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role of the extracellular matrix in bone tissue, specifically cell differentiation effectively and model the mechanical
in regulating cell adhesion, proliferation, growth factor strength and biological 3D structure of bone. These
responsiveness, and differentiation, all of which influence materials can generally be categorized by shape into
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the functional characteristics of mature bone. In organoid hydrogels, sponge-like porous scaffolds, nanofiber
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research, extracellular matrix components, such as collagen, materials, micro/nanoparticles and vesicles, and
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fibronectin, and laminin, are often employed as scaffolds to 3D-printed scaffolds. The development of innovative
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simulate the native tissue microenvironment, which more bioscaffolds and 3D bioprinting technologies provides the
effectively guides the proliferation and differentiation of structural support necessary to mimic the natural tissue
stem cells (e.g., mesenchymal stem cells) and osteocytes. environment for organoids. Future efforts may focus on
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This approach reveals the interaction of critical biological enhancing the compatibility and functionality of materials
processes in bone organoids and highlights emerging used in bone/cartilage organoid development, which is
research directions in the field. crucial for their clinical translation.
5. Future direction (iii). Regenerative medicine and clinical applications
Journals play a vital role in disseminating academic The use of bone/cartilage organoids in regenerative
research findings. Our research constructed a co-citation medicine represents an advanced approach to personalized
visualization network that highlights the leading journals therapies and tissue repair. Recent developments in the
in the bone/cartilage organoid field, providing valuable stem cell field have enabled the derivation of various tissue
guidance for researchers in selecting appropriate journals organoids from patient-specific pluripotent and adult stem
for manuscript submission. Prestigious journals such as cells. Combined with advanced genome-editing tools, such
Nature, Cell, and Biomaterials ranked among the top. The as CRISPR/CRISPR-associated protein 9, organoids can
distinct clusters illustrated in Figure 6 reveal contributions be engineered to replicate the disease-relevant genetic and
from journals in stem cell biology, materials science, and epigenetic profiles of individual patients. This advancement
regenerative medicine, emphasizing the potential for has accelerated the development of sophisticated in vitro
interdisciplinary collaboration across these domains. By disease models, offering a unique platform for fundamental
analyzing these fields, we can identify crucial trajectories biomedical research and the advancement of personalized
for the further development of bone/cartilage organoids. medicine. 17,74 For tissue repair, a promising direction is the
(i). Stem cells and the biological microenvironment on integration of organoids with organ-on-a-chip technology.
bone/cartilage organoids By combining organoids with microfluidic systems,
dynamic physical and chemical environments such as
Organoids are ex vivo 3D cell culture systems designed
to replicate the multicellular relationships, spatial structure, nutrient delivery, mechanical stress, and fluid flowds, can
be simulated, closely mimicking the human physiological
and physiological functions of real organs. For example, environment. This approach could allow for more accurate
Eiraku et al. reported in Nature a dynamic, autonomously 45,75
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forming optic cup structure from the ex vivo 3D culture of modeling of tissue repair and regeneration processes.
mouse embryonic stem cells. Similarly, Boj et al. in Cell (iv). Disease modeling and drug screening
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performed a comprehensive transcriptomic and proteomic Bone/cartilage organoids are self-organizing, self-
analysis of mouse pancreatic organoids, revealing genes renewing mini-tissues that mimic the structure and function
and pathways altered during pancreatic cancer progression. of bone and cartilage under both normal and pathological
Takebe et al. utilized induced pluripotent stem cell- conditions. They are used for complex disease modeling,
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9
derived organ bud transplants to generate functional including osteoporosis, osteoarthritis, and cartilage injury,
human livers. Given that bone/cartilage organoids rely 76-78
heavily on stem cell and molecular biology, as evidenced in as well as for simulating bone metabolism processes.
studies published in Nature and Cell, future research could In addition, using organoids for drug testing helps avoid
further explore stem cell differentiation mechanisms, gene errors caused by significant biological differences between
regulation, and the influence of the microenvironment on animals and humans and allows for high-throughput
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bone and cartilage formation. drug screening. One challenge in using organoids for
drug screening is the need to produce a large quantity of
(ii). Advanced biomaterials for organoid growth and homogeneous organoids suitable for high-throughput
functionalization assays. Unlike traditional cell cultures, organoids require
While stem cell differentiation is intricately regulated more complex growth conditions, making large-scale
in vivo, replicating all the necessary cues ex vivo remains production difficult. To fully realize their potential, issues
challenging. In recent years, a range of biocompatible related to standardization, scalability, microenvironment
materials has been designed and applied to guide stem replication, and cost must be addressed.

Volume 1 Issue 3 (2025) 12 doi: 10.36922/or.8295