We developed an innovative millifluidic organ-on-a-chip device, named MINERVA 2.0, that is optically accessible and suitable to serial connection. In the present work, we evaluated MINERVA 2.
View Article and Find Full Text PDFLiver-related drug metabolism is a key aspect of pharmacokinetics and possible toxicity. From this perspective, the availability of advanced in vitro models for drug testing is still an open need, also to the end of reducing the burden of in vivo experiments. In this scenario, organ-on-a-chip is gaining attention as it couples a state-of-the art in vitro approach to the recapitulation of key in vivo physiological features such as fluidodynamics and a tri-dimensional cytoarchitecture.
View Article and Find Full Text PDFEpilepsy is a common neurological disease characterized by the enduring predisposition of the brain to generate seizures. Among the recognized causes, a role played by the gut microbiota in epilepsy has been hypothesized and supported by new investigative approaches. To dissect the microbiota-gut-brain (MGB) axis involvement in epilepsy, in vitro modeling approaches arouse interest among researchers in the field.
View Article and Find Full Text PDFThe Organ-on-a-Chip (OoC) technology shows great potential to revolutionize the drugs development pipeline by mimicking the physiological environment and functions of human organs. The translational value of OoC is further enhanced when combined with patient-specific induced pluripotent stem cells (iPSCs) to develop more realistic disease models, paving the way for the development of a new generation of patient-on-a-chip devices. iPSCs differentiation capacity leads to invaluable improvements in personalized medicine.
View Article and Find Full Text PDFThe way the human microbiota may modulate neurological pathologies is a fascinating matter of research. Epilepsy is a common neurological disorder, which has been largely investigated in correlation with microbiota health and function. However, the mechanisms that regulate this apparent connection are scarcely defined, and extensive effort has been conducted to understand the role of microbiota in preventing and reducing epileptic seizures.
View Article and Find Full Text PDFChondroitin sulfates (CS) are a class of sulfated glycosaminoglycans involved in many biological processes. Several studies reported their protective effect against neurodegenerative conditions like Alzheimer's disease. CS are commonly derived from animal sources, but ethical concerns, the risk of contamination with animal proteins, and the difficulty in controlling the sulfation pattern have prompted research towards non-animal sources.
View Article and Find Full Text PDFThe gut microbiota directly impacts the pathophysiology of different human body districts. Consequently, microbiota investigation is an hot topic of research and its in vitro culture has gained extreme interest in different fields. However, the high sensitivity of microbiota to external stimuli, such as sampling procedure, and the physicochemical complexity of the gut environment make its in vitro culture a challenging task.
View Article and Find Full Text PDFHuman microbiota communicates with its host by secreting signaling metabolites, enzymes, or structural components. Its homeostasis strongly influences the modulation of human tissue barriers and immune system. Dysbiosis-induced peripheral immunity response can propagate bacterial and pro-inflammatory signals to the whole body, including the brain.
View Article and Find Full Text PDFRecently, researchers have focused on the role of gut microbiota on human health and reported the existence of a bidirectional relationship between intestinal microbiota and the brain, referred to as microbiota-gut-brain axis (MGBA). In this context, the development of an organ-on-a-chip platform recapitulating the main players of the MGBA would help in the investigations of the biochemical mechanisms involved. In this work, we focused on the development of a new, hydrogel-based, 3D brain-like tissue model to be hosted in the brain compartment of the aforementioned platform.
View Article and Find Full Text PDFRecent findings have highlighted an interconnection between intestinal microbiota and the brain, referred to as microbiota-gut-brain axis, and suggested that alterations in microbiota composition might affect brain functioning, also in Alzheimer's disease. To investigate microbiota-gut-brain axis biochemical pathways, in this work we developed an innovative device to be used as modular unit in an engineered multi-organ-on-a-chip platform recapitulating the main players of the microbiota-gut-brain axis, and an innovative three-dimensional model of brain cells based on collagen/hyaluronic acid or collagen/poly(ethylene glycol) semi-interpenetrating polymer networks and β-amyloid precursor protein-Swedish mutant-expressing H4 cells, to simulate the pathological scenario of Alzheimer's disease. We set up the culturing conditions, assessed cell response, scaled down the three-dimensional models to be hosted in the organ-on-a-chip device, and cultured them both in static and in dynamic conditions.
View Article and Find Full Text PDFThe steady increase in life-expectancy of world population, coupled to many genetic and environmental factors (for instance, pre- and post-natal exposures to environmental neurotoxins), predispose to the onset of neurodegenerative diseases, whose prevalence is expected to increase dramatically in the next years. Recent studies have proposed links between the gut microbiota and neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Human body is a complex structure where bacterial and human cells are almost equal in numbers, and most microbes are metabolically active in the gut, where they potentially influence other target organs, including the brain.
View Article and Find Full Text PDFWe are accumulating evidence that intestinal microflora, collectively named gut microbiota, can alter brain pathophysiology, but researchers have just begun to discover the mechanisms of this bidirectional connection (often referred to as microbiota-gut-brain axis, MGBA). The most noticeable hypothesis for a pathological action of gut microbiota on the brain is based on microbial release of soluble neurotransmitters, hormones, immune molecules and neuroactive metabolites, but this complex scenario requires reliable and controllable tools for its causal demonstration. Thanks to three-dimensional (3D) cultures and microfluidics, engineered in models could improve the scientific knowledge in this field, also from a therapeutic perspective.
View Article and Find Full Text PDFThe liver is a key organ that can communicate with many other districts of the human body. In the last few decades, much interest has focused on the interaction between the liver and the gut microbiota, with their reciprocal influence on biosynthesis pathways and the integrity the intestinal epithelial barrier. Dysbiosis or liver disorders lead to0 epithelial barrier dysfunction, altering membrane permeability to toxins.
View Article and Find Full Text PDFAfter decades of research, the etiology of neurodegenerative disorders such as Alzheimer's or Parkinson's disease is still mostly unknown. Recent findings indicate that the microorganisms in the human gut might be involved in neurodegenerative pathways. Here, we discuss an innovative groundbreaking bioengineering approach that could make a difference in this intriguing scenario.
View Article and Find Full Text PDF: The microbiota-gut brain (MGB) axis is the bidirectional communication between the intestinal microbiota and the brain. An increasing body of preclinical and clinical evidence has revealed that the gut microbial ecosystem can affect neuropsychiatric health. However, there is still a need of further studies to elucidate the complex gene-environment interactions and the role of the MGB axis in neuropsychiatric diseases, with the aim of identifying biomarkers and new therapeutic targets, to allow early diagnosis and improving treatments.
View Article and Find Full Text PDFIntestinal mucus is a biological structure that acts as a barrier between the external environment and the epithelium. It actively selects nutrient and drug intake, regulates the symbiosis with the intestinal microbiota and keeps the epithelium protected from the attack of pathogens. All these functions are closely connected to the chemical and structural complexity of this biological material, on which its viscoelastic and diffusive properties depend.
View Article and Find Full Text PDFHydraulic sealing is a crucial condition for the maintenance of sterility during long term operation of microfluidic bioreactors. We developed a miniaturized optically accessible bioreactor (MOAB) allowing perfused culture of 3D cellularised constructs. In the MOAB, the culture chambers are sealed by magnets that generate a weak static magnetic field (SMF).
View Article and Find Full Text PDFNeurodegenerative diseases, as Parkinson's disease (PD), involve irreversible neural cell damage and impairment. In PD, there is a selective degeneration of the dopaminergic neurons leading to motor symptoms. A common finding in PD neurodegeneration is the increase of reactive oxygen species (ROS), leading to oxidative stress.
View Article and Find Full Text PDFJ Appl Biomater Funct Mater
July 2016
Introduction: The effect of scaffold pore size and interconnectivity is undoubtedly a crucial factor for most tissue engineering applications. The aim of this study was to examine the effect of pore size and porosity on cartilage construct development in different scaffolds seeded with articular chondrocytes.
Methods: We fabricated poly-L-lactide-co-trimethylene carbonate scaffolds with different pore sizes, using a solvent-casting/particulate-leaching technique.
Human Hsp70-2 is a chaperone expressed mainly in the nervous system. Up to now, no study has reported on the recombinant expression of this important human chaperone. Herein, we describe the successful purification and characterization of recombinant human Hsp70-2 in Escherichia coli in both the full-length and the chimeric protein containing the protein transduction domain corresponding to the trans-activator of transcription (Tat) from HIV.
View Article and Find Full Text PDFThe central nervous system shows a limited regenerative capacity, and injuries or diseases, such as those in the spinal, brain and retina, are a great problem since current therapies seem to be unable to achieve good results in terms of significant functional recovery. Different promising therapies have been suggested, the aim being to restore at least some of the lost functions. The current review deals with the use of hydrogels in developing advanced devices for central nervous system therapeutic strategies.
View Article and Find Full Text PDFJ Appl Biomater Funct Mater
December 2015
Aims: The possibility of developing engineered tissue in vitro and maintaining the cell viability and functionality is primarily related to the possibility of controlling key culture parameters such as oxygen concentration and cell-specific oxygen consumption. We measured these parameters in a three-dimensional (3D) cellularized construct maintained under interstitially perfused culture in a miniaturized bioreactor.
Methods: MG63 osteosarcoma cells were seeded at high density on a 3D polystyrene scaffold.
Carbomers, cross-linked poly(acrylic acid) microgels, have been widely used in pharmaceutical formulations as swollen hydrogels. Agarose, whose thermoreversibility may be exploited for drug loading, forms a gel with a mechanism involving coil-helix transition at about 36 °C. In this work carbomer microgels were combined with agarose networks in a semi-interpenetrating polymer network structure, aiming at obtaining suitable delivery systems for the loading and release of molecules with poor bioavailability but high therapeutic interest, like resveratrol.
View Article and Find Full Text PDFHydrogel-based materials are widely employed in the biomedical field. With regard to central nervous system (CNS) neurodegenerative disorders, the design of injectable nanocomposite hydrogels for in situ drug or cell release represents an interesting and minimally invasive solution that might play a key role in the development of successful treatments. In particular, biocompatible and biodegradable hydrogels can be designed as specific injectable tools and loaded with nanoparticles (NPs), to improve and to tailor their viscoelastic properties upon injection and release profile.
View Article and Find Full Text PDFPurpose: Our aim was to assess the use of injectable, biocompatible and resorbable, hydrogel-based tools for innovative therapies against brain-related neurodegenerative disorders like Alzheimer's (AD) and Parkinson's (PD) diseases.
Methods: Two compositions of semi-interpenetrating polymer networks (semi-IPNs) based on collagen and poly(ethylene glycol) (PEG) were investigated. We examined their viscoelastic properties, flow behavior, functional injectability, as well as in vitro biocompatibility with SH-SY5Y human neuroblastoma cells and murine primary neurons.