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Tendon degeneration is typically described as an overuse injury with little distinction made between magnitude of load (overload) and number of cycles (overuse). Further, in vivo animal models of tendon degeneration are mostly overuse models, where tendon damage is caused with high number of load cycles. As a result, there is a lack of knowledge of how isolated overload leads to degeneration. A surgical model of synergist ablation (SynAb) overloads the target tendon, plantaris, by ablating its synergist tendon, Achilles. The objective of this study was to evaluate the structural and functional changes that occur following overload of plantaris tendon in a rat SynAb model. Tendon cross-sectional area and shape changes were evaluated by longitudinal MR imaging up to 8-weeks post-surgery. Tissue-scale structural changes were evaluated by semi-quantified histology and second harmonic generation microscopy. Fibril level changes were evaluated with Serial Block Face Scanning Electron Microscopy (SBF-SEM). Functional changes were evaluated using tension tests at the tissue and microscale using a custom testing system allowing both video and microscopy imaging. At 8 weeks, overloaded plantaris tendons exhibited degenerative changes including increases in CSA, cell density, collagen damage area fraction, and fibril diameter, and decreases in collagen alignment, modulus, and yield stress. To interpret the differences between overload and overuse in tendon, we introduce a new framework for tendon remodeling and degeneration that differentiates between the inputs of overload and overuse. In summary, isolated overload induces multiscale degenerative structural and functional changes in plantaris tendon.

The meniscus serves important load-bearing functions and protects the underlying articular cartilage. Unfortunately, meniscus tears are common and impair the ability of the meniscus to distribute loads, increasing the risk of developing osteoarthritis. Therefore, surgical repair of the meniscus is a frequently performed procedure; however, repair does not always prevent osteoarthritis. This is hypothesized to be due to altered joint loading post-injury and repair, where the functional deficit of the meniscus prevents it from performing its role of distributing forces. The objective of this study was to quantify joint kinematics in an intact joint, after a meniscus root tear, and after suture repair in cadaveric porcine knees, a frequently used in vivo model. We utilized an magnetic resonance images-compatible loading device and novel use of a T1 vibe sequence to measure meniscus and femur displacements under physiological axial loads. We found that anterior root tear led to large meniscus displacements under physiological axial loading and that suture anchor repair reduced these displacements but did not fully restore intact joint kinematics. After tear and repair, the anterior region of the meniscus moved posteriorly and medially as it was forced out of the joint space under loading, while the posterior region had small displacements as the posterior attachment acted as a hinge about which the meniscus pivoted in the axial plane. Methods from this study can be applied to assess altered joint kinematics following human knee injuries and evaluate repair strategies aimed to restore joint kinematics.

Load-induced volume change is an important aspect of knee meniscus function because volume loss creates fluid pressure, which minimizes friction and helps support compressive loads. The knee meniscus is unusual amongst cartilaginous tissues in that it is loaded not only in axial compression, but also in circumferential tension between its tibial attachments. Despite the physiologic importance of the knee meniscus' tensile properties, its volumetric strain in tension has never been directly measured, and predictions of volume strain in the scientific literature are inconsistent. In this study, we apply uniaxial tension to bovine knee meniscus and use biplanar imaging to directly observe the resulting three-dimensional volume change and unloaded recovery, revealing that tension causes volumetric contraction. Compression is already known to also cause contraction; therefore, all major physiologic loads compress and pressurize the meniscus, inducing fluid outflow. Although passive unloaded recovery is often described as slow relative to loaded loss, here we show that at physiologic strains the volume recovery rate in the meniscus upon unloading is faster than the rate of volume loss. These measurements of volumetric strain are an important step toward a complete theory of knee meniscus fluid flow and load support.

Nucleotomy is a common surgical procedure and is also performed in ex vivo mechanical testing to model decreased nucleus pulposus (NP) pressurization that occurs with degeneration. Here, we implement novel and noninvasive methods using magnetic resonance imaging (MRI) to study internal 3D annulus fibrosus (AF) deformations after partial nucleotomy and during axial compression by evaluating changes in internal AF deformation at reference loads (50 N) and physiological compressive loads (∼10% strain). One particular advantage of this methodology is that the full 3D disc deformation state, inclusive of both in-plane and out-of-plane deformations, can be quantified through the use of a high-resolution volumetric MR scan sequence and advanced image registration. Intact grade II L3-L4 cadaveric human discs before and after nucleotomy were subjected to identical mechanical testing and imaging protocols. Internal disc deformation fields were calculated by registering MR images captured in each loading state (reference and compressed) and each condition (intact and nucleotomy). Comparisons were drawn between the resulting three deformation states (intact at compressed load, nucleotomy at reference load, nucleotomy at compressed load) with regard to the magnitude of internal strain and direction of internal displacements. Under compressed load, internal AF axial strains averaged −18.5% when intact and −22.5% after nucleotomy. Deformation orientations were significantly altered by nucleotomy and load magnitude. For example, deformations of intact discs oriented in-plane, whereas deformations after nucleotomy oriented axially. For intact discs, in-plane components of displacements under compressive loads oriented radially outward and circumferentially. After nucleotomy, in-plane displacements were oriented radially inward under reference load and were not significantly different from the intact state at compressed loads. Re-establishment of outward displacements after nucleotomy indicates increased axial loading restores the characteristics of internal pressurization. Results may have implications for the recurrence of pain, design of novel therapeutics, or progression of disc degeneration.

Fibrous soft tissues are biopolymeric materials that are made of extracellular proteins, such as different types of collagen and proteoglycans, and have a high water content. These tissues have nonlinear, anisotropic, and inelastic mechanical behaviors that are often categorized into viscoelastic behavior, plastic deformation, and damage. While tissue's elastic and viscoelastic mechanical properties have been measured for decades, there is no comprehensive theoretical framework for modeling inelastic behaviors of these tissues that is based on their structure. To model the three major inelastic mechanical behaviors of tissue's fibrous matrix, we formulated a structurally inspired continuum mechanics framework based on the energy of molecular bonds that break and reform in response to external loading (reactive bonds). In this framework, we employed the theory of internal state variables (ISV) and kinetics of molecular bonds. The number fraction of bonds, their reference deformation gradient, and damage parameter were used as state variables that allowed for consistent modeling of all three of the inelastic behaviors of tissue by using the same sets of constitutive relations. Several numerical examples are provided that address practical problems in tissue mechanics, including the difference between plastic deformation and damage. This model can be used to identify relationships between tissue's mechanical response to external loading and its biopolymeric structure.

This paper describes a new method, based on a recent analytical model (Hertzian biphasic theory (HBT)), to simultaneously quantify cartilage contact modulus, tension modulus, and permeability. Standard Hertzian creep measurements were performed on 13 osteochondral samples from three mature bovine stifles. Each creep dataset was fit for material properties using HBT. A subset of the dataset (N = 4) was also fit using Oyen's method and FEBio, an open-source finite element package designed for soft tissue mechanics. The HBT method demonstrated statistically significant sensitivity to differences between cartilage from the tibial plateau and cartilage from the femoral condyle. Based on the four samples used for comparison, no statistically significant differences were detected between properties from the HBT and FEBio methods. While the finite element method is considered the gold standard for analyzing this type of contact, the expertise and time required to setup and solve can be prohibitive, especially for large datasets. The HBT method agreed quantitatively with FEBio but also offers ease of use by nonexperts, rapid solutions, and exceptional fit quality (R2 = 0.999 ± 0.001, N = 13).

The quasi-linear viscoelastic (QLV) model was applied to incremental stress-relaxation tests and an expression for the stress was derived for each step. This expression was used to compare two methods for normalizing stress data prior to estimating QLV parameters. The first and commonly used normalization method was shown to be strain-dependent. Thus, a second normalization method was proposed and shown to be strain-independent and more sensitive to QLV time constants. These analytical results agreed with representative tendon data. Therefore, this method for normalizing stress data was proposed for future studies of incremental stress-relaxation, or whenever comparing stress-relaxation at different strains.

Tendons are exposed to complex loading scenarios that can only be quantified by mathematical models, requiring a full knowledge of tendon mechanical properties. This study measured the anisotropic, nonlinear, elastic material properties of tendon. Previous studies have primarily used constant strain-rate tensile tests to determine elastic modulus in the fiber direction. Data for Poisson's ratio aligned with the fiber direction and all material properties transverse to the fiber direction are sparse. Additionally, it is not known whether quasi-static constant strain-rate tests represent equilibrium elastic tissue behavior. Incremental stress-relaxation and constant strain-rate tensile tests were performed on sheep flexor tendon samples aligned with the tendon fiber direction or transverse to the fiber direction to determine the anisotropic properties of toe-region modulus (E0), linear-region modulus (E), and Poisson's ratio (v). Among the modulus values calculated, only fiber-aligned linear-region modulus (E1) was found to be strain-rate dependent. The E1 calculated from the constant strain-rate tests were significantly greater than the value calculated from incremental stress-relaxation testing. Fiber-aligned toe-region modulus (E(1)0 = 10.5 +/- 4.7 MPa) and linear-region modulus (E1 = 34.0 +/- 15.5 MPa) were consistently 2 orders of magnitude greater than transverse moduli (E(2)0 = 0.055 +/- 0.044 MPa, E2 = 0.157 +/- 0.154 MPa). Poisson's ratio values were not found to be rate-dependent in either the fiber-aligned (v12 = 2.98 +/- 2.59, n = 24) or transverse (v21 = 0.488 +/- 0.653, n = 22) directions, and average Poisson's ratio values in the fiber-aligned direction were six times greater than in the transverse direction. The lack of strain-rate dependence of transverse properties demonstrates that slow constant strain-rate tests represent elastic properties in the transverse direction. However, the strain-rate dependence demonstrated by the fiber-aligned linear-region modulus suggests that incremental stress-relaxation tests are necessary to determine the equilibrium elastic properties of tendon, and may be more appropriate for determining the properties to be used in elastic mathematical models.

The intervertebral disc functions to permit motion, distribute load, and dissipate energy in the spine. It performs these functions through its highly heterogeneous structural organization and biochemical composition consisting of several tissue substructures: the central gelatinous nucleus pulposus (NP), the surrounding fiber-reinforced layered AF, and the cartilaginous endplates that are positioned between the NP and vertebral endplates [1]. Disruption of any of the disc's tissues through aging, degeneration, or injury will not only alter the affected tissue mechanical properties but also the mechanical behavior of adjacent tissues and, ultimately, the overall disc segment function. Thus, there is a need to measure disc tissue and segment mechanics in the intact disc segment so that interactions between tissue structures are not disrupted. Such measurements would be valuable to study mechanisms of disc function and of disc degeneration, to design functional tissue engineered discs, and to develop and evaluate surgical procedures and therapeutic implants. Disc mechanical behavior has been quantified through a number of measures including external displacements [2–5] and internal pressure [6–9]; however, these do not fully establish internal tissue mechanics. Internal disc mechanics have also been measured through marker insertion or disc bisection [10–14]. These studies have provided important data about disc mechanical function and how it changes with degeneration. Yet the disc is composed of soft hydrated, pressurized, and fibrous tissues that may deform separately from the inserted markers and may depressurize when bisected. Thus, it has remained a challenge to quantify internal disc mechanics. Magnetic resonance imaging (MRI) before and after an applied load, combined with image registration, is a promising method to quantify internal disc mechanics. Important advances have been made using MRI to measure internal disc deformation in a 2D plane [15–19]. Strains within several AF regions (e.g., anterior, posterior, and lateral) were measured under applied axial compression, and the effect of loading position, degeneration, and nucleotomy was determined [16–18], demonstrating inhomogeneous strains across AF regions and differential effects of nucleotomy that depend on the initial state of degeneration [16–18]. A nonrigid image registration method was employed by [19] to calculate midsagittal strain after creep loading. Displacement encoded MRI, an image tagging method that enables direct displacement measurements from MRI data, was used in Ref. [15] to calculate strain across the entire disc under cyclic loading. While these are important advances, the 2D nature of recent MRI-based studies do not account for out-of-plane deformation nor provide the 3D strain components that are key to evaluating disc mechanical function. The objectives of this study were to develop, validate, and apply a method to measure 3D internal deformations in intact human discs subjected to axial compression. This was achieved by using a custom-built loading device that permitted long relaxation times outside of the MRI scanner and maintained compression and hydration during imaging, by acquiring MR images at a high resolution (300 μm isotropic), and by applying state-of-the-art image registration methods.

Planar biaxial tension remains a critical loading modality for fibrous soft tissue and is widely used to characterize tissue mechanical response, evaluate treatments, develop constitutive formulas, and obtain material properties for use in finite element studies. Although the application of tension on all edges of the test specimen represents the in situ environment, there remains a need to address the interpretation of experimental results. Unlike uniaxial tension, in biaxial tension the applied forces at the loading clamps do not transmit fully to the region of interest (ROI), which may lead to improper material characterization if not accounted for. In this study, we reviewed the tensile biaxial literature over the last ten years, noting experimental and analysis challenges. In response to these challenges, we used finite element simulations to quantify load transmission from the clamps to the ROI in biaxial tension and to formulate a correction factor that can be used to determine ROI stresses. Additionally, the impact of sample geometry, material anisotropy, and tissue orientation on the correction factor were determined. Large stress concentrations were evident in both square and cruciform geometries and for all levels of anisotropy. In general, stress concentrations were greater for the square geometry than the cruciform geometry. For both square and cruciform geometries, materials with fibers aligned parallel to the loading axes reduced stress concentrations compared to the isotropic tissue, resulting in more of the applied load being transferred to the ROI. In contrast, fiber-reinforced specimens oriented such that the fibers aligned at an angle to the loading axes produced very large stress concentrations across the clamps and shielding in the ROI. A correction factor technique was introduced that can be used to calculate the stresses in the ROI from the measured experimental loads at the clamps. Application of a correction factor to experimental biaxial results may lead to more accurate representation of the mechanical response of fibrous soft tissue.

The highly organized structure and composition of the annulus fibrosus provides the tissue with mechanical behaviors that include anisotropy and nonlinearity. Mathematical models are necessary to interpret and elucidate the meaning of directly measured mechanical properties and to understand the structure-function relationships of the tissue components, namely, the fibers and extrafibrillar matrix. This study models the annulus fibrosus as a combination of strain energy functions describing the fibers, matrix, and their interactions. The objective was to quantify the behavior of both nondegenerate and degenerate annulus fibrosus tissue using uniaxial tensile experimental data. Mechanical testing was performed with samples oriented along the circumferential, axial, and radial directions. For samples oriented along the radial direction, the toe-region modulus was 2× stiffer with degeneration. However, no other differences in measured mechanical properties were observed with degeneration. The constitutive model fit well to samples oriented along the radial and circumferential directions (R2≥0.97). The fibers supported the highest proportion of stress for circumferential loading at 60%. There was a 70% decrease in the matrix contribution to stress from the toe-region to the linear-region of both the nondegenerate and degenerate tissue. The shear fiber-matrix interaction (FMI) contribution increased by 80% with degeneration in the linear-region. Samples oriented along the radial and axial direction behaved similarly under uniaxial tension (modulus=0.32 MPa versus 0.37 MPa), suggesting that uniaxial testing in the axial direction is not appropriate for quantifying the mechanics of a fiber reinforcement in the annulus. In conclusion, the structurally motivated nonlinear anisotropic hyperelastic constitutive model helps to further understand the effect of microstructural changes with degeneration, suggesting that remodeling in the subcomponents (i.e., the collagen fiber, matrix and FMI) may minimize the overall effects on mechanical function of the bulk material with degeneration.