Standardization and consensus in the development and application of bone organoids

Abstract

Organoids, self-organized structures derived from stem cells cultured in a specific three-dimensional (3D) in vitro microenvironment, have emerged as innovative platforms that closely mimic in vivo cellular behavior, tissue architecture, and organ function. Bone organoids, a frontier in organoid research, can replicate the complex structures and functional characteristics of bone tissue. Recent advancements have led to the successful development of bone organoids, including models of callus, woven bone, cartilage, trabecular bone, and bone marrow. These organoids are widely utilized in establishing bone-related disease models, bone injury repair, and drug screening. However, significant discrepancies remain between current bone organoids and human skeletal tissues in terms of morphology and functionality, limiting their ability to accurately model human bone physiology and pathology. To address these challenges and promote standardization in the construction, evaluation, and application of bone organoids, we have convened experts and research teams with substantial expertise in the field. By integrating existing research findings, this consortium aims to establish a consensus to guide future research and application of bone organoids.

Keywords: bone organoids; bone tissue engineering; disease modeling; in vitro modeling; organoid development; standardization.

Figure 1

Key milestones in organoid research. Timeline of major advancements in organoid development, from early tissue culture in 1907 to recent models like vascularized organoids in 2019.

Figure 2

Overview of bone organoids: definition, cellular origin, key characteristics, and classification by developmental stage. (A) Bone organoids are complex, 3D tissue constructs cultured in vitro, replicating the structure and function of bone. (B) The cellular sources of bone organoids include iPSCs, ESCs, MSCs, and somatic cells. (C) Bone organoids are characterized by multicellularity, a 3D bone tissue structure, mineralization capacity, and mechanical support. (D) Our team's perspective on the developmental stages of bone organoids.

Figure 3

Construction strategies of bone organoids. Strategies for constructing bone organoids include using various stem cell sources, such as iPSCs derived from somatic cells, ESCs from blastocysts, and MSCs from bone marrow, adipose tissue, and dental pulp. These stem cells can be cultured and assembled into bone-like structures using techniques like scaffold-assisted approaches, cellular self-assembly, 3D bioprinting, and AI-assisted construction. Common materials used in the construction process include hydroxyapatite, cytokines, extracellular vesicles (EVs), natural and synthetic organic polymers, which are often combined to create composite materials for bone organoids.

Figure 4

Applications of bone organoids. (A) Bone organoids are used for bone regeneration and repair, including the development of osteogenic and vascularized bone organoids for addressing bone defects and femoral head necrosis. (B) Bone organoids facilitate drug screening, allowing for the testing of compounds in a controlled environment. (C) Bone organoids are valuable in studying bone development processes. (D) Bone organoid-based models provide insights into various bone diseases, such as osteoporosis, osteoarthritis, bone tumors, osteomyelitis, and genetic bone diseases. (E) Bone organoids can be used to evaluate bone implants, assessing their compatibility and performance. (F) Bone organoids hold potential in precision medicine by enabling personalized treatment approaches based on patient-specific cellular data.

Figure 5

Multidimensional and comprehensive identification of bone organoids. (A) Morphological identification of bone organoids. (B) Biological function identification of bone organoids. (C) Molecular biology identification of bone organoids.