Reduced Protein Adsorption Research Articles

Lactobacillus plantarum F25‐4 assisted rice soaking reduces the cooking strength of japonica rice for Chinese rice wine brewing

SummaryThis study investigated the effect of Lactobacillus plantarum F25‐4 assisted rice soaking (LAS) on the cooking properties of japonica rice used for Chinese rice wine (CRW) production. The effects of LAS and natural soaking were compared based on the chemical composition, thermal characteristics, infrared spectroscopy and sodium dodecyl sulphate‐polyacrylamide gel electrophoresis of rice flour. After LAS, the protein content of the rice was reduced by 17.63%, and the initial temperature (To), peak temperature (Tp) and conclusion temperature (Tc) were reduced by 36.86%, 17.89% and 1.61%, respectively, as revealed by differential scanning calorimetry analysis. The Zeta (ζ) potential value changed from −8.75 mV to −3.99 mV, and the minimum cooking time was reduced by 40% to only 15 min. The viscoelasticity of LAS rice increased after gelatinisation, as confirmed by confocal laser scanning microscope images. The glutelin precursor of the LAS rice disappeared, and the disorder of protein secondary structure increased, but there was no significant difference in the starch crystal area. LAS effectively improved the cooking properties of rice by changing the protein configuration on the surface of starch granules and reducing protein adsorption, leading to increased starch water absorption and decreased rice gelatinisation temperature. Our research suggests that LAS can reduce the cooking temperature of rice in CRW production, thus saving steam consumption during cooking.

Polyglycerol-Decorated Hollow Mesoporous Ruthenium Nanoparticles for Long Circulation and Antitumor Effect

Hollow mesoporous ruthenium nanoparticles (HMRu NPs) are especially beneficial for drug delivery and photothermal therapy due to their distinguished specific surface area and photothermal properties. However, poor circulation performance in vivo means that the NPs are subject to rapid clearance before reaching the target tissue. Polyethylene glycol (PEG) modified nanoparticles have become the classical standard to extend circulation by reducing protein adsorption and escaping macrophage phagocytosis, but PEGylation tends to have an accelerated blood clearance effect after repeated use. Considering that the hyperbranched polymers exhibit excellent performance in protein shielding, that makes it possible for them to have the potential to replace PEG. Thus, HMRu NPs were decorated by polyglycerol (PG) in this work compared to PEGylation. The antiprotein adsorption capacity and macrophage escape were assayed by the bicinchoninic acid method and confocal microscopy, suggesting that PG-coating could avoid macrophage phagocytosis more efficiently than PEGylation. Finally, the resultant HMRu-PG could be used as drug carrier for synergistic chemotherapy and photothermal therapy in tumor treatment. This work provides a promising multimodal and versatile nanocarrier in tumor therapy.

Modification of a PES microfiltration membrane to enhance sterile filtration by inhibiting protein adsorption

Microfiltration membranes are increasingly used in sterilization processes in the pharmaceutical industry. However, in the pharmaceutical industry, product loss caused by the adsorption of high value-added proteins to membranes during the sterilization process is a critical problem. Hence, it is necessary to reduce protein adsorption and fouling through the hydrophilic modification of the entire membrane, not just the surface. We developed a method for fabricating a porous poly(ethersulfone) (PES) microfiltration membrane using vapor-induced phase separation (VIPS) and then conducting hydrophilic modification of the membrane. Two types of symmetric membranes with 0.2 μm pores were prepared using two different additives, one of which was an amphiphilic copolymer (Pluronic® PE6400) that is known to increase the hydrophilicity of PES membranes. Both membranes had high water permeability and suitable mechanical strength. However, protein filtration testing, including an adsorption study, revealed that the hydrophilicity imparted by Pluronic was not sufficient to effectively inhibit protein adhesion. In contrast, the modification via the atom transfer radical polymerization of a hydrophilic oligomer (poly(ethyleneglycol) methacrylate) significantly increased the hydrophilicity of the entire membrane while reducing the surface roughness. These properties reduced protein adsorption and membrane fouling, to the benefit of sterile filtration and protein filtration processes.

Defined Coadsorption of Prostate Cancer Targeting Ligands and PEG on Gold Nanoparticles for Significantly Reduced Protein Adsorption in Cell Media

A study on the surface chemistry of gold nanoparticles (AuNPs) utilizing gel electrophoresis is presented. The molecular design of targeting and stabilizing PEG ligands allows one to combine them in mixed ligand layers with control of relative composition. For all tested targeting and control ligands, coadsorption of PEG significantly reduces protein adsorption and matrix effects of cell media as compared to conjugates without PEG. Introducing carboxylic acid groups into the PEG ligand layer does not lead to increased protein adsorption as shown with carboxylic acid terminated PEG ligands. The controlled adsorption of PEG ligands with different molecular weights is used to disentangle the effects of particle charge and hydrodynamic diameter. Taken together, this study provides directions for the functionalization of nanoparticles to obtain conjugates which are well-defined in terms of composition and colloidally stable in complex media. This is in particular relevant for targeting applications and cell experiments.

Improving properties of thin film nanocomposite membrane via temperature-controlled interfacial polymerization for nanofiltration process

Research on the effect of interfacial polymerization (IP) temperature during polyamide layer synthesis is lacking, especially for thin film nanocomposite (TFN) nanofiltration membrane. Typically, polyamide composite membranes are fabricated at room temperature, ignoring the potential impact of reaction temperature. In this work, we varied the organic solvent temperature to study its impacts on the properties of TFN membrane containing surface-functionalized graphene oxide (GO) for nanofiltration process. A more cross-linked and rougher polyamide layer could be formed at 55 °C due to higher reaction kinetics and more volatile IP reaction. This membrane exhibited excellent Na2SO4 rejection (99 %) with a water-salt permselectivity ratio of 11.0, i.e., >2 folds compared to the commercial membrane (4.88). However, its rougher surface resulted in a higher protein adhesion even with the enhanced antifouling property brought by GO hydrophilicity. In comparison, the TFN membrane developed at 0 °C displayed very thin yet smooth polyamide layer, resulting in a higher water flux and improved antifouling performance. Furthermore, the TFN membrane demonstrated stable filtration performance for 12 h and GO nanosheets were still well accommodated within selective layer after testing. Overall, the improved filtration performance and reduced protein adsorption demonstrated the feasibility of IP temperature variation in TFN membrane fabrication.

High durability of food due to the flow cytometry proved antibacterial and antifouling properties of TiO2 decorated nanocomposite films.

Although polymeric membrane has superior properties, its applications in biomedical and food industrial fields are minimal. Biofouling is a significant concern in the membrane, created from particular interactions between the membrane and untreated water content. This research showed that a careful superhydrophilic modification of polyethersulfone membrane could address those drawbacks that have hindered their utility. Hence, a combination of chemical and physical modification showed far-reaching effects on surface behavior, affecting manifold aspects of its bacterial attachment, protein adsorption resistance, and hydrophilicity. The contact angle measurement results decreased from 30° to 0° in 26s, and surface free energy increased by 33%, demonstrating the shifting surface wettability behavior toward the Superhydrophilicity. Besides, increasing the average surface roughness on the nanoscale and forming 70-110nm jagged structures results in a marked reduction in protein adsorption, bacterial adhesion, and biofouling formation, confirmed by the results of Flow cytometry analysis and microtiter plate assay. An improved understanding of antifouling and antibacterial properties will greatly assist in food industries since it can be applied to enhance the durability of food and chemical materials. This is important as it gives us a simple way of improving packing reliability, reducing costs and amounts of undesirable waste products.

Impact of Hydrophilic Modification of Synthetic Dialysis Membranes on Hemocompatibility and Performance.

The dialyzer is the core element in the hemodialysis treatment of patients with end-stage kidney disease (ESKD). During hemodialysis treatment, the dialyzer replaces the function of the kidney by removing small and middle-molecular weight uremic toxins, while retaining essential proteins. Meanwhile, a dialyzer should have the best possible hemocompatibility profile as the perpetuated contact of blood with artificial surfaces triggers complement activation, coagulation and immune cell activation, and even low-level activation repeated chronically over years may lead to undesired effects. During hemodialysis, the adsorption of plasma proteins to the dialyzer membrane leads to a formation of a secondary membrane, which can compromise both the uremic toxin removal and hemocompatibility of the dialyzer. Hydrophilic modifications of novel dialysis membranes have been shown to reduce protein adsorption, leading to better hemocompatibility profile and performance stability during dialysis treatments. This review article focuses on the importance of performance and hemocompatibility of dialysis membranes for the treatment of dialysis patients and summarizes recent studies on the impact of protein adsorption and hydrophilic modifications of membranes on these two core elements of a dialyzer.

AIE-Featured Redox-Sensitive Micelles for Bioimaging and Efficient Anticancer Drug Delivery.

In the present study, an amphiphilic polymer was prepared by conjugating methoxy poly(ethylene glycol) (mPEG) with tetraphenylethene (TPE) via disulfide bonds (Bi(mPEG-S-S)-TPE). The polymer could self-assemble into micelles and solubilize hydrophobic anticancer drugs such as paclitaxel (PTX) in the core. Combining the effect of TPE, mPEG, and disulfide bonds, the Bi(mPEG-S-S)-TPE micelles exhibited excellent AIE feature, reduced protein adsorption, and redox-sensitive drug release behavior. An in vitro intracellular uptake study demonstrated the great imaging ability and efficient internalization of Bi(mPEG-S-S)-TPE micelles. The excellent anticancer effect and low systemic toxicity were further evidenced by the in vivo anticancer experiment. The Bi(mPEG-S-S)-TPE micelles were promising drug carriers for chemotherapy and bioimaging.

Modification of Tubings for Peristaltic Pumping of Biopharmaceutics

Protein particle formation during peristaltic pumping of biopharmaceuticals is due to protein film formation on the inner tubing surface followed by rupture of the film by the roller movement. Protein adsorption can be prevented by addition of surfactants as well as by increasing the hydrophilicity of the inner surface. Attempts based on covalent surface coating were mechanically not stable against the stress of roller movement. We successfully incorporated surface segregating smart polymers based on a polydimethylsiloxane (PDMS) backbone and polyethylene glycol (PEG) side blocks in the tubing wall matrix. For this we applied an easy, reproducible and cost-effective process based on soaking of tubing in toluene containing the PDMS-PEG copolymer. With this tubing modification we could drastically reduce protein particle formation during peristaltic pumping of a monoclonal antibody and human growth hormone (HGH) formulation in silicone and thermoplastic elastomer-based tubing. The modification did not impact the tubing integrity during pumping while hydrophilicity was increased and protein adsorption was prevented. Free PDMS-PEG copolymer might have an additional stabilizing effect, but less than 50 ppm of the PDMS-PEG copolymer leached from the modified tubing during 1 h of pumping in the experimental setup. In summary, we present a new method for the modification of tubings which reduces protein adsorption and particle formation during any operation involving peristaltic pumping, e.g. transfer, filling, or tangential flow filtration.

Hydroxylpropyl-β-cyclodextrin as Potential Excipient to Prevent Stress-Induced Aggregation in Liquid Protein Formulations.

Due to the growing demand for patient-friendly subcutaneous dosage forms, the ability to increasing protein solubility and stability in formulations to deliver on the required high protein concentrations is crucial. A common approach to ensure protein solubility and stability in high concentration protein formulations is the addition of excipients such as sugars, amino acids, surfactants, approved by the Food and Drug Administration. In a best-case scenario, these excipients fulfil multiple demands simultaneously, such as increasing long-term stability of the formulation, reducing protein adsorption on surfaces/interfaces, and stabilizing the protein against thermal or mechanical stress. 2-Hydroxylpropyl-β-cyclodextrin (derivative of β-cyclodextrin) holds this potential, but has not yet been sufficiently investigated for use in protein formulations. Within this work, we have systematically investigated the relevant molecular interactions to identify the potential of Kleptose®HPB (2-hydroxylpropyl-β-cyclodextrin from Roquette Freres, Lestrem, France) as “multirole” excipient within liquid protein formulations. Based on our results three factors determine the influence of Kleptose®HPB on protein formulation stability: (1) concentration of Kleptose®HPB, (2) protein type and protein concentration, and (3) quality of the protein formulation. Our results not only contribute to the understanding of the relevant interactions but also enable the target-oriented use of Kleptose®HPB within formulation design.

Preparation and blood compatibility of polyethersulfone dialysis membrane modified by apixaban as coagulation factor Xa inhibitor.

Blood purification therapy is widely used in the treatment of critically ill patients. However, most dialysis membranes are prone to thrombosis. Activated coagulation factor X (FXa) functions at the intersection of intrinsic, extrinsic, and common coagulation pathways and plays a central role in thrombogenesis. To date, few dialysis membranes that directly inhibit FXa have been reported. We modified a polyethersulfone(PES) membrane using apixaban as an FXa inhibitor and investigated the performance of this membrane (AMPES). The contact angle of the modified membrane was reduced. PWF and retention rates of BSA were increased, demonstrating good hydrophilicity and dialysis performance. Albumin adsorption was reduced from 141.8±15.5 to 114.1±6.9μgcm-2. Reduced protein adsorption, especially targeted anti-FXa effect, inhibited the activation of intrinsic, extrinsic, and common coagulation pathways, as evidenced by significant prolongations of activated partial thromboplastin time, prothrombin time, and thrombin time by 145.04, 46.84 and 11.46s, respectively. Furthermore, we determined the FXa concentration of each group, and found that the modified membrane had better anticoagulant performance through the inhibition of FXa. Favorable antiplatelet activity was also demonstrated. Thromboelastogram was used to comprehensively evaluate the anticoagulant and antithrombotic activities of the modified membrane. The R value was increased by 43.1min, while the reduction in α angle was 42.5°. The coagulation comprehensive index reduction was 34.3. In addition, C3a and C5a were decreased by 15.3% and 30.4%, respectively. Furthermore, in vitro cytotoxicity and erythrocyte stability testing as well as in vivo murine experiments demonstrated the biosafety of the modified membrane. These results indicate that the AMPES dialysis membrane has an excellent potential for clinical applications.

Multifunctional membranes for lipidic nanovesicle capture

Tangential flow filtration membrane systems are employed for the isolation and concentration of extracellular vesicles. However, interfacial interactions between the membrane surface and species influence the flux and membrane performance. Here we propose a strategy aimed at introducing functional ligands over the membrane surface to improve the separation process through combined size-exclusion and affinity-based mechanisms, avoiding the binding of contaminants and other non-target molecules. Polysulfone membranes were modified by a nanometric coating of differently functionalized copolymers with the dual purpose of limiting non-specific interactions while promoting the chemoselective conjugation of a membrane-sensing peptide ligand (BPt) for lipid nanovesicles capture. Copoly azide polymer coating positively affects the physico-chemical properties of the membrane, improving filtration performance and antifouling capacity. A decrease of the flux decline ratio from 38.7 ± 3.9% to 21.2 ± 2.4% and an increase of the ratio of protein permeate concentration (Cp) to the respective feed concentration (Cf) to values of 0.97 was measured after coating the membrane with c-(DMA-N3-BP-MAPS) highlighting its capability to reduce protein adsorption. In addition, the BPt-functionalized membrane displayed a high capturing efficiency towards synthetic liposomes which, notably, can be promptly released upon mild treatment with a divalent cation solution. Overall, our work integrates conventional TFF principles with affinity-based isolation, broadening TFF perspective applications.

In-situ forming PEG-engineering hydrogels with anti-fouling characteristics as an artificial vitreous body

Endotamponade is in huge demand for vitrectomy, while current vitreous substitutes exhibit instability and foreign body reactions that impede long-term implantation. Herein, we report an in-situ forming hydrogel (PEGBAA) with prominent stability and anti-fouling properties as a long-term vitreous substitute consisting of two main components: functional-modified multi-arm poly(ethylene glycol) (8sPEG-SH/Mal) and zwitterionic poly(carboxybetaine) (pCBAA). The former is bioinert to provide long-term stability via the thiol-ene Michael addition reaction. The latter possesses anti-fouling characteristics to prevent adsorption of protein and cells due to its strong hydrophilicity. The PEGBAA hydrogel formed fast in situ exhibits reduced protein adsorption and cell adhesion compared to pure PEG-based hydrogels, good in vitro biocompatibility, and very similar critical parameters (i.e., light transmittance, refractive index, water content, modulus, high stability) to the natural vitreous humor. After a 180-day implantation through injection with a double syringe via standard vitrectomy procedures in rabbit models, the hydrogels acts as a very stable vitreous substitute without abnormal complications. Therefore, the strategy of in-situ forming hydrogels with anti-fouling properties offers a new avenue to improve the in vivo stability of long-term vitreous endotamponades.

A Dense Layer of Polyethyleneglycol and Zwitterionic Bone Targeting Peptide on the Surface of Stereocomplex Polylactide-Polyethyleneglycol Nanoparticles Improves Shelf-storage Stability and the Serum Compatibility

The surface properties of nanoparticles (NPs) affect their stability and formation of the protein corona, which influence their targeting abilities. We evaluated these properties using bone (hydroxyapatite; HAP) targeting peptide on tamoxifen (TAM)-loaded stereocomplexformed polylactide-polyethyleneglycol (SC-PLA-PEG) NPs. Octaaspartic acid-octaglycine-cysteine (D8G8C) anionic derivative (Ani. pep.) and octa-aspartic acid-octa lysine-cysteine (D8K8C), a zwitterionic derivative (Zwi. pep.) were conjugated with SC-PLA-PEG NPs as HAP-targeting peptides. The addition of hydrophobic PLA homopolymers increased the surface PEG density on the NPs. Denser PEG chains on NPs decreased their specific surface area, reducing protein adsorption on the NPs and TAM release from NPs. NPs with dense PEG chains and Zwi. pep. showed superior shelf stability and lower protein adsorption than NPs with dense PEG chains and Ani. pep. in murine serum. Furthermore, the HAP-binding ability of NPs with Zwi. pep. was significantly higher than that of NPs with Ani. pep. These results indicate that decreasing the specific surface area and zwitterionization of HAP-targeting peptides on NPs are promising approaches to improve the serum compatibility and stability of NPs.

Role of fibronectin and IOL surface modification in IOL: Lens capsule interactions

Posterior Capsule Opacification (PCO) is one of the most common complications of cataract surgery. While studies have shown that IOL material properties and fibronectin adsorption may affect IOL-induced PCO in the clinical setting, the mechanism governing such interactions is not totally understood. Since strong adhesion forces between IOLs and posterior capsules (PCs) have been shown to impede cell infiltration and thus reduce PCO formation, this study was designed to assess whether fibronectin adsorption and IOL material properties would impact the IOL:PC adhesion force and cell infiltration using a PCO predictive in vitro model and a macromolecular dye imaging model, respectively. Our results showed that fibronectin adsorption significantly increased the adhesion forces and reduced simulated cell infiltration between acrylic foldable IOLs and the PC at physiological temperature in comparison to fibronectin-free controls. This fibronectin-mediated strong IOL: PC bond may be contributing to low PCO rates in the clinic for acrylic foldable IOLs. In addition, acrylic foldable IOLs coated with Di(ethylene glycol) (Diglyme), a hydrophilic coating known to reduce protein adsorption, was tested for its ability to alter adhesion force and cell infiltration. We observed that IOLs coated with Diglyme coating greatly reduced surface hydrophobicity and fibronectin adsorption of acrylic foldable IOLs. Furthermore, Diglyme coated IOLs showed significantly reduced adhesion force and increased simulated cell infiltration at the IOL:PC interface. The overall results support the hypothesis that IOL surface properties and their ability to adsorb fibronectin may have great impact on the IOL:PC adhesion force. A tight binding between IOLs and PC may contribute to the reduction of cell infiltration and thus the PCO incidence rate in the clinic.

In vitro hemocompatibility screening of a slippery liquid impregnated surface coating for extracorporeal organ support applications.

Clot formation, infection, and biofouling are unfortunate but frequent complications associated with the use of blood-contacting medical devices. The challenge of blood-foreign surface interactions is exacerbated during medical device applications involving substantial blood contact area and extended duration of use, such as extracorporeal life support (ECLS). We investigated a novel surface modification, a liquid-impregnated surface (LIS), designed to minimize protein adsorption and thrombus development on medical plastics. The hemocompatibility and efficacy of LIS was investigated first in a low-shear model with LIS applied to the lumen of blood incubation vials and exposed to human whole blood. Additionally, LIS was evaluated in a 6 h ex vivo circulation model with swine blood using full-scale ECLS circuit tubing and centrifugal pumps with clinically relevant flow rate (1.5 L/min) and shear conditions for extracorporeal carbon dioxide removal. Under low-shear, LIS preserved fibrinogen concentration in blood relative to control polymers (+40 ± 6 mg/dL vs polyvinyl chloride, p < .0001), suggesting protein adsorption was minimized. A fibrinogen adhesion assay demonstrated a dramatic reduction in protein adsorption under low shear (87% decrease vs polyvinyl chloride, p = .01). Thrombus deposition and platelet adhesion visualized by scanning electron microscopy were drastically reduced. During the 6 h ex vivo circulation, platelets in blood exposed to LIS tubing did not become significantly activated or procoagulant, as occurred with control tubing; and again, thrombus deposition was visually reduced. A LIS coating demonstrated potential to reduce thrombus formation on medical devices. Further testing is needed specialized to clinical setting and duration of use for specific medical target applications.

Dual detection high-speed capillary electrophoresis for simultaneous serum protein analysis and immunoassays

Serum protein electrophoresis (SPE) separates serum proteins into bands whose shape and amplitude can alert clinicians to a range of disorders. This is followed by more specific immunoassays to quantify important antigens and confirm a diagnosis. Here we develop a high-speed capillary electrophoresis (HSCE) platform capable of simultaneous SPE and immunoassay measurements. A single laser excitation source is focused into the detection zone of the capillary to measure both refractive index (SPE) and fluorescence signals (immunoassays). The refractive index signal measures characteristic SPE profiles for human serum separated in 100 mM boric acid (pH 10), 100 mM arginine (pH 11), and 20 mM CHES (pH 10). For the immunoassay, the fluorescence electropherograms reveal that CHES provides the optimal buffer for measuring the immunocomplex and separating it from the free antigen. Immunoassays in CHES yield a LOD of 23 nM and a LOQ of 70 nM for the detection of fluorescein. The high pH reduces protein adsorption but reduces antibody affinity. Preliminary studies carried out in 50 mM barbital at pH 8 show improved stability of the immunocomplex and better separation for immunoassay quantification. Further optimization will open new capabilities for measuring orthogonal diagnostic signals in seconds with HSCE.

Superhydrophilic hydroxyapatite/hydroxypropyltrimethyl ammonium chloride chitosan composite coating for enhancing the antibacterial and corrosion resistance of magnesium alloy

Bacterial infection and excessive corrosion rate are two major concerns of Mg alloy orthopedic implants. Compared with single-function antibacterial coating, dual-function antibacterial coatings with both bacteria-resisting and bacteria-killing properties exhibit excellent performance in anti-bacterial adhesion and preventing biofilm formation. In this work, a dual-function antibacterial composite coating of hydroxyapatite (HA)/hydroxypropyltrimethyl ammonium chloride chitosan (HACC) was successfully prepared on Mg alloy by hydrothermal and electrodeposition methods. Electrochemical tests and immersion experiments have shown that the dense composite coating could provide effective protection for Mg alloy. Compared with the naked Mg alloy, the composite coating exhibited superhydrophilicity with a contact angle of 4°, which significantly reduced protein adsorption and bacterial adhesion. Meanwhile, HACC had excellent bactericidal properties, due to the presence of the quaternary ammonium groups in the molecular chain that changed bacterial cell membrane permeability. The bacterial-killing efficiency of the composite coating was 99.9% against S. aureus and 94.7% against E. coli. Moreover, the cell viability experiments indicated that the composite coating had good biocompatibility on MC3T3-E1 cells with above 84% cell viability. This work provided a strategy for designing surface coatings on Mg alloy implants with desirable corrosion resistance and antibacterial property simultaneously.

Polysaccharide-based layer-by-layer nanoarchitectonics with sulfated chitosan for tuning anti-thrombogenic properties

The development of blood-interacting surfaces is critical to fabricate biomaterials for medical use, such as prostheses, implants, biosensors, and membranes. For instance, thrombosis is one of the leading clinical problems when polymer-based materials interact with blood. To overcome this limitation is necessary to develop strategies that limit platelets adhesion and activation. In this work, hyaluronan (HA)/chitosan (Chi) based-films, recently reported in the literature as platforms for tumor cell capture, were developed and, subsequently, functionalized with sulfated chitosan (ChiS) using a layer-by-layer technique. ChiS, when compared to native Chi, presents the unique abilities to confer anti-thrombogenic properties, to reduce protein adsorption, and also to limit calcification. Film physicochemical characterization was carried out using FTIR and XPS for chemical composition assessment, AFM for the surface morphology, and contact angle for hydrophilicity evaluation. The deposition of ChiS monolayer promoted a decrease in both roughness and hydrophilicity of the HA/Chi films. In addition, the appearance of sulfur in the chemical composition of ChiS-functionalized films confirmed the film modification. Biological assay indicated that the incorporation of sulfated groups limited platelet adhesion, mainly because a significant reduction of platelets adhesion to ChiS-functionalized films was observed compared to HA/Chi films. On balance, this work provides a new insight for the development of novel antithrombogenic biomaterials, opening up new possibilities for devising blood-interaction surfaces.

Membrane patterning through horizontally aligned microchannels developed by sulfated chopped carbon fiber for facile permeability of blood plasma components in low-density lipoprotein apheresis

Low-density lipoprotein (LDL) apheresis via membrane filtration process is an extracorporeal blood purification technique using for the treatment of patients suffering from familial hypercholesterolemia (FH) and severe coronary artery disease (CAD). As much as the importance of LDL separation, the maximum permeability of beneficial blood plasma components through the membrane is regarded as an important issue in this method. Herein, patterned membranes are produced by the effect of horizontally aligned microchannels that formed by the incorporation of sulfated chopped carbon fiber (SCCF) in the membrane structure. Characterization studies verified the binding of carrageenan as a sulfated polysaccharide on the surface of chopped carbon fiber (CCF). Transmission and reflective optical micrographs demonstrated the orientation of SCCFs in a horizontally aligned direction in the membrane structure. Surface analyses including water contact angle and zeta potential revealed the improvement of hydrophilicity and negative charge density of membranes containing SCCF, respectively. Moreover, membrane surface roughness was enhanced with the addition of SCCF that led to a better selectivity. With the enhancement of SCCF concentration, the ratio of molecular weight cut-off to molecular weight retention onset (MWCO/MWRO) that is a marker of membrane selectivity was decreased effectively. The morphology study displayed the formation of an interfacial distance between SCCF and the polymeric matrix that produced horizontally parallel microchannels in the membrane structure. Blood plasma filtration and cardiovascular disease (CVD) risk factors verified that the M−SCCF3 (containing 0.7 wt% SCCF) due to having desired morphology and characteristics had the best performance for the LDL separation, and permeability of beneficial plasma components like high-density lipoprotein (HDL), and albumin protein. Furthermore, cell cytotoxicity analysis revealed no cytotoxicity in membranes which endorsed desired interaction of developed membranes with L-929 cells as the representation of physiological ambient. Also, reduction of protein adsorption on the membrane surface, and prolongation of coagulation times endorsed the hemocompatibility of membranes. The overall results certified that the M−SCCF3 due to having the best performance and desired structural properties was the best membrane for use in LDL apheresis.