Abstract The development of biocompatible and biologically responsive scaffolds remains a key challenge for bone tissue engineering. Here, we report an enzyme-degradable, metal-free click-cross-linked organic–inorganic nanohybrid (Enz-Deg-Click-ON) scaffold with high biocompatibility for bone repair. The formulation was synthesized using a cyclooctyne-functionalized poly(propylene fumarate) polyphosphoester (PPF-poly(PE-BCN)) and azide-terminated dendritic polycaprolactone (PCL) with a polyhedral oligomeric silsesquioxane core (POSS-PCL-N3) via strain-promoted alkyne-azide cycloaddition (SPAAC) bioorthogonal click chemistry. The incorporation of phosphate-containing linkages enabled alkaline phosphatase (ALP)-responsive degradation. The scaffold exhibited rapid catalyst-free crosslinking, tunable swelling, and suitable mechanical properties. In vitro studies demonstrated excellent cytocompatibility, robust stem cell proliferation, and enhanced osteogenic differentiation with an elevated level of ALP and Runx2 expression. Enzyme-triggered degradation was confirmed in the presence of ALP. In the in vivo rat calvarial defect model, the scaffold significantly improved bone regeneration, as shown by an increased bone volume, mineral density, and defect coverage. Histological and immunofluorescence analyses revealed enhanced collagen deposition, angiogenesis, and osteogenesis. These results indicate that the Enz-Deg-Click-ON system provides a dynamic, bioresponsive platform for bone repair.
Impact of Anterior Load Carriage on Dynamic Sagittal Spinal Alignment
American Journal of Physical Medicine & Rehabilitation | August 13, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Objectives: To examine the effects of anterior load carriage on dynamic sagittal spinal alignment during the gait cycle in younger (<65 y) and older (≥65 y) adults. Design: Cross-sectional study of 47 participants aged 20–80 years categorized as young and older adults. Participants walked at self-selected speeds with and without a 4.5 kg anterior chest load. Whole-body kinematics were recorded using a 19-camera infrared motion capture system. Outcome measures included lumbar lordosis (LL), thoracic kyphosis (TK), trunk inclination (TI), sagittal trunk shift (STS), and pelvic tilt (PT). Gait-cycle–dependent differences were analyzed using statistical parametric mapping. Results: The mean age was 41 years in young adults (n=28) and 70 years in older adults (n=19). Anterior load carriage increased LL during portions of the gait cycle and reduced TI throughout the entire gait cycle. Younger adults demonstrated greater LL and lower TI than older adults. A significant age-by-load interaction for TI was observed during portions of the gait cycle. Conclusions: Anterior load carriage alters spinal alignment by increasing LL and reducing TI during walking, with distinct age-related patterns. These results provide valuable reference data and a foundation for future studies on load management and ergonomic interventions across the adult lifespan.
A Viscoelastic Modeling for Failure Analysis of Human Vertebral Bone Undergoing Quasi-Static and Dynamic Compression
Vertebral fractures are among the most common skeletal injuries and present significant clinical and biomechanical challenges, particularly in older adults and individuals with low bone density. Accurate prediction of vertebral mechanical response and failure under varying loading conditions is essential for improving understanding of spinal injury mechanisms. This study develops a density-dependent viscoelastic analytical model to predict the stiffness and fracture force of human vertebral specimens subjected to different compression rates. The vertebral body is represented as a composite structure consisting of a cortical shell and a trabecular core. Cortical bone is modeled as a linear elastic material, whereas trabecular bone is described using a Kelvin–Voigt viscoelastic formulation. Density-dependent constitutive relationships are incorporated for the elastic modulus and viscous coefficient of trabecular bone. Unknown material parameters are identified through optimization using the Nelder–Mead algorithm, based on experimental compression data from cadaveric vertebral specimens tested under quasi-static and dynamic loading conditions. The calibrated model reproduced the overall trend of specimen-to-specimen mechanical variation observed experimentally. Predicted stiffness values were in reasonable agreement with measured data. Fracture force predictions showed moderate agreement for dynamically tested specimens (R2 = 0.60), which improved to R2 = 0.88 after exclusion of one statistically identified outlier. Compared with a purely linear elastic formulation, the proposed viscoelastic model demonstrated modest improvement in stiffness prediction and more substantial improvement in fracture force prediction. These findings indicate that incorporating density-dependent viscoelastic effects improves representation of vertebral mechanical behavior, particularly at higher loading rates. Owing to its simplicity and computational efficiency, the proposed model requires only limited imaging input and may be useful for future biomechanical investigations, rapid screening, and injury risk prediction.
Bioorthogonal “Click Chemistry” Bone Cement Enables Pro-Translational Spinal Fusion in a Large Animal Sheep Model
ABSTRACT Accurately predicting vertebral fracture risk in metastatic spines remains a critical challenge in clinical practice. This study developed and validated a QCT‐based finite element analysis (QCT/FEA) approach to investigate the combined effects of baseline bone strength and tumor size on vertebral structural integrity. Areal bone mineral density (aBMD) was also calculated from QCT data to evaluate the reduction in bone density with increasing defect size. Nine cadaveric vertebral bodies were analyzed under varying tumor sizes (0%, 20%, 35%, and 50%). The results demonstrated a strong correlation between experimentally measured and computationally predicted failure forces ( r = 0.97, p < 0.001) and aBMD values ( r = 0.96, p < 0.001). Vertebral strength decreased linearly with increasing tumor size. Importantly, the study revealed that baseline vertebral strength plays a crucial role in fracture risk assessment, often surpassing the impact of tumor size alone. Tumor size reduced vertebral strength at a rate 84% faster than bone density ( p = 0.009), highlighting a greater impact of tumor defects on bone fracture force than on bone density. These findings suggest that relying solely on tumor size for fracture risk prediction may be insufficient. Incorporating baseline bone strength into predictive models significantly enhances accuracy and reliability, providing valuable insights for clinical decision‐making and personalized treatment strategies. This study underscores the importance of advanced computational tools in improving vertebral fracture risk assessment in metastatic spine cases.
Evaluating longitudinal changes of gait parameters following shunt placement in patients with idiopathic normal pressure hydrocephalus
OBJECTIVE Idiopathic normal pressure hydrocephalus (iNPH) is characterized by gait deterioration, cognitive disturbances, and urinary incontinence. Gait deficits pose safety hazards due to frequent falls, yet objective investigations of gait improvement following ventriculoperitoneal shunt (VPS) placement are limited. Therefore, the aim of this study was to assess objective improvement in gait parameters for patients with iNPH after VPS placement. METHODS All patients treated with a VPS for iNPH by the senior author at a single tertiary care center from December 2017 to January 2023 were retrospectively reviewed. Patients who underwent detailed motion analysis testing before surgery with > 1 follow-up assessment were included. Analyzed parameters included gait velocity, gait cadence, stride length, stride width, gait stability ratio, total support, and single support. Time-dependent linear mixed-effects models and generalized additive mixed-effects models (GAMMs) were used to model short-term and longitudinal gait parameter changes, respectively. RESULTS A total of 212 patients (137 male, median age was 75.2 years) who underwent VPS placement for iNPH were included, with a total of 747 gait analyses performed at a median last-gait analysis follow-up duration of 12.0 months. Statistically significant changes in all gait parameter values were seen between the preoperative time point and first postoperative follow-up (within 3 months) time point (paired Wilcoxon p < 0.001), with a statistically significant majority of patients experiencing improvement (binominal p < 0.0001). Longitudinal analyses using a GAMM showed increased gait velocity, single support, and stride length, with decreased stability ratio, step width, and total support at early time points, while a plateau was achieved around 6 months. CONCLUSIONS A detailed gait analysis demonstrated significant improvements in objective ambulation metrics, particularly in the gait velocity, stride length, and gait stability ratio, following VPS placement in patients with iNPH. Most patients maintained marked improvement from baseline to the last follow-up assessment, although a plateau of the benefit was experienced over longer follow-up.
Effects of Age and Muscle Activation on Three-Dimensional Spine Kinematics and Asymmetry in Elderly Adults
Background/Objectives: Limited spinal range of motion (ROM) is linked to low back disorders, emphasizing the need to maintain mobility in the elderly. This study measured maximum spinal ROM, asymmetrical patterns, and the effects of age and muscle activation on spinal mobility. Methods: Forty healthy participants aged 50 and older were recruited. An optical motion capture system recorded three-dimensional coordinates of reflective markers placed on spinal landmarks. Asymmetry was analyzed in sidebending and axial rotation. Electromyography (EMG) data were collected bilaterally from paraspinal muscles at L3 during flexion, extension, sidebending, and axial rotation. Results: Trunk ROM averaged 111° in flexion, 38° in extension, 46° in sidebending, and 87° in axial rotation. Kinematic asymmetry was observed in sidebending and axial rotation. ROM decreased with age in flexion motion (p ≤ 0.04). EMG activity was significantly correlated with ROM data for all combined motions (p = 0.0002). The strongest EMG signal was recorded during flexion, whereas the weakest signal was observed during extension. EMG activity also correlated with kinematic asymmetry (p ≤ 0.03). Conclusions: Age and muscle activation significantly influence spinal ROM in the elderly. Lumbar kinematic asymmetry can be partially attributed to paraspinal muscle activation, underscoring the importance of analyzing asymmetrical motions in conjunction with EMG activity.
Bone Enzyme-Responsive Biodegradable Poly(propylene fumarate) and Polycaprolactone Polyphosphoester Dendrimer Cross-Linked via Click Chemistry for Bone Tissue Engineering