Cell-generated traction forces and the resulting matrix deformation modulate microvascular alignment and growth during angiogenesis.

The details of the mechanical factors that modulate angiogenesis remain poorly understood. Previous in vitro studies of angiogenesis using microvessel fragments cultured within collagen constructs demonstrated that neovessel alignment can be induced via mechanical constraint of the boundaries (i.e.

Extracellular matrix density regulates the rate of neovessel growth and branching in sprouting angiogenesis.

Angiogenesis is regulated by the local microenvironment, including the mechanical interactions between neovessel sprouts and the extracellular matrix (ECM). However, the mechanisms controlling the relationship of mechanical and biophysical properties of the ECM to neovessel growth during sprouting angiogenesis are just beginning to be understood. In this research, we characterized the relationship between matrix density and microvascular topology in an in vitro 3D organ culture model of sprouting angiogenesis.

Mechanical interaction of angiogenic microvessels with the extracellular matrix.

Angiogenesis is the process by which new blood vessels sprout from existing blood vessels, enabling new vascular elements to be added to an existing vasculature. This review discusses our investigations into the role of cell-matrix mechanics in the mechanical regulation of angiogenesis. The experimental aspects of the research are based on in vitro experiments using an organ culture model of sprouting angiogenesis with the goal of developing new treatments and techniques to either promote or inhibit angiogenic outgrowth, depending on the application.

Effects of decorin proteoglycan on fibrillogenesis, ultrastructure, and mechanics of type I collagen gels.

The proteoglycan decorin is known to affect both the fibrillogenesis and the resulting ultrastructure of in vitro polymerized collagen gels. However, little is known about its effects on mechanical properties. In this study, 3D collagen gels were polymerized into tensile test specimens in the presence of decorin proteoglycan, decorin core protein, or dermatan sulfate (DS).

Effect of elastin digestion on the quasi-static tensile response of medial collateral ligament.

Elastin is a structural protein that provides resilience to biological tissues. We examined the contributions of elastin to the quasi-static tensile response of porcine medial collateral ligament through targeted disruption of the elastin network with pancreatic elastase. Elastase concentration and treatment time were varied to determine a dose response.

A computational model of in vitro angiogenesis based on extracellular matrix fibre orientation.

Recent interest in the process of vascularisation within the biomedical community has motivated numerous new research efforts focusing on the process of angiogenesis. Although the role of chemical factors during angiogenesis has been well documented, the role of mechanical factors, such as the interaction between angiogenic vessels and the extracellular matrix, remains poorly understood. In vitro methods for studying angiogenesis exist; however, measurements available using such techniques often suffer from limited spatial and temporal resolutions.

Effect of sulfated glycosaminoglycan digestion on the transverse permeability of medial collateral ligament.

Dermatan and chondroitin sulfate glycosaminoglycans (GAGs) comprise over 90% of the GAG content in ligament. Studies of their mechanical contribution to soft tissues have reported conflicting results. Measuring the transient compressive response and biphasic material parameters of the tissue may elucidate the contributions of GAGs to the viscoelastic response to deformation.

Contribution of glycosaminoglycans to viscoelastic tensile behavior of human ligament.

The viscoelastic properties of human ligament potentially guard against structural failure, yet the microstructural origins of these transient behaviors are unknown. Glycosaminoglycans (GAGs) are widely suspected to affect ligament viscoelasticity by forming molecular bridges between neighboring collagen fibrils. This study investigated whether GAGs directly affect viscoelastic material behavior in human medial collateral ligament (MCL) by using nondestructive tensile tests before and after degradation of GAGs with chondroitinase ABC (ChABC).

The effect of bioreactor induced vibrational stimulation on extracellular matrix production from human derived fibroblasts.

To study the affect of mechanical stimuli on human laryngeal fibroblasts, we developed bioreactors capable of vibrating cell seeded substrates at frequencies and displacements comparable to measured phonation values in human subjects. In addition, we developed a means of harvesting the secreted matrix as a bulk biomaterial by removing the polymer foam using an organic solvent. Using the system human derived laryngeal fibroblasts were subjected to vibrational stimuli (100 Hz) for 1-21 days.

Effect of mechanical boundary conditions on orientation of angiogenic microvessels.

Aim: Mechanical forces are important regulators of cell and tissue phenotype. We hypothesized that mechanical loading and boundary conditions would influence neovessel activity during angiogenesis.

Methods And Results: Using an in vitro model of angiogenesis sprouting and a mechanical loading system, we evaluated the effects of boundary conditions and applied loading.

Effect of dermatan sulfate glycosaminoglycans on the quasi-static material properties of the human medial collateral ligament.

The glycosaminoglycan of decorin, dermatan sulfate (DS), has been suggested to contribute to the mechanical properties of soft connective tissues such as ligaments and tendons. This study investigated the mechanical function of DS in human medial collateral ligaments (MCL) using nondestructive shear and tensile material tests performed before and after targeted removal of DS with chondroitinase B (ChB). The quasi-static elastic material properties of human MCL were unchanged after DS removal.

Spatial distribution and orientation of dermatan sulfate in human medial collateral ligament.

The proteoglycan decorin and its associated glycosaminoglycan (GAG), dermatan sulfate (DS), regulate collagen fibril formation, control fibril diameter, and have been suggested to contribute to the mechanical stability and material properties of connective tissues. The spatial distribution and orientation of DS within the tissue are relevant to these mechanical roles, but measurements of length and orientation from 2D transmission electron microscopy (TEM) are prone to errors from projection. The objectives of this study were to construct a 3D geometric model of DS GAGs and collagen fibrils, and to use the model to interpret TEM measurements of the spatial orientation and length of DS GAGs in the medial collateral ligament of the human knee.