Advance in the application of organoids in bone diseases.

Bone diseases such as osteoporosis and osteoarthritis have become important human health problems, requiring a deeper understanding of the pathogenesis of related diseases and the development of more effective treatments. Bone organoids are three-dimensional tissue masses that are useful for drug screening, regenerative medicine, and disease modeling because they may mimic the structure and physiological activities of organs. Here, we describe various potential methods for culturing bone-related organoids from different stem cells, detailing the construction processes and highlighting the main applications of these bone organoid models. The application of bone organoids in different skeletal diseases is highlighted, and current and promising bone organoids for drug screening and regenerative medicine as well as the latest technological advancements in bone organoids are discussed, while the future development of bone organoids is discussed. Looking forward, it will provide a reference for constructing bone organoids with more complete structures and functions and applying them to biomedical research.

Quantum dots for bone tissue engineering.

In confronting the global prevalence of bone-related disorders, bone tissue engineering (BTE) has developed into a critical discipline, seeking innovative materials to revolutionize treatment paradigms. Quantum dots (QDs), nanoscale semiconductor particles with tunable optical properties, are at the cutting edge of improving bone regeneration. This comprehensive review delves into the multifaceted roles that QDs play within the realm of BTE, emphasizing their potential to not only revolutionize imaging but also to osteogenesis, drug delivery, antimicrobial strategies and phototherapy. The customizable nature of QDs, attributed to their size-dependent optical and electronic properties, has been leveraged to develop precise imaging modalities, enabling the visualization of bone growth and scaffold integration at an unprecedented resolution. Their nanoscopic scale facilitates targeted drug delivery systems, ensuring the localized release of therapeutics. QDs also possess the potential to combat infections at bone defect sites, preventing and improving bacterial infections. Additionally, they can be used in phototherapy to stimulate important bone repair processes and work well with the immune system to improve the overall healing environment. In combination with current trendy artificial intelligence (AI) technology, the development of bone organoids can also be combined with QDs. While QDs demonstrate considerable promise in BTE, the transition from laboratory research to clinical application is fraught with challenges. Concerns regarding the biocompatibility, long-term stability of QDs within the biological environment, and the cost-effectiveness of their production pose significant hurdles to their clinical adoption. This review summarizes the potential of QDs in BTE and highlights the challenges that lie ahead. By overcoming these obstacles, more effective, efficient, and personalized bone regeneration strategies will emerge, offering new hope for patients suffering from debilitating bone diseases.

Engineering Large-Scale Self-Mineralizing Bone Organoids with Bone Matrix-Inspired Hydroxyapatite Hybrid Bioinks.

Addressing large bone defects remains a significant challenge owing to the inherent limitations in self-healing capabilities, resulting in prolonged recovery and suboptimal regeneration. Although current clinical solutions are available, they have notable shortcomings, necessitating more efficacious approaches to bone regeneration. Organoids derived from stem cells show great potential in this field; however, the development of bone organoids has been hindered by specific demands, including the need for robust mechanical support provided by scaffolds and hybrid extracellular matrices (ECM). In this context, bioprinting technologies have emerged as powerful means of replicating the complex architecture of bone tissue. The research focused on the fabrication of a highly intricate bone ECM analog using a novel bioink composed of gelatin methacrylate/alginate methacrylate/hydroxyapatite (GelMA/AlgMA/HAP). Bioprinted scaffolds facilitate the long-term cultivation and progressive maturation of extensive bioprinted bone organoids, foster multicellular differentiation, and offer valuable insights into the initial stages of bone formation. The intrinsic self-mineralizing quality of the bioink closely emulates the properties of natural bone, empowering organoids with enhanced bone repair for both in vitro and in vivo applications. This trailblazing investigation propels the field of bone tissue engineering and holds significant promise for its translation into practical applications.

The Application of Organoids in the Research of Skeletal Diseases: Current Status and Prospects.

Organoids, which are clumps of cells formed after in vitro 3D culture utilizing autologous tissue and stem cells, possess the 3D structure and corresponding functional and genetic features of the original tissue and organ. This model has immense potential in modeling the ontogeny of specific organismal organs, as well as in drug screening and studying molecular mechanisms. The newly developed concept of bone organoids, a special type of complex hard tissues that can be created in vitro using tissue engineering 3D culture technology, mimics the complex biological functions of bone tissue in vivo. These bone organoids are highly useful in elucidating the regulatory mechanisms of bone regeneration, screening tissue engineering materials, and promoting bone regeneration and repair. They offer promising applications in bone regeneration research.

Organoids as Innovative Models for Bone and Joint Diseases.

Bone is one of the key components of the musculoskeletal system. Bone and joint disease are the fourth most widespread disease, in addition to cardiovascular disease, cancer, and diabetes, which seriously affect people's quality of life. Bone organoids seem to be a great model by which to promote the research method, which further could improve the treatment of bone and joint disease in the future. Here, we introduce the various bone and joint diseases and their biology, and the conditions of organoid culture, comparing the in vitro models among 2D, 3D, and organoids. We summarize the differing potential methods for culturing bone-related organoids from pluripotent stem cells, adult stem cells, or progenitor cells, and discuss the current and promising bone disease organoids for drug screening and precision medicine. Lastly, we discuss the challenges and difficulties encountered in the application of bone organoids and look to the future in order to present potential methods via which bone organoids might advance organoid construction and application.

432A perspective on light-based bioprinting of DNA hydrogels for advanced bone regeneration: Implication for bone organoids.

Light-based three-dimensional (3D) printing of hydrogels has been widely adopted for accelerating bone regeneration. However, the design principles of traditional hydrogels do not take into consideration the biomimetic regulation of multiple stages throughout the bone healing, and the hydrogels made cannot effectively induce sufficient osteogenesis, which in turn greatly limits their capacity in guiding bone regeneration. The recent progress achieved in DNA hydrogel, which is based on synthetic biology, could facilitate the innovation of the current strategy due to its advantages, such as resistance to enzymatic degradation, programmability, structural controllability, and mechanical properties. However, 3D printing of DNA hydrogel is not well defined and appears to have a few distinct early forms. In this article, a perspective on the early development of 3D printing of DNA hydrogels is presented, and a potential implication of the hydrogel-based bone organoids built-up for bone regeneration is proposed.

A new strategy for bone defect repair: bone organoids / 中华创伤杂志

Bone tissue repair has long been a hot topic and difficult issue in the field of regenerative medicine research. Although the rapid development of bone tissue engineering technology significantly accelerates the level of bone repair in recent years, bone regeneration research still faces many challenges such as difficulty in regeneration under pathological condition and unclear regenerative regulatory mechanisms. As a result, the evelopment of bone tissue engineering technology encounters a bottleneck, restricting more researches over bone regeneration and repair. As a novel concept, bone organoids are proposed and constructed in vitro with the help of tissue engineering technology based on biological theory, and can simulate the complex biological functions of bone in vivo. Bone organoids show broad application prospects in the research of bone regeneration, including elucidating regulatory regeneration mechanisms, screening biomaterials and promoting regeneration, etc. In this study, the authors preliminarily discuss the features, construction and value of bone organoids so as to provide new insight for the treatment of bone defect.

Ontogenic Identification and Analysis of Mesenchymal Stromal Cell Populations during Mouse Limb and Long Bone Development.

Bone-derived mesenchymal stromal cells (MSCs) differentiate into multiple lineages including chondro- and osteogenic fates and function in establishing the hematopoietic compartment of the bone marrow. Here, we analyze the emergence of different MSC types during mouse limb and long bone development. In particular, PDGFRαposSCA-1pos (PαS) cells and mouse skeletal stem cells (mSSCs) are detected within the PDGFRαposCD51pos (PαCD51) mesenchymal progenitors, which are the most abundant progenitors in early limb buds and developing long bones until birth. Long-bone-derived PαS cells and mSSCs are most prevalent in newborn mice, and molecular analysis shows that they constitute distinct progenitor populations from the earliest stages onward. Differential expression of CD90 and CD73 identifies four PαS subpopulations that display distinct chondro- and osteogenic differentiation potentials. Finally, we show that cartilage constructs generated from CD90pos PαS cells are remodeled into bone organoids encompassing functional endothelial and hematopoietic compartments, which makes these cells suited for bone tissue engineering.