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Cutaneous squamous cell carcinoma is not uncommon in patients affected by malignant lymphoma, mostly in elderly; the contemporary management of these diseases presents some difficulties, since they require different modalities of treatment. Only small case series and single case report are described in literature about synchronous or metachronous metastatic cutaneous cell carcinoma and lymphoma/chronic lymphocytic leukaemia; in addiction, we report our experience in order to illustrate difficulties encountered in the management of these patients. We conclude that these patients need a close follow-up, and that US-guided FNAC and 18F-fluorodeoxyglucose PET in addiction to MRI are useful for staging. cSCC, having a poorer prognosis, has to be treated first; nevertheless, mortality in these patients is obviously higher than expected in immunocompetent people.

Este estudo tem como objetivo analisar como a comunicação e o feedback contribuem para a melhoria dos negócios empreendedores, pois, as empresas dependem de uma comunicação bem-sucedida para melhorar seu desempenho, seja em seus níveis hierárquicos internos ou nas relações com seus parceiros, clientes internos e externos. A pesquisa é de natureza qualitativa, exploratória e descritiva e a entrevista apoiada em um roteiro semiestruturada foi utilizada como instrumento de coleta de dados. Foram entrevistados 28 empreendedores e 4 agentes locais de inovação do programa ALI. Os dados foram categorizados e analisados por meio da análise de conteúdo, com o apoio do software Atlas ti. Os principais resultados apontam que a comunicação acontece efetuvamente quando existe qualidade no relacionamento entre os interlocutores. A afetividade e a cognição reforçaram os resultados, pois evidenciaram que a confiança e o comprometimento, por exemplo, estão entre os principais alicerces da comunicação e do feedback. Portanto, instituições como, unversidades públicas ou privadas, bem como o SEBRAE poderiam desenvolver planos de ensino que destaquem a importância da comunicação com qualidade, bem como o relaciomanento humano, com base nos processos de feedback, com o objetivo de preparar o empreendedor para superar estes desafios.

Liver tissue engineering approaches aim to support drug testing, assistance devices, or transplantation. However, their suitability for clinical application remains unsatisfactory. Herein, we demonstrate the beneficial and biocompatible use of porous pullulan-dextran hydrogel for the self-assembly of hepatocytes and biliary-like cells into functional 3D microtissues. Using HepaRG cells, we obtained 21 days maintenance of engineered liver polarity, functional detoxification and excretion systems, as well as glycogen storage in hydrogel. Implantation on two liver lobes in mice of hydrogels containing 3800 HepaRG 3D structures of 100 ​μm in diameter, indicated successful engraftment and no signs of liver toxicity after one month. Finally, after acetaminophen-induced liver failure, when mice were transplanted with engineered livers on left lobe and peritoneal cavity, the survival rate at 7 days significantly increased by 31.8% compared with mice without cell therapy. These findings support the clinical potential of pullulan-dextran hydrogel for liver failure management.

Abstract Vascularization of 3D models represents a major challenge of tissue engineering and a key prerequisite for their clinical and industrial application. The use of prevascularized models built from dedicated materials could solve some of the actual limitations, such as suboptimal integration of the bioconstructs within the host tissue, and would provide more in vivo‐like perfusable tissue and organ‐specific platforms. In the last decade, the fabrication of vascularized physiologically relevant 3D constructs has been attempted by numerous tissue engineering strategies, which are classified here in microfluidic technology, 3D coculture models, namely, spheroids and organoids, and biofabrication. In this review, the recent advancements in prevascularization techniques and the increasing use of natural and synthetic materials to build physiological organ‐specific models are discussed. Current drawbacks of each technology, future perspectives, and translation of vascularized tissue constructs toward clinics, pharmaceutical field, and industry are also presented. By combining complementary strategies, these models are envisioned to be successfully used for regenerative medicine and drug development in a near future.

Scaffolds for bone regeneration have been engineered by a plethora of manufacturing technologies and biomaterials. However, the performance of these systems is often limited by lack of robustness in the process design, that hampers their scalability to clinical application. In the present study, Design of Experiment (DoE) was used as statistical tool to design the biofabrication of hybrid hydroxyapatite (HA)/collagen scaffolds for bone regeneration and optimize their integration in a multilayer osteochondral device. The scaffolds were synthesized via a multi-step bioinspired process consisting in HA nano-crystals nucleation on the collagen self-assembling fibers and ribose glycation was used as collagen cross-linking method to modulate the mechanical and physical properties. The process design was performed by selecting hydrogel concentration, HA/collagen ratio and cross-linker content as key variables and the fabrication was carried out basing on a full factorial design. Scaffold performances were tested by evaluating porosity, swelling ratio, degradation rate and mechanical behavior as model output responses while physicochemical properties of the constructs were evaluated by TGA, ICP, FT-IR spectroscopy, and XRD analysis. Physicochemical characterizations confirmed the nucleation of a biomimetic inorganic phase and the interaction of the HA and collagenic components. The DoE model revealed a significant interaction between HA content and collagen cross-linking in determining porosity, swelling and mechanical properties of the scaffolds. The combined effect of hydrogel concentration and mineral phase played a key role on porosity and swelling while degradation resulted to be mainly affected by the HA loading and ribose content. The model was then used to determine the suitable input parameters for the synthesis of multi-layer scaffolds with graded mineralization rate, that can be used to mimic the whole cartilage-bone interface. This work proved that experimental design applied to complex biofabrication processes represents an effective and reliable way to design hybrid constructs with standardized and tunable properties for osteochondral tissue engineering.

Leveraging the advantageous material properties of recently developed soft thermoplastic elastomer materials, this work presents the facile and rapid fabrication of composite membrane-integrated microfluidic devices consisting of FlexdymTM polymer and commercially available porous polycarbonate membranes. The three-layer devices can be fabricated in under 2.5 h, consisting of a 2-min hot embossing cycle, conformal contact between device layers and a low-temperature baking step. The strength of the FlexdymTM-polycarbonate seal was characterized using a specialized microfluidic delamination device and an automated pressure controller configuration, offering a standardized and high-throughput method of microfluidic burst testing. Given a minimum bonding distance of 200 μm, the materials showed bonding that reliably withstood pressures of 500 mbar and above, which is sufficient for most microfluidic cell culture applications. Bonding was also stable when subjected to long term pressurization (10 h) and repeated use (10,000 pressure cycles). Cell culture trials confirmed good cell adhesion and sustained culture of human dermal fibroblasts on a polycarbonate membrane inside the device channels over the course of one week. In comparison to existing porous membrane-based microfluidic platforms of this configuration, most often made of polydimethylsiloxane (PDMS), these devices offer a streamlined fabrication methodology with materials having favourable properties for cell culture applications and the potential for implementation in barrier model organ-on-chips.

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In tissue engineering, the composition and the structural arrangement of molecular components within the extracellular matrix (ECM) determine the physical and biochemical features of a scaffold, which consequently modulate cell behavior and function. The microenvironment of the ECM plays a fundamental role in regulating angiogenesis. Numerous strategies in tissue engineering have attempted to control the spatial cues mimicking in vivo angiogenesis by using simplified systems. The aim of this study was to develop 3D porous crosslinked hydrogels with different spatial presentation of pro-angiogenic molecules to guide endothelial cell (EC) behavior. Hydrogels with pores and preformed microchannels were made with pharmaceutical-grade pullulan and dextran and functionalized with novel pro-angiogenic protein polymers (Caf1-YIGSR and Caf1-VEGF). Hydrogel functionalization was achieved by electrostatic interactions via incorporation of diethylaminoethyl (DEAE)–dextran. Spatial-controlled coating of hydrogels was realized through a combination of freeze-drying and physical absorption with Caf1 molecules. Cells in functionalized scaffolds survived, adhered, and proliferated over seven days. When incorporated alone, Caf1-YIGSR mainly induced cell adhesion and proliferation, whereas Caf1-VEGF promoted cell migration and sprouting. Most importantly, directed cell migration required the presence of both proteins in the microchannel and in the pores, highlighting the need for an adhesive substrate provided by Caf1-YIGSR for Caf1-VEGF to be effective. This study demonstrates the ability to guide EC behavior through spatial control of pro-angiogenic cues for the study of pro-angiogenic signals in 3D and to develop pro-angiogenic implantable materials. [ABSTRACT FROM AUTHOR]

Vascularization of 3D models represents a major challenge of tissue engineering and a key prerequisite for their clinical and industrial application. The use of prevascularized models built from dedicated materials could solve some of the actual limitations, such as suboptimal integration of the bioconstructs within the host tissue, and would provide more in vivo‐like perfusable tissue and organ‐specific platforms. In the last decade, the fabrication of vascularized physiologically relevant 3D constructs has been attempted by numerous tissue engineering strategies, which are classified here in microfluidic technology, 3D coculture models, namely, spheroids and organoids, and biofabrication. In this review, the recent advancements in prevascularization techniques and the increasing use of natural and synthetic materials to build physiological organ‐specific models are discussed. Current drawbacks of each technology, future perspectives, and translation of vascularized tissue constructs toward clinics, pharmaceutical field, and industry are also presented. By combining complementary strategies, these models are envisioned to be successfully used for regenerative medicine and drug development in a near future. [ABSTRACT FROM AUTHOR]

Silks have been widely used as biomaterials due to their biocompatibility, biodegradability, and excellent mechanical properties. In the present work, native spider silk was used as organic template for controlled nucleation of hydroxyapatite (HA) nano‐coating that can act as biomimetic interface. Different bio‐inspired neutralization methods and process parameters were evaluated to optimize the silk functionalization. The morphology and chemical composition were investigated by scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, Fourier transform infrared spectroscopy, and X‐ray diffraction analysis and mechanical properties were studied through tensile tests. Results showed that the optimized protocol enabled a controlled and homogeneous nucleation of apatite nano‐crystals while maintaining silk mechanical performances after mineralization. This study reports the optimization of a simple and effective bio‐inspired nucleation process for precise nucleation of HA onto spider silk templates, suitable to develop high‐performance hybrid interfaces for bone tissue engineering. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48739. [ABSTRACT FROM AUTHOR]

Background Infertility affects ~10-15% of couples trying to have children, in which the rate of male fertility problems is approximately at 30-50%. Copy number variations (CNVs) are DNA sequences greater than or equal to 1 kb in length sharing a high level of similarity and present at a variable number of copies in the genome; in our study, we used the canine species as an animal model to detect CNVs responsible for male infertility. We aim to identify CNVs associated with male infertility in the dog genome with a two-pronged approach: we performed a sperm analysis using the CASA system and a cytogenetic-targeted analysis on genes involved in male gonad development and spermatogenesis with fluorescence in situ hybridization (FISH), using dog-specific clones. This analysis was carried out to evaluate possible correlations between CNVs on targeted genes and spermatogenesis impairments or infertility factors. Results We identified two genomic regions hybridized by BACs CH82-321 J09 and CH82-509B23 showing duplication patterns in all samples except for an azoospermic dog. These two regions harbor two important genes for spermatogenesis: DNM2 and TEKT1. The genomic region encompassed by the BAC clone CH82-324I01 showed a single-copy pattern in all samples except for one dog, assessed with low-quality sperm, displaying a marked duplication pattern. This genomic region harbors SOX8, a key gene for testis development. Conclusion We present the first study involving functional and genetic analyses in male infertility. We set up an extremely reliable analysis on dog sperm cells with a highly consistent statistical significance, and we succeeded in conducting FISH experiments on sperm cells using BAC clones as probes. We found copy number differences in infertile compared with fertile dogs for genomic regions encompassing TEKT1, DNM2, and SOX8, suggesting they could have a role in fertility if deleted or duplicated with respect to the reference copy number in fertility biology. This method is of particular interest in the canine species due to the recognized role of this species as an animal model for the study of human genetic diseases and could be useful for other species of economic interest and for endangered animal species. [ABSTRACT FROM AUTHOR]

Leveraging the advantageous material properties of recently developed soft thermoplastic elastomer materials, this work presents the facile and rapid fabrication of composite membrane-integrated microfluidic devices consisting of FlexdymTM polymer and commercially available porous polycarbonate membranes. The three-layer devices can be fabricated in under 2.5 h, consisting of a 2-min hot embossing cycle, conformal contact between device layers and a low-temperature baking step. The strength of the FlexdymTM-polycarbonate seal was characterized using a specialized microfluidic delamination device and an automated pressure controller configuration, offering a standardized and high-throughput method of microfluidic burst testing. Given a minimum bonding distance of 200 μm, the materials showed bonding that reliably withstood pressures of 500 mbar and above, which is sufficient for most microfluidic cell culture applications. Bonding was also stable when subjected to long term pressurization (10 h) and repeated use (10,000 pressure cycles). Cell culture trials confirmed good cell adhesion and sustained culture of human dermal fibroblasts on a polycarbonate membrane inside the device channels over the course of one week. In comparison to existing porous membrane-based microfluidic platforms of this configuration, most often made of polydimethylsiloxane (PDMS), these devices offer a streamlined fabrication methodology with materials having favourable properties for cell culture applications and the potential for implementation in barrier model organ-on-chips. [ABSTRACT FROM AUTHOR]