Nucleus Augmentation

Thomas J. Raley, Qi-Bin Bao and Hansen A. Yuan

Low back pain (LBP) is a common condition that affects the majority of the population 1,2 and economically impacts our society.^3,4 In fact, LBP is second only to the common cold for lost time at work.⁵ The probability of returning to work decreases dramatically with increased time off work (roughly 50% at 6 months).^6,7 The true cause of LBP is unknown, but most likely it is associated with the degeneration of the intervertebral disc (IVD) and age-related deterioration.^8,9 With aging, the incidence of LBP, stiffness, and IVD changes increases,¹⁰ preceding other degenerative changes in the spine.^11–13

Normal Intervertebral Disc Function

The normal mechanical function of the IVD can be summarized as follows:

The nucleus pulposus (NP) acts predominantly as a fluid under static loading conditions and generates large hydrostatic pressures. The swelling pressure mechanism, due to a high concentration of negatively charged proteoglycans in the NP, maintains disk height and contributes to the pressure mechanism of load support and transfer.¹⁴
The high hydraulic permeability of the cartilage endplates allows load transfer uniformly across the anulus fibrosus (AF) and NP.
The outer anulus, with the highest tensile modulus, is well suited for minimizing IVD bulging and AF strains generated during loading of the spine in compression, bending, or torsional loading.
In contrast, the lower modulus of the AF allows viscoelastic dissipation. This fluid-flow generated frictional dissipation mechanism in the AF, along with dissipation resulting from NP deformation, is likely to be the mechanisms for energy dissipation and shock absorption for the entire IVD.

Nucleus Replacement for Intervertebral Disc Degeneration

After failure of all conservative treatment, the patient is eligible for surgical intervention. However, the appropriate surgical procedure must address the proposed pain generator. Many treatment options have resulted in poor long-term outcomes. This has led to newer alternative technologies, including NP replacement, IVD replacement, and interbody fusion techniques. In this chapter we will focus on nucleus replacement.

Nucleus replacement is a novel approach to replace the degenerated NP and stop the degenerative cascade. Nucleus replacement is meant to mimic the normal function of the functional spinal unit by preserving motion and preventing adjacent segment degeneration. Nucleus replacements may be useful for the treatment of patients with early symptomatic disc disruption. In the future, they may be performed at the time of discectomy to maintain normal biomechanics of the spine and prevent future degeneration.

History

The idea of nucleus replacements originates in the 1950s. Initial attempts at maintaining disc space height and motion involved injection of polymethyl-methacrylate¹⁵ or silicone¹⁶ into the disc space after nucleotomy. Poor clinical results led to the abandonment of these procedures in favor of inserting preformed devices.

Historically, the first human implanted nucleus prosthesis was the Fernstrom ball in 1966. This device was a spherical endoprosthesis made of stainless steel.¹⁷ It was meant as a spacer that allowed movement between the adjacent vertebral bodies. It did not restore normal load distribution and was abandoned because of concerns of implant migration and subsidence. However, encouraging long-term results led to further efforts in designing other nucleus replacements.¹⁸ Failures with metal ball bearings led to Urbaniak’s study on nucleus replacement with a silicone-Dacron composite device in chimpanzees.¹⁹ This work spawned the idea for a preformed or contained implant. In 1981, Edeland²⁰ suggested the implantation of a device that behaved biologically and biomechanically similar to the NP. The device behaved in a viscoelastic fashion and the properties changed to adapt to the loads applied. In 1988, Ray and Corbin²¹ developed a device based on Edeland’s principles. It consisted of an outer woven polyethylene capsule, with thixotropic gel injected into the collapsed bags after implantation. This device exhibited swelling pressures similar to the natural NP. In 1991 and 1993, Bao and Higham patented hydrogel for nucleus replacement.^21,22 The Aquarelle hydrogel nucleus is composed of polyvinyl alcohol (PVA), which has a water content of 70% under physiologic loading conditions, much like the natural nucleus. Three of 25 implants extruded through the annulotomy and one through a preexisting tear.23 In the mid-1990s, Ray modified his device to a hydrogel core encased with a polyethylene jacket. This prosthetic disc nucleus was implanted in pairs. The device was implanted in a dehydrated state to facilitate insertion.

Biomechanics of Nucleus Replacement Implants

Biologically, the NP functions as a fluid pump, facilitating body fluid diffusion, which carries the nutrients and removes the metabolites from the avascular disc. Biomechanically, the nucleus inflates the anulus and shares a significant portion of compressive load with the anulus. Therefore, the main objective of nucleus replacement implants is to reestablish normal disc function by restoring disc turgor, tension in the AF, and the disc’s ability to uniformly transfer loads across the disc space.

In addition to biocompatibility and fatigue strength, several features should be taken into consideration with the design of the nucleus replacement. First, the nucleus replacement should restore the normal and uniform load distribution to avoid excessive endplate wear. Second, the prosthesis should have sufficient stability in the disc space to avoid implant migration. Third, it should restore the normal body fluid pumping function to enhance nutrient diffusion for the remaining nucleus and inner anulus. Lastly, the implant should be able to be easily implanted.²⁴

The nucleus replacement implants must be biocompatible and be able to endure a considerable amount of loading before failure. Assuming the average individual takes ~2 million strides per year, the average implant would be expected to take the loads of 100 million cycles over 40 years.²⁵ In addition to biocompatibility and withstanding load, the device must also (1) exhibit low wear characteristics with minimal wear debris; (2) allow uniform stress distribution under various physiological loading conditions to avoid subsidence and extrusion of the device; (3) fill the disc space to prevent excessive movement that may lead to extrusion; and (4) enable minimally invasive surgical implantation limiting destruction of the tissues and enhancing the stability of the implant.²⁴ Conceptually and ideally, the nucleus replacement should have the same mechanical properties, such as stiffness and viscoelastic property, as the natural nucleus. The key is to assure a good uniform stress distribution.

Materials and Types of Nucleus Replacement Implants

Choosing the appropriate material is paramount in preventing potential failures. Higher modulus of elasticity devices used in the past are believed to be too stiff for nucleus devices. Most current nucleus prosthesis designs use various elastomers or designs having viscoelastic properties. At this time, nucleus replacements are categorized into two groups: intradiscal implants and in situ curable polymers. The intradiscal devices are biomechanically more similar to the native nucleus and the in situ curable polymers harden after implantation and allow for a less-invasive approach for implantation.

The first attempt of in situ formed nucleus prostheses was by Nachemson in 1960.^26,27 The main advantage is that it can be injected through a small annular window to reduce the risk of extrusion. It also has the advantage of better implant conformity leading to better stress distribution and implant stability. However, there are several challenges including fatigue of the material, biocompatibility, and leakage of the injectate through the annular incision or another annular defect. Preformed nucleus implants have more consistent polymer properties and biocompatibility. The disadvantages include mismatch with size and shape of the cavity and the need for a larger annular incision for implantation and therefore a risk of device extrusion.²⁸ Another preformed design concept is a device whose shape can be reduced or altered during implantation and restored after implantation. This may be achieved by inflating a balloon with incompressible fluid or by implanting dehydrated hydrogel that rehydrates in the disc.

Current materials used for nucleus augmentation include elastomeric materials, including both hydrogels and nonhydrogels, mechanical devices, and tissue-engineered implants. For the nucleus replacement devices made of elastomeric materials, they can be further divided into preformed and in situ formed.

Preformed Elastomeric Devices

Hydrogel materials closely mimic the functions of a normal disc. It has been demonstrated that PVA (nonionic hydrogel) has a similar swelling pressure characteristic as the natural nucleus; three-dimensional expandable polymers with variable water content and biomechanical properties suitable for nucleus replacement. These polymers increase in size and fill the disc space by absorbing water. Their high water content potentially mimics the hydrostatic load bearing and load distribution properties of an intact nucleus. One of the most important characteristics is the ability to absorb and release water depending on the applied load, much like the native nucleus.²⁹ Examples include:

Aquarelle (Stryker, Kalamazoo, MI): Aquarelle is made of PVA. Extensive preclinical studies have been conducted, including biocompatibility studies, swelling pressure studies, biomechanical studies using human cadaver models, fatigue studies (to 23.5 million cycles), and animal studies.
Prosthetic disc nucleus (Raymedica, Bloomington, MN): The current design is a pellet-shaped hydrogel encased within a polyethylene jacket. It absorbs water up to 80% of its weight. Biomechanical endurance tests have shown that the device is able to maintain its properties up to 50 million cycles with loads ranging from 200 to 800 N. The device shows a 10% implant migration rate.30 The U.S. Food and Drug Administration (FDA) investigational device exemption feasibility studies have not been completed for its newer version of prosthetic disc nucleus (Hydraflex).
NeuDisc (Replication Medical, Inc., Cranbury, NJ): NeuDisc has been designed to replace the NP and restore function to the disc. The unique feature of this material is that it responds biomechanically and biologically like a natural NP. It can take up to 90% of its weight in water and can dehydrate and increase its stiffness when subjected to increased loads much like the native nucleus. The device is implanted in the dehydrated state and rehydrates anisotropically in the vertical direction. A jacket is not required because the implant has a “stacked” configuration, which includes layers of medical-grade polyester fiber mesh within the hydrogel layers. These layers restrict radial deformability (bulging) so that the device will not creep through a defect in the anulus. This product is not commercially available in the United States, but is being implanted in Europe.
Newcleus (Zimmer, Warsaw, IN): Newcleus is a polycarbonate urethane elastomer curled into a preformed spiral. The unique feature 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. Polycarbonate urethane has shown biodurability up to 50 million cycles with loads up to 1200 N.^31,32

In situ Formed Elastomeric Devices

These products are injected in a liquid state and solidify within the disc space. Current substrates used include serum albumin polymers, silk-protein polymers, silicone, and polyurethanes. The perceived advantage is that the injection can be done through a minimally invasive approach that will reduce the risk of migration after curing. Examples include

DASCOR (Disc Dynamics, Inc., Eden Prairie, MN): The DASCOR device consists of a two-part curable polyurethane polymer and expandable balloon, inserted into the disc after the nucleus has been removed. The polymer is then delivered under controlled pressure and completely fills the void created by the balloon, thus decreasing the risk of migration. The implant conforms to the shape and size of the nucleus cavity while distracting the disc space and maintaining disc height. DASCOR has been in clinical use outside the United States since 2003 and is currently under an investigational device exemption feasibility study.
NuCore (Spine Wave, Inc., Shelton, CT): NuCore is an injectable protein-based nucleus replacement. The NuCore material cures rapidly in situ forming a durable, adhesive hydrogel. It has been shown to be very resistant to extrusion due to a mechanical barrier that is formed since the bolus of the cured injectate is larger than the entry site and the adhesive hydrogel properties resist extrusion. The binary liquid of the silk elastin polymer with the chemical cross-linking agent is injected through a syringe after the nucleus material is removed. NuCore is currently under an investigational device exemption feasibility study.
Sinux ANR (DePuy Spine, Raynham, MA): Sinux ANR is a liquid polymethylsiloxane (PMSO) polymer that is injected into the disc space after the nucleus is removed. The polymer cures into an elastic mass in approximately 15 minutes and then the anulus is sutured. It has been commercially available in Europe since 2004.
BioDisc System (Cryolife, Inc., Kennesaw, GA): The BioDisc system is comprised of a protein solution (serum albumin) and a cross-linking component (glutaraldehyde). After the nucleus is removed, the two solutions are injected into the disc space and solidify to form a spacer that provides disc space distraction while acting as a glue to bind the vertebral bodies. The BioDisc system is not commercially available but has enrolled 10 patients in a pilot study being conducted in the United Kingdom in 2006. In 2009, Cryolife is still awaiting CE marketing and study results are still pending.
Geliflex (Synthes, Inc., West Chester, PA): Polymer-based hydrogels remain liquid at room temperature and solidify at body temperature. These hydrogels are injectables through a minimally invasive technique. This product is undergoing preclinical testing and is not commercially available in the United States at this time.
PNR (percutaneous nucleus replacement; TranS1, Wilmington, NC): PNR is an in situ formed nucleus replacement. The approach is transsacral to the lumbar spine, preserving the anulus and ligaments. Then, silicone is injected through the screw to fill the cavity and help maintain motion.

Mechanical Nucleus Replacements

The favorable clinical outcomes in both short-term follow-ups of Fernstrom’s device recently prompted several companies to revisit the mechanical nucleus replacement. These new developments have been focused on using less stiff materials and having designs to allow better stress distribution to minimize subsidence. Some of the materials used include polyetheretherketone (PEEK), metal alloys, pyrolytic carbon, and Zirconia ceramics. Examples include

Regain Disc (Biomet Corp., Warsaw, IN): The Regain Disc is a rigid one-piece device made of pyrolytic carbon with a Young’s modulus similar to cortical bone. The geometry of the device was designed to conform to the bony anatomy of the vertebral endplates. The lumbar device has been implanted in eight baboons, and 1-year follow-up has revealed no operative complications, no device migration, and no subsidence. The device is not commercially available in the United States, but clinical trials have started in Europe.

NUBAC (Pioneer Surgical Technology, Marquette, MI): NUBAC is made from PEEK. It is the only intradiscal device that utilizes articulating PEEK on PEEK. Extensive preclinical studies have been conducted.33 It is a load-sharing device that provides uniform stress distribution. This design is intended to minimize potential subsidence and extrusion while maintaining disc height. It is currently commercially available in Europe under the CE (“Conformite Europeenne”) mark and is under investigational device exemption feasibility study in the United States.

Nucleus Regeneration

It has been shown that reinserting NP cells may preserve the disc by slowing down the degenerative process.³³ The seeded cells could be mesenchymal progenitor cells or IVD cells. This matrix would serve as a scaffold to produce adequate mechanical properties, but would not be able to restore disc height. These tissue-engineered scaffolds would be natural or synthetic. Such approaches are currently under study.

See Fig. 22.1 for a summary of all nucleus implants.

Diagnosis and Surgical Indications

The relationship between degenerative disc disease (DDD) and LBP is very controversial. There has been a poor correlation between DDD on imaging studies and symptoms reported by the general population. A high percentage of asymptomatic individuals have abnormal imaging studies.^34,35 Because of this, the decision of surgical intervention is patient dependent and requires a meticulous presurgical workup that includes a thorough history relating to spinal complaints, a thorough physical examination looking for any abnormalities, and a diagnosis that correlates with the imaging studies.