Mechanical Regulation of Microvascular Growth and Remodeling

Microvascular growth and remodeling processes are essential to tissue maintenance and repair. While several biochemical regulators have been elucidated, the effects of dynamic mechanical regulatory factors, including local tissue deformation, extracellular matrix mechanical properties, and both luminal and abluminal flow, are incompletely understood. Mechanical regulation is particularly relevant to the field of tissue engineering and regenerative medicine. Recent experimental evidence suggests that microvessels are highly sensitive to changes in local tissue properties like stiffness, ECM density, and external loading. However, an integrated understanding of how microvascular networks are regulated by mechanical factors has not been fully established. In this review, we discuss the microvascular responses to mechanical factors first in terms of cell-based responses and then describe the nuances of these responses when integrated into a multicellular microvessel structure. Finally, we consider the progress in computational modeling approaches to study angiogenesis, wherein the integration of multiple synergistic, antagonistic, or competing stimuli driving the process of microvascular growth and remodeling can be studied, providing better control over experimentally inaccessible variables. By creating a loop wherein experimental data informs computational experiments and vice versa, mechanical effects on microvasculature can be more fully understood and leveraged for engineered tissues.