Deep learning enables accurate soft tissue tendon deformation estimation in vivo via ultrasound imaging.

Image-based deformation estimation is an important tool used in a variety of engineering problems, including crack propagation, fracture, and fatigue failure. These tools have been important in biomechanics research where measuring in vitro and in vivo tissue deformations are important for evaluating tissue health and disease progression. However, accurately measuring tissue deformation in vivo is particularly challenging due to limited image signal-to-noise ratio.

Integrin mechanosensing relies on a pivot-clip mechanism to reinforce cell adhesion.

Cells intricately sense mechanical forces from their surroundings, driving biophysical and biochemical activities. This mechanosensing phenomenon occurs at the cell-matrix interface, where mechanical forces resulting from cellular motion, such as migration or matrix stretching, are exchanged through surface receptors, primarily integrins, and their corresponding matrix ligands. A pivotal player in this interaction is the αβ integrin and fibronectin (FN) bond, known for its role in establishing cell adhesion sites for migration.

Review of state-of-the-art micro and macro-bioreactors for the intervertebral disc.

Lower back pain continues to be a global epidemic, limiting quality of life and ability to work, due in large part to symptomatic disc degeneration. Development of more effective and less invasive biological strategies are needed to treat disc degeneration. In vitro models such as macro- or micro-bioreactors or mechanically active organ-chips hold great promise in reducing the need for animal studies that may have limited clinical translatability, due to harsher and more complex mechanical loading environments in human discs than in most animal models.

Effect of Passaging on Bovine Chondrocyte Gene Expression and Engineered Cartilage Production.

Tissue engineering strategies show great potential for repairing osteochondral defects in osteoarthritic joints; however, these approaches often rely on passaging cells multiple times to obtain enough cells to produce functional tissue. Unfortunately, monolayer expansion culture causes chondrocyte dedifferentiation, which is accompanied by a phenotypical and morphological shift in chondrocyte properties that leads to a reduction in the quality of cartilage produced. Thus, the objective of this study was to evaluate transcriptional variations during expansion culture and determine how differences in cell phenotype from monolayer expansion alter development of functional engineered cartilage.

Understanding the etiopathogenesis of lumbar intervertebral disc herniation: From clinical evidence to basic scientific research.

Lumbar intervertebral disc herniation, as a leading cause of low back pain, productivity loss, and disability, is a common musculoskeletal disorder that results in significant socioeconomic burdens. Despite extensive clinical and basic scientific research efforts, herniation etiopathogenesis, particularly its initiation and progression, is not well understood. Understanding herniation etiopathogenesis is essential for developing effective preventive measures and therapeutic interventions.

Priming chondrocytes during expansion alters cell behavior and improves matrix production in 3D culture.

Objective: Cartilage tissue engineering strategies that use autologous chondrocytes require in vitro expansion of cells to obtain enough cells to produce functional engineered tissue. However, chondrocytes dedifferentiate during expansion culture, limiting their ability to produce chondrogenic tissue and their utility for cell-based cartilage repair strategies. The current study identified conditions that favor cartilage production and the mechanobiological mechanisms responsible for these benefits.

Non-enzymatic glycation increases the failure risk of annulus fibrosus by predisposing the extrafibrillar matrix to greater stresses.

Growing clinical evidence suggests a correlation between diabetes and more frequent and severe intervertebral disc failure, partially attributed to accelerated advanced glycation end-products (AGE) accumulation in the annulus fibrosus (AF) through non-enzymatic glycation. However, in vitro glycation (i.e.

Design of a flexing organ-chip to model loading of the intervertebral disc.

The leading cause of disability of all ages worldwide is severe lower back pain. To address this untreated epidemic, further investigation is needed into the leading cause of back pain, intervertebral disc degeneration. In particular, microphysiological systems modeling critical tissues in a degenerative disc, like the annulus fibrosus (AF), are needed to investigate the effects of complex multiaxial strains on AF cells.

Disc geometry measurement methods affect reported compressive mechanics by up to 65.

Mechanical testing is a valuable tool for assessing intervertebral disc health, but the wide range of testing protocols makes it difficult to compare results from different studies. Normalizing mechanical properties by disc geometry allows for such comparisons, but there is little consistency in the methods by which disc geometry is measured. As such, we hypothesized that methods used to measure disc geometry would impact reported mechanical properties.

Addition of collagen type I in agarose created a dose-dependent effect on matrix production in engineered cartilage.

Extracellular-matrix composition impacts mechanical performance in native and engineered tissues. Previous studies showed collagen type I-agarose blends increased cell-matrix interactions and extracellular matrix production. However, long-term impacts on protein production and mechanical properties of engineered cartilage are unknown.

Torque- and Muscle-Driven Flexion Induce Disparate Risks of In Vitro Herniation: A Multiscale and Multiphasic Structure-Based Finite Element Study.

The intervertebral disc is a complex structure that experiences multiaxial stresses regularly. Disc failure through herniation is a common cause of lower back pain, which causes reduced mobility and debilitating pain, resulting in heavy socioeconomic burdens. Unfortunately, herniation etiology is not well understood, partially due to challenges in replicating herniation in vitro.

Non-enzymatic glycation of annulus fibrosus alters tissue-level failure mechanics in tension.

Advanced-glycation end products (AGEs) are known to accumulate in biological tissues with age and at an accelerated rate in patients with diabetes and chronic kidney disease. Clinically, diabetes has been linked to increased frequency and severity of back pain, accelerated disc degeneration, and an increased risk of disc herniation. Despite significant clinical evidence suggesting that diabetes-induced AGEs may play a role in intervertebral disc failure and substantial previous work investigating the effects of AGEs on bone, cartilage, and tendon mechanics, the effects of AGEs on annulus fibrosus (AF) failure mechanics have not yet been reported.

Relations Between Bone Quantity, Microarchitecture, and Collagen Cross-links on Mechanics Following In Vivo Irradiation in Mice.

Humans are exposed to ionizing radiation via spaceflight or cancer radiotherapy, and exposure from radiotherapy is known to increase risk of skeletal fractures. Although irradiation can reduce trabecular bone mass, alter trabecular microarchitecture, and increase collagen cross-linking, the relative contributions of these effects to any loss of mechanical integrity remain unclear. To provide insight, while addressing both the monotonic strength and cyclic-loading fatigue life, we conducted total-body, acute, gamma-irradiation experiments on skeletally mature (17-week-old) C57BL/6J male mice ( = 84).

Saline-polyethylene glycol blends preserve in vitro annulus fibrosus hydration and mechanics: An experimental and finite-element analysis.

Precise control of tissue water content is essential for ensuring accurate, repeatable, and physiologically relevant measurements of tissue mechanics and biochemical composition. While previous studies have found that saline and polyethylene glycol (PEG) blends were effective at controlling tendon and ligament hydration levels, this work has yet to be extended to the annulus fibrosus (AF). Thus, the first objective of this study was to determine and validate an optimal buffer solution for targeting and maintaining hydration levels of tissue-level AF specimens in vitro.

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

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 fiber mechanics, finite element models have been widely employed in spinal biomechanics research.

Spine biomechanical testing methodologies: The controversy of consensus vs scientific evidence.

Biomechanical testing methodologies for the spine have developed over the past 50 years. During that time, there have been several paradigm shifts with respect to techniques. These techniques evolved by incorporating state-of-the-art engineering principles, in vivo measurements, anatomical structure-function relationships, and the scientific method.

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

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.

Fiber engagement accounts for geometry-dependent annulus fibrosus mechanics: A multiscale, Structure-Based Finite Element Study.

A comprehensive understanding of biological tissue mechanics is crucial for designing engineered tissues that aim to recapitulate native tissue behavior. Tensile mechanics of many fiber-reinforced tissues have been shown to depend on specimen geometry, which makes it challenging to compare data between studies. In this study, a validated multiscale, structure-based finite element model was used to evaluate the effect of specimen geometry on multiscale annulus fibrosus tensile mechanics through a fiber engagement analysis.

Influence of testing environment and loading rate on intervertebral disc compressive mechanics: An assessment of repeatability at three different laboratories.

In vitro mechanical testing of intervertebral discs is crucial for basic science and pre-clinical testing. Generally, these tests aim to replicate in vivo conditions, but simplifications are necessary in specimen preparation and mechanical testing due to complexities in both structure and the loading conditions required to replicate in vivo conditions. There has been a growing interest in developing a consensus of testing protocols within the spine community to improve comparison of results between studies.

Transient swelling behavior of the bovine caudal disc.

The intervertebral disc is an avascular composite structure, comprised of the nucleus pulposus (NP) and the annulus fibrosus (AF). Previous tissue-level experiments either examined relative differences in swelling capacity of the two disc regions at a single time point or tested explant structures that did not replicate in situ boundary conditions. Previous joint-level studies that investigated time-dependent fluid flow into the disc provided limited information about swelling-induced intradiscal strains with respect to time and boundary constraints.

Nonlinear stress-dependent recovery behavior of the intervertebral disc.

The intervertebral disc exhibits complex mechanics due to its heterogeneous structure, inherent viscoelasticity, and interstitial fluid-matrix interactions. Sufficient fluid flow into the disc during low loading periods is important for maintaining mechanics and nutrient transport. However, there is a lack of knowledge on the effect of loading magnitude on time-dependent recovery behavior and the relative contribution of multiple recovery mechanisms during recovery.

Direct Quantification of Intervertebral Disc Water Content Using MRI.

Background: Water content is a key parameter for simulating tissue swelling and nutrient diffusion. Accurately measuring water content throughout the intervertebral disc (NP = nucleus pulposus; AF = annulus fibrosus) is important for developing patient-specific models. Water content is measured using destructive techniques, Quantitative MRI has been used to estimate water content and detect early degeneration, but it is dependent on scan parameters, concentration of free water molecules, and fiber architecture.

Three-dimensional myocardial strain correlates with murine left ventricular remodelling severity post-infarction.

Heart failure continues to be a common and deadly sequela of myocardial infarction (MI). Despite strong evidence suggesting the importance of myocardial mechanics in cardiac remodelling, many MI studies still rely on two-dimensional analyses to estimate global left ventricular (LV) function. Here, we integrated four-dimensional ultrasound with three-dimensional strain mapping to longitudinally characterize LV mechanics within and around infarcts in order to study the post-MI remodelling process.

Multiscale composite model of fiber-reinforced tissues with direct representation of sub-tissue properties.

In many fiber-reinforced tissues, collagen fibers are embedded within a glycosaminoglycan-rich extrafibrillar matrix. Knowledge of the structure-function relationship between the sub-tissue properties and bulk tissue mechanics is important for understanding tissue failure mechanics and developing biological repair strategies. Difficulties in directly measuring sub-tissue properties led to a growing interest in employing finite element modeling approaches.