Hydrogels for bone organoid construction: From a materiobiological perspective

Bone organoids, which simulate and construct special organs in vitro with complex biological functions based on tissue engineering technology, provide dramatically realistic models for bone regenerative medicine development and lay the foundation for a new therapeutic strategy. The matrix microenvironment around tissues and cells plays a key role in the physiological functions and phenotypes of bone organoids. Traditionally, the commercially available Matrigel has been widely applied for organoid cultures. However, Matrigel is still facing challenges, including xenogenous origins and variable composition. To address these issues, newly developed hydrogels become an appropriate candidate to alternate Matrigel for bone organoid culture. In this review, we summarized the development and limitations of ECM-based matrix (Matrigel) in the bone organoid cultures. Then we highlighted various hydrogel alternatives, including PEG, collagen, alginate, gelatin, chitosan, skin fibroin, and DNA derivative hydrogels, which have shown a promising application in bone tissue engineering and organoid cultures. Additionally, the effects of material properties (stiffness, viscoelasticity, charge, et al.) in hydrogels on cell culture and bone organoid culture were deeply investigated. Finally, we predicted that hydrogel-based biomaterials have a great potential for the construction and application of bone organoids.