Publications of the team

In vitro models replicating the human intestinal epithelium for absorption and metabolism studies: A systematic review

In this review, we provide an overview of in vitro models aimed at mimicking the intestinal barrier for pharmaceutical screening. After briefly describing how the human small intestine works, we present i) conventional 2D synthetic and cell-based systems, ii) 3D models replicating the main features of the intestinal architecture, iii) micro-physiological systems (MPSs) reproducing the dynamic stimuli to which cells are exposed in the native microenvironment. Absorption, distribution, metabolism and excretion (ADME) studies represent a fundamental step in the early stages of drug discovery. In particular, the absorption of orally administered drugs, which occurs at the intestinal level, has [...]

3D fluid-dynamic ovarian cancer model resembling systemic drug administration for efficacy assay

In this recent scientific result, our team demonstrates that the in vivo-like dynamic environment provided by the MIVO® device allows for better modeling of the 3D tumor environment and predicting drug efficacy in vivo compared to a static in vitro model. Recently, 3D in vitro cancer models have become important alternatives to animal tests for establishing the efficacy of anticancer treatments. In this work, 3D SKOV-3 cell-laden alginate hydrogels were established as ovarian tumor models and cultured within a fluid-dynamic bioreactor (MIVO®) device able to mimic the capillary flow dynamics feeding the tumor. Cisplatin efficacy tests were performed within [...]

In vitro demonstration of intestinal absorption mechanisms of different sugars using 3D organotypic tissues in a fluidic device

The team describes the use of MiVO in combination with 3D human intestinal tissues for highly reliable in vitro intestinal permeation tests Intestinal permeability is crucial in regulating the bioavailability and the biological effects of drugs and compounds. However, systematic and quantitative studies of absorption of molecules are quite limited due to the lack of reliable experimental models able to mimic in vivo responses. A recent study published in Altex sought to answer some of these questions. They adopted the fluidic MIVO® device for hosting and culturing 3D reconstructed intestinal epithelium, resembling in vitro the human fluid-dynamic intestinal environment. The [...]

Improved cell activity on biodegradable photopolymer scaffolds using titanate nanotube coatings

The team describes a nanocoating of surfaces for improved cell activity The development of bioactive materials is in the premise of tissue engineering. For several years, surface functionalization of scaffolds has been one of the most promising approaches to stimulate cellular activity and finally improve implant success. Herein, we describe the development of a bioactive composite scaffold composed of a biodegradable photopolymer scaffold and titanate nanotubes (TNTs). The biodegradable photopolymer scaffolds were fabricated by applying mask-projection excimer laser photocuring at 308 nm. TNTs were synthesized and then spin-coated on the porous scaffolds. Upon culturing fibroblast cells on scaffolds, we [...]

Cell-Laden Hydrogel as a Clinical-Relevant 3D Model for Analyzing Neuroblastoma Growth, Immunophenotype, and Susceptibility to Therapies

The team describes a Clinical-Relevant reliable 3D neuroblastoma Model towards immunotherapies testing    Neuroblastoma (NB) represents an aggressive, metastatic solid tumors of childhood, with a very poor survival rate, despite the use of combination therapies including novel immunotherapies. Treatment failures are mainly due to the lack of adequate in vitro models for studying the efficacy of potential therapeutics, including those aimed to enhance anti-tumor immune responses. A recent study published in Frontiers in Immunology shows a 3D cell laden hydrogel as tumor model to evaluate the effects of the three-dimensionality on biological and immunological properties of NB cells. This 3D model highlighted [...]

A new cell-laden 3D Alginate-Matrigel hydrogel resembles human breast cancer cell malignant morphology, spread and invasion capability observed “in vivo

The team describes a 3D breast tumor model cultured within the multi in vitro organ device Breast cancer is the most common cancer in women and one of the leading causes of cancer related deaths worldwide. Mortality is mainly associated with the development of metastases, the spread of a tumor from its primary site to other parts of the body. Thus, a deeper understanding of the pathways that give rise to metastasis is one of the key challenges for developing new therapies to fight breast cancer.  Metastasis is a complex and multistep process: in order to generate secondary tumors, [...]

Green-reduced graphene oxide induces in vitro an enhanced biomimetic mineralization of polycaprolactone electrospun meshes

The team describes an electrospun mesh as permeable porous model A novel green method for graphene oxide (GO) reduction via ascorbic acid has been adopted to realize bio-friendly reduced graphene oxide (RGO)/polycaprolactone (PCL) nanofibrous meshes, as substrates for bone tissue engineering applications. PCL fibrous mats enriched with either RGO or GO (0.25 wt%) were fabricated to recapitulate the fibrillar structure of the bone extracellular matrix (ECM) and the effects of RGO incorporation on the structural proprieties, biomechanics and bioactivity of the nano-composites meshes were evaluated. RGO/PCL fibrous meshes displayed superior mechanical properties (i.e. Young's Modulus and ultimate tensile strength) besides [...]

A combined low-frequency electromagnetic and fluidic stimulation for a controlled drug release from superparamagnetic calcium phosphate nanoparticles: potential application for cardiovascular diseases

The team describes a bioreactor for cardiac applications Cardiovascular diseases still represent the leading cause for morbidity and mortality in the western world, giving rise to many disabilities in patients. Current clinical regimens largely rely on the use of drugs, medical devices and changes in lifestyle but, despite large beneficial outcomes, none of these treatments is as yet fully efficient in preventing the progression of the pathology. In this context, the identification of alternative therapeutic approaches is urgently needed. Alternative drug delivery approaches to treat cardiovascular diseases are currently under intense investigation. In this domain, the possibility to target [...]

Design and development of a 3D fluidic bioreactor platform for a combined mechanical/perfusing stimulation of articular substitutes

A. Marella, V. Alberi, S. Scaglione describes a 3D fluidic bioreactor platform for articular tissue applications Due to its avascular nature, articular cartilage exhibits a very limited capacity to regenerate and to repair. Although much of the engineered cartilage grafts so far proposed have successfully shown to mimic the morphological and biochemical appearance of hyaline cartilage, they are generally mechanically inferior to the natural tissue. In this study a new bioreactor device was realized to test innovative scaffolds under physiological stimulation (i.e. perfusion fluid flow and dynamic compression), with the aim to produce a more functional engineered tissue construct [...]

Microenvironment complexity and matrix stiffness regulate breast cancer cells activity in a 3D in vitro model

Cavo M, Fato M, Peñuela L, Beltrame F, Raiteri R, Scaglione S, describes a 3D cell laden breast cancer model Mechanical stimuli from the cell microenvironment play a key role in affecting several types of cell behaviour, both in healthy and in pathological conditions. In particular, cells sense their microenvironment via trans-membrane proteins and consequently regulate several physiological processes such as migration, proliferation, differentiation, morphology and gene expression, as well as the response to drugs. In vivo, cells are embedded within a complex three-dimensional gel – the Extracellular Matrix (ECM) – that provides mechanical support while directing cellular behavior. Interestingly, more and more literature show [...]

Oriented collagen nanocoatings for tissue engineering

The team describes the collagen-based functionalization of substrates for enhanced cellular response   Collagens are among the most widely present and important proteins composing the human total body, providing strength and structural stability to various tissues, from skin to bone. In this paper, we report an innovative approach to bioactivate planar surfaces with oriented collagen molecules to promote cells proliferation and alignment. The Langmuir-Blodgett technique was used to form a stable collagen film at the air-water interface and the Langmuir-Schaefer deposition was adopted to transfer it to the support surface. The deposition process was monitored by estimating the mass [...]

Mesenchymal stem cell culture in convection-enhanced hollow fibre membrane bioreactors for bone tissue engineering

The team describes the use of bioreactors for bone tissue engineering applications   Preparation of tissue engineered bone constructs to repair large size defects is limited by the difficult supply of oxygen and nutrients to cells deep inside the constructs. Hollow fibre membrane bioreactors (HFMBs) with medium flowing in membrane lumen have structural and functional analogy with cortical bone. In fact, membranes resemble the Haversian canals and provide for a distributed and delocalized source of nutrients and oxygen to surrounding cells. HFMBs where oxygen and nutrients diffuse to cells have been proposed for bone tissue engineering. HFMBs may also [...]

Bioactive TGF-β1/HA alginate-based scaffolds for osteochondral tissue repair: design, realization and multilevel characterization

The team describes the alginate-based hydrogels as osteochindral tissue model The design of an appropriate microenvironment for stem cell differentiation constitutes a multitask mission and a critical step toward the clinical application of tissue substitutes. With the aim of producing a bioactive material for orthopedic applications, a transforming growth factor-β (TGF- β1)/hydroxyapatite (HA) association within an alginate-based scaffold was investigated. The bioactive scaffold was carefully designed to offer specific biochemical cues for an efficient and selective cell differentiation toward the bony and chondral lineages. Highly porous alginate scaffolds were fabricated from a mixture of calcium cross-linked alginates by means [...]

Effects of fluid flow and calcium phosphate coating on human bone marrow stromal cells cultured in a defined 2D model system

The team describes the effect of shear stress induced fluid flow on stem cell differentiation In this study, we investigated the effect of the long-term (10 days) application of a defined and uniform level of fluid flow (uniform shear stress of 1.2 x 10(-3) N/m(2)) on human bone marrow stromal cells (BMSC) cultured on different substrates (i.e., uncoated glass or calcium phosphate coated glass, Osteologictrade mark) in a 2D parallel plate model. Both exposure to flow and culture on Osteologic significantly reduced the number of cell doublings. BMSC cultured under flow were more intensely stained for collagen type I [...]

A three-dimensional traction/torsion bioreactor system for tissue engineering

The team describes the use of bioreactors for ligament tissue engineering applications The aim of this study was to design, develop and validate a simple, compact bioreactor system for tissue engineering. The resulting bioreactor was designed to achieve ease-of-use and low costs for automated cell-culturing procedures onto three-dimensional scaffolds under controlled torsion/traction regimes. Highly porous poly-caprolactone-based scaffolds were used as substrates colonized by fibroblast cells (3T3 cell line). Constructs were placed within the cylindrical culture chamber, clumped at the ends and exposed to controlled sequences of torsional stimuli (forward/back-forward sequential cycles of 100 degrees from neutral position at a [...]

Engineering of osteoinductive grafts by isolation and expansion of ovine bone marrow stromal cells directly on 3D ceramic scaffolds

The team describes the effect of perfused fluid flow for generating osteogenic grafts In this work, we investigated whether osteoinductive constructs can be generated by isolation and expansion of sheep bone marrow stromal cells (BMSC) directly within three-dimensional (3D) ceramic scaffolds, bypassing the typical phase of monolayer (2D) expansion prior to scaffold loading. Nucleated cells from sheep bone marrow aspirate were seeded into 3D ceramic scaffolds either by static loading or under perfusion flow and maintained in culture for up to 14 days. The resulting constructs were exposed to enzymatic treatment to assess the number and lineage of extracted [...]

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