Mechanical properties,hemocompatibility, cytotoxicity and systemic toxicity of carbon fibers/poly(ether-ether-ketone) composites with different fiber lengths as orthopedic implants

Abstract

Poly(ether-ether-ketone) (PEEK) has attracted more and more attention due to its chemical resistance, biocompatibility and other properties. Furthermore, carbon fibers-PEEK composite (CF-PEEK) has been considered as a novel implant because of its high mechanical strength and elastic modulus that matching with human bones. However, the length of CF has a great influence on mechanical strength and elastic modulus of the randomly distributed chopped CF-PEEK composites. In this work, CF-PEEK composites with more than 10 times length difference of fibers (length of short CF: 150–200?μm and length of long CF: 2–3?mm) were studied. As the results shown, the mechanical strength (including tensile strength, bending strength and compressive strength) of long CF-PEEK composites were more than two times of that of short CF-PEEK composites. Meanwhile, tensile modulus and bending modulus of the two kinds of composites matched well with the modulus of human cortical bone. In addition, according to the results of cytotoxicity test and hemocompatibility assessment, it indicated that the two kinds of CF-PEEK composites showed mild toxicity and no hemolytic reaction. And the histopathological section of systemic toxicity test showed that the CF-PEEK composites had no obvious acute toxicity to organisms.     

Preparations and properties of a novel grafted segmented polyurethane-bearing glucose groups

Novel grafted polyurcthane-bearing glucose groups were synthesized through a graft copolymerization of a prefabricated polyurethane containing poly(butadiene) glycol (PBD) and hydrogenated poly(butadiene) glycol (HPBD) soft segments, and 4,4'-methylenediphenyl diisocyanate (MDI) hard segment with a hydrophilic monomer glycosylethyl methacrylate (GEMA) in solution in the presence of 2,2'-azobis(isobutyronitrile) (AIBN) as an initiator. The bulk characteristics of the grafted polyurethanes were investigated by infra-red (IR) spectroscopy and gel permeation chromatography (GPC) measurements. The glucose groups were oriented on the surface of the cast film of grafted polyurethane with different graft-on percentages as revealed by electron spectroscopy for chemical analysis (ESCA), attenuated total reflectance infra-red spectroscopy (ATR-FTIR), and water contact angle. The grafted polyurethane surfaces which showed decreased water contact angles also indicate that hydrophilic glucose groups are present at the surface. The hemocompatibilities of these polymer surfaces were evaluated by platelet-rich plasma (PRP) contacting tests. It was found that the surface of grafted polyurethane with a graft-on percentage of 23.4% showed a good hemocompatibility in terms of platelet adhesion and shape variation. It indicates that glucose groups on the surface are effective for the improvement of hydrophilicity as well as hemocompatibility.     

Differences of platelet adhesion and thrombus activation on amorphous silicon carbide,magnesium alloy,stainless steel,and cobalt chromium stent surfaces

Background: Coronary stenting is considered to be the gold standard of percutaneous coronary interventions, because stents are able to reduce early and late elastic recoil (negative remodeling) and restenosis in comparison with balloon angioplasty alone. Objective: It is known that stent thrombogenicity and neointimal formation are determined by the surface characteristics of the stent platform, electrochemical features of the stent surface, and the degree of degradation after implantation. Metallic stents coated with amorphous silicon carbide and biodegradable stents made of magnesium alloy have been introduced clinically, but there are no data available comparing the biocompatibility of these novel stent materials with conventional stents. Methods: We demonstrate simple and reproducible in vitro methods assessing the rate of platelet adhesion and thrombus activation for biocompatibility tests of different stent surfaces. Results: We show that amorphous silicon carbide and magnesium alloy stent surfaces markedly lower the rate of platelet adhesion and platelet/fibrin activation when compared with uncoated stainless steel or cobalt chromium alloy surfaces. Semiconductor materials on the stent surface reduce platelet and fibrin activation by increasing the critical electron gap to greater than 0.9 eV resulting in a lower electron transfer out of the stent material. Conclusion: Passive stent coatings with specific semiconducting properties such as amorphous silicon carbide or magnesium alloy reduce thrombogenicity and may improve biocompatibility of a stent platform. © 2009 Wiley‐Liss, Inc.     

Evaluation of in vitro hemolysis and platelet activation of a newly developed maglev LVAD and two clinically used LVADs with human blood

In vitro hemolysis testing remains one of the most important performance measures to judge the hemocompatibility of a left ventricular assist device (LVAD). Clinically relevant operating conditions and appropriate testing blood are essential to infer in vitro data for potential clinical use. This in vitro study was carried out to evaluate and compare the hemolytic performance of a newly developed magnetically levitated (maglev) LVAD (CH‐VAD) with two clinically used LVADs (HVAD and HeartMate II (HMII)) using fresh human blood. A small volume (~300 mL) in vitro circulating flow loop was constructed with a LVAD generated flow of 4.5 L/min at the nominal or reported clinical operating speed for each LVAD. The blood was circulated in the loop for 4 hours with samples drawn at baseline and hourly. Plasma‐free hemoglobin (PFH) concentrations in the hourly blood samples were determined with spectrophotometry. Normalized index of hemolysis (NIH) was calculated to compare the hemolytic performance of the CH‐VAD and the two reference LVADs. Platelet activation was measured with flow cytometry. The experimental test for each device was repeated at least 7 times. The data from this study showed that all the three LVADs generated very low hemolysis (NIH <0.01 g/100 L). The CH‐VAD was found to have a significantly lower NIH value (0.00135 ± 0.00032 g/100 L) compared to the HVAD (0.00525 ± 0.00183 g/100 L) and the HMII (0.00583 ± 0.00182 g/100 L). No statistically significant difference in device‐generated hemolysis was found between the HVAD and the HMII. The level of platelet activation induced by the CH‐VAD is significantly lower than those by the HVAD and the HMII. The data suggest that the shear‐induced hemolysis and platelet activation of the CH‐VAD are acceptable relative to the two LVADs currently in clinical use.     

肝素铁复合物纳米修饰提高异种移植血管的血液相容性

目的:采用肝素铁复合物纳米修饰去细胞异种血管以提高其血液相容性。方法:采用层层自组装技术将二羟基铁和肝素交替固定在去细胞牛颈静脉(DC-BJV) 表面,构建一种新型的多层肝素铁复合物(HICMs) 抗凝表面,并通过扫描电镜(SEM) 检测其表面微结构、拉力器检测其生物力学稳定性、抗凝血活性实验和血小板黏附实验检测其血液相容性。结果:每组装一次,约有(808±86) μg/cm² 肝素固定在BJV 表面;SEM 图片显示HICMs 是均匀地包裹在胶原纤维表面并形成纳米膜;组织切片甲苯胺蓝染色提示肝素主要结合在DC-BJV 的表层;拉力试验提示实验组的生物力学稳定性有显著提高;经过1 d 及1,2,3,4,6,8 周的洗脱,肝素的释放量分别为(281±43),(422±60),(729±81),(1053±116),(1317±157),(1618±187),(1945±228 ) μg/cm²;抗凝血活性检测显示实验组凝血酶原时间(PT)和活化部分凝血酶原时间(APTT) 高于正常值范围;血小板黏附试验显示每10000 μm² HICMs 层层自组装修饰的牛颈静脉(LBL-BJV) 和DC-BJV 的血小板计数分别为8±4 和48±16。结论:HICMs 牢固地结合在DC-BJV 表层,形成纳米厚度的抗凝表面,并长时间地缓慢释放肝素。HICMs 纳米修饰能够提高去细胞异种血管的血液相容性。     

The effect of anti-CD133/fucoidan bio-coatings on hemocompatibility and EPC capture

Surface modification by immobilizing biomolecules has been widely proved to enhance biocompatibility of cardiovascular implanted devices. Here, we aimed at developing a multifunctional surface that not only provides good hemocompatibility but also functions well in capturing circulating endothelial progenitor cells (EPCs) in the blood flow to improve the surface endothelialization. In the present work, we preferred to chemically co-immobilize (Michael addition and Schiff base reaction) the anti-CD133 (EPC-specific antibody) and fucoidan (EPC-mobilization factor, which also contribute to better hemocompatibility) onto a polydopamine (PDA) film which is famous for its stability and endothelial cell (EC) compatibility. The quantality of anti-CD133 and other surface characterization (X-ray photoemission spectroscopy, atomic force microscopy and water contact angle measurement) demonstrated successful preparation of the CD133/fucoidan coating. The platelets adhesion/activation test suggested improved hemocompatibility of this bio-coating. The ex vivo experiment on New Zealand white rabbits showed that the anti-CD133/fucoidan coating had good ability on capture the circulating EPC. In addition, the quartz crystal microbalance-D indicated that the EPC behaviors, including adhesion, spreading and extracellular matrix re-molding, were related to the density of anti-CD133 in the coating. We hope this anti-CD133/fucoidan multi-functional coating may provide potential application on surface modification of cardiovascular biomaterials.     

Bioactive zwitterionic polymer brushes grafted from silicon wafers via SI-ATRP for enhancement of antifouling properties and endothelial cell selectivity

Zwitterionic copolymers keep good resistance to platelet adhesion and nonspecific protein adsorption. In this study, A block copolymer brushes consisting of carboxybetaine methacrylate (CBMA) and glycidyl methacrylate (GMA) were grafted from silicon wafers via surface-initiated atom transfer radical polymerization, and then the Arg-Glu-Asp-Val (REDV) peptide was attached to the polymer brush via an reactive epoxy group of the P(GMA) unit to improve endothelial cells (ECs) selectivity. These modified surfaces were evaluated with scanning electron microscopy, atomic force microscopy, attenuated total reflectance-Fourier transform infrared spectra, X-ray photoelectron spectroscopy, and static water contact angle measurement. The results showed that REDV-modified zwitterionic brushes were successfully constructed on silicon wafers. The biocompatibility of the membrane was determined by plasma recalcification time assay and platelet adhesion test. The results showed that the modified substrate exhibited good blood compatibility. Moreover, the proliferation of ECs and smooth muscle cells onto the REDV-modified copolymer brushes were examined to demonstrate the synergistic effect of CBMA with antifouling property and REDV peptide with ECs selectivity. All assays showed that the silicon wafers displayed excellent EC selectivity after modification. In summary, REDV-modified zwitterionic brushes had great potential for cardiovascular stent implantation.     

小儿生物可降解血管支架新型材料血液相容性评价

目的 评价以对二氧环已酮(PDO)为材料的生物可降解血管支架的血液相容性.方法 通过体外动态凝血试验、凝血时间测定、血小板黏附试验、溶血率测定,在体外评价PDO可降解血管支架的血液相容性,并和目前已广泛应用于临床的316L不锈钢金属支架进行比较.结果 PDO可降解血管支架与316L不锈钢金属支架抗血液凝固性能相仿,二者对内源性及外源性凝血因子均无激活作用.与316L不锈钢金属支架相比,PDO可降解血管支架对血小板黏附和激活作用较轻.PDO可降解血管支架与316L不锈钢金属支架的溶血率均<5%.结论 对二氧环己酮生物可降解血管支架有较好的血液相容性.     

Bio-/haemocompatibility: implications and outcomes for sensors?

Sensors are a sample contacting technology, and when exposed to biological matrices tend to suffer from the problem of poor biocompatibility and surface fouling. The effects are evidenced by time dependant signal drift (particularly for those devices which are implanted intravascularly). Practical methods to reduce such effects require an understanding of the interface between the electrode and its environment prior to assessment of the potential areas for improvement. Current procedures employed to overcome the observed losses in electrode sensitivity (following exposure to whole blood) include surface modification of the outer diffusion limiting membrane (via variation in film porosity) or even biomimicry of the fluid cell membrane. At amperometric electrodes incorporation of additional inner perm-selective membranes has achieved a reduction in electrode passivation from undesirable surface active compounds as has the use of low polarisation potentials. Other studies have attempted to induce an aqueous barrier between the matrix and the electrode tip which physically prevents passage of cellular components from the sensor surface.
Careful choice of the system and materials will ultimately lead to biocompatible non-fouling devices capable of functioning in an array of bio-environments suitable for clinical monitoring of the critically ill patient.