Annals of Biomedical Engineering最新文献

Purpose: This study investigated the direct (cigarette smoke extract, CSE) and indirect (low nutrient) effects of cigarette smoking on intervertebral disc cell energy metabolism, with a focus on glucose consumption and lactate production in lumbar discs.

Methods: Lumbar IVDs from Sprague-Dawley rats were harvested and dissected into nucleus pulposus (NP), annulus fibrosus (AF), and cartilaginous endplate (CEP) regions. Minced tissue cultures from each region were exposed to physiological control (5.5 mM glucose, 5% oxygen), CSE-treated (physiological + 10% CSE), or low-nutrient conditions (1.5 mM glucose, 1% oxygen). Glucose consumption rates (GCR) and lactate production rates (LPR) were measured using a biochemical analyzer. A finite element model was developed to simulate nutrient transport and adenosine triphosphate (ATP) synthesis in the IVD under experimental conditions.

Results: Both CSE and low-nutrient conditions significantly reduced GCR and LPR in AF and NP, where NP cells exhibited the greatest metabolic activity. Low-nutrient conditions increased the LPR:GCR ratio, indicating an increase in glycolysis. CEP metabolism was marginally impacted by treatments. Computational modeling revealed that CSE conserved oxygen but reduced ATP synthesis, while low-nutrient conditions severely depleted glucose, oxygen, and ATP. Combined effects of CSE and nutrient deprivation exacerbated the reduction in ATP availability.

Conclusions: Cigarette smoking impairs IVD cellular energy metabolism through both direct toxic exposure and indirect nutrient deprivation mechanisms, with the modeled low-nutrient conditions having a more pronounced effect. The NP is the most metabolically sensitive region in the IVD, while the CEP is more resilient to fluctuations with its environment. These findings provide insights into IVD metabolic adaptations to smoking.

Percutaneous puncture techniques have been widely adopted across various domains of modern clinical interventional therapy due to their high diagnostic specificity, minimal invasiveness, and rapid postoperative recovery. However, the nonholonomic kinematics arising from the interaction between flexible needles and soft tissues, combined with the complexity of human anatomical structures, pose significant challenges to robot-assisted flexible needle insertion. To address these challenges, this paper proposes an improved rapidly-exploring random tree (RRT) path planning algorithm incorporating soft actor critic (SAC)-guided sampling. By integrating SAC-guided sampling strategies, the algorithm offers effective sampling guidance for path planning, significantly reducing the randomness of the search process, minimizing the generation of invalid nodes, accelerating convergence, and improving both path quality and planning efficiency. A hybrid sampling strategy is employed to balance global exploration and local exploitation capabilities, thereby enhancing adaptability and planning performance in complex anatomical environments. Furthermore, a navigation and positioning robot is integrated to autonomously guide the needle toward the target, thereby improving the autonomy of the insertion procedure. Target insertion experiments demonstrate an error of 0.97 ± 0.41 mm in synthetic biomimetic tissue, demonstrating strong potential for clinical translation.

Purpose: Clinical outcomes of peripheral artery disease (PAD) stenting, particularly in the highly dynamic regions of the femoropopliteal artery at the adductor hiatus and behind the knee, leave significant room for improvement. Despite the availability of various stent designs, few are capable of accommodating the severe deformations induced by limb flexion at these locations without causing adverse stent-artery interactions.

Methods: This study employed finite element analysis and response surface methodology to optimize the geometric design of nitinol PAD stents, with the objectives of improving stent-artery apposition, reducing arterial wall stress, minimizing stress concentrations, and decreasing arterial pinching under limb flexion-induced deformations. Five geometric parameters - strut width, thickness, amplitude, number, and link amplitude - were analyzed to assess their influence on stent performance.

Results: Strut width, thickness, amplitude, and the number of struts significantly impacted arterial stress and apposition, while link amplitude had an insignificant effect. We identified two optimized stent configurations that achieved > 97% stent-artery apposition, < 0.6% of the artery with stress > 100 kPa, an average arterial stress of < 29 kPa, and pinching of < 1.15. The findings revealed that lower strut amplitude and reduced strut cross-sections improved apposition and stress distribution but required careful balancing to minimize arterial pinching and maintain structural integrity.

Conclusion: This study underscores the potential of multi-objective optimization in stent design, paving the way for PAD stents that more effectively accommodate femoropopliteal biomechanics and promote favorable mechanical conditions for healing.

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are an important source of engineered cardiac tissue; however, the immaturity of their structure and function considerably limits their application. During heart development, cardiomyocytes gradually align in parallel and generate contractile force, which hints that the orderly alignment and dynamic stretch of cells are essential for hiPSC-CM maturation. Our findings indicate that hiPSC-CMs exhibit increased cellular elongation, sarcomere length, and expression of cardiac troponin T (cTnT) when cultured on 10-50 μm microgroove substrates. Additionally, myocardial connexin expression and mitochondrial occupancy were enhanced on 10 and 30 μm microgroove substrates. Furthermore, cyclic stretching with 20 and 30 μm microgroove substrates further augmented the expression of cTnT and MLC2v, as well as sarcomere length and mitochondrial occupancy in hiPSC-CMs. Importantly, the action potential recordings demonstrated the electrophysiological properties of hiPSC-CMs were improved when subjected to cyclic stretching with 20 and 30 μm microgroove substrates. Our study suggests that coordinated microgroove and cyclic stretch act as a stem cell gym to promote the structural, metabolic, and electrophysiological maturation of hiPSC-CMs, thereby enhancing their utility in cardiac regeneration and disease modeling.

Purpose: Vasomotor function plays a critical role in blood pressure (BP) regulation and organ perfusion, and its dysfunction is a major risk factor for cardiovascular disease. Despite the clinical importance of early detection, no noninvasive, quantitative, and widely accessible method for evaluating vasomotor function currently exists. To address this gap, we propose a novel smartphone-based technique for assessing vasomotor activity by measuring fingertip arteriolar elasticity.

Methods: A smartphone (iPhone) equipped with green light photoplethysmography (gPPG) was coupled to a detachable fingertip pressurization unit to enable volume-oscillometric measurement of arteriolar BP and elasticity indices (stiffness and distensibility) as functions of distending pressure. Vasoconstriction was induced by cold stimulation to validate the method.

Results: Thirteen healthy volunteers underwent measurements before and during cold water immersion of the contralateral hand. The method successfully quantified arteriolar BP and elasticity indices, revealing significant increases in stiffness and decreases in distensibility (p < 0.01), consistent with expected vasoconstrictive responses.

Conclusion: This smartphone-based approach demonstrates feasibility as a practical, noninvasive, and accessible tool for assessing vasomotor activity. With further validation in larger cohorts, it may enable early detection of vasomotor dysfunction and support cardiovascular disease prevention through convenient self-assessment.

Purpose: Forward dynamic musculoskeletal simulation is a powerful computational approach for investigating the biomechanics of human locomotion. However, existing models often oversimplify foot anatomy, thereby limiting our understanding of the role of detailed foot morphology in gait mechanics. In this study, we developed an anatomically accurate three-dimensional finite element (FE) model of the human foot to simulate its dynamic behavior during the stance phase of walking using an explicit forward dynamics approach.

Methods: The model incorporated detailed representations of bones, soft tissues, ligaments, and the plantar aponeurosis and was driven by experimentally measured tibial kinematics and estimated muscle forces.

Results: Simulation results were consistent with experimental data on ground reaction forces, plantar pressure distributions, and bone movements, confirming the model's ability to replicate key aspects of foot-ground interactions during walking. Moreover, the model enabled the estimation of internal forces, stresses, and strains in foot structures that are not directly measurable in vivo, offering new insights into the biomechanics underlying foot pathologies.

Conclusions: This study potentially provides a robust framework for exploring the form-function relationship of the human foot, with applications in evolutionary biology, clinical interventions, and the study of locomotor disorders.

Sophisticated biofidelic finite element (FE) models of sideways falls are an emerging tool for predicting hip fracture risk. We adapted an existing experimental setup for in-silico trials by creating an automated workflow to build FE models of the experiment and characterizing it with respect to the effects of limited CT scan coverage. Limited CT scan coverage was simulated by shortening the femur (25-175mm distal to the greater trochanter), misaligning the femur up to 5 degrees, and using a morphed template pelvis. We compared impact force error (E_BL) of the FE results to the existing experimental results. We then characterized the limited CT scan coverage with respect to the impact force (E_I), femur force (E_F), and fragility ratios based on the impact force (E_FRI) and the femur force (E_FRF) by comparing results to a model without any of these scan-related errors introduced. In general, the baseline simulations agreed well with the experiments (E_BL: μ = - 0.007 kN, σ = 0.409 kN). When scan coverage errors were introduced, the errors were small (E_I: μ = 0.082kN, σ = 0.232kN; E_F: μ = 0.063 kN, σ = 0.228 kN; E_FRI: μ = - 0.00, σ = 0.058; E_FRF: μ = - 0.012, σ = 0.074). The pelvis template used explained the most variance of the output measures (E_I R² = 0.876; E_F R² = 0.880; E_FRI R² = 0.901; E_FRFR² = 0.884). These results indicate that this automated methodology is suitable for typical scan coverages encountered clinically, and future work should use this workflow to explore fragility fractures in larger clinical cohorts.

Camptothecin (CPT) is a naturally occurring alkaloid recognized for its broad spectrum of biological activities, including potent anticancer, anti-inflammatory, antibacterial, and antioxidant effects. Its clinical application, however, is restricted by inherent limitations such as poor aqueous solubility, instability of the pharmacologically active lactone ring, and severe systemic toxicity. To overcome these challenges, a variety of nanotechnology-based delivery systems, including liposomes, polymeric nanoparticles, solid lipid nanoparticles (SLNs), and micelles, have been developed to enhance the physicochemical stability and pharmacokinetic profiles of CPT. Despite considerable progress, a comprehensive review integrating recent advances in CPT nanoformulation strategies, preparation techniques, and therapeutic applications has been lacking in the past two years. This review systematically examines the design principles, delivery platforms, and fabrication methods for CPT-loaded nanoformulations and critically analyzes how these approaches improve bioavailability and therapeutic efficacy. In addition, this review integrates recent advances in CPT nanomedicines, summarizes the current patent landscape and clinical trial developments, and highlights how formulation strategies are designed to facilitate clinical translation. By comparing diverse nanoformulations strategies and identifying design principles that have shown translational promise, this work uniquely bridges material innovation with therapeutic optimization, providing a critical insight into how nanotechnology can address the pharmacological barriers of CPT and inspire next-generation drug delivery systems.