iridoids and Intervertebral-Disc-Displacement

Back pain commonly arises from intervertebral disc (IVD) damage including annulus fibrosus (AF) defects and nucleus pulposus (NP) loss. Poor IVD healing motivates developing tissue engineering repair strategies. This study evaluated a composite injectable IVD biomaterial repair strategy using carboxymethylcellulose-methylcellulose (CMC-MC) and genipin-crosslinked fibrin (FibGen) that mimic NP and AF properties, respectively. Bovine ex vivo caudal IVDs were evaluated in cyclic compression-tension, torsion, and compression-to-failure tests to determine IVD biomechanical properties, height loss, and herniation risk following experimentally-induced severe herniation injury and discectomy (4 mm biopsy defect with 20% NP removed). FibGen with and without CMC-MC had failure strength similar to discectomy injury suggesting no increased risk compared to surgical procedures, yet no biomaterials improved axial or torsional biomechanical properties suggesting they were incapable of adequately restoring AF tension. FibGen had the largest failure strength and was further evaluated in additional discectomy injury models with varying AF defect types (2 mm biopsy, 4 mm cruciate, 4 mm biopsy) and NP removal volume (0%, 20%). All simulated discectomy defects significantly compromised failure strength and biomechanical properties. The 0% NP removal group had mean values of axial biomechanical properties closer to intact levels than defects with 20% NP removed but they were not statistically different and 0% NP removal also decreased failure strength. FibGen with and without CMC-MC failed at super-physiological stress levels above simulated discectomy suggesting repair with these tissue engineered biomaterials may perform better than discectomy alone, although restored biomechanical function may require additional healing with the potential application of these biomaterials as sealants and cell/drug delivery carriers.

Topics: Animals; Annulus Fibrosus; Biocompatible Materials; Biomechanical Phenomena; Carboxymethylcellulose Sodium; Cattle; Cross-Linking Reagents; Disease Models, Animal; Diskectomy; Fibrin; Hydrogels; In Vitro Techniques; Injections, Spinal; Intervertebral Disc Displacement; Iridoids; Materials Testing; Methylcellulose; Nucleus Pulposus

The mechanical stability of cross-linked and control spinal motion segments was evaluated using neutral zone, range of motion (ROM), and instability score metrics.. To determine if exogenous cross-linking could increase the stability of spinal motion segments.. The microstructure of the anulus fibrosus extracellular matrix can affect the stability of the intervertebral joint. Parallel testing in our laboratory has shown that exogenous cross-linking can improve the fatigue resistance of anulus fibrosus.. There were 3 separate experimental protocols conducted. The first study used calf lumbar intervertebral joints randomly divided into a genipin cross-linked group and phosphate buffered saline-soaked controls. After 2 days of soaking, flexion-extension ramp cycles were applied to the specimens. The second study repeated the test protocol using 22 moderately and severely degenerated human lumbar intervertebral joints. The third experiment compared the effect of cross-linking treatment on human discs with known degrees of preexisting mechanical instability. Each data set was used to assess joint instability by 3 calculations: ROM, neutral zone, and an instability score. Joint instability for each data set was evaluated using 3 calculations: ROM, neutral zone, and a novel instability score.. These results show that cross-link augmentation can effectively reduce instability of intervertebral discs. The stabilizing effect was observed to be higher in the more mechanically unstable discs. However, cross-linking did not appear to affect the total range of sagittal motion.. By reducing the neutral zone, exogenous cross-linking may help combat the progression of instability in degenerative disc disease.

Topics: Adhesives; Animals; Biomechanical Phenomena; Cattle; Cross-Linking Reagents; Humans; In Vitro Techniques; Intervertebral Disc; Intervertebral Disc Displacement; Iridoid Glycosides; Iridoids; Joint Instability; Joints; Lumbar Vertebrae; Pyrans; Range of Motion, Articular