Development of an Oral Epithelial Ex Vivo Organ Culture Model for Biocompatibility and Permeability Assessment of Biomaterials.

In the present study, a customized device (Epi-ExPer) was designed and fabricated to facilitate an epithelial organ culture, allowing for controlled exposure to exogenous chemical stimuli and accommodating the evaluation of permeation of the tissue after treatment. The Epi-ExPer system was fabricated using a stereolithography (SLA)-based additive manufacturing (AM) method. Human and porcine oral epithelial mucosa tissues were inserted into the device and exposed to resinous monomers commonly released by dental restorative materials.

simulations of diffusion tensors and tortuosity in cells grown on 3D-printed scaffolds for tissue engineering.

Tissue engineering is set to revolutionise regenerative medicine, drug discovery, and cancer biology. For this to succeed, improved 3D imaging methods that penetrate non-invasively into the developing tissue is fundamental to guide the design of new and improved 3D supports. In particular, it is very important to characterise the time- and space-heterogeneous pore network that continuously changes as the tissue grows, since delivery of nutrients and removal of waste is key to avoid the development of necrotic tissues.

Tissue-Engineered Oral Epithelium for Dental Material Testing: Toward Biomimetic Models.

Tissue-engineered oral epithelium (ΤΕΟΕ) was developed after comparing various culture conditions, including submerged (SUB) and air-liquid interface (ALI) human cell expansion options. Barrier formation was evaluated via transepithelial electrical resistance (TEER) and calcein permeation via spectrofluorometry. TEOE was further assessed for long-term viability via live/dead staining and development of intercellular connections via transmission electron microscopy.

Correlative three-dimensional X-ray histology (3D-XRH) as a tool for quantifying mammalian placental structure.

Mammalian placentas exhibit unparalleled structural diversity, despite sharing a common ancestor and principal functions. The bulk of structural studies in placental research has used two-dimensional (2D) histology sectioning, allowing significant advances in our understanding of mammalian placental structure. However, 2D histology sectioning may be limited if it does not provide accurate information of three-dimensional (3D) tissue architecture.

Quantitative microCT imaging of a whole equine placenta and its blood vessel network.

Placental structure is linked to function across morphological scales. In the placenta, changes to gross anatomy, such as surface area, volume, or blood vessel arrangement, are associated with suboptimal physiological outcomes. However, quantifying each of these metrics requires different laborious semi-quantitative methods.

Three-dimensional reconstruction of high latitude bamboo coral via X-ray microfocus Computed Tomography.

The skeletons of long-lived bamboo coral (Family Keratoisididae) are promising archives for deep-water palaeoceanographic reconstructions as they can record environmental variation at sub-decadal resolution in locations where in-situ measurements lack temporal coverage. Yet, detailed three dimensional (3D) characterisations of bamboo coral skeletal architecture are not routinely available and non-destructive investigations into microscale variations in calcification are rare. Here, we provide high-resolution micro-focus computed tomography (µCT) data of skeletal density for two species of bamboo coral (Acanella arbuscula: 5 specimens, voxel size, 15 µm (central branch scans) and 50 µm (complete structure scan); Keratoisis sp.

A floating 3D printed polypill formulation for the coadministration and sustained release of antihypertensive drugs.

Polypharmacy is a common issue, especially among elderly patients resulting in administration errors and patient inconvenience. Hypertension is a prevalent health condition that frequently leads to polypharmacy, as its treatment typically requires the co-administration of more than one different Active Pharmaceutical Ingredients (API's). To address these issues, floating hollow torus-shaped dosage forms were developed, aiming at providing prolonged gastric retention and sustained drug release.

Convergently evolved placental villi show multiscale structural adaptations to differential placental invasiveness.

Despite having a single evolutionary origin and conserved function, the mammalian placenta exhibits radical structural diversity. The evolutionary drivers and functional consequences of placental structural diversity are poorly understood. Humans and equids both display treelike placental villi, however these villi evolved independently and exhibit starkly different levels of invasiveness into maternal tissue (i.

A Systematic Review and Meta-Analysis of the Pathology Underlying Aneurysm Enhancement on Vessel Wall Imaging.

Intracranial aneurysms are common, but only a minority rupture and cause subarachnoid haemorrhage, presenting a dilemma regarding which to treat. Vessel wall imaging (VWI) is a contrast-enhanced magnetic resonance imaging (MRI) technique used to identify unstable aneurysms. The pathological basis of MR enhancement of aneurysms is the subject of debate.

A high-throughput 3D X-ray histology facility for biomedical research and preclinical applications.

Background: The University of Southampton, in collaboration with the University Hospital Southampton (UHS) NHS Foundation Trust and industrial partners, has been at the forefront of developing three-dimensional (3D) imaging workflows using X-ray microfocus computed tomography (μCT) -based technology. This article presents the outcomes of these endeavours and highlights the distinctive characteristics of a μCT facility tailored explicitly for 3D X-ray Histology, with a primary focus on applications in biomedical research and preclinical and clinical studies.

Methods: The UHS houses a unique 3D X-ray Histology (XRH) facility, offering a range of services to national and international clients.

3D Printing of Personalised Carvedilol Tablets Using Selective Laser Sintering.

Selective laser sintering (SLS) has drawn attention for the fabrication of three-dimensional oral dosage forms due to the plurality of drug formulations that can be processed. The aim of this work was to employ SLS with a CO laser for the manufacturing of carvedilol personalised dosage forms of various strengths. Carvedilol (CVD) and vinylpyrrolidone-vinyl acetate copolymer (Kollidon VA64) blends of various ratios were sintered to produce CVD tablets of 3.

Ga-bisphosphonates for the imaging of extraosseous calcification by positron emission tomography.

Radiolabelled bisphosphonates (BPs) and [F]NaF (F-fluoride) are the two types of radiotracers available to image calcium mineral (e.g. bone), yet only [F]NaF has been widely explored for the non-invasive molecular imaging of extraosseous calcification (EC) using positron emission tomography (PET) imaging.

Fabrication of 3D Printed Hollow Microneedles by Digital Light Processing for the Buccal Delivery of Actives.

In the present study, two different microneedle devices were produced using digital light processing (DLP). These devices hold promise as drug delivery systems to the buccal tissue as they increase the permeability of actives with molecular weights between 600 and 4000 Da. The attached reservoirs were designed and printed along with the arrays as a whole device.

Correlative multiscale microCT-SBF-SEM imaging of resin-embedded tissue.

Three-dimensional biological microscopy presents a trade-off between spatial resolution and field of view. Correlative approaches applying multiple imaging techniques to the same sample can therefore mitigate against these trade-offs. Here, we present a workflow for correlative microscopic X-ray microfocus computed tomography (microCT) and serial block face scanning electron microscopy (SBF-SEM) imaging of resin-embedded tissue, using mammalian placental tissue samples as an example.

3D printing of LEGO® like designs with tailored release profiles for treatment of sleep disorder.

3D printed LEGO®-like designs are an attractive approach for the development of compartmental delivery systems due to their potential for dose personalisation through the customisation of drug release profiles. Additive manufacturing technologies such as Fused Deposition Modelling (FDM) are ideal for the printing of structures with complex geometries and various sizes. This study is a paradigm for the fabrication of 3D printed LEGO® -like tablets by altering the design of the modular units and the filament composition for the delivery of different drug substances.

Electrospun Nanofiber Films Suppress Inflammation and Eradicate Endodontic Bacterial Infection in an -Infected Human Tooth Culture Model.

Treatment failure of endodontic infections and their concurrent inflammations is commonly associated with microbial persistence and reinfection, also stemming from the anatomical restrictions of the root canal system. Aiming to address the shortcomings of current treatment options, a fast-disintegrating nanofibrous film was developed for the intracanal coadministration of an antimicrobial (ZnO nanoparticles) and an anti-inflammatory (ketoprofen) agent. The electrospun films were fabricated based on polymers that dissolve rapidly to constitute the actives readily available at the site of action, aiming to eliminate both microbial infection and inflammation.

Immunofluorescence-guided segmentation of three-dimensional features in micro-computed tomography datasets of human lung tissue.

Micro-computed tomography (µCT) provides non-destructive three-dimensional (3D) imaging of soft tissue microstructures. Specific features in µCT images can be identified using correlated two-dimensional (2D) histology images allowing manual segmentation. However, this is very time-consuming and requires specialist knowledge of the tissue and imaging modalities involved.

The role of extracellular matrix phosphorylation on energy dissipation in bone.

Protein phosphorylation, critical for cellular regulatory mechanisms, is implicated in various diseases. However, it remains unknown whether heterogeneity in phosphorylation of key structural proteins alters tissue integrity and organ function. Here, osteopontin phosphorylation level declined in hypo- and hyper- phosphatemia mouse models exhibiting skeletal deformities.

Fabrication of an osmotic 3D printed solid dosage form for controlled release of active pharmaceutical ingredients.

In pharmaceutical formulations, pharmacokinetic behavior of the Active Pharmaceutical Ingredients (API's) is significantly affected by their dissolution profiles. In this project, we attempted to create personalized dosage forms with osmotic properties that exhibit different API release patterns via Fused Deposition Modelling (FDM) 3D printing. Specifically, cellulose acetate was employed to create an external shell of an osmotically active core containing Diltiazem (DIL) as model drug.

X-ray Micro-Computed Tomography for Nondestructive Three-Dimensional (3D) X-ray Histology.

Historically, micro-computed tomography (μCT) has been considered unsuitable for histologic analysis of unstained formalin-fixed, paraffin-embedded soft tissue biopsy specimens because of a lack of image contrast between the tissue and the paraffin. However, we recently demonstrated that μCT can successfully resolve microstructural detail in routinely prepared tissue specimens. Herein, we illustrate how μCT imaging of standard formalin-fixed, paraffin-embedded biopsy specimens can be seamlessly integrated into conventional histology workflows, enabling nondestructive three-dimensional (3D) X-ray histology, the use and benefits of which we showcase for the exemplar of human lung biopsy specimens.

Synergistic Antitumor Potency of a Self-Assembling Peptide Hydrogel for the Local Co-delivery of Doxorubicin and Curcumin in the Treatment of Head and Neck Cancer.

Combination therapy has been conferred with manifold assets leveraging the synergy of different agents to achieve a sufficient therapeutic outcome with lower administered drug doses and reduced side effects. The therapeutic potency of a self-assembling peptide hydrogel for the co-delivery of doxorubicin and curcumin was assessed against head and neck cancer cells. The dual loaded peptide hydrogel enabled control over the rate of drug release based on drug's aqueous solubility.

Small airways disease in mild and moderate chronic obstructive pulmonary disease: a cross-sectional study.

Background: The concept that small conducting airways less than 2 mm in diameter become the major site of airflow obstruction in chronic obstructive pulmonary disease (COPD) is well established in the scientific literature, and the last generation of small conducting airways, terminal bronchioles, are known to be destroyed in patients with very severe COPD. We aimed to determine whether destruction of the terminal and transitional bronchioles (the first generation of respiratory airways) occurs before, or in parallel with, emphysematous tissue destruction.

Methods: In this cross-sectional analysis, we applied a novel multiresolution CT imaging protocol to tissue samples obtained using a systematic uniform sampling method to obtain representative unbiased samples of the whole lung or lobe of smokers with normal lung function (controls) and patients with mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1), moderate COPD (GOLD 2), or very severe COPD (GOLD 4).

Controlled Release of 5-Fluorouracil from Alginate Beads Encapsulated in 3D Printed pH-Responsive Solid Dosage Forms.

Three-dimensional printing is being steadily deployed as manufacturing technology for the development of personalized pharmaceutical dosage forms. In the present study, we developed a hollow pH-responsive 3D printed tablet encapsulating drug loaded non-coated and chitosan-coated alginate beads for the targeted colonic delivery of 5-fluorouracil (5-FU). A mixture of Eudragit® L100-55 and Eudragit® S100 was fabricated by means of hot-melt extrusion (HME) and the produced filaments were printed utilizing a fused deposition modeling (FDM) 3D printer to form the pH-responsive layer of the tablet with the rest comprising of a water-insoluble poly-lactic acid (PLA) layer.