Life is 3D: Boosting Spheroid Function for Tissue Engineering

Spheroids are increasingly used as building blocks in tissue engineering, because they ideally mimic the physiological 3D environment of tissues. Automatized large-scale production of spheroids is technically feasible. Compared to 2D cell systems, spheroids exhibit an enhanced regenerative capacity, which can be improved during the production process by adjusting the culture conditions and incorporation of biomaterials. The complexity of tissues can be mimicked by incorporation of multiple cell types in coculture spheroids. Macrotissues can be generated by seeding spheroids on scaffolds or by scaffold-free fusion of spheroids. Spheroids provide a 3D environment with intensive cell–cell contacts. As a result of their excellent regenerative properties and rapid progress in their high-throughput production, spheroids are increasingly suggested as building blocks for tissue engineering. In this review, we focus on innovative biotechnological approaches that increase the quality of spheroids for this specific type of application. These include in particular the fabrication of coculture spheroids, mimicking the complex morphology and physiological tasks of natural tissues. In vitro preconditioning under different culture conditions and incorporation of biomaterials improve the function of spheroids and their directed fusion into macrotissues of desired shapes. The continuous development of these sophisticated approaches may markedly contribute to a broad implementation of spheroid-based tissue engineering in future regenerative medicine. Spheroids provide a 3D environment with intensive cell–cell contacts. As a result of their excellent regenerative properties and rapid progress in their high-throughput production, spheroids are increasingly suggested as building blocks for tissue engineering. In this review, we focus on innovative biotechnological approaches that increase the quality of spheroids for this specific type of application. These include in particular the fabrication of coculture spheroids, mimicking the complex morphology and physiological tasks of natural tissues. In vitro preconditioning under different culture conditions and incorporation of biomaterials improve the function of spheroids and their directed fusion into macrotissues of desired shapes. The continuous development of these sophisticated approaches may markedly contribute to a broad implementation of spheroid-based tissue engineering in future regenerative medicine. development of new blood vessels from pre-existing ones. compatibility with living tissue by not being toxic, injurious, or physiologically reactive, and not causing immunological rejection. multipotent stromal cells that can differentiate into a variety of other cell types. the part of the circulatory system composed of the smallest vessels, including arterioles, capillaries, and venules. spatial differences in the shape, structure, and function of cells. molecules and ions of oxygen that have an unpaired electron, thus rendering them extremely reactive. natural or synthetic material serving as a 3D matrix for tissue formation. artificially generated tissue substitute. formation of blood vessels in living tissue, resulting in a red blood cell-perfused microvascular network. de novo formation of blood vessels by assembly of endothelial cells or endothelial progenitor cells.