Exogenous Collagen Crosslinking of the Intervertebral Disc Restores Joint Stability After Lumbar Posterior Decompression Surgery

Popovich, John M.; Yau, David; Chuang, Shih-Youeng; Hedman, Thomas P.

doi:10.1097/brs.0b013e3181e8b1d5

Cited by 12 publications

(12 citation statements)

References 11 publications

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“…The relative change in NZ after nuclectomy was larger than the relative change in the ROM, as has been reported previously 37–39. After NPP implantations, the NZ values in FE and LB improved significantly and those in AR tended to improve.…”

Section: Discussionsupporting

confidence: 80%

“…The relative change in NZ after nuclectomy was larger than the relative change in the ROM, as has been reported previously. [37][38][39] After NPP implantations, the NZ values in FE and LB improved significantly and those in AR tended to improve. These findings are clinically relevant because a reduction in NZ is associated with a decrease in spinal pain.…”

Section: Discussionmentioning

confidence: 97%

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Design, synthesis, imaging, and biomechanics of a softness‐gradient hydrogel nucleus pulposus prosthesis in a canine lumbar spine model

et al. 2012

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A hydrogel nucleus pulposus prosthesis (NPP) was designed to swell in situ, have intrinsic radiopacity, and restore intervertebral disc height and biomechanical functionality. These features were examined using an ex vivo canine lumbar model. Nine NPPs were implanted in five spines and their visibility was assessed on radiography, computed tomography (CT), and magnetic resonance imaging (MRI). The NPPs were visible on all imaging modalities and 8/9 NPPs stayed intact and in situ. Six other NPPs were tested biomechanically in six canine lumbar spines. Removal of the nucleus pulposus (nuclectomy) caused significant changes in biomechanical parameters. After implantation and swelling of the NPP, values were not significantly different from the native state for range of motion (ROM) of flexion-extension (FE) and lateral bending (LB), the neutral zone (NZ) of all motion directions, and the NZ stiffness (NZS) of FE. Biomechanical restoration by the NPP compared with the nuclectomized state was significant for the ROM of FE and axial rotation, the NZ of FE and LB, and the NZS of FE and LB. Disc height was significantly restored and 6/6 NPPs stayed intact and in situ. In conclusion, the NPPs swell in situ, have intrinsic radiopacity and restored disc height and aforementioned biomechanical properties.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 97%

Design, synthesis, imaging, and biomechanics of a softness‐gradient hydrogel nucleus pulposus prosthesis in a canine lumbar spine model

et al. 2012

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“…Degeneration of the IVD is commonly associated with back pain, a major chronic healthcare problem [Williams and Sambrook, 2011]. Current clinical treatments focus on alleviating pain as well as restoring the structure and function of the disc [Popovich et al, 2011]. Understanding the pathogenesis of IVD disorders will help provide a better approach to facilitate restoring the structure and function of the IVD.…”

mentioning

confidence: 99%

Overexpression of hTERT extends replicative capacity of human nucleus pulposus cells, and protects against serum starvation‐induced apoptosis and cell cycle arrest

Liang

Dai

et al. 2012

J of Cellular Biochemistry

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The nucleus pulposus (NP) cells are chondrocyte-like cells that are required for the resistance of compressive loads through the synthesis of collagen fibrils and proteoglycan aggrecans, and the generation of a hydrostatic swelling pressure, and thus play an important role in the intervertebral disc. Here, we report the production and characterization of an immortalized human NP cell line from normal NP cells using stable transfection of recombinant human telomerase reverse transcriptase (hTERT) gene. The hTERT-transfected NP cells exhibited morphological characteristics typical of native cells. When compared with the first generation of normal NP cells, the hTERT-transfected NP cells grew faster and had an increased level of IGF-1 and TGF-β gene expression. They were successfully passaged over 20 generations without significant change in the levels of type II collagen and proteoglycan aggrecan expression. In addition, they showed resistance to serum starvation-induced apoptosis, G1 cell cycle arrest, and gene expression of p53, CCNE1, Fas, and Caspase 3. Moreover, histology revealed that no tumorigenicity of NP cells over expressing hTERT was observed after they were implanted in nude mice. Taken together, an immortalized human NP cell line was established, which has an extended lifespan, retains phenotypic features similar to primary parent NP cells, and should provide a suitable model for studying the biology of NP cells.

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“…By impairing the structural integrity of the AF torsional ROM and torsional NZ of the FSU are increased [41]. The IVD loses elasticity and the capacity for energy preservation is diminished [41]. Cruciate damage to the AF also resulted in considerable disc height loss.…”

Section: Discussionmentioning

confidence: 99%

Feasibility of the annulus fibrosus repair with in situ gelating hydrogels – A biomechanical study

et al. 2018

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The surgical standard of care for lumbar discectomy leaves the annulus fibrosus (AF) defect unrepaired, despite considerable risk for a recurrent herniation. Identification of a viable defect repair strategy has until now been elusive. The scope of this ex vivo biomechanical study was to evaluate crosslinking hydrogels as potentially promising AF defect sealants, and provide a baseline for their use in combination with collagen scaffolds that restore disc volume. This study directly compared genipin crosslinked fibrin hydrogel (FibGen) as a promising preclinical candidate against a clinically available adhesive composed of glutaraldehyde and albumin (BioGlue). Forty-two bovine coccygeal functional spine units (FSU) were randomly allocated into four groups, namely untreated (control, n = 12), repaired with either one of the tested hydrogels (BioGlue, n = 12; FibGen, n = 12), or FibGen used in combination with a collagen hydrogel scaffold (FibGen+Scaffold, n = 6). All specimens underwent a moderate mechanical testing protocol in intact, injured and repaired states. After completion of the moderate testing protocol, the samples underwent a ramp-to-failure test. Lumbar discectomy destabilized the FSU as quantified by increased torsional range of motion (28.0° (19.1, 45.1) vs. 41.39° (27.3, 84.9), p<0.001), torsional neutral zone (3.1° (1.2, 7.7) vs. 4.8° (2.1, 12.1), Z = -3.49, p < 0.001), hysteresis(24.4 J (12.8, 76.0) vs. 27.6 J (16.4, 54.4), Z = -2.61, p = 0.009), with loss of both disc height (7.0 mm (5.0, 10.5) vs 6.1 mm (4.0, 9.3), Z = -5.16, p < 0.001) and torsional stiffness (0.76 Nmdeg-1 (0.38, 1.07) vs. 0.66 Nmdeg-1 (0.38, 0.97), Z = -3.98, p < 0.001). Most FibGen repaired AF endured the entire testing procedure whereas only a minority of BioGlue repaired AF and all FibGen+Scaffold repaired AF failed (6/10 vs. 3/12 vs. 0/6 respectively, p = 0.041). Both BioGlue and FibGen+Scaffold repaired AF partially restored disc height (0.47 mm (0.07, 2.41), p = 0.048 and 1.52 mm (0.41, 2.57), p = 0.021 respectively) compared to sham treatment (0.08 mm (-0.63, 0.88)) whereas FibGen-only repaired AF had no such effect (0.04 mm (-0.73, 1.13), U = 48.0, p = 1). The AF injury model demonstrated considerable change of FSU mechanics that could be partially restored by use of an AF sealant. While inclusion of a volumetric collagen scaffold led to repair failure, use of FibGen alone demonstrated clinically relevant promise for prevention of mechanical reherniation, outperforming an FDA approved sealant in this ex vivo test series.

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Exogenous Collagen Crosslinking of the Intervertebral Disc Restores Joint Stability After Lumbar Posterior Decompression Surgery

Cited by 12 publications

References 11 publications

Design, synthesis, imaging, and biomechanics of a softness‐gradient hydrogel nucleus pulposus prosthesis in a canine lumbar spine model

Design, synthesis, imaging, and biomechanics of a softness‐gradient hydrogel nucleus pulposus prosthesis in a canine lumbar spine model

Overexpression of hTERT extends replicative capacity of human nucleus pulposus cells, and protects against serum starvation‐induced apoptosis and cell cycle arrest

Feasibility of the annulus fibrosus repair with in situ gelating hydrogels – A biomechanical study

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