Tumor‐Exocytosed Exosome/Aggregation‐Induced Emission Luminogen Hybrid Nanovesicles Facilitate Efficient Tumor Penetration and Photodynamic Therapy

The development of novel photosensitizing agents with aggregation‐induced emission (AIE) properties has fueled significant advances in the field of photodynamic therapy (PDT). An electroporation method was used to prepare tumor‐exocytosed exosome/AIE luminogen (AIEgen) hybrid nanovesicles (DES) that could facilitate efficient tumor penetration. Dexamethasone was then used to normalize vascular function within the tumor microenvironment (TME) to reduce local hypoxia, thereby significantly enhancing the PDT efficacy of DES nanovesicles, and allowing them to effectively inhibit tumor growth. The hybridization of AIEgen and biological tumor‐exocytosed exosomes was achieved for the first time, and combined with PDT approaches by normalizing the intratumoral vasculature as a means of reducing local tissue hypoxia. This work highlights a new approach to the design of AIEgen‐based PDT systems and underscores the potential clinical value of AIEgens.     

Angiopoietin-1 variant, COMP-Ang1 attenuates hydrogen peroxide-induced acute lung injury

Reactive oxygen species (ROS) play a crucial role in acute lung injury. Tissue inflammation, the increased vascular permeability, and plasma exudation are cardinal features of acute lung injury. Angiopoietin-1 (Ang1) has potential therapeutic applications in preventing vascular leakage and also has beneficial effects in several inflammatory disorders. Recently developed COMP-Ang1 is more potent than native Ang1 in phosphorylating tyrosine kinase with immunoglobulin and EGF homology domain 2 receptor in endothelial cells. However, there are no data on effects and related molecular mechanisms of COMP- Ang1 on ROS-induced acute lung injury. We used hydrogen peroxide (H2O2)-inhaled mice to evaluate the effect of COMP-Ang1 on pulmonary inflammation, bronchial hyper-responsiveness, and vascular leakage in acute lung injury. The results have revealed that VEGF expression, the levels of IL-4, TNF-alpha, IL-1beta, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in lungs, the levels of hypoxia-inducible factor-1alpha (HIF-1alpha) and NF-kappaB in nuclear protein extracts, phosphorylation of Akt, and vascular permeability were increased after inhalation of H2O2 and that the administration of COMP-Ang1 markedly reduced airway hyper-responsiveness, pulmonary inflammation, plasma extravasation, and the increases of cytokines, adhesion molecules, and VEGF in lungs treated with H2O2. We have also found that the activation of HIF-1a and NF-kB and the increase of phosphoinositide 3-kinase activity in lung tissues after H2O2 inhalation were decreased by the administration of COMP-Ang1. These results suggest that COMP-Ang1 ameliorates ROS-induced acute lung injury through attenuating vascular leakage and modulating inflammatory mediators.     

Preparation of Small‐Diameter Tissue‐Engineered Vascular Grafts Electrospun from Heparin End‐Capped PCL and Evaluation in a Rabbit Carotid Artery Replacement Model

Aiming to construct small diameter (ID <6 mm) off‐the‐shelf tissue‐engineered vascular grafts, the end‐group heparinizd poly(ε‐caprolactone) (PCL) is synthesized by a three‐step process and then electrospun into an inner layer of double‐layer vascular scaffolds (DLVSs) showing a hierarchical double distribution of nano‐ and microfibers. Afterward, PCL without the end‐group heparinization is electrospun into an outer layer. A steady release of grafted heparin and the existence of a glycocalyx structure give the grafts anticoagulation activity and the conjugation of heparin also improves hydrophilicity and accelerates degradation of the scaffolds. The DLVSs are evaluated in six rabbits via a carotid artery interpositional model for a period of three months. All the grafts are patent until explantation, and meanwhile smooth endothelialization and fine revascularization are observed in the grafts. The composition of the outer layer of scaffolds exhibits a significant effect on the aneurysm dilation after implantation. Only one aneurysm dilation is detected at two months and no calcification is formed in the follow‐up term. How to prevent aneurysms remains a challenging topic.     

Hard‐block degradable thermoplastic urethane‐elastomers for electrospun vascular prostheses

Thermoplastic polyurethane (TPU) elastomers with biodegradable chain extenders were synthesized and tested for mechanical performance and biocompatibility. The design of the TPUs was based on structural modification of a mechanically appropriate aromatic isocyanate‐based TPU. As the aromatic isocyanate was substituted with a less toxic but also less “hard” aliphatic isocyanate, the chain extender plays an important role on the mechanical properties. Here, the terephthalate ester chain extender was found to work better than hydroxyl ethyl lactate in providing polymers with mechanical properties similar to commercial aromatic isocyanate‐based TPUs. The polymers were degraded in aqueous solutions at elevated temperatures and compared to polylactic acid (PLA) to partially simulate biodegradation. The lactate‐based TPUs degraded about twice as fast as PLA while the terephthalate‐based TPU degraded much more slowly. The latter material was processed by electrospinning to give a tubular graft approximately the size of a large rat blood vessel. Initial results from implantation of these TPUs into rats are promising and indicate that biodegradation occurs and is likely beneficial to cell proliferation. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

The discovery of placenta growth factor and its biological activity

Angiogenesis is a complex biological phenomenon crucial for a correct embryonic development and for post-natal growth. In adult life, it is a tightly regulated process confined to the uterus and ovary during the different phases of the menstrual cycle and to the heart and skeletal muscles after prolonged and sustained physical exercise. Conversly, angiogenesis is one of the major pathological changes associated with several complex diseases like cancer, atherosclerosis, arthritis, diabetic retinopathy and age-related macular degeneration. Among the several molecular players involved in angiogenesis, some members of VEGF family, VEGF-A, VEGF-B and placenta growth factor (PlGF), and the related receptors VEGF receptor 1 (VEGFR-1, also known as Flt-1) and VEGF receptor 2 (VEGFR-2, also known as Flk-1 in mice and KDR in human) have a decisive role. In this review, we describe the discovery and molecular characteristics of PlGF, and discuss the biological role of this growth factor in physiological and pathological conditions.     

共价键合多层肝素薄膜修饰涂有硅橡胶的人工血管

报道一种采用医用硅橡胶涂层作软支撑共价键合多层肝素薄膜修饰人工血管等生物医学装置使其表面具有抗凝血性能的方法. 该项技术首先在人工血管的表面上涂上医用硅橡胶作为软支撑, 再在硅橡胶涂层的表面上涂上全氟磺酸(Nafion), 为接下来的层层静电组装提供活性基团. 然后将带正电荷的二苯胺重氮树脂(PA)和带负电荷的肝素分子(Hep)通过静电吸引作用交替沉积到全氟磺酸涂层的表面上. 紫外可见吸收光谱和傅立叶红外光谱数据表明, 在紫外光照射下, 重氮树脂的重氮基团与肝素的硫酸基团之间发生光化学反应, 生成硫酸酯, 使膜内层间离子键转变成共价键, 从而使肝素多层膜的稳定性大大提高. 研究表明经层层自组装和光化学反应后肝素分子呈现良好的抗凝血性能. 人工血管肝素化表面中的肝素分子以壁面结合的方式存在, 在人工血管表面固化肝素和抗凝血酶-III (AT-III)形成的络合物显示出较好的抗凝血性. 硅橡胶涂层使肝素分子与人工血管表面有一定距离, 有利于提高抗凝血性能. 在四个双层之内, 肝素对凝血酶失活的影响随着PA/Hep双层数目增加而增加, 说明了只有最外层的肝素才对凝血酶失活有直接影响. 该方法操作工艺简单, 重复性好, 可较广泛地适用于在多种生物医用装置和多孔组织工程支架材料的表面制备稳定的抗凝血涂层, 具有良好的应用前景.     

Synthesis of Tetrahydropyridinyltriazolothiadiazines as Possible Muscarinic Agonists

4-Amino-5-(pyridin-3-yl)-4H-l,2,4-triazole-3-thiol 1 were condensed with 2-bromo-l-(substituted phenyl)ethanone to give pyridinyltriazolothiadiazines 2a-c, which were quaternarized with methyl iodide and oxidized with 30 % hydrogen peroxide to afford the corresponding methyl pyridinium salts 3a-c and pyridine- 1 -oxides 4a-c, respectively. The redtiction of compounds 3 and 4 with NaBH4 in methanol produced the target compounds 1-methyl- 1.2.5.6-tetrahydropyridin-3-yl)-6-aryl-s-triazolothiadiazines 5a-c and 3-( l-hydroxyl- 1, 2, 5, 6-tetrahydropyridin -3-yl)-6-aryl-s-triazolothiadiazines 6a-c, respectively. The endothelium vascular relaxing activity of the target compounds was screened.     

Three‐Layered PCL Grafts Promoted Vascular Regeneration in a Rabbit Carotid Artery Model

In this study, a three layered poly (ε‐caprolactone) (PCL) graft (tPCL) was fabricated by electrospinning PCL and electrospraying poly (ethylene oxide) (PEO), which has a thin dense inner layer, a loose middle layer, and a dense outer layer. Regular PCL grafts (rPCL) with only a dense layer were used as control. In vivo evaluation was performed in rabbit carotid artery. Enhanced cell infiltration, rapid regeneration of endothelium and smooth muscle layers, and increased elastin deposition were observed within the tPCL graft wall. After 3 months, tPCL grafts showed faster PCL degradation than the rPCL grafts. Infiltrated macrophages in the tPCL grafts secreted higher level of monocyte chemoattractant protein‐1 (MCP‐1) and vascular endothelial growth factor (VEGF) which enhanced vascular regeneration. In conclusion, the tPCL graft may be a useful vascular prosthesis and worth for further investigation.

     

Diazonium salts for surface‐confined visible light radical photopolymerization

The surface chemistry of aryl diazonium salts has progressed at a remarkable pace in the last two decades, and opened many avenues in materials science. These compounds are excellent coupling agents for polymers to surfaces via several surface‐confined polymerization methods. For the first time, we demonstrate that diazonium salts are efficient for surface initiating radical photopolymerization in the visible light of methyl methacrylate (MMA) and 2‐hydroxyethyl methacrylate (HEMA) taken as model monomers. To do so, 4‐(dimethylamino)benzenediazonium salt was electroreduced on gold plates or flexible ITO sheets to provide 4‐(dimethylamino)phenyl (DMA) hydrogen donor layers; while excited state camphorquinone acted as the free hydrogen abstractor. In the same way, we co‐polymerized HEMA and MMA with ethylene glycol dimethacrylate in order to obtain crosslinked polymer grafts. We demonstrate by XPS that gold was efficiently screened by the polymer layers and that the wettability of the surfaces accounts for the hydrophilic or hydrophobic characters of the tethered polymers. Homo‐ and crosslinked PMMA grafts were found to resist removal by the paint stripper methyl ethyl ketone. The grafted DMA/camphorquinone system operating in the visible light holds great promises in terms of adhesion of in situ designed continuous or patterned polymer coatings on various substrates. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3506–3515     

Self-Healing Polymer Composites: Prospects,Challenges, and Applications

Self-healing polymer composites possess the inherent ability to heal the damage event autonomically or non-autonomically with external intervention. These advanced materials can be commercialized if the challenges and limitations of different self-healing mechanisms are well known and considered. These include capsule-based healing systems, vascular healing systems, and intrinsic healing systems. To date, most of the reviews have studied and reported on different self-healing mechanisms including their response to impact, fatigue, and corrosion tests. This review focuses mostly on extrinsic and intrinsic self-healing polymer composites which have been reported during the past five years by comparing their healing efficiency, advantages, and challenges in the prospect of their future development as well as their possible applications across various industries such as aerospace, automobile, coating, electronics, energy, etc.