Biomechanics of Intervertebral Disk Degeneration

Low-back pain often coincides with altered neuromuscular control, possibly due to changes in spine stability resulting from injury or degeneration, or due to effects of nociception. The relative importance of these mechanisms, and their possible interaction, are unknown. In spine bending, the bulk of the load is borne by the IVD, yet the acute effects of intervertebral disc (IVD) injury on bending mechanics have not been investigated. In the present study, we aimed to quantify the acute effects of a stab lesion of the disc on its mechanical properties, because such changes can be expected to elicit compensatory changes in neuromuscular control. L4/L5 spinal segments were collected from 27 Wistar rats within two hours after sacrifice and stored at −20℃. Following thawing, bending tests were performed to assess the intersegmental angle-moment characteristics. Specimens were loaded in right bending, left bending and flexion, before and after a stab lesion of the IVD fully penetrating the nucleus pulposus. In the angle-moment curves, we found reduced moments at equal bending angles after IVD lesion in left bending, right bending and flexion. Peak stiffness, peak moment, and hysteresis were significantly decreased (by 7.8–27.7 %) after IVD lesion in all directions. In conclusion, L4/L5 IVD lesion in the rat caused small to moderate acute changes in IVD mechanical properties. Our next steps will be to evaluate the longer term effects of IVD lesion on spine mechanics and the neural control of trunk muscles.

With the lack of effective treatments for low back pain, the use of extracellular matrix (ECM)-based biomaterials have emerged with undeniable promise for IVD regeneration. Decellularized scaffolds can recreate an ideal microenvironment inducing tissue remodeling and repair. In particular, fetal tissues have a superior regenerative capacity given their ECM composition. In line with this, we unraveled age-associated alterations of the nucleus pulposus (NP) matrisome. Thus, the aim of the present work was to evaluate the impact of ECM donor age on IVD de/regeneration.

Accordingly, we optimized an SDS (0.1 %, 1 h)-based decellularization protocol that preserves ECM cues in bovine NPs from different ages. After repopulation with adult NP cells, younger matrices showed the highest repopulation efficiency. Most importantly, cells seeded on younger scaffolds produced healthy ECM proteins suggesting an increased capacity to restore a functional IVD microenvironment. In vivo, only fetal matrices decreased neovessel formation, showing an anti-angiogenic potential.

Our findings demonstrate that ECM donor age has a strong influence on angiogenesis and ECM de novo synthesis, opening new avenues for novel therapeutic strategies for the IVD. Additionally, more appropriate 3D models to study age-associated IVD pathology were unveiled.

Intervertebral disc degeneration (IVDD) has been associated with causing chronic back pain. Lower back pain is a common cause of doctor’s visits and disability and affects 11.9% of the worldwide population. To the best of our knowledge, this work is the first to develop a tool for predicting the risk of IVDD using machine learning algorithms (MLAs) to aid in the earlier detection of the disease. MLAs utilized in this study include logistic regression, decision tree, artificial neural network, boosting, bagging, and random forest. The Synthetic Minority Oversampling Technique (SMOTE) method was performed on the unbalanced data set to up sample the minority class (patients with disc degeneration). The cluster-then-predict technique was also utilized to determine clusters in the data to be used as another risk factor or input variable into the classification algorithms. Results showed that the bagging algorithm developed the best-performing model. Results also demonstrated that the performance of the models improved after using the cluster-then-predict technique, which supports previous literature. Moreover, an improvement in the prediction of the minority class was also observed when the SMOTE method was applied. The finding from this study can be utilized to develop a predictive tool for the early detection of disc degeneration. This predictive tool can be used by doctors and physicians in the office with patients to closely monitor and assess disc degeneration risk.