Osteodegenerative disease and bone fractures lead to bone damage or loss, requiring new bone formation to replace the damaged tissues. Classical ‘top-down’ tissue engineering relies on seeding cell suspensions into biomaterial scaffolds, and then guiding cell fate by growth factors. However, complex tissue fabrication using this approach has important limitations. ‘Bottom-up’ tissue engineering has the potential to overcome the drawbacks of the top-down approach, by using ‘building blocks’ of cell spheroids for tissue biofabrication without a scaffold. Spheroids are 3D structures that resemble the physiological tissue microenvironment and can be produced in vitro by different methods. Spheroids of mesenchymal stem cells (MSC) and adipose stem cells (ASC) have regenerative properties. Here we review, the use of spheroids as ‘building blocks’ in the 3D bioprinting of large-scale bone tissue and as a promising alternative for the treatment of osteodegenerative diseases and in bone engineering, including endochondral ossification (or developmental engineering).