Biology subjects

Kersh, M. E.

Publications and source records attributed to Kersh, M. E..

6 recordsLinked to original sources

bioRxiv2026

The effect of microstructural variations in tendon and ligament on diffusion tensor MRI

The fibrous microstructure of tendons and ligaments is an important determinant of their mechanical behavior and integrity. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that enables the inference of microstructural features within fibrous tissues and has recently been used to characterize the microstructure of dense connective tissues such as tendon and ligament. However, the effect of microstructural variations in tendon and ligament on DTI metrics remains unclear. To address this gap, we simulated diffusion MRI of second harmonic generation (SHG) image-informed square lattice fiber networks to determine which microstructural features have the strongest influence on DTI metrics. Then, we performed a second set of diffusion MRI simulations for randomly dispersed fibers within synthetic tendon volumes to relate DTI metrics to the influential microstructural features, including fiber dispersion. All DTI metrics were insensitive to collagen fiber crimp. Fiber dispersion did not affect mean diffusivity, decreased axial diffusivity, increased radial diffusivity, and decreased fractional anisotropy. These results provide valuable insight into the relationships between DTI metrics and microstructural properties of tendon and ligament, which is particularly relevant for inferring microstructural changes in impaired tissue using DTI. Furthermore, our findings are an important step in the translation of DTI for clinical and computational studies of dense connective tissues such as tendon and ligament.

bioengineering↗

bioRxiv2024

A simple analytical model for predicting locomotive ground reaction forces

Equine models are useful in biomechanics research of locomotion due to their similarity in musculoskeletal tissue to humans, their athletic nature, and rapid skeletal development which permits ontogenetic studies. However, a continuing challenge in musculoskeletal models for large animal biomechanics is measuring the ground reaction force (GRF) during locomotion. This gap has resulted in a lack of reporting of gait measures such as joint torques. Here we propose an analytical method for predicting ground reaction forces in foals (growing horses) based on the Froude number. Motion capture, GRF, and subject mass data during walking and trotting gaits were collected longitudinally. To account for differences in subject size, we calculated the dimensionless Froude number (Fr=v2/(g*l)). The walk-trot transition speed occurred near Fr=0.5, v=1.75-2.15 m/s and was consistent for all evaluated ages. Of the analytical regression models tested, linear regression models had the best performance for predicting vertical GRF data in foals with an average absolute error percent of 7.97% during trotting and 2.39% during walking, compared to a non-linear logistic model with an error of 8.38%. The model was converted to Python and implemented to predict GRF data for foals using the subject velocity and limb length as input. Our resulting analytical model can be used to estimate the GRF profile of equine gait enabling comparative studies of locomotion.

developmental biology↗

bioRxiv2024

Impact of long-term rapamycin treatment on age-related osteoarthritis in common marmoset

PurposeGenetic deletion of mTOR has protected against post-traumatic osteoarthritis (OA) in male mice, however, effects of pharmacological mTOR-inhibition are equivocal and have not been tested in aging models nor in female subjects. Therefore, the goal of this study was to determine if mTOR-inhibition by rapamycin can modify OA pathology in aging non-human primates and female mice. MethodsCommon marmosets were administered oral rapamycin (1mg/kg/day) or vehicle starting near mid-life until death. Five-month-old, female C57BL/6J mice were treated with vehicle or rapamycin (IP, 2mg/kg, 3x/week) for 8-weeks following non-invasive ACL rupture. Knee OA pathology was assessed via microCT and histology. Phosphorylation of mTORC1 (p-RPS6S235/36) and mTORC2 (p-AktS473, p-NDRG1T638, p-PKCT348) substrates were evaluated via western blot in articular cartilage, meniscus, and/or infrapatellar fat pad. ATDC5 cells were cultured with rapamycin to determine time and dose effects on mTORC1/2 signaling. ResultsIn marmosets, rapamycin did not impact age-related radiographic OA severity or cartilage pathology but increased medial meniscus calcification and lowered lateral tibia subchondral thickness, particularly in females. In female mice, rapamycin worsened ACLR-induced meniscus calcification and cartilage pathology. In marmoset and mouse joint tissues, rapamycin inhibited mTORC1 and increased p-AktS473 but not p-NDRG1T638 or p-PKCT348. This mTOR signaling pattern was replicated in ATDC5 cells during exposure to low concentrations of rapamycin. ConclusionsRapamycin attenuated mTORC1 signaling with feedback activation of AktS473 in articular cartilage, meniscus, and/or infrapatellar fat pad and was accompanied by deleterious effects on meniscus calcification and/or cartilage pathology in female mice and common marmosets.

physiology↗

bioRxiv2024

A registration strategy to characterize DTI-observed changes in skeletal muscle architecture due to passive shortening

Skeletal muscle architecture is a key determinant of muscle function. Architectural properties such as fascicle length, pennation angle, and curvature can be characterized using Diffusion Tensor Imaging (DTI), but acquiring these data during a contraction is not currently feasible. However, an image registration-based strategy may be able to convert muscle architectural properties observed at rest to their contracted state. As an initial step toward this long-term objective, the aim of this study was to determine if an image registration strategy could be used to convert the whole-muscle average architectural properties observed in the extended joint position to those of a flexed position, following passive rotation. DTI and high-resolution fat/water scans were acquired in the lower leg of seven healthy participants on a 3T MR system in +20{degrees} (plantarflexion) and -10{degrees} (dorsiflexion) foot positions. The diffusion and anatomical images from the two positions were used to propagate DTI fiber-tracts from seed points along a mesh representation of the aponeurosis of fiber insertion. The -10{degrees} and +20{degrees} anatomical images were registered and the displacement fields were used to transform the mesh and fiber-tracts from the +20{degrees} to the -10{degrees} position. Students paired t-tests were used to compare the mean architectural parameters between the original and transformed fiber-tracts. The whole-muscle average fiber-tract length, pennation angle, curvature, and physiological cross-sectional areas estimates did not differ significantly. DTI fiber-tracts in plantarflexion can be transformed to dorsiflexion position without significantly affecting the average architectural characteristics of the fiber-tracts. In the future, a similar approach could be used to evaluate muscle architecture in a contracted state.

physiology↗

bioRxiv2020

Tough and Tunable Scaffold-Hydrogel Composite Biomaterial for Soft-to-Hard Musculoskeletal Tissue Interfaces

Biological interfaces connecting tissues with dissimilar mechanical and structural properties are ubiquitous throughout the musculoskeletal system. Tendons attach to bone via a fibrocartilaginous interface (enthesis) that reduces mechanical strain and resultant tissue failure. Despite this toughening mechanism, tears at the enthesis occur due to acute (overload) or degradative (aging) processes. Repair involves surgical fixation of the torn tendon to bone, but results in the formation of a narrow fibrovascular scar tissue with inferior biomechanical properties. Progress toward enthesis regeneration requires biomaterial approaches to protect exogenously added or endogenously recruited cells from high levels of strain at the interface between dissimilar materials. Here, we describe an innovative reinforcement strategy to address this need. We report a stratified scaffold containing collagen bone and tendon tissue compartments linked by a continuous polyethylene glycol (PEG) hydrogel interface. Tuning the gelation kinetics of the hydrogel modulates its integration with the surrounding biomaterial compartments and yields biomechanical performance advantages. Notably, the continuous hydrogel interface reduces the deleterious effects of strain concentrations that form between tissue compartments in conventional stratified biomaterials. This design of mechanically robust stratified composite biomaterials may be appropriate for a broad range of tendon and ligament-to-bone insertions.

bioengineering↗

bioRxiv2018

Murine bone properties and their relationship to gait during growth

Allometric relationships have been queried over orders of mammals to understand how bone accommodates the mechanical demands associated with increasing mass. However, less attention has been given to the scaling of bone within a single lifetime. We aimed to determine if bone morphology and apparent density is related to (1) bending and compressive strength, and (2) gait dynamics. Longitudinal in vivo computed tomography and gait data were collected from female rats (n=5, age 8 - 20 weeks). Cross sectional properties and apparent density were measured at the diaphysis, distal, and proximal regions of the tibia and scaling exponents were calculated. Finite-element models were used to simulate four-point bending and axial compression using time-specific ground reaction forces (GRF) to calculate the mean strain energy density (SED) at the midshaft. Second moment of area at the diaphysis followed strain similarity based allometry, while bone area was positively allometric. The average SED at the diaphysis decreased, especially after the age of 10 weeks (R2=0.99), while it increased in compression (R2=0.96). The apparent density in all regions initially increased and converged by 11 weeks of age and this was correlated with changes in joint angle. The scaling analyses implies that rodent tibia is (re)modeled in order to sustain bending at the midshaft during growth. The finite element results and relatively constant density after 10 weeks of age indicate that structural parameters may be the primary determinant of bone strength in the growing rodent tibia. The correlations between bone properties and joint angles imply that the changes in posture may affect bone growth in specific regions.

bioengineering↗