Engineered in vitro cardiac tissues are being developed and increasingly used for disease modeling and drug evaluation, but reproducing cardiac cell composition and three-dimensional architecture alone does not ensure physiologically meaningful function. Native myocardial performance arises from coordinated electrical activation, active force generation, and passive mechanical resistance governed by stiffness, anisotropy, nonlinear elasticity, and viscoelastic relaxation. Failure to reproduce these coupled properties can alter force transmission, tissue deformation, mechanosensitive cellular responses, and the interpretation of disease phenotypes or drug effects. Yet myocardial mechanics, computational modeling, biomaterial design, and biofabrication are commonly developed as separate domains. This review integrates these areas through a biomechanics-guided property-parameter-function framework. We first examine the multiscale structural determinants of myocardial mechanics and critically compare cellular, continuum, phenomenological, microstructure-informed, viscoelastic, and pathology-informed models with respect to predictive scope, computational demand, parameter identifiability, experimental validation, and engineering relevance. We then show how model-derived descriptors-including active stress, baseline and nonlinear stiffness, anisotropy, relaxation behavior, and remodeling-related parameters-can be translated into controllable biomaterial properties, scaffold architecture, fabrication and conditioning protocols, and mechanical boundary conditions. Emerging approaches involving artificial intelligence, inverse design, uncertainty quantification, and digital twins are discussed as routes toward adaptive and patient-relevant tissue models. By positioning computational biomechanics as a design and validation tool, this review provides a systematic basis for engineering cardiac tissues with more predictable mechanical function and more reproducible disease- and drug-response readouts.
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To investigate the effects of young human red blood cell-derived extracellular vesicles (Y-RBCEVs) on fracture healing. Associations of RBC-related indicators with bone mineral density and mortality in fracture populations were analyzed using NHANES data (1999-2020). A murine femoral fracture model was established to investigate RBC transfusion effects. Y-RBCEVs and O-RBCEVs were isolated to examine their effects on osteogenic differentiation and BMM polarization in vitro. In vivo distribution was assessed by IVIS, and therapeutic efficacy was evaluated in fracture mice. Proteomic sequencing identified differentially expressed proteins between Y-RBCEVs and O-RBCEVs, and key protein function was investigated by transcriptomic analysis and in vitro validation. The observational study revealed associations between RBC count and bone mineral density with fracture populations mortality. RBC transfusion modulated the expression of osteogenic and M2 macrophage polarization-related genes. In vitro, RBCEVs were efficiently internalized by BMSCs and BMMs, with Y-RBCEVs enhancing osteogenic activity in BMSCs and promoting M2 macrophage polarization, thereby partially restoring osteogenesis impaired by inflammatory conditions. In vivo, Y-RBCEVs accumulated at fracture sites and enhanced bone regeneration without detectable toxicity, accompanied by increased OCN and CD206 expression. Proteomic analysis identified VCAN as one of the potential functional cargos. Mechanistically, Y-RBCEV-derived VCAN interacted with CD44 on macrophages and was associated with activation of the PI3K/AKT pathway, contributing to M2 polarization. Y-RBCEVs enhance fracture repair by modulating osteogenesis and macrophage polarization, with VCAN-associated CD44/PI3K/AKT signaling contributing to their osteo-immunomodulatory effects. These findings highlight RBCEVs as a potential therapeutic strategy for bone regeneration.
Analyzing foot biomechanics is essential for understanding plantar load distribution, particularly in relation to structural variations, including deformities such as flat foot and high arch, relative to the normal arch. Finite element analysis (FEA) is widely used to model foot biomechanics; however, traditional FEA approaches rely on detailed anatomical data from computed tomography (CT) scans, which are costly, expose subjects to radiation, and require substantial computational resources. This proof-of-concept study presents a novel pipeline for generating a simplified, parametric 3D foot bone model from weight-bearing X-ray images in four views: lateral, dorsoplantar, anteroposterior, and hindfoot alignment. Image-derived bone lengths, angles, and offsets defined geometric primitives for constructing a personalized bone assembly, which was embedded into the subject's scanned foot surface and evaluated using FEA under static standing conditions. Plantar pressure served as the primary validation metric, comparing results from the simplified model with experimental measurements and a CT-based model. The simplified model reproduced the experimental plantar pressure pattern with relative errors of 4.38, 8.33, and 3.66% in the hindfoot, midfoot, and forefoot, respectively, while reducing computation time by approximately 90%. A supplementary evaluation across four additional subjects with various foot conditions showed consistent performance, with less than 9% deviation in regional peak pressure compared with experimental measurements. These findings demonstrate the feasibility of X-ray-based parametric modeling as a lightweight and scalable alternative for personalized foot analysis, with potential applications in rapid orthotic and insole design, subject-specific assessment in low-resource settings, and large-scale biomechanical screening.
Predation pressure shapes ecosystems via selection on locomotor form and function. To explore this link, we grouped 48 species of predatory mammals into five hunting-strategy clusters: Anteaters, Opportunistic Grapplers, Large Grapplers, Opportunistic Pouncers, and Social Hunters, and asked whether their locomotor shape (limb posture through the stride) reliably distinguished these clusters. We digitised 115 side-view stride sequences across these species, performed Procrustes alignment and principal component analysis on per-stride shapes, and analysed symmetrical (walking) and asymmetrical (galloping/bounding) gaits. In symmetrical gaits, phylogeny accounted for the largest share of locomotor variation, but hunting strategy still explained a significant portion, whereas gait type made only a weak contribution and body mass was not significant. These slower, more economical gaits showed relatively broad overlap among hunting groups, although Social Hunters tended to use more upright limb postures and Grappling species more crouched and extended forelimb configurations. In asymmetrical gaits, differences among hunting strategies were stronger, while gait type and body mass again contributed little. Social Hunters showed larger limb and spinal excursions, whereas Opportunistic Pouncers occupied a more restricted region of locomotor space. The stronger separation among hunting groups during asymmetrical gaits suggests that ecological specialization is expressed most clearly in high-performance behaviours such as acceleration, manoeuvring, and prey capture, rather than in economical walking. We then placed the extinct marsupial predator, the thylacine (Thylacinus cynocephalus), within this framework using archival footage of walking. Its symmetrical-gait centroid was predominantly associated to Opportunistic Pouncer across classifiers. These results show that locomotor biomechanics are associated with hunting ecology, but that these ecological patterns are embedded within substantial phylogenetic structure; they also suggest that this relationship may help inform ecological inference in extinct species.
Windsurfing pumping is a key manoeuvre in the Olympic iQFOiL class, yet its on-water biomechanics and coordination remain undescribed. This exploratory study quantified in situ kinematics and inter-element coordination during upwind pumping in seven elite windsurfers. A board-mounted camera recorded 36 race-pace upwind pumping sequences, and OpenPose-based markerless motion capture was used to estimate centre of mass (COM), knee and trunk angles, and COM-to-sail (CTS) and COM-to-board (CTB) distances. We conducted laboratory validation trials of the pumping motion to compare the markerless approach with a marker-based motion capture system. Field data showed large ranges of motion in the knee (58.8 ± 12.0°), trunk (37.1 ± 10.8°), CTS (16.1 ± 4.0 %H; % of body height) and CTB (10.9 ± 3.0 %H). Cross-correlation analysis revealed synchronous coordination between CTS, knee and trunk (lags < 5% of the cycle) and antiphase coordination between CTS and CTB. Together, these findings identify a whole-body pumping strategy in which knee and trunk motion are tightly coordinated to drive CTS and provide quantitative targets for coaching, simulator design and lab to field integration.
The aim of this scoping review was to map the key biomechanical and physiological variables explored in the wheelchair racing literature, with additional attention to data collection environments and technologies. Relevant articles published up to 3 February 2025 were identified using four databases (PubMed, Web of Science, SPORTDiscus, Scopus). After screening, 31 studies were included in the final analysis: 15 on biomechanics, 7 on physiology, and 9 contained elements of both. Most athletes measured were male (78%) and competing in the T51-54 classification; females and athletes with coordination impairment (T32-34) were underrepresented. Various distances and protocols were examined, ranging from the first six pushes to 90 min, with 100 m being the most frequently studied distance. Most data were collected in laboratory settings using roller systems, motorised treadmills or ergometers. Biomechanical data indicated push technique, including increasing upper-arm angular velocity, and optimising acceleration are fundamental to achieve competitive speeds. Physiological studies measured parameters such as V˙O2peak, blood lactate concentration and heart rate, though direct links to performance remain limited. This review highlights methodological diversity across studies and suggests that integrating technologies such as inertial measurement units, three-dimensional motion capture, and force-instrumented rollers/wheels may enhance understanding of determinants in wheelchair racing.
To evaluate whether a non-invasive approach to treat keratoconus with corneal cross-linking (CXL) using oral riboflavin and natural sunlight could represent a cost-effective alternative. In a prospective, controlled study, 16 male New Zealand White rabbits (32 eyes) underwent a two-step protocol. Step 1 quantified stromal riboflavin in 4 rabbits (8 eyes) after 14 days of oral riboflavin (6 mg/kg/day). Step 2 randomized the remaining 12 rabbits (24 eyes) 1:1 to oral riboflavin plus natural sunlight or sunlight alone. After a 2,700 klux·h cumulative sunlight dose, corneal biomechanics were assessed by optical coherence tomography elastography and uniaxial stress-strain extensometry. The mean stromal riboflavin concentration after oral administration was 0.000081% ± 0.000011%. Stress-strain testing showed no significant differences in stress at 0.1 strain (152 ± 11.5 kPa in controls vs 146 ± 7.0 kPa in treated eyes; P = .57) or mean elastic modulus between 0.1 and 0.2 strain (4.1 vs 4.0 MPa; P = .870). OCT elastography demonstrated significantly higher posterior corneal strain in treated eyes (0.551‰ vs 0.398‰; P = .039), consistent with reduced apparent stiffness. Oral riboflavin combined with ambient sunlight did not induce corneal stiffening under the tested conditions. Stromal riboflavin levels were nearly 500-fold lower than those achieved with standard CXL, indicating the tested approach is unlikely to serve as an effective standalone cross-linking strategy. The observed posterior corneal stiffness reduction may reflect ultraviolet-A-induced stromal degradation or subthreshold photochemical effects rather than true cross-linking.
Competitive freestyle swimming performance depends on the interaction between stroke rate (SR) and stroke length (SL), yet this relationship has generally been examined using linear approaches. This study investigated the nonlinear biomechanical interaction between SR and SL to identify the conditions associated with maximal swimming velocity. Data were collected from fifty highly trained freestyle swimmers performing maximal-effort 50-m sprint trials. Swimming velocity was analyzed using polynomial regression, response-surface methodology, stationary-point analysis, and Hessian determinant testing to identify and verify optimal biomechanical interaction. The nonlinear interaction model explained 68% of the variance in swimming velocity and improved predictive performance by 20% compared with the linear model. Response-surface optimization identified a constrained biomechanical interaction corridor rather than a single optimal combination of SR and SL. Stationary-point analysis, confirmed by the Hessian determinant, demonstrated that this region represented a statistically significant local maximum, providing evidence that swimming velocity is governed by nonlinear rather than purely additive relationships between SR and SL. The findings demonstrate the value of integrating nonlinear regression, response-surface methodology, and mathematical optimization to characterize swimming biomechanics. The proposed analytical framework offers a reproducible approach for optimizing biomechanical performance and has practical applications in training prescription, performance monitoring, and future real-time coaching systems.
Non-traumatic avascular necrosis (AVN) of the femoral head is primarily attributed to vascular compromise; however, the potential role of spinopelvic alignment in its development remains insufficiently defined. This study aimed to evaluate whether sagittal spinopelvic parameters differ between patients with non-traumatic AVN and asymptomatic individuals. A retrospective case-control radiographic study was performed including 21 adults with bilateral Ficat-Arlet stage II-III non-traumatic AVN and 100 age- and sex-matched asymptomatic controls. Standardised standing full-length lateral radiographs were analysed to measure pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), thoracic kyphosis (TK), and sagittal vertical axis (SVA). Spinopelvic morphology was classified using the Roussouly and Barrey systems. Interobserver reliability was evaluated using intraclass correlation coefficients (ICC), and statistical significance was set at p < 0.05. Patients with AVN demonstrated significantly lower PI, PT, SS, and LL values compared with controls (all p < 0.01), whereas TK did not differ significantly between groups. Although no statistically significant differences were observed in the distribution of Barrey and Roussouly types, a higher prevalence of Roussouly type 3 morphology was noted in the AVN cohort. Sex-related differences evident in the control group were not observed among AVN patients, and age showed minimal association with sagittal parameters. Inter-observer reliability was excellent for all measurements (ICC > 0.90). Patients with non-traumatic AVN exhibit a distinct spinopelvic alignment profile characterised by reduced PI-derived sagittal parameters and limited compensatory pelvic orientation. These findings indicate that altered lumbopelvic biomechanics may be associated with increased mechanical stress on the femoral head and may reflect a biomechanical profile linked to AVN susceptibility. Further prospective studies are warranted to clarify the clinical implications of this association.
 Primary traumatic anterior shoulder dislocations are common and can have long-term personal implications for quality of life and the use of the arm for occupational activities and sport participation. A patient care pathway has been reported to contribute to improved quality of care and a reduction in re-dislocations. We developed clinical practice guidelines intended to provide healthcare professionals with an updated pathway for the optimal diagnosis and management of traumatic primary anterior shoulder dislocations.  The clinical practice guidelines were developed by a multidisciplinary committee for the following topics: (i) diagnostic evaluation, (ii) reduction technique, (iii) pain management during reduction, (iv) immobilization, (v) physical therapy, (vi) risk factors for recurrent dislocation, and (vii) primary surgical shoulder stabilization.  On admission, dislocations require prompt treatment after diagnostic imaging. The choice of reduction technique is based on individual experience, favoring a biomechanical approach without analgesics. If reduction fails, procedural sedation and analgesia are recommended. To confirm reduction and rule out complications, imaging is repeated, and 1 week of relative immobilization is initiated. Following the acute phase, physical therapy targets early restoration of function, coordination, and proprioception. Risk factors of recurrence include young age and male sex, and surgical intervention may be discussed in the case of age < 40 years, contact athletes, and significant bone loss. The recommendations given are mostly based on data of low GRADE evidence, supplemented with expert opinion. These guidelines emphasize the importance of timely, efficient, and safe management in the emergency department. Pre- and post-reduction diagnostics are crucial for safe reduction and appropriate management. In the case of complications or recurrent instability, timely management enhances long-term outcomes.
Magnetic microrobotics holds promise for minimally invasive biomedical applications, yet imaging in this field still relies predominantly on external modalities. Endoscopic imaging offers an alternative route for in situ visualization and micro-agent guidance, but its use in microrobotics has so far remained limited to standard endoscopic modalities. This study demonstrates two-photon endomicroscopy (TPE) for real-time fluorescence imaging of magnetically actuated micro-agents. Dynamic experiments under rotating magnetic fields support motion analysis across multiple actuation frequencies. In addition, dual-color imaging enables analysis of mixed magnetic and non-magnetic micro-agent populations labeled with distinct fluorescent dyes. Imaging through biological tissue shows that magnetic micro-agents remain detectable through a 140 μ m rat mammary gland tissue layer. The feasibility of image-guided re-centering of a HeLa cell spheroid within the TPE field of view is also shown, compensating for displacement induced by the magnetic micro-agents. These results extend TPE from passive observation to active image-guided functionality in microrobotic systems.
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Therapeutic interventions for diseases such as leukemia and autoimmune disorders are increasingly designed to selectively target and deplete specific immune cell subsets over prolonged periods. This can disrupt the homeostasis of the adaptive immune system, with consequences not only for peripheral blood but also for the "cradle of the immune system", the bone marrow. This study hypothesized that such immune imbalance due to immune cell depletion therapies impairs the differentiation capacity of mesenchymal stromal cells (MSCs), which are key progenitors of bone cells and are thus essential for maintaining bone health. To validate this hypothesis, a series of cell culture experiments were conducted in which MSCs were stimulated with immune-conditioned media derived from various immune cell subsets. A comprehensive analytical approach was employed to evaluate the differentiating MSCs, including their associated supernatants, deposited collagen, mineralized matrix, and lipid deposition at defined time points during their maturation. Therefore, fluorescence and nonfluorescent histological staining, enzyme-linked immunosorbent assays (ELISAs), and expression analyses with Ribonucleic acid (RNA) were performed. This study demonstrated that, compared with immune-conditioned media from T cells or peripheral blood mononuclear cells (PBMCs), B cell-immune-conditioned media enriched with interleukin 4, bone morphogenetic protein 2 and Dickkopf 1 enhanced the osteogenic differentiation of MSCs in vitro. This positive osteogenic effect is driven primarily by elevated cytokine secretion by stimulated B cells, which in vivo in turn potentially stimulate bone turnover and modulate immune system function. In summary, these data demonstrate an pro-osteogenic and pro-adipogenic influence of B cells on differentiating MSCs in vitro, suggesting that an imbalance in immune cells in the bone marrow perturbs bone homeostasis.
Ankle fractures are among the most common fractures in adults. Despite significant advancements in surgical techniques, the postoperative treatment regimens remain conservative. This study aims to objectively evaluate gait recovery following early mobilization and weight-bearing after surgical ankle fracture treatment using instrumented gait analysis. This prospective, single-armed, longitudinal study enrolled adult patients following surgical treatment for isolated ankle fractures with early pain dependent weightbearing. Gait analysis, utilizing a treadmill integrated with a pressure plate and IMU-based motion capture systems, was conducted at 6 weeks, 3-, 6-, and 12-months post-surgery, assessing spatio-temporal and kinematic parameters. Results were compared longitudinally and against a healthy control group. Longitudinal data were available for 44 patients. Significant (p<.001) improvements of self-paced walking velocity (SPV) were observed from 6 weeks (2.2 ± 1.1 km/h), to 3 (2.9 ± 0.9 km/h) and 6 months (3.4 ± 0.9 km/h). The spatio-temporal parameters showed significant changes between 6 weeks and all further time points only at SPV. Kinematic parameters showed significant longitudinal improvements at SPV for hip, knee, and ankle motion (including all three ankle planes). Patient gait parameters at 6 and 12 months were comparable to healthy controls, except for persistent limitations in ankle sagittal kinematics. Patients undergoing surgical ankle fracture repair with early mobilization and full weight-bearing showed substantial gait recovery within 6 weeks. By 12 weeks, patient gait closely resembled healthy controls, highlighting the efficacy of a pain-adapted postoperative regimen for rapid functional recovery and return to previous activity levels. Level II.
Therapeutic resistance in breast cancer, driven by tumor-intrinsic adaptive mechanisms and microenvironmental survival cues, remains a critical barrier to curative treatment. To address this dual challenge, we developed a redox-responsive polymeric micelle system (TPSP) functionalized with telmisartan for simultaneous targeting of angiotensin II type 1 receptor-overexpressing tumor cells and cancer-associated fibroblasts (CAFs). This platform co-encapsulates doxorubicin (DOX), a classic topoisomerase IIα (Topo IIα) poison, and aconitine linoleate (L29), a novel catalytic Topo IIα inhibitor with a distinct mechanism of action compared with conventional agents. The TPSP micelles exhibit dual therapeutic synergism: (1) L29 disrupts DNA replication through G1/S cell cycle arrest via Topo IIα catalytic inhibition, complementing DOX's DNA double-strand break induction to counter acquired resistance, and (2) telmisartan-mediated CAF depletion disrupts stromal-mediated drug resistance by eliminating metabolic symbiosis and biomechanical barriers. In vivo evaluations across resistant breast cancer models revealed superior tumor growth inhibition (>72%) with CAF ablation. This combinatorial nanomedicine strategy pioneers a paradigm shift in overcoming multidrug resistance by concurrently targeting tumor plasticity and microenvironmental protection, providing a clinically translatable blueprint for treatment-refractory malignancies.
Achilles tendon rupture is a common injury among active adults and frequently requires surgical repair in high-demand patients. Augmentation techniques have been developed to improve repair strength and reduce re-rupture risk, particularly in cases of degenerative tendon tissue. TeKBrace, a woven polyester mesh, provides mechanical reinforcement while allowing biologic integration. We present the case of a 36-year-old recreational athlete who underwent open Achilles tendon repair with TeKBrace augmentation following an acute rupture. Intraoperative findings of degenerative tendon tissue and mild gapping under tension supported the decision to augment the repair. At 6 months, the patient demonstrated symmetric ankle range of motion and approximately 90% restoration of plantarflexion strength compared with the contralateral limb. The patient demonstrated excellent functional recovery and returned to recreational basketball without pain or limitation at 9 months, and no complications or re-rupture were observed. This case highlights the biomechanical rationale and clinical utility of TeKBrace scaffold augmentation in selected patients, although larger studies with longer follow-up are needed to better define its clinical effectiveness.
In thrombi, fibrin formation is accompanied by neutrophil activation, which leads to the release of neutrophil extracellular traps (NETs). Citrullination is a post-translational modification of arginine catalyzed by peptidylarginine deiminases, which are released during NET formation and modify extracellular proteins. Citrullinated fibrin has been detected within thrombi, but its impact on clot stabilization by activated Factor XIII (FXIIIa) has not been investigated. To characterize the effect of FXIIIa on the mechanical strength and lytic susceptibility of citrullinated fibrin. FXIII cross-linking sites in fibrin were identified by mass spectrometry. Fibrinolysis was investigated by turbidimetry and viscoelastometry in clots containing plasminogen and tissue plasminogen activator (tPA). Mechanical and viscoelastic parameters of the same clots were determined by oscillatory rheometry and viscoelastometry. Non-crosslinked fibrin formed from citrullinated fibrinogen showed lower stability in the applied biomechanical and fibrinolytic assays. However, citrullination increased the number of heterochain crosslinks formed by FXIIIa from 27 to 36, and that of homochain crosslinks from 29 to 30. In line with this finding, the antifibrinolytic effect of FXIII crosslinking was consistently more pronounced in citrullinated fibrin. While FXIIIa increased the maximal clot firmness of native fibrin by 10% in the viscoelastometric assay, this FXIII-related rise in mechanical strength was 38% in citrullinated fibrin. Similarly, in the rheometric assays, the FXIII-associated increment in the critical shear stress required to disassemble the clot was higher in citrullinated fibrin than in the native one. FXIIIa is essential to counteract the weakening effects of citrullination in fibrin clots.
Low back pain (LBP) is frequently classified as non-specific, which reduces the capacity of the healthcare system to offer targeted rehabilitation. Previous work has suggested a link between motor control and low back dysfunction. Identifying motor control phenotypes indicative of dysfunction often requires complex and costly laboratory equipment. Recent advancements in computer vision and the widespread availability of smartphones have made human motion capture more accessible. This study aimed to examine whether outcomes derived from consumer-grade video and open-source pose estimation tools are associated with motor control patterns linked to self-reported low back dysfunction. A self-guided online questionnaire was employed to gather data from 448 participants, worldwide. Participants completed validated questionnaires and video-recorded themselves performing four functional movements. Pose-derived kinematic features were extracted and reduced using principal component analysis (PCA), followed by a stepwise linear regression modelling to examine associations between movement features and individual participant reported outcome measures as well as a composite index of low back function. Participants were split into low and high function groups. PCA-derived features of movement were significantly associated with measures of disability, kinesiophobia, pain catastrophizing, and physical activity. Trunk flexion demonstrated the strongest association with the composite index (R2 = 0.71). The results between low vs high function participants depict biomechanically relevant differences (i.e. reduced movement speed and range of motion) typically found in the low back pain (LBP) population. Results highlight the feasibility of using consumer-grade video and open-source pose estimation tools for large-scale biomechanical data collections, to enhance our understanding of LBP. Although strong associations were observed between video-derived movement features and self-reported dysfunction, prospective validation and external testing may be required before clinical screening performance can be established. With appropriate validation, this approach has the potential to support the development of a scalable and accessible digital movement assessment tool for low back dysfunction.