The relation between the biochemical composition of knee articular cartilage and quantitative MRI: a systematic review and meta-analysis.

OBJECTIVE: Early and non-invasive detection of osteoarthritis (OA) is required to enable early treatment and monitoring of interventions. Some of the earliest signs of OA are the change in proteoglycan and collagen composition. The aim of this study is to establish the relations between quantitative magnetic resonance imaging (MRI) and biochemical concentration and organization in knee articular cartilage. METHODS: A preregistered systematic literature review was performed using the databases PubMed and Embase. Papers were included if quantitative MRI and a biochemical assay or polarized light microscopy (PLM) was performed on knee articular cartilage, and a quantified correlation was described. The extracted correlations were pooled using a random effects model. RESULTS: 21 papers were identified. The strongest pooled correlation was found for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) vs proteoglycan concentration (r = 0.59). T1ρ relaxation times are inversely correlated to proteoglycan concentration (r = -0.54). A weak correlation between T2 relaxation times and proteoglycans was found (r = -0.38). No correlation between T2 relaxation time and collagen concentration was found (r = -0.02). A heterogeneous set of correlations between T2 relaxation times and PLM were identified, including strong correlations to anisotropy. CONCLUSION: DGEMRIC measures are significantly correlated to proteoglycan concentration. The needed contrast agent is however a disadvantage; the T1ρ sequence was found as a non-invasive alternative. Remarkably, no correlation was found between T2 relaxation times and collagen concentration. T2 relaxation times is related to organization, rather than concentration of collagen fibers. PROSPERO ID: CRD42020168337.

Modelling the catabolic environment of the moderately degenerated disc with a caprine ex vivo loaded disc culture system.

Low-back pain affects 80 % of the world population at some point in their lives and 40 % of the cases are attributed to intervertebral disc (IVD) degeneration. Over the years, many animal models have been developed for the evaluation of prevention and treatment strategies for IVD degeneration. Ex vivo organ culture systems have also been developed to better control mechanical loading and biochemical conditions, but a reproducible ex vivo model that mimics moderate human disc degeneration is lacking. The present study described an ex vivo caprine IVD degeneration model that simulated the changes seen in the nucleus pulposus during moderate human disc degeneration. Following pre-load under diurnal, simulated physiological loading (SPL) conditions, lumbar caprine IVDs were degenerated enzymatically by injecting collagenase and chondroitinase ABC (cABC). After digestion, IVDs were subjected to SPL for 7 d. No intervention and phosphate-buffered saline injection were used as controls. Disc deformation was continuously monitored to assess disc height recovery. Histology and immunohistochemistry were performed to determine the histological grade of degeneration, matrix expression, degrading enzyme and catabolic cytokine expression. Injection of collagenase and cABC irreversibly affected the disc mechanical properties. A decrease in extracellular matrix components was found, along with a consistent increase in degradative enzymes and catabolic proteins [interleukin (IL)-1ß, -8 and vascular endothelial growth factor (VEGF)]. The changes observed were commensurate with those seen in moderate human-IVD degeneration. This model should allow for controlled ex vivo testing of potential biological, cellular and biomaterial treatments of moderate human-IVD degeneration.

Early changes in the extracellular matrix of the degenerating intervertebral disc, assessed by Fourier transform infrared imaging.

OBJECTIVE: Mechanical overloading induces a degenerative cell response in the intervertebral disc. However, early changes in the extracellular matrix (ECM) are challenging to assess with conventional techniques. Fourier Transform Infrared (FTIR) imaging allows visualization and quantification of the ECM. We aim to identify markers for disc degeneration and apply these to investigate early degenerative changes due to overloading and katabolic cell activity. DESIGN: Three experiments were conducted; Exp 1.: In vivo, lumbar spines of seven goats were operated: one disc was injected with chondroitinase ABC [cABC (mild degeneration)] and compared to the adjacent disc (control) after 24 weeks. Exp 2a: Ex vivo, caprine discs received physiological loading (n = 10) or overloading (n = 10) in a bioreactor. Exp 2b: Cell activity was diminished prior to testing by freeze-thaw cycles, 18 discs were then tested as in Exp 2a. In all experiments, FTIR images (spectral region: 1000-1300 cm-1) of mid-sagittal slices were analyzed using multivariate curve resolution. RESULTS: In vivo, FTIR was more sensitive than biochemical and histological analysis in identifying reduced proteoglycan content (P = 0.046) and increased collagen content in degenerated discs (P < 0.01). Notably, FTIR analysis additionally showed disorganization of the ECM, indicated by increased collagen entropy (P = 0.011). Ex vivo, the proteoglycan/collagen ratio decreased due to overloading (P = 0.047) and collagen entropy increased (P = 0.047). Cell activity affected collagen content only (P = 0.044). CONCLUSION: FTIR imaging allows a more detailed investigation of early disc degeneration than traditional measures. Changes due to mild overloading could be assessed and quantified. Matrix remodeling is the first detectable step towards intervertebral disc degeneration.

Mechanics and biology in intervertebral disc degeneration: a vicious circle.

Intervertebral disc degeneration is a major cause of low back pain. Despite its long history and large socio-economical impact in western societies, the initiation and progress of disc degeneration is not well understood and a generic disease model is lacking. In literature, mechanics and biology have both been implicated as the predominant inductive cause; here we argue that they are interconnected and amplify each other. This view is supported by the growing awareness that cellular physiology is strongly affected by mechanical loading. We propose a vicious circle of mechanical overloading, catabolic cell response, and degeneration of the water-binding extracellular matrix. Rather than simplifying the disease, the model illustrates the complexity of disc degeneration, because all factors are interrelated. It may however solve some of the controversy in the field, because the vicious circle can be entered at any point, eventually leading to the same pathology. The proposed disease model explains the comparable efficacy of very different animal models of disc degeneration, but also helps to consider the consequences of therapeutic interventions, either at the cellular, material or mechanical level.

Poroelastic behaviour of the degenerating human intervertebral disc: a ten-day study in a loaded disc culture system.

The intervertebral disc (IVD) allows flexibility to the vertebral column, and transfers the predominant axial loads during daily activities. Its axial biomechanical behaviour is poroelastic, due to the water-binding and releasing capacity of the nucleus pulposus. Degeneration of the intervertebral disc presumably affects both the instantaneous elastic response to the load on the IVD and the subsequent interstitial flow of fluid. This study aims to quantify the poroelastic behaviour of the IVD and its change with degeneration, as defined by the magnetic resonance imaging-based Pfirrmann Score (PS). For a period of ten days, 36 human lumbar IVDs were loaded with a simulated physiological axial loading regime, while deformation was monitored. The IVDs responded to the loads with instantaneous elastic and slow poroelastic axial deformation. Several mechanical parameters changed throughout the first five days of the experiment, until the IVDs settled into a dynamic equilibrium. In this equilibrium, degeneration was significantly related to a decrease in disc height loss during the daytime high load phase (ρ = -0.49), and to a decrease in the rate of this deformation during the final half hour of each day (ρ = -0.53). These properties were related to the nucleus glycosaminoglycan/hydroxyproline (GAG/HYP) ratio, rather than GAG content alone, indicating that remodelling of the extracellular matrix reduces poroelastic properties of the IVD. This implies that the degenerated discs have a reduced capacity to bind water and/or a reduced resistance against fluid flow. The resulting loss in hydrostatic pressure may further change cell behaviour in the nucleus pulposus.

Minced Autologous Chondral Fragments with Fibrin Glue as a Simple Promising One-Step Cartilage Repair Procedure: A Clinical and MRI Study at 12-Month Follow-Up.

OBJECTIVE: The aim of this study was to investigate early radiological and clinical outcome of autologous minced cartilage treatment as a single-step treatment option in patients with a chondral or osteochondral lesion (OCL) in the knee. DESIGN: Eighteen patients with an OCL in the knee were included. Cartilage from healthy-appearing loose bodies and/or the periphery of the defect were minced into small chips and sealed in the defect using fibrin glue. Preoperatively, and at 3 (n = 14) and 12 (n = 18) months follow-up, magnetic resonance imaging (MRI) was performed. The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 score was used to assess the cartilage repair tissue on MRI at 12 months. The International Knee Documentation Score, Knee Injury and Osteoarthritis Outcome Score, EuroQoL-5D, and Visual Analogue Scale pain were collected preoperatively and 12 months after surgery. RESULTS: Three months postoperative, MRI showed complete defect filling in 11 out of 14 patients. Mean MOCART 2.0 score at 12 months was 65.0 ± 18.9 with higher scores for lateral femoral chondral lesions compared to medial femoral chondral lesions (75.8 ± 14.3, 52.5 ± 15.8 respectively, P = 0.02). Clinical and statistical significant improvements were observed in the patient-reported outcome measures at 12 months postoperatively compared to preoperatively. CONCLUSION: Treatment of OCLs using the autologous minced cartilage procedure resulted in good cartilage repair measured by MOCART 2.0. Clinically relevant improvements were observed in the clinical scores. This study suggests autologous minced cartilage as a promising, single-step treatment for OCLs.

Data-driven quantification of the effect of wind on athletics performance.

So far, the relationship between wind and athletics performance has been studied mainly for 100 m sprint, based on simulation of biomechanical models, requiring several assumptions. In this study, this relationship is quantified empirically for all five horizontal jump and sprint events where wind is measured, with freely available competition results. After systematic scraping several elite and sub-elite results sites, the obtained results (n = 150,169) were filtered and matched to athletes. A quadratic mixed effects model with athlete and season as random effects was applied to express the influence of wind velocity on performance in each event. Whether this effect differs with performance level was investigated by applying the model on subgroups based on performance level. In the fitted quadratic model, the linear coefficients were significant (p < .001) for all events; the quadratic coefficients were significant for all events (p < .001) except long jump (p = .138). A 2.0 m s-1 tail wind provides an average advantage of 0.125, 0.140 and 0.146-s for the 100, 200 and 100/110 m hurdles, respectively, and an advantage of 0.058 and 0.102 m for long jump and triple jump, respectively. Performance level had a significant effect on the wind influence only for 100 m (p < .001). Amateur athletes (∼13 s) benefit 69% more from a 2.0 m s-1 tail wind than elite athletes (∼10 s). Practical formulas are presented for each event. These can easily be used correct results for wind speed, allowing better talent scouting and championship selection. This study demonstrates the efficacy of answering scientific questions empirically, through freely available data.

Translational challenges for the development of a novel nucleus pulposus substitute: Experimental results from biomechanical and in vivo studies.

Nucleus pulposus replacement therapy could offer a less invasive alternative to restore the function of moderately degenerated intervertebral discs than current potentially destructive surgical procedures. Numerous nucleus pulposus substitutes have already been investigated, to assess their applicability for intradiscal use. Still, the current choice of testing methods often does not lead to efficient translation into clinical application. In this paper, we present the evaluation of a novel nucleus pulposus substitute, consisting of a hydromed core and an electrospun envelope. We performed three mechanical evaluations and an in vivo pilot experiment. Initially, the swelling pressure of the implant was assessed in confined compression. Next, we incorporated the implant into mechanically damaged caprine lumbar intervertebral discs to determine biomechanical segment behaviour in bending and torsion. Subsequently, segments were serially tested in native, damaged and repaired conditions under dynamic axial compressive loading regimes in a loaded disc culture system. Finally, nucleus pulposus substitutes were implanted in a live goat spine using a transpedicular approach. In confined compression, nucleus pulposus samples as well as implants showed some load-bearing capacity, but the implant exhibited a much lower absolute pressure. In bending and torsion, we found that the nucleus pulposus substitute could partly restore the mechanical response of the disc. During dynamic axial compression in the loaded disc culture system, on the other hand, the implant was not able to recover axial compressive behaviour towards the healthy situation. Moreover, the nucleus pulposus substitutes did not remain in place in the in vivo situation but migrated out of the disc area. From these results, we conclude that implants may mimic native disc behaviour in simple mechanical tests, yet fail in other, more realistic set-ups. Therefore, we recommend that biomaterials for nucleus pulposus replacement be tested in testing modalities of increasing complexity and in their relevant anatomical surroundings, for a more reliable prediction of clinical potential.