Vascularization

Vascularization refers to the development and organization of blood vessels within tissues, ensuring delivery of oxygen and nutrients and removal of wastes. It includes vasculogenesis, the de novo formation of vessels during embryogenesis, and angiogenesis, the sprouting and remodeling of existing vascular networks. In mature organisms, arteriogenesis describes the enlargement of pre-existing arteries in response to altered flow or demand.

Molecular regulation is central to vascularization. Hypoxia upregulates HIF-1 and promotes expression of vascular endothelial growth factor (VEGF), a key driver of endothelial proliferation and sprouting. Other soluble factors involved include fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and angiopoietins. Notch signaling helps shape sprout formation and vessel maturation. Extracellular matrix remodeling by matrix metalloproteinases facilitates endothelial migration, while pericytes and smooth muscle cells stabilize and regulate vessel diameter.

Roles in health and disease are diverse. During development, vascular networks guide organ formation and growth. In adulthood, vascular remodeling supports wound healing and organ function. Pathological neovascularization occurs in cancer, diabetic retinopathy, and age-related macular degeneration, where abnormal, leaky vessels can contribute to tissue damage. Therapeutic strategies in oncology often aim to normalize or prune tumor vasculature by anti-angiogenic approaches.

In regenerative medicine and tissue engineering, achieving timely vascularization is critical for graft survival and function. Approaches include delivering pro-angiogenic factors, co-culturing endothelial and supporting cells, prevascularizing constructs, designing scaffolds with interconnected porosity, and employing microfluidic or 3D bioprinting techniques to form functional networks.

Assessment of vascularization uses measures such as microvessel density, perfusion imaging, and functional blood flow studies, with imaging modalities including MRI, CT angiography, and ultrasound.