Journal of Biomechanical Engineering-Transactions of the Asme最新文献

Intradiscal injection is required to deliver therapeutic agents to the intervertebral disc (IVD) nucleus pulposus (NP). However, injectate leakage following needle retraction may result in decreased treatment efficacy and adverse side effects. While enzymatic digestion is a common research approach for simulating degeneration in healthy animal IVDs, contributions to the leakage phenomenon are unknown. In this study, bovine caudal discs were treated with injection into the NP of either a tris buffer control, collagenase (to primarily target collagen), or trypsin (to primarily target proteoglycans) and then injected with fluorescent saline using a through-puncture defect protocol. Pressure-volume records during injection were used to determine volume and pressure at leakage. Discs were then frozen, transected, and photographed to visualize injectate dispersion. Collagenase treatment resulted in a large increase in injectate dispersion, along with a decrease in injection pressure relative to control. Trypsin treatment resulted in a moderate increase in dispersion, with no associated effect on pressure. This study concludes that care should be taken when employing enzymatic digestion to simulate IVD degeneration, as NP tissue disruption may affect both retention and dispersion of subsequent therapeutic injections.

Skeletal muscle architecture is a strong predictor of in vivo functional capacity and is evaluated in fixed tissues, accommodating the study of human muscles from cadaveric donors. Previous studies evaluating the pelvic floor muscles (PFMs) demonstrated that the rat is the most appropriate small animal model for the study of female PFM architecture, but the rat's suitability for the study of male PFMs is undetermined. We aimed to determine (1) whether PFM architecture exhibits sexual dimorphism in rats or humans, and (2) if the rat is also a suitable animal model for the study of male human PFMs. PFMs were fixed in situ and harvested en bloc from male and female cadaveric donors and 3-month-old male and female Sprague-Dawley rats. Three architectural parameters influenced by species size were used to compare male versus female PFMs within species, while four size-independent measures compared species within sex. All comparisons were made with two-way analysis of variances and Tukey's multiple comparisons tests post hoc. Sarcomere length (rats and humans, p = 0.016 and = 0.002) and normalized fiber length (rats, p < 0.001) were significantly larger in male PFMs. Three of the size-independent measures exhibited similar species trends in both sexes, while the size-independent sarcomere length measure (Ls/Lso) differed between male rats and humans (p < 0.001). Thus, sexual dimorphism is present in rat and human PFM architecture, and the male rat is suitable for studies of human male PFMs.

A bone bruise is generated by a bony collision that could occur when the anterior cruciate ligament (ACL) is injured, and its pattern reflects the injury mechanism and skeletal maturity. Thus, the bone bruise pattern is useful to predict a subject-specific injury mechanism, although the sensitivity and/or effect of the material property and the knee position at injury is still unclear. The objective of the present study was to determine the effect of the material property and knee position on the bone bruise pattern in skeletally mature and immature subjects using finite element analysis. Finite element models were created from a magnetic resonance (MR) image in the sagittal plane of a skeletally mature (25 y. o.) and immature (9 y. o.) male subject. The femur and tibia were collided at 2 m/s to simulate the impact trauma and determine the maximum principal stress. The analysis was performed at 15, 30, and 45 deg of knee flexion, and neutral, 10 mm anterior and posterior translated position at each knee flexion angle. Although high stress was distributed toward the metaphysis area in the mature model, the stress did not cross the growth plate in the immature model. The size of the stress area was larger in the mature model than those in the immature model. The location of the stress area changed depending on the joint position. Young's modulus of cartilage and trabecular bone also affected the location of the stress area. The Young's modulus for the cartilage affected peak stress during impact, while the size of the stress area had almost no change. These results indicate that the bone bruise pattern is strongly associated with subject-specific parameters. In addition, the bone bruise pattern was affected not only by knee position but also by tissue qualities. In conclusion, although the bone bruise distribution was generally called footprint of the injury, the combined evaluation of the quality of the structure and the bone bruise distribution is necessary for properly diagnosing tissue injury based on the MR imaging.

Tendinopathy is a leading cause of mobility issues. Currently, the cell-matrix interactions involved in the development of tendinopathy are not fully understood. In vitro tendon models provide a unique tool for addressing this knowledge gap as they permit fine control over biochemical, micromechanical, and structural aspects of the local environment to explore cell-matrix interactions. In this study, direct-write, near-field electrospinning of gelatin solution was implemented to fabricate micron-scale fibrous scaffolds that mimic native collagen fiber size and orientation. The stiffness of these fibrous scaffolds was found to be controllable between 1 MPa and 8 MPa using different crosslinking methods (EDC, DHT, DHT+EDC) or through altering the duration of crosslinking with EDC (1 h to 24 h). EDC crosslinking provided the greatest fiber stability, surviving up to 3 weeks in vitro. Differences in stiffness resulted in phenotypic changes for equine tenocytes with low stiffness fibers (∼1 MPa) promoting an elongated nuclear aspect ratio while those on high stiffness fibers (∼8 MPa) were rounded. High stiffness fibers resulted in the upregulation of matrix metalloproteinase (MMPs) and proteoglycans (possible indicators for tendinopathy) relative to low stiffness fibers. These results demonstrate the feasibility of direct-written gelatin scaffolds as tendon in vitro models and provide evidence that matrix mechanical properties may be crucial factors in cell-matrix interactions during tendinopathy formation.

Individuals with transtibial amputation (TTA) experience asymmetric lower-limb loading which can lead to joint pain and injuries. However, it is unclear how walking over unexpected uneven terrain affects their loading patterns. This study sought to use modeling and simulation to determine how peak joint contact forces and impulses change for individuals with unilateral TTA during an uneven step and subsequent recovery step and how those patterns compare to able-bodied individuals. We expected residual limb loading during the uneven step and intact limb loading during the recovery step would increase relative to flush walking. Further, individuals with TTA would experience larger loading increases compared to able-bodied individuals. Simulations of individuals with TTA showed during the uneven step, changes in joint loading occurred at all joints except the prosthetic ankle relative to flush walking. During the recovery step, intact limb joint loading increased in early stance relative to flush walking. Simulations of able-bodied individuals showed large increases in ankle joint loading for both surface conditions. Overall, increases in early stance knee joint loading were larger for those with TTA compared to able-bodied individuals during both steps. These results suggest that individuals with TTA experience altered joint loading patterns when stepping on uneven terrain. Future work should investigate whether an adapting ankle-foot prosthesis can mitigate these changes to reduce injury risk.

Cervical remodeling is critical for a healthy pregnancy. Premature tissue changes can lead to preterm birth (PTB), and the absence of remodeling can lead to post-term birth, causing significant morbidity. Comprehensive characterization of cervical material properties is necessary to uncover the mechanisms behind abnormal cervical softening. Quantifying cervical material properties during gestation is challenging in humans. Thus, a nonhuman primate (NHP) model is employed for this study. In this study, cervical tissue samples were collected from Rhesus macaques before pregnancy and at three gestational time points. Indentation and tension mechanical tests were conducted, coupled with digital image correlation (DIC), constitutive material modeling, and inverse finite element analysis (IFEA) to characterize the equilibrium material response of the macaque cervix during pregnancy. Results show, as gestation progresses: (1) the cervical fiber network becomes more extensible (nonpregnant versus pregnant locking stretch: 2.03 ± 1.09 versus 2.99 ± 1.39) and less stiff (nonpregnant versus pregnant initial stiffness: 272 ± 252 kPa versus 43 ± 43 kPa); (2) the ground substance compressibility does not change much (nonpregnant versus pregnant bulk modulus: 1.37 ± 0.82 kPa versus 2.81 ± 2.81 kPa); (3) fiber network dispersion increases, moving from aligned to randomly oriented (nonpregnant versus pregnant concentration coefficient: 1.03 ± 0.46 versus 0.50 ± 0.20); and (4) the largest change in fiber stiffness and dispersion happen during the second trimester. These results, for the first time, reveal the remodeling process of a nonhuman primate cervix and its distinct regimes throughout the entire pregnancy.

Skin undergoes mechanical alterations due to changes in the composition and structure of the collagenous dermis with aging. Previous studies have conflicting findings, with both increased and decreased stiffness reported for aging skin. The underlying structure-function relationships that drive age-related changes are complex and difficult to study individually. One potential contributor to these variations is the accumulation of nonenzymatic crosslinks within collagen fibers, which affect dermal collagen remodeling and mechanical properties. Specifically, these crosslinks make individual fibers stiffer in their plastic loading region and lead to increased fragmentation of the collagenous network. To better understand the influence of these changes, we investigated the impact of nonenzymatic crosslink changes on the dermal microstructure using discrete fiber networks representative of the dermal microstructure. Our findings suggest that stiffening the plastic region of collagen's mechanical response has minimal effects on network-level stiffness and failure stresses. Conversely, simulating fragmentation through a loss of connectivity substantially reduces network stiffness and failure stress, while increasing stretch ratios at failure.

Healthy articular cartilage is a remarkable bearing material optimized for near-frictionless joint articulation. Because its limited self-repair capacity renders it susceptible to osteoarthritis (OA), approaches to reinforce or rebuild degenerative cartilage are of significant interest. While exogenous collagen crosslinking (CXL) treatments improve cartilage's mechanical properties and increase its resistance to enzymatic degradation, their effects on cartilage lubrication remain less clear. Here, we examined how the collagen crosslinking agents genipin (GP) and glutaraldehyde (GTA) impact cartilage lubrication using the convergent stationary contact area (cSCA) configuration. Unlike classical configurations, the cSCA sustains biofidelic kinetic friction coefficients (μk) via superposition of interstitial and hydrodynamic pressurization (i.e., tribological rehydration). As expected, glutaraldehyde- and genipin-mediated CXL increased cartilage's tensile and compressive moduli. Although net tribological rehydration was retained after CXL, GP or GTA treatment drastically elevated μk. Both healthy and "OA-like" cartilage (generated via enzymatic digestion) sustained remarkably low μk in saline- (≤0.02) and synovial fluid-lubricated contacts (≤0.006). After CXL, μk increased up to 30-fold, reaching values associated with marked chondrocyte death in vitro. These results demonstrate that mechanical properties (i.e., stiffness) are necessary, but not sufficient, metrics of cartilage function. Furthermore, the marked impairment in lubrication suggests that CXL-mediated stiffening is ill-suited to cartilage preservation or joint resurfacing.

Aging is a primary risk factor for degenerative tendon injuries, yet the etiology and progression of this degeneration are poorly understood. While aged tendons have innate cellular differences that support a reduced ability to maintain mechanical tissue homeostasis, the response of aged tendons to altered levels of mechanical loading has not yet been studied. To address this question, we subjected young and aged murine flexor tendon explants to various levels of in vitro tensile strain. We first compared the effect of static and cyclic strain on matrix remodeling in young tendons, finding that cyclic strain is optimal for studying remodeling in vitro. We then investigated the remodeling response of young and aged tendon explants after 7 days of varied mechanical stimulus (stress deprivation, 1%, 3%, 5%, or 7% cyclic strain) via assessment of tissue composition, biosynthetic capacity, and degradation profiles. We hypothesized that aged tendons would show muted adaptive responses to changes in tensile strain and exhibit a shifted mechanical setpoint, at which the remodeling balance is optimal. Interestingly, we found that 1% cyclic strain best maintains native physiology while promoting extracellular matrix (ECM) turnover for both age groups. However, aged tendons display fewer strain-dependent changes, suggesting a reduced ability to adapt to altered levels of mechanical loading. This work has a significant impact on understanding the regulation of tissue homeostasis in aged tendons, which can inform clinical rehabilitation strategies for treating elderly patients.

Wildland firefighters (WLFFs) experience lung function decline due to occupational exposure to fire smoke. WLFFs typically do not wear respiratory personal protective equipment, and if they do, it is a simple bandana, which is not effective at filtering smoke. To pinpoint the biological underpinnings of abnormal respiratory function following 3-7 years of WLFF service, we exposed mice to Douglas fir smoke (DFS) over 8 weeks. Following exposure, we assessed changes in lung structure through Magnetic Resonance Imaging (MRI) and histological analysis, which was supported by immunohistochemistry staining. With MRI, we found that the signal decay time, T2*, from ultrashort echo time (UTE) images was significantly shorter in mice exposed to DFS compared to air controls. In addition, the variation in T2* was more heterogeneously distributed throughout the left lung in DFS-exposed mice, compared to air controls. As confirmed by histological analysis, shorter T2* was caused by larger parenchyma airspace sizes and not fibrotic remodeling. Destruction of the alveolar spaces was likely due to inflammation, as measured by an influx of CD68+ macrophages and destruction due to enhanced neutrophil elastase. In addition, measurements of airspace dimensions from histology were more heterogeneously distributed throughout the lung, corroborating the enhanced relative dispersion of T2*. Findings from this study suggest that the decline in lung function observed in WLFFs may be due to emphysema-like changes in the lung, which can be quantified with MRI.