Multi-scale simulation of early kidney branching morphogenesis.

An important feature of the branch morphogenesis during kidney development is the termination of the tips on the outer surface of a kidney. This feature requires the avoidance of the intersection between the tips and existing ducts inside the kidney. Here, we started from a continuous model and implemented the coarse grained rules into a fast and discrete simulations. The ligand-receptor-based Turing mechanism suggests a repulsion that decreases exponentially with distance between interacting branches, preventing the intersection between neighboring branches. We considered this repulsive effect in numerical simulations and successfully reproduce the key features of the experimentally observed branch morphology for an E15.5 kidney. We examine the similarity of several geometrical parameters between the simulation results and experimental observations. The good agreement between the simulations and experiments suggests that the concentration decay caused by the absorption of glial cell line derived neurotrophic factor might be the key factor to affect the geometry in early kidney development.

Diameters of lingual, facial, and maxillary arteries measured according to an objective protocol on 3D computed tomography angiography images.

PURPOSE: Retrograde superselective intra-arterial chemoradiotherapy is a radical treatment for advanced oral cancer. The catheter tip is placed into tumor-feeding arteries-the lingual, facial, or maxillary arteries. The diameter of the tumor-feeding arteries newly bifurcated from the external carotid artery is crucial for determining the requirement of a catheter navigation system. This study aimed to measure the diameter and distribution of the tumor-feeding artery according to an objective protocol using 3D computed tomography angiography images reproducibly. METHODS: Angiographic data of 20 noncatheterized carotid arteriesof 10 randomly selected patients were analyzed. We followed the external carotid artery to the entrance of each feeding artery to determine the center point where the artery diameter was measured. The diameter of the optimum circle measured at the adopted center point was taken as the diameter of each tumor-feeding artery. RESULTS: The diameters (mean ± standard deviation) were 3.5 ± 0.45, 2.9 ± 0.56, and 3.5 ± 0.56 mm for the maxillary, lingual, and facial arteries, respectively. The diameters of the maxillary and facial arteries were similar (p = 0.877), whereas the diameter of the lingual artery was smaller than that of the maxillary and facial arteries (p < 0.001). CONCLUSION: The findings of this study will be beneficial in determining the need of a new catheter navigation system and diameter of catheters to be used in the clinical practice. From the viewpoint of measurement automation and reproducibility, 3DCTA vessel measurement taken according to the proposed protocol was considered to be effective.

Design consideration on integration of mechanical intravascular ultrasound and electromagnetic tracking sensor for intravascular reconstruction.

PURPOSE: Considering vessel deformation, endovascular navigation requires intraoperative geometric information. Mechanical intravascular ultrasound (IVUS) with an electromagnetic (EM) sensor can be used to reconstruct blood vessels with thin diameter. However, the integration design should be evaluated based on the factors affecting the reconstruction error. METHODS: The interference between the mechanical IVUS and EM sensor was measured in different relative positions. Two designs of the integrated catheter were evaluated by measuring the reconstruction errors using a rigid vascular phantom. RESULTS: When the distance from the EM sensor to the field generator was 75 mm, the interference from mechanical IVUS to an EM sensor was negligible, with position and rotation errors less than 0.1 mm and 0.6°, respectively. The reconstructed vessel model for proximal IVUS transducer had a smooth surface but an inaccurate shape at large curvature of the vascular phantom. When the distance to the field generator was 175 mm, the error increased significantly. CONCLUSION: Placing the IVUS transducer on the proximal side of the EM sensor is superior in terms of interference reduction but inferior in terms of mechanical stability compared to a distal transducer. The distal side is preferred due to better mechanical stability during catheter manipulation at larger curvature. With this configuration, surface reconstruction errors less than 1.7 mm (with RMS 0.57 mm) were achieved when the distance to the field generator was less than 175 mm.

Multi-scale design of the chela of the hermit crab Coenobita brevimanus.

The chela of the hermit crab protects its body against the attack from predators. Yet, a deep understanding of this mechanical defense is still lacking. Here, we investigate the chela of hermit crab, Coenobita brevimanus, and establish the relationships between the microstructures, chemical compositions and mechanical properties to gain insights into its biomechanical functions. We find that the chela is a multi-layered shell composed of five different layers with distinct features of the microstructures and chemical compositions, conferring different mechanical properties. Especially, an increase of the calcium carbonate content towards the layer furthest from the exterior, unlike the chemical gradients of many crustacean exoskeletons, provides a strong resistance to deformation. Nanoindentation measurements reveal that the overall gradient of the elastic modulus and hardness in the cross-section displays a sandwich profile, i.e., a soft core clamped by two stiff surface layers. Further mechanics modeling demonstrates that the high curvature and stiff innermost sublayer enhance the structural rigidity of the chela. In conjunction with the experimental observations, dynamic finite element analysis maps the time-spatial distribution of principal stress and indicates that fiber bridging might be the major mechanism against crack propagation at microscale. The lessons gained from the study of this multiphase biological composite could provide important insights into the design and fabrication of bioinspired materials for structural applications. STATEMENT OF SIGNIFICANCE: Multiple hierarchical structures have been discovered in a variety of exoskeletons. They are naturally designed to maintain the structural integrity and act as a protective layer for the animals. However, each kind of the hierarchical structures has its unique topology, chemical gradients as well as mechanical properties. We find that the chela is multi-layered shell composed of five different layers with distinct features of the microstructures and chemical compositions, conferring different mechanical properties. Especially, a large amount of helicoidal organic fibrils form highly organized 3D woven matrix in the innermost layer, providing a strong mechanical resistance to avoid catastrophic failure. The overall gradient of the elastic modulus and hardness in the cross-section display a sandwich profile, effectively minimizing the stress concentration and deformation. The lessons gained from the multiscale design strategy of the chela provide important insights into the design and fabrication of bioinspired materials.