Rupture of sinus of Valsalva aneurysm: case report and review of contemporary literature.

Sinus of Valsalva aneurysm rupture is a rare condition with a great potential for morbidity and mortality if not promptly diagnosed and managed. We present an unusual non-infected sinus of Valsalva aneurysm rupture in a 47-year-old female. This case report, a likely presentation of a late congenital heart defect, highlights the need for a high index of suspicion in a patient with atypical history of congestive cardiac failure.

Adult cardiac surgery in Trinidad and Tobago during the COVID-19 pandemic: Lessons from a developing country.

BACKGROUND AND AIM: The coronavirus disease 2019 (COVID-19) pandemic has seen the cancellation of elective cardiac surgeries worldwide. Here we report the experience of a cardiac surgery unit in a developing country in response to the COVID-19 crisis. METHODS: From 6th April to 12th June 2020, 58 patients underwent urgent or emergency cardiac surgery. Data was reviewed from a prospectively entered unit-maintained cardiac surgery database. To ensure safe delivery of care to patients, a series of strict measures were implemented which included: a parallel healthcare system maintaining a COVID-19 cold site, social isolation of patients for one to 2 weeks before surgery, polymerase chain reaction testing for COVID-19, 72 hours before surgery, discrete staff assigned only to cardiac surgical cases socially isolated for 2 weeks as necessary. RESULTS: The mean age at surgery was 59.7 ± 11 years and 41 (70.7%) were male. Fifty-two patients were hypertensive (90%), and 32 were diabetic (55.2%). There were three emergency type A aortic dissections. Forty-seven patients underwent coronary artery bypass graft surgery with all but three performed off-pump. Fourteen cases required blood product transfusion. One patient had postoperative pneumonia associated with chronic obstructive pulmonary disease. The median length of stay was 5.7 ± 1.8 days. All patients were discharged home after rehabilitation. There were no cases of COVID-19 infection among healthcare workers during the study period. CONCLUSION: These strategies allowed us to maintain a service for urgent and emergency procedures and may prove useful for larger countries when there is decrease in COVID-19 cases and planning for the restart of elective cardiac surgery.

In vitro cyto-biocompatibility study of thin-film transistors substrates using an organotypic culture method.

Thin-Film-Transistors Liquid-Crystal Display has become a standard in the field of displays. However, the structure of these devices presents interest not only in that field, but also for biomedical applications. One of the key components, called here TFT substrate, is a glass substrate with a dense and large array of thousands of transparent micro-electrodes that can be considered as a large scale multi-electrode array(s). Multi-electrode array(s) are widely used for in vitro electrical investigations on neurons and brain, allowing excitation, registration, and recording of their activity. However, the range of application of conventional multi-electrode array(s) is usually limited to some tens of cells in a homogeneous cell culture, because of a small area, small number and a low density of the micro-electrodes. TFT substrates do not have these limitations and the authors are currently studying the possibility to use TFT substrates as new tools for in vitro electrical investigation on tissues and organoids. In this respect, experiments to determine the cyto-biocompatibility of TFT substrates with tissues were conducted and are presented in this study. The investigation was performed using an organotypic culture method with explants of brain and liver tissues of chick embryos. The results in term of morphology, cell migration, cell density and adhesion were compared with the results from Thermanox®, a conventional plastic for cell culture, and with polydimethylsiloxane, a hydrophobic silicone. The results with TFT substrates showed similar results as for the Thermanox®, despite the TFT hydrophobicity. TFT substrates have a weak cell adhesion and promote cell migration similarly to Thermanox®. It could be concluded that the TFT substrates are cyto-biocompatible with the two studied organs.

Effect of a neonatal low-protein diet on the morphology of myotubes in culture and the expression of key proteins that regulate myogenesis in young and adult rats.

AIM: To investigate the effects of a neonatal low-protein diet on the morphology of myotubes in culture and the expression of key proteins that regulate myogenesis in young and adult rats. METHODS: Male Wistar rats (n = 18) were suckled by mothers fed diets containing 17% protein (controls, C) or 8% protein (undernourished, UN). All rats were fed a normal protein diet after weaning. Muscles were removed from the legs of 42-, 60- and 90-day-old rats. Muscle cells were cultured to assess cell number, morphology and the expression of major proteins involved in myogenesis (Pax7, cadherins, ß1 integrin, IL-4Rα and myogenin) by western blotting. IL-4 levels in culture supernatants were measured by ELISA. RESULTS: Offspring from mothers fed a low-protein diet showed a lower body weight gain. Cell number and myotube expansion were reduced in cultured muscle cells from UN, but the expression of myogenic marker proteins was unaltered. CONCLUSIONS: Dietary restriction during lactation had no impact on the synthesis of myogenic marker proteins, and myocyte differentiation occurred normally in the muscles of offspring aged 42, 60 or 90 days. Nevertheless, the number and morphology of the myotubes are altered.

Heparin coating of poly(ethylene terephthalate) decreases hydrophobicity, monocyte/leukocyte interaction and tissue interaction.

Woven poly(ethylene terephthalate) (PET) is widely used in implantable medical devices. Upon implantation, fibrinogen interacts with the PET and changes conformation, such that the fibrinogen P2 epitope may become exposed. This allows inflammatory cells to interact with the material. In this study we have coated PET with heparin and show that this decreases PET hydrophobicity and the presence of the fibrinogen P2 epitope on the material surface. In addition, we show that heparin-induced reduction of PET hydrophobicity correlates with decreased exposure of the fibrinogen P2 epitope and reduced adhesion of monocytes. Reduction of PET hydrophobicity was furthermore associated with reduced PMN elastase production and decreased interaction between PET and embryonic chicken tissue. We conclude that the heparin coating-induced decrease in PET hydrophobicity is associated with decreased interaction between PET and inflammatory cells. Independent of this interaction, the hydrophobic nature of the heparin coating is related to tissue interaction as demonstrated by a reduction in adhesion, growth and spreading of tissue on PET. The combination of these properties makes heparin coating a candidate for improving biocompatibility of PET.

Poly(ε-caprolactone)/Hydroxyapatite 3D Honeycomb Scaffolds for a Cellular Microenvironment Adapted to Maxillofacial Bone Reconstruction.

The elaboration of biomimetic materials inspired from the specific structure of native bone is one the main goal of tissue engineering approaches. To offer the most appropriate environment for bone reconstruction, we combined electrospinning and electrospraying to elaborate an innovative scaffold composed of alternating layers of polycaprolactone (PCL) and hydroxyapatite (HA). In our approach, the electrospun PCL was shaped into a honeycomb-like structure with an inner diameter of 160 µm, capable of providing bone cells with a 3D environment while ensuring the material biomechanical strength. After 5 days of culture without any differentiation factor, the murine embryonic cell line demonstrated excellent cell viability on contact with the PCL-HA structures as well as active colonization of the scaffold. The cell differentiation, as tested by RT-qPCR, revealed a 6-fold increase in the expression of the RNA of the Bglap involved in bone mineralization as compared to a classical 2D culture. This differentiation of the cells into osteoblasts was confirmed by alkaline phosphatase staining of the scaffold cultivated with the cell lineage. Later on, organotypic cultures of embryonic bone tissues showed the high capacity of the PCL-HA honeycomb structure to guide the migration of differentiated bone cells throughout the cavities and the ridge of the biomaterial, with a colonization surface twice as big as that of the control. Taken together, our results indicate that PCL-HA honeycomb structures are biomimetic supports that promotes in vitro osteocompatibility, osteoconduction, and osteoinduction and could be suitable for being used for bone reconstruction in complex situations such as the repair of maxillofacial defects.

Algorithms for left atrial wall segmentation and thickness - Evaluation on an open-source CT and MRI image database.

Structural changes to the wall of the left atrium are known to occur with conditions that predispose to Atrial fibrillation. Imaging studies have demonstrated that these changes may be detected non-invasively. An important indicator of this structural change is the wall's thickness. Present studies have commonly measured the wall thickness at few discrete locations. Dense measurements with computer algorithms may be possible on cardiac scans of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). The task is challenging as the atrial wall is a thin tissue and the imaging resolution is a limiting factor. It is unclear how accurate algorithms may get and how they compare in this new emerging area. We approached this problem of comparability with the Segmentation of Left Atrial Wall for Thickness (SLAWT) challenge organised in conjunction with MICCAI 2016 conference. This manuscript presents the algorithms that had participated and evaluation strategies for comparing them on the challenge image database that is now open-source. The image database consisted of cardiac CT (n=10) and MRI (n=10) of healthy and diseased subjects. A total of 6 algorithms were evaluated with different metrics, with 3 algorithms in each modality. Segmentation of the wall with algorithms was found to be feasible in both modalities. There was generally a lack of accuracy in the algorithms and inter-rater differences showed that algorithms could do better. Benchmarks were determined and algorithms were ranked to allow future algorithms to be ranked alongside the state-of-the-art techniques presented in this work. A mean atlas was also constructed from both modalities to illustrate the variation in thickness within this small cohort.

Organotypic culture to assess cell adhesion, growth and alignment of different organs on silk fibroin.

Glass sheets covered with aligned electrospun silk fibroin (Bombyx mori) were compared to tissue culture-treated Thermanox® coverslips, using an organotypic culture method. Different chick embryo organ behaviours were analysed in terms of circularity, cell growth and cell adhesion after being cultivated in contact with these two materials. The circularity (cell layer shape corresponding to the trend of the biomaterials to induce a specific directionality) depends on the organ used when in contact with silk fibroin. This biomaterial induced higher cell adhesion (kidney) or lower cell adhesion (spine) compared to Thermanox. Cell growth, represented by the cell layer area (mm2 ), was also drastically reduced (gonad) or increased (blood vessel) on the silk fibroin. Organotypic culture is a rapid, cost effective and relatively simple method to evaluate different parameters, allowing prescreening of morphology and cytocompatibility to select the appropriate applications for new biomaterials. In the present study we compared the morphology of different organotypic cultures on orientated silk and Thermanox as growth supports to rapidly evaluate the benefit of a silk-based biomaterial for tissue engineering. Copyright © 2014 John Wiley & Sons, Ltd.

Evaluation of Fibrin-Based Interpenetrating Polymer Networks as Potential Biomaterials for Tissue Engineering.

Interpenetrating polymer networks (IPNs) have gained great attention for a number of biomedical applications due to their improved properties compared to individual components alone. In this study, we investigated the capacity of newly-developed naturally-derived IPNs as potential biomaterials for tissue engineering. These IPNs combine the biologic properties of a fibrous fibrin network polymerized at the nanoscale and the mechanical stability of polyethylene oxide (PEO). First, we assessed their cytotoxicity in vitro on L929 fibroblasts. We further evaluated their biocompatibility ex vivo with a chick embryo organotypic culture model. Subcutaneous implantations of the matrices were subsequently conducted on nude mice to investigate their biocompatibility in vivo. Our preliminary data highlighted that our biomaterials were non-cytotoxic (viability above 90%). The organotypic culture showed that the IPN matrices induced higher cell adhesion (across all the explanted organ tissues) and migration (skin, intestine) than the control groups, suggesting the advantages of using a biomimetic, yet mechanically-reinforced IPN-based matrix. We observed no major inflammatory response up to 12 weeks post implantation. All together, these data suggest that these fibrin-based IPNs are promising biomaterials for tissue engineering.

Analysis of the biocompatibility of perfluoropolyether dimethacrylate network using an organotypic method.

In this work, we have investigated the potential of perfluoropolyether (PFPE) polymers for use in biomaterial applications, especially in cell culture and tissue engineering. PFPE substrates were synthesized by the photocuring of liquid PFPE urethane dimethacrylate. These surfaces were then modified by ECM protein coatings and microstructuration, to promote cell adhesion and migration. The surface properties of PFPE and PDMS (used as a reference) samples were studied by static contact angle measurements and AFM imaging. Both polymer surfaces were hydrophobic, having sessile air-water contact angles superior to 100°. Collagen and fibronectin coatings were found to change the wettability of PFPE and PDMS samples. The biological testing of substrates was done using a liver organotypic culture to evaluate the migration and density of liver cells. The results over seven days of culture demonstrated that the migration and density of cells cultured under untreated PFPE were higher than the migration and density of cells cultured under PDMS. ECM protein coatings enhanced cell migration from liver explants cultured on PFPE or PDMS. Furthermore, these coatings were more efficient in the case of a PFPE sample. From a second series of tests, in which the PFPE was microstructured, it was found that microstructures promoted the formation of a 3D cell layer. These results indicate that PFPE polymers have a potential for use in the development of biomaterials for tissue engineering and cell culture.

Biocompatibility study of lithium disilicate and zirconium oxide ceramics for esthetic dental abutments.

PURPOSE: The increasing demand for esthetically pleasing results has contributed to the use of ceramics for dental implant abutments. The aim of this study was to compare the biological response of epithelial tissue cultivated on lithium disilicate (LS2) and zirconium oxide (ZrO2) ceramics. Understanding the relevant physicochemical and mechanical properties of these ceramics will help identify the optimal material for facilitating gingival wound closure. METHODS: Both biomaterials were prepared with 2 different surface treatments: raw and polished. Their physicochemical characteristics were analyzed by contact angle measurements, scanning white-light interferometry, and scanning electron microscopy. An organotypic culture was then performed using a chicken epithelium model to simulate peri-implant soft tissue. We measured the contact angle, hydrophobicity, and roughness of the materials as well as the tissue behavior at their surfaces (cell migration and cell adhesion). RESULTS: The best cell migration was observed on ZrO2 ceramic. Cell adhesion was also drastically lower on the polished ZrO2 ceramic than on both the raw and polished LS2. Evaluating various surface topographies of LS2 showed that increasing surface roughness improved cell adhesion, leading to an increase of up to 13%. CONCLUSIONS: Our results demonstrate that a biomaterial, here LS2, can be modified using simple surface changes in order to finely modulate soft tissue adhesion. Strong adhesion at the abutment associated with weak migration assists in gingival wound healing. On the same material, polishing can reduce cell adhesion without drastically modifying cell migration. A comparison of LS2 and ZrO2 ceramic showed that LS2 was more conducive to creating varying tissue reactions. Our results can help dental surgeons to choose, especially for esthetic implant abutments, the most appropriate biomaterial as well as the most appropriate surface treatment to use in accordance with specific clinical dental applications.

Enhanced cellular adhesion on titanium by silk functionalized with titanium binding and RGD peptides.

Soft tissue adhesion on titanium represents a challenge for implantable materials. In order to improve adhesion at the cell/material interface we used a new approach based on the molecular recognition of titanium by specific peptides. Silk fibroin protein was chemically grafted with titanium binding peptide (TiBP) to increase adsorption of these chimeric proteins to the metal surface. A quartz crystal microbalance was used to quantify the specific adsorption of TiBP-functionalized silk and an increase in protein deposition by more than 35% was demonstrated due to the presence of the binding peptide. A silk protein grafted with TiBP and fibronectin-derived arginine-glycine-aspartic acid (RGD) peptide was then prepared. The adherence of fibroblasts on the titanium surface modified with the multifunctional silk coating demonstrated an increase in the number of adhering cells by 60%. The improved adhesion was demonstrated by scanning electron microscopy and immunocytochemical staining of focal contact points. Chick embryo organotypic culture also revealed strong adhesion of endothelial cells expanding on the multifunctional silk peptide coating. These results demonstrated that silk functionalized with TiBP and RGD represents a promising approach to modify cell-biomaterial interfaces, opening new perspectives for implantable medical devices, especially when reendothelialization is required.

Cytocompatibility of titanium metal injection molding with various anodic oxidation post-treatments.

Metal injection molding (MIM) is a near net shape manufacturing method that allows for the production of components of small to moderate size and complex shape. MIM is a cost-effective and flexible manufacturing technique that provides a large innovative potential over existing methods for the industry of implantable devices. Commercially pure titanium (CP-Ti) samples were machined to the same shape as a composite feedstock with titanium and polyoxymethylene, and these metals were injected, debinded and sintered to assess comparative biological properties. Moreover, we treated MIM-Ti parts with BIOCOAT®, BIODIZE® and BIOCER®, three different anodic oxidation techniques that treat titanium using acid, alkaline and anion enriched electrolytes, respectively. Cytocompatibility as well as morphological and chemical features of surfaces was comparatively assessed on each sample, and the results revealed that MIM-Ti compared to CP-Ti demonstrated a specific surface topography with a higher roughness. MIM-Ti and BIOCER® samples significantly enhanced cell proliferation, cell adhesion and cell differentiation compared to CP-Ti. Interestingly, in the anodization post-treatment established in this study, we demonstrated the ability to improve osseointegration through anionic modification treatment. The excellent biological response we observed with MIM parts using the injection molding process represents a promising manufacturing method for the future implantable devices in direct contact with bones.

Modulating in vitro bone cell and macrophage behavior by immobilized enzymatically tailored pectins.

Previous work has reported the results of a multidisciplinary effort producing a proof-of-concept on the use of pectic polysaccharides in the surface modification of medical devices. This study was designed to learn more about the capability of engineered rhamnogalacturonan-I (RG-I) fractions of apple pectin to control bone cell and macrophage behavior. Thermanox or polystyrene Petri dishes were surface modified with two different modified hairy regions (MHRs) obtained by different enzymatic liquefaction processes of apples differing in relative amounts and lengths of their neutral side chains: (long-haired) MHR-alpha and (short-haired) MHR-B. Bone explants from 14-day-old chick embryos were cultured for 14 days on both pectic substrata. MHR-B promoted cell migration and differentiation, MHR-alpha did not. On MHR-alpha, J774.2 macrophages grew well, their percentage in G1 phase was decreased and in S phase increased, and they did not secrete either proinflammatory-cytokines or nitrites. Contrasting results were gained from macrophages on MHR-B, except for nitrite secretion. Thus, we conclude that coatings from tailored pectins show different biological activities in vitro and are potential innovative candidates for improving the biocompatibility of medical devices in various applications.