BACKGROUND CONTEXT: The contribution of anatomical structures to the stability of the spine is of great relevance for diagnostic, prognostic and therapeutic evaluation of spinal pathologies. Although a plethora of literature is available, the contribution of anatomical structures is still not well understood. PURPOSE: We aimed to quantify the biomechanical relevance of each of the passive spinal structure trough deliberate biomechanical test series using a stepwise reduction approach on cadavers. STUDY DESIGN: Biomechanical cadaveric study. METHODS: Fifty lumbar spinal segments originating from 22 human lumbar cadavers were biomechanically tested in a displacement-controlled stepwise reduction study: the intertransverse ligaments, the supraspinous and interspinous ligaments, the facet joint capsules (FJC), the facet joints (FJ), the ligamentum flavum (LF), the posterior longitudinal ligament (PLL), and the anterior longitudinal ligament were subsequently reduced. In the intact state and after each transection step, the segments were physiologically loaded in flexion, extension, axial rotation (AR), lateral bending (LB) and with anterior (AS), posterior (PS) and lateral shear (LS). Thirty-two specimens with only minor degeneration, representing a reasonably healthy subpopulation, were selected for the here presented evaluation. Quantitative values for load and spinal level dependent contribution patterns for the anatomical structures were derived. RESULTS: Small variability between of the contribution patterns are observed. The intervertebral disc (IVD) is exposed to about 67% of the applied load in LB and during shear loading, but less by load in flexion, extension and AR (less than 35%). The FJ&FJC are the main stabilizers in AR with 49%, but provide only 10% of the stability in extension. Beside the IVD, the LF and the PLL contribute mainly in flexion (22% and 16%, respectively), while the ALL plays a major role during extension (40%) and also contributes during LB (15%). The contribution of the intertransverse ligaments and the supraspinous and interspinous ligaments are very small in all loading directions (<2% and <6%, respectively). CONCLUSION: The IVD takes the main load in LB and absorbs shear loading, while the FJ&FJC stabilize AR. The ALL resists extension while LF and PLL stabilize flexion. With the small variability of contribution patterns, suggesting distinct adaptation of the structures to one another, the biomechanical characteristics of one structure have to be put in context of the whole spinal segment.

Appropriate macrophage response to an implanted biomaterial is crucial for successful tissue healing outcomes. In this work we investigated how intrinsic topological cues from electrospun biomaterials and extrinsic mechanical loads cooperate to guide macrophage activation and macrophage-tendon fibroblast cross-talk. We performed a series of in vitro and in vivo experiments using aligned or randomly oriented polycaprolactone nanofiber substrates in both mechanically loaded and unloaded conditions. Across all experiments a disorganized biomaterial fiber topography was alone sufficient to promote a pro-inflammatory signature in macrophages, tendon fibroblasts, and tendon tissue. Extrinsic mechanical loading was found to strongly regulate the character of this signature by reducing pro-inflammatory markers both in vitro and in vivo. We observed that macrophages generally displayed a stronger response to biophysical cues than tendon fibroblasts, with dominant effects of cross-talk between these cell types observed in mechanical co-culture models. Collectively our data suggest that macrophages play a potentially important role as mechanosensory cells in tendon repair, and provide insight into how biological response might be therapeutically modulated by rational biomaterial designs that address the biomechanical niche of recruited cells.

Appropriate mechanical load is essential for tendon homeostasis and optimal tissue function. Due to technical challenges in achieving physiological mechanical loads in experimental tendon model systems, the research community still lacks well-characterized models of tissue homeostasis and physiological relevance. Toward this urgent goal, we present and characterize a novel ex vivo murine tail tendon explant model. Mouse tail tendon fascicles were extracted and cultured for 6 days in a load-deprived environment or in a custom-designed bioreactor applying low magnitude mechanical load (intermittent cycles to 1% strain, at 1 Hz) in serum-free tissue culture. Cells remained viable, as did collagen structure and mechanical properties in all tested conditions. Cell morphology in mechanically loaded tendon explants approximated native tendon, whereas load-deprived tendons lost their native cell morphology. These losses were reflected in altered gene expression, with mechanical loading tending to maintain tendon specific and matrix remodeling genes phenotypic of native tissue. We conclude from this study that ex vivo load deprivation of murine tendon in minimal culture medium results in a degenerative-like phenotype. We further conclude that onset of tissue degeneration can be suppressed by low-magnitude mechanical loading. Thus a minimal explant culture model featuring serum-free medium with low mechanical loads seems to provide a useful foundation for further investigations. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1383-1390, 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.

Background Vertebral endplate signal intensity changes visualized by magnetic resonance imaging termed Modic changes (MC) are highly prevalent in low back pain patients. Interconvertibility between the three MC subtypes (MC1, MC2, MC3) suggests different pathological stages. Histologically, granulation tissue, fibrosis, and bone marrow edema are signs of inflammation in MC1 and MC2. However, different inflammatory infiltrates and amount of fatty marrow suggest distinct inflammatory processes in MC2. Aims The aims of this study were to investigate (i) the degree of bony (BEP) and cartilage endplate (CEP) degeneration in MC2, (ii) to identify inflammatory MC2 pathomechanisms, and (iii) to show that these marrow changes correlate with severity of endplate degeneration. Methods Pairs of axial biopsies (n = 58) spanning the entire vertebral body including both CEPs were collected from human cadaveric vertebrae with MC2. From one biopsy, the bone marrow directly adjacent to the CEP was analyzed with mass spectrometry. Differentially expressed proteins (DEPs) between MC2 and control were identified and bioinformatic enrichment analysis was performed. The other biopsy was processed for paraffin histology and BEP/CEP degenerations were scored. Endplate scores were correlated with DEPs. Results Endplates from MC2 were significantly more degenerated. Proteomic analysis revealed an activated complement system, increased expression of extracellular matrix proteins, angiogenic, and neurogenic factors in MC2 marrow. Endplate scores correlated with upregulated complement and neurogenic proteins. Discussion The inflammatory pathomechanisms in MC2 comprises activation of the complement system. Concurrent inflammation, fibrosis, angiogenesis, and neurogenesis indicate that MC2 is a chronic inflammation. Correlation of endplate damage with complement and neurogenic proteins suggest that complement system activation and neoinnervation may be linked to endplate damage. The endplate-near marrow is the pathomechanistic site, because MC2 occur at locations with more endplate degeneration. Conclusion MC2 are fibroinflammatory changes with complement system involvement which occur adjacent to damaged endplates.

Purpose Dorsal screw-rod instrumentations are used for a variety of spinal disorders. Cross-links (CL) can be added to such constructs, however, no clear recommendations exist. This study aims to provide an overview of the available evidence on the effectiveness of CL, potentially allowing to formulate recommendations on their use. Methods A systematic literature review was performed on PubMed and 37 original articles were included and grouped into mechanical, biomechanical, finite element and clinical studies. The change in range of motion (ROM) was analyzed in mechanical and biomechanical studies, ROM, stiffness and stress distribution were evaluated in finite element studies and clinical outcome parameters were analyzed in clinical studies. Results A relative consistent reduction in ROM in axial rotation with CL-augmentation was reported, while minor and less consistent effects were observed in flexion–extension and lateral bending. The use of CLs was clinical beneficial in C1/2 fusion, while the limited clinical studies on other anatomic regions show no significant benefit for CL-augmentation. Conclusion While CL provides some additional axial rotation stability in most situations, lateral bending and flexion–extension are less affected. Based on clinical data, CL-augmentation can only be recommended for C1/2 instrumentations, while for other cases, further clinical studies are needed to allow for evidence-based recommendations.

Supervised exercise training has been shown to improve walking capacity in several studies of patients with intermittent claudication. However, data on long-term outcome are quite limited. The aim of this prospective study was to evaluate long-term effects of supervised exercise training on walking capacity and quality of life in patients with intermittent claudication. Patients and methods: Sixty-seven consecutive patients with intermittent claudication who completed a supervised 12-week exercise training program were asked for follow up evaluation 39 ± 20 months after program completion. Pain-free walking distance (PWD) and maximum walking distances (MWD) were assessed by treadmill test and several questionnaires. Results: Forty (60%) patients agreed to participate, 22 (33%) refused participation, and 5 (7%) died during follow-up. PWD and MWD significantly improved at completion of 12-weeks supervised exercise training as compared to baseline (PWD 114 ± 100 vs. 235 ± 248, p = 0.002; MWD 297 ± 273 vs. 474 ± 359, p = 0.001). Improvement of PWD and MWD could be maintained at follow up (197 ± 254, p = 0.014; 390 ± 324, p = 0.035, respectively) with non-smokers showing significantly better sustained PWD and MWD improvement as compared to baseline. Overall, walking capacity correlated with functional status of quality of life. Conclusions: Major findings of this investigation were that improvement in walking capacity is sustained after completion of supervised exercise training program with best results in patients who quitted or never smoked. Improved walking capacity is associated with increased functional status of quality of life.