The extracellular matrix (ECM) comprises a complex milieu of proteins and other growth factors that provide mechanical, biophysical, and biochemical cues to cells. The ECM is organ specific, and its ...detailed composition varies across organs. Bioinks are material formulations and biological molecules or cells processed during a bioprinting process. Organ-derived decellularized ECM (dECM) bioinks have emerged as arguably the most biomimetic bioinks. Here, we review bioinks derived from different decellularized organs, the techniques used to obtain these bioinks, and the characterization methods used to evaluate their quality. We emphasize that obtaining a good-quality bioink depends on the choice of organ, animal, and decellularization method. Finally, we explore potential large-scale applications of bioinks and challenges in manufacturing such bioinks.
Many individual ECM components, including collagen, fibrin, gelatin, alginate, and others, have been used as bioinks, but the natural ECM offers many physical, chemical, and biological cues that are difficult to recapitulate using only a single or just a few components. dECM bioinks could be revolutionary in terms of offering a complete biomimetic ink.
dECM bioinks could be used to print more functional and relevant tissues, which would have applications for drug screening, disease modeling, and regenerative medicine.
A dECM bioink is a softer material with lower mechanical strength; therefore, to ensure the integrity of the bioprinted structure, it is important to fine-tune the mechanical properties of this bioink by mixing it with either natural or synthetic materials.
cell culture models are emerging as promising tools to understand human development, disease progression, and provide reliable, rapid and cost-effective results for drug discovery and screening. In ...recent years, an increasing number of
models with complex organization and controlled microenvironment have been developed to mimic the
organ structure and function. The invention of organoids, self-organized organ-like cell aggregates that originate from multipotent stem cells, has allowed a whole new level of biomimicry to be achieved. Microfluidic organoid-on-a-chip platforms can facilitate better nutrient and gas exchange and recapitulate 3D tissue architecture and physiology. They have the potential to transform the landscape of drug development and testing. In this review, we discuss the challenges in the current organoid models and describe the recent progress in the field of organoid-on-a-chip.
Different three-dimensional (3D) printing techniques are being increasingly used to produce medical apparatus due to their ability to print intended designs with high dimensional accuracy. Indeed, ...the major credit for the broad use of 3D printing techniques in medical fields stems from the ability of this method to prepare patient-matched devices due to the conventional manufacturing methods limitations such as economically inefficiency and multiple steps processing for complex geometries. This review manuscript aims to present brief insights of various 3D printing concepts and technologies used in the medical field. Biomaterials and bioprinting are pinpointed. Finally, the pharmaceutical potentials of 3D printing are discussed.
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•The contributions of Three-dimensional Printing in Healthcare and Medicine.•A comprehensive review of technologies types used in 3D printing.•Discussing the foremost applications and approaches to Bio-materials-based Additive Manufacturing technology.•Addressing the advantages of three-dimensional printing in relation to medical implants.
Dry eye disease is a common clinical problem encountered by ophthalmologists worldwide. Interest in this entity has increased in recent years due to the consequences it has on the ocular surface ...after any surface procedure. With changing times, several new factors have come to light that can influence this disease. The effect of the COVID-19 pandemic has also been greatly felt, with a range of causes, starting from increased screen work to inflammatory processes, exacerbating the condition in many. With changes in the concepts of the etiopathogenesis of the disease, a paradigm shift has taken place in the approaches to treatment. More researchers are in favor of a new tear film-oriented approach that tries to localize the disease to a single component in the tear film. Innovation of newer techniques for the treatment of meibomian gland disease has also made its foray into clinical ophthalmology. Newer drug formulations and molecules are underway to better treat the inflammatory component of the disease. Many other receptors and targets for the treatment of dry eyes are being researched. This review hopes to provide a succinct, narrative summary of the relevant research on dry eye disease to date to increase awareness about the nature and future course of this disease and its management.
Industry 4.0 integrates the physical, digital, and biological realms by applying digital automation in systems, processes, and manufacturing facilities. Industry 4.0 is actively shaping the ...development of intelligent food processing industries in cultivated meat (CM) sector. This integration plays a crucial role in accelerating progress within the global CM sector, facilitating the achievement of its objectives related to food sustainability, security, human health, environmental concerns, and hygiene. Incorporating Industry 4.0 into CM manufacturing systems empowers upstream and downstream production processes to become more intelligent and capable of self‐optimisation. However, enabling rapid adoption of Industry 4.0 by emerging startups and small to medium‐sized enterprises in the CM industry necessitates a thorough understanding of prerequisites and evaluation of technological and biological limitations. Challenges include the substantial initial costs associated with establishing Industry 4.0 infrastructure, robust cybersecurity measures to ensure effective risk management, and acquiring skilled professionals proficient in both operational and maintenance roles. Integrating Industry 4.0 with the evolving CM sector presents an exciting opportunity to foster business‐to‐business investments across various domains, including local markets, export opportunities, and the broader global consumer ecosystem.
Integrating Industry 4.0 with the evolving cultivated meat sector presents an exciting opportunity to foster business‐to‐business investments across various domains, including local markets, export opportunities, and the broader global consumer ecosystem.
Disruption of the blood–brain barrier (BBB) leads to various neurovascular diseases. Development of therapeutics required to cross the BBB is difficult due to a lack of relevant in vitro models. We ...have developed a three‐dimensional (3D) microfluidic BBB chip (BBBC) to study cell interactions in the brain microvasculature and to test drug candidates of neurovascular diseases. We isolated primary brain microvascular endothelial cells (ECs), pericytes, and astrocytes from neonatal rats and cocultured them in the BBBC. To mimic the 3D in vivo BBB structure, we used type I collagen hydrogel to pattern the microchannel via viscous finger patterning technique to create a matrix. ECs, astrocytes, and pericytes were cocultured in the collagen matrix. The fluid flow in the BBBC was controlled by a pump‐free strategy utilizing gravity as driving force and resistance in a paper‐based flow resistor. The primary cells cultured in the BBBC expressed high levels of junction proteins and formed a tight endothelial barrier layer. Addition of tumor necrosis factor alpha to recapitulate neuroinflammatory conditions compromised the BBB functionality. To mitigate the neuroinflammatory stimulus, we treated the BBB model with the glucocorticoid drug dexamethasone, and observed protection of the BBB. This BBBC represents a new simple, cost‐effective, and scalable in vitro platform for validating therapeutic drugs targeting neuroinflammatory conditions.
A microfluidic platform that mimics the BBB structure under physiological conditions. The fluid flow in the collagen‐lined microchannel is controlled by a pump‐free strategy. The 3D dynamic co‐culture of primary endothelial cells, pericytes and astrocytes forms a tight layer of endothelial barrier inside the BBB chip.
Cell-derived matrices (CDM) are the decellularised extracellular matrices (ECM) of tissues obtained by the laboratory culture process. CDM is developed to mimic, to a certain extent, the properties ...of the needed natural tissue and thus to obviate the use of animals. The composition of CDM can be tailored for intended applications by carefully optimising the cell sources, culturing conditions and decellularising methods. This unique advantage has inspired the increasing use of CDM for biomedical research, ranging from stem cell niches to disease modelling and regenerative medicine. However, while much effort is spent on extracting different types of CDM and exploring their utilisation, little is spent on the scale-up aspect of CDM production. The ability to scale up CDM production is essential, as the materials are due for clinical trials and regulatory approval, and in fact, this ability to scale up should be an important factor from the early stages. In this review, we first introduce the current CDM production and characterisation methods. We then describe the existing scale-up technologies for cell culture and highlight the key considerations in scaling-up CDM manufacturing. Finally, we discuss the considerations and challenges faced while converting a laboratory protocol into a full industrial process. Scaling-up CDM manufacturing is a challenging task since it may be hindered by technologies that are not yet available. The early identification of these gaps will not only quicken CDM based product development but also help drive the advancement in scale-up cell culture and ECM extraction.
•Bioprinting can be used to fabricate organ-on-a-chip models owing to its ability to print multiple materials and cell types simultaneously with good spatial resolution and reproducibility.•The ...combination of bioprinting with microfluidic organ-on-a-chip technologies enables the creation of a biomimetic microenvironment with a heterogeneous 3D structure.•Functional tissue structure can be printed directly on microfluidic chips using computerized printing programs.
Bioprinting is a revolutionary technology to assemble scaffolds for growing tissues. Microfluidic organs-on-a-chip is a useful platform with widespread applications mainly in drug screening and pathological studies. Organ-on-a-chip models are created to recapitulate the structural, microenvironmental and physiological functions of human organs. Recently, bioprinting has been applied to fabricate organ-on-a-chip models owing to its ability to print multiple materials and cell types simultaneously with good spatial resolution and reproducibility. This enables the creation of a biomimetic microenvironment with heterogeneous 3D structures. Functional vascularized tissue structure can be printed directly enabling fluid flow for transport of nutrition, gaseous exchange and removal of waste. We examine the integration of microfluidic and bioprinting technologies for organ-on-a-chip applications and discuss the future trends and challenges.
We have developed a microfluidic system suitable to be incorporated with a metabolic imaging method to monitor the drug response of cells cultured on a chip. The cells were perfusion-cultured to ...mimic the blood flow in vivo. Label-free optical measurements and imaging of nicotinamide adenine dinucleotide and flavin adenine dinucleotide fluorescence intensity and morphological changes were evaluated non-invasively. Drug responses calculated using redox ratio imaging were compared with the drug toxicity testing results obtained with a traditional well-plate system. We found that our method can accurately monitor the cell viability and drug response and that the IC50 value obtained from imaging analysis was sensitive and comparable with a commonly used cell viability assay: MTS (3–(4,5-dimethylthiazol-2-yl)–5–(3-carboxymethoxyphenyl)-2–(4-sulfo-phenyl)-2H-tetrazolium) assay. Our method could serve as a fast, non-invasive, and reliable way for drug screening and toxicity testing as well as enabling real-time monitoring of in vitro cultured cells.
Brain microvascular cells such as brain microvascular endothelial cells (BMEC), pericytes, and astrocytes are major components of the blood–brain barrier (BBB). The BBB regulates substance transport ...from the blood into the brain and is involved in the progression of many neurological diseases. This has led to significant interest in developing in vitro models to study the characteristics of brain primary microvascular cells and the BBB. However, BMECs only account for 1–2% of the total cell population in the brain and are extremely difficult to obtain. We report a microfluidic immunopanning chip (MIC) for the on-chip isolation and purification of multiple types of primary brain microvascular cells simultaneously. The cell isolation efficiency and purity achieved with the MIC are higher compared with conventional bench-top immunopanning method. We incorporated microcarriers in the MIC as a means to increase cell capturing efficiency and a substrate for subsequent cell culture. With low reagents consumption, multiplexing capabilities, and high isolation efficiency, the MIC shows great potential as a tool for rare cell isolation and have potential broader applications in cell therapy.
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