Schreiber, Areonna

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.

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.