Composite biomaterial repair strategy to restore biomechanical function and reduce herniation risk in an ex vivo large animal model of intervertebral disc herniation with varying injury severity

Abstract

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.

Using embedded alginate microparticles to tune the properties of in situ forming poly(N‐isopropylacrylamide)‐graft‐chondroitin sulfate bioadhesive hydrogels for replacement and repair of the nucleus pulposus of the intervertebral disc

“…Potted porcine IVDs (n = 7 per group) were loaded on an MTS 831 Elastomer Test System using cycles of compression and tension, as has been reported prior in biomechanical studies with human, 63 bovine, 19 , 64 and caprine IVD. 65 The motion segments were compressed to −1000 N and tensed to 100 N for 10 cycles at a rate of 0.1 Hz while maintained in a 37°C saline bath during testing.…”

Experimental and Computational Comparison of Intervertebral Disc Bulge for Specimen-Specific Model Evaluation Based on Imaging

“…Bovine caudal IVDs were used in this study due to the similarities to human discs (Beckstein et al, 2008) and the lack of facet joints; this tissue is also often used in preclinical assessment of intervertebral disc repair (e.g., Chan et al, 2010;Miles et al, 2016;Hom et al, 2019; among other groups). The tissue was obtained from food-chain animals for which no ethical approval was required.…”

Putting the Pieces in Place: Mobilizing Cellular Players to Improve Annulus Fibrosus Repair

“…44 Another AF sealant that has been extensively investigated and developed over the years is a fibrin-genipin (FibGen) hydrogel adhesive. [50][51][52][53][54]56,70,71 FibGen is composed of fibrinogen and thrombin, which are widely used as sealants due to their adhesive strength. 52 The mixture is crosslinked with genipin, a natural collagen cross-linking agent that links amino acid groups through intramolecular, intermolecular, and intermicrofibrillar bonds that enhance gel stiffness to approximate the shear properties of the native AF.…”

“…70 In a bovine ex vivo herniation model, AF repair with FibGen with or without NP replacement (using carboxymethylcellulose-methylcellulose) demonstrated failure at supraphysiologic stresses, suggesting that the biomaterials could improve the mechanical performance of the IVD compared to discectomy alone. 54 In vivo; small animal 10-to 12-week-old athymic rat 40,41,47,48 In vivo; large animal 4-to 7-year-old sheep morphological and biomechanical outcomes observed compared to untreated groups 12 months postinjury (Fig. 2b).…”