Intervertebral disc (IVD) degeneration is the most common diagnosis for lower back pain, a debilitating condition that affects 15-30% of the United States population, with associated annual costs of $100 billion. Degeneration of the IVD often causes disc herniation, a condition in which tissue is extruded from the disc space and impinges on nearby nerves. Lumbar discectomy is the most frequent surgical treatment for herniated discs, during which portions of the disc tissue are resected to decompress affected nerve roots. However, this treatment has a high recurrence rate (5-15%), and often requires secondary intervention. For heavily degenerated discs, spinal fusion is typically employed. However, this procedure limits mobility and produces damage to adjacent discs over time. Several products are under development for disc tissue replacement including Newcleus (Zimmer) and NucleoFix (Replication Medical), with none approved for use in the United States. Clinical application of these devices has been limited due to migration out of the disc space, wear debris formation, and fatigue or fracture failure of the surrounding tissues. Thus, current surgical treatment options are inadequate for long-term disease management, and existing commercial implants do not sufficiently restore disc structure and function. Replacing the disc tissue with an injectable disc-like material may help restore IVD mechanical functionality and limit disease progression. This project is centered on the utilization of injectable plant-based gels that form in the intradiscal space to replace resected IVD tissue. The technology represents an important contribution to translational biomaterials research, and has the potential to significantly impact patient health and quality of life.
This I-Corps team has developed a technology based on the use of injectable, crosslinked carboxymethylcellulose (CMC) hydrogels for engineering intervertebral disc (IVD) tissue. CMC is a plant-derived, negatively-charged polysaccharide similar to those found in the native disc, which provides an environment more conducive to swelling, nutrient transport and extracellular matrix organization in comparison to inert polymers, such as poly(ethylene oxide). As a derivative of cellulose, the most abundant naturally occurring organic compound on the planet, CMC is inherently renewable and a "green" alternative to synthetic polymers and animal-derived proteins and polysaccharides used for the repair of cartilaginous tissues. Further, CMC is more cost-effective than other polysaccharides (i.e., chondroitin sulfate and hyaluronic acid) currently used for similar applications, and obviates risks associated with animal or bacterial by-products. In addition, the covalently crosslinked CMC gels are stable and not susceptible to enzymatic degradation by mucopolysaccharidases in humans (i.e., hyaluronidase), as the polysaccharide can only be cleaved by cellulase, an enzyme absent in humans. Evaluation of these in situ-forming hydrogels has demonstrated restoration of the mechanical function of injured discs in an animal explant model, and the mechanical properties (i.e., equilibrium Young's modulus) have been found to match those of native human disc tissue. Thus, these injectable cellulosic implants have the potential to significantly impact a sizable patient population suffering from pathological conditions associated with IVD injury and degeneration. The hydrogels have also been shown to exhibit tunable material properties and cytocompatibility, extending the possible applications beyond disc replacement, for uses such as soft tissue fillers or as cell carriers for regenerative therapies.
