Schematic representation of 3D scaffold-based and alternative bottom-up approaches to bone tissue engineering. In the traditional 3D scaffold-based bottom-up approaches, growth factors, peptides, cytokines and/or cells are utilized as building blocks to create a functionalized 3D scaffold that is ultimately used either with or without pre-seeded cells for engineering bone tissue. In the emerging alternative approaches, cell sheets, cell aggregates, cell laden microgels, or 3D/bioprinting technologies are used for assembling/stacking/layering components to generate 3D constructs.