External Training Loads and Soft-Tissue Injury Occurrence During Congested Versus Noncongested Periods in Football.

OBJECTIVE: To analyze the influence of congested and noncongested fixture periods during 2 seasons in a professional male football team on soft-tissue injury incidence and external load. METHODS: Thirty-three professional football players from a Portuguese Liga I team participated in this study. Weekly external load and soft-tissue injury rate and burden of 2 consecutive seasons (2021-22 and 2022-23) were analyzed. RESULTS: Total soft-tissue injury rate and burden for the 2 seasons were 3.9 and 3.2 injuries per 1000 hours and 71.8 and 60.5 days per 1000 hours for congested and noncongested periods, respectively. No significant differences were observed between congested and noncongested periods. Total high-speed running, sprint distance, distance above 80% and 90% of maximal velocity, and meters accelerating and decelerating above 2 m/s2 were significantly higher for noncongested weeks. Match accelerations and decelerations above 3 m/s2 were higher during congested periods and training during noncongested periods. No differences between the 2 periods were observed for the total number of accelerations and decelerations above 3 m/s2. Overall, physical outputs per week were higher for training during noncongested weeks, whereas matches during congested periods registered higher external load. CONCLUSIONS: No effect of a congested schedule was observed on soft-tissue injury rates and injury burden. Higher match exposure during congested periods increased external load performed per week, and during noncongested periods, training load was superior to congested weeks.

Comparing Sagittal-Plane Biomechanics of Drop Jump Landing in Athletes With and Without Knee Osteoarthritis 2-Year Post-Anterior Cruciate Ligament Reconstruction.

The study aimed to determine differences in sagittal-plane joint biomechanics between athletes with and without knee osteoarthritis (OA) during drop vertical jump 2 years after anterior cruciate ligament reconstruction (ACLR). Forty-one athletes with ACLR completed motion analysis testing during drop vertical jump from 30 cm. Sagittal-plane peak joint angles and moments and joint contributions to total support moment (TSM) were calculated during first landing. Medial compartment knee OA of the reconstructed knee was evaluated using Kellgren-Lawrence scores (ACLR group: Kellgren-Lawrence <2; ACLR-OA group: Kellgren-Lawrence ≥2). The ACLR-OA group (n = 13) had higher hip and lower knee contributions in the surgical limb than the ACLR group and their nonsurgical limb. Further, the ACLR-OA group had higher peak hip extension moment than the ACLR group (P = .024). The ACLR-OA group had significantly lower peak knee extension and ankle plantar flexion moments and TSM (P ≤ .032) than ACLR group. The ACLR-OA group landed with increased hip extension moment, decreased knee extension and ankle plantar flexion moments and TSM, and decreased knee and increased hip contributions to TSM compared with ACLR group. The ACLR-OA group may have adopted movement patterns to decrease knee load and compensated by shifting the load to the hip. Clinicians may incorporate tailored rehabilitation programs that mitigate the decreased knee load to minimize the risk of knee OA after ACLR.

Mechanical Behavior of Five Different Morse Taper Implants and Abutments with Different Conical Internal Connections and Angles: An In Vitro Experimental Study.

The present study evaluated the mechanical behavior of five designs of Morse taper (MT) connections with and without the application of loads. For this, the detorque of the fixing screw and the traction force required to disconnect the abutment from the implant were assessed. A total of 100 sets of implants/abutments (IAs) with MT-type connections were used, comprising five groups (n = 20/group): (1) Group Imp 11.5: IA sets with a cone angulation of 11.5°; (2) Group SIN 11.5: with a cone angulation of 11.5°; (3) Group SIN 16: with a cone angulation of 16°; (4) Group Neo 16: with a cone angulation of 16°; and (5) Group Str 15: with a cone angulation of 15°. All sets received the torque recommended by the manufacturer. After applying the torque, the counter torque of the fixing screws was measured in ten IA sets of each group without the application of cyclic loads (frequencies ≤ 2 Hz, 360,000 cycles, and force at 150 Ncm). The other ten sets of each group were subjected to cyclic loads, after which the detorque was measured. Afterwards, the force for disconnection between the implant and the abutment was measured by traction on all the samples. The untwisting of the abutment fixation screws showed a decrease in relation to the initial torque applied in all groups. In the unloaded samples, it was found to be -25.7% in Group 1, -30.4% in Group 2, -36.8% in Group 3, -29.6% in Group 4, and -25.7% in Group 5. After the applied loads, it was found to be -44% in Group 1, -43.5% in Group 2, -48.5% in Group 3, -47.2% in Group 4, and -49.8% in Group 5. The values for the IA sets were zero for SIN 16 (Group 3) and Neo16 (Group 4), both without and with loads. In the other three groups, without loads, the disconnection value was 56.3 ± 2.21 N (Group 1), 30.7 ± 2.00 N (Group 2), and 26.0 ± 2.52 N (Group 5). After applying loads, the values were 63.5 ± 3.06 N for Group 1, 34.2 ± 2.45 N in Group 2, and 23.1 ± 1.29 N in Group 5. It was concluded that in terms of the mechanical behavior of the five designs of MT IA sets, with and without the application of loads, the Imp 11.5, SIN 11.5, and Srt 15 groups showed better results compared to the SIN 16 and Neo 16 groups, showing that lower values of cone angulation increase the friction between the parts (IA), thus avoiding the need to maintain the torque of the fixing screw to maintain the union of the sets.

A new animal model of lumbar disc degeneration in rabbits.

BACKGROUND CONTEXT: There are many models of lumbar disc degeneration, but mechanical stress-induced lumbar disc degeneration is rare. Here we propose a mechanical stress-induced lumbar disc degeneration model to better understand the molecular mechanism of lumbar disc degeneration under stress stimulation. PURPOSE: To design a new model of lumbar disc degeneration under mechanical stress. STUDY DESIGN: The anatomic approach of the oblique lateral approach to lumbar fusion surgery was used to design a longitudinal compression device across the vertebral body of the rabbit to impose longitudinal load on the lumbar disc. METHODS: New Zealand white rabbits (n=30) were used. Screws were used to cross the rabbits' lumbar vertebral bodies, and both sides of the screws were pressurized. Continuous compression was then performed for 28 days. Adjacent unpressurized lumbar discs serve as controls for pressurized lumbar discs. At 28 days after surgery, micro-computed tomography (CT) and magnetic resonance imaging (MRI) were performed on the rabbits' lumbar discs. After the imaging examination, lumbar disc samples were removed, Safranin-O fast green and immunofluorescence was performed to detect the expression level of intervertebral disc degeneration-related proteins. RESULTS: The CT results showed that the disc height did not decrease significantly after mechanical loading. The MRI results showed that the signals in the pressurized disc decreased 28 days after loading. The results of Safranin-O fast green showed that the cartilage component of the intervertebral disc after mechanical compression was significantly reduced. The immunofluorescence results showed that the expression of ADAMTS5 and MMP13 protein in the nucleus pulposus of the intervertebral disc after mechanical compression increased, while the expression of SOX9 decreased, and the difference was statistically significant. Aggrecan's protein expression decreased, but was not statistically significant. CONCLUSIONS: This study designed a reliable model of disc degeneration in rabbits. It is more likely to mimic disc compression in the human body. CLINICAL SIGNIFICANCE: This animal model can be used as a basic model to study the molecular physiological mechanisms of discogenic low back pain.

Repetitive strikes loading organ culture model to investigate the biological and biomechanical responses of the intervertebral disc.

Background: Disc degeneration is associated with repetitive violent injuries. This study aims to explore the impact of repetitive strikes loading on the biology and biomechanics of intervertebral discs (IVDs) using an organ culture model. Methods: IVDs from the bovine tail were isolated and cultured in a bioreactor, with exposure to various loading conditions. The control group was subjected to physiological loading, while the model group was exposed to either one strike loading (compression at 38% of IVD height) or repetitive one strike loading (compression at 38% of IVD height). Disc height and dynamic compressive stiffness were measured after overnight swelling and loading. Furthermore, histological morphology, cell viability, and gene expression were analyzed on Day 32. Glycosaminoglycan (GAG) and nitric oxide (NO) release in conditioned medium were also analyzed. Results: The repetitive one strike group exhibited early disc degeneration, characterized by decreased dynamic compression stiffness, the presence of annulus fibrosus clefts, and degradation of the extracellular matrix. Additionally, this group demonstrated significantly higher levels of cell death (p < 0.05) and glycosaminoglycan (GAG) release (p < 0.05) compared to the control group. Furthermore, upregulation of MMP1, MMP13, and ADAMTS5 was observed in both nucleus pulposus (NP) and annulus fibrosus (AF) tissues of the repetitive one strike group (p < 0.05). The one strike group exhibited annulus fibrosus clefts but showed no gene expression changes compared to the control group. Conclusions: This study shows that repetitive violent injuries lead to the degeneration of a healthy bovine IVDs, thereby providing new insights into early-stage disc degeneration.

MyoLoop: Design, development and validation of a standalone bioreactor for pathophysiological electromechanical in vitro cardiac studies.

Mechanical load is one of the main determinants of cardiac structure and function. Mechanical load is studied in vitro using cardiac preparations together with loading protocols (e.g., auxotonic, isometric). However, such studies are often limited by reductionist models and poorly simulated mechanical load profiles. This hinders the physiological relevance of findings. Living myocardial slices have been used to study load in vitro. Living myocardial slices (LMS) are 300-µm-thick intact organotypic preparations obtained from explanted animal or human hearts. They have preserved cellular populations and the functional, structural, metabolic and molecular profile of the tissue from which they are prepared. Using a three-element Windkessel (3EWK) model we previously showed that LMSs can be cultured while performing cardiac work loops with different preload and afterload. Under such conditions, LMSs remodel as a function of the mechanical load applied to them (physiological load, pressure or volume overload). These studies were conducted in commercially available length actuators that had to be extensively modified for culture experiments. In this paper, we demonstrate the design, development and validation of a novel device, MyoLoop. MyoLoop is a bioreactor that can pace, thermoregulate, acquire and process data, and chronically load LMSs and other cardiac tissues in vitro. In MyoLoop, load is parametrised using a 3EWK model, which can be used to recreate physiological and pathological work loops and the remodelling response to these. We believe MyoLoop is the next frontier in basic cardiovascular research enabling reductionist but physiologically relevant in vitro mechanical studies.

Abnormal types of intervertebral disc structure and related mechanical loading with biomechanical factors / 中国组织工程研究

BACKGROUND:The problem of intervertebral disc injury and degeneration has been studied in many ways.Many studies have shown that intervertebral disc injury and degeneration is driven by mechanical loading factors.However,the potential relationship between common phenotypes of intervertebral disc injury and degeneration and mechanical loading factors has been rarely summarized. OBJECTIVE:To summarize the types of common structural abnormalities exhibited by intervertebral disc injury and degeneration in the published literature,and sum up the potential links to the types of mechanical loading that lead to these structural abnormalities in in vitro and ex vivo experimental studies. METHODS:Using the terms"intervertebral disc failure,intervertebral disc injury,mechanical load,mechanical factor,load factor,biomechanics"as Chinese and English key words in PubMed,CNKI,and WanFang databases,articles related to intervertebral disc injury degeneration and mechanical load factors were retrieved.Literature screening was performed according to the inclusion and exclusion criteria,and 88 articles were finally included. RESULTS AND CONCLUSION:(1)Common structural abnormalities of intervertebral discs include decreased intervertebral disc height,disc bulge,osteophyte formation,annulus fibrosus tear,intervertebral disc herniation or disc prolapse,endplate damage,Schmorl nodes and intervertebral disc calcification.Intervertebral discs are susceptible to mechanical load types such as compression,bending,axial rotation,and compound loads.(2)The compressive load mainly causes the decrease of the proteoglycan content and the water-binding ability of the intervertebral disc,leading to the decrease or swelling of the intervertebral disc and further damage and degeneration of the intervertebral disc.In addition,the excessive compressive load causes greater damage to the endplate.(3)Bending load and axial rotation load damage the annulus fibrosus more than the endplate,and prolonged or repeated bending loads can cause tearing of the fibrous annulus and herniation or prolapse of the intervertebral disc,while pure axial rotation loads can induce less damage to the intervertebral disc and only cause the tear of the annulus fibrosus.(4)However,when different load types act in combination,it is more likely to result in high stress on the disc and a greater risk of disc injury.(5)Injury and degeneration of the intervertebral disc present progressive structural damage,and early prevention and protection are particularly important in clinical practice.Future tissue engineering research can start with early repair of the intervertebral disc.

Maintenance of internal load despite a stepwise reduction in external load during moderate intensity heart rate clamped cycling with acute graded normobaric hypoxia in males.

OBJECTIVES: To investigate the acute effects of graded hypoxia on external and internal loads during 60 min of endurance cycling at a clamped heart rate. DESIGN: Repeated measures. METHODS: On separate visits, 16 trained males cycled for 60 min at a clamped heart rate corresponding to 80 % of their first ventilatory threshold at sea-level and 2500 m, 3000 m, 3500 m and 4000 m simulated altitudes (inspired oxygen fractions of 20.9 %, 15.4 %, 14.5 %, 13.6 % and 12.7 %, respectively). Markers of external (power output) and internal (blood lactate concentration, tissue saturation index, cardio-respiratory and perceptual responses) loads were measured every 15 min during cycling. Neuromuscular function of knee extensors was characterised pre- and post-exercise. RESULTS: Compared to sea-level (101 ±â€¯22 W), there was a stepwise reduction in power output with increasing hypoxia severity (-17.9 ±â€¯8.9 %, -27.1 ±â€¯10.7 %, -34.2 ±â€¯12.0 % and - 44.6 ±â€¯15.1 % at 2500 m, 3000 m, 3500 m, and 4000 m, respectively, all p < 0.05). Blood lactate and tissue saturation index were not different across hypoxia severities, and perceptual responses were exacerbated at 4000 m only, with increased breathing difficulty. Knee extensor torque decreased post-exercise (-14.5 ±â€¯9.0 %, p < 0.05), independent of condition. CONCLUSIONS: Increasing hypoxia severity reduces cycling power output and arterial oxygen saturation in a stepwise fashion without affecting exercise responses between sea-level and simulated altitudes up to 3500 m despite breathing difficulty being elevated at 4000 m.

Osteopontin Upregulation, Induced by the Continuous Mechanical Load in Adipose Tissue-Derived Mesenchymal Stem Cells, is Strongly Restricted in INF-γ/TNF-α/IL-22 Microenvironment.

The osteogenic potential of mesenchymal stem cells (MSc) in axial spondyloarthritis (AxSpA) depends on the interplay of inflammation and multiple hormonal and local mechanical factors. In this study, MCs, derived from the adipose tissue of a healthy donor, were cultured under or without continuous mechanical load in the osteogenic differentiation medium with or without the addition of testosterone, cocktail of INF-γ/TNF-α/IL-22, or both. Real-time PCR for osteogenic transcription factors demonstrated that in the absence of INF-γ/TNF-α/IL-22, mechanical load causes significant upregulation of SPP1 (osteopontin), while the presence of the inflammatory cytokines almost completely abolishes this effect. In addition, exposure to INF-γ/TNF-α/IL-22 slightly upregulated BMP2, but suppressed the expression of ALPL, Col1A1, and SPP1, reinforcing the hypothesis that the inflammatory environment allows MSc to commit toward the IL-22-driven osteogenic differentiation but can restrict the later stages of osteogenesis. In summary, osteopontin can play a role in the pathogenesis of AxSpA, linking between mechanical load and pathological bone formation.

Relationship between mechanical load and surface erosion degradation of a shape memory elastomer poly(glycerol-dodecanoate) for soft tissue implant.

Poly(glycerol-dodecanoate) (PGD) has aroused increasing attention in biomedical engineering for its degradability, shape memory and rubber-like mechanical properties, giving it potential to fabricate intelligent implants for soft tissues. Adjustable degradation is important for biodegradable implants and is affected by various factors. The mechanical load has been shown to play an important role in regulating polymer degradation in vivo. An in-depth investigation of PGD degradation under mechanical load is essential for adjusting its degradation behavior after implantation, further guiding to regulate degradation behavior of soft tissue implants made by PGD. In vitro degradation of PGD under different compressive and tensile load has proceeded in this study and describes the relationships by empirical equations. Based on the equations, a continuum damage model is designed to simulate surface erosion degradation of PGD under stress through finite element analysis, which provides a protocol for PGD implants with different geometric structures at varied mechanical conditions and provides solutions for predicting in vivo degradation processes, stress distribution during degradation and optimization of the loaded drug release.

Influence of sex hormones status and type of training on regional bone mineral density in exercising females.

The primary objective of this study was to examine the influence of hormonal ovarian profile and training characteristics on spine, pelvis, and total body bone mineral density (BMD) in a group of well-trained females. Forty-two eumenorrheic females, twenty-eight monophasic oral contraceptive (OC) users and thirteen postmenopausal females participated in this study. Body composition was measured by total body dual-energy X-ray absorptiometry (DXA) to determine BMD of the areas of interest. Endurance-trained premenopausal females showed lower spine BMD compared to resistance-trained premenopausal females (1.03 ± 0.1 vs. 1.09 ± 0.09 g/cm2; p = 0.025). Postmenopausal females reported lower BMD level in comparison to eumenorrheic females in pelvis (1.079 ± 0.082 vs 1.19 ± 0.115 g/cm2; p = 0.005), spine (0.969 ± 0.097 vs 1.069 ± 0.109 g/cm2; p = 0.012) and total (1.122 ± 0.08 vs 1.193 ± 0.077 g/cm2; p = 0.018) and OC users whose duration of OC use was less than 5 years (OC < 5) in pelvis (1.235 ± 0.068 g/cm2; p < 0.001) and spine (1.062 ± 0.069 g/cm2; p = 0.018). In addition, lower BMD values were found in OC users who had been using OC for more than 5 years (OC ≥ 5) than eumenorrheic females in pelvis (1.078 ± 0.086 g/cm2; p = 0.029) and spine (0.966 ± 0.08 g/cm2; p = 0.05). Likewise, OC ≥ 5 showed lower values than and OC < 5 in pelvis (p = 0.004) and spine (p = 0.047). We observed a lower spine BMD value in premenopausal endurance-trained females compared to premenopausal resistance-trained females. Moreover, this research observed that prolonged use of OCs may reduce bone mass acquisition in the spine and pelvis, even in well-trained females. Finally, postmenopausal showed lower BMD despite being exercising women.Trial registration: ClinicalTrials.gov identifier: NCT04458662.Highlights Ovarian hormonal profile should be considered when assessing BMD in female athletes.The duration of oral contraceptive use influences spine and pelvis regional BMD in exercising females.Postmenopausal women show lower BMD when compared to premenopausal females despite being exercising females.

Chemical and mechanical activation of resident cardiac macrophages in the living myocardial slice ex vivo model.

Resident cardiac macrophages (rcMACs) are among the most abundant immune cells in the heart. Plasticity and activation are hallmarks of rcMACs in response to changes in the microenvironment, which is essential for in vitro experimentation. The in vivo investigation is confounded by the infiltration of other cells hindering direct studies of rcMACs. As a tool to investigate rcMACs, we applied the ex vivo model of living myocardial slices (LMS). LMS are ultrathin ex vivo multicellular cardiac preparations in which the circulatory network is interrupted. The absence of infiltration in this model enables the investigation of the rcMACs response to immunomodulatory and mechanical stimulations. Such conditions were generated by applying interferon-gamma (IFN-γ) or interleukine-4 (IL-4) and altering the preload of cultured LMS, respectively. The immunomodulatory stimulation of the LMS induced alterations of the gene expression pattern without affecting tissue contractility. Following 24 h culture, low input RNA sequencing of rcMACs isolated from LMS was used for gene ontology analysis. Reducing the tissue stretch (unloading) of LMS altered the gene ontology clusters of isolated rcMACs with intermediate semantic similarity to IFN-γ triggered reaction. Through the overlap of genes affected by IFN-γ and unloading, we identified Allograft inflammatory factor 1 (AIF-1) as a potential marker gene for inflammation of rcMACs as significantly altered in whole immunomodulated LMS. MicroRNAs associated with the transcriptomic changes of rcMACs in unloaded LMS were identified in silico. Here, we demonstrate the approach of LMS to understand load-triggered cardiac inflammation and, thus, identify potential translationally important therapeutic targets.

Optimal microstructure and mechanical properties of open-cell porous titanium structures produced by selective laser melting.

Three-dimensional printing technology enables the production of open cell porous structures. This has advantages but not only in terms of weight reduction. In implant structures, the process of osseointegration is improved, mechanical integration is better, the open cell porous structures resemble a trabecular structure that mimics bone tissue. In this work, we investigated titanium structures made porous by cutting spheres. Based on the patterns of different types of crystal models we created porosity with different strategies. We have shown that there are significant differences in mechanical properties between the porous structures formed with different strategies. We determined the structure that loses the least load-bearing capacity compared to the solid structure, with the same porosity levels and mechanical stresses. We characterized the possibility location and environment of becoming an open cell structure. We performed the calculations with mechanical simulations, which were validated experimentally. The quality of the three-dimensional printing of samples was checked by computed tomography reconstruction analysis.

Cyclic uniaxial mechanical load enhances chondrogenesis through entraining the molecular circadian clock.

The biomechanical environment plays a key role in regulating cartilage formation, but the current understanding of mechanotransduction pathways in chondrogenic cells is incomplete. Among the combination of external factors that control chondrogenesis are temporal cues that are governed by the cell-autonomous circadian clock. However, mechanical stimulation has not yet directly been proven to modulate chondrogenesis via entraining the circadian clock in chondroprogenitor cells. The purpose of this study was to establish whether mechanical stimuli entrain the core clock in chondrogenic cells, and whether augmented chondrogenesis caused by mechanical loading was at least partially mediated by the synchronised, rhythmic expression of the core circadian clock genes, chondrogenic transcription factors, and cartilage matrix constituents at both transcript and protein levels. We report here, for the first time, that cyclic uniaxial mechanical load applied for 1 h for a period of 6 days entrains the molecular clockwork in chondroprogenitor cells during chondrogenesis in limb bud-derived micromass cultures. In addition to the several core clock genes and proteins, the chondrogenic markers SOX9 and ACAN also followed a robust sinusoidal rhythmic expression pattern. These rhythmic conditions significantly enhanced cartilage matrix production and upregulated marker gene expression. The observed chondrogenesis-promoting effect of the mechanical environment was at least partially attributable to its entraining effect on the molecular clockwork, as co-application of the small molecule clock modulator longdaysin attenuated the stimulatory effects of mechanical load. This study suggests that an optimal biomechanical environment enhances tissue homoeostasis and histogenesis during chondrogenesis at least partially through entraining the molecular clockwork.

Impact of External Mechanical Loads on Coda Waves in Concrete.

During their life span, concrete structures interact with many kinds of external mechanical loads. Most of these loads are considered in advance and result in reversible deformations. Nevertheless, some of the loads cause irreversible, sometimes unnoticed changes below the macroscopic scale depending on the type and dimension of the impact. As the functionality of concrete structures is often relevant to safety and society, their condition must be known and, therefore, assessed on a regular basis. Out of the spectrum of non-destructive monitoring methods, Coda Wave Interferometry using embedded ultrasonic sensors is one particularly sensitive technique to evaluate changes to heterogeneous media. However, there are various influences on Coda waves in concrete, and the interpretation of their superimposed effect is ambiguous. In this study, we quantify the relations of uniaxial compression and uniaxial tension on Coda waves propagating in normal concrete. We found that both the signal correlation of ultrasonic signals as well as their velocity variation directly reflect the stress change in concrete structures in a laboratory environment. For the linear elastic range up to 30% of the strength, we calculated a velocity variation of -0.97‱/MPa for compression and 0.33%/MPa for tension using linear regression. In addition, these parameters revealed even weak irreversible changes after removal of the load. Furthermore, we show the time-dependent effects of shrinkage and creep on Coda waves by providing the development of the signal parameters over time during half a year together with creep recovery. Our observations showed that time-dependent material changes must be taken into account for any comparison of ultrasonic signals that are far apart in time. The study's results demonstrate how Coda Wave Interferometry is capable of monitoring stress changes and detecting even small-size microstructural changes. By indicating the stated relations and their separation from further impacts, e.g., temperature and moisture, we anticipate our study to contribute to the qualification of Coda Wave Interferometry for its application as an early-warning system for concrete structures.

The efficacy of different sealer removal protocols on the microtensile bond strength of adhesives to a bioceramic sealer-contaminated dentin.

Background: The optimal bonding of adhesives to dentin requires the sealer to be completely removed from the dentinal walls. Aim: This study compared the efficacy of different sealer removal protocols on the microtensile bond strengths (MTBS) of single-step adhesives to a calcium silicate-based bioceramic root canal sealer-contaminated dentin. Materials and Methods: Standardized box-shaped Class I cavities were prepared in human lower third molars (N = 50). All cavities were contaminated with a bioceramic root canal sealer (Endosequence BC Sealer, Brasseler, Savannah, USA), except the control group (G1) cavities. For the experimental groups, contaminated dentin surfaces were wiped with a dry cotton pellet (G2), wiped with a cotton pellet saturated with water (G3), rinsed with the air/water spray (G4), and passively applied aqueous ultrasonic energy with an ultrasonic scaler (G5) before the restoration procedure. All the cavity surface was restored with a one-bottle universal adhesive and composite resin. All the specimens were subjected to both thermocycling (2,500 thermal cycles from 5 to 55°C, with a 30-s dwelling time and a 10-s transfer time) and mechanical loading (50 N load for 100,000 cycles). The restored specimens were sectioned into resin-dentin beams for MTBS evaluation. Additional specimens were prepared for the scanning electron microscopy (SEM) to examine the dentin-adhesive interface (n = 10). Results: No significant difference was found between the mean bond strengths of the groups. In SEM examination, no residual sealer was found in any group. Conclusion: Calcium silicate-based bioceramic sealer was removed from the dentin surface with all removal protocols when evaluated with MTBS after the thermal and mechanical cycle tests.

Myocardial Fatigue: a Mechano-energetic Concept in Heart Failure.

PURPOSE OF REVIEW: This review combines existing mechano-energetic principles to provide a refreshing perspective in heart failure (HF) and examine if the phenomenon of myocardial fatigue can be rigorously tested in vitro with current technological advances as a bridge between pre-clinical science and clinical practice. RECENT FINDINGS: As a testament to the changing paradigm of HF pathophysiology, there has been a shift of focus from structural to functional causes, as reflected in its modern universal definition and redefined classification. Bolstered by recent landmark trials of sodium-glucose cotransport-2 inhibitors across the HF spectrum, there is a rekindled interest to revisit the basic physiological tenets of energetic efficiency, metabolic flexibility, and mechanical load on myocardial performance. Indeed, these principles are well established in the study of skeletal muscle fatigue. Since both striated muscles share similar sarcomeric building blocks, is it possible that myocardial fatigue can occur in the face of sustained adverse supra-physiological load as a functional cause of HF? Myocardial fatigue is a mechano-energetic concept that offers a novel functional mechanism in HF. It is supported by current studies on exercise-induced cardiac fatigue and reverse translational science such as from recent landmark trials on sodium glucose co-transporter 2 inhibitors in HF. We propose a novel framework of myocardial fatigue, injury, and damage that aligns with the contemporary notion of HF as a continuous spectrum, helps determine the chance and trajectory of myocardial recovery, and aims to unify the plethora of cellular and molecular mechanisms in HF.

Heat Shock Protein Overexpression-Mediated Periodontal Ligament Regeneration: A Fundamental Approach to Generate a Potential Biomaterial.

The periodontal ligament (PDL) is a cell-rich fibrous connective tissue supporting the tooth roots. The tissue helps to maintain homeostasis and exhibits regenerative and repairing ability, which is mediated by the heat shock protein (HSP). Here, we experimentally created PDL tissue with notable ability to regenerate hard tissue and evaluated it as a potential biomaterial. We immunohistochemically examined the mechanical load-induced HSP overexpression in mouse PDL. Following mechanical load application and release, HSP70 localization in the PDL was altered immediately, suggesting that the HSP70 function may differ with the timing of its expression in PDL. HSP70 expressed in the cytoplasm and nucleus of fibroblasts in PDL on the tension side not only participated in periodontium repair, but also functioned as a molecular chaperone during protein expression involved in osteogenesis to restructure injured tissue. This study highlights the potential of artificially created highly functional PDL tissues as biomaterials.

Effects of Geometry and Loading Mode on the Stress State in Asphalt Mixture Cracking Tests.

Currently, a variety of asphalt mixture cracking characterization tests are available as screening tools for the better selection of high-quality raw materials and also for the optimization of mixture design for different applications. However, for a same evaluation index, using different sample geometries and loading modes might lead to obtaining different values, which prevents the application of the evaluation index as a fundamental parameter in pavement design. In this paper, the effects of geometry and loading mode on the stress state in the experimental characterization of asphalt mixture cracking were discussed using numerical simulation. The results showed that applying thermally-induced load in restrained uniaxial test configuration should be considered when performing an asphalt mixture cracking test. Compared with direct tensile configuration, compressive stress clearly existed in other common test configurations, which may prevent the initiation and propagation of cracks. Moreover, it was revealed that nonuniform stress state exists in the dog-bone geometry, which makes it possible to know the failure plane in advance and place gauges at the failure plane for measuring fundamental deformation-related properties.

Mechanosensitive molecular mechanisms of myocardial fibrosis in living myocardial slices.

AIMS: Altered mechanical load in response to injury is a main driver of myocardial interstitial fibrosis. No current in vitro model can precisely modulate mechanical load in a multicellular environment while maintaining physiological behaviour. Living myocardial slices (LMS) are a 300 µm-thick cardiac preparation with preserved physiological structure and function. Here we apply varying degrees of mechanical preload to rat and human LMS to evaluate early cellular, molecular, and functionality changes related to myocardial fibrosis. METHODS AND RESULTS: Left ventricular LMS were obtained from Sprague Dawley rat hearts and human cardiac samples from healthy and failing (dilated cardiomyopathy) hearts. LMS were mounted on custom stretchers and two degrees of diastolic load were applied: physiological sarcomere length (SL) (SL = 2.2 µm) and overload (SL = 2.4 µm). LMS were maintained for 48 h under electrical stimulation in circulating, oxygenated media at 37°C. In overloaded conditions, LMS displayed an increase in nucleus translocation of Yes-associated protein (YAP) and an up-regulation of mechanotransduction markers without loss in cell viability. Expression of fibrotic and inflammatory markers, as well as Collagen I deposition were also observed. Functionally, overloaded LMS displayed lower contractility (7.48 ± 3.07 mN mm-2 at 2.2 SL vs. 3.53 ± 1.80 mN mm-2 at 2.4 SL). The addition of the profibrotic protein interleukin-11 (IL-11) showed similar results to the application of overload with enhanced fibrosis (8% more of collagen surface coverage) and reduced LMS contractility at physiological load. Conversely, treatment with the Transforming growth factor ß receptor (TGF-ßR) blocker SB-431542, showed down-regulation of genes associated with mechanical stress, prevention of fibrotic response and improvement in cardiac function despite overload (from 2.40 ± 0.8 mN mm-2 to 4.60 ± 1.08 mN mm-2 ). CONCLUSIONS: The LMS have a consistent fibrotic remodelling response to pathological load, which can be modulated by a TGF-ßR blocker. The LMS platform allows the study of mechanosensitive molecular mechanisms of myocardial fibrosis and can lead to the development of novel therapeutic strategies.