Additively manufactured(3D-printed) anatomical bone models are used for medical education and surgical training. Manufacturing of patient-specific anatomies and rare pathologies has improved rapidly in the recent past, enabling training opportunities that were previously restricted to limitedly available anatomic specimens. However, the imitation of patient-specific trabecular bone in additively manufactured bone models remains complex and thus inadequately addressed. Test specimens in the form of Gyroid and Voronoi lattice cubes were manufactured via fused filament fabrication(FFF)-printing at varying densities with polylactide, polylactide /carbon fiber composite and polyamide /glass fiber composite filaments, and submerged in gelatin. Additionally, trabecular bone test cubes were removed from bovine femoral specimens, and the bone mineral density (BMD) was assessed utilizing quantitative computed-tomography (QCT). Subsequently, haptic drill resistance of all test cubes was evaluated by four orthopedic and trauma surgeons, and the mechanical drill resistance was assessed using a load frame. Multiple polymer lattice structures and material configurations were evaluated by the surgeons as suitable to mimic actual trabecular bone (Likert ratings between 2.60 and 3.00). Regression analyses of the surgeons' evaluations of both the trabecular bone (R2 = 0.82) and the polymer lattice cubes (0.66 ≤ R2 ≤ 0.89) enabled the extraction of practical manufacturing parameters linking them with patient-specific BMD. The imitation of trabecular bone models via FFF-printing is feasible and could substantially enhance the haptic feedback in additively manufactured anatomical bone models. Applying the presented manufacturing framework enables the cost- and time-efficient production of patient-specific anatomical models to enhance preoperative planning and surgical training.

This study suggests a new analysis pipeline of MEG data, uniquely designed for neural decoding of small-sized datasets. It combines classic methods that assume stationarity of the data together with non-stationary methods to compensate for the distortions created by the classic approach. Popular Fourier-based methods are applied in a classic fashion, followed by additional filters using empirical mode decomposition and principal component analysis to further clean the data. An automated approach for epoch rejection is proposed as well. In this work, we propose a novel approach for data augmentation. Unlike most other solutions, combinations' averaging technique can be used on real data rather than synthetic one, making it more reliable from the neuroscientific point of view. It is also shown that this approach does not create any unnatural patterns within the augmented data. The proposed approach allows for application of machine learning algorithms on small-sized datasets. This broadens the list of available analyses for datasets with limited number of recorded examples. An image naming task was used for in-subject neural decoding estimations. In this work, we propose and compare four different machine learning designs. It is shown that a careful selection of the used channels, reduction of the feature dimensions, and averaging of the recorded epochs may significantly increase the accuracy of neural decoding.

Sickle cell disease (SCD) is a debilitating genetic disorder affecting hemoglobin in red blood cells. Patients with SCD are at risk of cerebrovascular disease in the Circle of Willis (CoW), with strokes occurring from early childhood into adulthood. Despite this lifelong risk, stroke prevention guidelines using transcranial Doppler ultrasound (TCD) exist only for children, leaving a critical gap for adults. This study aimed to characterize cerebral hemodynamics in the CoW of adults with SCD to support future risk stratification and treatment guidelines. Numerical simulations were performed using 3D vascular geometries segmented from high-resolution, patient-specific magnetic resonance imaging in healthy controls (n=3), SCD patients without stroke (n=3), and SCD patients post-stroke (n=3). Key hemodynamic parameters including time-averaged wall shear stress (TAWSS), surface area exposed to low or high WSS, time-averaged mean of maximum velocity (TAMMV), and pressure drop across the CoW were quantified and compared. Preliminary results show distinct hemodynamic differences were observed across groups. SCD patients post-stroke had lower TAMMV at TCD-equivalent CoW locations (except one with ICA stenosis), the lowest average TAWSS, and the greatest surface area exposed to WSS Pa. In contrast, SCD patients without stroke had the highest TAWSS and greatest area exposed to WSS >7 Pa. Despite similar total cerebral blood flow to controls, post-stroke patients showed a lower pressure drop across the CoW. Patient-specific simulations can quantify cerebral hemodynamics in adults with SCD, offering insight into stroke-related changes and informing future stroke risk assessment and personalized treatment strategies.

Gait analyses are becoming increasingly relevant in digital medicine. For implementation in clinical practice, knowledge on differences between gait patterns of separate bone fracture types is required. The aim of this study was to compare longitudinal changes in gait of patients with proximal tibial, tibial shaft, and malleolar fractures, as well as nonunion. Patients with a proximal tibial, tibial shaft, or malleolar fracture requiring surgery were prospectively enrolled in this longitudinal observational study. A healthy control group received one measurement. Optical motion capture was used to obtain spatiotemporal gait parameters and kinematics at 6weeks, 3months, and 6months after surgery. In total, 73 patients (51.1 ± 16.9years) and 43 controls (50.5 ± 17.7years) were included. Only in malleolar fractures, all gait parameters had returned to normal after 6months. Differences between fracture types at 6weeks were found in step height (P = 0.01), knee range of motion (ROM, P < 0.001), and its asymmetry (P < 0.001). At 6months, knee ROM was still lower in proximal tibial than tibial shaft and malleolar fractures (P = 0.04; 0.047). Tibial shaft fractures with and without nonunion differed in stance time (P = 0.007; 0.02) and its asymmetry (P = 0.007; 0.009) after 6weeks and 6months, but not at 3months. When monitoring fracture healing with motion capture, differences between fracture types and their timely appearance should be considered. The study was prospectively registered in the German Clinical Trials Register DRKS00025108.

Overcoming the limitations of synthetic vascular grafts in the development of biocompatible and regenerative vessels remains a long-term objective in tissue engineering. In this study, we engineered large-diameter fibrin-based vascular grafts with a target inner diameter of 21mm replicating all three layers of the native human vessel wall in vitro. The Tunica media was reconstructed using a compressed high-density (25mg/mL) fibrin matrix seeded with smooth muscle cells expressing α-SMA and calponin, differentiated from adipose-derived mesenchymal stem cells (ASCs). The Adventitia-equivalent was formed in a 5mg/mL fibrin gel containing ASCs, human umbilical vein endothelial cells (HUVECs), and normal human dermal fibroblasts (NHDFs) to enable the formation of a capillary-like network resembling the native adventitial Vasa vasorum. The luminal surface was endothelialized with HUVECs to replicate the Tunica intima. While controls were cultured statically for 7days, other grafts were evaluated under pulsatile perfusion at physiological pressures using the TransMedics® "Organ Care System Heart™". The stepwise fabrication technique resulted in three-layered bioartificial vessel equivalents with a mean inner diameter of 21mm. All constructed vessels (n = 3) maintained sufficient biomechanical stability to withstand physiological pressure (120.9 ± 1.2 to 61.4 ± 12.5mmHg) at 60bpm throughout the perfusion period. The aortic grafts exhibited a cyclic stretch (8.95 ± 2.03%) within the physiological range of native vessels. Mechanical stimulation induced a layer-specific physiological cell morphology and alignment across all three layers of the vascular wall. Endothelial coverage was high on static grafts (81.39 ± 2.37%) and on one of three dynamic grafts. Shear stress during perfusion (0.38 ± 0.03 dyn cm-2) remained below physiological levels, and further evaluation under prolonged perfusion (> 21days) is required to assess long-term biomechanical stability and vascular functionality. This approach may be considered a proof of concept and constitutes a first step toward the development of biometric and functional large-diameter vessel replacements.

The pricing of high-performance hand prostheses and grasp limitations of low-cost hand prostheses indicate a need for the creation of a cost-effective upper limb prosthesis with high-performance capabilities. The need is particularly relevant for pediatric recreational applications, as it is difficult to finance multiple high-performance devices to match the growth of a child. We propose a low-cost upper limb prosthesis, the HelpingHand, to address these concerns through modification of the publicly available e-NABLE Phoenix Hand v2. Custom flexible finger modules and a user-adjustable whippletree mechanism were developed, allowing for swapping between power and precision grasp positions based on selected tension levels. The two designs were then compared through user performance tests with various common household objects and grasp positions. The HelpingHand device features wrist actuation and incorporation of various adjustable power and precision grasp patterns with a material price point of under $10. In addition, bioinspired flexible finger modules were created to improve device grasp functionality. User tests demonstrated improvements in device performance in both power and precision grasp positions over current low-cost prosthetic standards. Implementation of user-adjusted grasp positions in an upper limb prosthesis developed with accessible manufacturing methods represents a promising step forward in low-cost device development. With further optimization and validation, the HelpingHand could provide an advancement in low-cost recreational prosthetic technology.

The escalating demand for functional tissue-engineered constructs has highlighted the critical need for scaffolds that are not only biocompatible but also cost-effective and scalable, qualities that are often lacking in traditional synthetic or animal-derived materials. Driven by this necessity, plant-derived biomaterials have emerged as promising candidates due to their natural abundance and structurally versatile architecture. Primarily composed of cellulose-rich extracellular matrices, hemicellulose, lignin, and pectin, these materials provide physicochemical properties that can be tailored to emulate specific tissue microenvironments. Notably, native plant vasculature contains intrinsic microchannels that facilitate perfusion, making them uniquely advantageous for cell infiltration and angiogenesis. This review aims to synthesize current progress in plant-based scaffolds for tissue engineering, with emphasis on structure-function relationships, processing strategies, and translational readiness. We outline key biofabrication workflows centered on decellularization and preservation of ultrastructure, followed by recellularization approaches and considerations of degradation behavior and mechanical stability. This review also summarizes mechanistic foundations of regeneration, including cell-material interactions, hierarchical microarchitecture, and contributions of intrinsic or incorporated bioactive constituents. Finally, we discuss therapeutic applications across soft and hard tissues and highlight performance enhancement strategies. Importantly, it is worth noting that the current evidence base remains strictly preclinical, with no human clinical trials reported to date. Significant challenges persist, including incomplete decellularization, limited long-term mechanical stability under physiological loading, and the lack of standardized manufacturing protocols. Overall, plant-based scaffolds represent a maturing and sustainable platform with strong potential for future regenerative strategies, contingent upon rigorous standardization and comprehensive safety evaluation.

The extracellular matrix (ECM) is crucial for tissue structure and cell behavior, positioning decellularized ECM (dECM) as a valuable biomaterial for regenerative medicine. The human placenta, abundant and bioactive, is an ideal ECM source. This study optimized decellularization protocols for human placental tissue to balance cellular removal with ECM integrity. Four protocols (P1-P4) were compared, using combinations of ionic/non-ionic detergents (SDS, Triton X-100), enzymatic agents (trypsin, DNase), and sterilizing treatments. Lyophilized dECM was processed into injectable hydrogels, characterized for mechanical, rheological, and degradation properties. DNase-treated protocols reduced DNA to < 50ng/mg dry weight, confirming effective cell removal, but ECM retention varied. P2, containing the highest concentrations of SDS among our tested protocols, results in depletion of glycosaminoglycans (GAGs), loss of fibronectin, and disruption of collagen organization. Milder protocols regarding SDS concentration, including P1 and P3, preserved GAGs and ECM proteins (collagen IV, fibronectin, laminin), as shown by immunofluorescence and histology. All protocols successfully formed stable hydrogels, but mechanical stiffness and viscoelastic properties differed. The high-SDS protocol without DNase treatment (P2-) exhibited the lowest storage modulus (G':13.7 ± 2.9Pa), likely due to excessive ECM disruption. In contrast, the NaOH protocol (P3) with a lower SDS concentration than P2 showed the most consistent performance, with comparable G' values in DNase-treated (53.0 ± 20.0Pa) and untreated (49.3 ± 3.3Pa) hydrogels. Detergent choice and DNase treatment influence ECM retention and hydrogel functionality. The NaOH protocol with DNase treatment (P3+) offers superior ECM preservation for placenta-derived dECM scaffolds, laying a foundation for regenerative medicine applications.

This study aims to investigate the relationship between increasing internal tibial torque (ITT) and the distribution of stress on the anterior cruciate ligament (ACL), with a focus on identifying the location of tear initiation and propagation. In particular, the study emphasizes the femoral enthesis as a potential site of geometric vulnerability during pivot landing. A three-dimensional finite element model of the ACL was developed and combined with an extended finite element method framework to simulate tear initiation and propagation. The model was driven by torque-indexed, three-dimensional knee kinematics obtained from previous in silico knee simulations that were validated against in vitro cadaveric knee tests (15 specimens). ITT was applied in graded steps to reproduce pivot landing-relevant internal rotation loading. Stress/strain fields were evaluated, and tear initiation/propagation were tracked to quantify damage evolution. Maximum von Mises stress increased proportionally with ITT and localized near the femoral enthesis, with a mean increase of 26.56% for each 5Nm increase in torque. Stress concentration consistently occurred at the posterolateral bundle attachment on the femoral side, where tear initiation was predicted. With further ITT increases, the tear propagated from the femoral enthesis, indicating a torque-dependent damage progression mechanism. Increased ITT produced reproducible stress/strain concentration at the femoral enthesis, supporting structural vulnerability during pivot landing. This approach extends stress-only analyses by predicting rupture initiation and tear progression. These findings may inform prevention and rehabilitation by highlighting the roles of ITT and femoral insertion morphology in ACL tear initiation and propagation.

This study evaluated tibiofemoral loading and medial meniscal stress distribution in individuals with flexible flatfoot (FFF) during walking under different foot progression angle (FPA) conditions. This study analyzed the gait of 28 FFF patients (16 males, 12 females) under three FPA conditions (neutral, toe-in, toe-out). Kinematic (Vicon) and kinetic (Kistler) data were used to estimate tibiofemoral forces in OpenSim. Subsequently, joint angles and muscle forces at peak tibiofemoral forces were used to drive a finite element (FE) model of the knee, enabling the comparison of meniscal von Mises stress, maximum shear stress, and contact pressure across FPA conditions. Tibiofemoral force increased during early stance (9-11%) in the toe-in condition with this increase reaching statistical significance in males (p = 0.008, mean partial within the SPM-identified cluster). FE analysis showed that peak stresses and contact pressure were primarily localized in the anterior region of the medial meniscus. A consistent directional response to FPA was observed with the lowest peak values occurring in the toe-in condition and the highest values in the toe-out condition. Adjusting FPA modulates intra-articular knee loading via the kinetic chain. For FFF patients, neutral FPA provides stable loading. The toe-in condition presents a complex mechanism: despite increasing tibiofemoral force (notably in males), it reduces peak stress by altering contact mechanics and stress distribution. Therefore, FFF gait interventions must be individualized based on factors like foot morphology, sex, and functional goals.