Search

Kefiran is an exopolysaccharide produced by microorganisms present in kefir grains, with several health promoting properties. A optimized protocol was developed for the separation of kefiran from kefir grains, allowing to reach a yield 4÷5 % without using toxic or expensive chemicals. The capability of kefiran to produce scaffold via Thermally Induced Phase Separation (TIPS) technique was investigated and porous scaffolds structure was obtained. Separated kefiran and scaffolds were analyzed via DSC and different thermal properties between purified kefiran and scaffold were revealed. XRD analysis revealed different structure between kefiran and scaffolds. The porous scaffold structure can be modulated by modifiying the thermal path of the solution during the phase separation. The citotoxicity of kefiran was evaluated with cell viability test and a significant faster cell proliferation in the treated colture medium with kefiran was evidenced.

Bone Tissue Engineering offers promising clinical alternative substitutes for bone defects, focusing on the use of polymer/ceramic composites. Hydroxyapatite (HA), a bioactive ceramic, has been implemented in bone substitution and regeneration due to its biocompatibility, osteoconductivity and close resemblance to the mineralized phase of human bone. Several techniques have been adopted to characterize composite scaffolds in terms of morphology, pore size and interconnection, filler content and distribution, but most of them are destructives. In this work, composite Poly-L-Lactic Acid (PLLA)-HA scaffolds (17.6 mm diameter and35.7 mm height) were prepared via Thermally Induced Phase Separation (TIPS) by using a ternary PLLA- dioxane-water solution (polymer-solvent-nonsolvent). Two different concentrations (10% and 20% wt/wt filler/polymer ratio) of HA particles were chosen. The samples were characterized via Scanning Electron Microscopy (SEM) and Microcomputed Tomography (µCT), a non-invasive technique capable to analyze the internal structure of the sample. After the µCT reconstruction, an investigation of the distribution and average sizes of the filler was carried out through a 3D analysis software (CTAn). The obtained results demonstrated the possibility to analyze the internal distribution of the particles via a non-invasive technique; furthermore a homogeneous HA content and a uniform size distribution in the whole sample was observed, which allows one to assess that the scaffold production technique does not create neither a filler gradient nor a particle sedimentation.

Tissue engineering offers a promising new approach to repair bone fractures, fractures that do not heal, and fractures due to bone tumors. In this work, two different approaches were tested in order to obtain Poly-L- Lactic Acid (PLLA) porous scaffolds via Thermally Induced Phase Separation (TIPS) for bone tissue engineering application. First, the possibility to produce a composite material, by incorporating Hydroxyapatite (HA) particles in a Poly-L-lactic acid (PLLA) matrix was investigated. Two PLLA/HA weight ratios (70/30 and 50/50) were tested. The results showed that the presence of HA does not influence the phase separation process, i.e. the composite scaffolds microstructure is similar to pure PLLA scaffolds. WAXD analysis confirmed the full incorporation of HA particles into the polymer matrix. Moreover, compression tests showed a fourfold increase of Young module with respect to pure PLLA scaffold. Since the production of scaffolds for bone tissue regeneration is a challenging target, scaffolds must mimic the bone morphology, thus requiring a gradient of pore dimension and morphology along one dimension. To attain this goal, the second part of the work describes the design, set up and test of an experimental apparatus able to set different thermal histories on the two sides of a sample. Scaffolds were produced by following various thermal protocols on both sample surfaces. The results showed that through this technique it is possible to produce scaffolds with a pore size that increases along sample thickness. As a matter of fact, the obtained average pore dimension on one side of the sample was about 70 µm, whereas it was around 240 µm on the opposite surface. By moving along the sample thickness, the pore dimension increased steadily. All things considered, a reliable route for the production of composite PLLA/HA scaffolds with a controlled pore size distribution was assessed, thus offering a valid support to bone tissue engineering.

Monitoring of the intrauterine growth retarded fetus in order to improve fetal outcome and define precisely the timing of delivery, when necessary, is based on the study of changes in vital functions observable in cases of hypoxemia. It is easy to believe that ultrasound equipment with Doppler facilities is present in the majority if not in all gynecological units. Cardiotocography is also widely used and the addition of a computerized evaluation system is not expensive and therefore should be available when facing high risk pregnancies such as intrauterine growth retarded cases. IUGR can be recognized through the use of ultrasound fetal biometry and clinical examination of maternal conditions in order to assess fetal conditions. If the above technologies are available further action, such as fetal Doppler study of fetal vessels and cardiotocography, can then be undertaken. In this paper, we will be discussing the issue of monitoring the fetus for fetal wellbeing, particularly in cases of intrauterine growth retarded fetuses. [ABSTRACT FROM AUTHOR]

Background: Direct bile ducts visualization through cholangioscopy has gained popularity due to its better diagnostic accuracy than a standard ERCP in indeterminate biliary stricture., Methods: We aimed to review our catheter-based cholangioscopy interventions in patients with indeterminate biliary stenosis, using the SpyGlass Direct Visualization System (SDVS) and summarize our experience in terms of procedures and results. We collected 25 consecutive patients with indeterminate biliary stricture over 3 years., Results: The overall procedural success in our cohort amounted to 96% (24/25). If we focus on the diagnostic procedures, the ability to merely visualize the region of interest/lesion and perform biopsy of the lesion was possible in 96% (24/25) In our cohort localization in the common bile duct (P=0.03; 95% CI: 0.27-0.96) was found as positive determining factor for diagnosis. Sensitivity, specificity and accuracy for visual diagnosis by SDVS in our cohort were 100, 83.3 and 96%, respectively. The use of biopsy or obtaining a histological diagnosis to assist in identifying patients with malignant stenosis, to exclude malignancy and to correctly classify diagnosed patients resulted in a sensitivity of 100%, a specificity of 73% with an overall accuracy of 94.4%. Only a mild adverse event (cholangitis, treated conservatively) occurred., Conclusions: Today, the SDVS should be considered essential in diagnosing indeterminate biliary strictures, since the procedure is associated with high procedural success in terms of diagnostic accuracy, alters clinical outcome in over 80% of considered insolvable cases, with an acceptable safety profile.

Background and Aims: Adequate bowel cleansing is essential for colonoscopy quality. A novel 1 L polyethylene glycol plus ascorbate (1 L PEG+ASC) solution has been recently introduced. Nevertheless, the efficacy of 1 L PEG+ASC as compared to that of high-volume bowel preparation in both inpatients and outpatients is still unclear., Patients and Methods: This single-blinded, non-inferiority study randomized patients undergoing colonoscopy to receive split-dose 1 L PEG+ASC or 4 L PEG. The primary endpoint was the overall cleansing success. Secondary endpoints were excellent cleansing and high-quality cleansing of the right colon, as well as lesions detection rate, patient compliance, tolerability and safety., Results: Overall, 478 patients were randomized to 1 L PEG+ASC (N = 236) or 4 L PEG (N = 242). The 1 L PEG+ASC showed higher cleansing success rate (91.8% vs 83.6%; P=0.01) and a high-quality cleansing of the right colon (52.3% and 38.5%; P=0.004) compared to 4 L PEG. Moreover, 1 L PEG+ASC achieved a higher cleansing success in out-patients (96.3%% vs 88.6%; P=0.018), and a similar success rate in the in-patients (84.7% vs 76.7%; P=0.18). Adenoma detection rate, tolerability and incidence of adverse events were comparable between preparations., Conclusions: The 1 L PEG+ASC showed higher efficacy in achieving adequate colon cleansing compared with 4 L PEG, particularly in the right colon. No differences in the tolerability and safety were detected., Competing Interests: Conflict of interest Roberto Vassallo received consultation fees from AlfaSigma and Norgine. Marcello Maida and Roberto Di Mitri served as advisory board member and received lecture grants from Norgine. Other authors have no proprietary, financial, professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of this manuscript., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: In clinical practice, standard endoscopic treatment of biliary stones fails in up to 10% of patients, and more invasive procedures such as percutaneous trans-hepatic interventions or surgery might become necessary. The aim of this multicenter retrospective study, based on prospectively-collected data, was to evaluate both the efficacy and the safety of digital-single operator cholangioscopy (D-SOC) to treat difficult biliary stones in cases with a previous failure of conventional endoscopic methods., Methods: Only patients with a previous failure of endoscopic standard treatment and a D-SOC-based biliary stone treatment using electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) were included. The primary endpoint was to evaluate the stone clearance rate per procedure and per patient., Results: Out of 1258 ERCP performed at our centers, 31 cholangioscopes in 21 patients were solely performed for the treatment of difficult biliary stones using EHL or LL. A complete biliary stone removal was achieved in 67.7% (21/31) of all procedures including initial and repeated examinations, while in 35.4% (11/31) of all procedures an incomplete removal was accomplished of which 36.3% had a partial stone removal. In 22 procedures EHL was adopted as techniques to fragment and remove biliary stones, while in 9 procedures LL was used. In both the techniques, the complete stone removal rate and the incomplete stone removal rate were similar (75% vs. 77.7%, P>0.05). Furthermore, the success rate of digital D-SOC to treat difficult biliary stones was assessed per patient: overall, 100% of patients with difficult biliary stones were successfully treated using D-SOC. Only one patient experienced mild cholangitis classified ad mild adverse event following ASGE (American Society of Gastrointestinal Endoscopy) lexicon., Conclusions: Our data indicate that digital D-SOC assisted biliary stone treatment is highly efficient for the treatment of difficult biliary stones even in such patients in whom previous conventional endoscopic methods to treat biliary stones have failed. Therefore, D-SOC might be considered the new standard of care for these patients, being both, effective and safe.

The clinical course of Crohn's disease (CD) is often complicated by intestinal strictures, which can be fibrotic, inflammatory, or mixed, therefore leading to stenosis and eventually symptomatic obstruction. We report two cases of subclinical CD diagnosed after fruit pit ingestion, causing bowel obstruction; additionally, we conducted a narrative review of the scientific literature on cases of intestinal obstruction secondary to impacted bezoars due to fruit pits. Symptoms of gastrointestinal bezoars in CD patients are not diagnostic; and the diagnosis should be based on a combined assessment of history, clinical presentation, imaging examination and endoscopy findings. This report corroborates the concept that CD patients are at a greater risk of bowel obstruction with bezoars generally and shows that accidental ingestion of fruit pits may lead to an unusual presentation of the disease. Therapeutic options in this group of patients differ from the usual approaches implemented in other patients with strictures secondary to CD.

The gut microbiota is emerging as an important player in neurodevelopment and aging as well as in brain diseases including stroke, Alzheimer's disease, and Parkinson's disease. The complex interplay between gut microbiota and the brain, and vice versa, has recently become not only the focus of neuroscience, but also the starting point for research regarding many diseases such as inflammatory bowel diseases (IBD). The bi-directional interaction between gut microbiota and the brain is not completely understood. The aim of this review is to sum up the evidencesconcerningthe role of the gut-brain microbiota axis in ischemic stroke and to highlight the more recent evidences about the potential role of the gut-brain microbiota axis in the interaction between inflammatory bowel disease and ischemic stroke.

Chronic idiopathic intestinal pseudo-obstruction (CIIPO) is a disease characterized by symptoms and signs of small bowel obstruction in the absence of displayable mechanical obstruction. Due to the known neuropathic capacity of several viruses, and their localization in the intestine, it has been hypothesized that such viruses could be involved in the pathogenesis of CIIPO. The most frequently involved viruses are John Cunningham virus, Herpesviridae, Flaviviruses, Epstein-Barr virus and Citomegalovirus. Therefore, the present narrative review aims to sum up some new perspectives in the etiology and pathophysiology of CIIPO.

An adequate bowel preparation is essential for a successful colonoscopy, in particular, in the setting of colorectal cancer screening. However, up to one-quarter of colonoscopies are associated with inadequate bowel preparation, which may result in reduced polyp and adenoma detection rates, prolonged procedural time, and an increased likelihood of repeat the procedure. The ideal intestinal preparation should provide an optimal observation of the mucosa (at least > 90% of the visible surface), with adequate acceptability and safety for the patient. With this premise, a very low-volume 1 L PEG-ASC solution (Plenvu; Norgine, Harefield, United Kingdom) has been recently introduced to improve patients' experience in colonoscopy by reducing the total intake of liquids to be consumed. This could represent a valid option for bowel cleansing, considering CRC screening and surveillance programs, improving both the quality of the examination and the patients' compliance. Nevertheless, it must be emphasized that a "one size fits all" preparation strategy is not feasible and that a bowel preparation regime must always be selected and tailored by the clinician for each patient, evaluating the best options on a case by case basis. This narrative review aims to sum up the evidence regarding new bowel preparation regimens in order to help clinicians to tailor the best choice for patients undergoing colonoscopy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Colonoscopy remains the standard strategy for screening for colorectal cancer around the world due to its efficacy in both detecting adenomatous or pre-cancerous lesions and the capacity to remove them intra-procedurally. Computer-aided detection and diagnosis (CAD), thanks to the brand new developed innovations of artificial intelligence, and especially deep-learning techniques, leads to a promising solution to human biases in performance by guarantying decision support during colonoscopy. The application of CAD on real-time colonoscopy helps increasing the adenoma detection rate, and therefore contributes to reduce the incidence of interval cancers improving the effectiveness of colonoscopy screening on critical outcome such as colorectal cancer related mortality. Furthermore, a significant reduction in costs is also expected. In addition, the assistance of the machine will lead to a reduction of the examination time and therefore an optimization of the endoscopic schedule. The aim of this opinion review is to analyze the clinical applications of CAD and artificial intelligence in colonoscopy, as it is reported in literature, addressing evidence, limitations, and future prospects., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Irritable bowel syndrome with constipation is associated with higher rates of functional impairment, as compared to other subtypes of the syndrome. Conventional laxative-based pharmacologic therapy of IBS-C, which is mostly symptom-based, is often unsatisfactory. Tenapanor represents a first-in-class orally available inhibitor of NHE3, which is minimally absorbed in the GI tract, what constitutes a significant therapeutic benefit, as it may act on the drug target., Areas Covered: Aim of this article is to sum up the evidences about pharmacodynamics and pharmacokinetics of tenapanor, focusing on animal models and in vitro studies, but also discuss clinical trials on tenapanor's safety and efficacy in view of its important potential role in IBS-C treatment., Expert Opinion: In the challenging setting of irritable bowel syndrome with constipation, tenapanor represents a novel strategy in the pipeline of the therapies of IBS-C. Its pharmacokinetic and pharmacodynamic profile provides that it is minimally absorbed from the intestinal lumen and that its action is local, but not systemic action, therefore guaranteeing the reduction of drug-drug interactions, toxicity and severe adverse effects. Phase 2b and 3 trials showed an optimal satisfaction of primary and secondary endpoints.

Background: The effectiveness of colonoscopy strictly depends on adequate bowel cleansing. Recently, a 1 L polyethylene glycol plus ascorbate (PEG-ASC) solution (Plenvu; Norgine, Harefield, United Kingdom) has been introduced on the evidence of three phase-3 randomized controlled trials, but it had never been tested in the real-life., Aim: To assess the effectiveness and tolerability of the 1 L preparation compared to 4 L and 2 L- PEG solutions in a real-life setting., Methods: All patients undergoing a screening or diagnostic colonoscopy after a 4, 2 or 1 L PEG preparation, were consecutively enrolled in 5 Italian centers from September 2018 to February 2019. The primary endpoints of the study were the assessment of bowel cleansing success and high-quality cleansing of the right colon. The secondary endpoints were the evaluation of tolerability, adherence and safety of the different bowel preparations. Bowel cleansing was assessed through the Boston Bowel Preparation Scale. Adherence was defined as consumption of at least 75% of each dose, while tolerability was evaluated through a semi-quantitative scale. Safety was systematically monitored through adverse events reporting., Results: Overall, 1289 met the inclusion criteria and were enrolled in the study. Of these, 490 patients performed a 4 L-PEG preparation (Selgesse ® ), 566 a 2 L-PEG cleansing (Moviprep ® or Clensia ® ) and 233 a 1 L-PEG preparation (Plenvu ® ). Bowel cleansing by Boston Bowel Preparation Scale was 6.5 ± 1.5 overall and 6.3 ± 1.5, 6.2 ± 1.5, 7.3 ± 1.5 ( P < 0.001) in the subgroups of 4 L, 2 L and 1 L-PEG preparation, respectively. Cleansing success was achieved in 72.4%, 74.1% and 90.1% ( P < 0.001), while a high-quality cleansing of the right colon in 15.9%, 12.0% and 41.4% ( P < 0.001) for 4 L, 2 L and 1 L-PEG preparation groups, respectively. The 1 L preparation was the most tolerated compared to the 2 and 4 L-PEG solutions in the absence of serious adverse events within any of the three groups. Multiple regression models confirmed 1 L PEG-ASC preparation as an independent predictor of overall cleansing success, high-quality cleansing of the right colon and of tolerability., Conclusion: This study supports the effectiveness and tolerability of 1 L PEG-ASC, also showing it is an independent predictor of overall cleansing success, high-quality cleansing of the right colon and of tolerability., Competing Interests: Conflict-of-interest statement: The authors have no proprietary, financial, professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of this manuscript., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Tissue engineering offers new approaches to repair bone defects, which cannot be repaired physiologically, developing scaffolds that mimic bone tissue architecture. Furthermore, biomechanical stimulation induced by bioreactor, provides biomechanical cues that regulate a wide range of cellular events especially required for cellular differentiation and function. The improvement of human mesenchymal stem cells (hMSCs) colonization in poly-l-lactic-acid (PLLA)/nano-hydroxyapatite (nHA) composite scaffold was evaluated in terms of cell proliferation (dsDNA content), bone differentiation (gene expression and protein synthesis) and ultrastructural analysis by comparing static (s3D) and dynamic (d3D) 3D culture conditions at 7 and 21 days. The colonization rate of hMSCs and osteogenic differentiation were amplified by d3D when physical stimulation was provided by a perfusion bioreactor. Increase in dsDNA content (p < 0.0005), up-regulation of RUNX2, ALPL, SPP1 (p < 0.0005) and SOX9 (p < 0.005) gene expression, and more calcium nodule formation (p < 0.0005) were observed in d3D cultures in comparison to s3D ones over time. Dynamic 3D culture, mimicking the mechanical signals of bone environment, improved significantly osteogenic differentiation of hMSCs on PLLA/nHA scaffold, without the addition of growth factors, confirming this composite scaffold suitable for bone regeneration., (Copyright © 2019 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Damage of hyaline cartilage such as nasoseptal cartilage requires proper reconstruction, which remains challenging due to its low intrinsic repair capacity. Implantation of autologous chondrocytes in combination with a biomimetic biomaterial represents a promising strategy to support cartilage repair. Despite so far mostly tested for bone tissue engineering, bioactive glass (BG) could exert stimulatory effects on chondrogenesis. The aim of this work was to produce and characterize composite porous poly(L-lactide) (PLLA)/1393BG scaffolds via thermally induced phase separation (TIPS) technique and assess their effects on chondrogenesis of nasoseptal chondrocytes. The PLLA scaffolds without or with 1, 2.5, 5% BG1393 were prepared via TIPS technique starting from a ternary solution (polymer/solvent/non-solvent) in a single step. Scaffolds were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and differential scanning calorimetric analysis (DSC). Human nasoseptal chondrocytes were seeded on the scaffolds with 1 and 2.5% BG for 7 and 14 days and cell survival, attachment, morphology and expression of SOX9 and cartilage-specific extracellular cartilage matrix (ECM) components were monitored. The majority of chondrocytes survived on all PLLA scaffolds functionalized with BG for the whole culture period. Also inner parts of the scaffold were colonized by chondrocytes synthesizing an ECM which contained glycosaminoglycans. Type II collagen and aggrecan gene expression increased significantly in 1% BG scaffolds during the culture. Chondrocyte protein expression for cartilage ECM proteins indicated that the chondrocytes maintained their differentiated phenotype in the scaffolds. BG could serve as a cytocompatible basis for future scaffold composites for osteochondral cartilage defect repair. Abbreviations : AB : alcian blue ACAN: gene coding for aggrecan; BG: Bioactive glass; 2D: two-dimensional; 3D: three-dimensional; COL2A1: gene coding for type II collagen; DAPI: 4',6-diamidino-2-phenylindole; DMEM: Dulbecco's Modified Eagle's Medium; DMMB: dimethylmethylene blue; DSC: Differential scanning calorimetric analysis; ECM: extracellular matrix; EDTA: ethylenediaminetetraacetic acid; EtBr: ethidium bromide; FCS: fetal calf serum; FDA: fluorescein diacetate; GAG: glycosaminoglycans; HDPE: high density polyethylene; HE: hematoxylin and eosin staining; HCA: hydoxylapatite; PBE: phosphate buffered EDTA100 mM Na 2 HPO 4 and 5 mM EDTA, pH8; PBS: phosphate buffered saline; PFA: paraformaldehyde; PG: proteoglycans; PI: propidium iodide; PLLA: Poly-L-Lactic Acid Scaffold; RT: room temperature; SD: standard deviation; SEM: scanning electron microscopy; sGAG: sulfated glycosaminoglycans; SOX9/Sox9: SRY (sex-determining region Y)-box 9 protein; TBS: TRIS buffered saline; TIPS: Thermally Induced Phase Separation; XRD: X-ray diffraction analysis.

A galvanic method to deposit chitosan coatings on stainless steel substrate is reported. Deposition of suitable coatings is desired to improve biocompatibility and corrosion resistance of metallic medical devices to be implanted in human body. In the present work, a thin hydrogel layer of chitosan was deposited on 304SS by a galvanic displacement reaction, which is advantageous first as it does not require external power supply. 304SS was immersed into an aqueous solution of chitosan/lactic acid and electrochemically coupled with magnesium acting as a sacrificial anode. SEM images showed the formation of a uniform layer of chitosan with a thickness controlled by deposition time. Corrosion tests in simulating body fluid showed that chitosan coatings shift the corrosion potential of 304 substrates toward nobler values. Finally, the cytotoxicity of the coating was investigated through cell viability assays with osteoblastic cell MC3T3-E1. The results revealed highly satisfying biocompatibility of the coating.

In a large number of medical devices, a key feature of a biomaterial is the ability to successfully bond to living tissues by means of engineered mechanisms such as the enhancement of biomineralization on a bone tissue engineering scaffold or the mimicking of the natural structure of the extracellular matrix (ECM). This ability is commonly referred to as "bioactivity". Materials sciences started to grow interest in it since the development of bioactive glasses by Larry Hench five decades ago. As the main goal in applications of biomedical devices and tissue scaffolds is to obtain a seamless tissue-material interface, achieving optimal bioactivity is essential for the success of most biomaterial-based tissue replacement and regenerative approaches. Polymers derived from lactic acid are largely adopted in the biomedical field, they are versatile, FDA approved and relatively cost-effective. However, as for many other widespread biomedical polymers, they are hydrophobic and lack the intrinsic ability of positively interacting with surrounding tissues. In the last decades scientists have studied many solutions to exploit the positive characteristics of polylactide-based materials overcoming this bottleneck at the same time. The efforts of this research fruitfully produced many effective tissue engineering technologies based on PLA and related biopolymers. This review aims to give an overview on the latest and most promising strategies to improve the bioactivity of lactic acid-based materials, especially focusing on biomolecule-free bulk approaches such as blending, copolymerization or composite fabrication. Avenues for future research to tackle current needs in the field are identified and discussed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this work, the possibility to produce composite Poly-L-lactic acid (PLLA)/Hydroxyapatite (HA) porous scaffolds via Thermally Induced Phase Separation (TIPS) for bone tissue engineering applications was investigated. Several PLLA/HA wt/wt ratios (95/5, 90/10, 70/30, 50/50, 34/66) were tested and the as-obtained scaffolds were characterized via Scanning Electron Microscopy, Wide Angle X-Ray Diffraction, Thermogravimetric analysis, Gas Pycnometry, Differential Scanning Calorimetry and mechanical compression test. Morphological analysis revealed an open structure with interconnected pores and HA particles embedded in the polymer matrix. Finally, cell cultures were carried out into the composite scaffolds in order to evaluate the effect of HA on the proliferation and differentiation of osteoblastic cells, showing a higher alkaline phosphatase activity on composite scaffolds compared to neat PLLA ones., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Damage of hyaline cartilage species such as nasoseptal or joint cartilage requires proper reconstruction, which remains challenging due to the low intrinsic repair capacity of this tissue. Implantation of autologous chondrocytes in combination with a biomimetic biomaterial represents a promising strategy to support cartilage repair. The aim of this work was to assess the viability, attachment, morphology, extracellular matrix (ECM) production of human articular and nasoseptal chondrocytes cultured in vitro in porous poly(l-lactic) (PLLA) scaffolds of two selected pore sizes (100 and 200μm). The PLLA scaffolds with 100 and 200μm pore sizes were prepared via ternary thermally induced phase separation (TIPS) technique and analyzed using scanning electron microscopy (SEM). Articular and nasoseptal chondrocytes were seeded on the scaffold and cultures maintained for 7 and 14days. Live/dead staining, (immuno-)histology and gene expression analysis of type II, type I collagen, aggrecan and SOX9 were performed to assess scaffold cytocompatibility and chondrocyte phenotype. The majority of both chondrocyte types survived on both scaffolds for the whole culture period. Hematoxylin-eosin (HE), alcian blue (visualizing glycosaminoglycans) stainings, immunoreactivity and gene expression of ECM proteins and cartilage marker (type II, I collagen, aggrecan, SOX9) of the chondrocyte scaffold constructs indicated that the smaller pore dimensions promoted the differentiation of the chondrocytes compared with the larger pore size. The present work revealed that the scaffold pore size is an important factor influencing chondrocyte differentiation and indicated that the scaffolds with 100μm pores serve as a cytocompatible basis for further future modifications., (Copyright © 2017. Published by Elsevier B.V.)

Next generation bioreactors are being developed to generate multiple human cell-based tissue analogs within the same fluidic system, to better recapitulate the complexity and interconnection of human physiology [1, 2]. The effective development of these devices requires a solid understanding of their interconnected fluidics, to predict the transport of nutrients and waste through the constructs and improve the design accordingly. In this work, we focus on a specific model of bioreactor, with multiple input/outputs, aimed at generating osteochondral constructs, i.e., a biphasic construct in which one side is cartilaginous in nature, while the other is osseous. We next develop a general computational approach to model the microfluidics of a multi-chamber, interconnected system that may be applied to human-on-chip devices. This objective requires overcoming several challenges at the level of computational modeling. The main one consists of addressing the multi-physics nature of the problem that combines free flow in channels with hindered flow in porous media. Fluid dynamics is also coupled with advection-diffusion-reaction equations that model the transport of biomolecules throughout the system and their interaction with living tissues and C constructs. Ultimately, we aim at providing a predictive approach useful for the general organ-on-chip community. To this end, we have developed a lumped parameter approach that allows us to analyze the behavior of multi-unit bioreactor systems with modest computational effort, provided that the behavior of a single unit can be fully characterized., Competing Interests: The authors have declared that no competing interests exist.

A giant omphalocele is a liver-containing protrusion through an abdominal defect wider than 5 cm in diameter. The giant form with a small abdominal wall defect is a rare condition which, to our knowledge, has not been described previously. We describe three cases with the typical features of elongated vascular liver pedicle and angiomatosis of the hepatic portal system. The abnormal liver organogenesis, due to extra-abdominal development, represented a significant risk factor for hepatic thrombosis after visceral reduction and liver rotation. All the neonates underwent surgery on the first day of postnatal life. One died because of a postoperative liver infarction, and the survivors needed prolonged respiratory support. Prenatal sonographic features, timing, delivery, type of surgical repair, and postnatal outcome are reviewed. A prenatal sonographic diagnosis could be useful to evaluate the abdominal ring and serial ultrasound examinations are recommended to detect promptly ominous signs of hepatic and bowel damage. Color Doppler may be useful to assess the anatomy of the abdominal vessels and their relationships with the herniated organs, although it was not used in any of the cases reported here. This congenital malformation might be considered as a pathological entity separate from giant omphalocele with large abdominal defect, with a severe prognosis due possibly to its different embryological development.