NuCore Injectable Disk Nucleus

Scott H. Kitchel, Lawrence M. Boyd, and Andrew J. Carter

Injectable Biomaterials for Nucleus Pulposus Augmentation

The use of an injectable material for nucleus replacement gives the flexibility of allowing treatment of partial nucleotomies such as are found following microdiskectomy treatment of disk herniation, as well as indications such as early stage degenerative disk disease (DDD), where complete nucleus removal and replacement are required.

Clinical symptoms resulting from a protruding or painful intervertebral disk (IVD) are commonly treated by the surgical removal of all or part of the intradiskal structure (diskectomy). Diskectomy is the most common spinal surgical treatment, frequently used to treat radicular pain resulting from nerve impingement. Approximately 350,000 diskectomies were performed in 2003 in the United States. During a total diskectomy, a substantial amount (and usually all) of the volume of the nucleus pulposus and inner annulus fibrosus is removed and immediate loss of disk height and volume can result. Even with a partial diskectomy, loss of disk height can ensue. The sudden decrease in disk volume caused by the surgical removal of the disk or disk nucleus results in both local and global effects on the IVD and spinal segment, as will be discussed later.

This procedure is typically performed in a relatively young patient population, with a mean age reported in the literature of between 25 and 40 years.^1–3 However, the impact of altered biomechanics and long-term sequelae in this young patient population may be significant. Specifically, the local and global effects of reduced disk height following diskectomy may be important.

Substantial disk height reduction following diskectomy may occur and is evident soon following the diskectomy procedure. Disk height loss has been found to be proportional to the amount of nucleus removed in an in vitro study.⁴ Clinically, the operated disk spaces of patients postoperatively are significantly narrower following diskectomy (p = .01) than controls.⁵ Scoville and Corkill⁶ found a 50% incidence of narrowing following surgery at the 3-month follow-up. In another study, Tibrewal and Pearcy⁷ found disk space narrowing evident within 3 months following surgery as compared with nonoperated controls.

Proper disk height is necessary to ensure proper functioning of the intervertebral disk and spinal column. On the local (or cellular) level, decreased disk height results in increased pressure in the nucleus pulposus, which can lead to a decrease in cell matrix synthesis and an increase in cell necrosis and apoptosis. It has been shown in other cartilaginous tissues that increased static loading decreases matrix protein biosynthesis.^8–10 Animal models have shown that overloading of the intervertebral disk can initiate disk degeneration.^11,12 In addition, an increase in intradiskal pressure creates an unfavorable environment for fluid transfer into the disk, which can cause a further decrease in disk height.

Decreased disk height also results in significant changes in the global mechanical stability of the spine, which may result in further degeneration of the spinal segment. With decreasing height of the disk, the facet joints bear increasing loads and may undergo hypertrophy and degeneration, which may act as a source of pain over time.^13,14 Decreased stiffness of the spinal column and increased range of motion resulting from loss of disk height can lead to further instability of the spine.¹⁴ Excessive motion can manifest itself in abnormal muscle, ligament, and tendon loading, which can ultimately be a source of back pain.

Radicular pain may result from a decrease in foraminal volume caused by decreased disk height. Specifically, as disk height decreases, the volume of the foraminal canal, through which the spinal nerve roots pass, decreases. This decrease may lead to spinal nerve impingement, with associated radiating pain and dysfunction. Finally, adjacent segment loading increases as the disk height decreases at a given level.^14,15 The disks that must bear additional loading are now susceptible to accelerated degeneration and compromise, which may eventually propagate along the destabilized spinal column.

A further issue with microdiskectomy surgery is the occurrence of reherniation. Atlas et al¹⁶ reported a reoperation rate of 25% at 10-year follow-up of a study of patients with lumbar disk herniation, with the median time to reoperation 24 months. Carragee et al¹⁷ reported an 11.5% reherniation rate, with 6.5% reoperation at 5 years.

The objectives of augmentation of the nucleus pulposus following disk removal are to prevent disk height loss and the associated biomechanical and biochemical changes resulting from reduced disk height and volume. Use of an injectable biomaterial to restore disk volume and prevent loss of disk height is currently being evaluated. The ability of an injectable material to seal the disk and prevent or reduce the incidence of reherniation is also being studied.

Injectable Biomaterials for Nucleus Pulposus Augmentation

An injectable biomaterial is ideal for restoration of disk volume removed during diskectomy and for preventing loss of disk height. Flowable materials may be injected via a small incision, allowing minimally invasive access to the disk space. Fluids can interdigitate with the irregular surgical defects and may, depending on the material used, physically bond to the adjacent tissue. The use of an injectable material allows for complete filling of the disk, a task that is not possible with preformed implants. Complete filling allows pressurization of the annulus ensuring load transfer, and load sharing between the annulus and nucleus. Injectable biomaterials may also allow for incorporation and uniform dispersion of either or both cells and therapeutic agents. Growth factors, such as members of the bone morphogenetic protein (BMP), transforming growth factor (TGF), and insulin-like growth factor (IGF) families, may be valuable in enhancing the repair process. Inhibitors of inflammatory cytokines (e.g., interleukins, tumor necrosis factors) and proteases (e.g., matrix metalloproteinases) may act to retard matrix degradation and the potential effects of these cytokines on surrounding tissue and neural (especially nociceptive) structures.

Generally, the candidate biomaterials are injected as viscous fluids and then cured through methods such as thermosensitive cross-linking, pH-sensitive cross-linking, photopolymerization, or addition of a solidifying agent to form a gel-like substance. It is important to consider the amount of time it takes for the material to set. The setting time should be long enough to allow for accurate placement during the procedure yet short enough so as not to prolong the surgical procedure. If the material experiences a temperature change while curing, the increase in temperature should be small. Heat generated during this process should not cause harm to surrounding tissue. The viscosity or fluidity of the material should balance the need for the substance to remain at the site of its introduction into the disk, with the ability of the surgeon to manipulate its placement, and with the need to assure complete filling of the intradiskal space or voids. Ease in accessing the disk space also needs to be considered. For example, polymers that cure through a photopolymerization procedure could pose a problem due to a limited ability to access the small cavities of the disk space with light needed to initiate cross-linking.

Injectable biomaterials have been considered as an augment to a diskectomy for over 40 years. As early as 1962, Nachemson suggested the injection of room temperature vulcanizing silicone into a degenerated disk using an ordinary syringe.18 In 1974, Schneider and Oyen studied the use of silicone elastomer in the intervertebral disk.^19,20 Since then, injectable biomaterials or scaffolds have been developed that may act as a substitute for the disk nucleus pulposus, such as hyaluronic acid, fibrin glue, alginate, elastin-like polypeptides, collagen type 1 gel, and others. Several patents and publications have been issued concerning various injectable biomaterials that may have utility for nucleus augmentation, including cross-linkable silk elastin copolymer,^21–26 polyurethane-filled balloons,^27,28 collagen-polyethylene glycol (PEG),^29–31 chitosan,^32–34 various injectable synthetic polymers,³⁵ recombinant bioelastic materials,^36–38 light-curable PEG polymers,³⁹ and other multicomponent precursor systems.⁴⁰ Several groups are actively pursuing the development of an injectable biomaterial for use in the intervertebral disk.^41,42

Recent efforts have focused on the evaluation of a recombinant protein copolymer consisting of amino acid sequence blocks derived from silk and elastin structural proteins as an injectable biomaterial for augmentation of the nucleus pulposus. These proteins have been well-characterized over more than a decade of intensive research and development. The material appears to have ideal characteristics for the augmentation of the nucleus pulposus following diskectomy procedures. Cappello and coworkers have reported on the development and characterization of structural protein polymers, especially those derived from the structural proteins silk and elastin.^43,44

Only gold members can continue reading. Log In or Register to continue