Upgrading prevascularization in tissue engineering: A review of strategies for promoting highly organized microvascular network formation.

Functional and perfusable vascular network formation is critical to ensure the long-term survival and functionality of engineered tissues after their transplantation. Although several vascularization strategies have been reviewed in past, the significance of microvessel organization in three-dimensional (3D) scaffolds has been largely ignored. Advances in high-resolution microscopy and image processing have revealed that the majority of tissues including cardiac, skeletal muscle, bone, and skin contain highly organized microvessels that orient themselves to align with tissue architecture for optimum molecular exchange and functional performance. Here, we review strategies to develop highly organized and mature vascular networks in engineered tissues, with a focus on electromechanical stimulation, surface topography, micro scaffolding, surface-patterning, microfluidics and 3D printing. This review will provide researchers with state of the art approaches to engineer vascularized functional tissues for diverse applications. STATEMENT OF SIGNIFICANCE: Vascularization is one of the critical challenges facing tissue engineering. Recent technological advances have enabled researchers to develop microvascular networks in engineered tissues. Although far from translational applications, current vascularization strategies have shown promising outcomes. This review emphasizes the most recent technological advances and future challenges for developing organized microvascular networks in vitro. The next critical step is to achieve highly perfusable, dense, mature and organized microvascular networks representative of native tissues.