Spatial Configurations of 3D Extracellular Matrix Collagen Density and Anisotropy Simultaneously Guide Angiogenesis.

Extracellular matrix (ECM) collagen density and fibril anisotropy are thought to affect the development of new vasculatures during pathologic and homeostatic angiogenesis. Computational simulation is emerging as a tool to investigate the role of matrix structural configurations on cell guidance. However, prior computational models have only considered the orientation of collagen as a model input.

Dynamic Biophysical Cues Near the Tip Cell Microenvironment Provide Distinct Guidance Signals to Angiogenic Neovessels.

The formation of new vascular networks via angiogenesis is a crucial biological mechanism to balance tissue metabolic needs, yet the coordination of factors that influence the guidance of growing neovessels remain unclear. This study investigated the influence of extracellular cues within the immediate environment of sprouting tips over multiple hours and obtained quantitative relationships describing their effects on the growth trajectories of angiogenic neovessels. Three distinct microenvironmental cues-fibril tracks, ECM density, and the presence of nearby cell bodies-were extracted from 3D time series image data.

Matrix anisotropy promotes angiogenesis in a density-dependent manner.

Angiogenesis is necessary for wound healing, tumorigenesis, implant inosculation, and homeostasis. In each situation, matrix structure and mechanics play a role in determining whether new vasculatures can establish transport to new or hypoxic tissues. Neovessel growth and directional guidance are sensitive to three-dimensional (3-D) matrix anisotropy and density, although the individual and integrated roles of these matrix features have not been fully recapitulated in vitro.

Ventricular-vascular coupling is predictive of adverse clinical outcome in paediatric pulmonary arterial hypertension.

Aims: Ventricular-vascular coupling, the ratio between the right ventricle's contractile state (E) and its afterload (E), may be a useful metric in the management of paediatric pulmonary arterial hypertension (PAH). In this study we assess the prognostic capacity of the ventricular-vascular coupling ratio (E/E) derived using right ventricular (RV) pressure alone in children with PAH.

Methods: One hundred and thirty paediatric patients who were diagnosed with PAH via right heart catheterisation were retrospectively reviewed over a 10-year period.

A Nonparametric Approach for Estimating Three-Dimensional Fiber Orientation Distribution Functions (ODFs) in Fibrous Materials.

Many biological tissues contain an underlying fibrous microstructure that is optimized to suit a physiological function. The fiber architecture dictates physical characteristics such as stiffness, diffusivity, and electrical conduction. Abnormal deviations of fiber architecture are often associated with disease.

Stromal Cells Promote Neovascular Invasion Across Tissue Interfaces.

Vascular connectivity between adjacent vessel beds within and between tissue compartments is essential to any successful neovascularization process. To establish new connections, growing neovessels must locate other vascular elements during angiogenesis, often crossing matrix and other tissue-associated boundaries and interfaces. How growing neovessels traverse any tissue interface, whether part of the native tissue structure or secondary to a regenerative procedure (e.

Imaging the Dynamic Interaction Between Sprouting Microvessels and the Extracellular Matrix.

Thorough understanding of growth and evolution of tissue vasculature is fundamental to many fields of medicine including cancer therapy, wound healing, and tissue engineering. Angiogenesis, the growth of new vessels from existing ones, is dynamically influenced by a variety of environmental factors, including mechanical and biophysical factors, chemotactic factors, proteolysis, and interaction with stromal cells. Yet, dynamic interactions between neovessels and their environment are difficult to study with traditional fixed time imaging techniques.

Chronic kidney disease and aging differentially diminish bone material and microarchitecture in C57Bl/6 mice.

Chronic kidney disease (CKD) is a common disease of aging and increases fracture risk over advanced age alone. Aging and CKD differently impair bone turnover and mineralization. We thus hypothesize that the loss of bone quality would be greatest with the combination of advanced age and CKD.

A new open-source tool for measuring 3D osteocyte lacunar geometries from confocal laser scanning microscopy reveals age-related changes to lacunar size and shape in cortical mouse bone.

Osteocytes can participate in systemic mineral homeostasis through perilacunar maintenance and remodeling, where changes to osteocyte lacunar morphology may affect bone structural integrity, tissue strains, and osteocyte mechanosensitivity. Though aging is associated with both decreased bone quality and altered mineral metabolism, it is not known if osteocyte lacunae undergo age-related changes in geometry. In order to survey lacunar changes with age, we developed an open-source program whereby 3D osteocyte lacunae are automatically segmented and then subsequently reconstructed from confocal laser scanning microscopy (CLSM) depth stacks for quantitative analysis of geometry and orientation.