Lu, Lichun

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.

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.

AbstractThe growing aging population, with its associated chronic diseases, underscores the urgency for effective tissue regeneration strategies. Biomaterials play a pivotal role in the realm of tissue reconstruction and regeneration, with a distinct shift toward minimally invasive (MI) treatments. This transition, fueled by engineered biomaterials, steers away from invasive surgical procedures to embrace approaches offering reduced trauma, accelerated recovery, and cost‐effectiveness. In the realm of MI tissue repair and cargo delivery, various techniques are explored. While in situ polymerization is prominent, it is not without its challenges. This narrative review explores diverse biomaterials, fabrication methods, and biofunctionalization for injectable pre‐formed scaffolds, focusing on their unique advantages. The injectable pre‐formed scaffolds, exhibiting compressibility, controlled injection, and maintained mechanical integrity, emerge as promising alternative solutions to in situ polymerization challenges. The conclusion of this review emphasizes the importance of interdisciplinary design facilitated by synergizing fields of materials science, advanced 3D biomanufacturing, mechanobiological studies, and innovative approaches for effective MI tissue regeneration.

AbstractDegenerative spinal pathology is a widespread medical issue, and spine fusion surgeries are frequently performed. In this study, we fabricated an injectable bioactive click chemistry polymer cement for use in spinal fusion and bone regrowth. Taking advantages of the bioorthogonal click reaction, this cement can be crosslinked by itself eliminating the addition of a toxic initiator or catalyst, nor any external energy sources like UV light or heat. Furthermore, nano‐hydroxyapatite (nHA) and microspheres carrying recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and recombinant human vascular endothelial growth factor (rhVEGF) were used to make the cement bioactive for vascular induction and osteointegration. After implantation into a rabbit posterolateral spinal fusion (PLF) model, the cement showed excellent induction of new bone formation and bridging bone, achieving results comparable to autograft control. This is largely due to the osteogenic properties of nano‐hydroxyapatite (nHA) and the released rhBMP‐2 and rhVEGF growth factors. Since the availability of autograft sources is limited in clinical settings, this injectable bioactive click chemistry cement may be a promising alternative for spine fusion applications in addressing various spinal conditions.

Abstract Segmental bone defects, often clinically treated with nondegradable poly(methylmethacrylate) (PMMA) in multistage surgeries, present a significant clinical challenge. Our study investigated the efficacy of 3D printed biodegradable polycaprolactone fumarate (PCLF)/PCL spacers in a one‐stage surgical intervention for these defects, focusing on early bone regeneration influenced by spacer porosities. We compared nonporous PCLF/PCL and PMMA spacers, conventionally molded into cylinders, with porous PCLF/PCL spacers, 3D printed to structurally mimic segmental defects in rat femurs for a 4‐week implantation study. Histological analysis, including tissue staining and immunohistochemistry with bone‐specific antibodies, was conducted for histomorphometry evaluation. The PCLF/PCL spacers demonstrated compressive properties within 6 ± 0.5 MPa (strength) and 140 ± 15 MPa (modulus). Both porous PCLF/PCL and Nonporous PMMA formed collagen‐rich membranes (PCLF/PCL: 92% ± 1.3%, PMMA: 86% ± 1.5%) similar to those induced in the Masquelet technique, indicating PCLF/PCL's potential for one‐stage healing. Immunohistochemistry confirmed biomarkers for tissue regeneration, underscoring PCLF/PCL's regenerative capabilities. This research highlights PCLF/PCL scaffolds' ability to induce membrane formation in critical‐sized segmental bone defects, supporting their use in one‐stage surgery. Both solid and porous PCLF/PCL spacers showed adequate compressive properties, with the porous variants exhibiting BMP‐2 expression and woven bone formation, akin to clinical standard PMMA. Notably, the early ossification of the membrane into the pores of porous scaffolds suggests potential for bone interlocking and regeneration, potentially eliminating the need for a second surgery required for PMMA spacers. The biocompatibility and biodegradability of PCLF/PCL make them promising alternatives for treating critical bone defects, especially in vulnerable patient groups.