Vascularization is a critical challenge in tissue engineering. Without a functional blood supply, engineered tissues larger than a few hundred micrometers cannot survive due to limitations in nutrient and oxygen diffusion and waste removal. This section explores key strategies employed to achieve vascularization in engineered constructs.

The fundamental problem is the limited diffusion distance for essential molecules like oxygen and nutrients. As engineered tissues grow in size, the core cells become increasingly hypoxic and starved, leading to cell death and construct failure. Overcoming this requires the integration of a pre-formed or in-situ generated vascular network.

Several approaches are used to promote vascularization in tissue-engineered constructs. These can be broadly categorized into pre-formed vascular networks and in-situ vascularization methods.

This strategy involves fabricating a vascular network that is integrated into the scaffold before implantation. This provides an immediate vascular supply upon implantation.

Sacrificial templating uses materials that can be removed after the scaffold is formed, leaving behind channels that can be subsequently seeded with endothelial cells or infiltrated by host vessels. Common sacrificial materials include sugar spheres, gelatin, or fugitive inks.

Microfluidic techniques allow for the precise printing or molding of complex vascular networks with controlled branching patterns and vessel diameters, often mimicking the hierarchical structure of natural capillary beds.

This approach relies on stimulating the host's own angiogenic processes to form blood vessels within the engineered construct. It often involves seeding the scaffold with specific cell types or incorporating signaling molecules.

Seeding scaffolds with endothelial cells (ECs) and supporting cells like pericytes or smooth muscle cells can promote the formation of functional blood vessels. These cells can self-assemble into capillary-like structures or guide host vessel ingrowth.

Incorporating angiogenic growth factors, such as Vascular Endothelial Growth Factor (VEGF), into the scaffold can stimulate endothelial cell proliferation, migration, and tube formation, thereby promoting neovascularization.

Despite significant progress, challenges remain in achieving fully functional, stable, and integrated vascular networks. These include ensuring proper lumen patency, preventing thrombosis, matching the hierarchical structure of native vasculature, and achieving long-term integration with the host circulatory system. Future research focuses on advanced biomaterials, sophisticated biofabrication techniques, and a deeper understanding of the complex signaling pathways involved in angiogenesis.