Article
Biochemistry & Molecular Biology
Andreas S. Croft, Ysaline Roth, Katharina A. C. Oswald, Slavko Corluka, Paola Bermudez-Lekerika, Benjamin Gantenbein
Summary: The study revealed that excessive torsion combined with compression may lead to key features of intervertebral disc degeneration (IDD), such as significant loss of relative disc height, decreased cell viability, and reduced glycosaminoglycan content in the tissue. Additionally, in the high-stress regime, the mechanosensitive gene CILP was significantly downregulated, and the Hippo-pathway gene MST1 was significantly upregulated, suggesting a potential correlation between IDD and the Hippo-YAP/TAZ pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Andrea Vernengo, Helen Bumann, Nadine Kluser, Astrid Soubrier, Amra Secerovic, Jan Gewiess, Jan Ulrich Jansen, Cornelia Neidlinger-Wilke, Hans-Joachim Wilke, Sibylle Grad
Summary: Chemonucleolysis is an established method for creating organ culture models of intervertebral disc degeneration. The effects of different enzymes used in chemonucleolysis need to be compared to gain a better understanding of how these models mimic human degeneration. The study induced chemonucleolysis in bovine IVDs and evaluated the cellular, biochemical, and histological properties after 7 days.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Orthopedics
Shangbin Cui, Wenyue Li, Graciosa Q. Teixeira, Cornelia Neidlinger-Wilke, Hans-Joachim Wilke, Lisbet Haglund, Hongwei Ouyang, R. Geoff Richards, Sibylle Grad, Mauro Alini, Zhen Li
Summary: This study investigates the spatial and temporal changes of aggrecan and collagen neoepitopes during intervertebral disc degeneration. The results show that different degeneration types are associated with specific neoepitope expression profiles, which may serve as biomarkers for early disc degeneration and indicators of different degeneration phenotypes.
Article
Biochemistry & Molecular Biology
Franziska Widmayer, Cornelia Neidlinger-Wilke, Fiona Witz, Jan U. Jansen, Anita Ignatius, Melanie Haffner-Luntzer, Graciosa Q. Teixeira
Summary: Postmenopausal women have an increased risk of intervertebral disc degeneration, possibly due to decreased estrogen levels. This study investigated the effects of 17-beta-estradiol (E2) and low-magnitude, high-frequency vibration (LMHFV) on intervertebral discs (IVDs). The results showed that E2 treatment had minor effects on gene expression, cellularity, and matrix metabolism, while LMHFV alone led to cell loss and increased production of IL-6. However, the combination of E2 and LMHFV had a protective effect against cell loss and decreased IL-6 production.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Maria Molinos, Morena F. Fiordalisi, Joana Caldeira, Catarina R. Almeida, Mario A. Barbosa, Raquel M. Goncalves
Summary: Aging is a major cause of intervertebral disc degeneration and low back pain. In this study, the main alterations in nucleus pulposus (NP) cells with aging were investigated using bovine coccygeal discs from young and old animals. The results showed that elderly NP cells exhibited upregulated expression of bIL-6 and bMMP1 genes, as well as decreased percentages of CD29+, CD44+, CD45+, and Tie2+ cells compared to young NP cells. However, the expression of GD2, CD146, Stro-1, and CD34 remained consistent with age. Morphological analysis also revealed that aging increased NP cell area, diameter, and vesicles. These findings provide insights into NP cell aging and identify potential targets for mitigating age-related disc diseases.
Article
Engineering, Biomedical
Aapo Ristaniemi, Amra Secerovic, Vincent Dischl, Francesco Crivelli, Sarah Heub, Diane Ledroit, Gilles Weder, Sibylle Grad, Stephen J. Ferguson
Summary: The physiological and degenerative levels of maximum principal strains and stresses in bovine intervertebral disc tissue were determined through finite element analysis. It was found that when applying 0.1 MPa of compression and +/- 2-3 degrees of flexion and +/- 1-2 degrees of torsion, the mechanical parameters remained at physiological levels. However, with +/- 6-8 degrees of flexion in combination with +/- 2-4 degrees of torsion, the stresses in the outer annulus fibrosus exceeded degenerative levels. These findings provide important guidelines for bioreactor experiments with bovine intervertebral discs.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2023)
Article
Clinical Neurology
Mohamad Kanan, Oliver Eby, Amey Kelkar, Hassan Serhan, Yehuda Zodak, Sulaiman Aldoohan, Haitham Elsamaloty, Vijay Goel, Eda Yildirim-Ayan
Summary: This study investigates the effectiveness of electrical stimulation as an early intervention method for degenerative disc disease. The results show that electrical stimulation can promote the regeneration of intervertebral discs and prevent nucleus pulposus herniation.
Article
Chemistry, Multidisciplinary
Zhiwei Liao, Hui Liu, Liang Ma, Jie Lei, Bide Tong, Gaocai Li, Wencan Ke, Kun Wang, Xiaobo Feng, Wenbin Hua, Shuai Li, Cao Yang
Summary: EVs deliver antioxidant proteins to protect against pyroptosis of nucleus pulposus cells; Cavin-2-modified engineering EVs exhibit an improved uptake rate in TNF-alpha-treated NPCs, ameliorating cell death and retarding IDD progression.
Article
Materials Science, Multidisciplinary
Wanqing Xie, Yuan Xing, Li Xiao, Pu Zhang, Richard Oh, Yangpu Zhang, Xiaoyu Yu, Yi He, Eunha G. Oh, Ruofan Cao, Melur K. Ramasubramanian, Yong Wang, Li Jin, Jose Oberhozler, Xudong Li
Summary: This study developed an ex vivo organ-on-a-chip model to investigate the effects of mechanical loading and nutrition on intervertebral disc health. The cultured discs in the optimized system showed preferred disc health similar to native discs for up to 21 days, while discs in a static culture showed degenerative changes. The Disc-on-a-Chip(MF) system provides a valuable platform for studying disc health and degeneration, as well as testing new therapies.
ADVANCED MATERIALS TECHNOLOGIES
(2023)
Article
Chemistry, Applied
Wei Guo, Luzia Douma, Ming Hsien Hu, David Eglin, Mauro Alini, Sibylle Grad, Xinsheng Peng, Xuenong Zou, Matteo D'Este, Marianna Peroglio
Summary: A hybrid IPN hydrogel based on covalently cross-linked HA and HA-pNIPAM was developed, showing good physicochemical properties and supporting cell encapsulation and matrix deposition in in vitro and ex vivo models. The results suggest the therapeutic potential of this HA-based IPN hydrogel for IVD regeneration.
CARBOHYDRATE POLYMERS
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Marcus Raudner, Markus M. Schreiner, Tom Hilbert, Tobias Kober, Michael Weber, Anna Szelenyi, Reinhard Windhager, Vladimir Juras, Siegfried Trattnig
Summary: The study evaluated GRAPPATINI, an accelerated T-2 mapping sequence that combines undersampling and model-based reconstruction to facilitate clinical implementation of T-2 mapping of the lumbar intervertebral disc. Results showed that T2 values obtained using GRAPPATINI were significantly different for normal discs compared to bulging or herniated discs, as well as discs with and without annular tears. The study concluded that GRAPPATINI can be used as a quantitative imaging biomarker to detect disc pathologies while significantly reducing acquisition time.
EUROPEAN RADIOLOGY
(2021)
Review
Orthopedics
Shirley N. Tang, Andres F. Bonilla, Nadeen O. Chahine, Aimee C. Colbath, Jeremiah T. Easley, Sibylle Grad, Lisbet Haglund, Christine L. Le Maitre, Victor Leung, Annette M. McCoy, Devina Purmessur, Simon Y. Tang, Stephan Zeiter, Lachlan J. Smith
Summary: Intervertebral disc degeneration is a common cause of low back pain, and appropriate preclinical models are crucial for research and treatment development. This article presents contrasting arguments for in vivo animal models and ex vivo organ culture models for disc studies, aiming to reach a consensus on model selection and implementation. The authors conclude that combining multiple model types and leveraging their unique advantages can lead to high-impact research in most cases.
Review
Biochemistry & Molecular Biology
Alberto Ruffilli, Giovanni Viroli, Simona Neri, Matteo Traversari, Francesca Barile, Marco Manzetti, Elisa Assirelli, Marco Ialuna, Fabio Vita, Cesare Faldini
Summary: Low back pain, often caused by degenerative disc disease (DDD), is a common condition that can have severe consequences. This study aimed to systematically review the existing literature on the mechanobiology of the human intervertebral disc (IVD), identify the main pathways involved in DDD, and find potential therapeutic targets. The review included 15 studies that demonstrated promising results confirming the importance of mechanobiology in DDD and providing insights for possible treatment and prevention strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Benjamin T. Raines, James T. Stannard, Olivia E. Stricklin, Aaron M. Stoker, Theodore J. Choma, James L. Cook
Summary: This controlled laboratory study investigated the impact of caffeine concentrations on intervertebral disc cell viability and extracellular matrix composition. The results suggest that caffeine intake may be a risk factor for intervertebral disc degeneration, especially in conjunction with disc injury. Further studies are needed to elucidate mechanistic pathways and potential benefits for caffeine restriction.
GLOBAL SPINE JOURNAL
(2022)
Article
Engineering, Biomedical
J-Y Wang, J. C. Mansfield, S. Brasselet, C. Vergari, J. R. Meakin, C. P. Winlove
Summary: Needle injection is widely used in spinal therapeutic or diagnostic processes, but it has been suspected to cause mild disc degeneration leading to long-term back pain. This study found that needle punctures cause local microscopic damage to collagen and cell nuclei, resulting in progressive damage. The size of the needle used did not significantly affect the damage, with more damage observed using larger needles.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2021)
Article
Biophysics
T. Di Pauli von Treuheim, L. Zengerle, A. C. Hecht, J. C. Iatridis, H. J. Wilke
Summary: This study aimed to determine the most sensitive method for quantifying instability in human spines, comparing different neutral zone calculation methods. It was found that trilinear, zero load, and extrapolated elastic zone methods were the most sensitive in this human cadaveric dataset, able to capture expected neutral zone changes effectively.
JOURNAL OF BIOMECHANICS
(2021)
Review
Engineering, Biomedical
Tyler J. DiStefano, Keti Vaso, George Danias, Henry N. Chionuma, Jennifer R. Weiser, James C. Iatridis
Summary: Research has shown that stem cell-derived EVs can slow down the progression of IVDD at the molecular, cellular, and organ levels. The pathophysiological and differentiation state of the EV parent cell affects downstream treatment responses and therapeutic outcomes. These findings support the use of EVs as a promising cell-free strategy for treating IVDD and enhancing endogenous repair.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Orthopedics
Danielle N. D'Erminio, Divya Krishnamoorthy, Alon Lai, Robert C. Hoy, Devorah M. Natelson, Jashvant Poeran, Andrew Torres, Damien M. Laudier, Philip Nasser, Deepak Vashishth, Svenja Illien-Junger, James C. Iatridis
Summary: High fat diet can lead to weight gain, glucose intolerance, and reduced vertebral structure and function, with noticeable sex differences. The effects of RAGE-KO on spinal structures are limited, with significant interactions in the biomechanical properties of coccygeal motion segments.
JOURNAL OF ORTHOPAEDIC RESEARCH
(2022)
Article
Clinical Neurology
Dennis M. Bienstock, Dhruv Shankar, Jinseong Kim, Michael Gao, Komal Srivastava, Wesley H. Bronson, Saad B. Chaudhary, Jashvant Poeran, James C. Iatridis, Andrew C. Hecht
Summary: This prospective study used wearable accelerometers to track the recovery of lumbar laminectomy patients and compared the accelerometer data with PROMs. The results showed that accelerometer data could help identify different stages of postoperative recovery, but PROMs are still necessary to capture subjective elements of recovery.
WORLD NEUROSURGERY
(2022)
Review
Rheumatology
Uruj Zehra, Marianna Tryfonidou, James C. Iatridis, Svenja Illien-Junger, Fackson Mwale, Dino Samartzis
Summary: Intervertebral disc calcification is a frequently overlooked phenotype that can have significant clinical implications, leading to severe disc degeneration and low back pain. While not uncommon in aging and degenerative spinal conditions, it is often ignored. Calcification in the intervertebral disc may also cause endplate changes and generate pain, affecting the management and prognosis of degenerative spinal changes.
NATURE REVIEWS RHEUMATOLOGY
(2022)
Article
Engineering, Biomedical
Christopher J. Panebianco, Sanjna Rao, Warren W. Hom, James H. Meyers, Tiffany Y. Lim, Damien M. Laudier, Andrew C. Hecht, Michael D. Weir, Jennifer R. Weiser, James C. Iatridis
Summary: This study developed an injectable composite biomaterial using degradable oxidized alginate microbeads for delivering annulus fibrosus cells to injured intervertebral discs. The composite material achieved a balance between biomechanical and biological demands, providing promising results for cell delivery and repair.
Article
Engineering, Biomedical
Dalin Wang, Alon Lai, Jennifer Gansau, Philip Nasser, Yunsoo Lee, Damien M. Laudier, James C. Iatridis
Summary: This study established an ex-vivo rat lumbar endplate injury model and characterized the effects of endplate injury on motion segment biomechanical properties. Compared to annulus fibrosus injury, endplate injury had the greatest impact on axial biomechanical properties, while annulus fibrosus injury primarily affected torsional properties.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2022)
Article
Orthopedics
Changli Zhang, Katherine M. Joseph, Nazir M. Khan, Martha Elena Diaz-Hernandez, Hicham Drissi, Svenja Illien-Junger
Summary: The deficiency of PHLPP1 protects against age-related intervertebral disc (IVD) degeneration by preventing NP phenotypic changes, extracellular matrix degradation, and cell apoptosis, possibly through the activation of FOXO1.
Article
Orthopedics
Shaghayegh Basatvat, Frances C. Bach, Marcos N. Barcellona, Abbie L. Binch, Conor T. Buckley, Brian Bueno, Nadeen O. Chahine, Ana Chee, Laura B. Creemers, Stefan Dudli, Bailey Fearing, Stephen J. Ferguson, Jennifer Gansau, Benjamin Gantenbein, Rahul Gawri, Juliane D. Glaeser, Sibylle Grad, Julien Guerrero, Lisbet Haglund, Paula A. Hernandez, Judith A. Hoyland, Charles Huang, James C. Iatridis, Svenja Illien-Junger, Liufang Jing, Petra Kraus, Lisanne T. Laagland, Gernot Lang, Victor Leung, Zhen Li, Thomas Lufkin, Josette C. van Maanen, Emily E. McDonnell, Chris J. Panebianco, Steven M. Presciutti, Sanjna Rao, Stephen M. Richardson, Sarah Romereim, Tara C. Schmitz, Jordy Schol, Lori Setton, Dmitriy Sheyn, Joseph W. Snuggs, Y. Sun, Xiaohong Tan, Marianna A. Tryfonidou, Nam Vo, Dong Wang, Brandon Williams, Rebecca Williams, S. Tim Yoon, Christine L. Le Maitre
Summary: This study aims to standardize the extraction and expansion techniques for nucleus pulposus (NP) cells, in order to reduce variability between laboratories and improve comparability of results. The most commonly used methods for NP cell extraction, expansion, and re-differentiation were identified through a global survey. Recommended protocols for NP cell culture in different species were provided to support harmonization and cross-lab comparisons.
Article
Engineering, Biomedical
Michael R. Arul, Changli Zhang, Ibtihal Alahmadi, Isaac L. Moss, Yeshavanth Kumar Banasavadi-Siddegowda, Sama Abdulmalik, Svenja Illien-Junger, Sangamesh G. Kumbar
Summary: In this proof-of-concept study, a nanoparticle delivery system was developed to efficiently deliver high- and low-solubility drug molecules for the treatment of intervertebral disc damage. The nanoparticles showed enhanced solubility and stability, and were successfully taken up by human IVD cells. This platform technology has the potential to deliver therapeutic agents to IVDs and other tissues that require localized drug injections.
JOURNAL OF FUNCTIONAL BIOMATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Alon Lai, Denise Iliff, Kashaf Zaheer, Dalin Wang, Jennifer Gansau, Damien M. Laudier, Venetia Zachariou, James C. Iatridis
Summary: In this rat study, it was found that endplate injury leads to spinal cord sensitization, neuroinflammation, and pain-related behaviors. Additionally, increased macrophages were observed in the endplate and vertebrae, and there was a correlation between spinal cord sensitization, neuroinflammation, IVD degeneration, and macrophage presence. These findings suggest that therapies targeting neural pathologies, IVD degeneration, and chronic spinal inflammation are necessary.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Orthopedics
Zachary S. Gallate, Danielle N. D'Erminio, Philip Nasser, Damien M. Laudier, James C. Iatridis
Summary: Back and neck pain are major causes of disability, with intervertebral disc degeneration being a contributing factor. Accumulation of advanced glycation endproducts (AGEs) is associated with oxidative stress and collagen damage in the intervertebral disc. The receptors for AGEs (RAGE) and Galectin 3 (Gal3) play important roles in the response to AGEs in the intervertebral disc.
Article
Cell & Tissue Engineering
A. Levillain, S. Ahmed, D-M Kaimaki, S. Schuler, S. Barros, D. Labonte, J. C. Iatridis, N. C. Nowlan
Summary: Embryonic muscle forces play a crucial role in vertebral and intervertebral disc development, with muscle contractions affecting notochord involution, vertebral segmentation, and the mechanical properties of the intervertebral disc. Absence of muscle contractions leads to vertebral fusion, displacement of the nucleus pulposus, structural disruption of collagen in the annulus fibrosus, and increased viscosity in the annulus fibrosus. These findings highlight the importance of mechanical forces and muscle loading in proper intervertebral disc formation and potential tissue engineering therapies for intervertebral disc degeneration.
EUROPEAN CELLS & MATERIALS
(2021)
Article
Biophysics
Nathan D. Camarillo, Rafael Jimenez-Silva, Frances T. Sheehan
Summary: This article discusses the statistical dependence between multiple measurements from the same participant and provides recommendations for using these measurements when they are not independent.
JOURNAL OF BIOMECHANICS
(2024)
Article
Biophysics
J. Huet, A. -S. Boureau, A. Sarcher, C. Cornu, A. Nordez
Summary: Standard compression in freehand 3D ultrasound induces a bias in volume calculations, but minimal compression and gel pad methods have similar results. With a trained examiner and precautions, the bias can be minimized and become acceptable in clinical applications.
JOURNAL OF BIOMECHANICS
(2024)
Article
Biophysics
C. Lariviere, A. H. Eskandari, H. Mecheri, F. Ghezelbash, D. Gagnon, A. Shirazi-Adl
Summary: Recent developments in musculoskeletal modeling have focused on model customization. Personalization of the spine profile may affect estimates of spinal loading and stability. This study investigates the biomechanical consequences of changes in the spinal profile and finds that personalizing the spine profile has medium to large effects on trunk muscle forces and negligible to small effects on spinal loading and stability.
JOURNAL OF BIOMECHANICS
(2024)
Article
Biophysics
Luke T. Mattar, Arash B. Mahboobin, Adam J. Popchak, William J. Anderst, Volker Musahl, James J. Irrgang, Richard E. Debski
Summary: Exercise therapy fails in about 25.0% of cases for individuals with rotator cuff tears, and one reason for this failure may be the inability to strengthen and balance the muscle forces that keep the humeral head in the correct position. This study developed computational musculoskeletal models to compare the net muscle force before and after exercise therapy between successfully and unsuccessfully treated patients. The study found that unsuccessfully treated patients had less inferiorly oriented net muscle forces, which may increase the risk of impingement.
JOURNAL OF BIOMECHANICS
(2024)
Article
Biophysics
Natsuki Sado, Takeshi Edagawa, Toshihide Fujimori, Shogo Hashimoto, Yoshikazu Okamoto, Takahito Nakajima
Summary: The existing methods for predicting hip and lumbosacral joint centres in Japanese adults are biased and differ between sexes. We propose new regression equations that consider soft-tissue thickness, sex differences, and a height-directional measure, and validate them using leave-one-out cross-validation.
JOURNAL OF BIOMECHANICS
(2024)
Article
Biophysics
Peimin Yu, Xuanzhen Cen, Qichang Mei, Alan Wang, Yaodong Gu, Justin Fernandez
Summary: This study aimed to explore the intra-foot biomechanical differences among individuals with chronic ankle instability (CAI), copers, and healthy individuals during dynamic tasks. The study found that copers and CAI individuals had smaller dorsiflexion angles and copers presented a more eversion position compared to healthy participants. Copers also had greater dorsiflexion angles in the metatarsophalangeal joint and more inversion moments in the subtalar joint during certain tasks. These findings can help in designing interventions to restore ankle joint functions in CAI individuals.
JOURNAL OF BIOMECHANICS
(2024)
Article
Biophysics
Jon Skovgaard Jensen, Anders Holsgaard-Larsen, Anders Stengaard Sorensen, Per Aagaard, Jens Bojsen-Moller
Summary: This study investigates the biomechanical effects of robot-assisted body weight unloading (BWU) on gait patterns in healthy young adults. The results show that dynamic robot-assisted BWU enables reduced kinetic requirements without distorting biomechanically normal gait patterns during overground walking.
JOURNAL OF BIOMECHANICS
(2024)