Nucleus Pulposus Replacement

SPINE Volume 30, Number 16S, pp S16 –S22
©2005, Lippincott Williams & Wilkins, Inc.
Nucleus Pulposus Replacement
Basic Science and Indications for Clinical Use
Alberto Di Martino, MD,*† Alexander R. Vaccaro, MD,‡ Joon Yung Lee, MD,†
Vincenzo Denaro, MD,* and Moe R. Lim, MD†
Study Design. A critical review of available and
emerging nucleus pulposus replacement implants.
Objectives. To review the biomechanics, design, and
clinical data of currently available and developing nucleus
pulposus replacement technologies.
Summary of Background Data. The interest in minimally invasive treatment of degenerative disc disease has
grown as the technology for intervertebral motion-sparing devices continues to improve. Replacement of nucleus pulposus without anular obliteration represents a
tempting alternative to spinal fusion procedures. The aim
in nucleus pulposus replacement is to slow adjacent level
degeneration, restore normal loads to the diseased level,
and restore segmental spinal biomechanics.
Methods. A literature review of currently available
biomaterials, biomechanics, and available preclinical and
clinical data on nucleus pulposus replacement implants.
Results. New synthetic biomaterials have recently
been developed to closely mimic native biomechanics
during compressive loading cycles of the intervertebral
disc. This, in conjunction with improved understanding of
global spine biomechanics, has allowed the development
of novel nucleus replacement implants. These implants
are currently at different stages of preclinical and clinical
investigations.
Conclusions. Although some of the newly designed
prosthesis have shown some promising results in preclinical studies, rigorous short- and long-term clinical evaluations will be critical in evaluating their true efficacy.
Key words: nucleus pulposus replacement, degenerative disc disease, motion sparing implants, anulus sparing implants. Spine 2005;30:S16 –S22
The intervertebral disc is a complex structure consisting
of a jelly-like inner nucleus pulposus (NP), surrounded
by an outer lamellar anulus fibrosus (Figure 1). The relationship between the semifluid NP and the rigid anulus
provides the biomechanical properties necessary for spinal stability. Degenerative disc disease disturbs this delFrom the *Department of Orthopaedic and Trauma Surgery, Campus
Bio-Medico University, Rome, Italy; †Department of Orthopaedic Surgery, Thomas Jefferson University Hospital, Philadelphia, PA; and
‡Delaware Valley Regional Spinal Cord Injury Center, Thomas Jefferson University, and the Rothman Institute, Philadelphia, PA.
Acknowledgment date: December 17, 2004. Acceptance date: May 24,
2005.
The device(s)/drug(s) that is/are the subject of this manuscript is/are not
FDA-approved for this indication and is/are not commercially available in the United States.
No funds were received in support of this work. One or more of the
authors has/have received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to
the subject of this manuscript: e.g., honoraria, gifts, consultancies,
royalties, stocks, stock options, decision making position.
Address correspondence and reprint requests to Alexander R. Vaccaro,
MD, Rothman Institute, 925 Chestnut Street, 5th Floor, Philadelphia,
PA 19107; E-mail: [email protected]
S16
icate balance, with gradual loss of the aqueous content of
the NP, loss of proteoglycans, and eventually loss of disc
height. Since the intervertebral disc is avascular, its regenerative ability is limited.1,2
Damage to the anulus fibrosus, as it occurs in either
progressive disc degeneration or in surgical discectomy,
causes gradual loss of disc height leading to the changes
in the biomechanical characteristics of the remaining
disc. This will ultimately place additional stress on the
facet joints and may lead to circumferential spinal segment degenerative changes.3–5
The trend in the surgical management of degenerative
disc disease over the last several years has been to minimize soft tissue dissection and to preserve the spinal motion segment. In this context, intradiscal replacement of
the NP represents a possible alternative to spinal fusion
procedures. The aim is to reconstruct the NP primarily
while preserving the biomechanics of anulus fibrosus and
cartilaginous endplate. Nucleus pulposus implants are
designed to provide stable motion, increase disc space
height, relieve or lessen transmission of shear forces on
the remaining anulus (restoring their natural length), and
stabilize spinal ligamentous structures.6
At present time, the indication for NP replacement is
for symptomatic lumbar discogenic back pain not responding to active conservative treatment for a minimum of 6 months. Imaging analysis should demonstrate
spondylolisthesis less than Grade I at the symptomatic
level, with disc height loss less than 50%. MRI should
demonstrate early stage degenerative changes with
disc height more than 5 mm and an absent Schmorl
herniation.7,8
Biomechanical Concepts
Artificial intervertebral disc characteristics need to resemble native discs in biomechanics to preserve both segmental motion and global stability. The vertebral column consists of 24 separate vertebrae and the sacrum,
connected by a complex system of facet joints, intervertebral discs, ligaments, and muscles. Replacing one part
of the vertebral column could affect the whole system
negatively.9
Adjacent vertebrae are linked by the triple joint complex; the intervertebral disc anteriorly, and the coupled
facet joints posteriorly. At approximately 30 years of
age, the NP begins to dehydrate and shrink.6 Instead of
transferring loads between the vertebral bodies with the
anular fibers of the disc in tension as in healthy nucleus,
the anulus begins to collapse, altering stress transfer due
to its slackened nature. This results in additional wear
Nucleus Pulposus Replacement • Di Martino et al S17
Figure 1. Rat intervertebral
disc, sagittal section. A, Hematoxylin and eosin stain, original
magnification ⫻4: the nucleus
pulposus (NP) contains chondrocyte-like cells immersed in
an abundant matrix, surrounded
by the anulus fibrosus (AF). B,
Alcian blue stain, original magnification ⫻10. The matrix in NP
is mostly proteoglycans (blue
stain) and type II collagen, and
is directly in contact with the vertebral endplate (EP). (Courtesy of Makarand V. Risbud, PhD.)
and tear of the anulus and increased loads applied to the
facet joints.5
When biomechanically tested in an experimental
model, the removal of the NP leads to an increase in
spinal mobility ranging between 38% and 100%, with
consequent anulus fissures and disc prolapse.10 Moreover, removal of the nucleus has been shown to cause the
outer region of the anulus to bulge outward, and the
inner region to bulge toward the center of the disc with
axial loading.11 These factors are currently thought
to provoke circumferential tears in the anulus, further
decreasing its ability to resist shear forces. When
whole allograft NP was reintroduced in an experimental
model, this maneuver has slowed the process of disc
degeneration.12
The principal aim of nucleus replacement procedures
is to restore the biomechanical functions of the anulus by
placing anular fibers in tension. To do so, the replacement device has to maintain and recreate the functional
characteristics of the disc. Nucleus pulposus implants
should be biocompatible without significant systemic reactions of toxicity or carcinogenicity. The device must
also be able to endure a considerable amount of loading
before failure. Assuming an average individual undergoes approximately 2 million strides per year, the average implant would be expected to experience loads of
approximately 100 million cycles over 40 years.13 In addition, the material should exhibit low wear characteristics with minimal formation of particulate debris. Implant components should have the similar stiffness of a
native disc to avoid stress shielding, atrophy, and bone
resorption that may lead to subsidence and extrusion of
the implant. The modulus of the component material
should be comparable to the vertebral endplates. Components with modular mismatches will lead to abnormal
load distribution and potential endplate subsidence. The
prosthesis must also fill the disc space to prevent excessive movement of the implant, which could lead to implant extrusion. Lastly, the design of the implant should
focus on minimally invasive approaches that limit destruction of surrounding tissue, enhancing stability of
implanted components.7,14
Finite element analysis has shown that nuclear cavity
filling implants can restore the normal mechanical behavior of the anulus, where as smaller, noncavity filling
implants could not do so. Moreover, if loads are carried
mainly by the implant, this will result in high stresses in
the underlying bone. If the stresses are greater than the
strength of the bone, subsidence into the vertebral body
could eventually develop. If the stresses are lower, the
changes in stress distribution may result in the remodeling of the vertebral body, so that it becomes better
adapted to support the new stresses (Wolff ’s law).15
The newly developed polymers have compatible stiffness to the contiguous vertebral body endplates. Many of
the components that are currently under clinical investigation are three-dimensional expanding polymers
known as hydrogels and newer elastomers.
At present time, NP replacement devices can be categorized into two groups: the intradiscal implants and
in situ curable polymers. Intradiscal devices are biomechanically more similar to the native NP tissue, despite
reported complications that range from extrusion of the
device to fracture of the endplate. In situ curable polymers consist of compounds that harden after implantation. This allows the surgeon to perform minimally invasive implantation procedures and may reduce the
implant migration risk, but these materials are still in the
initial phases of evaluation.
Materials and Implants
The use of synthetic viscous materials called hydrogels
has been extensively explored. These are three-dimensional
expandable polymers with variable water content and
mechanical properties suitable for nuclear replacement.
One of the most important characteristics of these materials is the ability to absorb and release water depending
on the applied load, similar to the native NP tissue.16
To date, the most extensively studied nucleus replacement device is the Prosthetic Disc Nucleus (Raymedica,
Inc., Bloomington, MN).17 The Prosthetic Disc Nucleus
(PDN) is a hydrogel pellet that is encased in a polyethylene jacket. The hydrogel component can absorb up to
80% of its weight in water, because of its hydrophilic
and nonhydrophilic nature of its main constituent copolymers (polyacrylamide and polyacrylonitrile). Water absorption allows the device to swell, restoring and maintaining the native disc height. The polyethylene jacket is
inelastic and restrains the height gain to avoid consequent fractures of the contiguous vertebral endplates
S18 Spine • Volume 30 • Number 16S • 2005
(Figure 2).18 The PDN has performed favorably in both
biologic compatibility and biomechanical tests. Biomechanical endurance tests have revealed that the device is
able to maintain disc height, implant form, and viscoelasticity up to 50 million cycles, with loads ranging
from 200 N to 800 N. The ability of the PDN to restore
disc height and function has been demonstrated in human cadaveric models. Eysel et al evaluated the biomechanical behavior of the PDN implant in 11 cadaveric
lumbar spinal motion segments.10 Physiologic testing of
intact lumbar segments, nucleotomized segments, and
segments with two implanted PDN prostheses were performed under variable loads to analyze changes in segmental mobility. Removal of only 5 to 6 g of NP led to an
increase in mobility ranging from 38% to 100%. Implantation of two PDN devices in the nucleotomized segment restored disc height and also reconstituted the
mobility of the implanted segment close to the prenucleotomized level.10,19 Biocompatibility testing of the PDN
device, according to the guidelines of the International
Standards Organization, did not reveal any systemic toxicity and carcinogenicity.20,21
Aquarelle (Stryker Spine, Allendale, NJ) nucleus replacement is made of a semihydrated poly vinyl alcohol
(PVA) hydrogel (Figure 3). Aquarelle has demonstrated
good biocompatibility when tested in animal models.
The implanted component contains 80% water, which is
principally responsible for its viscoelastic properties. The
component has shown biomechanical durability up to 40
million cycles. Aquarelle is inserted through a small anulotomy via a 4- to 5-mm tapered cannula. It is delivered
in the disc cavity by a pressurized trochar. The prosthesis
may be inserted through either a lateral or posterior approach (Figure 3B, C). The implant has recently been
tested in an experimental model of discectomy in 20 male
baboons. High rates of extrusion have been reported,
ranging from 20% (posterolateral approach) to 33%
(anterior approach) depending on the approach.22
Figure 2. PDN-SOLO device in dehydrated and hydrated states.
The PDN-SOLO device is designed to swell both in height and in
width within the disc space. The porous polyethylene weave
allows fluid to pass into the hydrophilic core, which causes the
device to expand vertically and horizontally (arrow). This process
maximizes the device’s footprint on the vertebral endplates. (Reprinted with permission from Raymedica Inc., Minneapolis, MN.)
Figure 3. The Aquerelle Poly(vinyl alcohol) hydrogel has a swelling
pressure similar to the nucleus pulposus in vivo. A, Once implanted, its final volume depends on the water content at equilibrium. B, Lateral radiograph showing the cavity dimension measurement after insertion of a 4- to 5-mm cannula in the disc space
via a lateral access in the cadaveric spine. C, Anteroposterior
radiograph of the implanted Aquarelle device in a cadaveric
specimen. (Reprinted with permission from Stryker Spine,
Allendale, NJ.)
NeuDisc (Replication Medical Inc., New Brunswick,
NJ) is an implant composed of two grades of a modified
hydrolyzed poly-acrylonitrile polymer (Aquacryl). The
Aquacryl polymer reinforced by a Dacron mesh closely
mimics the properties of the native NP (Figure 4A, B).
The NeuDisc is inserted in a dehydrated state, which
allows the implant to be placed using minimally invasive
methods (Figure 4C). Once inserted, it absorbs up to
90% of its weight in water in an anisotropic fashion
(expansion direction preferentially vertical) to restore
disc height and improve compressive axial load resistance. The NeuDisc has undergone biocompatibility testing in the paravertebral muscle of New Zealand rabbits,
and the analysis of the implanted specimen has not
shown any elicit toxic reactions. At present, the results of
mechanical testing of NeuDisc are not yet available (unpublished data from Replication Medical, Inc. New
Brunswick, NJ).
As early as the 1960s, surgeons have attempted the
insertion of a stand-alone prosthesis to replace a portion
of the nucleus pulposus. A spherical metallic endoprosthesis made of stainless steel was reported in a series of
patients by Fernstrom in 1966.23 A disproportionate
modulus mismatch between the vertebral body and the
device led to significant subsidence. In addition, frequent
loosening and extrusion of the implant led to abandoning its use.
Nucleus Pulposus Replacement • Di Martino et al S19
Figure 4. The Neudisc hydrogel,
prehydration (A) and posthydration (B). Hydration occurs in an
anisotropic fashion, mainly in the
vertical plane. Anteroposterior
(left) and lateral (right) fluoroscopy of the Neudisc device once
implanted in a patient (C). (Reprinted with permission from
Replication Medical, Inc., New
Brunswick, NJ.)
Newcleus (Zimmer, Spine) is an nucleus pulposus replacement made of a polycarbonate urethane (PCU) elastomer curled into a preformed spiral (Figure 5).24,25
Postimplantation, the device absorbs water up to 35% of
its net weight. A unique feature of this implant is that it
does not function on a fixed axis, thus resisting compressive forces while allowing motion even if the component
is not placed in the most optimal position. PCU has been
tested up to 50 million cycles with 1,200 N multidirectional loads. The test did not demonstrate significant
wear or micro cracks. Biocompatibility evaluation of the
PCU polymer was performed in an animal model. Histologic examination of the explanted device and host
tissue demonstrated excellent compatibility.24
The EBI Regain lumbar disc replacement device (Figure 6A) was developed using an innovative electromagnetic motion tracking system that allowed optimization
of its geometric profile. The motion tracking system
studied the spine kinematics after insertion of the implant during dynamic bending cycles. The electromagnetic minisensors in the tracking system captured
changes in implant position, translation, and rotation.
This allowed simultaneous analysis of motion above and
below the disc replacement site. The end result of motion
analysis allowed optimization of the geometric profile of
the device to achieve near normal position, motion, and
stability as compared to the intact disc (unpublished data
from EBI, Parsippany, NJ).
A modular intervertebral prosthetic disc (IPD; Dynamic Spine, Nahtomedi, MN) has recently been tested
in animal models (cows). This device is designed as an
anulus-sparing prosthesis. It is implanted after removal
of the nucleus and endplates and is actually fixed to the
vertebral bodies. The elastic component of this device
consists of metallic springs attached to a fixation component. By altering the mechanical properties of the device, it was possible to modify the load displacement
association of the lumbar discs in cows reconstructed
with IPD.26
In situ curing polymers are liquid-based compounds
with unique characteristics, which harden after implantation in vivo. This allows the introduction of the implant through a minimally invasive approach and mini-
mizes the risk of implant migration following polymer
curing. Currently, the most common injectable elastomers being used within the intervertebral disc space are
silicone and polyurethane. Both of these materials can be
implanted through a small anulotomy. The material in
its liquid phase conforms to the nucleotomized cavity,
maximizing the use of available space to improve segmental stability.7,14,15 These polymers are designed to
perform better with an intact or minimally violated anulus. This minimizes polymer spread beyond the physical
limits of any potential anular defect. The polymers themselves have a fast polymerization time, as most monomers are toxic when absorbed in high doses. Leaching of
these monomers may occur if polymerization time is long
or incomplete. Two in situ curable polymers currently
under development are the DASCOR Disc Arthroplasty
Device (Disc Dynamics, Inc., Eden Prairie, MN) and the
BioDisc. (Cryolife, Kennesaw, GA). The DASCOR Disc
Arthroplasty Device is made with an injectable polyurethane which polymerizes in minutes and is injected into a
polyurethane balloon via a catheter (Figure 7). The Bio-
Figure 5. The Newcleus Spiral Implant; once implanted, the device
reconstitutes its original spiral shape. It localizes in place of the
nucleus pulposus of which reconstitutes the volume, sparing
the anular fibers. (Reprinted with permission from Zimmer Spine,
Warsaw, IN.)
S20 Spine • Volume 30 • Number 16S • 2005
Figure 6. A, EBI Regain is a rigid
nuclear disc replacement device.
B, Implantation of the device in a
baboon spine through an anterior
approach. C, The postoperative
radiographic control. D, Postoperative fluoroscopy of the first
patient in which Regain was implanted, showing the device in
situ. (Reprinted with permission
from EBI, Parsippany, NJ.)
Disc is a protein hydrogel that cures in a few minutes
after direct injection into the Disc space.
Clinical Outcomes and Complications
Clinical outcomes are available only for the few commercially available nucleus replacement devices. The PDN
device has been used in clinical practice for almost 10
years. In 1996, the first clinical reports of the PDN device
noted an 83% success rate. Since this report, the device
has been modified in its shape, dimension, and water
absorption ability. Unfortunately, after these modifications, a lower success rate of 62% and increased device
migration was reported. To overcome the migration
problem, the shape of the device was changed to trapezoid with anterior and posterior wedges. These secondary modifications improved the clinical success rate
to 79%.8
In 1999, wide changes in protocol and surgical instrumentations were introduced. A study that included these
changes demonstrated a success rate of 91% (51 patients). Four-year follow-up data for PDN implants
showed a significant reduction in the symptoms of degenerative disc disease. Oswestry scores dropped from a
presurgical mean of 52% (severe disability) to a mean of
10% (minimal disability) after 2 years. This score further
decreased to a mean of 8.3% after 4 years.8,27,28
In earlier studies, the PDN protocol consisted of implantation of two individual devices into each disc being
treated. MRI analysis has shown that the anteroposterior
dimension of an average degenerative adult disc is less
than 37 mm and that the insertion of a single (larger)
implant could be sufficient to occupy the void left in the
disc after nucleotomy. The technique of using a single
PDN per disc has been evaluated in the past.20 Forty-five
patients surgically treated with single PDN per disc was
followed over a 6-month period. The patients’ level of
pain, walking tolerance, and neurologic deficit were all
improved in the study population. No device migration,
extrusion, or failure was detected.
A total of 423 patients have been treated with the
PDN device between 1996 and 2002. Of these, 10%
have been explanted. The main complications reported
Figure 7. DASCOR Disc Arthroplasty Device. A, Implantation of
the device with a trochar (arrow)
via a lateral approach in a sawbone model. Axial (B) and sagittal (C) lumbar MRI sections in a
patient 6 weeks after surgery.
(Reprinted with permission from
Disc Dynamics, Inc., Eden Prairie, MN.)
Nucleus Pulposus Replacement • Di Martino et al S21
Table 1. Summary of Prosthesis Currently Under Investigation
Device
Technology
Biomaterial
Studies
FDA Approval
Hydrogel pellet encased in a
polyethylene jacket
Semihydrated polyvinyl alcohol
(PVA) hydrogel
Implanted in more than 400
patients
Animal experiments (baboon)
plus cadaveric spine New
Zealand rabbits
New Zealand rabbits
Approved in the United States
for investigational use only
—
Prosthetic Disc
Nucleus
Aquarelle
Intradiscal implant
NeuDisc
Intradiscal implant
Newcleus
Intradiscal implant
Regain
Intradiscal implant
IPD
Intradiscal implant
Modular intervertebral
prosthetic disc
DASCOR Disk
Arthroplasty
Device
BioDisc
In situ curing polymer
Injectable polyurethane
Tested in an animal
experimental model in
cow
Implanted in 16 patients
In situ curing polymer
Protein hydrogel
Tested on animal models
Intradiscal implant
Modified hydrolyzed
polyacrylonitrile polymer
(Aquacryl) reinforced by a
Dacron mesh
Polycarbonate urethane (PCU)
elastomer curled into a
preformed spiral
—
with the PDN device are endplate failure with subsidence
and extrusion. Several different device shapes and materials have been used in the nineties in order to minimize
these complications. In addition, modifications of the
surgical technique, such as the use of lamina spreaders
and the anulus closing system, have been introduced.
Patient weight, disc size, and postoperative rehabilitation protocol have recently been considered important
parameters to be evaluated in the perioperative
setting.8,29
The surgical implantation of this device is commonly
performed via a posterior approach. To minimize the
potential for posterior device migration and dislocation
and to preserve spinal stability, Bertagnoli et al described
implantation of the PDN through an anterolateral
transpsoas approach. This is accomplished via a retroperitoneal approach that splits the psoas muscle and creates an anular flap in the lateral middle third of the disc.
In an analysis of 8 patients who received two PDN implants per nucleotomized disc, reported complications
were transient psoas neuropraxia and device migration.
The former was reported in 4 of first 5 patients, and all
of them recovered within 3 months. Anterior migration
of the two inserted devices was noted in 3 cases, perhaps
from the anular defect created at the time of implantation. Despite the anterior migration, these patients remained without symptoms and did not require revision.
Improvements in Oswestry and Prolo scores have been
noted using this particular surgical approach.30
A clinical trial on PDN is ongoing in Canada; and at
present time, the U.S. FDA is reviewing a proposal for a
pilot study in the United States.8
The Newcleus Spiral Implant has been used in 5 patients with a diagnosis of a disc herniation with radicular
symptoms. A clinical evaluation with a follow-up ranging from 6 to 64 months (mean, 23.6 months) demonstrated that all patients improved their Oswestry
Implanted in 5 patients
Implanted in few patients
—
—
United States Investigational
Device Exemption to start
—
—
—
scores.24,25 To date, there has been no documented migration of the device and no neurologic complications
associated with this device. Moreover, preservation of
motion in the discs and facets was documented on plain
radiographs and CT scans.
The DASCOR Disc Arthroplasty Device is not cleared
for use at this time in the United States. The European
pivotal trial to date has enrolled a total of 16 patients
(Figure 7B, C). The first long-term follow-up evaluation
is reported to show promising results (unpublished data
from Disc Dynamics, Inc.).
Conclusion
Several NP replacement implants are currently at different
stages of preclinical and clinical investigations. Characteristics of the implants are summarized in Table 1. NP replacement procedures have gained wide interest because of
its minimally invasive nature and its promise to spare and
control intervertebral motion. Newer hydrogel-derived
biomaterials appear to mimic the native ability of the NP to
swell and shrink during cyclic compression, preserving fluid
and nutrient diffusion inside the disc.
The goals of this new technology are to slow adjacent level degeneration, restore normal loads to the
diseased level, and restore global spinal biomechanics.
Rigorous animal and clinical evaluations of the new
devices still need to be done, and the issues of implantand procedure-related complications remain to be addressed.
Key Points
● Nucleus pulposus replacement devices are designed to maintain segmental motion while preserving anulus fibrosus integrity.
S22 Spine • Volume 30 • Number 16S • 2005
● Synthetic hydrogels show variable water content
and absorb or release water depending on the applied
load, similar to the native nucleus pulposus tissue.
● The newly developed polymers have compatible
stiffness to the contiguous vertebral body endplates, thus avoiding subsidence and endplate fractures.
● Early clinical studies have shown promising results, despite complications related to device migration.
● More extensive clinical evaluations are required
to determine the efficacy of these prostheses.
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