Facile surface modification of silicone rubber with zwitterionic polymers for improving blood compatibility

A facile approach to modify silicone rubber (SR) membrane for improving the blood compatibility was investigated. The hydrophobic SR surface was firstly activated by air plasma, after which an initiator was immobilized on the activated surface for atom transfer radical polymerization (ATRP). Three zwitterionic polymers were then grafted from SR membrane via surface-initiated atom transfer radical polymerization (SI-ATRP). The surface composition, wettability, and morphology of the membranes before and after modification were characterized by X-ray photoelectron spectroscopy (XPS), static water contact angle (WCA) measurement, and atomic force microscopy (AFM). Results showed that zwitterionic polymers were successfully grafted from SR surfaces, which remarkably improved the wettability of the SR surface. The blood compatibility of the membranes was evaluated by protein adsorption and platelet adhesion tests in vitro. As observed, all the zwitterionic polymer modified surfaces have improved resistance to nonspecific protein adsorption and have excellent resistance to platelet adhesion, showing significantly improved blood compatibility. This work should inspire many creative uses of SR based materials for biomedical applications such as vessel, catheter, and microfluidics.     

Hydroxyapatite–diamondlike carbon nanocomposite films

Hydroxyapatite is a bioactive ceramic that mimics the mineral composition of natural bone. Conventional plasma-sprayed hydroxyapatite coatings demonstrate poor adhesion and poor mechanical integrity. We have developed hydroxyapatite–diamondlike carbon bilayer film. The diamondlike carbon interlayer serves to prevent metal ion release and improve adhesion of the hydroxyapatite film. These films were characterized using X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Raman spectroscopy, nanoindentation, and microscratch adhesion testing. Based on the results of this study, hydroxyapatite–diamondlike carbon bilayers demonstrate promise for use in several orthopedic implants.     

Zwitterionic sulfobetaine-grafted poly(vinylidene fluoride) membrane with highly effective blood compatibility via atmospheric plasma-induced surface copolymerization

Development of nonfouling membranes to prevent nonspecific protein adsorption and platelet adhesion is critical for many biomedical applications. It is always a challenge to control the surface graft copolymerization of a highly polar monomer from the highly hydrophobic surface of a fluoropolymer membrane. In this work, the blood compatibility of poly(vinylidene fluoride) (PVDF) membranes with surface-grafted electrically neutral zwitterionic poly(sulfobetaine methacrylate) (PSBMA), from atmospheric plasma-induced surface copolymerization, was studied. The effect of surface composition and graft morphology, electrical neutrality, hydrophilicity and hydration capability on blood compatibility of the membranes were determined. Blood compatibility of the zwitterionic PVDF membranes was systematically evaluated by plasma protein adsorption, platelet adhesion, plasma-clotting time, and blood cell hemolysis. It was found that the nonfouling nature and hydration capability of grafted PSBMA polymers can be effectively controlled by regulating the grafting coverage and charge balance of the PSBMA layer on the PVDF membrane surface. Even a slight charge bias in the grafted zwitterionic PSBMA layer can induce electrostatic interactions between proteins and the membrane surfaces, leading to surface protein adsorption, platelet activation, plasma clotting and blood cell hemolysis. Thus, the optimized PSBMA surface graft layer in overall charge neutrality has a high hydration capability and the best antifouling, anticoagulant, and antihemolytic activities when comes into contact with human blood.     

Microstructure and magnetic properties of the FePt film on a membrane of anodized aluminum oxide

By making use of the dc magnetron sputtering system, the Au/FePt bilayers have been prepared on glass substrates and anodized aluminum oxide (AAO) membranes with an average pore diameter of around 200 nm. In both cases, the FePt films can be converted into the magnetically hard phase, namely L1₀ phase, after a heat treatment above 500 °C for 1 h. A nanoparticle-like structure can be observed in the 15-nm-thick FePt film on the AAO membrane. The experimental observations of the structure and the magnetism of the FePt films on the AAO membranes are firstly established.     

Benefits and limitations of porous substrates as biosensors for protein adsorption

Porous substrates have gained widespread interest for biosensor applications based on molecular recognition. Thus, there is a great demand to systematically investigate the parameters that limit the transport of molecules toward and within the porous matrix as a function of pore geometry. Finite element simulations (FES) and time-resolved optical waveguide spectroscopy (OWS) experiments were used to systematically study the transport of molecules and their binding on the inner surface of a porous material. OWS allowed us to measure the kinetics of protein adsorption within porous anodic aluminum oxide membranes composed of parallel-aligned, cylindrical pores with pore radii of 10-40 nm and pore depths of 0.8-9.6 μm. FES showed that protein adsorption on the inner surface of a porous matrix is almost exclusively governed by the flux into the pores. The pore-interior surface nearly acts as a perfect sink for the macromolecules. Neither diffusion within the pores nor adsorption on the surface are rate limiting steps, except for very low rate constants of adsorption. While adsorption on the pore walls is mainly governed by the stationary flux into the pores, desorption from the inner pore walls involves the rate constants of desorption and adsorption, essentially representing the protein-surface interaction potential. FES captured the essential features of the OWS experiments such as the initial linear slopes of the adsorption kinetics, which are inversely proportional to the pore depth and linearly proportional to protein concentration. We show that protein adsorption kinetics allows for an accurate determination of protein concentration, while desorption kinetics could be used to capture the interaction potential of the macromolecules with the pore walls.     

Multi‐Modal,Surface‐Focused Anticoagulation Using Poly‐2‐methoxyethylacrylate Polymer Grafts and Surface Nitric Oxide Release

This study examines platelet adhesion on surfaces that combine coatings to limit protein adsorption along with “anti‐platelet” nitric oxide (NO) release. Uncoated and poly‐2‐methoxyethylacrylate (PMEA) coated, gas permeable polypropylene (PP) membranes were placed in a bioreactor to separate plasma and gas flows. Nitrogen with 100/500/1000 ppm of NO was supplied to the gas side as a proof of concept. On the plasma side, platelet rich plasma (PRP, 1 × 108 cell/mL) was recirculated at low (60)/high (300) flows (mL/min). After 8 hours, adsorbed platelets on PP was quantified via a lactate dehydrogenase assay. Compared to plain PP, the PMEA coating alone reduced adsorption by 17.4 ± 9.2% and 29.6 ± 16.6% at low and high flow (p < 0.05), respectively. NO was more effective at low plasma flow. At 100 and 500 ppm of NO, adsorption fell by 37.9 ± 6.1% and 100 ± 4.7%, (p < 0.001), on plain PP. At high flow with 100, 500, and 1000 ppm of NO, adsorption reduced by 17.9 ± 17.8%, 46.4 ± 23.2%, and 100 ± 4.8%, (p < 0.001), respectively. On PMEA‐coated PP with only 100 ppm, adsorption fell by 69.7 ± 6.8 and 65.6% ± 16.9%, (p < 0.001), at low and high flows respectively. Therefore, the combination of an anti‐adsorptive coating with NO has great potential to reduce platelet adhesion and coagulation at biomaterial surfaces.     

纳米多孔铝阳极氧化膜的形成机理研究

为探讨多孔铝阳极氧化膜的形成机理,研究了不同气压条件下铝在磷酸溶液中的阳极氧化过程,发现在真空下进行阳极氧化,氧气析出非常明显。通过测定不同气压下的阳极氧化曲线,分析了致密膜向多孔氧化铝膜的转化和生长过程,结果显示氧气析出是导致氧化膜从致密膜向多孔膜转变的主要原因。提出了在氧化膜/电解液界面上氧气分子的聚集是造成表面条纹的新观点。通过氧化膜断面的SEM形貌表征,首次发现多孔膜的主孔道中存在分孔道。分孔道的产生说明析氧反应不但在致密膜/电解液界面发生,而且在多孔膜孔壁/电解液界面也同时发生。     

Electrically actuatable smart nanoporous membrane for pulsatile drug release

We report on the fabrication of electrically responsive nanoporous membrane based on polypyrrole doped with dodecylbenzenesulfonate anion (PPy/DBS) that was electropolymerized on the upper part of anodized aluminum oxide membrane. The membrane has regular pore size and very high pore density. Utilizing a large volume change of PPy/DBS depending on electrochemical state, the pore size was acutated electrically. The actuation of the pores was experimentally confirmed by in situ atomic force microscopy and in situ flux measurement. We also demonstrated successfully pulsatile (or on-demand) drug release by using fluorescently labeled protein as a model drug. Because of a fast switching time (less than 10 s) and high flux of the drugs, this membrane could be used for emergency therapy of angina pectoris and migraine, which requires acute and on-demand drug delivery, and hormone-related disease and metabolic syndrome.     

MMA/MPEOMA copolymers as coating materials for improved blood compatibility: protein adsorption study

Surface-induced thrombosis remains one of the main problems in the development of blood-contacting devices. When a foreign surface comes in contact with blood, the initial blood response is adsorption of blood proteins, followed by platelet adhesion and activation, leading to thrombus formation. A particularly effective polymer for the prevention of protein adsorption and platelet adhesion appears to be polyethylene oxide (PEO). In this study, water-insoluble copolymers of methyl methacrylate (MMA) and methoxy PEO monomethacrylates (MPEOMA) with different PEO molecular weights (200, 400, and 1000) and monomer composition were synthesized and characterized by gel permeation chromatography and ¹H-nuclear magnetic resonance spectroscopy. The synthesized copolymers were coated on glass slides by a spin coating method to prepare PEO-rich surfaces as blood-compatible surfaces. The surface properties of the copolymers and their interaction with blood proteins (albumin, γ-globulin, fibrinogen, and plasma proteins) were investigated by the measurement of water contact angles and by electron spectroscopy for chemical analysis, respectively. It was observed that the protein adsorption on the copolymer surfaces decreased with increasing PEO molecular weight and MPEOMA content in the copolymers. The copolymers with long PEO chains in MPEOMA (MMA/MPEO₀₀₀MA copolymers) were effective in preventing protein adsorption, even though their MPEOMA content was less than the copolymers with shorter PEO chains. © 1999 Kluwer Academic Publishers     

Biocompatibility studies of polyacrylonitrile membranes modified with carboxylated polyetherimide

Poly (ether-imide) (PEI) was carboxylated and used as the hydrophilic modification agent for the preparation of polyacrylonitrile (PAN) membranes. Membranes were prepared with different blend compositions of PAN and CPEI by diffusion induced precipitation. The modified membranes were characterized by thermo gravimetric analysis (TGA), mechanical analysis, scanning electron microscopy (SEM) and contact angle measurement to understand the influence of CPEI on the properties of the membranes. The biocompatibility studies exhibited reduced plasma protein adsorption, platelet adhesion and thrombus formation on the modified membrane surface. The complete blood count (CBC) results of CPEI incorporated membranes showed stable CBC values and significant decrease in the complement activation were also observed. In addition to good cytocompatibility, monocytes cultured on these modified membranes exhibited improved functional profiles in 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Thus it could be concluded that PAN/CPEI membranes with excellent biocompatibility can be useful for hemodialysis.     

Electrochemical Fabrication of Metallic Nanowires and Metal Oxide Nanopores

A nuclear track etched polycarbonate membrane filter with numerous cylindrical nanopores was applied as a nanoporous template for growing metallic nanowires. Nickel, cobalt, and iron nanowires were electrodeposited into the cylindrical nanopores. Cathodic polarization curves were measured to determine an optimum condition for growing nanowires. The shape of nanowires was observed using scanning electron microscope (SEM) and the crystal structure was analyzed using transmission electron microscopy (TEM). Diameter and length of nanowires corresponded to those of nanopores and each nanowire was composed of a single crystal. Anodized aluminum oxide films were also fabricated as a novel nanoporous template. The pore length and diameter was controlled changing anodizing conditions. Ordering behavior of nanopores array in an anodized aluminum oxide film was also investigated to make a novel nanoporous template with a highly ordered honeycomb array of nanopores.     

Effects of surface roughness on hydrogen gas sensing properties of single Pd nanowires

We report on the effects of surface roughness resulting from an ion milling technique on the hydrogen gas sensing performance of a single Pd nanowire grown by electrodeposition into nanochannels in anodized aluminum oxide templates. A combination of electron beam lithography and a lift-off process was utilized to fabricate four-terminal devices based on individual Pd nanowires. These results are the first demonstration of the effect of ion milling on the response time in a single Pd nanowire used as a hydrogen sensor. The response time of the single Pd nanowire surface-treated by ion milling was 20 times faster than that of a sample without surface treatment. The faster response time was due to the surface roughness effects of the surface treatment, an increase in the surface-to-volume ratio of the ion-milled nanowire.     

Antibacterial activity of zinc oxide-coated nanoporous alumina

Nanoporous alumina membranes, also known as anodized aluminum oxide membranes, are being investigated for use in treatment of burn injuries and other skin wounds. In this study, atomic layer deposition was used for coating the surfaces of nanoporous alumina membranes with zinc oxide. Agar diffusion assays were used to show activity of zinc oxide-coated nanoporous alumina membranes against several bacteria found on the skin surface, including Bacillus subtilis, Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis. On the other hand, zinc oxide-coated nanoporous alumina membranes did not show activity against Pseudomonas aeruginosa, Enterococcus faecalis, and Candida albicans. These results suggest that zinc oxide-coated nanoporous alumina membranes have activity against some Gram-positive and Gram-negative bacteria that are associated with skin colonization and skin infection.     

Influence of nanoporesize on platelet adhesion and activation

In this study we have evaluated the influence of biomaterial nano-topography on platelet adhesion and activation. Nano-porous alumina membranes with pore diameters of 20 and 200 nm were incubated with whole blood and platelet rich plasma. Platelet number, adhesion and activation were determined by using a coulter hematology analyzer, scanning electron microscopy, immunocytochemical staining in combination with light microscopy and by enzyme immunoassay. Special attention was paid to cell morphology, microparticle generation, P-selectin expression and beta-TG production. Very few platelets were found on the 200 nm alumina as compared to the 20 nm membrane. The platelets found on the 20 nm membrane showed signs of activation such as spread morphology and protruding filipodia as well as P-selectin expression. However no microparticles were detected on this surface. Despite the fact that very few platelets were found on the 200 nm alumina in contrast to the 20 nm membrane many microparticles were detected on this surface. Interestingly, all microparticles were found inside circular shaped areas of approximately 3 mum in diameter. Since this is the approximate size of a platelet we speculate that this is evidence of transient, non-adherent platelet contact with the surface, which has triggered platelet microparticle generation. To the authors knowledge, this is the first study that demonstrates how nanotexture can influence platelet microparticle generation. The study highlights the importance of understanding molecular and cellular events on nano-level when designing new biomaterials.     

Ultralow fouling and functionalizable surface chemistry based on a zwitterionic polymer enabling sensitive and specific protein detection in undiluted blood plasma

A crucial step in the development of implanted medical devices, in vivo diagnostics, and microarrays is the effective prevention of nonspecific protein adsorption from real-world complex media such as blood plasma or serum. In this work, a zwitterionic poly(carboxybetaine acrylamide) (polyCBAA) biomimetic material was employed to create a unique biorecognition coating with an ultralow fouling background, enabling the sensitive and specific detection of proteins in blood plasma. Conditions for surface activation, protein immobilization, and surface deactivation of the carboxylate groups in the polyCBAA coating were determined. An antibody-functionalized polyCBAA surface platform was used to detect a target protein in blood plasma using a sensitive surface plasmon resonance (SPR) sensor. A selective protein was directly detected from 100% human blood plasma with extraordinary specificity and sensitivity. The total nonspecific protein adsorption on the functionalized polyCBAA surface was very low (<3 ng/cm (2) for undiluted blood plasma). Because of the significant reduction of nonspecific protein adsorption, it was possible to monitor the kinetics of antigen-antibody interactions in undiluted blood plasma. The functionalization effectiveness and detection characteristics using a cancer protein marker candidate of polyCBAA were compared with those of the conventional nonfouling oligo(ethylene glycol)-based surface chemistry.     

Nanoheteroepitaxy of GaN on a nanopore array of Si(111) surface

Nanoheteroepitaxial (NHE) growth of GaN using AlN/AlGaN as a graded buffer layer by metalorganic chemical vapor deposition has been demonstrated on the nanoporous patterned Si(111) substrates. The nanopore array on Si(111) has been fabricated by using anodized aluminum oxide membrane as an induced couple plasma dry etching mask. The reduction of the threading dislocation density and relaxation of the tensile stress in NHE GaN are revealed by transmission electron microscopy (TEM), micro-Raman spectrum and photoluminescence spectrum, respectively. Cross-sectional TEM analysis shows that dislocations nucleated at the interface are forced to bend into (0001) basal plane. Red shift in the E₂ (TO) phonon peak of micro-Raman spectrum indicates the relaxation of tensile stress in the nanoheteroepitaxial lateral overgrowth of GaN. A single step ELO without mask on nanopatterned Si(111) substrates is a simple and promising way for the improvement of the quality of GaN on Si substrates.     

Microstructure and magnetic properties of the FePt film on a membrane of anodized aluminum oxide

By making use of the dc magnetron sputtering system, the Au/FePt bilayers have been prepared on glass substrates and anodized aluminum oxide (AAO) membranes with an average pore diameter of around 200 nm. In both cases, the FePt films can be converted into the magnetically hard phase, namely L1₀ phase, after a heat treatment above 500 °C for 1 h. A nanoparticle-like structure can be observed in the 15-nm-thick FePt film on the AAO membrane. The experimental observations of the structure and the magnetism of the FePt films on the AAO membranes are firstly established.     

丝氨酸配基PVDF亲和膜脱除人血浆中内毒素的研究

以L-丝氨酸(Ser)为配基,1,6-己二胺为间隔臂,制备了一种新型PVDF中空纤维亲和膜用于人血浆中内毒素的脱除.通过FTIR、XPS对PVDF中空纤维膜,亲水化改性膜以及亲和膜的结构进行了表征;探讨了离子强度、pH值对亲和膜吸附内毒素能力的影响以及内毒素分子在亲和膜上的吸附动力学.实验考察了自制的亲和膜组件用于人血浆中内毒素的脱除效果.结果表明,亲和膜对内毒素的吸附能力为0.058 EU/cm2;自制的亲和膜组件对内毒素含量为0.42 EU/mL的人血浆样品清除率为43.8%;亲和膜对人血浆样品的其它生化指标的影响不大.     

Laser Processing of Advanced Bioceramics

In this article, laser processing of diamondlike carbon‐metal nanocomposite films, hydroxyapatite‐osteoblast composites, and Ormocer® microdevices for medical applications is described. Pulsed laser deposition has been used to process diamondlike carbon‐silver‐platinum nanocomposite films that provide hardness, wear resistance, corrosion resistance, and antimicrobial functionalities to cardiovascular, orthopaedic, biosensor, and MEMS devices. Laser direct writing has been used for fabricating integrated cell‐scaffold structures. Two photon induced polymerization has been used to create Ormocer® tissue engineering scaffolds and microneedles with unique geometries. Pulsed laser deposition, laser direct write, and two photon induced polymerization techniques may provide medical engineers with advanced biomaterials that possess unique structures and functionalities.     

Cover Picture: Laser Processing of Advanced Bioceramics (Adv. Eng. Mater. 12/2005)

In this article, laser processing of diamondlike carbon‐metal nanocomposite films, hydroxyapatite‐osteoblast composites, and Ormocer® microdevices for medical applications is described. Pulsed laser deposition has been used to process diamondlike carbon‐silver‐platinum nanocomposite films that provide hardness, wear resistance, corrosion resistance, and antimicrobial functionalities to cardiovascular, orthopaedic, biosensor, and MEMS devices. Laser direct writing has been used for fabricating integrated cell‐scaffold structures. Two photon induced polymerization has been used to create Ormocer® tissue engineering scaffolds and microneedles with unique geometries. Pulsed laser deposition, laser direct write, and two photon induced polymerization techniques may provide medical engineers with advanced biomaterials that possess unique structures and functionalities.