Application of microtechnologies for the vascularization of engineered tissues

Progress in the development of large tissue-engineered organs has so far been limited by the inability to generate sophisticated three dimensional (3D) structures comprised of a functional vasculature. The vascular system is a dynamic environment comprised of a variety of cell types that constantly remodels itself under the influence of endothelial, immune, nervous and endocrine cells [1]. Vascular growth and remodeling are coupled with developmental and wound healing processes as well as the progression of various pathologies such as inflammation, cardiovascular diseases and cancer. Most of these processes depend on endothelial cells, which line the interior of blood vessels and form the endothelium. This interface between circulating blood and the surrounding tissues is responsible for proper solute transport and molecular exchange. It ensures the delivery of sufficient oxygen and nutrients to cells to maintain tissue homeostasis. Cells in vivo are found to be at most a few hundred microns away from the nearest capillary or blood vessel. Beyond this distance, diffusion is not effective and tends to reduce cell survival and function. Therefore, the inability to adequately vascularize engineered tissues results in inefficient transport of nutrients and metabolites and often leads to cell death and tissue necrosis. Moreover, vascularization of engineered tissues plays an important role in graft perfusion and is also crucial in facilitating the integration of the implanted material with the host vasculature [2,3].The fabrication of tissue constructs often requires cell seeding of 3D scaffolds. These scaffolds are generally made of gels, foams or fibrous meshes and usually have basic macroscale properties that enable cell adhesion, migration and proliferation [4]. Although these properties are often sufficient to allow the formation of functional connective tissues such as skin [5,6], bladder [7] and cornea [8,9] and 3D tubular structures like blood vessels [10,11] and