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Simulations of human-technology interaction in the context of product development require comprehensive knowledge of biomechanical in vivo behavior. To obtain this knowledge for the abdomen, we measured the continuous mechanical responses of the abdominal soft tissue of ten healthy participants in different lying positions anteriorly, laterally, and posteriorly under local compression depths of up to 30 mm. An experimental setup consisting of a mechatronic indenter with hemispherical tip and two time-of-flight (ToF) sensors for optical 3D displacement measurement of the surface was developed for this purpose. To account for the impact of muscle tone, experiments were conducted with both controlled activation and relaxation of the trunk muscles. Surface electromyography (sEMG) was used to monitor muscle activation levels. The obtained data sets comprise the continuous force-displacement data of six abdominal measurement regions, each synchronized with the local surface displacements resulting from the macro-indentation, and the bipolar sEMG signals at three key trunk muscles. We used inverse finite element analysis (FEA), to derive sets of nonlinear material parameters that numerically approximate the experimentally determined soft tissue behaviors. The physiological standard values obtained for all participants after data processing served as reference data. The mean stiffness of the abdomen was significantly different when the trunk muscles were activated or relaxed. No significant differences were found between the anterior-lateral measurement regions, with exception of those centered on the linea alba and centered on the muscle belly of the rectus abdominis below the intertubercular plane. The shapes and areas of deformation of the skin depended on the region and muscle activity. Using the hyperelastic Ogden model, we identified unique material parameter sets for all regions. Our findings confirmed that, in addition to the indenter force-displacement data, knowledge about tissue deformation is necessary to reliably determine unique material parameter sets using inverse FEA. The presented results can be used for finite element (FE) models of the abdomen, for example, in the context of orthopedic or biomedical product developments.

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Cervical remodeling is critical for a healthy pregnancy. Premature tissue changes can lead to preterm birth (PTB), and the absence of remodeling can lead to post-term birth, causing significant morbidity. Comprehensive characterization of cervical material properties is necessary to uncover the mechanisms behind abnormal cervical softening. Quantifying cervical material properties during gestation is challenging in humans. Thus, a nonhuman primate (NHP) model is employed for this study. In this study, cervical tissue samples were collected from Rhesus macaques before pregnancy and at three gestational time points. Indentation and tension mechanical tests were conducted, coupled with digital image correlation (DIC), constitutive material modeling, and inverse finite element analysis (IFEA) to characterize the equilibrium material response of the macaque cervix during pregnancy. Results show, as gestation progresses: (1) the cervical fiber network becomes more extensible (nonpregnant versus pregnant locking stretch: 2.03 ± 1.09 versus 2.99 ± 1.39) and less stiff (nonpregnant versus pregnant initial stiffness: 272 ± 252 kPa versus 43 ± 43 kPa); (2) the ground substance compressibility does not change much (nonpregnant versus pregnant bulk modulus: 1.37 ± 0.82 kPa versus 2.81 ± 2.81 kPa); (3) fiber network dispersion increases, moving from aligned to randomly oriented (nonpregnant versus pregnant concentration coefficient: 1.03 ± 0.46 versus 0.50 ± 0.20); and (4) the largest change in fiber stiffness and dispersion happen during the second trimester. These results, for the first time, reveal the remodeling process of a nonhuman primate cervix and its distinct regimes throughout the entire pregnancy.

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From biological organs to soft robotics, highly deformable materials are essential components of natural and engineered systems. These highly deformable materials can have heterogeneous material properties, and can experience heterogeneous deformations with or without underlying material heterogeneity. Many recent works have established that computational modeling approaches are well suited for understanding and predicting the consequences of material heterogeneity and for interpreting observed heterogeneous strain fields. In particular, there has been significant work toward developing inverse analysis approaches that can convert observed kinematic quantities (e.g., displacement, strain) to material properties and mechanical state. Despite the success of these approaches, they are not necessarily generalizable and often rely on tight control and knowledge of boundary conditions. Here, we will build on the recent advances (and ubiquity) of machine learning approaches to explore alternative approaches to detect patterns in heterogeneous material properties and mechanical behavior. Specifically, we will explore unsupervised learning approaches to clustering and ensemble clustering to identify heterogeneous regions. Overall, we find that these approaches are effective, yet limited in their abilities. Through this initial exploration (where all data and code are published alongside this manuscript), we set the stage for future studies that more specifically adapt these methods to mechanical data.

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The long head biceps tendon (LHBT) is presumed a common source of shoulder joint pain and injury. Despite common LHBT pathologies, diagnosis and preferred treatment remain frequently debated. This Short Communication reports the development of a subject-specific finite element model of the shoulder joint based on one subject's 3D reconstructed anatomy and 3D in vivo kinematics recorded from bone-fixed electromagnetic sensors. The primary purpose of this study was to use the developed finite element model to investigate the LHBT mechanical environment during a typical shoulder motion of arm raising. Furthermore, this study aimed to assess the viability of material models derived from uniaxial tensile tests for accurate simulation of in vivo motion. The findings of our simulations indicate that the LHBT undergoes complex multidimensional deformations. As such, uniaxial material properties reported in the existing body of literature are not sufficient to simulate accurately the in vivo mechanical behavior of the LHBT. Further experimental tests on cadaveric specimens, such as biaxial tension and combinations of tension and torsion, are needed to describe fully the mechanical behavior of the LHBT and investigate its mechanisms of injury.

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Biological soft tissues are constantly adapting to their mechanical environment and remodel to restore certain mechanobiological homeostatic conditions. These effects can be modeled using the constrained mixture theory, that assumes degradation of material over time and the gradual replacement of extant material by newly deposited material. While this theory presents an elegant way to grasp phenomena of growth and remodeling in soft biological tissues, implementation difficulties may arise. Therefore, we give a detailed overview of the mathematical description of the constrained mixture theory and its homogenized equivalent, and present practical suggestions to numerically implement the theories. These implementations are thoroughly tested with multiple example growth and remodeling models. Results show a good correspondence between both theories, with the homogenized theory favored in terms of time efficiency. Results of a step time convergence study show the importance of choosing a small enough time step, especially when using the classical theory.

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With the development of wearable technologies, the interfacial properties of skin and devices have become much more important. For research and development purposes, porcine skin is often used to evaluate device performance, but the differences between in vivo, in situ and ex vivo porcine skin mechanical properties can potentially misdirect investigators during the development of their technology. In this study, we investigated the significant changes to mechanical properties with and without perfusion (in vivo versus in vitro tissue). The device focus for this study was a skin-targeting Nanopatch vaccine microneedle device, employed to assess the variance to key skin engagement parameters - penetration depth and delivery efficiency - due to different tissue conditions. The patches were coated with fluorescent or 14C radiolabelled formulations for penetration depth and delivery efficiency quantification in vivo, and at time points up to 4 h post mortem. An immediate cessation of blood circulation saw mean microneedle penetration depth fell from ∼100 µm to ∼55 µm (∼45%). Stiffening of underlying tissues as a result of rigor mortis then augmented the penetration depths at the 4 h timepoint back to ∼100 µm, insignificantly different (p = 0.0595) when compared with in vivo. The highest delivery efficiency of formulation into the skin (dose measured in the skin excluding leftover dose on skin and patch surfaces) was also observed at this time point of ∼25%, up from ∼2% in vivo. Data obtained herein progresses medical device development, highlighting the need to consider the state and muscle tissues when evaluating prototypes on cadavers.

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Analysis of corneal tissue natural frequency was recently proposed as a biomarker for corneal biomechanics and has been performed using high-resolution optical coherence tomography (OCT)-based elastography (OCE). However, it remains unknown whether natural frequency analysis can resolve local variations in tissue structure. We measured heterogeneous samples to evaluate the correspondence between natural frequency distributions and regional structural variations. Sub-micrometer sample oscillations were induced point-wise by microliter air pulses (60-85 Pa, 3 ms) and detected correspondingly at each point using a 1,300 nm spectral domain common path OCT system with 0.44 nm phase detection sensitivity. The resulting oscillation frequency features were analyzed via fast Fourier transform and natural frequency was characterized using a single degree of freedom (SDOF) model. Oscillation features at each measurement point showed a complex frequency response with multiple frequency components that corresponded with global structural features; while the variation of frequency magnitude at each location reflected the local sample features. Silicone blocks (255.1 ± 11.0 Hz and 249.0 ± 4.6 Hz) embedded in an agar base (355.6 ± 0.8 Hz and 361.3 ± 5.5 Hz) were clearly distinguishable by natural frequency. In a beef shank sample, central fat and connective tissues had lower natural frequencies (91.7 ± 58.2 Hz) than muscle tissue (left side: 252.6 ± 52.3 Hz; right side: 161.5 ± 35.8 Hz). As a first step, we have shown the possibility of natural frequency OCE methods to characterize global and local features of heterogeneous samples. This method can provide additional information on corneal properties, complementary to current clinical biomechanical assessments, and could become a useful tool for clinical detection of ocular disease and evaluation of medical or surgical treatment outcomes.

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The ability of the urinary bladder to maintain low intravesical pressures while storing urine is key in ensuring proper organ function and highlights the key role that tissue mechanics plays in the lower urinary tract. Loss of supraspinal neuronal connections to the bladder after spinal cord injury can lead to remodeling of the structure of the bladder wall, which may alter its mechanical characteristics. In this study, we investigate if the morphology and mechanical properties of the bladder extracellular matrix are altered in rats 16 weeks after spinal cord injury as compared to animals who underwent sham surgery. We measured and quantified the changes in bladder geometry and mechanical behavior using histological analysis, tensile testing, and constitutive modeling. Our results suggest bladder compliance is increased in paraplegic animals 16 weeks post-injury. Furthermore, constitutive modeling showed that increased distensibility was driven by an increase in collagen fiber waviness, which altered the distribution of fiber recruitment during loading. STATEMENT OF SIGNIFICANCE: The ability of the urinary bladder to store urine under low pressure is key in ensuring proper organ function. This highlights the important role that mechanics plays in the lower urinary tract. Loss of control of neurologic connection to the bladder from spinal cord injury can lead to changes of the structure of the bladder wall, resulting in altered mechanical characteristics. We found that the bladder wall's microstructure in rats 16 weeks after spinal cord injury is more compliant than in healthy animals. This is significant since it is the longest time post-injury analyzed, to date. Understanding the extreme remodeling capabilities of the bladder in pathological conditions is key to inform new possible therapies.

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The purpose of this study is to demonstrate the capabilities of finite-element (FE) models to predict contraction of wounds managed with negative pressure wound therapy (NPWT). The features of wounds and surrounding tissues were analysed to gain insights into the mechanical effects of NPWT on them. 3D digital image correlation (DIC) measurement of soft tissue phantoms was used to investigate the effect of wound thickness, size, and shape, which were further compared with results of FE simulations. It was noticed that with an increased NP level the difference between DIC and FE in wound contraction became more pronounced, particularly for the thick wounds. In addition, the locations of the wounds were evaluated to predict their contraction characteristics, based on surrounding tissue structures, in 3D using the developed FE models. It was demonstrated that features and location of wounds influenced their deformations differently for the same pressure levels. Overall, this study, involving a combined experimental and computational approach, allowed the important insights into mechanical effects of NPWT.

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Collagen fibers are the primary load-bearing microstructural constituent of bodily soft tissues, and, when subjected to external loading, the collagen fibers reorient, uncrimp, and elongate. Specific to the atrioventricular heart valve leaflets, the collagen fiber kinematics form the basis of many constitutive models; however, some researchers claim that modeling the affine fiber kinematics (AFK) are sufficient for accurately predicting the macroscopic tissue deformations, while others state that modeling the non-affine kinematics (i.e., fiber uncrimping together with elastic elongation) is required. Experimental verification of the AFK theory has been previously performed for the mitral valve leaflets in the left-side heart; however, this same evaluation has yet to be performed for the morphologically distinct tricuspid valve (TV) leaflets in the right-side heart. In this work, we, for the first time, evaluated the AFK theory for the TV leaflets using an integrated biaxial testing-polarized spatial frequency domain imaging device to experimentally quantify the load-dependent collagen fiber reorientations for comparison to the AFK theory predictions. We found that the AFK theory generally underpredicted the fiber reorientations by 3.1°, on average, under the applied equibiaxial loading with greater disparity when the tissue was subjected to the applied non-equibiaxial loading. Furthermore, increased AFK errors were observed with increasing collagen fiber reorientations (Pearson coefficient r = -0.36, equibiaxial loading), suggesting the AFK theory is better suited for relatively smaller reorientations. Our findings suggest the AFK theory may require modification for more accurate predictions of the collagen fiber kinematics in the TV leaflets, which will be useful in refining modeling efforts for more accurate TV simulations.

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The active and passive mechanical behavior of a cosmetic tightening product for skin anti-aging is investigated based on a wide range of in vivo and in vitro measurements. The experimental data are used to inform a numerical model of the attained cosmetic effect, which is then implemented in a commercial finite-element framework and used to analyze the mechanisms that regulate the biomechanical interaction between the native tissue and the tightening film. Such a film reduces wrinkles and enhances skin consistency by increasing its stiffness by 48-107% and reducing inelastic, non-recoverable deformations (-47%). The substrate deformability influences both the extent of tightening and the reduction of wrinkle amplitude. The present findings allow, for the first time, to rationalize the mechanisms of action of cosmetic products with a tightening action and provide quantitative evidence for further optimization of this fascinating class of biomaterials.

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Here we mimic the mechanical properties of native fascia to design surgical mesh for fascia replacement. Despite the widespread acceptance of synthetic materials as tissue scaffolds for pelvic floor disorders, mechanical property mismatch between mesh and adjacent native tissue drives fibrosis and erosion, leading the FDA to remove several surgical meshes from the market. However, autologous tissue does not induce either fibrosis or adjacent tissue erosion, suggesting the potential for biomimetic surgical mesh. In this study, we determined the design rules for mesh that mimics native fascia by mathematically modeling multi-component polymer networks, composed of elastin-like and collagen-like fibers, using a spring-network model. To validate the model, we measured the stress-strain curves of native bovine and nonhuman primate (Macaca mulatta) abdominal fascia in both toe and linear regions. We find that the stiffer collagen-like fibers must remain limp until the elastin-like fibers extend to the initial length of spanning collagen-like fibers under uniaxial tension. Comparing model results to experiment determines the product of fiber volume fraction and elastic modulus, a critical design parameter. Dual fiber mesh with mechanical properties that mimic fascia are feasible. These results have broad application to a wide range of soft tissue replacements including ~200,000 surgeries/year for pelvic floor disorders, because standard-of-care mesh contain only stiffer polymers that behave more like collagen than native tissue.

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The non-homogeneous, anisotropic material properties, and triphasic nature of articular cartilage enables diarthrodial joints to withstand large and complex physiological loading conditions. To develop biomaterials that provide similar functional properties as those found in articular cartilage, it is vital to have knowledge of the strain distributions in cartilage for a large range of loading conditions. Applied stress vs. strain properties of articular cartilage have been measured primarily for static conditions, but the dynamic properties are thought to be more relevant for joint function and cartilage biosynthesis. Furthermore, the dynamic stress-strain properties are expected to vary significantly from those obtained for static, steady-state conditions. Here, we present a method for the determination of axial strain fields throughout the depth of articular cartilage for static loading conditions and dynamic conditions performed at different loading rates. For the conditions tested here, the strain distributions throughout the cartilage depth were more uniform for the dynamic than the static loading conditions, and more uniform for high compared to low strain rates.

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Mechanical loading is an important cue for directing stem cell fate and engineered tissue formation in vitro. Stem cells cultured on 2-dimensional (D) substrates and in 3D scaffolds have been shown to differentiate toward bone, tendon, cartilage, ligament, and skeletal muscle lineages depending on their exposure to mechanical stimuli. To apply this mechanical stimulus in vitro, mechanical bioreactors are needed. However, current bioreactor systems are challenged by their high cost, limited ability for customization, and lack of force measurement capabilities. We demonstrate the use of 3-dimensional printing (3DP) technology to design and fabricate a low-cost custom bioreactor system that can be used to apply controlled mechanical stimuli to cells in culture and measure the mechanical properties of small soft tissues. The results of our in vitro studies and mechanical evaluations show that 3DP technology is feasible as a platform for developing a low-cost, customizable, and multifunctional mechanical bioreactor system. • 3DP technology was used to print a multifunctional bioreactor system/tensile load frame for a fraction of the cost of commercial systems. • The system mechanically stimulated cells in culture and evaluated the mechanical properties of soft tissues. • This system is easily customizable and can be used to evaluate multiple types of soft tissues.

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Valvular heart diseases are complex disorders, varying in pathophysiological mechanism and affected valve components. Understanding the effects of these diseases on valve functionality requires a thorough characterization of the mechanics and structure of the healthy heart valves. In this study, we performed biaxial mechanical experiments with extensive testing protocols to examine the mechanical behaviors of the mitral valve and tricuspid valve leaflets. We also investigated the effect of loading rate, testing temperatures, species (porcine versus ovine hearts), and age (juvenile vs adult ovine hearts) on the mechanical responses of the leaflet tissues. In addition, we evaluated the structure of chordae tendineae within each valve and performed histological analysis on each atrioventricular leaflet. We found all tissues displayed a characteristic nonlinear anisotropic mechanical response, with radial stretches on average 30.7% higher than circumferential stretches under equibiaxial physiological loading. Tissue mechanical responses showed consistent mechanical stiffening in response to increased loading rate and minor temperature dependence in all five atrioventricular heart valve leaflets. Moreover, our anatomical study revealed similar chordae quantities in the porcine mitral (30.5 ±â€¯1.43 chords) and tricuspid valves (35.3 ±â€¯2.45 chords) but significantly more chordae in the porcine than the ovine valves (p < 0.010). Our histological analyses quantified the relative thicknesses of the four distinct morphological layers in each leaflet. This study provides a comprehensive database of the mechanics and structure of the atrioventricular valves, which will be beneficial to development of subject-specific atrioventricular valve constitutive models and toward multi-scale biomechanical investigations of heart valve function to improve valvular disease treatments.

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Finite element (FE)-based biomechanical simulations of the upper airway are promising computational tools to study abnormal upper airway deformations under obstructive sleep apnea (OSA) conditions and to help guide minimally invasive surgical interventions in case of upper airway collapse. To this end, passive biomechanical properties of the upper airway tissues, especially oropharyngeal soft tissues, are indispensable. This research aimed at characterizing the linear elastic mechanical properties of the oropharyngeal soft tissues including palatine tonsil, soft palate, uvula, and tongue base. For this purpose, precise indentation experiments were conducted on freshly harvested human tissue samples accompanied by FE-based inversion schemes. To minimize the impact of the probable nonlinearities of the tested tissue samples, only the first quarter of the measured force-displacement data corresponding to the linear elastic regime was utilized in the FE-based inversion scheme to improve the accuracy of the tissue samples' Young's modulus calculations. Measured Young's moduli of the oropharyngeal soft tissues obtained in this study are presented. They include first estimates for palatine tonsil tissue samples while measured Young's moduli of other upper airway tissues were obtained for the first time using fresh human tissue samples.

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Breast and bra motion research aims to understand how the breasts/bra move to aid development of apparel that minimizes motion. Most previously published research has tracked nipple motion to represent bra motion. However, this method does not provide information regarding regional tissue motion. A more comprehensive approach might facilitate understanding how the entire soft-tissue mass moves during physical activities. This study developed and tested an objective method to comprehensively measure 3-dimensional bra motion, including regional displacement and velocity, displacement phasing, and surface stretch. To test the method, 6 females were fitted with a minimally supportive, seamless bra (small bra n = 3; large bra n = 3). Data were collected as participants ran on a treadmill. Results indicated marker displacement, velocity, link stretch, and link stretch velocities reached as high as 52.6 (6.8) mm, 504.8 (88.7) mm/s, 29.5% (7.1%) of minimum length, and 3.8 (1.0) mm/s/mm, respectively, with the large bra having greater motions compared with the small. Most bra motion occurred above/below the nipple region and at the bra's strap-body interface, independent of bra size. Importantly, maximum marker displacement and velocity did not occur at the nipple. Measurements obtained from this new method may be important for designing innovative clothing that minimizes bra motion during physical activity.

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Synthesis of hydrogel networks capable of accurately replicating the biomechanical demands of musculoskeletal soft tissues continues to present a formidable materials science challenge. Current systems are hampered by combinations of limited moduli at biomechanically relevant strains, inefficiencies driven by undesirable hysteresis and permanent fatigue, and recovery dynamics too slow to accommodate rapid cycling prominent in most biomechanical loading profiles. Here, we report on a novel paradigm in hydrogel design based on prefabrication of an efficient nanoscale network architecture using the melt-state self-assembly of amphiphilic block copolymers. Rigorous characterization and mechanical testing reveal that swelling of these preformed networks produces hydrogels with physiologically relevant moduli and water compositions, negligible hysteresis, subsecond elastic recovery rates, and unprecedented resistance to fatigue over hundreds of thousands of compression cycles. Furthermore, by relying only on simple thermoplastic processing to form these nanostructured networks, the synthetic complexities common to most solution-based hydrogel fabrication strategies are completely avoided.

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Bioprosthetic heart valves (BHVs), derived from glutaraldehyde crosslinked (GLUT) porcine aortic valve leaflets or bovine pericardium (BP), are used to replace defective heart valves. However, valve failure can occur within 12-15 years due to calcification and/or progressive structural degeneration. We present a novel fabrication method that utilizes carbodiimide, neomycin trisulfate, and pentagalloyl glucose crosslinking chemistry (TRI) to better stabilize the extracellular matrix of BP. We demonstrate that TRI-treated BP is more compliant than GLUT-treated BP. GLUT-treated BP exhibited permanent geometric deformation and complete alteration of apparent mechanical properties when subjected to induced static strain. TRI BP, on the other hand, did not exhibit such permanent geometric deformations or significant alterations of apparent mechanical properties. TRI BP also exhibited better resistance to enzymatic degradation in vitro and calcification in vivo when implanted subcutaneously in juvenile rats for up to 30 days.

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PURPOSE: The goals of this study were to (1) investigate the in vivo elongation behaviour of the posterior cruciate ligament (PCL) during running in the uninjured knee and (2) evaluate changes in PCL elongation during running after anatomic or non-anatomic anterior cruciate ligament (ACL) reconstruction. METHODS: Seventeen unilateral ACL-injured subjects were recruited after undergoing anatomic (n = 9) or non-anatomic (n = 8) ACL reconstruction. Bilateral high-resolution CT scans were obtained to produce 3D models. Anterolateral (AL) and posteromedial (PM) bundles insertion sites of the PCL were identified on the 3D CT scan reconstructions. Dynamic knee function was assessed during running using a dynamic stereo X-ray (DSX) system. The lengths of the AL and PM bundles were estimated from late swing through mid-stance. The contralateral knees served as normal controls. RESULTS: Control knees demonstrated a slight decrease in AL bundle and a significant decrease in PM bundle length following foot strike. Length and elongation patterns of the both bundles of the PCL in the anatomic ACL reconstruction group were similar to the controls. However, the change in dynamic PCL length was significantly greater in the non-anatomic group than in the anatomic reconstruction group after foot strike (p < 0.05). CONCLUSION: The AL bundle length decreased slightly, and the PM bundle length significantly decreased after foot strike during running in uninjured knees. Anatomic ACL reconstruction maintained normal PCL elongation patterns more effectively than non-anatomic ACL reconstruction during high-demand, functional loading. These results support the use of anatomic ACL reconstruction to achieve normal knee function in high-demand activities. LEVEL OF EVIDENCE: Case-control study, Level III.

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