Passive Tissue Research Articles

Experimental validation of a novel spine model demonstrates the large contribution of passive muscle to the flexion relaxation phenomenon

When an individual enters a maximally flexed spine position, their largest extensor muscles become electrically inactive despite a substantial extensor moment demand being placed on the low back; this is termed flexion relaxation. Stresses within intervertebral discs, ligaments, and passive muscles are thought to support this moment thereby allowing the extensor muscles to ‘turn off’. While the mechanical behaviour of the intervertebral disc and ligaments have been studied extensively, less is known regarding the moment supported by passive muscle tissue during spine flexion. Here we estimated the L4/L5 moment supported by the passive musculature during spine flexion based on experimentally derived architectural and material properties. We then tested the validity of the passive muscle prediction by determining whether the cumulative passive tissue moment (including passive muscle, intervertebral discs, and ligaments) would support the extensor moment demand—calculated with inverse dynamics—near maximum spine flexion. The model predicted that the passive tissues were able to support the entire extensor moment demand, indicating that muscle activity was not required to support the weight of the upper body, consistent with the mechanism of flexion relaxation. The model further demonstrated that despite being inactive, spine muscles still greatly contribute to flexion relaxation by passively supporting ~47% of the extensor moment demand on the spine. Finally, there was strong agreement between the predicted active muscle moments and the recorded spine muscle activity (EMG); this strong agreement persisted when the external moment was manipulated using a pulley-system. These findings provide additional confidence that the estimated passive muscle moments are reasonably accurate throughout spine flexion.

Gut Homeostasis: Active Migration of Intestinal Epithelial Cells in Tissue Renewal.

A new study has uncovered a previously unknown feature of intestinal epithelial cells during gut homeostasis. Biophysical modeling combined with quantitative tissue imaging indicates that epithelial cells actively migrate up the gut villus, challenging the current concept of passive tissue renewal.

Lumbar posture and individual flexibility influence back muscle flexion-relaxation phenomenon while sitting

Although numerous studies have documented back muscle flexion-relaxation phenomenon (FRP) in standing postures, few studies have examined the FRP in various seated lumbar postures and individual flexibilities. This study, therefore, recruited 18 male students and assigned to low- and high-flexibility groups (9 in each). Activation of thoracic and lumbar erector spinae (ES) and lumbosacral angles were examined while participants sat in two postures (lordosis and kyphosis) and flexed their trunks at 15°, 30°, 45°, 60°, and maximum flexion. Results showed that kyphotic lumbar posture caused relatively low and unchangeable thoracic and lumbar ES activations, whereas lordotic lumbar posture engendered more contractive and varying thoracic and lumbar ES activations. Flexible participants exhibited higher thoracic ES activation than less flexible participants during lordotic sitting. Thoracic ES seemed to play a compensative role to stabilize the spine in the lordotic sitting posture, especially when the trunk was flexed over 45°. In lordotic lumbar posture, FRP occurred only in the lumbar ES; however, the activation and lumbosacral angles were still higher than those in kyphotic posture. The increased back muscle activation associated with lumbar lordosis may partially share the load on passive interspinous tissues, which are close to the discs during these flexed trunk positions. Relevance to industryThis study suggests that various lumbar postures and individual flexibilities may cause different FRP patterns when sitting. While performing seated tasks, people should exercise caution about the lumbar posture.

Prediction of Left Ventricular Mechanics Using Machine Learning.

The goal of this paper was to provide a real-time left ventricular (LV) mechanics simulator using machine learning (ML). Finite element (FE) simulations were conducted for the LV with different material properties to obtain a training set. A hyperelastic fiber-reinforced material model was used to describe the passive behavior of the myocardium during diastole. The active behavior of the heart resulting from myofiber contractions was added to the passive tissue during systole. The active and passive properties govern the LV constitutive equation. These mechanical properties were altered using optimal Latin hypercube design of experiments to obtain training FE models with varied active properties (volume and pressure predictions) and varied passive properties (stress predictions). For prediction of LV pressures, we used eXtreme Gradient Boosting (XGboost) and Cubist, and XGBoost was used for predictions of LV pressures, volumes as well as LV stresses. The LV pressure and volume results obtained from ML were similar to FE computations. The ML results could capture the shape of LV pressure as well as LV pressure-volume loops. The results predicted by Cubist were smoother than those from XGBoost. The mean absolute errors were as follows: XGBoost volume: 1.734 ± 0.584 ml, XGBoost pressure: 1.544 ± 0.298 mmHg, Cubist volume: 1.495 ± 0.260 ml, Cubist pressure: 1.623 ± 0.191 mmHg, myofiber stress: 0.334 ± 0.228 kPa, cross myofiber stress: 0.075 ± 0.024 kPa, and shear stress: 0.050 ± 0.032 kPa. The simulation results show ML can predict LV mechanics much faster than the FE method. The ML model can be used as a tool to predict LV behavior. Training of our ML model based on a large group of subjects can improve its predictability for real world applications.

Introduction of lactobionic acid ligand into mixed-charge nanoparticles to realize in situ triggered active targeting to hepatoma cells.

To overcome the dilemma between passive tissue targeting and active cell targeting, nanomaterials are often required to exhibit the transition from ‘stealth’ to ‘active targetable’ in response to the pathological microenvironment. Here, we introduced a ternary surface modification method that incorporating active targeting ligand lactobionic acid with pH-sensitive mixed-charge surface. The resulted mixed-charge gold nanoparticles (LA@MC-GNPs) showed resistance to non-specific adsorption of proteins and uptake by HepG2 cells at normal tissue pH 7.4, while they underwent pH-sensitive aggregation and recovered active targeting capability at tumor acidic pH 6.5. The ternary surface modification method provided a simplest strategy to solve the dilemma between passive and active targeting of nanomedicine.

Hydrophilic Small Molecules That Harness Transthyretin To Enhance the Safety and Efficacy of Targeted Chemotherapeutic Agents.

The hydrophobicity of many chemotherapeutic agents usually results in their nonselective passive distribution into healthy cells and organs causing collateral toxicity. Ligand-targeted drugs (LTDs) are a promising class of targeted anticancer agents. The hydrophilicity of the targeting ligands in LTDs limits its nonselective passive tissue distribution and toxicity to healthy cells. In addition, the small size of LTDs allows for better tumor penetration, especially in the case of solid tumors. However, the short circulation half-life of LTDs, due to their hydrophilicity and small size, remains a significant challenge for achieving their full therapeutic potential. Therefore, extending the circulation half-life of targeted chemotherapeutic agents while maintaining their hydrophilicity and small size will represent a significant advance toward effective and safe cancer treatment. Here, we present a new approach for enhancing the safety and efficacy of targeted chemotherapeutic agents. By endowing hydrophobic chemotherapeutic agents with a targeting moiety and a hydrophilic small molecule that binds reversibly to the serum protein transthyretin, we generated small hydrophilic drug conjugates that displayed enhanced circulation half-life in rodents and selectivity to cancer cells. To the best of our knowledge, this is the first demonstration of a successful approach that maintains the small size and hydrophilicity of targeted anticancer agents containing hydrophobic payloads while at the same time extending their circulation half-life. This was demonstrated by the superior in vivo efficacy and lower toxicity of our conjugates in xenograft mouse models of metastatic prostate cancer.

Prolonged Collagen Peptide Supplementation and Resistance Exercise Training Affects Body Composition in Recreationally Active Men.

We aimed to determine the effects of long-term collagen peptide (CP) supplementation and resistance exercise training (RET) on body composition, strength, and muscle fiber cross-sectional area (fCSA) in recreationally active men. Fifty-seven young men were randomly and double-blinded divided into a group receiving either collagen peptides (COL, 15 g/day) or a placebo (PLA). Strength testing, bioimpedance analysis, and muscle biopsies were used prior to and after an RET intervention. Food record protocols were performed during the RET intervention. The groups trained three times a week for 12 weeks. Baseline parameters showed no differences between groups, and the external training load and dietary food intake were also similar. COL showed a significant increase in fat-free mass (FFM) compared with the placebo group (p < 0.05). Body fat mass (BFM) was unchanged in COL, whereas a significant increase in BFM was observed in PLA. Both groups showed significant increases in all strength tests, with a trend for a slightly more pronounced effect in COL. The fCSA of type II muscle fibers increased significantly in both groups without differences between the two groups. We firstly demonstrated improved body composition in healthy, recreationally active men subsequent to prolonged CP supplementation in combination with RET. As the observed increase in FFM was not reflected in differences in fCSA hypertrophy between groups, we assume enhanced passive connective tissue adaptations in COL due to CP intake.

Active contractile properties of fascia.

The ubiquitous network of fascial tissues in the human body is usually regarded as a passive contributor to musculoskeletal dynamics. This review aims to highlight the current understanding of fascial stiffness regulation. Notably the ability for active cellular contraction which may augment the stiffness of fascial tissues and thereby contribute to musculoskeletal dynamics. A related narrative literature search via PubMed and Google Scholar reveals a multitude of studies indicating that the intrafascial presence of myofibroblasts may enable these tissues to alter their stiffness. This contractile tissue behavior occurs not only in several pathological fibrotic contractures but has also been documented in normal fasciae. When viewed at time frames of seconds and minutes the force of such tissue contractions is not sufficient for exerting a significant effect on mechanical joint stability. However, when viewed in a time-window of several minutes and longer, such cellular contractions can impact motoneuronal coordination. In addition, over a time frame of days to months, this cellular activity can induce long-term and severe tissue contractures. These findings tend to question the common clear distinction between active tissues and passive tissues in musculoskeletal dynamics. Clin. Anat. 32:891-895, 2019. © 2019 Wiley Periodicals, Inc.

A micromechanical muscle model for determining the impact of motor unit fiber clustering on force transmission in aging skeletal muscle

This study used a micromechanical finite element muscle model to investigate the effects of the redistribution of spatial activation patterns in young and old muscle. The geometry consisted of a bundle of 19 active muscle fibers encased in endomysium sheets, surrounded by passive tissue to model a fascicle. Force was induced by activating combinations of the 19 active muscle fibers. The spacial clustering of muscle fibers modeled in this study showed unbalanced strains suggesting tissue damage at higher strain levels may occur during higher levels of activation and/or during dynamic conditions. These patterns of motor unit remodeling are one of the consequences of motor unit loss and reinnervation associated with aging. The results did not reveal evident quantitative changes in force transmission between old and young adults, but the patterns of stress and strain distribution were affected, suggesting an uneven distribution of the forces may occur within the fascicle that could provide a mechanism for muscle injury in older muscle.

Activation-Dependent Changes in Soleus Length-Tension Behavior Augment Ankle Joint Quasi-Stiffness.

The triceps surae muscle-tendon units are important in governing walking performance, acting to regulate mechanical behavior of the ankle through interaction between active muscle and passive elastic structures. Ankle joint quasi-stiffness (the slope of the relation between ankle moment and ankle rotation, kA) is a useful aggregate measure of this mechanical behavior. However, the role of muscle activation and length-tension behavior in augmenting kA remains unclear. In this study, 10 subjects completed eccentric isokinetic contractions at rest and at 2 soleus activation levels (25% and 75% isometric voluntary contraction) prescribed using electromyographic biofeedback. Ultrasound imaging quantified activation-dependent modulation of soleus muscle length-tension behavior and its role in augmenting kA. The authors found that soleus muscle stiffness (kM) and kA exhibit nonlinear relations with muscle activation and both were more sensitive to the onset of activation than to subsequent increases in activation. Our findings also suggest that kA can be modulated via activation through changes in soleus muscle length-tension behavior. However, this modulation is more complex than previously appreciated-reflecting interaction between active muscle and passive elastic tissues. Our findings may have implications for understanding normal and pathological ankle joint function and the design of impedance-based prostheses.

Three‐dimensional reconstruction of Prdm family gene expression patterns during mouse development stage by tissue clearing technique

The Prdm family has recently spawned considerable interest as it has been implicated in fundamental aspects of cellular differentiation and exhibits expanding ties to human diseases. Several Prdm family members are deregulated in human diseases, most prominently in solid cancers, where they can act as both tumor suppressors or drivers of oncogenic processes. Some Prdm genes might play an essential role in gene expression were confined to the mammalian central nervous system. We hypothesized that the Prdm gene family may also significantly participate in the development of the mammalian nervous system is required to explore how the gene by the advanced pathological analysis. To assess Prdm family gene expressions patterns at the formation of central nervous system during mouse development stage. The study of the genetic regulation of embryonic development requires the three‐dimensional mapping of gene expression at the high‐resolution microscopic level. We generated transparent mouse embryos by new modified passive tissue clearing technique called mPACT method. Mouse embryos of sequential stage were obtained from three distinct developmental stages, intact embryos was optical transparency to mPACT methods in few days. We reconstructed three‐dimensional expression patterns of Prdm family and blood vessel using transparent mouse embryos. Partial Prdm gene expression was concentrated in the brain and spinal cord regions of each embryo. In this study, we developed embryo‐specific simple clearing method for creating see‐through mouse embryo complete with transparent organ. In addition, our study reconfirmed that some Prdm gene might be a transcriptional regulator for normal neural tissue differentiation during mouse embryonic development using three‐dimensional analysis and transparent embryos.Support or Funding InformationThis work was supported by the Brain Korea 21 PLUS Project for Medical Science, Yonsei University. In addition, this work was supported by a grant from the National Research Foundation of Korea (NRF‐2017R1D1A1B03030315).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A low noise stable radiometer front-end for passive microwave tissue thermometry

ABSTRACTA low noise, high gain, stable radiometer front-end is presented for non-invasive tissue thermometry using custom designed narrow band low noise amplifiers (LNAs) and band pass filter (BPF) with 1.3 GHz centre frequency and − 20 dB pass band of 332 MHz. The fabricated LNAs have >15 dB gain, unconditional gain stability and noise figure (NF) < 1.45 dB in the pass band. The maximum insertion loss of the BPF is <1 dB over 1.2–1.4 GHz with 50 dB suppression in the surrounding communication bands. The cascaded radiometer front-end has measured gain of 45–50 dB, NF < 1.75 dB in the pass band and > 30 dB suppression in the adjacent personal communication bands. The Allan deviation of the total power radiometer indicates long term system stability and presence of Gaussian thermal noise for integration time, . Radiometer measurements of a matched load at room temperature for indicate acceptably low influence of external electromagnetic interference (EMI) and system noise equivalent temperature of 145 K. The brightness temperature measured by the total power radiometer using a resonant slot antenna demonstrates the ability to detect a 0.3°C change in the test load temperature with better than 0.1°C accuracy.

Analysis of the main passive soft tissues associated with adult acquired flatfoot deformity development: A computational modeling approach

Adult acquired flatfoot deformity (AAFD) is a pathology with a wide range of treatment options. Physicians decide the best treatment based on their experience, so the process is entirely subjective. A better understanding of soft tissue stress and its contribution in supporting the plantar arch could help to guide the clinical decision. Traditional experimental trials cannot consistently evaluate the contribution of each tissue. Therefore, in this research a 3-Dimensional FE foot model was reconstructed from a normal patient in order to measure the stress of the passive stabilizers of the arch, and its variation in different scenarios related with intermediate stages of AAFD development. All bones, the plantar fascia (PF), cartilages, plantar ligaments and the spring ligament (SL) were included, respecting their anatomical distribution and biomechanical characteristics. An AAFD evaluation scenario was simulated. The relative contribution of each tissue was obtained comparing each result with a normal case. The results show that PF is the main tissue that prevents the arch elongation, while SL mainly reduces the foot pronation. Long and short plantar ligaments play a secondary role in this process. The stress increment on both PF and SL when one of two fails suggests that these tissues complement each other. These findings support the theory that regards the tibialis posterior tendon as a secondary actor in the arch maintenance, compared with the PF and the SL, because this tendon is overstretched by the hindfoot pronation around the talonavicular joint. This approach could help to improve the understanding of AAFD.

Effects of exoskeleton use on movement kinematics during performance of common work tasks: A case study.

An exoskeleton may assist performance of basic work-related tasks. Its application should not alter user kinematics, which compromise user safety. This case study was used to assess whether people wearing a lower-body K-SRDTM exoskeleton could complete common work tasks without altering kinematics that may increase injury risk. Three males performed three tasks: kneeling and standing (kneel), lifting and lowering a weighted box floor-to-waist (lift), and stair-climbing with a weighted box (climb), all repeated with and without exoskeleton use (EXO, NONE). Kinematics with EXO often mimicked NONE. Hip and knee flexion with EXO often exceeded NONE without increasing heart rate for kneel. During lift with EXO, participants avoided greater lateral trunk flexion associated with injuries and used the preferred semi-squat technique. Participants produced more foot clearance with EXO than NONE during climb. Other outcomes of heart rate, perceived exertion, fatigue, and usability were mixed. EXO augmentation does not need to alter movement kinematics during performances of kneel, lift, and climb tasks. EXO kinematic alterations did not appear to compromise user safety in terms of lateral trunk bending. It may encourage good technique, such as greater foot clearance to avoid tripping, for some tasks, and changes in lifting strategies to avoid extreme flexion and protect passive tissues.

Fingering instabilities in tissue invasion: an active fluid model.

Metastatic tumours often invade healthy neighbouring tissues by forming multicellular finger-like protrusions emerging from the cancer mass. To understand the mechanical context behind this phenomenon, we here develop a minimalist fluid model of a self-propelled, growing biological tissue. The theory involves only four mechanical parameters and remains analytically trackable in various settings. As an application of the model, we study the evolution of a two-dimensional circular droplet made of our active and expanding fluid, and embedded in a passive non-growing tissue. This system could be used to model the evolution of a carcinoma in an epithelial layer. We find that our description can explain the propensity of tumour tissues to fingering instabilities, as conditioned by the magnitude of active traction and the growth kinetics. We are also able to derive predictions for the tumour size at the onset of metastasis, and for the number of subsequent invasive fingers. Our active fluid model may help describe a wider range of biological processes, including wound healing and developmental patterning.

The role of intra- and epimuscular fasciae beyond being passive structural elements: MRI analyses indicate that they interfere with and affect muscle’s active mechanics

Introduction: Contractile properties are central to skeletal muscles' contribution to joint range of movement (JROM) and force production. However, the contractile apparatus is integral to intramuscular fasciæ, which are continuous with epimuscular fasciæ. Altered properties of these due to pathological changes also affect activated muscles' mechanics (Yucesoy & Huijing 2007). This is not simply because the force developed in passive fasciæ is added to muscle force. Instead, mechanics of intra- and epimuscular fasciæ also affect sarcomeres (Yucesoy 2010). Diffusion tensor (DT) imaging measures local anisotropy of muscle tissue, describing local fiber architecture via tractography. Magnetic Resonance (MR) images compared with Demon's non-rigid registration provide local strains. In human medial gastrocnemius (GM), in vivo, we assessed strains within intra- and epimuscular fasciæ, and along muscle fibers: i.e., force transmission via passive connective tissues and consequent effects on sarcomere lengths, respectively.

A comparison of lumbar spine and muscle loading between male and female workers during box transfers

There is a clear relationship between lumbar spine loading and back musculoskeletal disorders in manual materials handling. The incidence of back disorders is greater in women than men, and for similar work demands females are functioning closer to their physiological limit. It is crucial to study loading on the spine musculoskeletal system with actual handlers, including females, to better understand the risk of back disorders. Extrapolation from biomechanical studies conducted on unexperienced subjects (mainly males) might not be applicable to actual female workers. For male workers, expertise changes the lumbar spine flexion, passive spine resistance, and active/passive muscle forces. However, experienced females select similar postures to those of novices when spine loading is critical. This study proposes that the techniques adopted by male experts, male novices, and females (with considerable experience but not categorized as experts) impact their lumbar spine musculoskeletal systems differently. Spinal loads, muscle forces, and passive resistance (muscle and ligamentous spine) were predicted by a multi-joint EMG-assisted optimization musculoskeletal model of the lumbar spine. Expert males flexed their lumbar spine less (avg. 21.9° vs 30.3–31.7°) and showed decreased passive internal moments (muscle avg. 8.9% vs 15.9–16.0%; spine avg. 4.7% vs 7.1–7.8%) and increased active internal moments (avg. 72.9% vs 62.0–63.9%), thus producing a different impact on their lumbar spine musculoskeletal systems. Experienced females sustained the highest relative spine loads (compression avg. 7.3 N/BW vs 6.2–6.4 N/BW; shear avg. 2.3 N/BW vs 1.7–1.8 N/BW) in addition to passive muscle and ligamentous spine resistance similar to novices. Combined with smaller body size, less strength, and the sequential lifting technique used by females, this could potentially mean greater risk of back injury. Workers should be trained early to limit excessive and repetitive stretching of their lumbar spine passive tissues.

Coupling between a fiber-reinforced model and a Hill-based contractile model for passive and active tissue properties of laryngeal muscles: A finite element study

In this work, a three-dimensional fiber-reinforced model was used to simulate passive stress response of vocal fold muscle tissue undergoing a series of isometric force measurement and a dynamic stretching. It was found that, with proper material constants, the fiber-reinforced model is able to reproduce literature data with acceptable deviation. A Hill-based contractile model was then coupled with the fiber-reinforced model to enable simulations of stretching-induced and activation-induced stress at the same time. For dynamic, concurrent tissue stimulation and stretching, the coupled model demonstrated a good agreement with past experimental data.

Lumbar Range of Motion and Flexion Relaxation Phenomenon Onset During Static Trunk Bending Postures

The purpose of the current study was to assess the changes in lumbar tissue load sharing mechanism and lumbar range of motion at different trunk flexion postures. Eight participants performed the tasks of changing lumbar posture from extended to flexed posture while maintaining fixed trunk postures (30°, 60°, or 90°). Results of the present study showed that FRP onset was observed in almost all the trials at two conditions of trunk posture (i.e. 60° and 90°). The results also showed that lumbar range of motion changed significantly between the different levels of trunk posture. Findings of the current study could help for better understanding of the dynamics of lumbar active and passive tissue loading during static trunk flexion.

Effects of lumbar tissue viscoelastic changes on lumbar-pelvic motion pattern

Lumbar passive tissue elongation is a potential risk factor for the development of low back pain. In this study, we explored the effect of lumbar passive tissue elongation on lumbar-pelvic coordination pattern during trunk flexion/extension task. Thirteen participants performed 5 trials of trunk flexion/extension task both before and after a lumbar passive tissue elongation protocol. Trunk kinematics were recorded to calculate lumbar–pelvic continuous relative phase (CRP) and CRP variability. Results showed that passive tissue elongation significantly decreased the mean lumbar-pelvic CRP and CRP variability. Our results indicate that prolonged experienced lumbar passive tissue elongation should be avoided in an occupational environment.