the Congress of Neurological Surgeons, and the North American Spine Society.

Federico P. Girardi, MD

Dr. Girardi is associate professor of orthopedic surgery, Weill Medical College of Cornell University and is

attending orthopedic surgeon at the Hospital for Special Surgery, New York, New York. He specializes in

the treatment of spinal disorders including degenerative disc disease (DDD), spinal deformities, metabolic

fractures, and spinal tumors. Dr. Girardi received his medical degree from the Universidad Nacional de

Rosario, Rosario, Argentina.

He has performed extensive clinical research in the areas of minimally invasive surgery, clinical outcomes,

and spinal imaging. He is also interested in basic research on bone, disc, and nerve tissue regeneration and

in the investigation of alternatives to spinal fusion for the treatment of DDD. His professional affiliations

include the North American Spine Society, Scoliosis Research Society, the European Spine Society, the

International Society for the Study of the Lumbar Spine, and the Spine Arthroplasty Society.

Frank P. Cammisa, Jr., MD, FACS

Dr. Cammisa is associate professor of clinical surgery, Weill Medical College of Cornell University and is the

Chief of Spinal Surgical Service at The Hospital for Special Surgery in New York, New York, where he also

serves as an associate scientist in the research division. Dr. Cammisa received his medical degree from theCollege of Physicians and Surgeons at Columbia University, New York, New York.

His clinical interests include non-fusion and motion preservation technologies, minimally invasive, laparo-

scopic, and computer-assisted spinal surgery, microsurgery, and athletic spinal injuries. He is an active mem-

ber of many spine societies, academic committees, and editorial review boards. He has lectured widely and

published in numerous peer-reviewed journals and books.

Deputy Editorial Board


5/48

Chapter 21 Nucleus ArthroplastyTechnologyPatient Demographics and Selecti

Barn Zrate-Kalfpulos, MD

DEPARTMENT OF ORTHOPEDICSInstituto Nacional de Rehabilitacin Mexico

Mexico City, Mexico 10700

Alejandro ReyesSnchez, MDHEAD OF SPECIAL SURGERGY DIVISION

Instituto Nacional de Rehabilitacin Mexico

Mexico City, Mexico 10700

John S. Thalgott, MDORTHOPEDIC SPINE SURGEON

International Spine Development & Research Foundation

Las Vegas, NV 89106

Viscogliosi Brothers, LLCNew York, NY 10022

KEYPOINTS

Based on estimates, nucleus arthroplasty technology may

represent up to 28% of the spinal motion preservation market

by the year 2015.

Potential benefits of nucleus arthroplasty include maintainingdisc height and improving function, while preserving the annulus

fibrosus, cartilaginous endplate, and ligamentous structures.

Nucleus arthroplasty is an attractive treatment method for degen-

erative disc disease as it either follows or accompanies discec-

tomy; it may serve to fill the treatment gap between conservative

therapies and more aggressive surgical measures.

3


6/48

INTRODUCTION

Over the last 15 years, the global spine industry has grownfrom a market that was less than $100 million in annualrevenues to approximately $6.5 billion in 2007. Current esti-

mates show the spine market is growing by 15%20% a year,

with certain niches in distinct geographical markets growing

by 40%100%.

While the spinal device market has grown dramatically, it is

still relatively small in comparison to the annual incidence of

back pain and the availability of approved treatments with

demonstrated clinical efficacy.

Recent trends in the surgical management are shifting toward

techniques that attempt to minimize soft tissue dissection and

preserve the spinal motion segment. The future market oppor-

tunity for such technologies is expected to be quite large($8.25 billion by 2015), with many applications being years

away from commercialization.

Based on this projection, in 2015 the nucleus arthroplasty/

replacement market represents 28% of the total motion preserva-

tion market, or roughly $2.25 billion dollars. The goal of nucleusarthroplasty is to address degenerative disc disease (DDD) by

replacing the diseased nucleus with a prosthetic implant that

mimics the behavior of the normal nucleus pulposus (NP).

Potential benefits include maintaining disc height and improving

function, while preserving the annulus fibrosus, cartilaginous

endplate, and ligamentous structures. Ideally, such technologies

can also be implemented to treat mechanical back pain, prevent

post-discectomy degeneration, and reduce the rate of recurrent

disc herniation.

CURRENT TREATMENTS FOR DDD

Patients suffering from DDD normally present with significant

pain. This manifests most commonly as debilitating low back

pain, with or without leg pain, or, in many cases, debilitating

radicular pain with a mild back pain component.

At this time, there are few treatment options to address DDD

at its various stages. The current treatment continuum has been

limited, consisting largely of conservative care, discectomy, and

fusion. In some instances, total disc replacement may also be

utilized; however, use of this application has been slower than

expected, principally due to reimbursement issues.

1. Conservative Treatment:Conservative therapy consists of

bed rest, pain medication, and physiotherapy. If this process

does not work, then surgery may be considered. The challenge

remains: when to pursue surgical intervention or when to staythe course with conservative management. There is a lack of

options for a surgeon who has a patient that is not responding

well to pain medication and bed rest, but is not ready to go

into the operating room.

2. Discectomy Surgery:The most common surgery for herni-

ated discs of the lumbar spine is a discectomy. This surgery is

an early-stage treatment, where the patient with a bulging disc

undergoes removal of the tissue which is causing nerve com-

pression. This is the first surgical option because it is relatively

less invasive than others and it directly treats the cause of the

pain, namely the herniated disc. Unfortunately, there are many

patients for whom a discectomy alone does not work and who

require an additional treatment option, but are not degenerated

to the point of being the perfect patient for fusion. These

patients have to make the difficult decision of either having

continued pain and/or discomfort without undergoing an

additional surgical procedure, or possibly receiving a fusion,

which is excessive surgery and may not solve their problem.

4

$2.25

28%

$2.0

24%

$1.75

21%

$1.5

18%

$.75

9%

2015 Motion Preservation Market

Facet Replacement

Total DiscReplacement

Nucleus Arthroplasty/Replacement

Interspinous ProcessSpacers

Posterior DynamicStabilization

$8.25 Billion

Source: Viscogliosi Bros., LLC

PATIENTS SUFFERING FROM DDD NORMALLY

PRESENT WITH SIGNIFICANT PAIN. THIS MANIFESTS

MOST COMMONLY AS DEBILITATING LOW BACK PAINWITH OR WITHOUT LEG PAIN, OR, IN MANY CASES,

DEBILITATING RADICULAR PAIN WITH A MILD BACK

PAIN COMPONENT.


7/48

3. Fusion:Fusion was originally developed to assist those

patients who were in unbearable clinical conditions, such as

those suffering from a spinal deformity. Soon enough, the

methods went outside of their intended patient population,

and were used in non-deformity patients to fuse painful seg-ments in the spine. While fusion immobilizes the painful area

within the spine and can provide stability to the spinal col-

umn, it is in many cases not the ideal option. Although con-

servative therapy does not necessarily get to the root of the

problem, fusion tends to over-treat patients. Fusing the

affected levels may afford some temporary relief of pain, but

it can also have a negative effect on the adjacent levels. 1 Some

opinion leaders believe, and it has been corroborated by clini-

cal evidence, that the adjacent levels can suffer from facet

hypertrophy, facet arthropathy, spinal stenosis, osteophyte

formation, and posterior muscular debilitation.

NUCLEUS ARTHROPLASTY TECHNOLOGY

Nucleus arthroplasty represents one of many opportunities to

expand upon the current treatment continuum. The technology

is primarily intended for early to mid-stage degenerative disc

disease in a patient population that is non-responsive to

extended conservative care. Should surgical intervention be pur-

sued, nucleus arthroplasty represents an attractive treatment

method as it either follows or accompanies discectomy and is

less invasive than total disc replacement (TDR).

Currently, there are two general types of nucleus replacement

implants: preformed implants that are inserted into the nucleus

space andin situformed implants that are injected into the

nucleus space in a viscous state. Preformed implants have the

advantage of providing more uniform implant polymer charac-

teristics and superior biocompatibility.In situpolymers, on theother hand, are designed to be injected through a smaller annular

window and cured within the nucleus cavity to improve implant

conformity and stress distribution, while decreasing the risk of

dislodgement. While the general indications between the two

types are similar, they are likely to undergo further refinement

as more clinical experience is gained.2, 3

The accompanying table provides an outline of the current

nucleus replacements by device name, company, device type,

and clinical stage.

5

NUCLEUS ARTHROPLASTY REPRESENTS ONE OF

MANY OPPORTUNITIES TO EXPAND UPON THE

CURRENT TREATMENT CONTINUUM.

DEVICE COMPANY TYPE CLINICAL STAGE

BioDisc CryoLife Injectable CE Mark Trial

DASCOR Disc Dynamics Injectable Pilot IDE Trial

DiscCell Gentis Injectable European Pilot Study

Geliflex SP Synthes Injectable Pre-Clinical Development

HydraFlex Raymedica Preformed Pilot IDE Trial

NeoDisc Nuvasive Preformed Pivotal IDE TrialNeuDisc Replication Medical Preformed European Trial

NUBAC Pioneer Surgical Preformed Pilot IDE Trial

NuCore Spine Wave Injectable Pilot IDE Trial

PNR TranS1 Injectable Filed for Pilot IDE Trial

Regain Biomet Preformed Pilot IDE Trial


8/48

PATIENT SELECTION

As with any medical device, proper patient selection for the use

of nucleus replacement technologies is crucial to clinical success.

The underlying principle of nucleus arthroplasty is to replace

only the diseased nucleus portion of the patients intervertebral

disc. The objective of the procedure is to restore or maintain disc

height necessary to re-establish annular tension and ligamentous

stability. The nucleus replacement device may also assist in shock

absorption and load transmission, a critical component lacking

in the design of total disc replacements.4

Ultimately, nucleus arthroplasty procedures are intended to pre-

serve the bone and ligamentous structures that are integral to the

patients spinal segment motion. To that end, it is of great impor-

tance that the patient has annular, endplate, and posterior ele-

ments that are still capable of functioning properly. Significantcompromise of these base components will directly affect the

ability of a nucleus replacement device to perform as intended,

potentially resulting in implant subsidence or migration.

A more detailed discussion of the indications/contraindications

specific to nucleus arthroplasty procedures is provided below.

Indications

Symptomatic degenerative disc disease (L2 to S1)

Discogenic low back pain, with or without leg pain

Failed conservative (non-operative) management

No significant osteophyte formation

Appropriate disc height at index level (device dependent)

Contraindications

Severe symptomatic central spinal, foraminal,

or lateral recess stenosis

Spondylolisthesis (greater than Grade I)

Segmental instability Fractured and/or degenerated facet joints (greater than Grade I)

Disc collapse of greater than 50% as compared to

a healthy adjacent level

Schmorls nodes or endplate irregularities

Significant disc herniation (extrusions)

Incompetent annulus (defect in annular contour)

Osteoporosis

Other BMI >35 Malignant tumors Systemic or localized infection

KEY FACTORS TO SUCCESS

For nucleus arthroplasty technologies to be successful, current con-

cepts must show acceptable clinical outcomes in relation to alter-

native treatments. In addition, a shift in mindset will be required in

regard to the importance of early surgical intervention.

Given that nucleus replacement is a nascent technology, the mar-

ket must adapt to its benefits and learn its downfalls. It is certainly

possible that the market for nucleus replacements can reach $2.25

billion because, not only can nucleus arthroplasty assist current

DDD patients, but it can also draw in those who were previouslyleft untreated, or are currently being over-treated.

With new technologies being developed and moved through the

commercialization pathways, surgeons will soon have a myriad of

options to choose from. It is then the responsibility of industry

to educate the surgeons and patients on the proper indications,

contraindications, surgical technique, etc., so that these new

minimally and less-invasive solutions can truly benefit patients.

REFERENCES

1. Fardon M, Milette P. Nomenclature and Classification of Lumbar Disc

Pathology. Spine 2001(26):E93-E113.

2. DiMartino A, Vaccaro A, Lee J, Denaro V, Lim M. Nucleus Pulposus

Replacement: Basic Science and Indication for Clinical Use. Spine 2005(30):

S16-S22.

3. Bao Q, Yuan H. New Technologies in Spine: Nucleus Replacement. Spine

2002(27):1245-1247.

4. Mulholland R. Arthroplasty of the Spine. J Bone Joint Surg Am 2005(87):591.

6

IT IS CERTAINLY POSSIBLE THAT THE MARKET FOR

NUCLEUS REPLACEMENTS CAN REACH $2.25 BILLION

BECAUSE, NOT ONLY CAN NUCLEUS ARTHROPLASTY

ASSIST CURRENT DDD PATIENTS, BUT IT CAN ALSO DRA

IN THOSE WHO WERE PREVIOUSLY LEFT UNTREATED,

OR ARE CURRENTLY BEING OVER-TREATED.


9/48

7

Chapter 22 Spinal MotionPreservation Technologies:Surgical Approach and Procedure

Dr. med. univ. Rudolf Bertagnoli

FOUNDERPro-Spine Medical Consulting

Straubing, Germany 94315

Gary A. Fantini, MD, FACSCLINICAL ASSOCIATE PROFESSOR OF SURGERY (VASCULAR)

Weill Medical College of Cornell University

New York, NY 10021

Salvador A. Brau, MD, FACSCLINICAL INSTRUCTOR OF SURGERY

Geffen School of Medicine UCLA

Los Angeles, CA 90095

Rick Delamarter, MDMEDIAL DIRECTOR

The Spine Institute

Santa Monica, CA 90404

INTRODUCTION

Over the last decade, the medical industry has invested signifi-cant resources in the development of new technologies forpatients suffering from spinal disorders. The result has been the

introduction of many new and promising concepts for the treat-

ment of degenerative discdisease. These concepts seek

to provide the surgeon with

a vast array of motion pre-

serving treatment alterna-

tives that extend beyond

traditional fusion.

DEGENERATIVE DISC DISEASE IS CHARACTERIZED BY

THE LOSS OF THE DISCS CAPACITY TO BIND WATER

RESULTING IN A REDUCTION IN DISC VOLUME AND

CORRESPONDING LOSS OF HEIGHT.


10/48

8

While this development process has been dynamic, it has also

proven to be systematic as the engineering of such implants is

more closely matched to the intended surgical approach and

corresponding implantation technique. This is particularly rele-

vant in the lumbar region where factors such as individualanatomical differences, previous surgeries or comorbidities may

favor a specific approach.

The goal of this chapter is to review the available motion preserv-

ing technologies that may be utilized to address degenerative disc

disease. The authors will then discuss the potential impact of each

technology in regard to the surgical approach and subsequent

challenges associated with the implantation technique.

DEGENERATIVE DISC DISEASE

Degenerative disc disease (DDD) is characterized by the loss of

the discs capacity to bind water resulting in a reduction in disc

volume and corresponding loss of height. This process has been

described and graded in three stages1 and can be one of many

causes for low back pain.

Proper diagnosis of DDD involves the use of diagnostic tools as

described in previous chapters. During evaluation, it is impor-

tant to identify the pain generator (e.g. the disc, degenerated

facet joints, or a nerve compression phenomenon), as low back

pain is often a multi-faceted condition.

DDD TECHNOLOGIES

The decision to pursue a surgical treatment option for DDD is

dependent on the degree of degeneration and the individual

patient circumstances. If surgery is deemed appropriate, several

motion preserving surgical options are available including par-

tial disc or nucleus replacement, total disc replacement, and pos-

terior dynamic stabilization. These technologies are based on the

lessons learned from the treatment of hips and knee in which

preserving motion provides the most desirable outcome.

For the spine surgeon, motion preserving technologies offer the

opportunity to treat patients at an earlier stage in the degenerative

process than traditional fusion techniques. While fusion has

known disadvantages such as adjacent level degeneration (35% at

10 years), symptomatic pseudarthrosis, and graft site morbidity,2

arthrodesis procedures will always remain an option for severe

mechanical instabilities such as fracture, tumors, spondylolisthesis

or deformities such as scoliosis and kyphosis.

NUCLEUS REPLACEMENT

The prime indications for nucleus replacements are mild to mod-

erate forms of DDD with a loss in disc height that is less than 50%

when compared to the adjacent healthy disc. The objective of

nucleus replacement is to replace only the diseased portion of the

disc with an implant that has similar biomechanical properties to

that of the native nucleus pulposus.

The ultimate goal is to maintain disc height and alleviate pain,

while preserving the segmental range of motion and bio-elastic

properties of the natural disc. Thus, for long-term viability, it is

paramount that the vertebral endplates, facets, and posterior lig-

amentous structures that provide the functional stability to the

spinal segment are in good condition.

One of the more challenging aspects of any nucleus replacement

technology is the ability to design a device that performs the func-tions of the native disc. This is largely due to the fact the nucleus

is an integral component in both load sharing and nutrient trans-

port within the intervertebral space. Multiple design concepts

have been developed to simulate the current working knowledge

of the native nucleus including hydrogels, polymers/synthetics,

and mechanical devices (Figures 1 & 2). The following is a list of

current nucleus replacement technologies:

Hydrogels

PDN-SOLO and HydraFlexRaymedica, LLC

NeuDiscReplication Medical

Gelifex family of hydrogelsSynthes, Inc.

Polymers/Synthetics

DASCORDisc Dynamics, Inc.

NuCore Injectable Nucleus DeviceSpineWave, Inc.

SINUX ANRSinitec, AG/DePuy Spine, Inc.

BioDiscCryoLife, Inc.

Mechanical

EBI RegainBiomet, Inc.

NUBACPioneer Medical, Inc.


11/48

As noted above, current nucleus replacement technologies are

designed specifically for the intervertebral space and supplement

the existing functional anatomy to maintain motion. As such,

use of these technologies leaves the door open for future

treatment options should the need arise.

TOTAL DISC REPLACEMENT

Total disc replacement (TDR) is applicable primarily when the

degenerative disease state has progressed to the point that it has

a significant impact on disc height and/or disc morphology.

Unlike nucleus arthroplasty, which aims to maintain disc height,

the treatment objective for TDR is to re-establish disc height,

while removing the pain generator (disc) and preserving motion

at the affected level.

In general, there are three basic concepts that define the motion

characteristics of TDRs which include unconstrained, semi-

constrained, and constrained implant designs. The range of

motion of unconstrained designs is normally limited by physio-

logical and anatomical structures; such designs have a floatingcenter of rotation. In contrast, semi-constrained devices and

constrained devices have prescribed flexion-extension limits

that define the allowable range of motion at or near normal

physiologic limits with a fixed center of rotation that is a func-

tion of the specific design (Figures 3 & 4). The following is a

list of current TDR technologies:

Unconstrained

CharitDePuy Spine, Inc.

Semi-Constrained

ProDisc LSynthes, Inc

MaverickMedtronic, Inc.

Constrained

FlexiCoreStryker Corp.

9

Figure 2Nubac

Figure 1HydraFlexdevice

ProDisc implantmotion preserva-

tion at L5-S1.

Figure 4a

Figure 4b

Figure 3Charit prosthesis


12/48

10

Similar to nucleus replacements, TDRs are also intended to be

used in conjunction with functional facets and posterior ligamen-

tous structures. Thus, the kinematics of each design has clinical

relevance as each device concept may have a different long-term

impact on the posterior elements. In addition, the surgical proce-dure requires sacrifice of the intervertebral disc and its compo-

nents and modification of the vertebral endplate; thus, future

treatment options may be somewhat limited.

POSTERIOR DYNAMIC STABILIZATION

Posterior dynamic stabilization systems are primarily utilized

to address stenosis; however, such systems can be utilized to

address DDD for specific indications. There are two basic

design concepts, interspinous spacers, and pedicle screw-based

systems. From a clinical perspective, the objective is to relievecompressive neurological symptoms and restore stabilization.

Additionally, both systems provide a certain degree of disc space

distraction which acts to unload the disc, potentially alleviating

pain of discogenic origin.

Biomechancially, such systems are different than nucleus

replacements or TDRs as the posterior placement is relatively

far away from the center of rotation of the disc. In addition,

the design intent is to control segmental motion by using the

device to define and/or limit the range of motion in flexion,

extension or both. The following is a list of current posteriorstabilization technologies:

Interspinous

CoflexParadigm Spine

WallisAbbott Spine, Inc.

DiamMedtronic

X-StopKyphon, Inc.

Pedicle Screw-Based

DSSParadigm Spine

DynesysZimmer Spine, Inc.

Stabilimax NZApplied Spine Technologies Inc.

The interspinous devices are mainly designed to prevent compres-

sion of the neural foramen during extension (Figures 5 & 6). A few

of the devices (Wallis, Diam) are designed to form a tension band

that provides increased segmental rigidity and limits flexion.

Pedicle screw-based stabilization concepts are similar to standard

rigid pedicle screw systems; however, the interconnecting elements

between the screw anchors are composed of flexible elements

(Figures 7 & 8). While there may be differences in regard to how

each system redistributes loads across the disc space,3 such devices

are intended to stabilize the affected segments by re-establishing

the natural anatomic position and controlling segmental motion.

Figure 6Wallis

Figure 7DSS

Figure 5CoflexInterspinousDynamic System


13/48

Figure 9ALPA approach.

THE CHOICE OF TECHNIQUE IS LARGELY DEPENDENT

ON THE LEVEL OF SURGERY, AND OTHER FACTORS

SUCH AS OBESITY, HISTORY OF PREVIOUS ABDOMINAL

SURGERIES, AND IMPLANT CHOICE.

DEVICE-RELATED SURGICAL APPROACH

The surgical approaches in current use are tailored to specific

device characteristics. The potential need for revision of the

index procedure, as well as performance of subsequent proce-

dures, has been taken into consideration where possible. This

section will provide a brief overview of the advantages and

disadvantages associated with the surgical approaches currently

being utilized.

Anterior

The anterior surgical approach is a muscle sparing procedure in

which access to the disc space is achieved by one of three princi-

pal techniques (Paramedian, ALPA and ARPA). The choice oftechnique is largely dependent on the level of surgery, and other

factors such as obesity, history of previous abdominal surgeries,

and implant choice.

Anterior Paramedian:A direct anterior approach is necessary

for implantation of the current generation of TDR devices. The

patient is placed in the supine position with the legs abducted

(da Vinci position), affording the spine surgeon a direct orthog-

onal view of the target disc space and vertebral bodies. A para-

median, muscle-sparing, retroperitoneal approach is utilized.4

Significant mobilization of the aortic terminus and iliac vessels is

generally required to permit discectomy, vertebral body distrac-

tion, and device placement in the midline. Degree of vessel

mobilization is a function of the index level and the profile

of the particular device chosen for implantation.

Potential approach-related complications include injury to the

vascular structures5, 6 and genitourinary tract. Manipulation of

the hypogastric plexus at L5-S1 in a male may result in retro-

grade ejaculation. From the standpoint of the functional

spinal unit, this procedure can be destabilizing, as the anterior

longitudinal ligament is sacrificed.7

AnteroLateral TransPsoatic Approach (ALPA): The ALPA

was developed specifically for implantation of the PDN-SOLO

nucleus replacement device, as an alternative to the traditional

posterior approach.8 In addition to providing improved exposure

and increased ease of disc denucleation and device implantation,

ALPA avoids the destabilization associated with disruption of the

posterior elements. For this approach, the patient is positioned

in a lateral decubitus position, allowing direct lateral access to

the disc through the mid-portion of the psoas muscle (Figure 9)

The use of ALPA poses the risk of neurapraxia to the exiting

nerve roots posteriorly and to the ventral ramus branches of L1

anteriorly, as a result of traction applied to the psoas muscle

during exposure of the disc space. The limitation of this

approach is that it cannot be used at L5-S1 due to obstructionby the iliac crest, and the lateral position of the iliac vessels at

this level.

11

Figure 8Dynesys pedicle screwsand ligament system withpolyurethane spacers.


14/48

Anterolateral Retroperitoneal Approach (ARPA):The ARPA

technique was developed as a total system approach for access

and placement of the HydraFlex nucleus replacement device,

and is described in detail in Volume III ofNucleus Arthroplasty

Technology in Spinal Care.9

The patient is placed in a supineposition allowing an easier and direct retroperitoneal access to

all lumbar levels. As the name implies, ARPA utilizes an oblique

pathway that is lateral to midline of the spine, yet anterior to

the trajectory of ALPA. As with ALPA, this is a muscle-sparing

approach, with the oblique musculature of the flank being split

along the direction of the respective fibers. The peritoneal sac is

then mobilized medially in standard retroperitoneal fashion

(Figure 10). This defined pathway limits the degree of vascular

mobilization and provides access to the disc space without sac-

rifice of the anterior longitudinal ligament. There is essentially

no vascular mobilization required during the course of nucleusarthroplasty at L2-L3 or L3-L4, and only minimally so at L4-L5

and L5-S1. As with ALPA, ARPA also provides good access to

the disc space, while allowing for closure of the annular flap.

Access to the upper lumbar levels is done from the left, while the

L5-S1 level is approached from the right. Previous pelvic and/or

abdominal surgery in the right lower quadrant can increase the

risk of adhesion formation, and may complicate access to the

L5-S1 disc space via this approach.10, 11

Posterior

The posterior approach avoids manipulation of the peritoneal

sac and large vessels. Access to the disc space is achieved by one

of two principal techniques (Midline, Paraspinal). The choice of

technique is mainly a function of the intended treatment and

device placement, but may also be influenced by the need to

address a disc herniation or perform decompression.

Posterior Midline:A direct posterior approach is used for

implantation of the current generation of interspinous devices

and can also be implemented for pedicle-based systems. The

patient is placed in a prone position and an incision is made

on midline. The muscular and ligamentous structures are then

dissected to reach the bony structures of the spine.

Paraspinal:A paraspinal or Wiltse-style technique can be per-

formed to achieve placement of pedicle screw-based systems.7

The patient is placed in a prone position and a pair of incisions is

made lateral to the midline. The deep longitudinal musculature is

then separated along muscle planes to gain access to the pedicle

and/or disc space (Figure 11). When applicable, use of this

approach can avoid significant muscle dissection and damage

to the ligamentous structures.

In general, the risks associated with the use of posterior

approaches are low, as the surgery tends to be less complicated.

Risks include damage to the neural structures and potential

spinal instability resulting from dissection and/or additional

procedures, such as a laminotomy or a hemifacetectomy that

may be required to properly access the disc space.

12

Figure 11Paraspinal approach.

Figure 10ARPA exposure of the L4-L5 disc space.


15/48

DEVICE-RELATED SURGICAL PROCEDURE

As noted previously, the challenges associated with the surgical

procedure can vary considerably, impacting both the short and

long-term clinical success. More than 90% of all device-related

complications revolve around patient selection, improper sizing,

and implantation technique. This section will touch on the

procedure-related elements and potential differences between

the spinal motion preservation technologies. While all of these

technologies are ultimately designed to stabilize the spine, the

manner in which this goal is achieved may provide or limit the

opportunities for additional surgical intervention.

Anterior Technologies:Currently, the devices that can be

effectively delivered using an anterior surgical approach

(Paramedian, ALPA, ARPA) are nucleus replacement and TDR

technologies. The use of an anterior approach allows adequatevisualization of the disc space, permitting discectomy and verte-

bral body distraction as necessary to accommodate sizing and

implant placement.

From a procedural perspective, nucleus replacements attempt to

preserve the annulus and the cartilaginous endplates. In contrast,

the TDR procedure entails removal of the entire pain-generating

disc and anterior annulus, as well as intentional sacrifice of the

cartilaginous endplate to allow for fixation of the prosthesis.

Posterior Technologies:Currently, the devices that can be effec-

tively delivered using a posterior surgical approach (Midline,Paraspinal) include interspinous spacers, pedicle screw-based

systems, and some nucleus replacements. The use of a posterior

approach provides more direct access to the lamina and pedicle

region, and can be much more desirable if a disc herniation or

decompression must also be performed.

From a procedural perspective, interspinous spacers require

minimal tissue dissection. Visualization is good and there is rela-

tive ease of insertion, resulting in high confidence in implant

placement. In contrast, pedicle screw-based systems require

much deeper tissue dissection, with far lateral placement of the

pedicle screw anchors that can be challenging. Anatomically,both systems require little, if any, modifications to the anatomy

leaving future surgical options open.

A posterior approach may also be applicable for certain nucleus

replacements. However, this approach can prove to be challeng-

ing for larger designs (mechanical or preformed), due to the lim-

ited anatomical space for nucleus cleanout, device insertion and

repair of the annulotomy upon exit.

Implant Sizing and Insertion

At this time, the clinical outcomes for many non-fusion tech-

nologies are heavily influenced by the procedural elements asso-

ciated with implant sizing and insertion techniques. Implant

sizing is the key to restoring the appropriate motion pattern

and/or stabilizing the spine segment. However, the corresponding

distraction necessary to establish correct spinal position, or pro-

vide a pathway for implant delivery and placement, has a direct

impact on sizing. Thus, the two variables are interrelated.

Regardless of approach, during the sizing process, care must be

taken to ensure that an appropriate level of distraction is applied

for a corresponding implant size. Improper distraction can cause

undue strain or injury of the ligamentous structures and facets that

are integral to maintaining the range of motion and corresponding

segmental stability.

Revision

Regardless of the procedure, it is important to ensure that rea-

sonable opportunities exist for potential revision or additional

surgeries at adjacent levels. Revision surgery may be deemed

necessary due to clinical performance issues such as persistent

pain, neurological disorders, and trauma. Alternatively, revision

may be required secondary to device-related complications such

as malpositioning, migration, subsidence, component failure or

the presence of infection/rejection. While no surgeon selects adevice or surgical approach based on the likelihood of a revision

consideration of this possibility will make any reoperation much

safer, should it be necessary.

From an anterior perspective, a strategic selection of the initial

approach, minimal mobilization of the vessels, and the use of an

anti-adhesion membrane between implant and vessels may reduce

surgical revision challenges.13 However, any anterior lumbar revi-

sion surgery should be performed in specialized centers that have

ready access to multidisciplinary services and experience in the

potential pitfalls involved.

The implant type, design, and index surgical approach of the ini-

tial and the corresponding revision implant technology can have a

significant impact on revision. For example, removal of a nucleus

replacement is expected to be low risk leaving reasonable options

open for the use of other technologies, including another nucleus

replacement, TDR, supplemental posterior fixation or fusion.

13


16/48

14

In contrast, revision of a TDR can be far more complex and is

highly dependent on implant design and the corresponding rea-

son for revision. TDR prostheses with a modular design may

provide the opportunity to replace a portion of the device, such

as the inner core, thus minimizing vascular mobilization and

contact with vertebral bone. However, if explantation is neces-

sary, en bloc designs or modular designs with keels and/or

bone ingrowth surfaces are far more difficult to remove.13 In

such instances, extensive pre-operative imaging, and possible

pre-emptive intervention with regard to the vascular and geni-

tourinary systems, is necessary in order to develop a safe and

coherent treatment strategy.6, 10

Posteriorly, the risks associated with revision are greatly reduced.

Removal of an interspinous spacer is expected to be low risk, leav-

ing reasonable options open for the use of other motion-sparing

technologies via an anterior or posterior approach. Similarly, a lowdegree of risk is expected for the revision of pedicle screw-based

systems, provided that screw breakage and/or pedicle damage is

not an issue.

CONCLUSION

This chapter provided a brief review of the current spinal motion

preservation technologies and the interrelationships that exist

between implant design, surgical approach, and surgical proce-

dure. While the selection of a particular treatment modality has

important implications for the initial surgery, it may have signifi-

cant impact on future surgeries associated with both treatment of

the adjacent levels and revision of the index level. In the future, it

is expected that such relationships will become more important

when evaluating surgical options for the treatment of DDD.

REFERENCES

1. Kirkaldy-Willis WH. Managing low back pain. N.Y. 1983 Churchill Livingston.

2. Ghiselli GWJ, Bhatia NN, Hsu WK, et al. Adjacent segment degeneration in

the lumbar spine. J Bone Joint Surg Am 2004; 86: 1497-503.

3. Segupta D. The mechanism of action of posterior dynamic stabilization

assessed by disc pressure profilometry. The Spine Journal Vol 6 (5) 2006:

148149.

4. Brau SA. Mini-open approach to the spine for anterior lumbar interbody

fusion: description of the procedure, results and complications. Spine J 2002;

2:216-23.

5. Brau SA, Delamarter RB, Schiffman ML, Williams LA, Watkins RG. Vascular

injury during anterior lumbar surgery. The Spine Journal 4 (2004): 409-412.

6. Fantini GA, Pappou IP, Girardi FP, Sandhu HS, Cammisa Jr FP. Major

vascular injury during anterior lumbar spinal surgery: Incidence, risk factors

and management. Spine (in press).

7. Lehman RA, Vaccaro AR, Bertagnoli R, Kuklo TR. Standard and minimally

invasive approaches to the spine. Orthop Clin N Am 36 (2005) 281292.

8. Bertagnoli R, Vazquez RJ. The AnteroLateral transPsoatic Approach (ALPA).J Spinal Disorders Tech 2003 Vol 16 (4) 398404.

9. Fantini GA, Brau SA. Nucleus Arthroplasty: Approach-Related Considerations.

In: Nucleus Arthroplasty in Spinal Care. Book III: Surgical Techniques and

Technologies Davis RJ, Girardi FP, Cammisa Jr FP (eds). Raymedica LLC,

Minneapolis, MN. 2007 (in press).

http://www.nucleusarthroplasty.com/surgical.html.

10. Kostiuk JP. Complications and surgical revision for failed disc arthroplasty.

The Spine Journal 4 (2004) 289S 291S.

11. Bertagnoli R, Zigler J, Karg A, Voigt S. Complications and strategies for revision

surgery in total disc replacement. Orthop Clin Am 36 (2005) 389395.

12. Ivanic GM, Pink PT, Schneider F, Stuecker M, Homann NC, Preidler KW.

Prevention of epidural scarring after microdiscectomy: A randomized clinical

trial comparing gel and expanded polytetrafluoroethylene. Eur Spine J (2006)15: 13601366.

13. David T. Long-term results of one-level lumbar arthroplasty. Spine 32 (6)

(2007) 661-666.

IN THE FUTURE, IT IS EXPECTED THAT SUCH RELATIONSHIPS WILL BECOME MORE

IMPORTANT WHEN EVALUATING SURGICAL OPTIONS FOR THE TREATMENT OF DDD.


17/48

15

Chapter 23 Nucleus Arthroplasty

Design and Evaluation Challenges

KEYPOINTS

Successful nucleus arthroplasty devices have numerous clinical

design challenges including anatomy preservation and restoration

of segmental spinal motion.

There are a number of methods that can be utilized to charac-

terize a nucleus arthroplasty device. It is important to selectand perform tests that are appropriate and representative of

the physiological conditions for a particular device type.

In addition to mechanical analyses, functional performance

under biological conditions should be studied using

in vivoexperiments.

INTRODUCTION

T

he science of nucleus arthroplasty represents an exciting

multidisciplinary challenge. The successful developmentof such technologies requires key input from individuals within

many disciplines including

biomechanical engineering,

design engineering, material

sciences, tissue engineering,

biology, microbiology, and

of course spine surgeons.

Prof. Dr. Hans-Joachim Wilke

PROFESSORInstitute of Orthopaedic Research and Biomechanics

University of Ulm

Ulm, Germany 89801

SUCCESSFUL NUCLEUS ARTHROPLASTY DEVICES

HAVE NUMEROUS CLINICAL DESIGN CHALLENGES

INCLUDING ANATOMY PRESERVATION AND

RESTORATION OF SEGMENTAL SPINAL MOTION


18/48

Integral to the process is a thorough understanding of the function

of the disc, the biomechanics of the spinal segment and the loading

of the entire spine. Furthermore, it requires additional knowledge in

regard to the corresponding biological responses, biomechanical

loads, and resulting deformations at the tissue level.

From a clinical perspective, the primary goal of nucleus arthro-

plasty technologies is to remove or reduce discogenic pain, while

seeking to preserve as many existing anatomical structures as

possible. Secondarily, it is also desirable to provide segment

stabilization and slow the progression of the degenerative cascade.

Thus, in theory, an optimal nucleus replacement should be capa-

ble of restoring the function of the spinal segment. This implies

that it should re-establish the intact disc height, motion, and the

load-sharing behavior between the different structures, thereby

restoring the nominal stresses and strains in the collagen fibers

of the annulus, remaining nucleus, and endplate.

Currently, there is a wide array of nucleus implants in clinical

application or under development.1 The major design concepts

include mechanical, preformed polymer,in situformed polymer,

and tissue engineered implants (Volume II, Chapter 8).2 However,

while each design concept has certain advantages or disadvantages,

to date, it is the authors opinion that there is no single device that

can be referred to as an optimal nucleus replacement implant.

The following chapter is intended to be multipurpose with Part I

focusing on the design challenges associated with nucleus arthro-

plasty devices. Unfortunately, there is limited data published about

the biomechanical or clinical performance of such systems. Thus,in most cases the information that is provided represents the per-

sonal opinion and judgment of the author. As such, certain items

may not apply to each device type or specific group.

Part II of this chapter provides a review of potential experimental

tests and corresponding methods that may be utilized to charac-

terize or benchmark nucleus replacement implants. The testing

schemes that are presented are only recommendations; specific

tests may not be appropriate for each device type or group.

CLINICAL DESIGN ASPECTS OF

NUCLEUS ARTHROPLASTY CONCEPTS

Nucleus replacement implants seek to maintain the anatomical

integrity of the disc and restore spinal segment motion. To

achieve these goals in design, requires proper consideration of

the anatomical and motion preservation characteristics of the

native disc.

Anatomical Considerations

From an anatomical perspective, it is important to address and

attempt to preserve the structures that compose the healthy

spinal segment. Anteriorly, it is important to preserve the ante-

rior longitudinal ligament and annulus, and protect the integrity

of the vertebral endplate when performing the nucleotomy.

Posteriorly, it is important to maintain the facet joint, capsule, and

posterior ligamentous structures. Implant systems that require sig-

nificant anatomic disruption may place more biomechanical

demands on the device, impacting long-term function.

Annulus Preservation

One of the big advantages of nucleus arthroplasty devices is that

the annulus can be preserved to a greater extent than artificial disc

prostheses. The degree of annular preservation is largely depend-

ent on the surgical technique, corresponding implant design

(preformed,in situ, other), and insertion technique. To assist in

healing and reduce the potential for implant mobility, it may be

of benefit to close the annular opening after implantation.

FR O M A CLI N I CAL P E R SP E CTI VE , THE P R I MAR Y G O AL O F N UCLE US

AR THR O PLASTY TE CHN O LO G I E S I S TO R E MO VE O R R E DUCE DI SCO G E N I C

P AI N , W HI LE SE E KI N G TO P R E SE R VE AS MAN Y E XI STI N G AN ATO MI CAL

STR UCTUR E S AS P O SSI B LE.

16


19/48


20/48

which are often genetically predetermined, can be corrected

using such an approach.

The future success of this challenging design space will be depend-

ent on our ability to develop and evaluate implants that meet the

specific clinical design aspects and physiological conditions.

CHARACTERIZATION OF THE NUCLEUS

ARTHROPLASTY DESIGN CONCEPTS

As noted above, there are significant challenges associated with

the design of a nucleus arthroplasty implant. To improve the

odds for success, each proposed design concept must be properly

evaluated or characterized using preclinical experiments.

Initially, the implant can be tested using several different meth-

ods to ensure that it can withstand the expected physiological

load environment. In addition to isolated implant testing, cadav-

eric studies must be performed with the implant to determine

the impact of the surgical approach and procedure. Finally, func-

tional performance under biological conditions should be studied

usingin vivoexperiments. The following paragraphs provide an

overview and describe a battery of tests that may be applicable in

evaluating an implant design.

Mechanical Characterization

Mechanical test standards (i.e. ISO, ASTM) for evaluatingnucleus replacement devices do not exist. Using FDA guidance

documents, test methods may be developed to adequately char-

acterize the device performance. Mechanical characterization

involves both static and dynamic tests. The test methods and the

justifications of the test parameters (i.e. loading mode, frequency

of testing, failure loads, test environment) need to be defined

prior to initiation.

Static Characterization

Static testing needs to be carried out to sufficiently characterize

the performance properties of the individual components and

the finished device in simulated physiologic conditions. Strength

testing should evaluate the robustness of the device construct

and/or device under extreme loads. Testing should be conducted

on both the device components (if applicable) and finished

device to a representative worst-case physiologic load or to

failure, whichever occurs first. At a minimum, static characteri-

zation should address the following: single cycle strength testing,

compression characterization testing, creep recovery testing,

subsidence testing and hydration/polymerization rate testing.

Test Rate, Temperature and Constraint Analysis

Most of the nucleus arthroplasty devices on the market are manu-

factured from materials that have viscoelastic, or rate dependent,

properties. Therefore, the test rate utilized in a characterization

test is critical. Based on the various designs, one rate may not

be appropriate. Testing needs to be performed on the individual

device to identify the appropriate test rate as this could bias the

test results.

The effect of temperature needs to be addressed when conduct-

ing tests on polymeric devices or tissue-based implants as

device properties may vary at body temperature compared

to room temperature.

For devices with unconstrained deformation that depend or expect

contact with the annulus during in vivouse, the various tests iden-

tified below should be performed in unconfined constraints and

confined constraints using special test setups (Figures 1 & 2). Based

on implant design and intended function, the bulk properties of

the implant may be greatly impacted by test constraints.

Figure 1:Unconfined testing of a tissueengineered nucleus implant in a materialtesting machine.

Load cell

Piston

Collagen implant

18


21/48

Single Cycle Device Burst Testing

A nucleus replacement device may be subjected to extremein

vivocompressive loads.In vivostudies performed in our lab

showed that the maximum load when bending over to lift a load

of 20 kg with straight legs was about 4000 N.13 Published litera-

ture reports peak compressive loads during lifting of heavy

objects to be as large as 7000 N through a vertebral segment,

with approximately 15% of the load carried through the facet

joints in an upright position.14, 15 Therefore, peak loads through

the anterior column are estimated at 6000 N maximum; similar

vertebral fracture loads are defined in the literature.16

In the anterior column, load is distributed nearly equally

between the nucleus and the annulus.17, 18

However, based onimplant design, a portion of, or all of the anterior column load

may pass through the device. Therefore, depending on the load-

sharing characteristics of the implant, a maximum device load

between 3000 N and 6000 N is representative of a single cycle

worst-case physiologic load. Upon completion of testing, the

data should identify where and how device failure initiated.

Load Deflection Testing

Loads passing through the spinal column are cyclic in nature.

Therefore, a nucleus arthroplasty device should ideally be able to

absorb loads representative of daily living and recover upon load

removal. In order to estimate how the device will function clini-

cally, compressive load deflection testing should be performed to

characterize the acute performance of the device. Relevant loads

may be determined based on a review of the literature. In vivo

research estimates a load of 200 N to represent supine disc loads,

800 N to represent relaxed standing, 2000 N to replicate standing

with flexion and up to 4000 N representing standing with flexion

while lifting 20 kg.13 Based on implant design and accounting for

load sharing between the facet joints and annulus, load-deflectionimplant characterization should be conducted to maximum load

between 1700 N-4000 N to be representative of physiologic loading.

Contact Footprint and Pressure Testing

Loads applied to the vertebral bodies are transferred through a

nucleus replacement device. This load transfer also occurs through

the endplate-implant interface. To understand the conformability

and endplate stress associated with a nucleus arthroplasty device,

contact stresses should be analyzed. For characterization purposes,

concave steel load platens are recommended to isolate device per-

formance and minimize variation in cadaveric tissue. Calibrated

Tekscan pressure film, or equivalent, provides a good measure of

contact footprint, contact stress and conformity for characteriza-

tion testing. As above, to represent a physiologic condition, testing

should be conducted to 1700 N-4000 N.

Subsidence Testing

In addition to the contact footprint and pressure testing, subsi-

dence testing in accordance with ASTM F2267-04 should be

performed to determine the relative resistance of the device to

subsidence in simulated cancelleous bone foam. To better

establish clinical relevance of the values calculated from the

ASTM test, it is recommended to utilize a control device with

documented clinical experience.

Figure 2:Confined testing of a tissue engineered nucleus implant using a porous stainlesssteel chamber (a, b) in a material testing machine (c).

a b c

19


22/48

Creep Recovery

Nucleus arthroplasty devices may be subjected to sustained loads;

therefore, characterizing the creep recovery response is important.

This test may be designed to generally comply with ASTM D2990-01

Standard Test Methods for Tensile, Compressive, and Flexural

Creep and Creep-Rupture of Plastics. The devices should be

subjected to various load ranges, load rates, and recovery times.

Dynamic Characterization

As with single cycle test rate analysis, for dynamic testing, test

rate analysis should be performed prior to dynamic characteriza-

tion. The dynamic testing may include load deflection hysteresis

testing, compression-shear fatigue testing, and cyclic wear test-

ing. The test methods and rationale will be somewhat dictated

by device design.

Load Deflection Hysteresis

To evaluate the device response and ability to withstand physi-

ologic loads representative of heavy lifting, the device should

be subjected to cyclic compression testing in representative

test platens.

Load sharing through a vertebral segment varies during activities

involving flexion, extension, and lateral bending. Compressive

loads during relaxed standing are reported to be 800 N and, during

lifting of 20 kg objects, can be as large as 4000 N through the verte-

bral segment.13

A worst-case scenario can be established by assum-ing that the majority of the loads may pass directly through the

device. Excluding the reported 15% compressive load sharing of

the facet joints and accounting for annulus load sharing, the

physiologic spinal segment compressive cyclic testing scheme rep-

resentative of standing and heavy lifting is 400 N to 2000 N. 13

Estimating that heavy lifting is performed twice a week for 20

years, each device should be subjected to 2000 peak load cycles

during the course of evaluation.

Compression Shear Fatigue

Due to the small amount of torsion in the lumbar spine, it is

believed that the potential failure modes in dynamic compression-

shear testing exemplify the worst-case loading condition seen by a

nucleus arthroplasty device.

Testing conducted at our laboratory, recorded compressive loads

experienced by the disc during typical daily activities (i.e. resting,standing, sitting, walking, stair climbing) ranges from 200 N to

1250 N.13 During walking, we measured a compressive load of

approximately 1150 N. Others have reported lumbar compression

and shear loads during walking to be as high as 1850 N and 560 N,

respectively.19 Shear loads in the literature are reported to be up to

1200 N at L5/S1 with more strenuous activities.20 Therefore, select-

ing loads measured during walking as representative of physio-

logic cyclic loads and accounting for load distribution across the

segment, a simultaneous axial compression of 925 N and 280 N

shear is recommended. It is generally recommended to evaluate

a minimum of six devices to a minimum of 10 million cycles.

Cyclic Wear Testing

Cyclic wear properties can vary with implant design and mate-

rial choice. Limited data is currently available for such tests as

they are often performed in-house during development with the

results used for regulatory purposes and not publication. Local

and systemic reaction from wear particulate is a risk with any

implantable device. Particle size, morphology, and quantity have

been demonstrated to be key factors in the bodys response to

wear debris. Therefore, testing should be conducted to determine

the wear debris generated over a representative device lifetime.

The compression shear fatigue loading described above may be

utilized to assess the durability and potential wear debris gen-

eration of nucleus arthroplasty devices. All devices should be

tested in Ringers solution to simulate thein vivoenviron-

ment. The Ringers solution should be analyzed after 5 million

and 10 million cycles to characterize any wear particulate.

TO EVALUATE THE DEVICE RESPONSE AND ABILITY TO WITHSTAND PHYSIOLOGIC

LOADS REPRESENTATIVE OF HEAVY LIFTING, THE DEVICE SHOULD BE SUBJECTED TO

CYCLIC COMPRESSION TESTING IN REPRESENTATIVE TEST PLATENS.

20


23/48

Cadaveric Studies

The nucleus arthroplasty device interactions with soft tissue

structures (i.e. annulus, ligamentous structures, facet joints) are

difficult to predict and replicate in bench tests. Therefore, upon

completion of the characterization bench tests, various cadaveric

studies should be performed to help bridge the characterization

test results to expected clinical performance.

Details and recommendations for a standardized in vitrostability

test, as well as information about handling of specimens, can be

found in another publication.21

Functional In VitroFlexibility Tests

In contrast to the pure mechanical tests, flexibility tests are designed

with the goal of evaluating thein situperformance. Ideally, suchevaluations incorporate the use of cadaveric specimens mounted

on mechanical testing machines that produce loads that simulate

the expected physiological motion (Figure 3).22

Testing should be carried out in flexion/extension, lateral bend-

ing, and axial rotation. After completing the basic tests, addi-

tional studies using shear loading, compression, muscle forces,

and other representativein vivoloads may also be considered.

To assess device performance and account for potential variation

in cadaveric specimens, it is recommended that suchin vitro

studies be performed for the intact, nucleotomized/degenerated,

and implanted states. It is also recommended for standardization

purposes that evaluations be performed under pure moments

without preload.21

The parameters of interest are the range of motion, the neutral

zone in the different motion planes, the shear translations, and

the corresponding changes in height. Additionally, information

such as the centers of rotation, helical axes, and load-sharing

capabilities of the different spinal structures, help to provide acomplete kinematic picture (Figure 4).

Test methods and corresponding results are included in Volume II

of the publication series. Details and recommendations for a

standardizedin vitrostability test, as well as information about

handling of specimens, can be found in another publication.21

Expulsion Testing

Depending on the type of device, expulsion or subsidence of the

implant may be a serious problem. In order to evaluate this type

of biomechanical failure, the specimens should be subjected to

complex cyclic loading regime, as during daily activities, the spine

is not only loaded axially, but rather eccentrically.

Figure 3:Custom-built spineloading apparatus to determinethe functional flexibility of acadaveric spinal segmentthe simulator consists of threeaxes with integrated motors,gears, and clutches, which allowapplication of pure moments.

Figure 4:Disc bulging canbe measured with a three-dimensional laser scanning

device fixed in the spineloading apparatus.

21


24/48

To simulate this complex loading, our lab has developed a test

setup such that during cyclic loading the specimen revolves

clockwise around an axis located in the center of the vertebral

body at a rate of 360/min (Figure 5).23 This setup provides

complex motion as during testing the specimen experiencesloading in flexion, left lateral bending, extension, and right

lateral bending in a continual manner.

A total of 100,000 cycles at 5 Hz with an eccentric load (lever

arm of 40 mm) and an amplitude between 100 N-600 N should

be applied.23 Depending on the type of implant, testing should

be performed in a Ringers solution; however, degradation of

the cadaveric tissue may influence the ability to perform long-

term tests (Figure 6).

Cyclic loading may also provoke subsidence or a loss in implant

height which can be quantified by measuring the overall height.Measurements should be taken pre and post-loading and after

every 20,000 cycles in the material testing machine (Figure 7).

In order to obtain reproducible measurements, the upper plane

of the PMMA block should be leveled horizontally with the spec-

imen loaded using a standardized preload, for example 100 N

axial preload. Following the cyclic test, secondary flexibility and

height measurement evaluations should also be performed.

Please note that the results obtained with the suggested test

setup may not correlate directly to clinical rates of device extru-

sion, but should serve as a basis for comparison of the relative

risk profile.

22

Figure 5:Setup in a dynamic material testing machine to load thecadaveric specimens cyclically with an eccentric preload (100 N-600 N,x 40 mm lever arm with 5 Hz) while the specimen is rotated aroundits own axis at 360/minute.

Collagen implant

with annulussutured

Textile implantwithout annulus

sutured

Figure 6:Examples forthe process of nucleusimplant extrusion(


25/48

Functional In Vivo Studies

The baboon model is considered a relevant model for the

human spine based on the baboons anatomy, physiology, in

vitromechanics, pseudo-bipedal gait and extremely active daily

activities.24, 25 In addition, the results from Ledet et al.25 suggest

the mechanical loads in baboons are equivalent to the human

spine. However, the disc space is smaller than the human spine

and requires miniaturized devices for implantation. Based on the

materials utilized in most nucleus arthroplasty devices, minia-

ture devices may not have equivalent performance characteristics

as those utilized for human implants. Thus, the baboon model

represents a worst-casein vivoevaluation and has been used for

numerous nucleus replacement technologies primarily to assess

the safety of the device material when exposed to daily move-

ments.24 One of the primary purposes in performing suchin vivo

baboon model testing is to assess device wear generation and the

associated local and systemic histological response to any such

wear debris. Other species like the sheep may also be considered,

but the limitations of these models have always to be discussed. 26

Biocompatibility Testing

Manufacturers should consider performing all relevant tests rec-

ommended by ISO 10993-1, FDAs Blue Book Memorandum

#G95-1, and possibly a carcinogenicity assay. Tests performed

included cytotoxicity; sensitization; irritation/intracutaneous

reactivity; acute systemic toxicity; subacute, subchronic, and

chronic systemic toxicity (for general systemic and local effects);

material-mediated pyrogenicity; and genotoxicity (bacterial,

andin vivoand in vitromammalian) and hemolysis.

CONCLUSION

Nucleus arthroplasty is an exciting and challenging technology

and may be a promising alternative to other non-fusion con-

cepts. While current patient demographics continue to support

the need for such innovative ideas, creating a nucleus arthro-

plasty device requires a multi-discipline approach with respect

to the design, development, and testing.

This chapter outlined the design challenges, methods of charac-

terization, and importance of biomechanical testing. Based on

the specific biomechanical demands, each type of nucleusarthroplasty device may have a target population in which it

works well clinically. The challenge is to balance the biomechan-

ics with the other surgical and pathology factors that are often

difficult to identify and control.

Although the described test methods may have limitations,

they provide important and useful information during devel-

opment and may provide relevant findings prior to clinical

application. Nevertheless, even if a particular implant performs

well in the lab, the ultimate test of the biomechanical data will

be the clinical outcomes.

23

Figure 7:Height measurements should be performedunder reproducible conditions, the upper vertebra

should be leveled horizontally with the specimen loadedusing a standardized preload.

NUCLEUS ARTHROPLASTY IS AN EXCITING AND CHALLENGING TECHNOLOGY

AND MAY BE A PROMISING ALTERNATIVE TO OTHER NON-FUSION CONCEPTS.


26/48

24

ACKNOWLEDGMENTS

A portion of the studies mentioned above have been supported

by the German Research Foundation (Deutsche

Forschungsgemeinschaft (WI 1352/8-1).

REFERENCES

1. Bao QB, Yuan HA. New technologies in spine: nucleus replacement. Spine

2002;27:1245-7.

2. Wilke HJ. Principles and Mechanical Requirements of Nucleus Implants. In

Davis RJD, Girardi FP, Cammisa FP, et al. eds. Nucleus Arthroplasty

Technology in Spinal Care. Minneapolis, MN: Raymedica, LCC, 2007:11-6.

3. Fernstrom U. Arthroplasty with intercorporal endoprothesis in herniated disc

and in painful disc. Acta Chir Scand Suppl 1966;357:154-9.

4. Schmidt H, Claes L, Wilke HJ. Instantaneous Axis of Rotation of a L4-5

Segment under Simple and Complex Load Situations. A Three Dimensional

Finite Element Analysis. Global Symposium on Motion Preservation

Technology 7th Annual Meeting. Berlin: Spine Arthroplasty Society, 2007:17.

5. Wilke HJ, Kettler A, Claes L. Range of motion or finite helical axis?

Comparison of different methods to describe spinal segmental motion in

vitro. Roundtables in Spine Surgery Spine Biomechanics 2005;1:13-21.

6. Neidlinger-Wilke C, Wurtz K, Liedert A, et al. A three-dimensional collagen

matrix as a suitable culture system for the comparison of cyclic strain and

hydrostatic pressure effects on intervertebral disc cells. J Neurosurg Spine

2005;2:457-65.

7. Neidlinger-Wilke C, Wrtz K, Urban JP, et al. Regulation of gene expression

in intervertebral disc cells by low and high hydrostatic pressure. Eur Spine J

2006;15:S372-S8.

8. Wilke HJ, Kavanagh S, Neller S, et al. Effect of a prosthetic disc nucleus on

the mobility and disc height of the L4-5 intervertebral disc postnucleotomy.

J Neurosurg 2001;95:208-14.

9. Wilke HJ, Heuer F, Neidlinger-Wilke C, et al. Is a collagen scaffold for a tissue

engineered nucleus replacement capable of restoring disc height and stability

in an animal model? Eur Spine J 2006;15 Suppl 3:S433-8.

10. Kaps HP, Kettler A, Haegele B, et al. Nearly Natural Biomechanical Properties

of a Nucleus Prosthesis Made of Knitted Titanium Filaments. Global

Symposium on Motion Preservation Technology 7th Annual Meeting. Berlin:

Spine Arthroplasty Society, 2007:66.

11. Urban JP, Smith S, Fairbank JC. Nutrition of the intervertebral disc. Spine

2004;29:2700-9.

12. Wuertz K, Urban JP, Klasen J, et al. Influence of extracellular osmolarity

and mechanical stimulation on gene expression of intervertebral disc cells.

J Orthop Res 2007.

13. Wilke HJ, Neef P, Caimi M, et al. Newin vivomeasurements of pressures in

the intervertebral disc in daily life. Spine 1999;24:755-62.

14. Han JS, Goel VK, Ahn JY, et al. Loads in the spinal structures during lifting:

development of a three-dimensional comprehensive biomechanical model.

Eur Spine J 1995;4:153-68.

15. Adams MA, Hutton WC. The effect of posture on the role of the apophysial

joints in resisting intervertebral compressive forces. J Bone Joint Surg Br

1980;62:358-62.

16. Brinckmann P, Biggemann M, Hilweg D. Prediction of the Compressive

Strength of Human Lumbar Vertebrae. Clin Biomech 1989;4:S1-S27.

17. Adams MA, McNally DS, Dolan P. Stress distributions inside intervertebral

discs. The effects of age and degeneration. J Bone Joint Surg Br

1996;78:965-72.

18. McNally DS, Adams MA. Internal intervertebral disc mechanics as revealed

by stress profilometry. Spine 1992;17:66-73.

19. Khoo B, Goh J, Bose K. A biomechanical model to determine lumbosacralloads during single stance phase in normal gait. Medical Engineering and

Physics, 1995. 17:p. 27-35.

20. Bazrgari B, Shirazi-Adl A, Arjmand N. Analysis of squat and stoop dynamic

liftings: muscle forces and internal spinal loads. Eur Spine J 2007;16:687-99.

21. Wilke H-J, Wenger K, Claes L. Testing Criteria for Spinal Implants:

Recommendations for the Standardization ofIn VitroStability Testing of

Spinal Implants. European Spine Journal 1998;7:148-54.

22. Wilke HJ, Claes L, Schmitt H, et al. A universal spine tester for in vitroexperi

ments with muscle force simulation. Eur Spine J 1994;3:91-7.

23. Wilke HJ, Mehnert U, Claes LE, et al. Biomechanical evaluation of vertebro-

plasty and kyphoplasty with polymethyl methacrylate or calcium phosphate

cement under cyclic loading. Spine 2006;31:2934-41.

24. Allen MJ, Schoonmaker JE, Bauer TW, et al. Preclinical evaluation of a poly

(vinyl alcohol) hydrogel implant as a replacement for the nucleus pulposus.

Spine 2004;29:515-23.

25. Ledet EH, et al. Direct real time measurements of the in vivoforces in the

lubmar spine. The Spine Journal 2005;5:8-94.

26. Alini M, Eisenstein SM, Ito K, et al. Are animal models useful for studying

human disc disorders/degeneration? Eur Spine J 2007.

BASED ON THE SPECIFIC BIOMECHANICAL DEMANDS, EACH TYPE OF NUCLEUS ARTHRO-

PLASTY DEVICE MAY HAVE A TARGET POPULATION IN WHICH IT WORKS WELL CLINICALLY.

THE CHALLENGE IS TO BALANCE THE BIOMECHANICS WITH THE OTHER SURGICAL ANDPATHOLOGY FACTORS THAT ARE OFTEN DIFFICULT TO IDENTIFY AND CONTROL.


27/48

25

KEY POINTS

A vast array of nucleus arthroplasty implants is currently

available including hydrogels, polymer/synthetics,

and mechanical devices.

Early pilot data with these devices has been promising

in clinical studies outside of the United States.

Pilot studies are underway in the United States and pivotal

studies will need to be designed and implemented to determinethe efficacy of nucleus replacement devices.

Chapter 24 Early Clinical Results of NucleusArthroplasty Technology

Robert Tatsumi, MD

CLINICAL FELLOWThe Spine Institute, Santa Monica


Jason Gallina, MDCLINICAL FELLOW

The Spine Institute, Santa Monica


Hyun Bae, MDDIRECTOR OF RESEARCH

The Spine Institute, Santa Monica



28/48

INTRODUCTION

A s people age, the lumbar discs undergo a progressivealteration of chemical composition and biomechanicalproperties.1-11 Such chemical and biomechanical changes can

lead to back pain.12 There are various surgical procedures for

the treatment of low back pain caused by degenerative disc

disease.13-19 Nucleus replacement is a newer option and this

chapter will discuss the early clinical results of this procedure.

At the present time, the Food and Drug Administration (FDA)

considers the term nucleus arthroplasty as broadly applicable

to any device that replaces the nucleus pulposus, while preserv-

ing the surrounding annulus. Nucleus arthroplasty has been

indicated for the treatment of early-stage degenerative disc dis-

ease with an intact annulus or status post-microdiscectomy

procedure where nucleus material has been removed. The goalsof nucleus arthroplasty surgery are to preserve the motion and

geometry of the index intervertebral disc, while preventing

adjacent segment degeneration.

NUCLEUS ARTHROPLASTY TECHNOLOGY

Early nucleus arthroplasty devices were focused on replacing

the nucleus with stainless steel ball bearings, silicone rubber, or

polymethylmethacrylate (PMMA) cement.16-19 Some of these

devices had inferior results due to hardware failure and our

misunderstanding of disc biomechanics. Currently, there aremore than 20 different nucleus arthroplasty devices in the con-

cept or development stages. These devices vary greatly in design

and function utilizing hydrogel, polymer/synthetic, or mechani-

cal technologies to preserve the motion and geometry of the

intervertebral disc.

UNITED STATES CLINICAL TRIALS

Currently, the United States has four nucleus replacement Pilot

Investigation Device Exemption (IDE) trials from three compa-

nies that have been actively enrolling patients. These pilot studies

have small sample numbers (10-40 patients) and are geared to

prove device safety. Data accumulated from each of these studies

will then be used to establish pivotal FDA IDE trials to determine

device efficacy. The pivotal FDA IDE trial will ultimately require

250 to 500 patients and have to prove efficacy against a random-

ized control. The proposed control arms at this point have not

been finalized. The possible groups that have been proposed are

non-operative treatment, lumbar interbody fusion, and total disc

replacement. The current pilot IDE trials are as follows:

Spine Wave, created in 2001, developed NuCore as an adjunct

following a standard microdiscectomy procedure. NuCore is aninjectable protein that cures rapidly in situforming a hydrogel

that adheres to the annulus. After a partial nuclectomy (


29/48

Raymedica, founded in 1990, has been a pioneer in the field of

disc nucleus arthroplasty with the invention of the paired pillow-

shaped hydrogel device in 1996 (PDN prosthetic disc nucleus).

Raymedica has since introduced single-device implants utilizing

the same hydrogel components and high molecular weight poly-

ethylene jacketed designsthe PDN-SOLO and HydraFlex

devices (Figures 2 a & b). The hydrogel core is a shaped pellet

that absorbs fluid after implantation and expands within the

disc space. A subtotal nuclectomy (34-66% of the nucleus

removed) is required to insert this device via a posterior orAnterolateral RetroPeritoneal Approach (ARPA). Currently,

Raymedica is conducting a trial evaluating patients with the

HydraFlex device.

Disc Dynamics, founded in 2000, applies an implant delivery

system similar to that used for interventional cardiology. The

DASCOR device is two-part curable polyurethane substrate

that is delivered via a catheter and balloon under controlled

pressure (Figure 3). A complete nuclectomy (67-100% of the

nucleus removed) needs to be performed for proper graft place-

ment usually through the AnteroLateral transPsoatic Appr

Nucleus Arthroplasty Volume IV

Documents

Transcript of Nucleus Arthroplasty Volume IV