A thrombin-triggered self-regulating anticoagulant strategy combined with anti-inflammatory capacity for blood-contacting implants

Interrelated coagulation and inflammation are impediments to endothelialization, a prerequisite for the longterm function of cardiovascular materials. Here, we proposed a self-regulating anticoagulant coating strategy combined with anti-inflammatory capacity, which consisted of thrombin-responsive nanogels with anticoagulant and anti-inflammatory components. As an anticoagulant, rivaroxaban was encapsulated in nanogels cross-linked by thrombin-cleavable peptide and released upon the trigger of environmental thrombin, blocking the further coagulation cascade. The superoxide dismutase mimetic Tempol imparted the antioxidant property. Polyphenol epigallocatechin gallate (EGCG), in addition to its anti-inflammatory function in synergy with Tempol, also acted as a weak cross-linker to stabilize the coating. The effectiveness and versatility of this coating were validated using two typical cardiovascular devices as models, biological valves and vascular stents. It was demonstrated that the coating worked as a precise strategy to resist coagulation and inflammation, escorted reendothelialization on the cardiovascular devices, and provided a new perspective for designing endothelium-like functional coatings

Platelet Membrane-Coated Nanocarriers Targeting Plaques to Deliver Anti-CD47 Antibody for Atherosclerotic Therapy

Atherosclerosis, the principle cause of cardiovascular disease (CVD) worldwide, is mainly characterized by the pathological accumulation of diseased vascular cells and apoptotic cellular debris. Atherogenesis is associated with the upregulation of CD47, a key antiphagocytic molecule that is known to render malignant cells resistant to programmed cell removal, or "efferocytosis." Here, we have developed platelet membrane-coated mesoporous silicon nanoparticles (PMSN) as a drug delivery system to target atherosclerotic plaques with the delivery of an anti-CD47 antibody. Briefly, the cell membrane coat prolonged the circulation of the particles by evading the immune recognition and provided an affinity to plaques and atherosclerotic sites. The anti-CD47 antibody then normalized the clearance of diseased vascular tissue and further ameliorated atherosclerosis by blocking CD47. In an atherosclerosis model established in ApoE-/- mice, PMSN encapsulating anti-CD47 antibody delivery significantly promoted the efferocytosis of necrotic cells in plaques. Clearing the necrotic cells greatly reduced the atherosclerotic plaque area and stabilized the plaques reducing the risk of plaque rupture and advanced thrombosis. Overall, this study demonstrated the therapeutic advantages of PMSN encapsulating anti-CD47 antibodies for atherosclerosis therapy, which holds considerable promise as a new targeted drug delivery platform for efficient therapy of atherosclerosis

A review of the development of interventional devices for mitral valve repair with the implantation of artificial chords

Mitral regurgitation (MR) was the most common heart valve disease. Surgical repair with artificial chordal replacement had become one of the standard treatments for mitral regurgitation. Expanded polytetrafluoroethylene (ePTFE) was currently the most commonly used artificial chordae material due to its unique physicochemical and biocompatible properties. Interventional artificial chordal implantation techniques had emerged as an alternative treatment option for physicians and patients in treating mitral regurgitation. Using either a transapical or a transcatheter approach with interventional devices, a chordal replacement could be performed transcatheter in the beating heart without cardiopulmonary bypass, and the acute effect on the resolution of mitral regurgitation could be monitored in real-time by transesophageal echo imaging during the procedure. Despite the in vitro durability of the expanded polytetrafluoroethylene material, artificial chordal rupture occasionally occurred. In this article, we reviewed the development and therapeutic results of interventional devices for chordal implantation and discuss the possible clinical factors responsible for the rupture of the artificial chordal material

Water consumption in hydrocarbon generation and its significance to reservoir formation

The geochemical effects of water consumption during hydrocarbon generation were studied on the basis of evolution laws of source rocks and simulation experiments on hydrocarbon generation. Water consumption statistics were obtained in order to study the relationship between water consumption during hydrocarbon generation and hydrocarbon migration and reservoir formation. The simulation experiments of hydrocarbon generation were performed under hydrous and anhydrous conditions for correlation. The geochemical characteristics of organic evolution under these two conditions were analyzed and the variations of hydrocarbon generation potential and carbon transformation ratio were emphasized. The results show the effects that organic matter and water have on each other during hydrocarbon generation: part of unavailable carbon is activated in kerogen and hydrogen is increased in degraded products, which leads to the increase of total hydrocarbon generation potential. According to water consumption mechanisms, the quantitative evaluation method of water consumption in hydrocarbon generation was put forward and used in the studies of the main source rocks in the Dongying Sag. Both of the water consumption and the depth range of the Upper Es4 Member are larger, while those of the Lower and Middle Es3 Members are smaller. Water consumption affects hydrocarbon migration and accumulation by increasing organic carbon degradation rate to increase fluid volume. Pore fluid pressure and oil-bearing saturation are consequently increased. The matching relationship between water-consuming hydrocarbon generation intervals and water-consuming diagenesis intervals enhances the dynamic forces of hydrocarbon migration, which benefits the formation of self-generating and self-preserving reservoirs or lower-generating and upper-preserving reservoirs. Key words: hydrocarbon generation, water consumption, reservoir formation, simulation, Dongying Sa

Dynamic difference and characterization of reservoir fluid in continental rift basins

In order to establish the relationship between hydrocarbon characteristic variations and dynamic environments, the differences of hydrocarbon geochemical characteristics of reservoirs in various pressure systems (overpressure zone, transitional pressure zone and normal pressure zone) were studied. The Dongying and Zhanhua sags in the Jiyang Depression of the Bohai Bay Basin were taken as examples in this paper, the variations of sterane isomerization parameter, sterane light/heavy ratio with depth were revealed. The transition from overpressure charging to normal pressure driving was clarified. The typical profiles of the Boxing (single pressure structure) and Bonan (composite pressure structure) sub-sags in the Dongying and Zhanhua sags, respectively, were selected for the differential analyses of geochemical parameters and corresponding dynamic conditions in various belts. The variations of the geochemical parameters showed high correlations to overpressure driving and buoyancy driving. The development ranges of abnormal pressure during reservoir formation were studied as well, which are much larger than the present abnormal pressure distribution ranges. Especially in the step-fault zone belt, historic overpressure had greatly extended outwards. According to the geochemical characterization of dynamic conditions, the reservoir formation systems and hydrocarbon supply ranges were described in detail

Electrospun silk fibroin/poly (L-lactide-ε-caplacton) graft with platelet-rich growth factor for inducing smooth muscle cell growth and infiltration

The construction of a smooth muscle layer for blood vessel through electrospinning method plays a key role in vascular tissue engineering. However, smooth muscle cells (SMCs) penetration into the electrospun graft to form a smooth muscle layer is limited due to the dense packing of fibers and lack of inducing factors. In this paper, silk fibroin/poly (L-lactide-ε-caplacton) (SF/PLLA-CL) vascular graft loaded with platelet-rich growth factor (PRGF) was fabricated by electrospinning. The in vitro results showed that SMCs cultured in the graft grew fast, and the incorporation of PRGF could induce deeper SMCs infiltrating compared to the SF/PLLA-CL graft alone. Mechanical properties measurement showed that PRGF-incorporated graft had proper tensile stress, suture retention strength, burst pressure and compliance which could match the demand of native blood vessel. The success in the fabrication of PRGF-incorporated SF/PLLA-CL graft to induce fast SMCs growth and their strong penetration into graft has important application for tissue-engineered blood vessels

Electrospun silk fibroin/poly (L-lactide-ε-caplacton) graft with platelet-rich growth factor for inducing smooth muscle cell growth and infiltration

The construction of a smooth muscle layer for blood vessel through electrospinning method plays a key role in vascular tissue engineering. However, smooth muscle cells (SMCs) penetration into the electrospun graft to form a smooth muscle layer is limited due to the dense packing of fibers and lack of inducing factors. In this paper, silk fibroin/poly (L-lactide-ε-caplacton) (SF/PLLA-CL) vascular graft loaded with platelet-rich growth factor (PRGF) was fabricated by electrospinning. The in vitro results showed that SMCs cultured in the graft grew fast, and the incorporation of PRGF could induce deeper SMCs infiltrating compared to the SF/PLLA-CL graft alone. Mechanical properties measurement showed that PRGF-incorporated graft had proper tensile stress, suture retention strength, burst pressure and compliance which could match the demand of native blood vessel. The success in the fabrication of PRGF-incorporated SF/PLLA-CL graft to induce fast SMCs growth and their strong penetration into graft has important application for tissue-engineered blood vessels