Novel High-Modulus Cell-Delivery Composite Biomaterial for Intervertebral Disc Repair and Regeneration

Lower back pain is the most common cause of disability, which domestically costs $134.5 billion per year. Back pain is strongly associated with intervertebral disc (IVD) pathologies like herniation, but the current standard of care for IVD herniation, discectomy, does not repair defects in the outer annulus fibrosus (AF) structure caused by the initial herniation. Defects in the AF can lead to accelerated degeneration, recurrent pain, and reherniation, highlighting a need to develop therapies capable of promoting IVD repair. Injectable cell delivery biomaterials are an attractive solution because they may provide immediate biomechanical stabilization after injury and deliver cells for long-term healing. However, research is required to develop high-modulus biomaterials that can be retained within the high loading environment of the IVD while supporting the function of delivered cells.

We developed a composite biomaterial for AF repair that uses cell-seeded, degradable oxidized alginate (OxAlg) microbeads to deliver AF cells seeded within high-modulus genipin-crosslinked fibrin (FibGen) hydrogels. The goal of this study was to evaluate the ability of this composite cell delivery biomaterial to repair bovine coccygeal IVDs in an ex-vivo loaded organ culture bioreactor system. We hypothesize that this composite will resist herniation, prevent disc height loss, and promote repair.

IVD viability in the organ culture system was confirmed by constant, low levels of nitric oxide and lactate dehydrogenase in the culture media at days 7, 21, and 42. Herniation risk was assessed by visual inspection of the repaired IVDs. The composite biomaterial remained in place after 96,000 cycles of compressive loading over 6 weeks without evidence for herniation. This herniation test is rigorous since very few ex-vivo studies test experimental IVD repair biomaterials for this many cycles or as extended a duration. Analysis of disc height change, the most sensitive metric for assessing IVD injury and repair, showed that injured IVDs had significantly greater disc height loss after 42-day culture than intact controls. Excitingly, repaired IVDs experienced significantly less disc height loss than injured IVDs, which was similar to intact controls. Future analyses will assess stiffness, track the fate of delivered AF cells, and measure extracellular matrix synthesis.

Overall, this work shows that FibGen hydrogels with AF cell-seeded OxAlg microbeads restore lost disc height without herniation and may offer promise for AF repair. This cell delivery composite, designed to balance biological and biomechanical performance, may also have relevance to repairing other tissues with limited regeneration and high mechanical demands.