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Mechanical signals are essential in regulating cell functions such as viability, differentiation, proliferation, and extracellular matrix (ECM) production in load-bearing tissues. However, the current understanding of how macroscopic tissue level strain is transferred to cells is confounded by the highly variable strain fields that arise within the ECM of both native and cell-seeded nanofibrous scaffolds. Moreover, it is unclear how these transmission mechanisms relate to native load bearing tissues. The current study investigates how applied macroscopic tensile strain is transferred to the intercellular ECM and cell nuclei in meniscus, tendon, single lamellar AF, and MSC-seeded scaffolds. The mean microscopic Lagrangian and principal strains in the loading direction (E 22 and e 2 ) of all native tissues and scaffolds were attenuated from the applied strains by 50% and 30–40% respectively. In aligned scaffold, a significant correlation was observed between the mean nuclear strain and E 22 (r2=0.98), where 100% of E 22 transferred to nuclei. Less pronounced strain attenuation in scaffolds compared to native tissues is likely due to more homogeneous microstructure and lack of ECM. In addition, the presence of pericellular matrix in native tissues, along with dense ECM, may shield and regulate strain transfer from the ECM to the subcellular space.

Intervertebral disc degeneration is a cell-mediated process that results in the disruption of its function. These changes are difficult to overturn; consequently, early diagnosis is key for the success of any treatment. Clinically, disc degeneration is diagnosed by analyzing morphological changes characteristic of moderate to advanced stages of degeneration. Therefore, there is a need of a reliable biomarker to characterize the compositional and structural integrity of the disc in early stages of degeneration. In this study, shear modulus is proposed as a new biomarker for disc degeneration and a non-invasive method to measure this mechanical property is presented.

Introduction: The cartilaginous endplate (CEP) is a thin layer of hyaline cartilage which functions as a mechanical barrier between the nucleus pulposus and the vertebral endplate and as a gateway for nutrient transport to the intervertebral disc. To date, the geometry of the CEP has not been well defined. This study visualizes the three-dimensional morphology of the CEP and quantifies CEP thickness via a semi-automatic analysis technique. Methods: Human lumbar motion segments (n=24) were imaged using an optimized 3D FLASH sequence. MRI data were evaluated in the axial and mid-sagittal imaging planes for CEP area, circumference, anterior-posterior width, lateral width, and thickness. CEP thickness was evaluated at five anterior-posterior locations. Results: There was no significant difference in CEP circumference, area, A-P width, or lateral width with respect to superior/inferior location (p>0.7) or disc level (p>0.6) except between L1L2 and L4L5 (p 0.5). Discussion: This study demonstrates the potential for MRI FLASH imaging coupled with automatic geometric quantification in evaluating the CEP as a potential contributor in the degenerative cascade.

Protein crosslinking and glycosaminoglycan (GAG) depletion are characteristic of disc degeneration. The objective of this study is to analyze the role of these biochemical changes on the mechanics of annulus fibrosus extra-fibrillar matrix (EFM). It was found that GAG depletion decreased ionic contribution, but not the nonionic contribution of the EFM. Additionally, crosslinking increased the stiffness of annulus fibrosus EFM.

Introduction: Advanced Normalization Tools (ANTs) is an image registration program that has been validated for analysis of several tissues, but not previously applied to the disc. The objectives of this study were to optimize ANTs for disc image registration and to validate ANTs strain measurements by comparison with Vic2D, a commercially available software previously applied to quantify disc strain, before and after nucleotomy. Methods: Human lumbar motion segments (n=5) underwent 1000 N compression before and after nucleotomy and MR images were acquired in a reference and deformed state. Image overlap statistics were used to select mapping parameters, and strain analysis was used to select the optimal number of splines. Once the optimal registration method was selected (elastic mapping, 0.01 outlier, 6×6 splines), axial and radial strains were measured in the AAF, PAF, and IVD. Results: Excellent overlap statistics were achieved. No significant differences were found for strains calculated with ANTs and Vic2D (p≥0.35). With nucleotomy, the axial compressive strain increased in the PAF (p=0.04) and there was a trend towards decrease in radial strain (p=0.07). Discussion: ANTs is an accurate and powerful tool to calculate disc strains from MR images.

The repair of dense fiber-reinforced tissues poses a significant challenge for the tissue engineering community. The function of these structures is largely dependent on their architectural form, and as such, scaffold organization is an important design parameter in generating tissue analogues. To address this issue, we have recently utilized electrospinning to instill controllable fiber anisotropy in nanofibrous scaffolds. This abstract details the mechanical characterization of the bulk and local properties of these scaffolds, and points to their potential application in the repair and/or generation of fiber- reinforced tissues that recapitulate the native form.

In previous studies mouse lumbar spines have been used to model the human lumbar spine in order to investigate disc degeneration. While disc stiffness has been know to increase with age in humans, how mouse mechanical properties change with respect to age has not been examined. Uniaxial mechanical testing was performed utilizing motion segments that were harvested from lumbar spines representing two age groups. Force and displacement data were normalized using disc geometry and used to calculate neutral zone and stiffness. Results showed a significant difference between the neutral zones of the two age groups and trends were found in normalized stiffness. Studies in human disc mechanics use stiffness as a measure of change in disc mechanics, but our testing methods have allowed us to generate a stress/strain curve that utilizes three parameters for measuring change in disc mechanics instead of one.

In this study uniaxial tensile testing of rabbit patellar tendon was used to determine whether constant strain rate ramp testing approximates equilibrium tendon behavior. Modulus and Poisson's ratio calculated from constant strain-rate ramp tests were compared with modulus and Poisson's ratio calculated from incremental stress-relaxation tests, which allow viscoelastic behaviors to dissipate. Samples were tested along the fiber direction and perpendicular to the fiber direction.