Past and Future Prevascularization Strategies with Clinical Relevance: Leading to a Dual Approach

Abstract

During the last decades, numerous approaches for the engineering of soft and hard tissues were developed. However, tissues with a thickness larger than 2 mm show limited diffusion of essential nutrients which underlines the need for vascularization (Griffith et al., Tissue Eng 11(1–2):257–266, 2005). It is therefore of utmost importance to generate functional prevascularized thick tissues, which can be surgically connected to host tissues. First prevascularization strategies started in the early 1980s when Judah Folkman published his work about the role of endothelial cells in angiogenesis by trying to identify endothelial cell function during blood vessel formation (Folkman, Lab Investig 51(6):601–604, 1984). This was the decade when first prevascularization strategies began in polymeric scaffolds. The discovery of growth factors and cytokines led to the development of growth factor loaded constructs for delivery during the last decade of the twentieth century. Over the years, protocols for the decellularization or extraction of biological materials were developed which led to a boom of vascularization strategies in these matrices since the early 2000s. Technical progress during the last years makes now the 3D bioprinting of tissues and vasculature possible, although the use of this method in microvascular tissue engineering is still in its infancy. Independent of which matrix is used for the prevascularization strategy, the growing knowledge about cell interactions and pathways in angiogenesis as well as vasculogenesis led to the conclusion that the use of 3D cultures instead of 2D formed networks and the combination of endothelial cells with cells displaying angiogenesis stimulating properties led to the most promising results.