Publications

Endothelium, the lining in this blood vessel, orchestrates three main critical functions such as protecting blood components, modulating of hemostasis by secreting various inhibitors, and directing clot digestion (fibrinolysis) by activating tissue plasminogen activator. No other surface can perform these tasks; thus, the contact of blood and blood-contacting medical devices inevitably leads to the activation of coagulation, often causing device failure, and thromboembolic complications. This perspective, first, discusses the biological mechanisms of activation of coagulation and highlights the efforts of advanced coatings to recapitulate one characteristic of endothelium, hereafter single functions of endothelium and noting necessity of the synergistic integration of its three main functions. Subsequently, it is emphasized that to overcome the challenges of blood compatibility an endothelium-mimicking system is needed, proposing a synergy of bottom-up synthetic biology, particularly synthetic cells, with passive- and bioactive surface coatings. Such integration holds promise for developing advanced biomaterials capable of recapitulating endothelial functions, thereby enhancing the hemocompatibility and performance of blood-contacting medical devices. The activation of coagulation on the surface of blood-contacting medical devices often leads to thromboembolic complications. A concept for the next generation of hemocompatbile surfaces inspired by endothelium is proposed. This concept not only contribute to the fundamental understanding of hemocompatibility but also offer practical implications for the design and development of biomedical devices with enhanced biocompatibility and functionality. image

JTD Keywords: Antifouling coatings, Antifouling polymer brushes, Coagulation-factor-xii, Endothelium-inspired, Hemocompatibility, Hemocompatible surface coatings, Heparin-induced thrombocytopenia, Nitric-oxide release, Of-the-art, Peptide macrocycle inhibitor, Plasma contact system, Protein-adsorption, Self-assembled monolayers, Surface modificatio, Synthetic endotheliu

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.

JTD Keywords: adsorption, binding, c1-esterase-inhibitor, coatings, contact activation, factor-xii, fxii activation, hemocompatibility, hemocompatible surface modification, heparin, polymer brushes, system, thrombosis, Adsorption, Anticoagulation, Antifouling agent, Article, Beta-fxiia, Biocompatibility, Blood, Blood clotting, Blood clotting factor 12, Blood clotting factor 12a, Blood clotting factor 12a inhibitor, Blood coagulation, C1-esterase-inhibitor, Cell activation, Chemical activation, Coagulation, Coating (procedure), Complement component c1s inhibitor, Complement system, Controlled study, Dendrimers, Enzyme immobilization, Enzymes, Erythrocyte, Esters, Factor xii, Factor xii activation, Factor xiia, Fibrin deposition, Functional polymers, Fxii activation, Haemocompatibility, Hemocompatibility, Hemocompatible surface modification, Hemostasis, Heparin, Human, Hydrogel, Medical devices, Metabolism, Plasma kallikrein, Plasma protein, Plastic coatings, Platelet count, Polymer, Polymer brushes, Polymerization, Polymers, Property, Root cause, Surface plasmon resonance, Surface property, Surface reactions, Surface-modification, Thrombocyte adhesion, Β-fxiia

Many cell therapies rely on the ability of mesenchymal stromal cells (MSCs) to diffuse and localize throughout the target tissue-such as tumoral and ischemic tissues-, in response to specific cytokine signals, rather than being concentrated at the site of implantation. Therefore, it is fundamental to engineer biomaterial carriers as reservoirs, from which cells can migrate, possibly in a controlled manner. In this work, microcarriers (μCs) made of polylactic acid are characterized as MSC delivery vehicles capable of modulating key chemotactic pathways. The effect of different functionalization strategies on MSC migratory behavior from the μCs is studied in vitro in relation to SDF-1α/CXCR4 axis,-a major actor in MSC recruitment, chemotaxis and homing. Collagen and arginine-glycine-aspartic acid (RGD) peptides were either covalently grafted or physisorbed on μC surface. While stable covalent modifications promoted better cell adhesion and higher proliferation compared to physisorption, the functionalization method of the μCs also affected the cells migratory behavior in response to SDF-1α (CXCL12) stimulation. Less stable coatings (physisorbed) showed sensibly higher number of migrating cells than covalent collagen/RGD coatings. The combination of physic-chemical cues provided by protein/peptide functionalization and stimuli induced by 3D culture on μCs improved MSC expression of CXCR4, and exerted a control over cell migration, a condition suitable to promote cell homing after transplantation in vivo. These are key findings to highlight the impact of surface modification approaches on chemokine-triggered cell release, and allow designing biomaterials for efficient and controlled cell delivery to damaged tissues.

JTD Keywords: Cell therapy, Chemotaxis, ECM (extracellular matrix), Mesenchymal stromal cells, Surface modification

CuInSe2 films were prepared onto Cu-cladded substrates by ultrasonic-assisted electrodeposition using different bath compositions and a fixed deposition potential of E=-1500 mV vs Ag/AgCl. In situ electrochemical treatments named selenization and electrocrystallization, in a Se4+ electrolyte were applied to modify the morphology, film structure and the phase composition. Films were characterized by scanning electron microscopy, X-ray diffraction, Raman spectroscopy and photocurrent response. A Cu2-xSe layer develops as the electrode is introduced into the electrolyte. The presence of Cu-In, In-Se, Cu-Se, cubic, hexagonal and tetragonal CuInSe2 phases as well as elemental In and Se was observed. After selenization, partial phase dissolution and Se deposition is observed and after the electrocrystallization treatment the secondary phases such as Cu-Se, Cu-In, In and Se reduce substantially and the grain sizes increase, as well as the photocurrent response. Phase diagrams are constructed for each set of films and reaction mechanisms are proposed to explain the phase evolution.

JTD Keywords: CuInSe2, Electrodeposition, In situ electrochemical treatments, Phase composition, Surface modification

Adhesion of tissue cells is a prerequisite for their growth and differentiation but prevents also apoptosis. Here the layer-by-layer technique (LbL) was used to design multilayer structures of poly(ethylene imine) (PEI) and heparin (HEP) on glass as model biomaterial to control the adhesion of primary human dermal fibroblasts. Distinct surface features like wettability, charge and lateral structures were controlled by changing the pH value of the HEP solution during multilayer assembly to acidic neutral or alkaline, values. While plain terminal layers were rather cytophobic, the pre-adsorption of serum or fibronectin (FN) caused a distinct change in cell morphology in dependence on the pH setup. The effect of serum was more prominent on PEI layers probably due to their positive surface charge, whereas the effect of FN was more pronounced on HEP terminated multilayers possibly due to its ability to bind FN specifically. Those layers which hampered cell adhesion also inhibited growth of human fibroblasts under serum conditions. Conversely, on layers where cell adhesion was increased also an elevated growth and, thus, metabolic activity was observed.

JTD Keywords: Surface modification, Layer-by-layer, Poly(ethylene imine), Heparin, Serum, Fibronectin