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1. Intervertebral Disc Mechanics With Nucleotomy: Differences Between Simple and Dual Loading

   https://doi.org/10.1115/1.4050538  

   Yang, Bo ; Klineberg, Eric ; O'Connell, Grace D. ( August 2021 , Journal of Biomechanical Engineering)

   null (Ed.)

   Abstract Painful herniated discs are treated surgically by removing extruded nucleus pulposus (NP) material (nucleotomy). NP removal through enzymatic digestion is also commonly performed to initiate degenerative changes to study potential biological repair strategies. Experimental and computational studies have shown a decrease in disc stiffness with nucleotomy under single loading modalities, such as compression-only or bending-only loading. However, studies that apply more physiologically relevant loading conditions, such as compression in combination with bending or torsion, have shown contradicting results. We used a previously validated bone–disc–bone finite element model (Control) to create a Nucleotomy model to evaluate the effect of dual loading conditions (compression with torsion or bending) on intradiscal deformations. While disc joint stiffness decreased with nucleotomy under single loading conditions, as commonly reported in the literature, dual loading resulted in an increase in bending stiffness. More specifically, dual loading resulted in a 40% increase in bending stiffness under flexion and extension and a 25% increase in stiffness under lateral bending. The increase in bending stiffness was due to an increase and shift in compressive stress, where peak stresses migrated from the NP–annulus interface to the outer annulus. In contrast, the decrease in torsional stiffness was due to greater fiber reorientation during compression. In general, large radial strains were observed with nucleotomy, suggesting an increased risk for delamination or degenerative remodeling. In conclusion, the effect of nucleotomy on disc mechanics depends on the type and complexity of applied loads. 

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2. A Robust Multiscale and Multiphasic Structure-Based Modeling Framework for the Intervertebral Disc

   https://doi.org/10.3389/fbioe.2021.685799  

   Zhou, Minhao ; Lim, Shiyin ; O’Connell, Grace D. ( June 2021 , Frontiers in Bioengineering and Biotechnology)

   A comprehensive understanding of multiscale and multiphasic intervertebral disc mechanics is crucial for designing advanced tissue engineered structures aiming to recapitulate native tissue behavior. The bovine caudal disc is a commonly used human disc analog due to its availability, large disc height and area, and similarities in biochemical and mechanical properties to the human disc. Because of challenges in directly measuring subtissue-level mechanics, such as in situ fiber mechanics, finite element models have been widely employed in spinal biomechanics research. However, many previous models use homogenization theory and describe each model element as a homogenized combination of fibers and the extrafibrillar matrix while ignoring the role of water content or osmotic behavior. Thus, these models are limited in their ability in investigating subtissue-level mechanics and stress-bearing mechanisms through fluid pressure. The objective of this study was to develop and validate a structure-based bovine caudal disc model, and to evaluate multiscale and multiphasic intervertebral disc mechanics under different loading conditions and with degeneration. The structure-based model was developed based on native disc structure, where fibers and matrix in the annulus fibrosus were described as distinct materials occupying separate volumes. Model parameters were directly obtained from experimental studies without calibration. Under the multiscale validation framework, the model was validated across the joint-, tissue-, and subtissue-levels. Our model accurately predicted multiscale disc responses for 15 of 16 cases, emphasizing the accuracy of the model, as well as the effectiveness and robustness of the multiscale structure-based modeling-validation framework. The model also demonstrated the rim as a weak link for disc failure, highlighting the importance of keeping the cartilage endplate intact when evaluating disc failure mechanisms in vitro . Importantly, results from this study elucidated important fluid-based load-bearing mechanisms and fiber-matrix interactions that are important for understanding disease progression and regeneration in intervertebral discs. In conclusion, the methods presented in this study can be used in conjunction with experimental work to simultaneously investigate disc joint-, tissue-, and subtissue-level mechanics with degeneration, disease, and injury. 

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3. Interjoint coupling of position sense reflects sensory contributions of biarticular muscles

   https://doi.org/10.1152/jn.00317.2019  

   Herter, Troy M. ; Kurtzer, Isaac ; Granat, Lauren ; Crevecoeur, Frédéric ; Dukelow, Sean P. ; Scott, Stephen H. ( April 2021 , Journal of Neurophysiology)

   null (Ed.)

   Perception of limb position and motion combines sensory information from spindles in muscles that span one joint (monoarticulars) and two joints (biarticulars). This anatomical organization should create interactions in estimating limb position. We developed two models, one with only monoarticulars and one with both monoarticulars and biarticulars, to explore how biarticulars influence estimates of arm position in hand ( x, y) and joint ( shoulder, elbow) coordinates. In hand coordinates, both models predicted larger medial-lateral than proximal-distal errors, although the model with both muscle groups predicted that biarticulars would reduce this bias. In contrast, the two models made significantly different predictions in joint coordinates. The model with only monoarticulars predicted that errors would be uniformly distributed because estimates of angles at each joint would be independent. In contrast, the model that included biarticulars predicted that errors would be coupled between the two joints, resulting in smaller errors for combinations of flexion or extension at both joints and larger errors for combinations of flexion at one joint and extension at the other joint. We also carried out two experiments to examine errors made by human subjects during an arm position matching task in which a robot passively moved one arm to different positions and the subjects moved their other arm to mirror-match each position. Errors in hand coordinates were similar to those predicted by both models. Critically, however, errors in joint coordinates were only similar to those predicted by the model with monoarticulars and biarticulars. These results highlight how biarticulars influence perceptual estimates of limb position by helping to minimize medial-lateral errors. NEW & NOTEWORTHY It is unclear how sensory information from muscle spindles located within muscles spanning multiple joints influences perception of body position and motion. We address this issue by comparing errors in estimating limb position made by human subjects with predicted errors made by two musculoskeletal models, one with only monoarticulars and one with both monoarticulars and biarticulars. We provide evidence that biarticulars produce coupling of errors between joints, which help to reduce errors. 

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4. Effective Modulation of Inflammation and Oxidative Stress for Enhanced Regeneration of Intervertebral Discs Using 3D Porous Hybrid Protein Nanoscaffold

   https://doi.org/10.1002/adma.202303021  

   Yang, Letao ; Bhujel, Basanta ; Hou, Yannan ; Luo, Jeffrey ; An, Seong Bae ; Han, Inbo ; Lee, Ki‐Bum ( July 2023 , Advanced Materials)

   Degeneration of fibrocartilaginous tissues is often associated with complex pro‐inflammatory factors. These include reactive oxygen species (ROS), cell‐free nucleic acids (cf‐NAs), and epigenetic changes in immune cells. To effectively control this complex inflammatory signaling, it developed an all‐in‐one nanoscaffold‐based 3D porous hybrid protein (3D‐PHP) self‐therapeutic strategy for treating intervertebral disc (IVD) degeneration. The 3D‐PHP nanoscaffold is synthesized by introducing a novel nanomaterial‐templated protein assembly (NTPA) strategy. 3D‐PHP nanoscaffolds that avoid covalent modification of proteins demonstrate inflammatory stimuli‐responsive drug release, disc‐mimetic stiffness, and excellent biodegradability. Enzyme‐like 2D nanosheets incorporated into nanoscaffolds further enabled robust scavenging of ROS and cf‐NAs, reducing inflammation and enhancing the survival of disc cells under inflammatory stress in vitro. Implantation of 3D‐PHP nanoscaffolds loaded with bromodomain extraterminal inhibitor (BETi) into a rat nucleotomy disc injury model effectively suppressed inflammation in vivo, thus promoting restoration of the extracellular matrix (ECM). The resulting regeneration of disc tissue facilitated long‐term pain reduction. Therefore, self‐therapeutic and epigenetic modulator‐encapsulated hybrid protein nanoscaffold shows great promise as a novel approach to restore dysregulated inflammatory signaling and treat degenerative fibrocartilaginous diseases, including disc injuries, providing hope and relief to patients worldwide.

    

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5. Upper Extremity Joint Torque Estimation Through an Electromyography-Driven Model

   https://doi.org/10.1115/1.4056255  

   Tahmid, Shadman ; Font-Llagunes, Josep M. ; Yang, James ( June 2023 , Journal of Computing and Information Science in Engineering)

   Abstract Cerebrovascular accidents like a stroke can affect the lower limb as well as upper extremity joints (i.e., shoulder, elbow, or wrist) and hinder the ability to produce necessary torque for activities of daily living. In such cases, muscles’ ability to generate forces reduces, thus affecting the joint’s torque production. Understanding how muscles generate forces is a key element to injury detection. Researchers have developed several computational methods to obtain muscle forces and joint torques. Electromyography (EMG) driven modeling is one of the approaches to estimate muscle forces and obtain joint torques from muscle activity measurements. Musculoskeletal models and EMG-driven models require necessary muscle-specific parameters for the calculation. The focus of this study is to investigate the EMG-driven approach along with an upper extremity musculoskeletal model to determine muscle forces of two major muscle groups, biceps brachii and triceps brachii, consisting of seven muscle-tendon units. Estimated muscle forces are used to determine the elbow joint torque. Experimental EMG signals and motion capture data are collected for a healthy subject. The musculoskeletal model is scaled to match the geometric parameters of the subject. Then, the approach calculates muscle forces and joint moment for two tasks: simple elbow flexion extension and triceps kickback. Individual muscle forces and net joint torques for both tasks are estimated. The study also has compared the effect of muscle-tendon parameters (optimal fiber length and tendon slack length) on the estimated results. 

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