分层多功能层层自组装肝素表面修饰技术

背景：涂层技术可以在不改变基材的前提下改善材料的表面性质,提高血液相容性,从而减少人工植入装置植入后的不良反应. 目的：观察分层多功能层层自组装肝素涂层的血液相容性及抗凝特性. 方法：利用层层自组装技术组装出有底层和表层两个功能层的多层自组装涂层,表层为多层肝素/Fe3＋层层自组装涂层,底层为壳聚糖层,通过共价键固定在钛金属表面,共5层肝素.以组装相同层数的肝素/壳聚糖层层自组装涂层作为多层对照组;单层对照组为肝素和壳聚糖共混溶液的单层涂层;空白对照组为裸钛片. 结果与结论：血液相容性测试结果显示,实验制备的多层自组装涂层溶血率低于多层对照组;甲苯胺蓝法测定结果显示实验制备的多层自组装涂层的肝素总量及4,24,48 h的肝素溶解释放量均明显高于多层对照组和单纯对照组;同时动态凝血实验显示实验制备的多层自组装涂层抗凝性能最好.可见分层多功能层层自组装肝素涂层具有良好的血液相容性和抗凝血性能.     

Hemocompatibility and anti-biofouling property improvement of poly(ethylene terephthalate) via self-polymerization of dopamine and covalent graft of lysine

Inspired by the composition of adhesive proteins in mussels, we used self-polymerized dopamine to form a thin and surface-adherent polydopamine layer onto poly(ethylene terephthalate) (PET) sheet, followed by covalently grafting lysine (Lys) to improve hemocompatibility and anti-biofouling property. The obtained surfaces were characterized by water contact angle measurements, attenuated total reflectance Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy analysis. The results of platelet adhesion and protein adsorption tests showed that Lys-immobilized PET was endowed with improved resistance to nonspecific protein adsorption and platelet adhesion. Cell assay results showed that PET-g-Lys surface could greatly inhibit NIH 3T3 cell adhesion. These works provide a facile hemocompatible and anti-fouling surface for biomedical applications.     

新型生物医学材料——类金刚石膜的研究进展

类金刚石因具有良好的细胞相容性、血液相容性及高耐磨性高硬度等特点 ,而成为一种很有发展前景的生物膜材料。本文综述了 2 0世纪 90年代以来类金刚石的理化性质、生物学方面的研究进展 ,并对未来的发展进行了展望。     

Hemostatic Changes Induced In Vitro by Hemoperfusion Over Activated Charcoal

The effect of hemoperfusion over charcoal on changes in platelet counts, coagulation factor concentrations and standard coagulation tests were determined during a two-hour in vitro perfusion of normal blood through a column containing 20 gm of activated charcoal, either uncoated or coated with 0.5% acrylonitrile/dimethylaminoethyl methacrylate copolymer (AN/DMAEMA). With citrated whole blood, platelet counts fell by 15% during hemoperfusion over coated or uncoated charcoal and also during passage through an identical empty chamber. On the other hand, with heparinized whole blood, platelet counts fell by 90% during hemoperfusion over uncoated charcoal, and 25% during hemoperfusion over coated charcoal. The concentrations of coagulation factors II, V, IX, X and XII were reduced during hemoperfusion over uncoated charcoal, while those of factors II and X were reduced and that of factor VII increased during hemoperfusion over coated charcoal. Perfusion with heparinized, platelet-rich plasma resulted in small reductions in platelet counts, suggesting that either erythrocyte disruption or the physical effects of intact red cells play a major role in producing the hemostatic abnormalities occurring during whole blood hemoperfusion. The method described may be used to assess the hemocompatibility of polymer coatings for charcoal particles, to investigate the nature of the interaction between platelets and artificial surfaces, and to assess the effect of platelet-active agents in reducing platelet adsorption on charcoal or other sorbents.     

Blood Compatibility of Cetyl Alcohol/Polysorbate-Based Nanoparticles

Purpose Pegylated and nonpegylated cetyl alcohol/polysorbate nanoparticles (E78 NPs) are being tested as drug carriers for specific tumor and brain targeting. Because these nanoparticle formulations are designed for systemic administration, it is important to test the compatibility of these lipid-based NPs with blood and blood cells. Methods The hemocompatibility of E78 NPs was evaluated with a particular focus on hemolytic activity, platelet function, and blood coagulation. Human red blood cell lysis was determined by measuring hemoglobin release. Activation and aggregation of human platelets were determined using flow cytometry and aggregometry, respectively. Finally, the whole blood clotting time was measured using human blood. Results E78 NPs did not cause in vitro red blood cell lysis at concentrations up to 1 mg/mL. In addition, under conditions tested, E78 and polyethylene glycol (PEG)-coated E78 NPs (PEG-E78 NPs) did not activate platelets. In fact, both NP formulations very rapidly inhibited agonist-induced platelet activation and aggregation in a dose-dependent manner. Additionally, E78 NPs significantly prolonged in vitro whole blood clotting time at a concentration of 500 μg/mL or greater. Conclusions It was concluded that PEG-coated and nonpegylated E78 NPs have potential blood compatibility at clinically relevant doses. Based on the calculated nanoparticle-to-platelet ratio, the concentration at which E78 NPs could potentially affect platelet function in vivo was approximately 1 mg/mL.     

FT-IR spectroscopic studies of polyurethanes: IV. Studies of the effect of the presence of processing aids on the hemocompatibility of polyurethanes

Many types of proprietary processing aids are used by the manufacturers of polymer medical devices, which are difficult to completely eliminate from the end product. In such cases, it is important to investigate how such processing aids affect the properties of the materials. One such material is Pellethane and a most commonly found processing aid is wax. We investigated the effect of the presence of such wax on hecompatibility properties, particularly on the adhesion and activation of human platelets, on a group of Pellethane samples with varying amounts of wax. The effectiveness of cleaning agents, like Freon, was examined for wax removal. The type and quantity of wax present within the near-surface regions of the Pellethane tubings was estimated by using the FT-IR-ATR technique. The presence of bis amide processing wax was found to affect the hemocompatibility properties of the Pellethane samples. Correlation between hemocompatibility and the amount of wax was made; platelet activation, as well as amount and density of fibrin formation, showed a linear correlation.     

Hemocompatibility of polymeric nanostructured surfaces

Tissue integration is an important property when inducing transplant tolerance, however, the hemocompatibility of the biomaterial surface also plays an important role in the ultimate success of the implant. Therefore, in order to induce transplant tolerance, it is critical to understand the interaction of blood components with the material surfaces. In this study, we have investigated the adsorption of key blood serum proteins, in vitro adhesion and activation of platelets and clotting kinetics of whole blood on flat polycaprolactone (PCL) surfaces, nanowire (NW) surfaces and nanofiber (NF) surfaces. Previous studies have shown that polymeric nanostructured surfaces improve cell adhesion, proliferation and viability; however it is unclear how these polymeric nanostructured surfaces interact with the blood and its components. Protein adsorption results indicate that while there were no significant differences in total albumin (ALB) adsorption on PCL, NW and NF surfaces, NW surfaces had higher total fibrinogen (FIB) and immunoglobulin-G (IgG) adsorption compared to NF and PCL surfaces. In contrast, NF surfaces had higher surface FIB and IgG adsorption compared to PCL and NW surfaces. Platelet adhesion and viability studies show more adhesion and clustering of platelets on the NF surfaces as compared to PCL and NW surfaces. Platelet activation studies reveal that NW surfaces have the highest percentage of unactivated platelets, whereas NF surfaces have the highest percentage of fully activated platelets. Whole blood clotting results indicate that NW surfaces maintain an increased amount of free hemoglobin during the clotting process compared to PCL and NF surface, indicating less clotting and slower rate of clotting on their surfaces.     

Chemiluminescent Analysis of Plasma Antioxidant Capacity in Uremic Patients Undergoing Hemodialysis

Objective. Hemodialysis is a common therapeutic strategy for patients with end stage renal failure. During the hemodialytic process, the neutrophils are activated (neutrophil burst) due to the hemoincompatibility induced by hemodialysis. As a result, the activated neutrophils release reactive oxygen species (ROS), such as hydrogen peroxide, singlet oxygen, and hypochlorite, into the bloodstream and cause oxidative damage. Methods. This study investigated the antioxidant alteration of plasma in uremic patients undergoing hemodialysis by chemiluminescent analysis. The antioxidant capacities of plasma in scavenging hydrogen peroxide, singlet oxygen, and hypochlorite were investigated in this experiment. In addition, investigation of the ferric-reducing ability of plasma (FRAP) would be covered in this study as well. Results. This study found that after hemodialysis, the antioxidant capacities of plasma in scavenging hydrogen peroxide, singlet oxygen, and hypochlorite decreases 7.9%, 18.8%, and 18.9%, respectively. Moreover, the FRAP is reduced by 56%. We speculate that the loss of dialyzable solutes (such as uremic solutes and antioxidants with small molecular weight) in plasma resulted in its decrease in antioxidant capacity. Conclusion. We therefore suggest that the supplement of antioxidants with small molecular weight is capable of regaining antioxidant defense in plasma and preventing oxidative damage induced by hemodialysis.     

HUVEC biocompatibility and platelet activation of segmented polyurethanes prepared with either glutathione or its amino acids as chain extenders

Novel biodegradable segmented polyurethanes (SPUs) were synthesized with polycaprolactone diol, 4,4′-methylen bis (cyclohexyl isocyanate) (HMDI), and either L-glutathione or its constituent amino acids (L-glutamic acid, L-cysteine and glycine) as chain extenders. Fourier transform infrared spectroscopy analysis revealed the feasibility of obtaining polyurethanes through the presence of NH (Amide II), C–N, C–O, and C=O bands and the absence of NCO band. Differential scanning calorimetry and X-ray diffraction revealed that a semicrystalline polymer (T _m?=?42–52?°C; 2θ?=?21.3° and 23°) was obtained in all cases, while dynamic mechanical analysis (DMA) revealed an amorphous phase (T _g?=??30 to ?36?^oC). These properties, in addition to their high molecular weight, led to high moduli and higher extensibilities when glycine and glutamic acid were used as chain extenders. Clotting times (Lee–White test) and activated partial thromboplastin time determined on these polyurethanes were longer than with glass. In addition, all synthesized SPU exhibited platelet activation indexes below the collagen type I positive control. Human umbilical vein endothelial cells viability was higher in SPUs containing either glycine or cysteine. The obtained results indicate that SPUs that use cysteine as chain extender are promising candidates for cardiovascular applications.     

血液对涂层血管支架作用的基础理论研究

目的探索血液对涂层血管支架作用的基本理论。方法①现今运用的不锈钢支架（ss）以新型生物材料氧化钛（Ti-0）涂层;②（Ti-0）通过氨丙基三乙氧基硅烷（APTE）的活性氨基偶联将清蛋白和肝素（ALB）再涂层在改性支架的表面;③体外血小板（PL）粘附试验;④动物犬股动脉内植入双涂层（SS＋Ti-0＋Alb）试验片分别与单涂层（SS＋Ti-0）试验片和光祼（SS）试验片作对照。6个月后扫描电镜观察支架表面粘附的PL的数量和形态。结果体外和体内试验的扫描电镜观察支架表面吸附和发生形态变化的PL量呈SS＋Ti-0＋Alb〈SS＋Ti-0〈SS。结论纤维蛋白原（FIG）对涂层支架不传出电子,并且与涂层支架表面材料有相近似的界面张力,保证了FIG与PL本身结构正常的构象稳定,在构象正常的FIG内对PL的作用靶位与FIG相互连接的位点不被暴露,不引发凝血。通过预处理使清蛋白与肝素以化学键方法与支架结合,FIG更难被支架吸附,保持自身的稳定性。