Abstract
Bone organoids,which simulate and construct special organs in vitro with complex biological func-tions 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 microenviron-ment 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 cul-tures.However,Matrigel is still facing challenges,including xenogenous origins and variable composi-tion.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 al-ternatives,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.