1. Introduction

Low back pain has a tremendous impact on society. Its damage is felt not only in the morbidity of afflicted individuals, but also through lost productivity and increased health care costs. Low back pain is the second leading cause of work absenteeism in this country, and it leads to more productivity loss than any other medical condition. (1)

Every year in the United States, more than $33 billion is spent on health care for low back pain. When additional costs such as disability and lost productivity are included, total costs for low back pain in this country are more than $100 billion per year.( )2 Approximately 80% of adults in the U.S. will experience low back pain that will affect their activities of daily living at some point during their lives; 1-2% of these individuals will require surgery. (3) The first episode of low back pain typically occurs in the third decade of life. The incidence of low back pain peaks between ages 55-64, and then decreases.

Intervertebral disc pathology is a common cause of low back pain. (4) Disc disorders encompass many conditions ranging from subtle disc degeneration to dramatic disc herniation. Annually, an estimated 4.1 million people in the United States report a prolapsed disc. Despite the high incidence and degree of morbidity associated with intervertebral disc disorders, there is little agreement regarding their etiology. In order to understand intervertebral disc disorders, it is useful to review the anatomy of the disc.

2. Anatomy of the Intervertebral Disc

The fibrocartilaginous intervertebral disc is a complex structure that supports the weight of the upper body while permitting a significant range of motion. Because of its viscoelastic properties, the disc dampens the impulses applied to the vertebral body. The disc is able to withstand forces of compression, bending, shear, and torsion because of the unique combination of materials forming the disc. The disc is composed of three histologically different, yet functionally and physically interdependent elements: 1) the nucleus pulposus, 2) the anulus fibrosus, and 3) the cartilaginous end plates.

The nucleus pulposus is a viscid, mucoprotein gel that is located in the center of the disc. The nucleus has a high water content, high fixed charge density, and random orientation of collagen fibrils. The composition of the nucleus allows it to function under hydrostatic pressure to distribute loads from the spine onto the superior and inferior vertebral body end-plates and the inner lamina of the anulus fibrosus.(5)

Positioned on the periphery of the nucleus, the anulus fibrosus forms the outer, lateral boundary of the disc. The anulus fibrosus consists of a series of 15 to 25 lamellae that create a network between the adjacent vertebral bodies. (6) The lamellae are composed of coarse collagen fibers that run parallel within each lamella and obliquely at approximately a 60-degree angle to the fibers in adjacent lamellae. (7) There are occasional areas of asymmetry that interrupt this tidy arrangement of collagen fiber bundles. In particular, the postero-lateral portions of the anulus experience the majority of incomplete laminae and asymmetrical collagen fiber bundle organization. Similar to the arrangement of plies in a modern automobile tire, the organization of collagen fibers and laminae in the anulus fibrosus allows the anulus to contain hydrostatic pressure loads. The anulus is also able to provide resistance to minor displace-ments of the adjacent vertebral bodies because of the variation in fiber orientation.

The endplate covers the cranial and caudal surfaces of the intervertebral disc while serving as the interface between the nucleus pulposus and the neighboring intervertebral bodies. Although it is composed of a thin layer of hyaline cartilage, the endplate lacks the zones of fibrillar and cellular organization characteristic of articular hyaline cartilage. The endplate's col-lagen fibers are oriented horizontally and parallel to the vertebral body surface. With its collagen fibers in this orientation, the endplate can best withstand the tension generated in the inner anulus. Another level of support is derived from the continuity between these collagen fibers of the endplate and the fibers of the inner third of annular lamellae. (8) At the juncture between the anulus and the vertebral epiphysis, elastin fibers contribute to the disc's flexibility and durability. (9)

The avascular nucleus receives most of its nutrition via diffusion through the endplate. Solutes are transported between the well-vascularized vertebral body and the disc nucleus via capillaries as well as areas of the vertebral bone marrow, which have direct contact with the hyaline cartilage of the central endplate. (10-14)

Approximately 95% of herniated intervertebral discs occur at the L4 and L5 levels in people between the ages of 25 and 55 years. (15,16) The high prevalence of pathology at L4 and L5 can be explained by several factors unique to the lower lumbar spine. First, the posterior longitudinal ligament is narrow at this level, and thus provides less support to the posterior anulus. Second, this site experiences a great deal of flexion, bending, and tor-sion, placing greater structural demands on the connective tis-sues. Finally, lumbar lordosis causes the vertebrae at L4 and L5 to bear more force in shear.(17) Although the disc between L5 and S1 is usually the smallest of the lower three lumbar discs, it bears the heaviest loads. Thus, L5-S1 disc stresses are much greater than those found in the other lumbar discs. (18) (Fig. 1) While disc degeneration typically begins in the lower lumbar spine, it progresses to successively higher levels as the affected discs become stiffer and an increased demand is placed on the superiorly adjacent discs. (19,20) Understanding the pathophysiol-ogy of disc degeneration helps explain why disc degeneration is more likely to occur in people who exert themselves either too much or too little.

3. Treatment for Disc Herniation

Surgical intervention is indicated for patients who have pain refractory to 6-8 weeks of non-operative therapy. (25) Any patient with a neurologic deficit secondary to disc herniation should be considered an operative candidate initially. Current surgical interventions for isolated herniated discs include microdiscectomy, routine laminotomy, and modern endoscopic approaches. (21,22) These approaches lead to disc height collapse with subsequent foraminal narrowing. At the present time, there has been no development of a satisfactory replace-ment for the intervertebral disc.

4. Risk Factors for Disc Degeneration

The literature emphasizes two categories of risk factors associated with back pain: extrinsic and intrinsic. Extrinsic risks include heavy physical labor, frequent bending and twist-ing, lifting and forceful movements, repetitive work, vibration, sedentary office work, and smoking. Truck drivers, (23) athletes (24) , and nurses (25) are more likely than others to suffer from back pain. Intrinsic risk factors for disc degeneration include undesirable anthropometric characteristics, spinal abnormalities, and genetic predispositions.

Goals of Present Study:

Intervertebral disc pathology is a common cause of low back pain. When disc degeneration occurs, a collapse of the disc space occurs. This collapse leads to neuroforaminal narrowing and nerve impingement. This nerve encroachment may cause significant pain, weakness, and disability. Furthermore, disc degeneration creates a disruption of the normal spinal biomechanics, with resultant instability leading to further potential injury and pain.

Previous attempts to develop a nucleus replacement have involved the use of hydrogels. (26) The poor results of these stud-ies have been due in part to the limited expansile properties of the hydrogels and their failure to withstand significant loads.

Work is currently underway at the Beth Israel Deaconess Medical Center (BIDMC) Orthopaedic Biomechanics Laboratory (OBL) to determine whether a bioelastic polymer is an appropriate material to replace an early degenerated nucleus pulposus of the intervertebral disc. The polymers being studied are made of pentapeptides consisting of glycine-valine-glycine- valine-proline. These polymers may have as many as 10-250 repeat sequences linked together. A fundamental property of bioelastic polypeptides is an inverse phase transition in which hydrophobic folding occurs as the temperature is elevated. This inverse temperature behavior provides a unique feature to bioelastic polypeptides which results in these materials being readily soluble at room temperature. The elastic matrices are produced by cross-linking the individual polymer chains, which is readily accomplished by gamma irradiation. Furthermore, the basic amino acid sequence can be modified to insert cell attachment sequences or impart other bioactive characteristics. The materials may also function as delivery matrices for bioactive substances, such as angiogenic factors, growth factors, antimicrobials, or vectors for gene delivery.

This initial study will assess the biomechanical stability of a cadaveric motion segment(one disc and the adjacent vertebral bodies) with and without the application of the bioelastic polymer as a nuclear replacement. Specifically, we will perform sta-tic loading of the motion segments before and after discectomy, and following the application of the polymer. The testing will involve loading in axial compression, flexion and extension, lat-eral side bending and axial rotation. We will also perform creep testing and non-destructive cyclic loading experiments.

The current salvage surgical approach for the treatment of facet joint arthritis often involves spinal fusion. The application of a nuclear disc replacement may limit this type of surgical intervention and thus preserve spinal motion.

The goals of injecting the bioelastic polymer into the disc space are to restore the biomechanical stability of the motion segment and to restore the intervertebral foraminal height. The advantages of this type of approach to the treatment of disc degeneration are numerous. The polymer could be delivered to the intervertebral space in a minimally invasive manner, using fluoroscopic guidance. This would limit the patient morbidity and hospital stay as compared to modern surgical intervention for disc herniations. Furthermore, the late com-plications of disc collapse, failed back syndrome, and post-operative facet joint arthropathy following disc surgery could be minimized.