Hybrid Materials for Vascular Applications: A Preliminary In Vitro Assessment.

The production of biomedical devices able to appropriately interact with the biological environment is still a great challenge. Synthetic materials are often employed, but they fail to replicate the biological and functional properties of native tissues, leading to a variety of adverse effects. Several commercial products are based on chemically treated xenogeneic tissues: their principal drawback is due to weak mechanical stability and low durability. Recently, decellularization has been proposed to bypass the drawbacks of both synthetic and biological materials. Acellular materials can integrate with host tissues avoiding/mitigating any foreign body response, but they often lack sufficient patency and impermeability. The present paper investigates an innovative approach to the realization of hybrid materials that combine decellularized bovine pericardium with polycarbonate urethanes. These hybrid materials benefit from the superior biocompatibility of the biological tissue and the mechanical properties of the synthetic polymers. They were assessed from physicochemical, structural, mechanical, and biological points of view; their ability to promote cell growth was also investigated. The decellularized pericardium and the polymer appeared to well adhere to each other, and the two sides were distinguishable. The maximum elongation of hybrid materials was mainly affected by the pericardium, which allows for lower elongation than the polymer; this latter, in turn, influenced the maximum strength achieved. The results confirmed the promising features of hybrid materials for the production of vascular grafts able to be repopulated by circulating cells, thus, improving blood compatibility.

Strongly Interacting Photons in 2D Waveguide QED.

One-dimensional confinement in waveguide quantum electrodynamics (QED) plays a crucial role to enhance light-matter interactions and to induce a strong quantum nonlinear optical response. In two or higher-dimensional settings, this response is reduced since photons can be emitted within a larger phase space, opening the question whether strong photon-photon interaction can be still achieved. In this study, we positively answer this question for the case of a 2D square array of atoms coupled to the light confined into a two-dimensional waveguide. More specifically, we demonstrate the occurrence of long-lived two-photon repulsive and bound states with genuine 2D features. Furthermore, we observe signatures of these effects also in free-space atomic arrays in the form of weakly subradiant in-band scattering resonances. Our findings provide a paradigmatic signature of the presence of strong photon-photon interactions in 2D waveguide QED.

The suprapatellar fat pad: A histotopographic comparative study.

The suprapatellar fat pad is an adipose tissue located in the anterior knee whose role in osteoarthritis is still debated. Considering that anatomy drives function, the aim of this histotopographic study was to investigate the specific morphological features of the suprapatellar fat pad versus the infrapatellar fat pad in the absence of osteoarthritis, for a broad comparative analysis. Suprapatellar fat pad and infrapatellar fat pad tissue samples (n = 10/group) underwent microscopical/immunohistochemical staining and transmission electron microscopy analysis; thus, tissue-specific characteristics (i.e., vessels and nerve endings presence, lobuli, adipocytes features, septa), including extracellular matrix proteins prevalence (collagens, elastic fibers), were focused. Multiphoton microscopy was also adopted to evaluate collagen fiber orientation within the samples by Fast Fourier Transform (coherency calculation). The absence of inflammation was confirmed, and comparable counted vessels and nerve endings were shown. Like the infrapatellar fat pad, the suprapatellar fat pad appeared as a white adipose tissue with lobuli and septa of comparable diameter and thickness, respectively. Tissue main characteristics were also proved by both semithin sections and transmission electron microscopy analysis. The suprapatellar fat pad adipocytes were roundish and with a smaller area, perimeter, and major axis than that of the infrapatellar fat pad. The collagen fibers surrounding them showed no significant difference in collagen type I and significantly higher values for collagen type III in the infrapatellar fat pad group. Regarding the septa, elastic fiber content was statistically comparable between the two groups, even though more represented by the suprapatellar fat pad. Total collagen was significantly higher in the infrapatellar fat pad and comparing collagen type I and type III they were similarly represented in the whole cohort despite collagen type I appearing to be higher in the infrapatellar fat pad than in the suprapatellar fat pad and vice versa for collagen type III. Second harmonic generation microscopy confirmed through coherency calculation an anisotropic distribution of septa collagen fibers. From a mechanical point of view, the different morphological characteristics determined a major stiffness for the infrapatellar fat pad with respect to the suprapatellar fat pad. This study provides, for the first time, a topographic description of the suprapatellar fat pad compared to the infrapatellar fat pad; differences between the two groups may be attributed to a different anatomical location within the knee; the results gathered here may be useful for a more complete interpretation of osteoarthritis disease, involving not only cartilage but the whole joint.

Silicon metaoptics for the compact generation of perfect vector beams in the telecom infrared.

Perfect vortices have attracted considerable attention as orbital angular momentum (OAM) beams with customizable ring-like intensity distribution. More recently, the non-separable combination of perfect vortices with opposite OAMs and spins, yielding so-called perfect vector beams, has further expanded their applications in the fields of optical manipulation and imaging, high-resolution lithography, and telecommunications. Exploiting the combined manipulation of dynamic and geometric phases using silicon anisotropic metaunits, here we present the design, fabrication, and characterization of novel, to the best of our knowledge, dielectric metaoptics for the compact generation of perfect vector beams in the telecom infrared using a single metasurface. These devices pave the way to integrated optical architectures with applications in information and communication technologies in both the classical and quantum regimes.

Dual-functional metalenses for the polarization-controlled generation of focalized vector beams in the telecom infrared.

The availability of static tiny optical devices is mandatory to reduce the complexity of optical paths that typically use dynamic optical components and/or many standard elements for the generation of complex states of light, leading to unprecedented levels of miniaturization and compactness of optical systems. In particular, the design of flat and integrated optical elements capable of multiple vector beams generation with high resolution in the visible and infrared range is very attractive in many fields, from life science to information and communication technology. In this regard, we propose dual-functional transmission dielectric metalenses that act simultaneously on the dynamic and geometric phases in order to manipulate independently right-handed and left-handed circularly polarized states of light and generate focused vector beams in a compact and versatile way. In the specific, starting from the mathematical fundamentals for the compact generation of vector beams using dual-functional optical elements, we provide the numerical algorithms for the computation of metaoptics and apply those techniques to the design and fabrication of silicon metalenses which are able to generate and focus different vector beams in the telecom infrared, depending on the linear polarization state in input. This approach provides new integrated optics for applications in the fields of high-resolution microscopy, optical manipulation, and optical communications, both in the classical and single-photon regimes.

Preliminary In Vitro Assessment of Decellularized Porcine Descending Aorta for Clinical Purposes.

Conduit substitutes are increasingly in demand for cardiovascular and urological applications. In cases of bladder cancer, radical cystectomy is the preferred technique: after removing the bladder, a urinary diversion has to be created using autologous bowel, but several complications are associated with intestinal resection. Thus, alternative urinary substitutes are required to avoid autologous intestinal use, preventing complications and facilitating surgical procedures. In the present paper, we are proposing the exploitation of the decellularized porcine descending aorta as a novel and original conduit substitute. After being decellularized with the use of two alternative detergents (Tergitol and Ecosurf) and sterilized, the porcine descending aorta has been investigated to assess its permeability to detergents through methylene blue dye penetration analysis and to study its composition and structure by means of histomorphometric analyses, including DNA quantification, histology, two-photon microscopy, and hydroxyproline quantification. Biomechanical tests and cytocompatibility assays with human mesenchymal stem cells have been also performed. The results obtained demonstrated that the decellularized porcine descending aorta preserves its major features to be further evaluated as a candidate material for urological applications, even though further studies have to be carried out to demonstrate its suitability for the specific application, by performing in vivo tests in the animal model.

Development and In Vitro/In Vivo Comparative Characterization of Cryopreserved and Decellularized Tracheal Grafts.

Tracheal reconstruction represents a challenge when primary anastomosis is not feasible. Within this scenario, the study aim was to develop a new pig-derived decellularized trachea (DecellT) to be compared with the cryopreserved counterpart (CryoT) for a close predictive analysis. Tracheal segments underwent decellularization by a physical + enzymatic + chemical method (12 cycles); in parallel, cryopreserved samples were also prepared. Once decellularized (histology/DNA quantification), the two groups were characterized for Alpha-Gal epitopes/structural proteins (immunohistochemistry/histology/biochemical assays/second harmonic generation microscopy)/ultrastructure (Scanning Electron Microscopy (SEM))/mechanical behaviour. Cytotoxicity absence was assessed in vitro (extract-test assay/direct seeding, HM1SV40 cell line) while biocompatibility was verified in BALB/c mice, followed by histological/immunohistochemical analyses and SEM (14 days). Decellularization effectively removed Alpha-Gal epitopes; cartilage histoarchitecture was retained in both groups, showing chondrocytes only in the CryoT. Cryopreservation maintained few respiratory epithelium sparse cilia, not detectable in DecellT. Focusing on ECM, preserved structural/ultrastructural organization and collagen content were observed in the cartilage of both; conversely, the GAGs were significantly reduced in DecellT, as confirmed by mechanical study results. No cytotoxicity was highlighted by CryoT/DecellT in vitro, as they were also corroborated by a biocompatibility assay. Despite some limitations (cells presence/GAGs reduction), CryoT/DecellT are both appealing options, which warrant further investigation in comparative in vivo studies.

Covalently Grafted Peptides to Decellularized Pericardium: Modulation of Surface Density.

The covalent functionalization of synthetic peptides allows the modification of different biomaterials (metallic, polymeric, and ceramic), which are enriched with biologically active sequences to guide cell behavior. Recently, this strategy has also been applied to decellularized biological matrices. In this study, the covalent anchorage of a synthetic peptide (REDV) to a pericardial matrix decellularized via Schiff base is realized starting from concentrated peptide solutions (10-4 M and 10-3 M). The use of a labeled peptide demonstrated that as the concentration of the working solution increased, the surface density of the anchored peptide increased as well. These data are essential to pinpointing the concentration window in which the peptide promotes the desired cellular activity. The matrices were extensively characterized by Water Contact Angle (WCA) analysis, Differential Scanning Calorimetry (DSC) analysis, geometric feature evaluation, biomechanical tests, and preliminary in vitro bioassays.

Tergitol Based Decellularization Protocol Improves the Prerequisites for Pulmonary Xenografts: Characterization and Biocompatibility Assessment.

Right ventricle outflow tract obstruction (RVOTO) is a congenital pathological condition that contributes to about 15% of congenital heart diseases. In most cases, the replacement of the right ventricle outflow in pediatric age requires subsequent pulmonary valve replacement in adulthood. The aim of this study was to investigate the extracellular matrix scaffold obtained by decellularization of the porcine pulmonary valve using a new detergent (Tergitol) instead of Triton X-100. The decellularized scaffold was evaluated for the integrity of its extracellular matrix (ECM) structure by testing for its biochemical and mechanical properties, and the cytotoxicity/cytocompatibility of decellularized tissue was assessed using bone marrow-derived mesenchymal stem cells. We concluded that Tergitol could remove the nuclear material efficiently while preserving the structural proteins of the matrix, but without an efficient removal of the alpha-gal antigenic epitope. Therefore, Tergitol can be used as an alternative detergent to replace the Triton X-100.

Small intestinal submucosa-derived extracellular matrix as a heterotopic scaffold for cardiovascular applications.

Structural cardiac lesions are often surgically repaired using prosthetic patches, which can be biological or synthetic. In the current clinical scenario, biological patches derived from the decellularization of a xenogeneic scaffold are gaining more interest as they maintain the natural architecture of the extracellular matrix (ECM) after the removal of the native cells and remnants. Once implanted in the host, these patches can induce tissue regeneration and repair, encouraging angiogenesis, migration, proliferation, and host cell differentiation. Lastly, decellularized xenogeneic patches undergo cell repopulation, thus reducing host immuno-mediated response against the graft and preventing device failure. Porcine small intestinal submucosa (pSIS) showed such properties in alternative clinical scenarios. Specifically, the US FDA approved its use in humans for urogenital procedures such as hernia repair, cystoplasties, ureteral reconstructions, stress incontinence, Peyronie's disease, penile chordee, and even urethral reconstruction for hypospadias and strictures. In addition, it has also been successfully used for skeletal muscle tissue reconstruction in young patients. However, for cardiovascular applications, the results are controversial. In this study, we aimed to validate our decellularization protocol for SIS, which is based on the use of Tergitol 15 S 9, by comparing it to our previous and efficient method (Triton X 100), which is not more available in the market. For both treatments, we evaluated the preservation of the ECM ultrastructure, biomechanical features, biocompatibility, and final bioinductive capabilities. The overall analysis shows that the SIS tissue is macroscopically distinguishable into two regions, one smooth and one wrinkle, equivalent to the ultrastructure and biochemical and proteomic profile. Furthermore, Tergitol 15 S 9 treatment does not modify tissue biomechanics, resulting in comparable to the native one and confirming the superior preservation of the collagen fibers. In summary, the present study showed that the SIS decellularized with Tergitol 15 S 9 guarantees higher performances, compared to the Triton X 100 method, in all the explored fields and for both SIS regions: smooth and wrinkle.

A Novel Hybrid Membrane for Urinary Conduit Substitutes Based on Small Intestinal Submucosa Coupled with Two Synthetic Polymers.

Among the urinary tract's malignancies, bladder cancer is the most frequent one: it is at the tenth position of most common cancers worldwide. Currently, the gold standard therapy consists of radical cystectomy, which results in the need to create a urinary diversion using a bowel segment from the patient. Nevertheless, due to several complications associated with bowel resection and anastomosis, which significantly affect patient quality of life, it is becoming extremely important to find an alternative solution. In our recent work, we proposed the decellularized porcine small intestinal submucosa (SIS) as a candidate material for urinary conduit substitution. In the present study, we create SIS-based hybrid membranes that are obtained by coupling decellularized SIS with two commercially available polycarbonate urethanes (Chronoflex AR and Chronoflex AR-LT) to improve SIS mechanical resistance and impermeability. We evaluated the hybrid membranes by means of immunofluorescence, two-photon microscopy, FTIR analysis, and mechanical and cytocompatibility tests. The realization of hybrid membranes did not deteriorate SIS composition, but the presence of polymers ameliorates the mechanical behavior of the hybrid constructs. Moreover, the cytocompatibility tests demonstrated a significant increase in cell growth compared to decellularized SIS alone. In light of the present results, the hybrid membrane-based urinary conduit can be a suitable candidate to realize a urinary diversion in place of an autologous intestinal segment. Further efforts will be performed in order to create a cylindrical-shaped hybrid membrane and to study its hydraulic behavior.

Bio-Engineered Scaffolds Derived from Decellularized Human Esophagus for Functional Organ Reconstruction.

Esophageal reconstruction through bio-engineered allografts that highly resemble the peculiar properties of the tissue extracellular matrix (ECM) is a prospective strategy to overcome the limitations of current surgical approaches. In this work, human esophagus was decellularized for the first time in the literature by comparing three detergent-enzymatic protocols. After decellularization, residual DNA quantification and histological analyses showed that all protocols efficiently removed cells, DNA (<50 ng/mg of tissue) and muscle fibers, preserving collagen/elastin components. The glycosaminoglycan fraction was maintained (70-98%) in the decellularized versus native tissues, while immunohistochemistry showed unchanged expression of specific ECM markers (collagen IV, laminin). The proteomic signature of acellular esophagi corroborated the retention of structural collagens, basement membrane and matrix-cell interaction proteins. Conversely, decellularization led to the loss of HLA-DR expression, producing non-immunogenic allografts. According to hydroxyproline quantification, matrix collagen was preserved (2-6 µg/mg of tissue) after decellularization, while Second-Harmonic Generation imaging highlighted a decrease in collagen intensity. Based on uniaxial tensile tests, decellularization affected tissue stiffness, but sample integrity/manipulability was still maintained. Finally, the cytotoxicity test revealed that no harmful remnants/contaminants were present on acellular esophageal matrices, suggesting allograft biosafety. Despite the different outcomes showed by the three decellularization methods (regarding, for example, tissue manipulability, DNA removal, and glycosaminoglycans/hydroxyproline contents) the ultimate validation should be provided by future repopulation tests and in vivo orthotopic implant of esophageal scaffolds.

A New Detergent for the Effective Decellularization of Bovine and Porcine Pericardia.

Human and animal pericardia are among the most widely exploited materials suitable to repair damaged tissues in the cardiovascular surgery context. Autologous, xenogeneic (chemically treated) and homologous pericardia are largely utilized, but they do exhibit some crucial drawbacks. Any tissue treated with glutaraldehyde is known to be prone to calcification in vivo, lacks regeneration potential, has limited durability, and can result in cytotoxicity. Moreover, autologous tissues have limited availability. Decellularized biological tissues represent a promising alternative: decellularization removes cellular and nuclear components from native tissues and makes them suitable for repopulation by autologous cells upon implantation into the body. The present work aims to assess the effects of a new detergent, i.e., Tergitol, for decellularizing bovine and porcine pericardia. The decellularization procedure successfully removed cells, while preserving the histoarchitecture of the extracellular matrix. No cytotoxic effect was observed. Therefore, decellularized pericardia showed potential to be used as scaffold for cardiovascular tissue regeneration.

Customized bioreactor enables the production of 3D diaphragmatic constructs influencing matrix remodeling and fibroblast overgrowth.

The production of skeletal muscle constructs useful for replacing large defects in vivo, such as in congenital diaphragmatic hernia (CDH), is still considered a challenge. The standard application of prosthetic material presents major limitations, such as hernia recurrences in a remarkable number of CDH patients. With this work, we developed a tissue engineering approach based on decellularized diaphragmatic muscle and human cells for the in vitro generation of diaphragmatic-like tissues as a proof-of-concept of a new option for the surgical treatment of large diaphragm defects. A customized bioreactor for diaphragmatic muscle was designed to control mechanical stimulation and promote radial stretching during the construct engineering. In vitro tests demonstrated that both ECM remodeling and fibroblast overgrowth were positively influenced by the bioreactor culture. Mechanically stimulated constructs also increased tissue maturation, with the formation of new oriented and aligned muscle fibers. Moreover, after in vivo orthotopic implantation in a surgical CDH mouse model, mechanically stimulated muscles maintained the presence of human cells within myofibers and hernia recurrence did not occur, suggesting the value of this approach for treating diaphragm defects.

Preclinical Development of Bioengineered Allografts Derived from Decellularized Human Diaphragm.

Volumetric muscle loss (VML) is the traumatic/surgical loss of skeletal muscle, causing aesthetic damage and functional impairment. Suboptimal current surgical treatments are driving research towards the development of optimised regenerative therapies. The grafting of bioengineered scaffolds derived from decellularized skeletal muscle may be a valid option to promote structural and functional healing. In this work, a cellular human diaphragm was considered as a scaffold material for VML treatment. Decellularization occurred through four detergent-enzymatic protocols involving (1) sodium dodecyl sulfate (SDS), (2) SDS + TergitolTM, (3) sodium deoxycholate, and (4) TergitolTM. After decellularization, cells, DNA (≤50 ng/mg of tissue), and muscle fibres were efficiently removed, with the preservation of collagen/elastin and 60%-70% of the glycosaminoglycan component. The detergent-enzymatic treatments did not affect the expression of specific extracellular matrix markers (Collagen I and IV, Laminin), while causing the loss of HLA-DR expression to produce non-immunogenic grafts. Adipose-derived stem cells grown by indirect co-culture with decellularized samples maintained 80%-90% viability, demonstrating the biosafety of the scaffolds. Overall, the tested protocols were quite equivalent, with the patches treated by SDS + TergitolTM showing better collagen preservation. After subcutaneous implant in Balb/c mice, these acellular diaphragmatic grafts did not elicit a severe immune reaction, integrating with the host tissue.

Porcine Small Intestinal Submucosa (SIS) as a Suitable Scaffold for the Creation of a Tissue-Engineered Urinary Conduit: Decellularization, Biomechanical and Biocompatibility Characterization Using New Approaches.

Bladder cancer (BC) is among the most common malignancies in the world and a relevant cause of cancer mortality. BC is one of the most frequent causes for bladder removal through radical cystectomy, the gold-standard treatment for localized muscle-invasive and some cases of high-risk, non-muscle-invasive bladder cancer. In order to restore urinary functionality, an autologous intestinal segment has to be used to create a urinary diversion. However, several complications are associated with bowel-tract removal, affecting patients' quality of life. The present study project aims to develop a bio-engineered material to simplify this surgical procedure, avoiding related surgical complications and improving patients' quality of life. The main novelty of such a therapeutic approach is the decellularization of a porcine small intestinal submucosa (SIS) conduit to replace the autologous intestinal segment currently used as urinary diversion after radical cystectomy, while avoiding an immune rejection. Here, we performed a preliminary evaluation of this acellular product by developing a novel decellularization process based on an environmentally friendly, mild detergent, i.e., Tergitol, to replace the recently declared toxic Triton X-100. Treatment efficacy was evaluated through histology, DNA, hydroxyproline and elastin quantification, mechanical and insufflation tests, two-photon microscopy, FTIR analysis, and cytocompatibility tests. The optimized decellularization protocol is effective in removing cells, including DNA content, from the porcine SIS, while preserving the integrity of the extracellular matrix despite an increase in stiffness. An effective sterilization protocol was found, and cytocompatibility of treated SIS was demonstrated from day 1 to day 7, during which human fibroblasts were able to increase in number and strongly organize along tissue fibres. Taken together, this in vitro study suggests that SIS is a suitable candidate for use in urinary diversions in place of autologous intestinal segments, considering the optimal results of decellularization and cell proliferation. Further efforts should be undertaken in order to improve SIS conduit patency and impermeability to realize a future viable substitute.

A New Decellularization Protocol of Porcine Aortic Valves Using Tergitol to Characterize the Scaffold with the Biocompatibility Profile Using Human Bone Marrow Mesenchymal Stem Cells.

The most common aortic valve diseases in adults are stenosis due to calcification and regurgitation. In pediatric patients, aortic pathologies are less common. When a native valve is surgically replaced by a prosthetic one, it is necessary to consider that the latter has a limited durability. In particular, current bioprosthetic valves have to be replaced after approximately 10 years; mechanical prostheses are more durable but require the administration of permanent anticoagulant therapy. With regard to pediatric patients, both mechanical and biological prosthetic valves have to be replaced due to their inability to follow patients' growth. An alternative surgical substitute can be represented by the acellular porcine aortic valve that exhibits less immunogenic risk and a longer lifespan. In the present study, an efficient protocol for the removal of cells by using detergents, enzyme inhibitors, and hyper- and hypotonic shocks is reported. A new detergent (Tergitol) was applied to replace TX-100 with the aim to reduce toxicity and maximize ECM preservation. The structural integrity and efficient removal of cells and nuclear components were assessed by means of histology, immunofluorescence, and protein quantification; biomechanical properties were also checked by tensile tests. After decellularization, the acellular scaffold was sterilized with a standard protocol and repopulated with bone marrow mesenchymal stem cells to analyze its biocompatibility profile.

Multipole-phase division multiplexing.

The control of structured waves has recently opened innovative scenarios in the perspective of radiation propagation, advanced imaging, and light-matter interaction. In information and communication technology, the spatial degrees of freedom offer a wider state space to carry many channels on the same frequency or increase the dimensionality of quantum protocols. However, spatial decomposition is much more arduous than polarization or frequency multiplexing, and very few practical examples exist. Among all, beams carrying orbital angular momentum gained a preeminent role, igniting a variety of methods and techniques to generate, tailor, and measure that property. In a more general insight into structured-phase beams, we introduce here a new family of wave fields having a multipole phase. These beams are devoid of phase singularities and described by two continuous spatial parameters which can be controlled in a practical and compact way via conformal optics. The outlined framework encompasses multiplexing, propagation, and demultiplexing as a whole for the first time, describing the evolution and transformation of wave fields in terms of conformal mappings. With its potentialities, versatility, and ease of implementation, this new paradigm introduces a novel playground for space division multiplexing, suggesting unconventional solutions for light processing and free-space communications.

Hybrid membranes for the production of blood contacting surfaces: physicochemical, structural and biomechanical characterization.

BACKGROUND: Due to the shortage of organs' donors that limits biological heart transplantations, mechanical circulatory supports can be implanted in case of refractory end-stage heart failure to replace partially (Ventricular Assist Device, VAD) or completely (Total Artificial Heart, TAH) the cardiac function. The hemocompatibility of mechanical circulatory supports is a fundamental issue that has not yet been fully matched; it mostly depends on the nature of blood-contacting surfaces. METHODS: In order to obtain hemocompatible materials, a pool of hybrid membranes was fabricated by coupling a synthetic polymer (polycarbonate urethane, commercially available in two formulations) with a decellularized biological tissue (porcine pericardium). To test their potential suitability as candidate materials for realizing the blood-contacting surfaces of a novel artificial heart, hybrid membranes have been preliminarily characterized in terms of physicochemical, structural and mechanical properties. RESULTS: Our results ascertained that the hybrid membranes are properly stratified, thus allowing to expose their biological side to blood and their polymeric surface to the actuation system of the intended device. From the biomechanical point of view, the hybrid membranes can withstand deformations up to more than 70 % and stresses up to around 8 MPa. CONCLUSIONS: The hybrid membranes are suitable for the construction of the ventricular chambers of innovative mechanical circulatory support devices.

Proteomic Exploration of Plasma Exosomes and Other Small Extracellular Vesicles in Pediatric Hodgkin Lymphoma: A Potential Source of Biomarkers for Relapse Occurrence.

Exosomes and other small extracellular vesicles (EVs) are potential sources of cancer biomarkers. Plasma-derived EVs have not yet been studied in pediatric Hodgkin lymphoma (HL), for which predictive biomarkers of relapse are greatly needed. In this two-part proteomic study, we used two-dimensional difference gel electrophoresis (2D-DIGE) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze EV proteins of plasma collected at diagnosis from children with nodular sclerosis HL, relapsed or not. EVs isolated using membrane affinity had radii ranging from 20 to 130 nm and contained the programmed cell death 6-interacting (ALIX) and the tumor susceptibility gene 101 (TSG101) proteins, whereas calnexin (CANX) was not detected. 2D-DIGE identified 16 spots as differentially abundant between non-relapsed and relapsed HL (|fold change| ≥ 1.5, p < 0.05). LC-MS/MS identified these spots as 11 unique proteins, including five more abundant in non-relapsed HL (e.g., complement C4b, C4B; fibrinogen γ chain, FGG) and six more abundant in relapsed HL (e.g., transthyretin, TTR). Shotgun LC-MS/MS on pooled EV proteins from non-relapsed HL identified 161 proteins, including 127 already identified in human exosomes (ExoCarta data). This EV cargo included 89 proteins not yet identified in exosomes from healthy plasma. Functional interrogation by the Database for Annotation, Visualization and Integrated Discovery (DAVID) revealed that the EV proteins participate in platelet degranulation and serine-type endopeptidase activity as the most significant Gene Ontology (GO) biological process and molecular function (p < 0.01).