DSpace Collection:
http://hdl.handle.net/2445/65294
2024-03-19T10:20:07Z
2024-03-19T10:20:07Z
Tackling the Root Cause of Surface-Induced Coagulation: Inhibition of FXII Activation to Mitigate Coagulation Propagation and Prevent Clotting
Witzdam L
Vosberg B
Große-Berkenbusch K
Stoppelkamp S
Wendel HP
Rodriguez-Emmenegger C
http://hdl.handle.net/2445/208657
2024-03-14T04:05:05Z
2024-03-13T10:10:58Z
Title: Tackling the Root Cause of Surface-Induced Coagulation: Inhibition of FXII Activation to Mitigate Coagulation Propagation and Prevent Clotting
Author: Witzdam L; Vosberg B; Große-Berkenbusch K; Stoppelkamp S; Wendel HP; Rodriguez-Emmenegger C
Abstract: Factor XII (FXII) is a zymogen present in blood that tends to adsorb onto the surfaces of blood-contacting medical devices. Once adsorbed, it becomes activated, initiating a cascade of enzymatic reactions that lead to surface-induced coagulation. This process is characterized by multiple redundancies, making it extremely challenging to prevent clot formation and preserve the properties of the surface. In this study, a novel modulatory coating system based on C1-esterase inhibitor (C1INH) functionalized polymer brushes, which effectively regulates the activation of FXII is proposed. Using surface plasmon resonance it is demonstrated that this coating system effectively repels blood plasma proteins, including FXII, while exhibiting high activity against activated FXII and plasma kallikrein under physiological conditions. This unique property enables the modulation of FXII activation without interfering with the overall hemostasis process. Furthermore, through dynamic Chandler loop studies, it is shown that this coating significantly improves the hemocompatibility of polymeric surfaces commonly used in medical devices. By addressing the root cause of contact activation, the synergistic interplay between the antifouling polymer brushes and the modulatory C1INH is expected to lay the foundation to enhance the hemocompatibility of medical device surfaces.© 2023 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.
2024-03-13T10:10:58Z
Cytoskeletal Safeguards: Protecting the Nucleus from Mechanical Perturbations
Kechagia, Zanetta
Roca-Cusachs Soulere, Pere
http://hdl.handle.net/2445/208643
2024-03-12T17:02:13Z
2024-03-11T17:54:18Z
Title: Cytoskeletal Safeguards: Protecting the Nucleus from Mechanical Perturbations
Author: Kechagia, Zanetta; Roca-Cusachs Soulere, Pere
Abstract: The cell nucleus plays a key role in cellular mechanoresponses. 3D genome organisation, gene expression, and cell behaviour, in general, are affected by mechanical force application to the nucleus, which is transmitted from the cellular environment via a network of interconnected cytoskeletal components. To effectively regulate cell responses, these cytoskeletal components must not only exert forces but also withstand external forces when necessary. This review delves into the latest research concerning how the cytoskeleton safeguards the nucleus from mechanical perturbations. Specifically, we focus on the three primary cytoskeletal polymers: actin, intermediate filaments, and microtubules, as well as their interactions with the cell nucleus. We discuss how the cytoskeleton acts as a protective shield for the nucleus, ensuring structural integrity and conveying context-specific mechanoresponses.
2024-03-11T17:54:18Z
The multivalency game ruling the biology of immunity
Aiassa, Lara
Battaglia, Giuseppe
Rizzello, Loris
http://hdl.handle.net/2445/207542
2024-03-12T17:02:13Z
2024-02-13T11:21:34Z
Title: The multivalency game ruling the biology of immunity
Author: Aiassa, Lara; Battaglia, Giuseppe; Rizzello, Loris
Abstract: Macrophages play a crucial role in our immune system, preserving tissue health and defending against harmful pathogens. This article examines the diversity of macrophages influenced by tissue-specific functions and developmental origins, both in normal and disease conditions. Understanding the spectrum of macrophage activation states, especially in pathological situations where they contribute significantly to disease progression, is essential to develop targeted therapies effectively. These states are characterized by unique receptor compositions and phenotypes, but they share commonalities. Traditional drugs that target individual entities are often insufficient. A promising approach involves using multivalent systems adorned with multiple ligands to selectively target specific macrophage populations based on their phenotype. Achieving this requires constructing supramolecular structures, typically at the nanoscale. This review explores the theoretical foundation of engineered multivalent nanosystems, dissecting the key parameters governing specific interactions. The goal is to design targeting systems based on distinct cell phenotypes, providing a pragmatic approach to navigating macrophage heterogeneity's complexities for more effective therapeutic interventions.
2024-02-13T11:21:34Z
Immunomodulatory IL-23 receptor antagonist peptide nanocoatings for implant soft tissue healing
Pizarek, John A.
Fischer, Nicholas G.
Aparicio, Conrado
http://hdl.handle.net/2445/207292
2024-03-12T17:02:13Z
2024-02-07T19:34:20Z
Title: Immunomodulatory IL-23 receptor antagonist peptide nanocoatings for implant soft tissue healing
Author: Pizarek, John A.; Fischer, Nicholas G.; Aparicio, Conrado
Abstract: Peri-implantitis, caused by an inflammatory response to pathogens, is the leading cause of dental implant failure. Poor soft tissue healing surrounding implants - caused by inadequate surface properties - leads to infection, inflammation, and dysregulated keratinocyte and macrophage function. One activated inflammatory response, active around peri-implantitis compared to healthy sites, is the IL-23/IL-17A cytokine axis. Implant surfaces can be synthesized with peptide nanocoatings to present immunomodulatory motifs to target peri-implant keratinocytes to control macrophage polarization and regulate inflammatory axises toward enhancing soft tissue healing.We synthesized an IL-23 receptor (IL-23R) noncompetitive antagonist peptide nanocoating using silanization and evaluated keratinocyte secretome changes and macrophage polarization (M1-like "pro-inflammatory" vs. M2-like "pro-regenerative").IL-23R antagonist peptide nanocoatings were successfully synthesized on titanium, to model dental implant surfaces, and compared to nonfunctional nanocoatings and non-coated titanium. IL-23R antagonist nanocoatings significantly decreased keratinocyte IL-23, and downstream IL-17A, expression compared to controls. This peptide noncompetitive antagonistic function was demonstrated under lipopolysaccharide stimulation. Large scale changes in keratinocyte secretome content, toward a pro-regenerative milieu, were observed from keratinocytes cultured on the IL-23R antagonist nanocoatings compared to controls. Conditioned medium collected from keratinocytes cultured on the IL-23R antagonist nanocoatings polarized macrophages toward a M2-like phenotype, based on increased CD163 and CD206 expression and reduced iNOS expression, compared to controls.Our results support development of IL-23R noncompetitive antagonist nanocoatings to reduce the pro-inflammatory IL-23/17A pathway and augment macrophage polarization toward a pro-regenerative phenotype. Immunomodulatory implant surface engineering may promote soft tissue healing and thereby reduce rates of peri-implantitis.Copyright © 2023 Elsevier Inc. All rights reserved.
2024-02-07T19:34:20Z
Engineering physiological environments to advance kidney organoid models from human pluripotent stem cells
Pahuja, A.
Goux Corredera, I.
Moya Rull, D.
Garreta, E.
Montserrat, N.
http://hdl.handle.net/2445/207221
2024-03-12T17:02:13Z
2024-02-06T11:37:01Z
Title: Engineering physiological environments to advance kidney organoid models from human pluripotent stem cells
Author: Pahuja, A.; Goux Corredera, I.; Moya Rull, D.; Garreta, E.; Montserrat, N.
Abstract: During embryogenesis, the mammalian kidney arises because of reciprocal interactions between the ureteric bud (UB) and the metanephric mesenchyme (MM), driving UB branching and nephron induction. These morphogenetic processes involve a series of cellular rearrangements that are tightly controlled by gene regulatory networks and signaling cascades. Here, we discuss how kidney developmental studies have informed the definition of procedures to obtain kidney organoids from human pluripotent stem cells (hPSCs). Moreover, bioengineering techniques have emerged as potential solutions to externally impose controlled microenvironments for organoid generation from hPSCs. Next, we summarize some of these advances with major focus On recent works merging hPSC-derived kidney organoids (hPSC-kidney organoids) with organ-on-chip to develop robust models for drug discovery and disease modeling applications. We foresee that, in the near future, coupling of different organoid models through bioengineering approaches will help advancing to recreate organ-to-organ crosstalk to increase our understanding on kidney disease progression in the human context and search for new therapeutics.
2024-02-06T11:37:01Z
Cardiac fibroblasts and mechanosensation in heart development, health and disease
Pesce, Maurizio
Duda, Georg N.
Forte, Giancarlo
Girao, Henrique
Raya Chamorro, Ángel
Roca-Cusachs Soulere, Pere
Sluijter, Joost P. G.
Tschöpe, Carsten
Van Linthout, Sophie
http://hdl.handle.net/2445/207161
2024-03-12T17:02:13Z
2024-02-05T10:14:01Z
Title: Cardiac fibroblasts and mechanosensation in heart development, health and disease
Author: Pesce, Maurizio; Duda, Georg N.; Forte, Giancarlo; Girao, Henrique; Raya Chamorro, Ángel; Roca-Cusachs Soulere, Pere; Sluijter, Joost P. G.; Tschöpe, Carsten; Van Linthout, Sophie
Abstract: The term 'mechanosensation' describes the capacity of cells to translate mechanical stimuli into the coordinated regulation of intracellular signals, cellular function, gene expression and epigenetic programming. This capacity is related not only to the sensitivity of the cells to tissue motion, but also to the decryption of tissue geometric arrangement and mechanical properties. The cardiac stroma, composed of fibroblasts, has been historically considered a mechanically passive component of the heart. However, the latest research suggests that the mechanical functions of these cells are an active and necessary component of the developmental biology programme of the heart that is involved in myocardial growth and homeostasis, and a crucial determinant of cardiac repair and disease. In this Review, we discuss the general concept of cell mechanosensation and force generation as potent regulators in heart development and pathology, and describe the integration of mechanical and biohumoral pathways predisposing the heart to fibrosis and failure. Next, we address the use of 3D culture systems to integrate tissue mechanics to mimic cardiac remodelling. Finally, we highlight the potential of mechanotherapeutic strategies, including pharmacological treatment and device-mediated left ventricular unloading, to reverse remodelling in the failing heart.
2024-02-05T10:14:01Z
Scalable, Lithography-Free Plasmonic Metasurfaces by Nano-Patterned/Sculpted Thin Films for Biosensing
López Muñoz, Gerardo
Cortés Reséndiz, Armando
Azcón, Javier Ramón
Rydosz, Artur
http://hdl.handle.net/2445/206264
2024-03-12T17:02:13Z
2024-01-24T12:17:00Z
Title: Scalable, Lithography-Free Plasmonic Metasurfaces by Nano-Patterned/Sculpted Thin Films for Biosensing
Author: López Muñoz, Gerardo; Cortés Reséndiz, Armando; Azcón, Javier Ramón; Rydosz, Artur
2024-01-24T12:17:00Z
Real-Time Polarimetry of Hyperpolarized 13C Nuclear Spins Using an Atomic Magnetometer
Mouloudakis, K.
Bodenstedt, S.
Azagra, M.
Mitchell, M. W.
Marco Rius, I.
Tayler, M. C. D.
http://hdl.handle.net/2445/206206
2024-03-12T17:02:13Z
2024-01-23T12:52:16Z
Title: Real-Time Polarimetry of Hyperpolarized 13C Nuclear Spins Using an Atomic Magnetometer
Author: Mouloudakis, K.; Bodenstedt, S.; Azagra, M.; Mitchell, M. W.; Marco Rius, I.; Tayler, M. C. D.
Abstract: We introduce a method for nondestructive quantification of nuclear spin polarization, of relevance to hyperpolarized spin tracers widely used in magnetic resonance from spectroscopy to in vivo imaging. In a bias field of around 30 nT we use a high-sensitivity miniaturized 87Rb-vapor magnetometer to measure the field generated by the sample, as it is driven by a windowed dynamical decoupling pulse sequence that both maximizes the nuclear spin lifetime and modulates the polarization for easy detection. We demonstrate the procedure applied to a 0.08 M hyperpolarized [1-13C]-pyruvate solution produced by dissolution dynamic nuclear polarization, measuring polarization repeatedly during natural decay at Earth's field. Application to real-time and continuous quality monitoring of hyperpolarized substances is discussed.
2024-01-23T12:52:16Z
Immunoaffinity‐Based Microfluidic Platform for Exosomal MicroRNA Isolation from Obese and Lean Mouse Plasma
Rodríguez Comas, Júlia
Castaño, Carlos
Ortega, María Alejandra
Tejedera Villafranca, Ainoa
Fernández González, Míriam
Novials, Anna
Párrizas, Marcelina
Ramón Azcón, Javier
http://hdl.handle.net/2445/205781
2024-03-12T17:02:13Z
2024-01-16T12:57:58Z
Title: Immunoaffinity‐Based Microfluidic Platform for Exosomal MicroRNA Isolation from Obese and Lean Mouse Plasma
Author: Rodríguez Comas, Júlia; Castaño, Carlos; Ortega, María Alejandra; Tejedera Villafranca, Ainoa; Fernández González, Míriam; Novials, Anna; Párrizas, Marcelina; Ramón Azcón, Javier
2024-01-16T12:57:58Z
An easy method for quantification of anaerobic and microaerobic gene expression with fluorescent reporter proteins
Pedraz López, Lucas
Torrents Serra, Eduard
http://hdl.handle.net/2445/205222
2024-03-12T17:02:13Z
2024-01-03T18:14:00Z
Title: An easy method for quantification of anaerobic and microaerobic gene expression with fluorescent reporter proteins
Author: Pedraz López, Lucas; Torrents Serra, Eduard
Abstract: Fluorescent proteins, such as green fluorescent proteins, are invaluable tools for detecting and quantifying gene expression in high-throughput reporter gene assays. However, they introduce significant inaccuracies in studies involving microaerobiosis or anaerobiosis, as oxygen is required for the maturation of these proteins' chromophores. In this study, the authors highlight the errors incurred by using fluorescent proteins under limited oxygenation by comparing standard fluorescence-based reporter gene assays to quantitative real-time PCR data in the study of a complex oxygen-regulated gene network. Furthermore, a solution to perform quantification of anaerobic and microaerobic gene expression with fluorescent reporter proteins using a microplate reader with an oxygen control system and applying pulses of full oxygenation before fluorescence measurements is provided.
2024-01-03T18:14:00Z