Fig. 6.

Main components of bone organoid production. Bone organoids, derived from stem cells, allow studying how cell–cell and cell-ECM interactions in 3D affect bone differentiation. iPSC organoids are suitable for researching primitive organ biology and physiology. iPSCs are generated by reprogramming fibroblasts with nuclear transcription factors, then adding osteoblast-specific factors for osteogenic differentiation. ASCs, like bone marrow or adipose-derived MSCs, produce single-cell type organoids without needing different differentiation conditions. Bioactive materials, like Matrigel and hydrogels, are key components. Matrigel is a solubilized extract of the basement membrane from Engelbreth-Holm-Swarm mouse sarcoma. Its high levels of collagen and growth factors promote cell adhesion. However, its application is restricted in various contexts because it originates from animals, has unpredictable composition, may be contaminated with xenobiotic contamination and exhibits batch-to-batch variability. Hydrogel is made up of polymers, which can be either natural or synthetic, and can be tailored to have specific chemical and physical properties, creating an optimized environment for cell culture. Its modifiable mechanical, physical, and biological characteristics enable a controlled response from cells. Natural hydrogels closely resemble the extracellular matrix (ECM) because they contain its primary components. Common examples of natural hydrogels include polysaccharides and proteins like collagen, hyaluronic acid, gelatin, chitosan, and alginate. On the other hand, synthetic hydrogels are composed of hydrophilic polymers such as polyethylene glycol, polyvinyl alcohol, polylactic acid, and polyacrylamide