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

The occurrence of blunt abdominal injuries resulting from thoracic high-rate non-penetrating impacts (NPBIs) are often missed and associated with increased mortality and morbidity. Diagnosis of penetrating gunshot wounds successfully predicts injury locations using bullet trajectory, but no similar correlation has been applied for blunt impacts. Historically, thoracic NPBIs have been studied on ovine subjects and have reported thoracic only and thoracoabdominal injuries for impacts at the same location. The purpose of this study is to investigate if the finite element ovine thorax model (FE-OTM) can indicate changes in multi-compartment injury risk based on impact angle and determine a method for measuring this change. Twelve thoracic NPBIs were run over six impact angles (0 - 25°). Tissue directly under the impactor and along the path of impact, was analyzed for changes in composition and strain. Tissue composition analysis identified abdominal, lung, and liver as key tissue types. Cumulative volume analysis was used to determine a combine strain - volume metric for regions of interest. Within each region, Spearman's rank correlation was used to determine the strength of the relationship between this metric and impact angle. The key tissues experienced very strong correlations with impact angles and directionalities that corresponded to their change in volume. In conclusion, the FE-OTM can be used to indicate changes to multi-compartment injury risk based on impact angle. A 1st principal strain-volume based metric in the key tissue types is recommended.

Pulmonary hypertension (PH) is a serious condition affecting patients with end-stage renal disease (ESRD), yet the hemodynamic mechanisms underlying development remain poorly understood. Novel alternative methods (NAMs), such as computational fluid dynamics (CFD), provide a powerful and ethical approach to investigate vascular physiology using patient-specific data. We developed a CFD model of the pulmonary artery (PA) informed by noninvasive magnetic resonance imaging (MRI) from an ESRD patient to characterize flow dynamics and wall shear metrics relevant to PH. Simulations were performed using image-based geometry, and velocity fields, wall shear stress (WSS), time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) were quantified. Results demonstrated physiologically consistent flow distributions, with higher velocities localized near outlet regions and lower velocities in branches. Spatially averaged TAWSS was approximately 9 dyn/cm2, in agreement with previously reported ranges. OSI values were low across the pulmonary vasculature, suggesting limited flow reversal. Together, these results highlight the feasibility of using patient-specific CFD to capture PA hemodynamics in ESRD and demonstrate consistency with published physiological values. This framework demonstrates the utility of NAMs to provide insight into complex biomechanical systems and a foundation for future studies seeking to clarify mechanistic links between ESRD development, arteriovenous fistula (AVF) creation, and eventual PH development, ultimately informing development of patient-specific diagnostic and therapeutic strategies. As NAMs gain regulatory and scientific traction, approaches like this will play an important role in reducing reliance on animal models while enabling ethically responsible, patient-specific discovery in cardiovascular research.

Cardiac fibrosis is a pathological condition involving remodeling that impairs cardiac function. Common forms include replacement fibrosis, where damaged myocytes are substituted by collagenous tissue, and interstitial fibrosis, involving matrix expansion between the myocytes. These occur alongside other remodeling processes, including myocardial stiffening and collagen alignment. The mechanical impact of each process remains an active area of investigation. In this work, we used a computational model with explicit myocyte and collagen geometries to study the microscale mechanical effects of fibrotic remodeling. Replacement fibrosis was simulated by substituting myocytes with extracellular matrix, while interstitial fibrosis was modeled by increasing transverse spacing between the cells. These geometric changes were combined with increased matrix and myocyte stiffness and collagen alignment to assess individual and combined effects during contraction and stretch. Structural changes alone led to substantially higher myocyte stresses during contraction (53.9 kPa for increased interstitial space and 35.4 kPa for myocyte replacement, versus 30.9 kPa at baseline). Collagen alignment and myocyte stiffening mitigated increased stress levels. Stretch experiments showed less structural differences in resulting tissue-level load values, which combined with stiffening were slightly higher for increased interstitial space. Individual and combined analyzes attributed total tissue stiffening more to myocyte than matrix stiffening. Our findings suggest that fibrotic remodeling leads to elevated stress in surviving myocytes. Myocyte stiffening and collagen alignment may serve compensatory roles, while also increasing tissue-level stiffness. Integrating microscale modeling with experimental data in future studies may offer deeper insights into the mechanical consequences of fibrotic remodeling.

Heart failure is the leading cause of death in patients with Duchenne muscular dystrophy (DMD), but the mechanisms underlying the associated dilated cardiomyopathy (DCM) are not fully understood. To address this gap, we generated engineered heart tissues (EHTs) using CRISPR-edited human induced pluripotent stem cell-derived cardiomyocytes that lack dystrophin. These dystrophic EHTs reproduced aspects of systolic and diastolic dysfunction seen in DMD-related DCM as they showed impaired contractile function and slower kinetics. Increased beat rate variability was also observed in dystrophic EHTs. Accompanying these facets of the DMD pathology were attenuated Ca2+ transients and delayed kinetics. Lastly, histological analysis of EHTs revealed that dystrophin-null cardiomyocytes had reduced size and shorter sarcomere lengths when compared to isogenic controls. Together, these findings demonstrate that EHTs provide a physiologically relevant human model of DMD-associated DCM and may serve as a valuable platform for mechanistic studies and therapeutic testing.

Nonanimal models (NAMs) provide an important platform for studying musculoskeletal tissue formation under controlled conditions while reducing reliance on vertebrate animal models. In this study, we advanced a simple, scaffold-free three-dimensional (3D) NAM system to guide the self-assembly of murine C3H/10T1/2 mesenchymal stem cells (MSCs) and C2C12 myoblast progenitor cells into neotendon and neomuscle structures. Custom 3D-printed molds and biologically inert agarose were used to form nonadherent wells that promoted high cell density and directed cell-cell adhesion without exogenous extracellular matrix (ECM) or biomaterial scaffolds. Transforming growth factor (TGF)β2 treatment enhanced actin cytoskeleton alignment in neotendons, with initial collagen fibril formation observed by day 7. C2C12 myoblasts exhibited progressive actin alignment, myotube formation, and desmin production by day 14. A custom bioreactor was used to apply cyclic tensile loading to the neotendons early in their development. Co-cultures of C3H/10T1/2 MSCs and C2C12 myoblasts formed cohesive structures, with aligned cytoskeletal organization and desmin distribution throughout, suggesting potential interactions at the developing myotendinous junction. This scaffold-free NAM system enables the evaluation of key biochemical and mechanical cues that regulate early musculoskeletal tissue formation in vitro. By recapitulating features of the embryonic environment, this approach refines current in vitro methods and establishes a simple, versatile platform to ultimately reduce the need for vertebrate animal models in developmental studies.

To better understand the mechanisms of bone stress injuries (BSI) in metatarsals, we developed an algorithm that adapts finite element (FE) models of metatarsals to simulate fatigue displacements through progressive stiffness loss. Twenty-two human metatarsals were imaged using computed tomography (CT) and then cyclically loaded in uniaxial compression until failure. CT images were used to generate specimen-specific FE models, and a custom program was developed to iteratively simulate cyclic loading and progressive stiffness loss associated with microdamage accumulation. Probability was incorporated into microdamage accumulation through a Weibull distribution. Simulations were able to accurately represent experimental trends in how metatarsal stiffness and displacement changed throughout the mechanical testing. Simulated displacement at failure was not significantly different from experimentally measured displacement. Simulated fatigue life, displacement, and rate of stiffness loss were significantly affected by (1) the Weibull scatter variable, m, and (2) the critical strain value, describing whether damage occurred before or after yielding. These simulations represent a novel alternative method that is significant because it helps us better understand the factors that influence fatigue life and observed mechanical behavior during fatigue testing in whole bones. Advanced adaptive simulations such as the one described here can be leveraged to reduce the reliance on physical testing, generate and test hypotheses regarding damage accumulation in materials, and eventually, be deployed in predictive algorithms with clinical applications.

Myocardial Infarction (MI) occurs when blood flow is blocked to a portion of the left ventricle and leads to necrosis and scar formation. Many therapies are under development to improve infarct healing, and three-dimensional engineered heart tissues (EHTs) offer an in vitro drug screening option to help reduce, refine, and potentially replace animal testing. Unfortunately, existing EHTs oversimplify cardiac mechanics and neglect the spatial variations of the infarcted ventricle in vivo, wherein the passive infarct zone is cyclically stretched under tension as the remote zone cyclically contracts with every heartbeat. We present an in vitro three-dimensional tissue culture platform focused on mimicking the heterogeneous mechanical environment of postinfarct myocardium. Herein, EHTs were subjected to a cryo-wound injury to induce localized cell death in a central portion of beating tissues composed of neonatal rat cardiomyocytes and fibroblasts. After injury, the remote zone continued to contract (i.e., negative strains) while the wounded zone was cyclically stretched (i.e., positive tensile strains) with intermediate strains in the border zone. We also observed increased tissue stiffnesses in the wounded zone and border zone following injury, while the remote zone did not show the same stiffening. Collectively, this work establishes a novel in vitro platform for characterizing myocardial mechanics after injury with both spatial and temporal resolution, contributing to a deeper understanding of MI and offering insights for potential therapeutic approaches.

Operative repair of the rotator cuff (RC) of the shoulder can return a patient to normal function but is not without complications. An understanding of the tissue strains in the RC of the shoulder under normal and pathological conditions can inform surgeons about the conditions needed for restoration of function and the state of the tissue under repair. The current work applied digital image correlation (DIC) to quantify rotator cuff strains with the goals of (1) determining whether the tension created by the supraspinatus (SS) muscle is transmitted without diversion by the structure of the cuff from the supraspinatus to the cuff insertion; and (2) whether releases of the SS tendons at their insertions alter the strain field in the region away from the cuff insertion. DIC methods recorded the bursal-side cuff strains created using a shoulder simulator, which could apply physiologic loads to the cuff muscles. The SS and infraspinatus (IS) insertions of the humerus were sequentially released while muscle loads were applied. The first principal strains and their directions showed changes after releases of both the anterior and posterior SS insertions and after the IS release. The results demonstrated (1) that the RC transmits SS muscle forces without diversion and (2) that RC releases do affect the strain field. Release of both heads of the SS led to statistically significant changes in strain magnitude and direction.

The uterine cervix is a soft biological tissue with critical biomechanical functions in pregnancy. It is a mechanical barrier that supports the growing fetus. As pregnancy progresses, the cervix becomes more compliant and eventually opens in late pregnancy to facilitate childbirth. This dual function is facilitated by extensive remodeling of the cervical extracellular matrix (ECM), giving rise to its complex time-dependent material properties. Premature cervical remodeling is known to result in preterm birth, defined as birth before 37 weeks of gestation. While previous work has studied cervical remodeling using various biomechanical methods, it remains unclear how the intrinsic or flow-independent viscoelastic behavior of the cervix is influenced by cervical remodeling. In this study, an anisotropic reactive viscoelastic material model was formulated and investigated under tensile deformation to understand material behavior in cervical remodeling. To calibrate the model, experimental force relaxation data was used from uniaxial tension tests on Rhesus macaque cervical specimens from four gestational time points. The results showed that cervical tissue equilibrium and instantaneous stiffness significantly decreased from the nonpregnant (NP) to the late pregnancy status. In addition, cervical tissue in the late third trimester relaxed faster to equilibrium than the other gestational groups, particularly at prescribed grip-to-grip strains greater than 30%. This fast relaxation to equilibrium helps the cervix dissipate tensile hoop stresses induced by the fetus during labor, preventing its rupture. This work provides insights into time-dependent cervical remodeling features, which are crucial for developing diagnostic methods and treatments for preterm birth.