Blood Vessel Maturation in Health and Disease and its Implications for Vascularization of Engineered Tissues

Engineered blood vessels have often been found to be immature and unstable. Similarly, numerous pathologies such as diabetic retinopathy and cancer are characterized by highly abnormal, defective, hypervascular networks, consisting of immature, leaky, and irregular vessels with a marked loss of perivascular cell coverage. An emerging therapeutic concept in treatment of such vascular diseases and their management is the potential to normalize blood vessels by strengthening the cellular components that form the vascular network. Vessel normalization is characterized by the reduction in the number and size of immature vessels, a decrease in interstitial fluid pressure, and increase in perivascular cell coverage. Understanding the molecular and cellular defects associated with abnormal blood vessels will allow us to find appropriate treatment options that can promote normal blood vessel development. These, in turn, can be applied to improve vessel maturation in engineered tissues. In this review, we describe the major perivascular abnormalities associated with various human diseases and engineered vasculatures and the major advances in obtaining mature vasculatures for translational applications.