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Amyotrophic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disease affecting upper and lower motor neurons with no cure available. Clinical and animal studies reveal that the neuromuscular junction (NMJ), a synaptic connection between motor neurons and skeletal muscle fibers, is highly vulnerable in ALS and suggest that NMJ defects may occur at the early stages of the disease. However, mechanistic insight into how NMJ dysfunction relates to the onset and progression of ALS is incomplete, which hampers therapy development. This is, in part, caused by a lack of robust in vitro models. The ability to combine microfluidic and induced pluripotent stem cell (iPSC) technologies has opened up new avenues for studying molecular and cellular ALS phenotypes in vitro. Microfluidic devices offer several advantages over traditional culture approaches when modeling the NMJ, such as the spatial separation of different cell types and increased control over the cellular microenvironment. Moreover, they are compatible with 3D cell culture, which enhances NMJ functionality and maturity. Here, we review how microfluidic technology is currently being employed to develop more reliable in vitro NMJ models. To validate and phenotype such models, various morphological and functional read-outs have been developed. We describe and discuss the relevance of these read-outs and specifically illustrate how these read-outs have enhanced our understanding of NMJ pathology in ALS. Finally, we share our view on potential future directions and challenges.

Organ-on-a-chip (OOC) platforms recapitulate human in vivo-like conditions more realistically compared to many animal models and conventional two-dimensional cell cultures. OOC setups benefit from continuous perfusion of cell cultures through microfluidic channels, which promotes cell viability and activities. Moreover, microfluidic chips allow the integration of biosensors for real-time monitoring and analysis of cell interactions and responses to administered drugs. Three-dimensional (3D) bioprinting enables the fabrication of multicell OOC platforms with sophisticated 3D structures that more closely mimic human tissues. 3D-bioprinted OOC platforms are promising tools for understanding the functions of organs, disruptive influences of diseases on organ functionality, and screening the efficacy as well as toxicity of drugs on organs. Here, common 3D bioprinting techniques, advantages, and limitations of each method are reviewed. Additionally, recent advances, applications, and potentials of 3D-bioprinted OOC platforms for emulating various human organs are presented. Last, current challenges and future perspectives of OOC platforms are discussed., Scientific and Technological Research Council of Turkey (TÜBİTAK); International Fellowship for Outstanding Researchers Award; Alexander von Humboldt Research Fellowship for Experienced Researchers; European Union(EU); Horizon 2020; Marie Sklodowska-Curie Individual Fellowship; Royal Academy Newton-Katip Celebi Transforming Systems Through Partnership

Microfluidics have been used for several decades to conduct a wide range of research in chemistry and the life sciences. The reduced dimensions of these devices give them advantages over classical analysis techniques such as increased sensitivity, shorter analysis times, and lower reagent consumption. However, current manufacturing processes for microfluidic chips either limit them to materials with unwanted properties, or are not cost-effective for rapid-prototyping approaches. Here the authors show that inlays for injection moulding can be 3D printed, thus reducing the skills, cost, and time required for tool fabrication. They demonstrate the importance of orientation of the part during 3D printing so that features as small as 100 × 200 µm can be printed. They also demonstrate that the 3D printed inlay is durable enough to fabricate at least 500 parts. Furthermore, devices can be designed, manufactured, and tested within one working day. Finally, as demonstrators they design and mould a microfluidic chip to house a plasmonic biosensor as well as a device to house liver organoids showing how such chips can be used in organ-on-a-chip applications. This new fabrication technique bridges the gap between small production and industrial scale manufacturing, while making microfluidics cheaper, and more widely accessible.

Cancer is a life‐threatening disease, and even upon successful treatment, recurrence often occurs. A wide variety of preclinical models exist to effectively study cancer and design more efficient treatments. However, a majority of cancer models cannot accurately recapitulate cancer as it exists in humans. Animal models physiologically differ from humans. In vitro models, such as organoids, allow construction with human‐based components, but most fail to accurately mimic the overall tumor microenvironment (TME), which is composed of stromal and immune cells, as well as a complex extracellular matrix (ECM). However, more recent versions of these in vitro tumor models are increasingly complex and include both engineered ECM and the bidirectional, biomolecular crosstalk between different stromal cell components, particularly fibroblasts which are key players in the TME. Therefore, studying these components gives a more detailed insight into how tumors develop, interface with surrounding stromal and tissue architecture, and respond to therapies. Herein, a range of in vitro tumor model form factors is described, and the role of fibroblasts and ECM in cancer is also discussed, with a focus on how their inclusion in bioengineered in vitro and ex vivo tumor models better recapitulate the physiological complexities of cancer.

In vitro derived simplified 3D representations of human organs or organ functionalities are predicted to play a major role in disease modeling, drug development, and personalized medicine, as they complement traditional cell line approaches and animal models. The cells for 3D organ representations may be derived from primary tissues, embryonic stem cells or induced pluripotent stem cells and come in a variety of formats from aggregates of individual or mixed cell types, self‐organizing in vitro developed “organoids” and tissue mimicking chips. Microfluidic devices that allow long‐term maintenance and combination with other tissues, cells or organoids are commonly referred to as “microphysiological” or “organ‐on‐a‐chip” systems. Organ‐on‐a‐chip technology allows a broad range of “on‐chip” and “off‐chip” analytical techniques, whereby “on‐chip” techniques offer the possibility of real time tracking and analysis. In the rapidly expanding tool kit for real time analytical assays, mass spectrometry, combined with “on‐chip” electrophoresis, and other separation approaches offer attractive emerging tools. In this review, we provide an overview of current 3D cell culture models, a compendium of current analytical strategies, and we make a case for new approaches for integrating separation science and mass spectrometry in this rapidly expanding research field.

Organ-on-a-chip platforms have recently seen tremendous progress. They have found potential applications in the study of physiology and pathology of tissues, drug toxicity, and development of tissue models for replacement of animal studies. However, their potential role in organ transplantation has hardly been discussed, so far. Organ transplantation represents a major medical advancement of the twenty-first century, yet it suffers from limitation due to the shortage of organ supply. Very often, organs harvested from donor's body are deemed non-usable because of being damaged or "marginal". Recently, developments of bioartificial devices such as artificial placenta and renal assist-devices have shown that it is possible to develop novel bioartificial organ support systems that can support the healing of damaged or marginal organs prior to their transplantation. In the current article, we introduce a novel concept for building bioartificial organ assist devices and systems by integrating arrays of numerous organ-on-a-chip platforms. The new system can be used in organ repair centers as means for temporary organ support and functional enhancement. We have also briefly reviewed the relevant organ-on-a-chip platforms developed so far, and related literature to form a basis for developing our new concept, device and its application. The proposed system may help to increase the number of organs available for transplantation and improve transplantation outcomes. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2006-2018, 2019.

Impaired white adipose tissue (WAT) function has been recognized as a critical early event in obesity-driven disorders, but high buoyancy, fragility, and heterogeneity of primary adipocytes have largely prevented their use in drug discovery efforts highlighting the need for human stem cell-based approaches. Here, human stem cells are utilized to derive metabolically functional 3D adipose tissue (iADIPO) in a microphysiological system (MPS). Surprisingly, previously reported WAT differentiation approaches create insulin resistant WAT ill-suited for type-2 diabetes mellitus drug discovery. Using three independent insulin sensitivity assays, i.e., glucose and fatty acid uptake and suppression of lipolysis, as the functional readouts new differentiation conditions yielding hormonally responsive iADIPO are derived. Through concomitant optimization of an iADIPO-MPS, it is abled to obtain WAT with more unilocular and significantly larger (≈40%) lipid droplets compared to iADIPO in 2D culture, increased insulin responsiveness of glucose uptake (≈2-3 fold), fatty acid uptake (≈3-6 fold), and ≈40% suppressing of stimulated lipolysis giving a dynamic range that is competent to current in vivo and ex vivo models, allowing to identify both insulin sensitizers and desensitizers.

Biosensors are devices that combine a biological material with a suitable platform for detection of pathogenic organisms, carcinogenic, mutagenic, and/or toxic chemicals or for reporting a biological effect. In recent years, an enormous number of different types of biosensors have been constructed and developed for several medical applications. The reason for that was primarily due to the numerous advantages and applications that can be offered by biosensors. This review article has been started with demonstrating the power of biosensor technologies versus analytical and conventional techniques. Subsequently, more emphasis has been added on the classification and the role of biosensors in several medical applications such as detection and monitoring of carcinogenic and mutagenic chemicals, reporting of endocrine disrupting compounds, and detection of pathogenic organisms. The most common reporter genes used in biosensors engineering and construction have also been summarized. Prospective strategies and recommendations for the future construction of biosensors have been highlighted.

The last few decades have witnessed diversified in vitro models to recapitulate the architecture and function of living organs or tissues and contribute immensely to advances in life science. Two novel 3D cell culture models: 1) Organoid, promoted mainly by the developments of stem cell biology and 2) Organ-on-a-chip, enhanced primarily due to microfluidic technology, have emerged as two promising approaches to advance the understanding of basic biological principles and clinical treatments. This review describes the comparable distinct differences between these two models and provides more insights into their complementarity and integration to recognize their merits and limitations for applicable fields. The convergence of the two approaches to produce multi-organoid-on-a-chip or human organoid-on-a-chip is emerging as a new approach for building 3D models with higher physiological relevance. Furthermore, rapid advancements in 3D printing and numerical simulations, which facilitate the design, manufacture, and results-translation of 3D cell culture models, can also serve as novel tools to promote the development and propagation of organoid and organ-on-a-chip systems. Current technological challenges and limitations, as well as expert recommendations and future solutions to address the promising combinations by incorporating organoids, organ-on-a-chip, 3D printing, and numerical simulation, are also summarized.

Engineering functional human tissues in vitro is currently limited by difficulty replicating the small caliber, complex connectivity, cellularity, and three-dimensional curvature of the native microvasculature. Multiphoton ablation has emerged as a promising technique for fabrication of microvascular structures with high resolution and full three-dimensional control, but cellularization and perfusion of complex capillary-scale structures has remained challenging. Here, multiphoton ablation combined with guided endothelial cell growth from pre-formed microvessels is used to successfully create perfusable and cellularized organ-specific microvascular structures at anatomic scale within collagen hydrogels. Fabrication and perfusion of model three-dimensional pulmonary and renal microvascular beds is demonstrated, as is replication and perfusion of a brain microvascular unit derived from in vivo data. Successful endothelialization and blood perfusion of a kidney-specific microvascular structure is achieved, using laser-guided angiogenesis. Finally, proof-of-concept hierarchical blood vessels and complex multicellular models are created, using multistep patterning with multiphoton ablation techniques. These successes open new doors for the creation of engineered tissues and organ-on-a-chip devices.

Organ‐on‐a‐chip technology promises to revolutionize how pre‐clinical human trials are conducted. Engineering an in vitro environment that mimics the functionality and architecture of human physiology is essential toward building better platforms for drug development and personalized medicine. However, the complex nature of these devices requires specialized, time consuming, and expensive fabrication methodologies. Alternatives that reduce design‐to‐prototype time are needed, in order to fulfill the potential of these devices. Here, a streamlined approach is proposed for the fabrication of organ‐on‐a‐chip devices with incorporated microactuators, by using an adaptation of xurography. This method can generate multilayered, membrane‐integrated biochips in a matter of hours, using low‐cost benchtop equipment. These devices are capable of withstanding considerable pressure without delamination. Furthermore, this method is suitable for the integration of flexible membranes, required for organ‐on‐a‐chip applications, such as mechanical actuation or the establishment of biological barrier function. The devices are compatible with cell culture applications and present no cytotoxic effects or observable alterations on cellular homeostasis. This fabrication method can rapidly generate organ‐on‐a‐chip prototypes for a fraction of cost and time, in comparison to conventional soft lithography, constituting an interesting alternative to the current fabrication methods., A microfabrication method based on xurography, capable of producing complex multilayered devices with integrated microactuators, suitable for organ‐on‐a‐chip applications, in a matter of hours is described. Microdevices fabricated with the technology are biocompatible and capable of mechanical actuation at physiological levels of strain. The method provides a fast alternative to current soft lithography methods, by reducing fabrication cost and time.

Despite the progress achieved in nanomedicine during the last decade, the translation of new nanotechnology-based therapeutic systems into clinical applications has been slow, especially due to the lack of robust preclinical tissue culture platforms able to mimic the in vivo conditions found in the human body and to predict the performance and biotoxicity of the developed nanomaterials. Organ-on-a-chip (OoC) platforms are novel microfluidic tools that mimic complex human organ functions at the microscale level. These integrated microfluidic networks, with 3D tissue engineered models, have been shown high potential to reduce the discrepancies between the results derived from preclinical and clinical trials. However, there are many challenges that still need to be addressed, such as the integration of biosensor modules for long-time monitoring of different physicochemical and biochemical parameters. In this review, recent advances on OoC platforms, particularly on the preclinical validation of nanomaterials designed for cancer, as well as the current challenges and possible future directions for an end-use perspective are discussed., This work is the result of the project NORTE-01-0145-FEDER-029394, RTChip4Theranostics, and was supported by Programa Operacional Regional do Norte–Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) and by Fundação para a Ciência e Tecnologia (FCT), IP, project reference PTDC/EMD-EMD/29394/2017. The authors also acknowledge the partial financial support by the projects UID/EEA/04436/2020, UID/ EMS/04077/2020, UID/EMS/00532/2020 from FCT; and by the projects NORTE-01-0145-FEDER-030171 (PTDC/EMD-EMD/30171/2017), NORTE01-0145-FEDER-000019, NORTE-01-0145-FEDER-031142, POCI-01-0145- FEDER-028237, funded by NORTE 2020 Portugal Regional Operational Programme, under PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund and by Fundação para a Ciência e Tecnologia (FCT); and by 2014–2020 INTERREG Cooperation Programme Spain–Portugal (POCTEP) through the project 0624_2IQBIONEURO_6_E.

After drug administration, the drugs are absorbed, distributed, metabolized, and excreted (ADME). Because ADME processes affect drug efficacy, various in vitro models have been developed based on the ADME processes. Although these models have been widely accepted as a tool for predicting the effects of drugs, the differences between in vivo and in vitro systems result in high attrition rates of drugs during the development process and remain a major limitation. Recent advances in microtechnology enable more accurate mimicking of the in vivo environment, where cellular behavior and physiological responses to drugs are more realistic; this has led to the development of novel in vitro systems, known as "organ-on-a-chip" systems. The development of organ-on-a-chip systems has progressed to include the reproduction of multiple organ interactions, which is an important step towards "body-on-a-chip" systems that will ultimately predict whole-body responses to drugs. In this review, we summarize the application of microtechnology for the development of in vitro systems that accurately mimic in vivo environments and reconstruct multiple organ models.

Microfluidics, featuring microfabricated structures, is a technology for manipulating fluids at the micrometer scale. The small dimension and flexibility of microfluidic systems are ideal for mimicking molecular and cellular microenvironment, and show great potential in translational research and development. Here, the recent progress of microfluidics in biological and biomedical applications, including molecular analysis, cellular analysis, and chip-based material delivery and biomimetic design is presented. The potential future developments in the translational microfluidics field are also discussed.

Current animal and 2-D cell culture models employed in metastasis research and drug discovery remain poor mimics of human cancer physiology. Here we describe a "metastasis-on-a-chip" system allowing real time tracking of fluorescent colon cancer cells migrating from hydrogel-fabricated gut constructs to downstream liver constructs within a circulatory fluidic device system that responds to environmental manipulation and drug treatment. Devices consist of two chambers in which gut and liver constructs are housed independently, but are connected in series via circulating fluid flow. Constructs were biofabricated with a hyaluronic acid-based hydrogel system, capable of a variety of customizations, inside of which representative host tissue cells were suspended and metastatic colon carcinoma tumor foci were created. The host tissue of the constructs expressed normal epithelial markers, which the tumor foci failed to express. Instead, tumor regions lost membrane-bound adhesion markers, and expressed mesenchymal and proliferative markers, suggesting a metastatic phenotype. Metastatic tumor foci grew in size, eventually disseminating from the intestine construct and entering circulation, subsequently reaching in the liver construct, thus mimicking some of the migratory events observed during metastasis. Lastly, we demonstrated the ability to manipulate the system, including chemically modulating the hydrogel system mechanical properties and administering chemotherapeutic agents, and evaluated the effects of these parameters on invasive tumor migration. These results describe the capability of this early stage metastasis-on-a-chip system to model several important characteristics of human metastasis, thereby demonstrating the potential of the platform for making meaningful advances in cancer investigation and drug discovery. Biotechnol. Bioeng. 2016;113: 2020-2032. © 2016 Wiley Periodicals, Inc.

Despite the complexity and structural sophistication that 3D organoid models provide, their lack of vascularization and perfusion limit the capability of these models to recapitulate organ physiology effectively. A microfluidic platform named IFlowPlate is engineered, which can be used to culture up to 128 independently perfused and vascularized colon organoids in vitro. Unlike traditional microfluidic devices, the vascularized organoid-on-chip device with an "open-well" design does not require any external pumping systems and allows tissue extraction for downstream analyses, such as histochemistry or even in vivo transplantation. By optimizing both the extracellular matrix (ECM) and the culture media formulation, patient-derived colon organoids are co-cultured successfully within a self-assembled vascular network, and it is found that the colon organoids grow significantly better in the platform under constant perfusion versus conventional static condition. Furthermore, a colon inflammation model with an innate immune function where circulating monocytes can be recruited from the vasculature, differentiate into macrophage, and infiltrate the colon organoids in response to tumor necrosis factor (TNF)- inflammatory cytokine stimulation is developed using the platform. With the ability to grow vascularized colon organoids under intravascular perfusion, the IFlowPlate platform could unlock new possibilities for screening potential therapeutic targets or modeling relevant diseases.

Retinal cells within neurovascular units generate the blood-retinal barrier (BRB) to regulate the local retinal microenvironment and to limit access to inflammatory cells. Breakdown of the endothelial junctional complexes in the BRB negatively affects neuronal signaling and ultimately causes vision loss. As new therapeutics are being developed either to prevent barrier disruption or to restore barrier function, access to physiologically relevant human in vitro tissue models that recapitulate important features of barrier biology is essential for disease modeling, target validation, and toxicity assessment. Here, a tunable organ-on-a-chip model of the retinal microvasculature using human retinal microvascular endothelial cells with integrated flow is described. Automated imaging and image analysis methods are employed for facile screening of leakage mediators and cytokine inhibitors on barrier properties. The developed retinal microvasculature-on-a-chip will enable improved understanding of BRB biology and provide an additional tool for drug discovery.

Exposure of aged mice to a young systemic milieu revealed remarkable rejuvenation effects on aged tissues, including skeletal muscle. Although some candidate factors have been identified, the exact identity and the underlying mechanisms of putative rejuvenating factors remain elusive, mainly due to the complexity of in vivo parabiosis. Here, we present an in vitro muscle parabiosis system that integrates young- and old-muscle stem cell vascular niche on a three-dimensional microfluidic platform designed to recapitulate key features of native muscle stem cell microenvironment. This innovative system enables mechanistic studies of cellular dynamics and molecular interactions within the muscle stem cell niche, especially in response to conditional extrinsic stimuli of local and systemic factors. We demonstrate that vascular endothelial growth factor (VEGF) signaling from endothelial cells and myotubes synergistically contribute to the rejuvenation of the aged muscle stem cell function. Moreover, with the adjustable on-chip system, we can mimic both blood transfusion and parabiosis and detect the time-varying effects of anti-geronic and pro-geronic factors in a single organ or multi-organ systems. Our unique approach presents a complementary in vitro model to supplement in vivo parabiosis for identifying potential anti-geronic factors responsible for revitalizing aging organs.

In recent years, engineering of various human tissues in microphysiologically relevant platforms, known as organs-on-chips (OOCs), has been explored to establish in vitro tissue models that recapitulate the microenvironments found in native organs and tissues. However, most of these models have overlooked the important roles of immune cells in maintaining tissue homeostasis under physiological conditions and in modulating the tissue microenvironments during pathophysiology. Significantly, gradual progress is being made in the development of more sophisticated microphysiologically relevant human-based OOC models that allow the studies of the key biophysiological aspects of specific tissues or organs, interactions between cells (parenchymal, vascular, and immune cells) and their extracellular matrix molecules, effects of native tissue architectures (geometry, dynamic flow or mechanical forces) on tissue functions, as well as unravelling the mechanism underlying tissue-specific diseases and drug testing. In this Progress Report, we discuss the different components of the immune system, as well as immune OOC platforms and immunocompetent OOC approaches that have simulated one or more components of the immune system. We also outline the challenges to recreate a fully functional tissue system in vitro with a focus on the incorporation of the immune system.

The inadequacy of conventional cell-monolayer planar cultures and animal experiments in predicting the toxicity and clinical efficacy of drug candidates has led to an imminent need for in vitro methods with the ability to better represent in vivo conditions and facilitate the systematic investigation of drug candidates. Recent advances in 3D bioprinting have prompted the precise manipulation of cells and biomaterials, rendering it a promising technology for the construction of in vitro tissue/organ models and drug screening devices. This review presents state-of-the-art in vitro methods used for preclinical drug screening and discusses the limitations of these methods. In particular, the significance of constructing 3D in vitro tissue/organ models and microfluidic analysis devices for drug screening is emphasized, and a focus is placed on the grafting process of 3D bioprinting technology to the construction of such models and devices. The in vitro methods for drug screening are generalized into three types: mini-tissue, organ-on-a-chip, and tissue/organ construct. The revolutionary process of the in vitro methods is demonstrated in detail, and relevant studies are listed as examples. Specifically, the tumor model is adopted as a precedent to illustrate the possible grafting of 3D bioprinting to antitumor drug screening.

Bioprinting holds great promise towards engineering functional cardiac tissue constructs for regenerative medicine and as drug test models. However, it is highly limited by the choice of inks that require maintaining a balance between the structure and functional properties associated with the cardiac tissue. In this regard, we have developed a novel and mechanically robust biomaterial-ink based on non-mulberry silk fibroin protein. The silk-based ink demonstrated suitable mechanical properties required in terms of elasticity and stiffness (~40 kPa) for developing clinically relevant cardiac tissue constructs. The ink allowed the fabrication of stable anisotropic scaffolds using a dual crosslinking method, which were able to support formation of aligned sarcomeres, high expression of gap junction proteins as connexin-43, and maintain synchronously beating of cardiomyocytes. The printed constructs were found to be non-immunogenic in vitro and in vivo. Furthermore, delving into an innovative method for fabricating a vascularized myocardial tissue-on-a-chip, the silk-based ink was used as supporting hydrogel for encapsulating human induced pluripotent stem cell derived cardiac spheroids (hiPSC-CSs) and creating perfusable vascularized channels via an embedded bioprinting technique. We confirmed the ability of silk-based supporting hydrogel towards maturation and viability of hiPSC-CSs and endothelial cells, and for applications in evaluating drug toxicity.

The immune system has remarkable capabilities to combat disease with exquisite selectivity. This feature has enabled vaccines that provide protection for decades, and more recently, advances in immunotherapies that can cure some cancers. Greater control over how immune signals are presented, delivered, and processed will help drive even more powerful options that are also safe. Such advances will be underpinned by new tools that probe how immune signals are integrated by immune cells and tissues. Biomaterials are valuable resources to support this goal, offering robust, tunable properties. This review highlights the growing role of biomaterials as tools to dissect immune function in fundamental and translational contexts. These technologies can serve as tools to understand the immune system across molecular, cellular, and tissue length scales. A common theme is exploiting biomaterial features to rationally direct how specific immune cells or organs encounter a signal. This precision strategy, enabled by distinct material properties, allows isolation of immunological parameters or processes in a way that is challenging with conventional approaches. The utility of these capabilities is demonstrated through examples in vaccines for infectious disease and cancer immunotherapy, as well as settings of immune regulation that include autoimmunity and transplantation.

Cancer is one of the leading causes of death worldwide, despite the large efforts to improve the understanding of cancer biology and development of treatments. The attempts to improve cancer treatment are limited by the complexity of the local milieu in which cancer cells exist. The tumor microenvironment (TME) consists of a diverse population of tumor cells and stromal cells with immune constituents, microvasculature, extracellular matrix components, and gradients of oxygen, nutrients, and growth factors. The TME is not recapitulated in traditional models used in cancer investigation, limiting the translation of preliminary findings to clinical practice. Advances in 3D cell culture, tissue engineering, and microfluidics have led to the development of "cancer-on-a-chip" platforms that expand the ability to model the TME in vitro and allow for high-throughput analysis. The advances in the development of cancer-on-a-chip platforms, implications for drug development, challenges to leveraging this technology for improved cancer treatment, and future integration with artificial intelligence for improved predictive drug screening models are discussed.