Modulus Of Tissue Research Articles

Characterizing the acoustic response of Thalassia testudinum leaves using resonator measurements and finite element modeling.

Seagrasses play an important role in coastal ecosystems and serve as important marine carbon stores. Acoustic monitoring techniques exploit the sensitivity of underwater sound to bubbles, which are produced as a byproduct of photosynthesis and present within the seagrass tissue. To make accurate assessments of seagrass biomass and productivity, a model is needed to describe acoustic propagation through the seagrass meadow that includes the effects of gas contained within the seagrass leaves. For this purpose, a new seagrass leaf model is described for Thalassia testudinum that consists of a comparatively rigid epidermis that composes the outer shell of the leaf and comparatively compliant aerenchyma that surrounds the gas channels on the interior of the leaf. With the bulk modulus and density of the seagrass tissue determined by previous work, this study focused on characterizing the shear moduli of the epidermis and aerenchyma. These properties were determined through a combination of dynamic mechanical analysis and acoustic resonator measurements coupled with microscopic imagery and finite element modeling. The shear moduli varied as a function of length along the leaves with values of 100 and 1.8 MPa at the basal end and 900 and 3.7 MPa at the apical end for the epidermis and aerenchyma, respectively.

The non-intuitive, in-vivo behavior of aponeuroses in a unipennate muscle

Experimental observations and theoretical models suggest that the loading of muscular aponeuroses is complex, causing strain patterns that are not reconcilable with the frequently assumed mechanical “in series” arrangement of aponeuroses with muscles and tendons. The purpose of this work was to measure the in-vivo longitudinal strains of the distal and proximal aponeuroses and force of the unipennate Medial Gastrocnemius (MG) muscle during locomotor activities. Sonomicrometry crystals and a force buckle transducer were implanted to measure aponeurosis strains and MG forces in the left hindlimb of four healthy female sheep while walking at different speeds and inclination angles on a motorized treadmill. The resulting aponeurosis strains versus the corresponding muscle forces resulted in a complex interaction that is not reconcilable with a mechanical “in series” arrangement of aponeuroses with either the free tendon or muscle, as has frequently been assumed when trying to determine the storage and release of mechanical energy in muscles or the stiffness and elastic modulus of in-vivo aponeurosis tissues. We conclude that the interaction of muscle tissue with aponeuroses in the sheep MG allows for elongation of the aponeuroses at low forces in the passive muscle, while elongation in the active muscle is greatly reduced possibly due to the complex shear forces and pressures produced when the muscle is activated. It is likely that the observed aponeurosis mechanics are similar in other unipennate skeletal muscles, but the current study was limited to a single muscle and therefore does not allow for such extrapolation at this time.

Effect of radiation-induced damage of trabecular bone tissue evaluated using indentation and digital volume correlation

Exposure to X-ray radiation for an extended amount of time can cause damage to the bone tissue and therefore affect its mechanical properties. Specifically, high-resolution X-ray Computed Tomography (XCT), in both synchrotron and lab-based systems, has been employed extensively for evaluating bone micro-to-nano architecture. However, to date, it is still unclear how long exposures to X-ray radiation affect the mechanical properties of trabecular bone, particularly in relation to lab-XCT systems. Indentation has been widely used to identify local mechanical properties such as hardness and elastic modulus of bone and other biological tissues. The purpose of this study is therefore, to use indentation and XCT-based investigative tools such as digital volume correlation (DVC) to assess the microdamage induced by long exposure of trabecular bone tissue to X-ray radiation and how this affects its local mechanical properties. Trabecular bone specimens were indented before and after X-ray exposures of 33 and 66 h, where variation of elastic modulus was evaluated at every stage. The resulting elastic modulus was decreased, and micro-cracks appeared in the specimens after the first long X-ray exposure and crack formation increased after the second exposure. High strain concentration around the damaged tissue exceeding 1% was also observed from DVC analysis. The outcomes of this study show the importance of designing appropriate XCT-based experiments in lab systems to avoid degradation of the bone tissue mechanical properties due to radiation and these results will help to inform future studies that require long X-ray exposure for in situ experiments or generation of reliable subject-specific computational models.

Heterogeneous matrix stiffness regulates the cancer stem-like cell phenotype in hepatocellular carcinoma

BackgroundSolid tumors are stiffer than their surrounding normal tissues; however, their interior stiffness is not uniform. Under certain conditions, cancer cells can acquire stem-like phenotypes. However, it remains unclear how the heterogeneous physical microenvironment affects stemness expression in cancer cells. Here, we aimed to evaluate matrix stiffness heterogeneity in hepatocellular carcinoma (HCC) tissues and to explore the regulation effect of the tumor microenvironment on stem-like phenotypic changes through mechanical transduction.MethodsFirst, we used atomic force microscopy (AFM) to evaluate the elastic modulus of HCC tissues. We then used hydrogel with adjustable stiffness to investigate the effect of matrix stiffness on the stem-like phenotype expression of HCC cells. Moreover, cells cultured on hydrogel with different stiffness were subjected to morphology, real-time PCR, western blotting, and immunofluorescence analyses to explore the mechanotransduction pathway. Finally, animal models were used to validate in vitro results.ResultsAFM results confirmed the heterogenous matrix stiffness in HCC tissue. Cancer cells adhered to hydrogel with varying stiffness (1.10 ± 0.34 kPa, 4.47 ± 1.19 kPa, and 10.61 kPa) exhibited different cellular and cytoskeleton morphology. Higher matrix stiffness promoted the stem-like phenotype expression and reduced sorafenib-induced apoptosis. In contrast, lower stiffness induced the expression of proliferation-related protein Ki67. Moreover, mechanical signals were transmitted into cells through the integrin–yes-associated protein (YAP) pathway. Higher matrix stiffness did not affect YAP expression, however, reduced the proportion of phosphorylated YAP, promoted YAP nuclear translocation, and regulated gene transcription. Finally, application of ATN-161 (integrin inhibitor) and verteporfin (YAP inhibitor) effectively blocked the stem-like phenotype expression regulated by matrix stiffness.ConclusionsOur experiments provide new insights into the interaction between matrix stiffness, cancer cell stemness, and heterogeneity, while also providing a novel HCC therapeutic strategy.

Technologien zur In-vivo-Untersuchung der Biomechanik der Hornhaut: Brillouin-Spektroskopie und Hydratationszustand – quo vadis?

ZusammenfassungUm die strukturelle Integrität der Kornea zu beurteilen, werden nicht invasive Verfahren für die lokale Messung ihrer mechanischen Eigenschaften benötigt. Neben einer Reihe von etablierten Verfahren und den damit assoziierten Vor- und Nachteilen ist die Brillouin-Spektroskopie als ein immer noch relativ neues Verfahren in der Lage, den Kompressionsmodul von biologischem Gewebe, speziell der Kornea, in vivo zu bestimmen. Im vorliegenden Beitrag werden diese verschiedenen existierenden und in der Entwicklung befindlichen Technologien zur Untersuchung der Biomechanik der Hornhaut diskutiert und zueinander in Korrelation gesetzt.

A novel reconstruction method for magnetic resonance elastography based on the Helmholtz decomposition

We present a novel reconstruction method for magnetic resonance elastography, in which the shear modulus and viscosity of biological tissues are estimated from the externally oscillated displacement field obtained using magnetic resonance imaging. The proposed method is based on an integral representation of the stress field derived from the Helmholtz identity for tensor fields and is more robust against measurement noise than conventional methods using the Laplacian of the measured displacement field. We tested the proposed method by numerical simulations and compared it with two methods: the standard “algebraic inversion of the differential equation” method and our previously proposed integral-based method that is restricted to two-dimensional cases. The results showed that the proposed method could reconstruct both the shear modulus and viscosity stably even when noise was added to the data. In the future, we intend to validate the method via experimental data.

Construction and tissue regeneration evaluation for mature chondrocyte/scaffold complex under optimal compression loading

The tissue engineering is a promising method for cartilage regeneration studies. The rough in vivo initial repair environment of articular cartilage is a challenge for the development of cartilage tissue engineering. Hereon, in this study, a silk fibroin/collagen type II scaffold was designed. The optimal mechanical environment for chondrocyte/scaffold complex in vitro maturation culture was determined and in vitro cultured mature artificial cartilage was evaluated for in vivo defect repair. Our research shows that the silk fibroin/collagen type II scaffold has good performance and can meet the special requirements of cartilage repair. 10 % compressive strain is the optimal compressive loading in vitro. Under optimal compression loading in vitro, chondrocytes can proliferate and grow rapidly on the scaffold to achieve better “maturation”. The in vitro cultured chondrocyte/scaffold complex effectively improves the cartilage repair effect after implantation. The compressive elastic modulus of the new tissue reached 0.682 ± 0.010 MPa after 12 weeks of repair (0.714 ± 0.011 MPa for the surrounding host cartilage). Therefore, this study not only enhance the effect of cartilage repair but also provides a promising strategy for mechanical stimulation to promote functional in situ regeneration of articular cartilage.

Dental Implant and Natural Tooth Micro-Movements during Mastication-In Vivo Study with 3D VIC Method.

In the paper, using the video image correlation method, a study of the micro-movement pattern of the dental implant and of a normal was performed. It is revealed that there are great differences between these two situations. The linear displacement type of the dental implant refers to the linear elastic modulus of bone tissue in the case of normal bite forces. It seems that the major influencing factor regarding the type and value of implant micro-movement is defined by the underlying bone tissue. It is to be considered that masticator force transmission inside a more stiff and dense bone could be attenuated by the antagonist teeth parodontium, dental implant and abutment connection type, and the elastic modulus of material of the dental crown. Because of the elasticity of the periodontal ligament system, during the loading of the dental implant, the natural tooth has been displaced slightly more, leaving the dental implant in an unfavorable position, having to bear the full amount of loading forces. When comparing the relative displacements in the case of the loaded tooth, it is shown that the dental implant has been moving almost symmetrically with the tooth. This could mean that large amounts of forces are transmitted towards the periimplant bone tissue, but in a more optimal, parabolic manner due to the action of the periodontal ligaments surrounding the natural tooth.

Impacts of aging on murine cartilage biomechanics and chondrocyte in situ calcium signaling

Aging is the most prominent risk factor for osteoarthritis onset, but the etiology of aging-associated cartilage degeneration is not fully understood. Recent studies by Guilak and colleagues have highlighted the crucial roles of cell-matrix interactions in cartilage homeostasis and disease. This study thus quantified aging-associated changes in cartilage biomechanics and chondrocyte intracellular calcium signaling, [Ca2+]i, activities in wild-type mice at 3, 12 and 22 months of age. In aged mice, articular cartilage exhibits reduced staining of sulfated glycosaminoglycans (sGAGs), indicating decreased aggrecan content. On cartilage surface, collagen fibrils undergo significant thickening while retaining their transverse isotropic architecture, and exhibit signs of fibril crimping in the 22-month group. These compositional and structural changes contribute to a significant decrease in cartilage modulus at 22 months of age (0.55 ± 0.25 MPa, mean ± 95 % CI, n = 8) relative to those at 3 and 12 months (1.82 ± 0.48 MPa and 1.45 ± 0.46 MPa, respectively, n ≥ 8). Despite the decreases in sGAG content and tissue modulus, chondrocytes do not exhibit significantly demoted [Ca2+]i activities in situ, in both physiological (isotonic) and osmotically instigated (hypo- and hypertonic) conditions. At 12 months of age, there exists a sub-population of chondrocytes with hyper-active [Ca2+]i responses under hypotonic stimuli, possibly indicating a phenotypic shift of chondrocytes during aging. Together, these results yield new insights into aging-associated biomechanical and mechanobiological changes of murine cartilage, providing a benchmark for elucidating the molecular mechanisms of age-related changes in cell-matrix interactions.

In situ measurement of the stiffness increase in the posterior sclera after UV-riboflavin crosslinking by optical coherence elastography.

Scleral crosslinking may provide a way to prevent or treat myopia by stiffening scleral tissues. The ability to measure the stiffness of scleral tissues in situ pre and post scleral crosslinking would be useful but has not been established. Here, we tested the feasibility of optical coherence elastography (OCE) to measure shear modulus of scleral tissues and evaluate the impact of crosslinking on different posterior scleral regions using ex vivo porcine eyes as a model. From measured elastic wave speeds at 6 - 16 kHz, we obtained out-of-plane shear modulus value of 0.71 ± 0.12 MPa (n = 20) for normal porcine scleral tissues. After riboflavin-assisted UV crosslinking, the shear modulus increased to 1.50 ± 0.39 MPa (n = 20). This 2-fold change was consistent with the increase of static Young's modulus from 5.5 ± 1.1 MPa to 9.3 ± 1.9 MPa after crosslinking, which we measured using conventional uniaxial extensometry on tissue stripes. OCE revealed regional stiffness differences across the temporal, nasal, and deeper posterior sclera. Our results show the potential of OCE as a noninvasive tool to evaluate the effect of scleral crosslinking.

Relaxation and creep response of the alveolar lung to diagnosis and treatments for respiratory and lung disorders.

The lung Extracellular Matrix (ECM) contains a considerable part of the parenchymal cells. It contains three essential components: elastin and collagen within a proteoglycan (PG) viscoelastic network. Elastin provides the lung's elasticity property, a necessity for normal breathing, while collagen prepares structural support and strength, and PGs give stability and cushioning within tissue loading. Bacterial and viral respiratory diseases are dependent on changes in the ECM ingredients, which result in an alteration of the lung tissue strength. In the present study, this variation was investigated by changing the volume ratio of the ECM ingredients in the viscoelastic model. As a result, the relaxation curves continuously declined by reducing the volume ratios of elastin, collagen, and PGs; subsequently, the lung stiffness decreased. Also, the Standard Linear Solid (SLS) model-based results demonstrated excellent accordance with empirical data with only minor deviations. The resting relaxation modulus and the creep modulus for the ECM tissue were 51kPa and approximately 0.02kPa, respectively, and the maximum total modulus of elasticity reached 121kPa. Moreover, this model demonstrates individual alveolar mechanical behaviours and adds another pathway to the generalized Kelvin-Voigt and Maxwell models in predicting the progress of lung diseases.

Subchondral bone structure and synovial fluid metabolism are altered in injured and contralateral limbs 7 days after non-invasive joint injury in skeletally-mature C57BL/6 mice

Post-traumatic osteoarthritis (PTOA) commonly develops after ACL injury, but early changes to the joint soon after injury are insufficiently understood. The objectives of this study were (1) evaluate the response of subchondral bone tissue modulus to joint injury and (2) identify which bone structural, material, and metabolic outcomes are local (i.e., injured joint only) or systemic (i.e., injured and contralateral-to-injured). Female C57Bl∖6N mice (19 weeks at injury) underwent tibial compression overload to simulate ACL injury (n=8) or a small pre-load (n=8). Synovial fluid was harvested at euthanasia 7 days later for metabolomic profiling. Bone outcomes included epiphyseal and SCB microarchitecture, SCB nanoindentation modulus, SCB formation rate, and osteoclast number density. Injury decreased epiphyseal bone volume fraction ([-5.29,-1.38%], P=0.0016) and decreased SCB thickness for injured vs sham-injured limbs ([2.2, 31.4μm], P=0.017)). Epiphyseal bone loss commonly occurred for contralateral-to-injured limbs. There was not sufficient evidence to conclude that SCB modulus changes with injury. Metabolomic analyses revealed dysregulated synovial fluid metabolism with joint injury but that many metabolic pathways are shared between injured and contralateral-to-injured limbs. This study demonstrates rapid changes to bone structure and synovial fluid metabolism after injury with the potential for influencing the progression to PTOA. These changes are often evidenced in the contralateral-to-injured limb, indicating that systemic musculoskeletal responses to joint injury should not be overlooked.

Effect of Bone Marrow Mesenchymal Stem Cells on Mechanical Dynamics and BALP/CTX-1 Expression in Rats with Osteoporotic Vertebral Fracture

To analyze the effects of bone marrow mesenchyml stem cells (BMSCs) on bone alkaline phosphatase (BALP)/C-terminal telopeptide of type-Ⅰ collagen (CTX-1) expression and mechanical dynamics in rats with osteoporotic (OP) vertebral fracture. A total of 60 female Sprague-Dawley rats were evenly divided into three groups, a control group that received sham operation (sham group), a group consisting of rats with OP vertebral fracture (OP group), and the last group consisting of OP vertebral fracture rats given BMSCs treatment (BMSCs group). Comparison of the three groups of animals was made in terms of bone dynamic change, bone quantitative broadband ultrasound attenuation (BUA) measurement, and bone mineral density (BMD). HE staining was done to examine the bone histological morphological parameters of the vertebral body. Serum CTX-1 and BALP levels were determined by ELISA. Mechanical comparison showed that there were significant differences in mechanical changes of L 5 vertebra body and right femur among the three experimental groups ( P<0.05). The elastic modulus and maximum load of the OP group significantly decreased compared with those of the sham group ( P<0.05). After the intervention, the maximum load and elastic modulus of the BMSCs group were significantly higher than those of the OP group ( P<0.05). Compared with the sham group, BUA and BMD values in the OP group were significantly downregulated ( P<0.05). After intervention, BUA and BMD of the BMSCs group were significantly higher than those of the OP group and were comparable to those of the sham group ( P<0.05). Compared with the sham group, the number of trabeculae in the OP group was significantly fewer, and the distribution of trabeculae was disorderly and lacked regularity. Compared with the OP group, there were more trabeculae in the BMSCs group, and their distribution was more regular. Compared with sham group, bone histological morphological parameters of the vertebral body of rats in the OP group were significantly changed--mean trabecular plate thickness (MTPT) and trabecular bone volume (TBV) parameters were significantly decreased, while mineral apposition rate (MAR) and trabecula bone surface (TRS) parameters were significantly upregulated (all P<0.05). After the experimental intervention, bone histological morphological parameters of the vertebral body in the BMSCs group showed significant improvement compared with those of the OP group ( P<0.05). Compared with the sham group, serum BALP content in the OP group was greatly decreased, while the CTX-1 level was upregulated ( P<0.05). After the intervention, the BMSCs group had higher serum BALP content than that of the OP group and substantially lower CTX-1 content than that of the OP group ( P<0.05). BMSCs can improve the mechanical changes in rats with OP vertebral fracture, and can increase the maximum load and elastic modulus of bone tissue. In addition, BMSCs can upregulate the expression of BALP in serum and downregulate the expression of CTX-1, thus helping rats with OP vertebral fracture heal early.

Dual-zone material assignment method for correcting partial volume effects in image-based bone models

In image-based finite element analysis of bone, partial volume effects (PVEs) arise from image blur at tissue boundaries and as a byproduct of geometric reconstruction and meshing during model creation. In this study, we developed and validated a material assignment approach to mitigate partial volume effects. Our validation data consisted of physical torsion testing of intact tibiae from N = 20 Swiss alpine sheep. We created finite element models from micro-CT scans of these tibiae using three popular element types (10-node tetrahedral, 8-node hexahedral, and 20-node hexahedral). Without partial volume management, the models over-predicted the torsional rigidity compared to physical biomechanical tests. To address this problem, we implemented a dual-zone material model to treat elements that overlap low-density surface voxels as soft tissue rather than bone. After in situ inverse optimization, the dual-zone material model produced strong correlations and high absolute agreement between the virtual and physical tests. This suggests that with appropriate partial volume management, virtual mechanical testing can be a reliable surrogate for physical biomechanical testing. For maximum flexibility in partial volume management regardless of element type, we recommend the use of the following dual-zone material model for ovine tibiae: soft-tissue cutoff density of 665 mgHA/cm3 with a soft tissue modulus of 50 MPa (below cutoff) and a density-modulus conversion slope of 10,225 MPa-cm3/mgHA for bone (above cutoff).

Young modulus of healthy and cancerous epithelial tissues from indirect measurements

We propose a new method to estimate the ratio between the Young modulus of a healthy epithelial tissue and a cancerous tissue. Our method is based on a mechanistic approach. We regard the epithelium as a thin layer made of an isotropic hyperelastic material between two material surfaces endowed with surface tension. We derive a mechanical model which takes into account thickness change through a kinematical descriptor whose value, in the absence of mechanical loads, is determined by the competition between surface tension and bulk elasticity. Based on this model, we derive a relation between equilibrium thickness, surface tension, and bulk energy, along with a formula for the ratio between the Young modulus of the healthy and the cancerous tissue in terms of apico-basal pMLC2 intensity and tissue thickness, which are accessible to direct observation at the tissue-wide level through recently-developed experimental techniques. When assessed on the basis of our result, available experimental data confirm that cancerous epithelial tissues are softer than healthy tissues.

Comparative Diagnostic Accuracy of Sonographic Strain Elastography and FNAC in Breast Lesions

Introduction: Various sonographic techniques have been developed to study the relationship between different structures and tissue elasticity. Detecting malignant tumors using ultrasound elastography is quite useful. The mechanical properties of the tissue under examination can be examined in real time using elastography to detect pathological changes. A high-frequency ultrasonic scanner measures a tissue's modulus of elasticity to compute stretching changes in displacement.&#x0D; Aims &amp; Objectives: To determine the diagnostic accuracy of sonographic strain elastography in breast lesions keeping FNAC as gold standard.&#x0D; Place and duration of study: Radiology Department of Benazir Bhutto Hospital from Aug 2019 to Jan 2020.&#x0D; Material &amp;Methods: The cross-sectional validation study was conducted at the Radiology Department of Benazir Bhutto Hospital, Rawalpindi Medical University, from Aug 2019 to Jan 2020. 259 patients were selected by consecutive non-probability sampling. After taking demographic information, all patients received sonographic elastography. Lesions were classified using the Ueno system and pressure bar, and FNAC was conducted. SPSS 20 was used to enter and evaluate the gathered data. The sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio, and accuracy of strain elastography were calculated using FNAC as the gold standard.&#x0D; Results: The sensitivity, specificity, PPV, NPV and accuracy of elastography to detect malignancy was 92.2 %, 96.2%, 91.0%, 96.7% and 94.98% respectively. Likelihood ratio was 215.449 (p value &lt;0.0001). The results showed no significant impact of confounders.&#x0D; Conclusion: The sensitivity, specificity, PPV, NPV and accuracy of elastography to detect malignancy was 92.2 %, 96.2%, 91.0%, 96.7% and 94.98% respectively. the likelihood ratio was 215.449 (p-value &lt;0.0001).

Correlation analysis of structural and biomechanical properties of hepatocellular carcinoma tissue

It is known that biomechanical and structural properties of tumor tissues are potential biomarkers for the diagnosis and prognosis of tumors such as Hepatocellular carcinoma (HCC). Although there are many studies on the characterization of biomechanical properties of HCC at the cellular level, limited information is known from in vitro studies. Here, tissue samples from 14 patients diagnosed with HCC were analyzed. Indentation tests showed the instantaneous shear modulus and long-term shear modulus of the HCC tissue were 1.19 ± 0.86 kPa and 0.29 ± 0.25 kPa, respectively. The volume fraction of collagen fibers estimated by analyzing the histology images was positively correlated with either instantaneous shear modulus (r = 0.64, p = 0.016) or long-term shear modulus (r = 0.76, p = 0.002). Diffusion-weighted images with 13b-values were also collected and the diffusivity from Intravoxel Incoherent Motion (IVIM) and Diffusion Kurtosis Imaging (DKI) models were 1.09 ± 0.47 ∙ 10-3 mm2/s and 2.06 ± 0.83∙10-3 mm2/s, respectively. Significant positive correlations were observed between long-term shear modulus and the diffusivity estimated from IVIM (r = 0.600, p = 0.026). The shifted apparent diffusion coefficient (ADC) estimated based on b = 600 and 2000 s/mm2 was negatively correlated with both instantaneous shear modulus (r = -0.745, p = 0.003) and long-term shear modulus (r = -0.591, p = 0.029). In addition, the diffusivity and non-Gaussian Kurtosis parameters estimated at different b values showed a significant negative correlation (r = -0.675, p = 0.010). Results revealed the close relationships between the structural and biomechanical properties of HCC tissue. The interrelation of diffusion and biomechanical properties are not only crucial for HCC characterization but could also provide helpful information for HCC diagnosis and prognosis.

Effect of Remote Myofascial Release on Lumbar Elasticity and Pain in Patients With Chronic Nonspecific Low Back Pain: A Randomized Clinical Trial

ObjectiveThe purpose of this study was to evaluate the effects of myofascial release technique of a remote area on lumbar elasticity and low back pain (LBP) in patients with chronic nonspecific LBP. MethodsFor this clinical trial, 32 participants with nonspecific LBP were assigned to a myofascial release group (n = 16) or a remote release group (n = 16). Participants in the myofascial release group received 4 sessions of myofascial release to the lumbar region. The remote release group received 4 myofascial release sessions to the crural and hamstring fascia of the lower limbs. Low back pain severity and elastic modulus of the lumbar myofascial tissue were assessed before and after treatment by the Numeric Pain Scale and ultrasonography examinations. ResultsThe mean pain and elastic coefficient in each group before and after myofascial release interventions were significantly different (P ≤ .0005). The results showed that the changes in mean pain and elastic coefficient of the 2 groups after myofascial release interventions were not significantly different from each other (F[1–22] = 1.48, P = .230, 95% confidence interval) (effect size = 0.22). ConclusionThe improvements in the outcome measures for both groups suggest that remote myofascial release was effective in patients with chronic nonspecific LBP. The remote myofascial release of the lower limbs reduced the elastic modulus of the lumbar fascia and LBP.

Passive mechanical properties of the left ventricular myocardium and extracellular matrix in hearts with chronic volume overload from mitral regurgitation.

Cardiac volume overload from mitral regurgitation (MR) is a trigger for left ventricular dilatation, remodeling, and ultimate failure. While the functional and structural adaptations to this overload are known, the adaptation of myocardial mechanical properties remains unknown. Using a rodent model of MR, in this study, we discern changes in the passive material properties of the intact and decellularized myocardium. Eighty Sprague‐Dawley rats (350–400 g) were assigned to two groups: (1) MR (n = 40) and (2) control (n = 40). MR was induced in the beating heart by perforating the mitral leaflet with a 23G needle, and rats were terminated at 2, 10, 20, or 40 weeks (n = 10/time‐point). Echocardiography was performed at baseline and termination, and explanted hearts were used for equibiaxial mechanical testing of the intact myocardium and after decellularization. Two weeks after inducing severe MR, the myocardium was more extensible compared to control, however, stiffness and extensibility of the extracellular matrix did not differ from control at this timepoint. By 20 weeks, the myocardium was stiffer with a higher elastic modulus of 1920 ± 246 kPa, and a parallel rise in extracellular matrix stiffness. Despite some matrix stiffening, it only contributed to 31% and 36% of the elastic modulus of the intact tissue in the circumferential and longitudinal directions. At 40 weeks, similar trends of increasing stiffness were observed, but the contribution of extracellular matrix remained relatively low. Chronic MR induces ventricular myocardial stiffening, which seems to be driven by the myocyte compartment of the muscle, and not the extracellular matrix.

O-266 Encapsulation of human preantral follicles in an optimized hydrogel with similar mechanical strength of reproductive-age ovarian tissue

Abstract Study question Could a hydrogel with similar mechanical properties of reproductive age ovarian cortex support the growth of human preantral follicles? Summary answer Yes, our optimized PEGylated fibrin hydrogel with tailored mechanical strength provides a suitable substrate for follicle survival and growth. What is known already The most challenging part of assembling an engineered ovary is developing an appropriate scaffold that can maintain follicle spatial architecture and allow them to have radial growth and development1-3. Fibrin is a promising biomaterial due to its biocompatibility and bioactivity. Although fibrin has been used as a scaffold in fabricating different tissues such as the ovary, it has a fast degradation rate resulting in loss of physical support for the isolated follicles4-6. Therefore, various approaches such as physical or chemical modifications have been investigated to overcome the fibrin limitation7-10. Study design, size, duration PEGylation as a chemical reaction was used to control fibrin degradation. Moreover, to create an appropriate scaffold for encapsulating human preantral follicles, the Response Surface Methodology was used to find a hydrogel formulation with similar mechanical properties to the reproductive-age ovarian cortex. The chosen hydrogel was used to in vitro culture isolated human preantral follicles for 7 days. Participants/materials, setting, methods Design-Expert® software was employed to optimize PEGylated fibrin formulation to match mechanical properties of human ovarian tissues. Preantral follicles isolated from reproductive age patients were embedded in the hydrogel and in vitro cultured for 7 days. Follicle viability and diameter were evaluated on days 1 and 7. Moreover, confocal microscopy analysis was performed on whole follicles to confirm their growth by Ki67 staining of granulosa cells. Main results and the role of chance In this study, the biomechanically optimized PEGylated fibrin formulation was obtained by mathematical modeling. The hydrogel formulation was established by setting the specific goal of targeting 3178 ± 245 Pa, Young’s modulus of ovarian tissue fragments in reproductive-age women11, in order to obtain the optimized concentration of PEGylated fibrinogen and thrombin. Our results showed that the optimum condition with the desirability of 97.5% occurred by the PEGylated fibrin hydrogel containing 39.06 mg/ml of PEGylated fibrinogen and 50.36 IU/ml of thrombin with Young’s modulus of 3512.31±656.97 pa. Isolated follicles cultured in our hydrogel significantly increased in their diameter from 48.5±10.8µm (day 1) to 222.5±84.5µm (day 7), indicating the suitability of the optimized PEGylated fibrin formulation to support radial follicle growth. Moreover, follicles survival on days 1 and 7 did not significantly differ (86.9±8.9% and 83.4±6.4%, respectively). Follicle growth was confirmed by the presence of Ki67-positive granulosa cells from follicles at day 7. Limitations, reasons for caution In this study, the optimized hydrogel was first evaluated only in vitro, which is different from the actual physiological condition. Therefore, it is essential to perform a study analyzing the follicles after their encapsulation in the optimized hydrogel and transplantation, which will be the next step of our study. Wider implications of the findings Our results introduced an appropriate biomaterial, which resembles Young’s modulus of ovarian tissues in reproductive age, for encapsulating human preantral follicles. The optimal concentration of PEGylated fibrin allowed follicles to maintain their viability and have radial growth. Moreover, PEGylation enhanced the fibrin stability and physical support of follicles. Trial registration number not applicable