Organoids are novel in vitro cell culture models that enable stem cells (including pluripotent stem cells and adult stem cells) to grow and undergo self-organization within a three-dimensional microenvironment during the process of differentiation into target tissues. Such miniature structures not only recapitulate the histological and genetic characteristics of organs in vivo, but also form tissues with the capacity for self-renewal and further differentiation. Recent advances in biomaterial technology, particularly hydrogels, have provided opportunities to improve organoid cultures; by closely integrating the mechanical and chemical properties of the extracellular matrix microenvironment, with novel synthetic materials and stem cell biology. This systematic review critically examines recent advances in various strategies and techniques utilized for stem-cell-derived organoid culture, with particular emphasis on the application potential of hydrogel technology in organoid culture. We hope this will give a better understanding of organoid cultures for modelling diseases and tissue engineering applications.

Epigenetic regulation provides new insights into the mechanisms of osteogenic differentiation and identifies potential targets for treating bone-related diseases. However, the specific regulatory networks and mechanisms involved still need further investigation. In this study, we identify PRMT7 as a novel epigenetic regulator of mesenchymal stem cells (MSCs) osteogenic commitment. Conditional knockout of Prmt7 in mice reveals a significant impairment in osteogenesis and bone regeneration, specifically in females, affecting both femurs and mandibles, with no noticeable effect in males. Mechanistically, PRMT7 modulates MSCs osteogenic differentiation by activating PTEN. Specifically, PRMT7 enhances PTEN transcription by increasing H3R2me1 levels at the PTEN promoter. Additionally, PRMT7 interacts with the PTEN protein and stabilizes nuclear PTEN, revealing an unprecedented pathway. Notably, overexpression of PTEN alleviates the osteogenic deficits observed in Prmt7-deficient mice. This research establishes PRMT7 as a potential therapeutic target for promoting bone formation/regeneration and offers novel molecular insights into the PRMT7–PTEN regulatory axis, underscoring its significance in bone biology and regenerative medicine.

The periosteum plays a central role in skeletal regeneration by serving as a reservoir of skeletal stem cells and a dynamic regenerative niche. However, in vitro models that faithfully preserve its cellular complexity, long‐term stability, and functional capacity remain limited, restricting mechanistic studies and translational applications. Here, we establish a long‐term expandable periosteal organoid system that can be stably propagated for over 20 passages while preserving cellular heterogeneity, multilineage differentiation potential, and genomic integrity. Single‐cell transcriptomic analysis reveals sustained maintenance of core periosteal lineages and regenerative signaling programs over extended culture. Functionally, these organoids reconstruct a niche‐like microenvironment that supports hematopoietic stem cell (HSC) maintenance, preserves stem cell fitness, and attenuates aging‐associated functional decline under prolonged ex vivo conditions. Upon transplantation, periosteal organoids robustly engraft and actively participate in tissue repair, promoting vascularized bone formation and reconstruction of marrow‐like structures across multiple defect models. Mechanistically, we identify ZFP575 as a 3D niche‐dependent regulator required for maintaining in vivo osteogenic competence. Together, our findings establish periosteal organoids as a physiologically relevant and functionally competent regenerative platform, providing a versatile system for modeling skeletal repair and stem cell‐niche interactions.