Long-term viability of thick three-dimensional engineered tissue constructs is a major challenge. Addressing it requires development of vessel-like network that will allow the survival of the construct in vitro and its integration in vivo owing to improved vascularization after implantation. Resulting from work of various research groups, several approaches were developed aiming engineered tissue vascularization: (1) embodiment of angiogenesis growth factors in the polymeric scaffolds for prolonged release, (2) coculture of endothelial cells with target tissue cells and angiogenesis signaling cells, (3) use of microfabrication methods for creating designed channels for allowing nutrients to flow and/or for directing endothelial cells attachment, and (4) decellularization of organs and blood vessels for creating extracellular matrix. A synergistic effect is expected by combining several of these approaches as already demonstrated in some of the latest studies. Current paper reviews the progress in each approach and recent achievements toward vascularization of engineered tissues.

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Natural polymers share recognition sequences that promote cell adhesion, rendering them attractive candidates for scaffolding in tissue engineering applications. However, challenges remain with regard to the fabrication of robust and porous structures of such raw materials for the design of extracellular matrix (ECM) mimics of living tissues. In this study, we present a fibrous scaffold that solely consists of albumin, the most abundant protein in mammalian blood plasma. The scaffold was fabricated using the electrospinning method, and resulted in microscale fibers that demonstrated mechanical properties which were similar to those of elastin fibers, a common component of connective tissue ECM. Albumin scaffolds proved nontoxic and supported adhesion and the spreading of fibroblasts, muscle cells, and endothelial cells (ECs) in vitro. In vivo studies demonstrated ∼50% biodegradation of the albumin scaffolds within 3 weeks of implantation. In addition, it was found that the fibers were encapsulated by dense fibrosis and evoked a weak inflammatory response, similar to that triggered by poly(L-lactide)/poly(lactic-co-glycolic acid) scaffolds. Albumin tubular structures fabricated to mimic blood vessels successfully guided the formation of blood vessel-like bi-layer structures made of fibroblasts and ECs. Thus, albumin scaffolds featuring biologically relevant characteristics pose a readily applicable alternative to synthetic scaffolding materials.

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