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.

骨类器官，在体外模拟和构建特殊器官具有基于组织工程技术的复杂生物学功能，为骨再生医学的发展提供了极其现实的模型，并为新的治疗策略奠定了基础。组织和细胞周围的基质微环境在骨类器官的生理功能和表型中起着关键作用。传统上，市售的基质胶已广泛应用于类器官培养。然而，Matrigel 仍面临挑战，包括异源起源和可变成分。为了解决这些问题，新开发的水凝胶成为替代基质凝胶进行骨类器官培养的合适候选者。在这篇综述中，我们总结了基于 ECM 的基质 (Matrigel) 在骨类器官培养中的发展和局限性。然后我们强调了各种水凝胶替代品，包括 PEG、胶原蛋白、海藻酸盐、明胶、壳聚糖、皮肤丝素和 DNA 衍生水凝胶，在骨组织工程和类器官培养中显示出广阔的应用前景。此外，还深入研究了水凝胶中材料特性（刚度、粘弹性、电荷等）对细胞培养和骨类器官培养的影响。最后，我们预测基于水凝胶的生物材料在骨类器官的构建和应用方面具有巨大的潜力。