Organoids: Promoting Innovation in Organoid Technology for Basic Research and Therapeutic Applications

Liver ductal organoids reconstruct intrahepatic biliary trees in decellularized liver grafts

9 - 3-D organ printing technologies for tissue engineering applications

11 - 3-D bioprinting technologies for tissue engineering applications

Kidney organoids, as three-dimensional microstructures derived from human pluripotent stem cells or adult stem cells, precisely simulate the cellular heterogeneity, spatial conformation, and some physiological functions of human kidney units in vitro. Kidney organoids are three-dimensional microstructures derived from human pluripotent stem cells (hPSCs). They precisely simulate the cellular heterogeneity, spatial conformation, and key physiological functions of human kidney units in vitro. This technology, by replicating the interaction network between the glomerulus and renal tubules, provides an unprecedented window for observing the dynamic development and pathological processes of human kidneys. This technology replicates the interaction network between the glomerulus and renal tubules. It thereby provides an unprecedented window into human kidney development and disease. Based on the strong similarity between organoids and native organs, as well as the human genetic information they carry, both iPSC-derived and patient-specific organoids have demonstrated significant value in kidney disease modeling, drug toxicity testing, and the development of regenerative treatment strategies. This review systematically elucidates the key advancements in the field of kidney organoids, including optimized strategies for stem cell-directed differentiation, innovations in culture systems driven by biomaterials engineering, technological breakthroughs in disease model construction, and applications of organoids in drug screening platforms and regenerative medicine. Additionally, it analyzes translational challenges such as the lack of vascularization, insufficient functional maturity, and obstacles in standardized production. These insights will deepen the understanding of kidney pathological mechanisms and propel organoid technology towards substantial clinical therapeutic applications. This review summarizes how convergent technologies in stem cell biology and bioengineering aim to bridge this functional gap. We examine the use of advanced organoids in disease modeling and drug discovery. We also highlight their current limitations. Our focus is on the core translational bottlenecks: vascularization, long-term maturation, and scalable production. Overcoming these hurdles is essential to transform kidney organoids from a research tool into a platform for precision medicine and regenerative therapy.

In this chapter, you will learn the significant advances in tissue engineering, and the techniques used to generate tissues that mimic the natural structure of the native tissues and organs. You will learn the most suitable cell type or a combination of cells that can build up the tissue and incorporate them into natural or synthetic scaffolds. The chapter will cover current advances in 3D printing technology and nanomaterials, and the important role they play in the generation of scaffolds that match the extracellular matrix of almost any tissue. The difference between the mechanical method of the extrusion-based bioprinting and stereolithography, and other bioprinting techniques will be discussed. The chapter will also examine the factors involved in the scaffold synthesis and how they act synergistically to generate high-quality tissues. Finally, it will cover the recent development in organoid technology, and their application in regenerative and personalized medicine.

A kidney organoid is a three-dimensional (3D) cellular aggregate grown from stem cells in vitro that undergoes self-organization, recapitulating aspects of normal renal development to produce nephron structures that resemble the native kidney organ. These miniature kidney-like structures can also be derived from primary patient cells and thus provide simplified context to observe how mutations in kidney-disease-associated genes affect organogenesis and physiological function. In the past several years, advances in kidney organoid technologies have achieved the formation of renal organoids with enhanced numbers of specialized cell types, less heterogeneity, and more architectural complexity. Microfluidic bioreactor culture devices, single-cell transcriptomics, and bioinformatic analyses have accelerated the development of more sophisticated renal organoids and tailored them to become increasingly amenable to high-throughput experimentation. However, many significant challenges remain in realizing the use of kidney organoids for renal replacement therapies. This review presents an overview of the renal organoid field and selected highlights of recent cutting-edge kidney organoid research with a focus on embryonic development, modeling renal disease, and personalized drug screening.

Organoid engineering is a rapidly expanding field that involves developing miniaturized, three-dimensional (3D) structures to mimic the architecture and function of real organs. It provides a powerful platform to investigate organ development, disease modeling, and personalized medicine. Recent advances in cell printing technology, also known as bioprinting, feature high-throughput potential, precise control, and enhanced reproducibility, enabling the deposition of living cells to generate complex, 3D biological structures. Cell printing with bioinks composed of cells and supportive biomaterials has been utilized to generate in vitro tissues and organs with intricate architectures and functionalities to investigate normal tissue morphogenesis and disease progression. The integration of cell printing technology and organoid engineering holds tremendous potential in biomedical research. Here, we summarize recent advances in cell printing technology in developing different organoid models, creating patient-specific tissue grafts, and utilizing these models and grafts in drug testing, as well as studying disease progression. Some of these bioprinted organoids have been utilized in clinical trials, highlighting the potential of cell printing technology in future applications in tissue and organ transplantation, as well as precision medicine. Impact Statement This article summarizes recent advances in integrating cell printing technology with three-dimensional tissue culture to develop organoid models. It discusses the advantages and limitations of three bioprinting technologies used in cell and organoid printing. The review also highlights the significant potential of cell printing technology in organoid model development and its applications in biomedical research and drug screening.

Organoids serve as pivotal models in both basic and applied research, offering transformative potential in biomedical applications. Herein is presented a comprehensive multi‐scale perspective encompassing dual‐scale construction, four‐dimensional evaluation, triple‐point application, and an analysis of the current challenges faced by organoid technology, aiming to advance organoid research and its biomedical applications. Dual‐scale construction integrates micro‐scale and macro‐scale strategies to optimize material selection and spatial organization, thereby enhancing the biological fidelity of organoids. Four‐dimensional evaluation systematically assesses functional performance and long‐term stability at the molecular, cellular, organ, and in vivo levels, ensuring robust characterization. Triple‐point application explores the translational potential of organoids in basic research, preclinical studies, and clinical applications, with a focus on disease modeling, drug screening, and regenerative medicine. By refining construction methodologies, improving evaluation frameworks and facilitating clinical translation, this multi‐scale approach provides critical insights into optimizing organoid technology for biomedical research and therapeutic applications. The introduction of artificial intelligence (AI) empowers organoid research by enabling intelligent construction strategy screening, efficient multi‐scale image analysis, rapid multi‐omics data interpretation, and accurate preclinical assessment.

Generation of expandable human pluripotent stem cell-derived hepatocyte-like liver organoids

Historical developmental biology experiments demonstrated the remarkable capacity of reaggregated vertebrate cells for self-organization, now exploited to rebuild human tissues, reminiscent of native organs, from somatic or pluripotent stem cells, namely, an organoid. Organoid technology is thus rapidly evolving and becoming an independent research field due to its potential for modelling human development and disease. Coupled with patient-derived stem cells, diseased organoid recapitulates a pathological state in a dish, promoting personalized medicine and drug development. Ultimately, organoid transplantation paves a way for organ replacement strategies against end-stage diseases. This article summarizes the evolutionary organoid technology backed by developmental biology and outlines its phenomenal potential for future therapeutic applications.

Organoids, which replicate the three-dimensional architecture and physiological functions of native organs, have emerged as a groundbreaking tool with significant therapeutic potential for tissue regeneration and functional reconstruction. Despite their broad applications in various fields, research on dental pulp organoids and their use in regenerative therapies remains in its early stages, presenting both opportunities and challenges. To advance the understanding of organoid technology and facilitate its translation into pulp regenerative medicine, this review provided a comprehensive overview of organoids, encompassing their developmental history, self-organization mechanisms, fundamental definitions, and current applications. Building on this foundation, we highlighted recent progress in oral and maxillofacial organoid research, with a particular focus on the construction of dental pulp organoids. Additionally, we systematically summarized the commonly employed construction methods and explored innovative bioengineering strategies that hold promise for future applications. Finally, we critically evaluated the existing challenges in applying organoid technology to pulp tissue regeneration and functional reconstruction, while proposing potential solutions to overcome these barriers. This review aimed to provide valuable insights and inspire further research in this rapidly evolving field.

The advent of medical advances has resulted in the development of an array of treatments aimed at restoring damaged organs in humans. However, when chemical treatments, such as drug therapies, are constrained, organ transplantation may ultimately emerge as the sole viable solution. Nevertheless, despite the continually increasing demand for organ donations, the actual number of donated organs remains insufficient to meet this demand. Recently, a variety of organoids have been generated using stem cells and have been demonstrated to exhibit functionality comparable to that of native organs. This indicates that organoids may be a viable option for use in organ transplantation. However, while numerous recent publications have documented the regenerative effects of diverse organoid types when implanted into damaged regions, significant technical and ethical considerations must be addressed before organoids can be utilized as a replacement for human organs. This review presents an overview of experimental endeavors in regenerative therapies through organoid transplantation, while also addressing the challenges that must be overcome to enhance the feasibility of organoid use as a surrogate organ. As organoid technology continues to advance, organoids may eventually become a widely utilized surrogate source for organ replacement in clinical settings.

Immunotherapy has led to groundbreaking advances in anti-tumor treatment, yet significant clinical challenges remain such as the low proportion of beneficiaries and the lack of effective platforms for predicting therapeutic response. Organoid technology provides a novel solution to these issues. Organoids are three-dimensional tissue cultures derived from adult stem cells or pluripotent stem cells that closely replicate the structural and biological characteristics of native organs, demonstrating particularly strong potential in modeling the tumor microenvironment (TME). Tumor organoids can simulate TME effectively by retaining endogenous matrix components, including various immune cells, or by adding immune cells, cancer-associated fibroblasts, and other components. This provides a novel platform for predicting immunotherapy outcomes, evaluating adoptive cell therapies, and selecting personalized treatment options for patients. Summarizing strategies for constructing tumor organoids that simulate the microenvironment and understanding their advancements in immunotherapy research and clinical application can provide new insights for the development of tumor immunotherapy.

Recent advances in 3D cell culture technology have enabled scientists to generate stem cell derived organoids that recapitulate the structural and functional characteristics of native organs. Current organoid technologies have been striding toward identifying the essential factors for controlling the processes involved in organoid development, including physical cues and biochemical signaling. There is a growing demand for engineering dynamic niches characterized by conditions that resemble in vivo organogenesis to generate reproducible and reliable organoids for various applications. Innovative biomaterial-based and advanced engineering-based approaches have been incorporated into conventional organoid culture methods to facilitate the development of organoid research. The recent advances in organoid engineering, including extracellular matrices and genetic modulation, are comprehensively summarized to pinpoint the parameters critical for organ-specific patterning. Moreover, perspective trends in developing tunable organoids in response to exogenous and endogenous cues are discussed for next-generation developmental studies, disease modeling, and therapeutics.

In the last decade, organoids have gained popularity for developing mini-organs to support advancements in the study of organogenesis, disease modeling, and drug screening and, subsequently, in the development of new therapies. To date, such cultures have been used to replicate the composition and functionality of organs such as the kidney, liver, brain, and pancreas. However, depending on the experimenter, the culture environment and cell conditions may slightly vary, resulting in different organoids; this factor significantly affects their application in new drug development, especially during quantification. Standardization in this context can be achieved using bioprinting technology—an advanced technology that can print various cells and biomaterials at desired locations. This technology offers numerous advantages, including the manufacturing of complex three-dimensional biological structures. Therefore, in addition to the standardization of organoids, bioprinting technology in organoid engineering can facilitate automation in the fabrication process as well as a closer mimicry of native organs. Further, artificial intelligence (AI) has currently emerged as an effective tool to monitor and control the quality of final developed objects. Thus, organoids, bioprinting technology, and AI can be combined to obtain high-quality in vitro models for multiple applications.