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The elevated concentration of low-density lipoprotein (LDL) is recognized as a leading factor of hyperlipidemia (HLP), and selective adsorption of serum LDL is regarded as a practical therapy. Based on the superior structure-function characteristics of stimuli-responsive materials, a photorenewable nanoadsorbent (SiO

Highly efficient removal of bilirubin from whole blood directly by hemoperfusion for liver failure therapy remains a challenge in the clinical field due to the low adsorption capacity, poor mechanical strength and low biocompatibility of adsorbents. In this work, a new class of nanocomposite adsorbents was constructed through an inorganic-organic co-crosslinked nanocomposite network between vinyltriethoxysilane (VTES)-functionalized hydroxyapatite nanoparticles (V-Hap) and non-ionic styrene-divinylbenzene (PS-DVB) resins (PS-DVB/V-Hap) using suspension polymerization. Notably, our adsorbent demonstrated substantially improved mechanical performance compared to the pure polymer, with the hardness and modulus increasing by nearly 3 and 2.5 times, respectively. Moreover, due to the development of a mesoporous structure, the prepared PS-DVB/V-Hap3 exhibited an ideal adsorption capacity of 40.27 mg g−1. More importantly, the obtained adsorbent beads showed outstanding blood compatibility and biocompatibility. Furthermore, in vivo extracorporeal hemoperfusion verified the efficacy and biosafety of the adsorbent for directly removing bilirubin from whole blood in pig models, and this material could potentially prevent liver damage and improve clinical outcomes. Taken together, the results suggest that PS-DVB/V-Hap3 beads can be used in commercial adsorption columns to threat hyperbilirubinemia patients through hemoperfusion, thus replacing the existing techniques where plasma separation is initially required.

Based on the LDL structural characteristics and intermolecular interactions, a tailored nano-adsorbent (Fe3O4@SiO2@PAA-PE) was prepared aimed at the removal of LDL from hyperlipemia serum with high selectivity.

Immunomagnetic nanoparticles (IMNs) have been widely developed as a detection tool to isolate rare circulating tumor cells (CTCs) from whole blood as a potential method for early cancer diagnosis, metastasis examination, and treatment guidance. However, a spontaneous interaction between nanoparticles and proteins results in the formation of a protein corona that reduces the performance of IMNs when they enter body fluids. To address this issue, the protein corona was precoated onto magnetic nanoparticles (C-MNs), and then their surfaces were conjugated with an immuno-antibody. The adsorption of proteins on C-MNs was decreased 6-fold and non-specific cell binding was reduced 5-fold, compared with magnetic nanoparticles (MNs). Furthermore, the immuno-antibody functionalized C-MNs (IC-MNs) maintained highly specific CTC capture performance when exposed to blood plasma. By using artificial spiked blood samples, IC-MNs exhibited 90.2% CTC isolation efficiency, compared with 60.3% by using IMNs. IC-MNs also successfully captured CTCs with high purity in 24 out of 26 female breast cancer patient blood samples. This work demonstrated that a novel preformed protein corona strategy can provide a useful clinically applicable diagnostic tool.

Lowering of low-density lipoprotein (LDL) levels in blood of patients with hyperlipidaemia can effectively prevent the progression of atherosclerosis and coronary heart disease. The present study demonstrated a facile synthesis strategy to prepare biomembrane-mimetic LDL adsorbent (PVA@COOH-PE) via directional immobilization of phospholipid onto macro-porous cross-linked poly(vinyl alcohol) spheres. The binding between the prepared adsorbent and LDL particles simulates the cytosolic lipid droplets to form a lipid-packing structure. The adsorbent possesses satisfactory removal efficiency for LDL and total cholesterol (TCH) in hyperlipemia serum, while remains high-density lipoprotein (HDL) concentration within the normal range. The adsorption capacities for LDL and TCH are about 1.13 and 1.74 mg/ml respectively, which are nearly three and four times higher than that of HDL (0.42 mg/ml). The adsorbent also possesses satisfactory anticoagulant properties, causes negligible effect on blood cells and produces low hemolysis ratios. The excellent blood compatibility plus LDL removal efficiency of PVA@COOH-PE indicates its good application prospect as hemoperfusion adsorbent in the treatment of hyperlipidaemia.

Elevated levels of low-density lipoproteins (LDL) are recognized as a crucial indicator of hyperlipidemia (HLP) and lowering of LDL levels represents an effective clinical treatment strategy. Inspired by the conjugation of phospholipid monolayers and the lipid content of the LDL particle, the current study describes the preparation of an innovative hemoperfusion adsorbent. The adsorbent was prepared by attachment of phosphatidyl ethanolamine to poly(acrylic acid) modified poly(vinyl alcohol-co-triallyl isocyanurate) beads (PVA@PAA-PE). The interaction between LDL and adsorbent mimics the lipoprotein microemulsion present in the blood and thus promotes efficient binding with high affinity. In vitro adsorption using serum from patients with HLP revealed that the LDL adsorption of PVA@PAA-PE was 4.44 times higher than that of controls and the removal rate of LDL using PVA@PAA-PE was about twice as high as that of the anti-atherogenic high-density lipoprotein (HDL). In vivo whole blood perfusion demonstrated the superior affinity of PVA@PAA-PE for LDL since LDL concentration was significantly reduced from 10.71 ± 2.36 mmol L-1 to 6.21 ± 1.45 mmol L-1, while the HDL level was not severely reduced (from 0.98 ± 0.12 mmol L-1 to 0.56 ± 0.15 mmol L-1). Additionally, PVA@PAA-PE exhibited excellent hemocompatibility and low cytotoxicity. Therefore, PVA@PAA-PE is a potential adsorbent for whole blood perfusion to treat hyperlipidemia.

Porous nanocomposite materials possess enhanced adsorption properties, but uniformly dispersing nanofillers in polymer matrices is still a challenging technical difficulty. In this study, modification through loading with SiO2 successfully improved the dispersibility of graphene in chitosan suspensions. By employing a phase-inversion method, cross-linked chitosan/SiO2-loaded graphene (CS/graphene-SiO2) composite beads were prepared. The resulting CS/graphene-SiO2 beads were characterized by scanning electron microscopy and Raman spectroscopy, which clearly showed that graphene was well-dispersed in the chitosan matrix. Adsorption results demonstrated that CS/graphene-SiO2 beads possessed much better adsorption capacity for bilirubin (77.87%) compared to pure chitosan (CS) beads (22.47%), mainly due to the synergistic effect between the hydrophobic forces of graphene and the electrostatic interactions provided by the amino groups of CS. The adsorption of bilirubin was found to match a monolayer model, as well as a pseudo-first-order kinetic model. The mechanical strength of composite beads was significantly improved as compared to CS beads, due to the incorporation of graphene. The effects on hemolytic activity and the components of blood were negligible, which indicate an excellent compatibility of the obtained composite beads with blood. Overall, the proposed CS/graphene-SiO2 beads as an efficient adsorbent for bilirubin have high potential in blood purification applications.

A novel nano-CaCO3 (nCaCO3) particle composite-derived polystyrene (PS) resin was successfully synthesized by a suspension polymerization method. The nCaCO3 reinforced PS material (PS/nCaCO3) possessed a structure with abundant mesopores of high porosity, high specific surface area (828.3 m2 g-1) and large pore volume (1.83 cm3 g-1). It was revealed that the incorporation of nCaCO3 into the PS matrix enhanced both the mechanical strength which can prevent the fragmentation and its adsorption capacity for interleukin-6 (IL-6, MW = 24.0 kDa) from human plasma. The adsorption isotherm could be described by the Langmuir model and classified as S-3 type, showing an IL-6 uptake of up to 25.6 ng g-1 at an equilibrium concentration of about 500 ng L-1. The adsorption capacity for IL-6 of PS/nCaCO3 is not only significantly higher than that of PS (without nCaCO3), but also superior to those of currently available adsorbents that are under clinical studies (e.g., CytoSorb™ towards cytokines). In addition, the PS/nCaCO3 adsorbent also had good hemocompatibility and showed no leakage of nCaCO3 in the plasma in a flowing model system. Therefore, the synthesized PS/nCaCO3 nano-composite has a great potential to be used as an efficient adsorbent for the removal of interleukin-6 (IL-6) from blood of inflammatory and auto-immune disease patients through hemoperfusion.

The cytokine network of tumour microenvironment (TME) plays an important role in cancer growth and progression. The current work aims to provide a new strategy for cancer therapy based on the targeted regulation of cytokines in the TME. Here, heparin-coupled polyvinyl alcohol (PVA-H) microspheres have been developed as an adsorbent for selectively remove tumour-induced immunosuppressive cytokines, such as vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β), but not tumour necrosis factor-alpha (TNF-α) which has an immune-stimulating effect and can inhibit tumour growth. The proliferation and apoptosis of breast cancer cells after perfusion were tested by cell viability assays, flow cytometry analysis and mRNA microarray assays. Results showed that the PVA-H microspheres efficiently absorbed the majority of VEGF (74.39%) and TGF-β (86.39%), but much less TNF-α (4.16%). The regulation of the cytokines had remarkable anti-proliferative and pro-apoptotic effects on breast cancer cells, which was further confirmed from the change of mRNA expression levels. Thus, targeting regulatory pathways within the TME by an affinity adsorbent that selectively depletes immunosuppressive cytokines is potentially a new and promising strategy for cancer therapy.

Highly efficient removal of bilirubin from whole blood directly by hemoperfusion for liver failure therapy remains a challenge in the clinical field due to the low adsorption capacity, poor mechanical strength and low biocompatibility of adsorbents. In this work, a new class of nanocomposite adsorbents was constructed through an inorganic-organic co-crosslinked nanocomposite network between vinyltriethoxysilane (VTES)-functionalized hydroxyapatite nanoparticles (V-Hap) and non-ionic styrene-divinylbenzene (PS-DVB) resins (PS-DVB/V-Hap) using suspension polymerization. Notably, our adsorbent demonstrated substantially improved mechanical performance compared to the pure polymer, with the hardness and modulus increasing by nearly 3 and 2.5 times, respectively. Moreover, due to the development of a mesoporous structure, the prepared PS-DVB/V-Hap3 exhibited an ideal adsorption capacity of 40.27 mg g−1. More importantly, the obtained adsorbent beads showed outstanding blood compatibility and biocompatibility. Furthermore, in vivo extracorporeal hemoperfusion verified the efficacy and biosafety of the adsorbent for directly removing bilirubin from whole blood in pig models, and this material could potentially prevent liver damage and improve clinical outcomes. Taken together, the results suggest that PS-DVB/V-Hap3 beads can be used in commercial adsorption columns to threat hyperbilirubinemia patients through hemoperfusion, thus replacing the existing techniques where plasma separation is initially required., Graphical abstract Image 1, Highlights • A hydroxyapatite reinforced organic-inorganic nanocomposite adsorbent was fabricated for bilirubin removal. • The addition of hydroxyapatite in the adsorbent had a positive effect on the development of mesopores and mechanical strength. • The adsorbent possessed excellent blood compatibility and biocompatibility. • In vivo hemoperfusion verified the efficacy and biosafety of the adsorbent for removing bilirubin from whole blood.

Tumor necrosis factor (TNF)-α has an important role in the pathogenesis of autoimmune and inflammatory diseases such as rheumatoid and septic arthritis. Removal of excess tumor necrosis factor-α (TNF-α) is a promising treatment. In this study, a series of functionalized carbon nanotube-embedded poly(vinyl alcohol) (PVA) nanocomposite adsorbents were prepared for TNF-α removal for the first time. The resulting nanocomposites were characterized by scanning electron microscopy and Raman spectroscopy, which demonstrated that carbon nanotubes were well-dispersed on the surface of PVA macroporous microspheres. Adsorption tests showed that the carboxylated carbon nanotube-embedded composite microspheres (PVA/MWCNTs-COOH) possessed much better adsorption capacity for TNF-α in both simulated serum solution and rat plasma compared to the aminated (PVA/MWCNTs-NH2) and raw carbon nanotube-embedded microspheres (PVA/MWCNTs-raw). In addition, the effects on hemolytic activity, the anticoagulant property, and the components of blood were negligible, indicating the excellent blood compatibility of composite beads. Our findings suggest that the carboxylated carbon nanotube-embedded composite microspheres may be potentially useful for the treatment of autoimmune and inflammatory diseases by removing TNF-α from the blood.

A novel nano-CaCO

A novel nano-CaCO3/polystyrene nanocomposite adsorbent (NPS-8) was synthesized for efficient bilirubin removal from human plasma. A comparison with the polystyrene adsorbent (PS-8), which was without the incorporation of nano-CaCO3, revealed that NPS-8 had superior bilirubin adsorption capacity and mechanical strength. The resulting nano-CaCO3 reinforced PS-8 (NPS-8) was tested by transmission electron microscopy (TEM), scanning electron microscopy (SEM), mechanical strength test, and bilirubin adsorption assays. The adsorption results indicated that NPS-8 displayed better adsorption capacity for bilirubin (91%) than that of PS-8 (75.88%). The mechanical strength of NPS-8 was significantly greater than that of PS-8. In addition, both PS-8 and NPS-8 possessed good blood compatibility properties (a negligible hemolytic activity and platelet adhesion). Therefore, a conclusion could be drawn that NPS-8 has a high potential as an efficient bilirubin adsorbent for blood purification in clinical practice. At the same time, the success of organic-inorganic nanocomposite adsorbents might provide a new insight into the improvement of adsorbents in hemoperfusion.

PS-DVB/nano-CaCO3, a novel abundant mesoporous structured polymer nano-composite, was successfully synthesized via suspension polymerization. Characterization of this type of bead nano-composite demonstrated that it exhibits significantly enhanced TNF-α adsorption from blood plasma and possesses good mechanical strength.

Synthetic hydroxyapatite (HAP) containing both Zn 2+ and SeO 3 2− was synthesized via a co-precipitation method and the effects of the two ion concentrations on the morphology, surface charge and composition of the HAP were studied. The Zn 2+ and SeO 3 2− co-substituted hydroxyapatite (ZnSeHAP) samples were characterized by various techniques. The synthetic ZnSeHAP products were well-crystallized with typical apatite structures. The zinc and selenium were incorporated into the HAP lattice by respectively replacing some of the Ca 2+ with Zn 2+ and some of the PO 4 3− with SeO 3 2− . As the Zn content increased, the a -axis of the HAP lattice increased and the c -axis decreased. An increase in Zn in the HAP lattice also led to a decrease in the surface charge when ZnSeHAP was suspended in simulated body fluid (pH 7.4). This study shows that the surface properties of hydroxyapatite can be controlled by adding suitable dopants, which is useful for biomedical applications.

Adsorbents are widely used in hemoperfusion for bilirubin removal. However, their performance is often compromised by the presence of plasma proteins. In this study, the bilirubin adsorption capacity of polyvinyl alcohol microspheres (PVAm) functionalized with different amino-alkane ligands has been investigated, with the aim of gaining binding selectivity over albumin. Octylamine-functionalized PVA microspheres (PVAm-8) exhibited an excellent adsorption capacity for bilirubin (75% and 3.95 mg/mL in PBS vs 72% and 3.84 mg/mL in albumin solution) when compared to the clinical adsorbent BPR (92% and 4.84 mg/mL in PBS vs 71%, and 3.80 mg/mL in albumin solution). The bilirubin adsorption capacities of PVAm-8 were largely unaffected by the presence of albumin. Adsorption of bilirubin to PVAm-8 occurs mainly through hydrophobic effects, with adsorption consistent with the monolayer model and the pseudo-first-order model operating in both PBS and albumin solution. The effects of PVAm-8 on hemolytic activity, blood component stability and coagulant activity were negligible, indicating that PVAm-8 has good potential as a high-affinity bilirubin adsorbent for hemoperfusion applications.

A novel nano-CaCO

PS-DVB/nano-CaCO

Single-crystal strontium hydroxyapatite (SrHAp) nanorods have been synthesized by a water-based low temperature sol–gel process using strontium nitrate and diammonium hydrogen phosphate as the starting materials. The SrHAp materials were characterized by powder X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy and transmission electron microscopy. The aging time was found to play a significant role in regulating the morphology of the nanoparticles and the best result was obtained for the sample aged at 60 °C for 48 h. This SrHAp sample consisted of monodipersed nanorods with lengths of 120–180 nm and diameters of around 30 nm. This synthesis strategy provides a simple pathway to obtain single-crystal SrHAp with high crystallinity and purity.

Rod-shaped hydroxyapatite (HAp) with mesoporous structure was synthesized by a hydrothermal method using Pluronic block co-polymer F127 as the template. The rod-shaped HAp was then tested as protein drug carriers by investigating their protein adsorption/release properties. Bovine serum albumin (BSA) and lysozyme (LSZ) were used as the model drugs. Various instrumental methods were used to characterize the structure, morphology, texture and protein drug adsorption/release properties of the samples. The amounts of BSA or LSZ adsorbed onto the rod-shaped HAp and their release profiles were evaluated in a simulated body fluid (SBF). The synthesized rod-shaped HAp had irregular mesostructures with lengths of 75–125 nm and diameters of about 25 nm. The rod-shaped HAp exhibited a higher loading capacity for BSA than for LSZ in the SBF. This adsorption behavior can be explained by the morphology of the rod-shaped HAp, which grew along the c-axis, leading to an a(b)-plane area that is larger than the c-plane area. Consequently, the number of positive charges on the surface of the rod-shaped HAp increased relative to the number of negative charges. The BSA release rate in SBF was slower than that of LSZ which is a result of the HAp surface properties.

A series of selenium-substituted hydroxyapatites (SeHAp) with different Se/P ratios has been synthesized via a hydrothermal method using sodium selenite as the Se source. The SeHAp materials were characterized by powder X-ray diffraction, Fourier transform infrared, scanning electron microscopy and transmission electron microscopy. The synthetic SeHAp samples were well-crystallized with a typical apatite structure and the SeHAp crystal lattice parameters increased slightly as the Se concentration increased when the Se/P ratios were less than 0.5. The selenium was incorporated into the hydroxyapatite lattice by replacing some of the phosphate groups with selenite groups.