Technological advances and challenges in constructing complex gut organoid systems.

Repair of critical-size bone defects remains a significant challenge. In recent years, organoid technology has emerged as a promising strategy for bone regeneration, but developing bone organoids with complex structure and function still faces many hurdles. Three-dimensional (3D) bioprinting, a revolutionary additive manufacturing technology, can precisely deposit bioink layer by layer with a specific pattern to construct the required 3D structure, which provides a simpler and more efficient method for generating bone organoids. This review summarizes the 3D bioprinting strategies of bone organoids and their application in bone regeneration in order to provide a reference for future research.

The organoid approach preserves the intricate molecular and genetic characteristics of tumor tissues, playing a pivotal role in advancing precision oncology. This preservation enables the exploration of cancer therapies and in vitro validation of drug efficacy. Organoids have emerged as indispensable tools in the study of urological cancers, facilitating research on tumorigenesis, drug testing, and the development of therapeutic combinations. Their superiority over traditional 2D cell cultures and patient-derived xenograft (PDX) models lies in their enhanced ability to more accurately replicate the in vivo environment. Modern organoid platforms integrate 3D bioprinting, co-culture systems, microfluidics, and artificial intelligence to significantly improve the precision, scalability, and efficiency of cancer research. These integrated systems serve as powerful analytical tools, propelling the development of personalized therapies for urological malignancies. This article provides a comprehensive review of the establishment and potential of organoid technologies in treating the three major urogenital system cancers-prostate, bladder, and renal-highlighting their trajectory from basic research to clinical applications and their expanding synergy with bioengineering innovations.

Animal organoid models derived from farm and companion animals have great potential to contribute to human health as a One Health initiative, which recognize a close inter-relationship among humans, animals and their shared environment and adopt multi-and trans-disciplinary approaches to optimize health outcomes. With recent advances in organoid technology, studies on farm and companion animal organoids have gained more attention in various fields including veterinary medicine, translational medicine and biomedical research. Not only is this because three-dimensional organoids possess unique characteristics from traditional two-dimensional cell cultures including their self-organizing and self-renewing properties and high structural and functional similarities to the originating tissue, but also because relative to conventional genetically modified or artificially induced murine models, companion animal organoids can provide an excellent model for spontaneously occurring diseases which resemble human diseases. These features of companion animal organoids offer a paradigm-shifting approach in biomedical research and improve translatability of in vitro studies to subsequent in vivo studies with spontaneously diseased animals while reducing the use of conventional animal models prior to human clinical trials. Farm animal organoids also could play an important role in investigations of the pathophysiology of zoonotic and reproductive diseases by contributing to public health and improving agricultural production. Here, we discuss a brief history of organoids and the most recent updates on farm and companion animal organoids, followed by discussion on their potential in public health, food security, and comparative medicine as One Health initiatives. We highlight recent evolution in the culturing of organoids and their integration with organ-on-a-chip systems to overcome current limitations in in vitro studies. We envision multidisciplinary work integrating organoid culture and organ-on-a-chip technology can contribute to improving both human and animal health.

Convergence: Multi-omics and AI are reshaping the landscape biomedical research.

The rapid advancement in the fabrication and culture of in vitro organs has marked a new era in biomedical research. While strides have been made in creating structurally diverse bioartificial organs, such as the liver, which serves as the focal organ in our study, the field lacks a uniform approach for the predictive assessment of liver function. Our research bridges this gap with the introduction of a novel, machine-learning-based "3P model" framework. This model draws on a decade of experimental data across diverse culture platform studies, aiming to identify critical fabrication parameters affecting liver function, particularly in terms of albumin and urea secretion. Through meticulous statistical analysis, we evaluated the functional sustainability of the in vitro liver models. Despite the diversity of research methodologies and the consequent scarcity of standardized data, our regression model effectively captures the patterns observed in experimental findings. The insights gleaned from our study shed light on optimizing culture conditions and advance the evaluation of the functional maintenance capacity of bioartificial livers. This sets a precedent for future functional evaluations of bioartificial organs using machine learning.

The Big Data era in Biomedical research has resulted in large-cohort data repositories such as The Cancer Genome Atlas (TCGA). These repositories routinely contain hundreds of matched patient samples for genomic, proteomic, imaging, and clinical data modalities, enabling holistic and multi-modal integrative analysis of human disease. Using TCGA renal and ovarian cancer data, we conducted a novel investigation of multi-modal data integration by combining histopathological image and RNA-seq data. We compared the performances of two integrative prediction methods: majority vote and stacked generalization. Results indicate that integration of multiple data modalities improves prediction of cancer grade and outcome. Specifically, stacked generalization, a method that integrates multiple data modalities to produce a single prediction result, outperforms both single-data-modality prediction and majority vote. Moreover, stacked generalization reveals the contribution of each data modality (and specific features within each data modality) to the final prediction result and may provide biological insights to explain prediction performance.

This special issue presents the abstracts of the Short Communications and Posters presented at the 12th International Congress of the European Association for Veterinary Pharmacology and Toxicology (EAVPT2012). Individual topics were introduced by keynote lectures as indicated. Only short summaries of these plenary and keynote lectures are presented here, but many of the keynote speakers have placed their presentations on the Congress Website. Moreover, keynote speakers have been invited to draft a review article on their respective topic(s). These reviews will be published in the forthcoming issues of this Journal. A short reference is also made to the different workshops organized within the Congress programme as a moment and opportunity to discuss in an informal way relevant and upcoming questions pertinent to veterinary therapeutics. Special information about these subjects can be obtained from the workshop coordinators. The programme of EAVPT 2012 was dense and covered many aspects of veterinary pharmacology and toxicology, the latter with emphasis on food safety assessment. Traditionally on the 1st day, investigations devoted to the pharmacokinetics of anti-infectives (antibiotics and antiparasitics) covered a prominent part of the programme. In the course of the Congress refined PD/PK models were presented, applied to establish optimal dosage regimens not only for antibiotics, but also for many other drugs commonly used in veterinary medicine. At the same time, the global emergence of antimicrobial resistance has added the demand of resistance avoidance-strategies to meet public health expectations. This aspect has to be considered in the overall assessment of therapeutic dosing regimens for antibiotics. An inherent part of kinetics is the investigation of biotransformation processes and the specific drug transporters that affect drug absorption and distribution. Understanding of the intraspecies (breed differences) and interspecies variation allows an individualization of therapeutic approaches and hence will improve drug efficacy and safety. At the same time, the (patho-)physiological variability within the treated group of animals (treated population) needs to be predicted and acknowledged (population kinetics). Drug research and development is more and more driven by modern molecular technologies. The increasing availability of -omic technologies, supported by worldwide activities to analyse the entire genome of all major target animal species in veterinary medicine, marks a new era in biomedical research. Research into inflammatory responses and pain control, but also in many other areas, utilizes these technologies to directly monitor a virtually unlimited number of signal transduction pathways and biological events. Hence, gene expression profiling and the targeted suppression (silencing) of selected genes (either in vitro or in the intact animal) are considered as powerful tools in modern drug development. Together with new drug delivery systems, supported by nanotechnology, ample opportunities are created for the identification of new drug classes in preventive (vaccines) and curative veterinary medicine. Gene expression profiling is also increasingly applied in all areas of toxicological research. In food safety, gene profiling is used to identify animals that have been exposed to (multiple) undesirable substances or that have been treated with illicit compounds. In general, food toxicology has evolved as a highly specialized area requiring the close cooperation of various disciplines in refined exposure assessment and hazard characterization (dose-response assessment). The advances in chemical analytical procedures towards multi-analyte techniques allow the simultaneous analysis of diverse food and feed contaminants. In turn, there is an increasing demand for new concepts in the toxicological assessment of complex mixtures, reflecting exposure of individuals and cohorts (human and animals) in real life. Last but not least, it should be mentioned that EAVPT Congresses always address veterinary education and a comparison of veterinary curricula from different continents and societies. Many participants from developing countries have an active interest in the educational programmes (particular distance learning programmes) and teaching materials used in undergraduate and graduate courses in veterinary pharmacology and toxicology (including food toxicology). Strengthening the multilateral communication about education and competence of veterinary professionals throughout the world will become a core objective of EAVPT in the forthcoming years. The education of veterinary specialists in pharmacology and toxicology in Europe is provided by the EBVS-recognized College for Veterinary Pharmacology and Toxicology (ECVPT). As an organization, ECVPT acts as a co-organizer of EAVPT Congresses in presenting training workshops and specific sessions. At EAVPT2012, a one-day pre-congress course in quantitative pharmacology was offered, and ECVPT diplomates were among the most active congress participants. The last session of an EAVPT Congress traditionally includes reflections of past and future objectives in veterinary pharmacology and toxicology and an invitation to the next EAVPT Congress. The forthcoming 13th International Congress of the European Association for Veterinary Pharmacology and Toxicology will be held in Nantes, France, in the summer of 2015.

Chapter 2 - Bioprinting of Biomimetic Tissue Models for Disease Modeling and Drug Screening

Organoids are three-dimensional tissue culture models derived from stem cells, and they have become one of the most valuable tools in biomedical research. These self-organizing miniature organs mimic the structure−function properties of their in vivo counterparts and offer an exceptional prospective for disease modeling, drug discovery, and regenerative medicine. By replicating the complexity of human tissue, organoids enable the study of disease pathophysiology, tissue development, and cellular interactions in a highly controlled and manipulable environment. Recent developments in organoid technology have enabled the production of functional organoids of various tissues. These systems have proven to be highly promising tools for personalized medicine. In addition, organoids have also raised hopes for the development of functional transplantable organs, transforming the study of regenerative medicine. This review provides an overview of the current state of organoid technology and its application and prospects and focuses on the transformative impact of organoid technology on biomedical research and its contribution to human health.

Advancements in sustainable bioprinting: Materials, challenges and opportunities in transition from 3D to 4D printing

Growing evidence propagates those alternative technologies (relevant human cell-based—e.g., organ-on-chips or biofabricated models—or artificial intelligence-combined technologies) that could help in vitro test and predict human response and toxicity in medical research more accurately. In vitro disease model developments have great efforts to create and serve the need of reducing and replacing animal experiments and establishing human cell-based in vitro test systems for research use, innovations, and drug tests. We need human cell-based test systems for disease models and experimental cancer research; therefore, in vitro three-dimensional (3D) models have a renaissance, and the rediscovery and development of these technologies are growing ever faster. This recent paper summarises the early history of cell biology/cellular pathology, cell-, tissue culturing, and cancer research models. In addition, we highlight the results of the increasing use of 3D model systems and the 3D bioprinted/biofabricated model developments. Moreover, we present our newly established 3D bioprinted luminal B type breast cancer model system, and the advantages of in vitro 3D models, especially the bioprinted ones. Based on our results and the reviewed developments of in vitro breast cancer models, the heterogeneity and the real in vivo situation of cancer tissues can be represented better by using 3D bioprinted, biofabricated models. However, standardising the 3D bioprinting methods is necessary for future applications in different high-throughput drug tests and patient-derived tumour models. Applying these standardised new models can lead to the point that cancer drug developments will be more successful, efficient, and consequently cost-effective in the near future.

Microfluidics is the science and technology of manipulating minute fluid volumes within micro-sized channels. It is an interdisciplinary technology that integrates physics, chemistry, biology, materials science, and microengineering, offering transformative potential for biomedical research. Recent innovations in the field of microfluidics such as organ-on-chip devices, droplet-based assays, 3D bioprinting, integration with artificial intelligence and CRISPR technologies have accelerated the development of physiologically close models and personalized medicine approaches. This review comprehensively examines the emerging field of microfluidics, including its design principles, fabrication techniques, and commonly materials used materials. Moreover, also highlights the key applications in stem cell culture, organ-mimicking systems, cancer and infectious disease research, drug discovery, and genome editing. Furthermore, it also compares with traditional methods, outlines the current challenges, along with future directions that emphasize smart, adaptive platforms for real-time monitoring and automated control.

Conductive and antioxidant biopolymeric hydrogel-based bioinks with nanohybrids of protein amyloid nanofibrils‑gold nanoparticles for cardiac 3D bioprinting.

Respiratory tissue engineering offers a robust framework for studying cell-cell and host-pathogen interactions in a tissue-like environment and offers a platform for studying lung tissue regeneration and disease mechanisms. However, the challenge of replicating dynamic three-dimensional (3D) microenvironments is a huge obstacle with existing technology. Current animal models and two-dimensional cell culture models do not replicate in vivo conditions seen in human lungs, thus research utilizing these techniques often fails to help alleviate the global burden of respiratory diseases. Respiratory tissue engineering has been drawing significant attention over the past decade. Particularly with the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many inspiring developments and advances have been reported. This review presents the recent advances of respiratory tissue engineering focusing on 3D bioprinting, organ-on-a-chip, and organoid technologies. It also provides an overview of recent attempts to integrate biomechanical stimulus with the aim of improving the integrity of 3D constructs and enhancing cellular propagation. This review addresses the challenges inherent in existing 3D respiratory models and discusses the future prospects of research in this field, urging continuing innovation and investment toward the success of respiratory tissue engineering and increasing clinical relevance.

3D bioprinting strategies for recapitulation of hepatic structure and function in bioengineered liver: A state-of-the-art review