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Therapeutic options for neurological disorders currently remain limited. The intrinsic complexity of the brain architecture prevents potential therapeutics from reaching their cerebral target, thus limiting their efficacy. Recent advances in microfluidic technology and organ-on-chip systems have enabled the development of a new generation of in vitro platforms that can recapitulate complex in vivo microenvironments and physiological responses. In this context, microfluidic-based in vitro models of the blood–brain barrier (BBB) are of particular interest as they provide an innovative approach for conducting research related to the brain, including modeling of neurodegenerative diseases and high-throughput drug screening. Here, we present the most recent advances in BBB-on-chip devices and examine validation steps that will strengthen their future applications. Microfluidic-based blood–brain barrier-on-chip (μBBB) technology is a powerful approach to study the physiological function of the BBB in vitro and to facilitate drug discovery targeting brain disorders.Mimicry of the complexity of multiple cell crosstalk and thin extracellular matrix as basal membrane are essential but challenging. Different biomaterials and chip designs have been explored in the fabrication of μBBBs.Other key features such as shear stress, cell type/origin, and cell co-culture spatial configuration must be carefully controlled and selected. Appropriate BBB permeability assays and parameters (e.g., TEER measurement, small molecule drugs, and fluorescent probes) should be standardized and compared with in vivo data.μBBBs hold great potential in disease modeling, drug discovery, neurotoxicity screening, and personalized medicine applications.

The gut microbiota remains relatively stable during adulthood; however, certain intrinsic and environmental factors can lead to microbiota dysbiosis. Its restoration towards a healthy condition using best-suited prebiotics requires previous development of in vitro models for evaluating their functionality. Herein, we carried out fecal cultures with microbiota from healthy normal-weight and morbid obese adults. Cultures were supplemented with different inulin-type fructans (1-kestose, Actilight, P95, Synergy1 and Inulin) and a galactooligosaccharide. Their impact on the gut microbiota was assessed by monitoring gas production and evaluating changes in the microbiota composition (qPCR and 16S rRNA gene profiling) and metabolic activity (gas chromatography). Additionally, the effect on the bifidobacterial species was assessed (ITS-sequencing). Moreover, the functionality of the microbiota before and after prebiotic-modulation was determined in an in vitro model of interaction with an intestinal cell line. In general, 1-kestose was the compound showing the largest effects. The modulation with prebiotics led to significant increases in the Bacteroides group and Faecalibacterium in obese subjects, whereas in normal-weight individuals, substantial rises in Bifidobacterium and Faecalibacterium were appreciated. Notably, the results obtained showed differences in the responses among the tested compounds but also among the studied human populations, indicating the need for developing population-specific products.

Increasing data on the infection indicate that maternal infections are severe. Under the realms of vaccine development, virus‐like particles (VLP)/nanoparticles (NPs) hold the promise of targeted control of therapeutics transfer across the placental barrier with the potential to trigger innate immune responses. Though the placenta is known to act as a barrier against exogenous materials, viruses exploit the transport systems and overcome the barrier properties. VLPs can be strategically designed to obtain the necessary mechanisms for navigation across the placenta and immune response. However, several knowledge gaps on the chemical, viral transmission strategies and the host defense response exist owing to the highly dynamic etiology of the placental barrier. This further complicates the toxicological analysis of the developed therapeutics. Herein, placental physiology and functions are discussed in significance with chemical toxicology, viral infections, and the host defense. Further, the promising applications of VLPs and perspective on their design to overcome the placental gatekeeper to gain the necessary immune response or therapy are provided. Finally, a holistic approach to various bioengineering models for studying chemical toxicants, viral infections, and effects of VLPs is provided to facilitate better translation of these VLPs to clinical applications. Herein, placental physiology and functions are discussed in significance with chemical toxicology, viral infections, and the host defense. Further, the promising applications of virus‐like particles and perspective on their design to overcome the placental gatekeeper to gain the necessary immune response or therapy are provided.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive memory loss and cognitive impairment, thereby disrupting the performance of daily activities. Numerous therapeutics have shown efficacy in animal AD models but failed in human patients. The key to understanding the etiology of AD lies in the development of effective disease models, which can ideally recapitulate all characteristics of the disease. Over the years, different approaches including in vitro, in vivo, and in silico models are able to resemble certain features of AD. In this review, the significance of different in vitro models including their merits and limitations in modeling AD is discussed, which will give a better perspective on the development of a comprehensive model that can mimic human AD. This starts with a brief introduction to AD and its pathology. Then it mainly focuses on the two‐dimensional, three‐dimensional and microfluidic in vitro models of AD that have made significant advancements in understanding AD pathology and aiding in screening effective therapeutics. Several 3D neural tissue engineering models developed in the last two decades along with a discussion on the future prospects in the development of efficient in vitro AD models are further highlighted. This work reviews the 2D, 3D, and microfluidic in vitro models of AD that have made significant advancements in not only understanding AD pathology but also aiding in screening effective therapeutics.

Various systemic metabolic diseases arise from prolonged crosstalk across multiple organs, triggering serious impairments in various physiological systems. These diseases are intricate systemic pathologies characterized by complex mechanisms and an unclear etiology, making the treatment challenging. Efforts have been made to develop in vitro models to understand these diseases and devise new treatments. However, there are limitations in reconstructing the causal relationships between diseases and interorgan crosstalk, including the tissue‐specific microenvironment. Alternatively, multi‐organ microphysiological systems (MOMPS) present new possibilities for capturing the complexity of systemic metabolic diseases by replicating human microphysiology and simulating diverse interorgan crosstalk. Controlled interactions and scalable representations of biological complexity in MOMPS offer a more accurate portrayal of organ interactions, enabling the identification of novel relationships between organ crosstalk, metabolism, and immunity. This, in turn, can yield valuable insights into disease mechanisms and drug development research and enhance the efficiency of preclinical studies. In this review, the examples and technical capabilities of MOMPS pathological modeling for various diseases are discussed, leveraging state‐of‐the‐art biofabrication technology of MOMPS. It evaluates the current opportunities and challenges in this field. Multi‐organ microphysiological systems (MOMPS) replicate human microphysiology and interorgan crosstalk. The precise fabrication of MOMPS requires various elements, including biomaterials, cell sources, accurate organ crosstalk, biofabrication techniques, and humanized design. The MOMPS enhances the understanding of systemic metabolic disease mechanisms, improves drug development, and increases the efficiency of preclinical studies by capturing the complexity of organ interactions and tissue‐specific microenvironments..

The synovium plays a crucial role in joint function and is a primary site of pathology in inflammatory joint diseases, such as rheumatoid arthritis (RA). Immune‐mediated inflammatory diseases (IMIDs), including RA, are becoming increasingly prevalent worldwide. However, the development of effective treatments remains hindered by the limitations of preclinical modeling techniques. Traditional methods, such as 2D in vitro monolayer cultures and animal models, often fail to replicate the complexity of human tissues. To address these challenges, tissue engineering (TE) and biofabrication strategies have emerged as promising alternatives. These approaches enable the creation of 3D in vitro models that better mimic physiological conditions. Techniques like 3D bioprinting allow researchers to replicate cellular interactions and the extracellular matrix, improving the accuracy of disease models. The application of 3D models in therapy development, drug screening, and personalized medicine has grown significantly. These platforms offer valuable insights into IMID pathophysiology by simulating relevant microenvironments. This review examines current synovium models used in IMID research and explores future directions in TE and 3D biofabrication. Additionally, the impact of inflammation on tissues and discuss the clinical potential of 3D disease models to address current disregarded aspects of coexistent diseases is highlighted. The synovium is key to joint function but is often affected by diseases like rheumatoid arthritis. Finding better treatments is challenging because current lab models do not fully mimic real tissues. New 3D technologies, like bioprinting, offer better methods to study these diseases, improve drug testing, and develop personalized treatments, bringing hope for future therapies.

This study presents an in vitro model using Caco‐2 cells that can mimic the bioadhesion properties of the human intestinal epithelium, aiming to reduce the use of animal tissues, in line with the 3Rs principle—replacement, reduction, and refinement. Specifically, a texture analyzer was used to assess the bioadhesive strength of hydrogels (i.e., alginate (Alg), chitosan (Chit), and gelatin (Gel)) under various applied forces (20–200 mN) and contact times (120–420 s). The results demonstrate that the in vitro model effectively predicts the bioadhesive strength of the tested hydrogels to ex vivo tissues (i.e., from mice, sheep, and pigs), including the effects of applied force and contact time. Also provided is an analysis of the effect of microvilli morphology on bioadhesion where an inverse relationship was observed between microvilli linear density and bioadhesion strength, explaining the variability in results across animal models. This Caco‐2‐based model offers a practical, accessible, and cost‐effective alternative to current ex vivo methods used for measuring bioadhesion fracture strength. It can be integrated into standardized testing protocols, providing a more ethical and scientifically robust approach to advancing bioadhesive drug delivery system research. This study introduces an in vitro Caco‐2 cell model for measuring intestinal bioadhesion, offering an alternative to animal‐based ex vivo methods. Using a texture analyzer, the model predicts the bioadhesive properties of materials under varying forces and durations, replicating ex vivo findings. Moreover, the study provides valuable insights into the influence of microvilli morphology on bioadhesion.

Herein, intestinal, skin, and pulmonary in vitro tissue models based on electrospun membranes of poly(ε‐caprolactone) (PCL) and cellulose acetate (CA), cellulose acetate phthalate (CAP), ethylcellulose (EC), or methylcellulose (MC) are presented. Physicochemical characterization and biocompatibility analyses of the scaffolds are carried out using colorectal adenocarcinoma cells (intestine), keratinocytes and fibroblasts (skin), and bronchial and alveolar epithelial cells (lung). PCL, PCL:CA, and PCL:EC are composed of nanofibers, whereas PCL:CAP and PCL:MC scaffolds comprise a combination of micro‐ and nanofibers. PCL, PCL:CA, PCL:CAP, and PCL:EC samples demonstrate water contact angles greater than 90° and are, therefore, hydrophobic, while PCL:MC mats display a hydrophilic behavior. In intestinal models, cells adhere and proliferate on all scaffolds; in turn, studies with skin cell models reveal that PCL:CA and PCL:CAP blends outperform all other substrates. Lung cell models show that, while 16HBE cells adhere to and proliferate in PCL, PCL:CA, PCL:EC, and PCL:MC scaffolds, A549 cells only have the same biological response on PCL, PCL:CA, and PCL:MC. In summary, all fibrous meshes prepared are biocompatible toward most cell types tested, thus suggesting the potential of PCL‐cellulose derivative blends as substrates suitable for in vitro epithelial tissue modeling and toxicity screening. Herein, the potential of different electrospun fibrous scaffolds for intestinal, skin, and lung in vitro tissue modeling is investigated. Electrospun membranes of poly(ε‐caprolactone), cellulose acetate (CA), cellulose acetate phthalate (CAP), ethylcellulose (EC), or methylcellulose (MC) are synthesized and physicochemically characterized, followed by biocompatibility analyses with epithelial cell lines. All fibrous meshes prepared are biocompatible, with cell‐specific differences.

Testing of all manufactured products and their ingredients for eye irritation is a regulatory requirement. In the last two decades, the development of alternatives to the in vivo Draize eye irritation test method has substantially advanced due to the improvements in primary cell isolation, cell culture techniques, and media, which have led to improved in vitro corneal tissue models and test methods. Most in vitro models for ocular toxicology attempt to reproduce the corneal epithelial tissue which consists of 4-5 layers of non-keratinized corneal epithelial cells that form tight junctions, thereby limiting the penetration of chemicals, xenobiotics, and Pharmaceuticals. Also, significant efforts have been directed toward the development of more complex threedimensional (3D) equivalents to study wound healing, drug permeation, and bioavailabiliry. This review focuses on in vitro reconstructed 3D corneal tissue models and their utilization in ocular toxicology as well as their application to pharmacology and ophthalmic research. Current human 3D corneal epithelial cell culture models have replaced in vivo animal eye irritation tests for many applications, and substantial validation efforts are in progress to verify and approve alternative eye irritation tests for widespread use. The validation of drug absorption models and further development of models and test methods for many ophthalmic and ocular disease applications is required.

Osteoarthritis (OA) is a progressive and disabling musculoskeletal disease affecting millions of people and resulting in major healthcare costs worldwide. It is the most common form of arthritis, characterised by degradation of the articular cartilage, formation of osteophytes, subchondral sclerosis, synovial inflammation and ultimate loss of joint function. Understanding the pathogenesis of OA and its multifactorial aetiology will lead to the development of effective treatments, which are currently lacking. Two-dimensional (2D) in vitro tissue models of OA allow affordable, high-throughput analysis and stringent control over specific variables. However, they are linear in fashion and are not representative of physiological conditions. Recent in vitro studies have adopted three-dimensional (3D) tissue models of OA, which retain the advantages of 2D models and are able to mimic physiological conditions, thereby allowing investigation of additional variables including interactions between the cells and their surrounding extracellular matrix. Numerous spontaneous and induced animal models are used to reproduce the onset and monitor the progression of OA based on the aetiology under investigation. This therefore allows elucidation of the pathogenesis of OA and will ultimately enable the development of novel and specific therapeutic interventions. This review summarises the current understanding of in vitro and in vivo OA models in the context of disease pathophysiology, classification and relevance, thus providing new insights and directions for OA research.