Pulmonary valve replacement in tetralogy of Fallot - who and how?

BACKGROUND AND AIM: Pulmonary regurgitation is the most common complication in repaired tetralogy of Fallot patients. Severe chronic pulmonary regurgitation can be tolerated for decades, but if not treated, it can progress to symptomatic, irreversible right ventricular dilatation and dysfunction. We investigated clinical associations with pulmonary valve replacement among patients with significative pulmonary regurgitation and how interventional developments can change their management. METHODS: All adult patients with repaired tetralogy of Fallot who were followed at an adult CHD Clinic at a single centre from 1980 to 2022 were included on their first outpatient visit. Follow-up was estimated from the time of correction surgery until one of the following events occurred first: pulmonary valve replacement, death, loss to follow-up or conclusion of the study. RESULTS: We included 221 patients (116 males) with a median age of 19 (18-25). At a median age of 33 (10) years old, 114 (51%) patients presented significant pulmonary regurgitation. Among patients with significant pulmonary regurgitation, pulmonary valve replacement was associated with male gender, older age at surgical repair, and longer QRS duration in adulthood. Pulmonary valve replacement was performed in 50 patients, including four transcatheter pulmonary valve implantations, at a median age of 34 (14) years. CONCLUSION: Pulmonary regurgitation affects a large percentage of tetralogy of Fallot adult patients, requiring a long-term clinical and imaging follow-up. Sex, age at surgical repair and longer QRS are associated with the need of PVR among patients with significative pulmonary regurgitation. Clinical practice and current literature support TPVI as the future gold standard intervention.

Hydroxyapatite-filled osteoinductive and piezoelectric nanofibers for bone tissue engineering.

Osteoporotic-related fractures are among the leading causes of chronic disease morbidity in Europe and in the US. While a significant percentage of fractures can be repaired naturally, in delayed-union and non-union fractures surgical intervention is necessary for proper bone regeneration. Given the current lack of optimized clinical techniques to adequately address this issue, bone tissue engineering (BTE) strategies focusing on the development of scaffolds for temporarily replacing damaged bone and supporting its regeneration process have been gaining interest. The piezoelectric properties of bone, which have an important role in tissue homeostasis and regeneration, have been frequently neglected in the design of BTE scaffolds. Therefore, in this study, we developed novel hydroxyapatite (HAp)-filled osteoinductive and piezoelectric poly(vinylidene fluoride-co-tetrafluoroethylene) (PVDF-TrFE) nanofibers via electrospinning capable of replicating the tissue's fibrous extracellular matrix (ECM) composition and native piezoelectric properties. The developed PVDF-TrFE/HAp nanofibers had biomimetic collagen fibril-like diameters, as well as enhanced piezoelectric and surface properties, which translated into a better capacity to assist the mineralization process and cell proliferation. The biological cues provided by the HAp nanoparticles enhanced the osteogenic differentiation of seeded human mesenchymal stem/stromal cells (MSCs) as observed by the increased ALP activity, cell-secreted calcium deposition and osteogenic gene expression levels observed for the HAp-containing fibers. Overall, our findings describe the potential of combining PVDF-TrFE and HAp for developing electroactive and osteoinductive nanofibers capable of supporting bone tissue regeneration.

Novel Electroactive Mineralized Polyacrylonitrile/PEDOT:PSS Electrospun Nanofibers for Bone Repair Applications.

Bone defect repair remains a critical challenge in current orthopedic clinical practice, as the available therapeutic strategies only offer suboptimal outcomes. Therefore, bone tissue engineering (BTE) approaches, involving the development of biomimetic implantable scaffolds combined with osteoprogenitor cells and native-like physical stimuli, are gaining widespread interest. Electrical stimulation (ES)-based therapies have been found to actively promote bone growth and osteogenesis in both in vivo and in vitro settings. Thus, the combination of electroactive scaffolds comprising conductive biomaterials and ES holds significant promise in improving the effectiveness of BTE for clinical applications. The aim of this study was to develop electroconductive polyacrylonitrile/poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PAN/PEDOT:PSS) nanofibers via electrospinning, which are capable of emulating the native tissue's fibrous extracellular matrix (ECM) and providing a platform for the delivery of exogenous ES. The resulting nanofibers were successfully functionalized with apatite-like structures to mimic the inorganic phase of the bone ECM. The conductive electrospun scaffolds presented nanoscale fiber diameters akin to those of collagen fibrils and displayed bone-like conductivity. PEDOT:PSS incorporation was shown to significantly promote scaffold mineralization in vitro. The mineralized electroconductive nanofibers demonstrated improved biological performance as observed by the significantly enhanced proliferation of both human osteoblast-like MG-63 cells and human bone marrow-derived mesenchymal stem/stromal cells (hBM-MSCs). Moreover, mineralized PAN/PEDOT:PSS nanofibers up-regulated bone marker genes expression levels of hBM-MSCs undergoing osteogenic differentiation, highlighting their potential as electroactive biomimetic BTE scaffolds for innovative bone defect repair strategies.

Loss and rescue of osteocalcin and osteopontin modulate osteogenic and angiogenic features of mesenchymal stem/stromal cells.

Noncollagenous proteins in the bone extracellular matrix, such as osteocalcin (OC) and osteopontin (OPN), inherent to evolution of bone as a skeletal tissue, are known to regulate bone formation and mineralization. However, the fundamental basis of this regulatory role remains unknown. Here, for the first time, we use mouse mesenchymal stem/stromal cells (MSC) lacking both OC and OPN to investigate the mechanistic roles of OC and OPN on the proliferation capacity and differentiation ability of MSC. We found that the loss of OC and OPN reduces stem cells self-renewal potential and multipotency, affects their differentiation into an osteogenic lineage, and impairs their angiogenic potential while maintaining chondrogenic and adipogenic lineages. Moreover, loss of OC and OPN compromises the extracellular matrix integrity and maturation, observed by an unexpected enhancement of glycosaminoglycans content that are associated with a more primitive skeletal connective tissue, and by a delay on the maturation of mineral species produced. Interestingly, exogenously supplemented OC and OPN were able to rescue MSC proliferative and osteogenic potential along with matrix integrity and mineral quality. Taken together, these results highlight the key contributions of OC and OPN in enhancing osteogenesis and angiogenesis over primitive connective tissue, and support a potential therapeutic approach based on their exogenous supplementation.

Glycosaminoglycan remodeling during chondrogenic differentiation of human bone marrow-/synovial-derived mesenchymal stem/stromal cells under normoxia and hypoxia.

Glycosaminoglycans (GAGs) are major components of cartilage extracellular matrix (ECM), which play an important role in tissue homeostasis not only by providing mechanical load resistance, but also as signaling mediators of key cellular processes such as adhesion, migration, proliferation and differentiation. Specific GAG types as well as their disaccharide sulfation patterns can be predictive of the tissue maturation level but also of disease states such as osteoarthritis. In this work, we used a highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to perform a comparative study in terms of temporal changes in GAG and disaccharide composition between tissues generated from human bone marrow- and synovial-derived mesenchymal stem/stromal cells (hBMSC/hSMSC) after chondrogenic differentiation under normoxic (21% O2) and hypoxic (5% O2) micromass cultures. The chondrogenic differentiation of hBMSC/hSMSC cultured under different oxygen tensions was assessed through aggregate size measurement, chondrogenic gene expression analysis and histological/immunofluorescence staining in comparison to human chondrocytes. For all the studied conditions, the compositional analysis demonstrated a notable increase in the average relative percentage of chondroitin sulfate (CS), the main GAG in cartilage composition, throughout MSC chondrogenic differentiation. Additionally, hypoxic culture conditions resulted in significantly different average GAG and CS disaccharide percentage compositions compared to the normoxic ones. However, such effect was considerably more evident for hBMSC-derived chondrogenic aggregates. In summary, the GAG profiles described here may provide new insights for the prediction of cartilage tissue differentiation/disease states and to characterize the quality of MSC-generated chondrocytes obtained under different oxygen tension culture conditions.

Sources of hepatic glycogen synthesis in mice fed with glucose or fructose as the sole dietary carbohydrate.

PURPOSE: The positional analysis of hepatic glycogen enrichment from deuterated water (2 H2 O) by 2 H NMR has been applied previously to resolve the contributions of glucose and fructose to glycogen synthesis in rodents fed a high sucrose diet. To further validate this method, this analysis was applied to mice fed with synthetic diets whose carbohydrate components consisted solely of either glucose or fructose. METHODS: Eight glucose-fed and 12 fructose-fed mice were given 2 H2 O followed by ad libitum feeding overnight. Mice were then euthanized, hepatic glycogen was isolated and derivatized to monoacetone glucose, and 2 H-enrichment of positions 2, 5, and 6S were measured by 2 H NMR. From these data, the fraction of overnight glycogen appearance from the direct pathway and/or glycogen cycling and indirect pathway were estimated. Indirect pathway fractions were resolved into Krebs cycle and triose-phosphate sources-the latter including contributions from fructose metabolism. RESULTS: After overnight feeding, the fraction of overnight glycogen appearance derived from direct pathway and/or glycogen cycling in glucose-fed-mice was 63 ± 1%. For the indirect pathway, Krebs cycle and triose-phosphate sources contributed 22 ± 1% and 15 ± 1%, respectively. For fructose-fed-mice, glycogen appearance was dominated by triose-phosphate sources (60 ± 2%) with lesser contributions from Krebs cycle (14 ± 1%) and direct and/or glycogen cycling (26 ± 2%). CONCLUSIONS: 2 H NMR analysis of hepatic glycogen 2 H enrichment from 2 H2 O provides realistic profiles of dietary glucose and fructose contributions to hepatic glycogen synthesis in mice fed with diets containing 1 or the other sugar as the sole carbohydrate source.

Determining contributions of exogenous glucose and fructose to de novo fatty acid and glycerol synthesis in liver and adipose tissue.

The de novo synthesis of triglyceride (TG) fatty acids (FA) and glycerol can be measured with stable isotope tracers. However, these methods typically do not inform the contribution of a given substrate to specific pathways on these synthetic processes. We integrated deuterated water (2H2O) measurement of de novo lipogenesis (DNL) and glycerol-3-phosphate (GLY) synthesis from all substrates with a 13C nuclear magnetic resonance (NMR) method that quantifies TG FA and glycerol enrichment from a specific [U-13C]precursor. This allowed the [U-13C]precursor contribution to DNL and GLY to be estimated. We applied this method in mice to determine the contributions of fructose and glucose supplemented in the drinking water to DNL and GLY in liver, mesenteric adipose tissue (MAT) and subcutaneous adipose tissue (SCAT). In liver, fructose contributed significantly more to DNL of saturated fatty acids (SFA) and oleate as well as to GLY compared to glucose. Moreover, its contribution to SFA synthesis was significantly higher compared to that of oleate. MAT and SCAT had lower fractional rates of total DNL and GLY compared to liver and glucose was utilized more predominantly than fructose for TG synthesis in these tissues. This novel 2H2O/13C integrated method revealed for the first time, tissue specific selection of substrates for DNL, particularly fructose in regard to glucose in liver. Also, this approach was able to resolve the distribution of specific FAs into the TG sn2 and sn1,3 sites. This stable isotope integrated approach yielded information so far uncovered by other lipidomic tools and should powerfully assist in other nutritional, pathological or environmental contexts.

Compositional and structural analysis of glycosaminoglycans in cell-derived extracellular matrices.

The extracellular matrix (ECM) is a highly dynamic and complex meshwork of proteins and glycosaminoglycans (GAGs) with a crucial role in tissue homeostasis and organization not only by defining tissue architecture and mechanical properties, but also by providing chemical cues that regulate major biological processes. GAGs are associated with important physiological functions, acting as modulators of signaling pathways regulating several cellular processes such as cell growth and differentiation. Recently, in vitro fabricated cell-derived ECM have emerged as promising materials for regenerative medicine due to their ability of better recapitulate the native ECM-like composition and structure, without the limitations of availability and pathogen transfer risks of tissue-derived ECM scaffolds. However, little is known about the molecular and more specifically, GAG composition of these cell-derived ECM. In this study, three different cell-derived ECM were produced in vitro and characterized in terms of their GAG content, composition and sulfation patterns using a highly sensitive liquid chromatography-tandem mass spectrometry technique. Distinct GAG compositions and disaccharide sulfation patterns were verified for the different cell-derived ECM. Additionally, the effect of decellularization method on the GAG and disaccharide relative composition was also assessed. In summary, the method presented here offers a novel approach to determine the GAG composition of cell-derived ECM, which we believe is critical for a better understanding of ECM role in directing cellular responses and has the potential for generating important knowledge to use in the development of novel ECM-like biomaterials for tissue engineering applications.

Cross-tolerance between nitric oxide synthase inhibition and atypical antipsychotics modify nicotinamide-adenine-dinucleotide phosphate-diaphorase activity in mouse lateral striatum.

Previous research indicates that the subchronic administration of NG-nitro-L-arginine (L-NOARG) produces tolerance to haloperidol-induced catalepsy in Swiss mice. The present study aimed to further investigate whether intermittent subchronic systemic administration of L-NOARG induces tolerance to the cataleptic effects of haloperidol as well as olanzapine or clozapine (Clz) in C57Bl mice after subchronic administration for 5 consecutive days. Striatal FosB protein expression was measured in an attempt to gain further insights into striatal mechanisms in antipsychotic-induced extrapyramidal symptoms side effects. An nicotinamide-adenine-dinucleotide phosphate-diaphorase histochemical reaction was also used to investigate whether tolerance could induce changes in the number of nitric oxide synthase-active neurons. Subchronic administration of all antipsychotics produced catalepsy, but cross-tolerance was observed only between L-NOARG (15 mg/kg, intraperitoneally) and Clz (20 mg/kg, intraperitoneally). This cross-tolerance effect was accompanied by decreased FosB protein expression in the dorsal striatum and the nucleus accumbens shell region, and reduced icotinamide-adenine-dinucleotide phosphate-diaphorase activity in the dorsal and ventral lateral striatum. Overall, these results suggest that interference with the formation of nitric oxide, mainly in the dorsal and ventral lateral-striatal regions, appears to improve the cataleptic effects induced by antipsychotics acting as antagonists of low-affinity dopamine D2 receptor, such as Clz.

Intestinal Microbial and Metabolic Profiling of Mice Fed with High-Glucose and High-Fructose Diets.

Increased sugar intake is implicated in Type-2 diabetes and fatty liver disease; however, the mechanisms through which glucose and fructose promote these conditions are unclear. We hypothesize that alterations in intestinal metabolite and microbiota profiles specific to each monosaccharide are involved. Two groups of six adult C57BL/6 mice were fed for 10-weeks with diets with glucose (G) or fructose (F) as sole carbohydrates, and a third group was fed with a normal chow carbohydrate mixture (N). Fecal metabolites were profiled by nuclear magnetic resonance (NMR) and microbial composition by real-time polymerase chain reaction (qPCR). Although N, G and F mice exhibited similar weight gains (with slight slower gains for F) and glucose tolerance, multivariate analysis of NMR data indicated that F mice were separated from N and G, with decreased butyrate and glutamate and increased fructose, succinate, taurine, tyrosine, and xylose. The different sugar diets also resulted in distinct intestinal microbiota profiles. That associated with fructose seemed to hold more potential to induce host metabolic disturbances compared to glucose, mainly by promoting bile acid deconjugation and taurine release and compromising intestinal barrier integrity. This may reflect the noted nonquantitative intestinal fructose absorption hence increasing its availability for microbial metabolism, a subject for further investigation.

Direct coupled electrical stimulation towards improved osteogenic differentiation of human mesenchymal stem/stromal cells: a comparative study of different protocols.

Electrical stimulation (ES) has been described as a promising tool for bone tissue engineering, being known to promote vital cellular processes such as cell proliferation, migration, and differentiation. Despite the high variability of applied protocol parameters, direct coupled electric fields have been successfully applied to promote osteogenic and osteoinductive processes in vitro and in vivo. Our work aims to study the viability, proliferation, and osteogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cells when subjected to five different ES protocols. The protocols were specifically selected to understand the biological effects of different parts of the generated waveform for typical direct-coupled stimuli. In vitro culture studies evidenced variations in cell responses with different electric field magnitudes (numerically predicted) and exposure protocols, mainly regarding tissue mineralization (calcium contents) and osteogenic marker gene expression while maintaining high cell viability and regular morphology. Overall, our results highlight the importance of numerical guided experiments to optimize ES parameters towards improved in vitro osteogenesis protocols.

Fabrication and Characterization of Porous PEGDA Hydrogels for Articular Cartilage Regeneration.

Functional articular cartilage regeneration remains an unmet medical challenge, increasing the interest for innovative biomaterial-based tissue engineering (TE) strategies. Hydrogels, 3D macromolecular networks with hydrophilic groups, present articular cartilage-like features such as high water content and load-bearing capacity. In this study, 3D porous polyethylene glycol diacrylate (PEGDA) hydrogels were fabricated combining the gas foaming technique and a UV-based crosslinking strategy. The 3D porous PEGDA hydrogels were characterized in terms of their physical, structural and mechanical properties. Our results showed that the size of the hydrogel pores can be modulated by varying the initiator concentration. In vitro cytotoxicity tests showed that 3D porous PEGDA hydrogels presented high biocompatibility both with human chondrocytes and osteoblast-like cells. Importantly, the 3D porous PEGDA hydrogels supported the viability and chondrogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cell (hBM-MSC)-based spheroids as demonstrated by the positive staining of typical cartilage extracellular matrix (ECM) (glycosaminoglycans (GAGs)) and upregulation of chondrogenesis marker genes. Overall, the produced 3D porous PEGDA hydrogels presented cartilage-like mechanical properties and supported MSC spheroid chondrogenesis, highlighting their potential as suitable scaffolds for cartilage TE or disease modelling strategies.

Synergy between 3D-extruded electroconductive scaffolds and electrical stimulation to improve bone tissue engineering strategies.

In this work, we propose a simple, reliable, and versatile strategy to create 3D electroconductive scaffolds suitable for bone tissue engineering (TE) applications with electrical stimulation (ES). The proposed scaffolds are made of 3D-extruded poly(ε-caprolactone) (PCL), subjected to alkaline treatment, and of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), anchored to PCL with one of two different crosslinkers: (3-glycidyloxypropyl)trimethoxysilane (GOPS) and divinyl sulfone (DVS). Both cross-linkers allowed the formation of a homogenous and continuous coating of PEDOT:PSS to PCL. We show that these PEDOT:PSS coatings are electroconductive (11.3-20.1 S cm-1), stable (up to 21 days in saline solution), and allow the immobilization of gelatin (Gel) to further improve bioactivity. In vitro mineralization of the corresponding 3D conductive scaffolds was greatly enhanced (GOPS(NaOH)-Gel - 3.1 fold, DVS(NaOH)-Gel - 2.0 fold) and cell colonization and proliferation were the highest for the DVS(NaOH)-Gel scaffold. In silico modelling of ES application in DVS(NaOH)-Gel scaffolds indicates that the electrical field distribution is homogeneous, which reduces the probability of formation of faradaic products. Osteogenic differentiation of human bone marrow derived mesenchymal stem/stromal cells (hBM-MSCs) was performed under ES. Importantly, our results clearly demonstrated a synergistic effect of scaffold electroconductivity and ES on the enhancement of MSC osteogenic differentiation, particularly on cell-secreted calcium deposition and the upregulation of osteogenic gene markers such as COL I, OC and CACNA1C. These scaffolds hold promise for future clinical applications, including manufacturing of personalized bone TE grafts for transplantation with enhanced maturation/functionality or bioelectronic devices.

Recent Advances on Electrospun Nanofibers for Periodontal Regeneration.

Periodontitis is an inflammatory infection caused by bacterial plaque accumulation that affects the periodontal tissues. Current treatments lack bioactive signals to induce tissue repair and coordinated regeneration of the periodontium, thus alternative strategies are needed to improve clinical outcomes. Electrospun nanofibers present high porosity and surface area and are able to mimic the natural extracellular matrix, which modulates cell attachment, migration, proliferation, and differentiation. Recently, several electrospun nanofibrous membranes have been fabricated with antibacterial, anti-inflammatory, and osteogenic properties, showing promising results for periodontal regeneration. Thus, this review aims to provide an overview of the current state of the art of these nanofibrous scaffolds in periodontal regeneration strategies. First, we describe the periodontal tissues and periodontitis, as well as the currently available treatments. Next, periodontal tissue engineering (TE) strategies, as promising alternatives to the current treatments, are addressed. Electrospinning is briefly explained, the characteristics of electrospun nanofibrous scaffolds are highlighted, and a detailed overview of electrospun nanofibers applied to periodontal TE is provided. Finally, current limitations and possible future developments of electrospun nanofibrous scaffolds for periodontitis treatment are also discussed.

Extrapyramidal Side Effects with Chronic Atypical Antipsychotic Can Be Predicted by Labeling Pattern of FosB and phosphoThr34-DARPP-32 in Nucleus Accumbens.

Extrapyramidal side effects (EPS) can be induced by neuroleptics that regulate the expression of transcription factor FosB and dopaminergic mediator DARPP-32 in the striatum. However, the long-term neurobiological changes in striatal projection neurons resulting from a cumulative dosage of typical and atypical antipsychotics are poorly understood. The present study aimed to determine the differential and long-lasting changes in FosB distribution and DARPP-32 phosphorylation in the striatum and nucleus accumbens (NAc) associated with chronic antipsychotic-induced EPS. Male C57Bl/6J mice received daily injections of Olanzapine (Olz, 15 mg/kg), Clozapine (Clz, 20 mg/kg), or Haloperidol (Hal, 1 mg/kg), for a period of 11 weeks with a 4-day withdrawal period before the last dosage. Catalepsy for detection of EPS, along with open-field and rotarod tests, were assessed as behavioral correlates of motor responses. Additionally, FosB and phosphorylated-DARPP-32 immunohistochemistry were examined in striatal regions after treatment. All antipsychotics produced catalepsy and reduced open-field exploration, such as impaired rota-rod performance after Olz and Hal. The washout period was critical for Clz-induced side effects reduction. Both Olz and Clz increased FosB in NAc Shell-region, and phosphoThr34-DARPP-32 in NAc. Only Clz reduced phosphoThr75-DARPP-32 in the dorsal striatum and showed FosB/phosphoThr34-Darpp-32-ir in the NAc Core region. This study provides evidence that atypical antipsychotics such as Olz and Clz also give rise to EPS effects frequently associated with a cumulative dosage of typical neuroleptics such as Hal. Nevertheless, FosB/phosphoThr34-Darpp-32-ir in the NAc Core region is associated with hypokinetic movements inhibition.

JANUS: an open-source 3D printable perfusion bioreactor and numerical model-based design strategy for tissue engineering.

Bioreactors have been employed in tissue engineering to sustain longer and larger cell cultures, managing nutrient transfer and waste removal. Multiple designs have been developed, integrating sensor and stimulation technologies to improve cellular responses, such as proliferation and differentiation. The variability in bioreactor design, stimulation protocols, and cell culture conditions hampered comparison and replicability, possibly hiding biological evidence. This work proposes an open-source 3D printable design for a perfusion bioreactor and a numerical model-driven protocol development strategy for improved cell culture control. This bioreactor can simultaneously deliver capacitive-coupled electric field and fluid-induced shear stress stimulation, both stimulation systems were validated experimentally and in agreement with numerical predictions. A preliminary in vitro validation confirmed the suitability of the developed bioreactor to sustain viable cell cultures. The outputs from this strategy, physical and virtual, are openly available and can be used to improve comparison, replicability, and control in tissue engineering applications.

Super-Strong Hydrogel Composites Reinforced with PBO Nanofibers for Cartilage Replacement.

Cartilage replacement materials exhibiting a set of demanding properties such as high water content, high mechanical stiffness, low friction, and excellent biocompatibility are quite difficult to achieve. Here, poly(p-phenylene-2,6-benzobisoxazole) (PBO) nanofibers are combined with polyvinyl alcohol (PVA) to form a super-strong structure with a performance that surpasses the vast majority of previously existing hydrogels. PVA-PBO composites with water contents in the 59-76% range exhibit tensile and compressive moduli reaching 20.3 and 4.5 MPa, respectively, and a coefficient of friction below 0.08. Further, they are biocompatible and support the viability of chondrocytes for 1 week, with significant improvements in cell adhesion, proliferation, and differentiation compared to PVA. The new composites can be safely sterilized by steam heat or gamma radiation without compromising their integrity and overall performance. In addition, they show potential to be used as local delivery platforms for anti-inflammatory drugs. These attractive features make PVA-PBO composites highly competitive engineered materials with remarkable potential for use in the design of load-bearing tissues. Complementary work has also revealed that these composites will be interesting alternatives in other industrial fields where high thermal and mechanical resistance are essential requirements, or which can take advantage of the pH responsiveness functionality.

Production of Blended Poly(acrylonitrile): Poly(ethylenedioxythiophene):Poly(styrene sulfonate) Electrospun Fibers for Neural Applications.

This study describes, for the first time, the successful incorporation of poly(ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) in Poly(acrylonitrile) (PAN) fibers. While electroconductive PEDOT:PSS is extremely challenging to electrospun into fibers. Therefore, PAN, a polymer easy to electrospun, was chosen as a carrier due to its biocompatibility and tunable chemical stability when cross-linked, particularly using strong acids. PAN:PEDOT:PSS blends, prepared from PEDOT:PSS Clevios PH1000, were electrospun into fibers (PH1000) with a diameter of 515 ± 120 nm, which after being thermally annealed (PH1000 24H) and treated with heated sulfuric acid (PH1000 H2SO4), resulted in fibers with diameters of 437 ± 109 and 940 ± 210 nm, respectively. The fibers obtained over the stepwise process were characterized through infra-red/Raman spectroscopy and cyclic voltammetry. The final fiber meshes showed enhanced electroconductivity (3.2 × 10-3 S cm-1, four-points-assay). Fiber meshes biocompatibility was evaluated using fibroblasts and neural stem cells (NSCs) following, respectively, the ISO10993 guidelines and standard adhesion/proliferation assay. NSCs cultured on PH1000 H2SO4 fibers presented normal morphology and high proliferation rates (0.37 day-1 vs. 0.16 day-1 for culture plate), indicating high biocompatibility for NSCs. Still, the low initial NSC adhesion of 7% calls for improving seeding methodologies. PAN:PEDOT:PSS fibers, here successful produced for the first time, have potential applications in neural tissue engineering and soft electronics.

Acute total occlusion of the unprotected left main coronary artery: Patient characteristics and outcomes.

INTRODUCTION AND OBJECTIVES: Acute total occlusion of the unprotected left main coronary artery (LMCA) is a dramatic event. There are limited data regarding this population. We aimed to describe the clinical presentation and outcomes of patients and to determine predictors of in-hospital mortality. METHODS: This retrospective study included patients presenting with acute (<12 h) myocardial infarction due to total occlusion of the LMCA (TIMI flow 0) between January 2008 and December 2020 in three tertiary hospitals. RESULTS: During this period, 11036 emergent coronary angiographies were performed, 59 (0.5%) of which revealed acute total occlusion of the LMCA. Patients' mean age was 61.2 (SD±12.2) years and 73% were male. No patients had left dominance. At presentation, 73% were in cardiogenic shock, aborted cardiac arrest occurred in 27% and 97% underwent myocardial revascularization. Primary percutaneous coronary intervention was performed in 90% of cases and angiographic success was achieved in 56% of procedures, while 7% of patients underwent surgical revascularization. In-hospital mortality was 58%. Among survivors, 92% and 67% were alive after one and five years, respectively. After multivariate analysis, only cardiogenic shock and angiographic success were independent predictors of in-hospital mortality. Use of mechanical circulatory support and presence of well-developed collateral circulation were not predictive of short-term prognosis. CONCLUSION: Acute total occlusion of the LMCA is associated with a dismal prognosis. Cardiogenic shock and angiographic success play a major role in predicting the prognosis of these patients. The effect of mechanical circulatory support on patient prognosis remains to be determined.

Corncob Cellulose Scaffolds: A New Sustainable Temporary Implant for Cartilage Replacement.

Tissue engineering using scaffolds is a promising strategy to repair damaged articular cartilage, whose self-repair is inefficient. Cellulose properties have been recognized for their application in the biomedical field. The aim of this study was to fabricate and characterize novel scaffolds based on poly(ɛ-caprolactone) (PCL) and sustainable cellulose. Thus, the performance of corncob-derived cellulose (CC) in scaffolds as an alternative to wood cellulose (WC) was also investigated to reduce the environmental footprint. Two concentrations of CC in scaffolds were tested, 1% and 2% (w/w), and commercial WC using the same concentrations, as a control. Morphologically, all the developed scaffolds presented pore sizes of ~300 µm, 10 layers, a circular shape and well-dispersed cellulose. Thus, all of these characteristics and properties provide the manufactured scaffolds suitable for use in cartilage-replacement strategies. The use of 2% CC results in higher porosity (54.24%), which promotes cell infiltration/migration and nutrient exchange, and has similar mechanical properties to WC. As for the effects of enzymatic degradation of the scaffolds, no significant changes (p > 0.05) were observed in resistance over time. However, the obtained compressive modulus of the scaffold with 2% CC was similar to that of WC. Overall, our results suggest that the integration of 2% corncob cellulose in PCL scaffolds could be a novel way to replace wood-cellulose-containing scaffolds, highlighting its potential for cartilage-replacement strategies.