Roles of irregularity of pore morphology in osteogenesis of Voronoi scaffolds: From the perspectives of MSC adhesion and mechano-regulated osteoblast differentiation.

Bone scaffolds designed based on the Voronoi-tessellation algorithm have been increasingly studied owing to their structural similarity with natural cancellous bone. The irregularity of pore morphology (IPM) influences the osteogenesis efficiency of Voronoi scaffolds since it may alter the static and hydromechanical microenvironments for the initial adhesion and mechano-regulated osteoblast differentiation (MrOD) of mesenchymal stem cells (MSCs). In this work, animal experiments were conducted to explore the relationship between IPM and osteogenesis efficiency in Voronoi scaffolds. A computational fluid dynamics (CFD) analysis based on discrete phase models was performed to predict the efficiency of MSC adhesion in different IPMs. Another combined finite element and CFD analysis based on the mechano-regulation algorithm was performed to predict the influence of IPM on the MrOD of the adhesive MSCs. The results showed that the osteogenesis efficiency of the Voronoi scaffolds increased as the IPM rose from low to moderate and then dropped as the IPM further rose. Same trends were also found in the MSC adhesion and MrOD, which caused by the changes of strain tensors on the strut surface and the tortuosity and fluid velocity of the fluid pathway. Moderate IPM induced the highest osteogenesis efficiency owing to its highest efficiencies of MSC adhesion and MrOD. This work identified the optimal IPM for the osteogenesis of Voronoi scaffolds and clarified its biomechanical mechanisms from the adhesion and mechano-regulated differentiation of MSCs, which is of great importance for guiding Voronoi scaffold design when it is used for bone defect repair.

Relationship between the elastic modulus of the cage material and the biomechanical properties of transforaminal lumbar interbody fusion: A logarithmic regression analysis based on parametric finite element simulations.

BACKGROUND AND OBJECTIVE: Conventional method for evaluating the biomechanical effects of a specific elastic modulus of cage (cage-E) on spinal fusions requires establishing a "one-on-one" biomechanical model, which seems laborious and inefficient when dealing with the emergence of numerous cage materials with various cage-Es. We aim to offer a much convenient method to instantly predicting the biomechanical effects of any targeted cage-E on transforaminal lumbar interbody fusion (TLIF) by using a parametric finite element (FE) analysis to determining the regression relationship between cage-E and biomechanical properties of TLIF. MATERIALS AND METHODS: A L4/5 FE TLIF construct was modeled. Cage-E was linearly increased from 0.1 GPa (cancellous bone) to 110 GPa (titanium alloy). The function equations for assessing the influence of cage-E on the biomechanical indexes of TLIF were established using a logarithmic regression analysis. EXPERIMENTAL RESULTS: As cage-E increased from 0.1 GPa to 110 GPa, all the biomechanical indexes initially increased or decayed rapidly, and then slowed over time. Logarithmic regression models and functional equations were successfully established between cage-E and these indexes (P<0.0001). Their determination coefficients ranged from 0.72 to 0.99. The range of motions decreased from 0.37-1.10° to 0.20-1.07°. The mean stresses of the central and peripheral grafts reduced from 0.10-0.41 and 0.25-0.42 MPa to 0.03-0.04 and 0.19-0.27 MPa, respectively. In addition, the maximum stresses of the screw-bone interface and posterior instrumentation reduced from 11.76-25.04 and 8.91-84.68 MPa to 9.71-18.92 and 6.99-70.59 MPa, respectively. Finally, the maximum stresses of the cage and endplate increased from 0.28-1.35 MPa and 3.90-8.63 MPa to 14.86-36.16 MPa and 11.01-36.55 MPa, respectively. CONCLUSIONS: The decrease of cage-E reduces the risks of cage subsidence, cage breakage, and pseudarthrosis, while increasing the risk of instrumentation failure. The logarithmic regression models optimally demonstrate the relationship between cage-E and biomechanical properties of TLIF. The functional equations based on these models can be adopted to predict the biomechanical effects of any targeted cage-Es on TLIF, which effectively simplifies the procedures for the biomechanical assessments of cage materials.

Peptide Receptor Radionuclide Therapy of Late-Stage Neuroendocrine Tumor Patients with Multiple Cycles of 177Lu-DOTA-EB-TATE.

This study aimed to evaluate the safety and efficacy of multiple cycles of 177Lu-DOTA-Evans blue (EB)-TATE peptide receptor radionuclide therapy (PRRT) at escalating doses in neuroendocrine tumors (NETs). Methods: Thirty-two NET patients were randomly divided into 3 groups and treated with escalating doses. Group A received 1.17 ± 0.09 GBq/cycle; group B, 1.89 ± 0.53 GBq/cycle; and group C, 3.97 ± 0.84 GBq/cycle. The treatment was planned for up to 3 cycles. Treatment-related adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Treatment response was evaluated according to the European Organisation for Research and Treatment of Cancer criteria and modified PERCIST. Results: Administration of PRRT was well tolerated, without life-threatening adverse events (CTCAE grade 4). CTCAE grade 3 hematotoxicity was recorded in 1 patient (16.6%) in group B (thrombocytopenia) and 3 patients (21.4%) in group C (thrombocytopenia in 3, anemia in 1). CTCAE grade 3 hepatotoxicity (elevated aspartate aminotransferase) was recorded in 1 patient in group A (8.3%) and 1 patient in group C (7.1%). No nephrotoxicity was observed. According to the criteria of the European Organisation for Research and Treatment of Cancer, the overall disease response rates were similar in groups A, B, and C (50.0%, 50.0%, and 42.9%, respectively), and the overall disease control rates were higher in groups B (83.3%) and C (71.5%) than in group A (66.7%). According to modified PERCIST, a lower disease response rate but a similar disease control rate were found. When a comparable baseline SUVmax ranging from 15 to 40 was selected, the percentage change in SUVmax increased slightly in group A (2.1% ± 40.8%) but decreased significantly in groups B and C (-38.7% ± 10.0% and -14.7% ± 20.0%, respectively) after the first PRRT (P = 0.001) and decreased in all 3 groups after the third PRRT (groups A, B, and C: -6.9% ± 42.3%, -49.2% ± 30.9%, -11.9% ± 37.9%, respectively; P = 0.044). Conclusion: Dose escalations of up to 3.97 GBq/cycle seem to be well tolerated for 177Lu-DOTA-EB-TATE. 177Lu-DOTA-EB-TATE doses of 1.89 and 3.97 GBq/cycle were effective in tumor control and more effective than 1.17 GBq/cycle.