Bilirubin Adsorption Capacity Research Articles

Preparing high-performance microspheres based on the chitosan-assisted dispersion of reduced graphene oxide in aqueous solution for bilirubin removal

The removal of excess bilirubin from blood is of great clinical importance. Reduced graphene oxide (rGO) is often used to efficiently remove bilirubin. However, thin rGO pieces tend to aggregate in the aqueous phase because they are hydrophobic. In this context, we propose an effective strategy based on the chitosan-assisted (CS-assisted) dispersion of rGO to produce high-performance bilirubin-adsorbing microspheres. CS possesses a hydrophobic CH structure, which offers strong hydrophobic interactions with rGO that assist its dispersion, and the large number of hydrophilic sites of CS increases the hydrophilicity of rGO. CS serves as a dispersant in a surfactant-like manner to achieve a homogeneous and stable CS/rGO dispersion by simply and gently stirring CS and rGO in a LiOH/KOH/urea/H2O system. Subsequently, CS/rGO hybrid microspheres were prepared by emulsification. CS ensures blood compatibility as a base material, and the entrapped rGO contributes to mechanical strength and a high adsorption capacity. The CS/rGO microspheres exhibited a high bilirubin adsorption capacity (215.56 mg/g), which is significantly higher than those of the rGO and CS microspheres. The determined mass-transfer factors revealed that the rich pores of the CS/rGO microspheres promote mass transfer during bilirubin adsorption (equilibrium is almost achieved within 30 min). The CS/rGO microspheres are promising candidates for bilirubin removal owing to a combination of high strength, blood compatibility, and high adsorption capacity.

TiO2/Polystyrene Nanocomposite Antibacterial Material as a Hemoperfusion Adsorbent for Efficient Bilirubin Removal and Prevention of Bacterial Infection.

The use of hemoperfusion adsorbents for the removal of bilirubin in patients with liver failure has become a critical treatment. However, the insufficient clearance of bilirubin and the possibility of bacterial infection during hemoperfusion limit the application. In this work, we designed a novel antibacterial bilirubin adsorbent (PSVT) through the suspension polymerization reaction between double-bond functionalized TiO2 nanoparticles and styrene. PSVT showed an excellent bilirubin adsorption ability and antibacterial performance, ensuring efficient clearance of bilirubin in liver failure patients during hemoperfusion and preventing bacterial infection. The experimental results indicated that TiO2 was uniformly dispersed in the microspheres, which improved the mesoporous structure and increased the specific surface area. Composite adsorbent PSVT showed an exceptional bilirubin adsorption capacity, with the maximum adsorption capacity reaching 24.3 mg/g. In addition, the introduction of TiO2 endowed PSVT with excellent antibacterial ability; the ultimate antibacterial rates against Escherichia coli and Staphylococcus aureus reached 97.31 and 96.47%, respectively. In summary, PSVT served as a novel antibacterial bilirubin adsorbent with excellent bilirubin clearance capacity and antibacterial performance, providing excellent application prospects for treating liver failure patients.

Fabricating polyacrylonitrile-polyethyleneimine nanofiber membranes with exceptional hemocompatibility and efficient bilirubin removal for hemoperfusion

Bilirubin, a severe endogenous toxin, underscores the critical need for the development of bilirubin adsorbents exhibiting both high removal efficiency and exceptional hemocompatibility. Such advancements are pivotal for augmenting the efficacy of hemoperfusion therapy in managing hyperbilirubinemia. Here, a polyacrylonitrile-polyethyleneimine (PAN-PEI) nanofiber membrane (NFM) with elevated amino content was prepared using a facile reflux method for bilirubin adsorption. The PAN-PEI NFMs exhibited a significantly augmented surface amino density of 23.5 mmol.m−2, consequently achieving a remarkable bilirubin adsorption capacity of 87.65 mg.g−1, along with an impressive removal efficiency of 92.3% for bilirubin. Additionally, these nanofiber membranes displayed excellent hemocompatibility, including minimal hemolysis rates, significant anti-protein and anti-hemocyte adhesion properties, as well as a certain degree of anticoagulant activity. These results indicate that the vast potential of using PAN-PEI nanofiber membranes for hyperbilirubinemia hemoperfusion therapy.

Novel hemoperfusion adsorbents based on collagen for efficient bilirubin removal – A thought from yellow skin of patients with hyperbilirubinemia

Hemoperfusion is a well-developed method for removing bilirubin from patients with hyperbilirubinemia. The performance of adsorbents is crucial during the process. However, most adsorbents used for bilirubin removal are not suitable for clinical applications, because they either have poor adsorption performance or limited biocompatibility. Patients with hyperbilirubinemia usually have distinctive yellow skin, indicating that collagen, a primary component of the skin, may be an effective material for absorbing bilirubin from the blood. Based on this idea, we designed and synthesized collagen (Col) and collagen-polyethyleneimine (Col-PEI) microspheres and employed them as hemoperfusion adsorbents for bilirubin removal. The microspheres have an efficient adsorption rate, higher bilirubin adsorption capacity, and competitive adsorption of bilirubin in the bilirubin/bovine serum albumin (BSA) solution. The maximum adsorption capacities of Col and Col-PEI microspheres for bilirubin are 150.2 mg/g and 258.4 mg/g, respectively, which are higher than those of most traditional polymer microspheres. Additionally, the microspheres exhibit excellent blood compatibility originating from collagen. Our study provides a new collagen-based strategy for the hemoperfusion treatment of hyperbilirubinemia.

Protein/Polysaccharide Composite toward Multi-in-One Toxin Removal in Blood with Self-Anticoagulation and Biocompatibility.

Biocompatible adsorbents play an essential role in hemoperfusion. Nevertheless, there are no hemoperfusion adsorbents that can simultaneously remove small and medium toxins, including bilirubin, urea, phosphor, heavy metals, and antibiotics. This bottleneck significantly impedes the miniaturization and portability of hemoperfusion materials and devices. Herein, a biocompatible protein-polysaccharide complex is reported that exhibits "multi-in-one" removal efficacy for liver and kidney metabolism wastes, toxic metal ions, and antibiotics. Through electrostatic interactions and polysaccharide-mediated coacervation, adsorbents can be prepared by simply mixing lysozyme (LZ) and sodium alginate (SA) together in seconds. The LZ/SA absorbent presented high adsorption capacities for bilirubin, urea, and Hg2+ of up to 468, 331, and 497mgg-1 , respectively, and the excellent anti-protein adsorption endowed LZ/SA with a record-high adsorption capacity for bilirubin in the interference of serum albumin to simulate the physiological environment. The LZ/SA adsorbent also has effective adsorption capacity for heavy metals (Pb2+ , Cu2+ , Cr3+ , and Cd2+ ) and multiple antibiotics (terramycin, tetracycline, enrofloxacin, norfloxacin, roxithromycin, erythromycin, sulfapyrimidine, and sulfamethoxazole). Various adsorption functional groups exposed on the adsorbent surface significantly contribute to the excellent adsorption capacity. This fully bio-derived protein/alginate-based hemoperfusion adsorbent has great application prospects in the treatment of blood-related diseases.

#6768 TIO2/TI3C2 NANOCOMPOSITES FOR BILIRUBIN CLEARANCE FROM BLOOD

Abstract Background and Aims The artificial liver treatment based on blood purification is an important and commonly used treatment for liver failure. Aggressive management of hyperbilirubinemia is one of the key steps to reduce mortality in patients with liver failure. Herein, targeting bilirubin in nano-sized, we synthesized a TiO2/Ti3C2 nanocomposite from Ti3C2 MXenes via hydrothermal oxidation for bilirubin clearance from whole blood. Method Firstly, Ti3C2 MXene was prepared by hydrofluoric acid etching method reported in our previous work [1]. Then, it was transferred into Teflon-lined stainless-steel autoclaves (2 mg/ml, 30 ml) and was undergone the hydrothermal process at 180 °C for 6 h and 12 h. TiO2/Ti3C2 nanocomposites were obtained after lyophilization. Hemocompatibility evaluation assays include hemolysis ratio test, complement activation (human complement fragment 5a (C5a)), contact activation (Thrombin–anti-thrombin (TAT) complex) and platelet activation (platelet factor 4 (PF 4)) were systemically conducted in vitro to evaluate the feasibility of the novel nanocomposites (0.5 mg/ml) in contact with blood. We evaluated the bilirubin adsorption capacity of original Ti3C2 (0 h) and TiO2/Ti3C2 (6 h and 12 h) at the concentration of 0.5 mg/ml, respectively, in bilirubin solution (250 mg/l, 10 ml) for 2 h at 37 °C in an air bath away from light. The sphere-forming properties of TiO2/Ti3C2 with polyethersulfone (PES), a commonly used blood purification material, were first verified using a liquid-liquid inversion method. Results TiO2/Ti3C2 (6 h and 12 h) showed better hemocompatibility than the original Ti3C2 (0 h) (Figure 1). The bilirubin adsorption capacities by the original Ti3C2 (0 h) and TiO2/Ti3C2 (6 h and 12 h) were 354.11 mg/g, 492.83 mg/g and 492.52 mg/g, respectively. From the original Ti3C2 (0 h) to TiO2/Ti3C2 (6 h), the clearance rate of bilirubin improved from 70.82% to 98.57%. Therefore, we chose TiO2/Ti3C2 (6 h) to verify the sphere-forming properties of TiO2/Ti3C2 with PES. TiO2/Ti3C2-PES spheres were constructed successfully by a liquid-liquid inversion method. More 3D porous structure on the surface and uniform distribution of TiO2/Ti3C2 (Ti element) in the substrate were observed via a scanning electron microscope (SEM) images and energy dispersive spectroscopy (EDS) mapping images (Figure 2). Conclusion The TiO2/Ti3C2 nanocomposite showed excellent bilirubin clearance capability, superior hemocompatibility, and the great application potential in the form of spheres for hemoperfusion, which may provide a promising choice in the performance enhancement of artificial liver characterized by bilirubin clearance. Importantly, the above properties are adjustable by the heating temperature and the time period, other application forms and strategies of the TiO2/Ti3C2 nanocomposite to target bilirubin in nano-sized are worth being explored and expected.

Heparin/polyethyleneimine dual-sided functional polyvinylidene fluoride plasma separation membrane for bilirubin removal

Herein, a novel heparin/polyethyleneimine (PEI) dual-sided functional polyvinylidene fluoride (PVDF) plasma separation membrane structure is proposed. Bilirubin is removed using this membrane via one-step “anticoagulation-adsorption”. When blood flows in the membrane, the inner side of the membrane can prolong clotting time. Meanwhile, bilirubin contained in plasma is filtrated through the membrane. Bilirubin is adsorbed on the outer side of the membrane to be removed. Herein, branched PEI was grafted on the outer side of the PVDF plasma separation membrane to construct the bilirubin adsorption functional layer. Then, heparin was grafted on the inner side to construct a self-anticoagulant functional layer. The dual-sided functional PVDF plasma separation membrane was prepared. The results showed that PEI and heparin could be grafted on the outer side and the inner side of the PVDF plasma separation membrane, separately. Bilirubin's competitive adsorption property of the outer side of the membrane was enhanced. Hemocompatibility of the inner side of the membrane was strengthened. The plasma permeability of the novel membrane gradually decreased to 250 L·m−2·h−1bar−1. The total plasma protein sieving coefficient of the novel membrane was larger than 80 %. Total bilirubin and direct bilirubin adsorption capacity reached 22.5 mg/g and 20.5 mg/g via one-step “anticoagulation-adsorption”. The novel membrane prepared in this work can effectively simplify traditional hemoperfusion therapy, implying its great potential application.

Enhanced Hemocompatibility of Lysine Grafted Polyacrylonitrile Electrospun Nanofiber Membranes as a Potential Bilirubin Adsorption in Hemoperfusion

Hyperbilirubinemia is one of most severe clinical diseases, which is caused by the accumulation of unconjugated bilirubin. Electrospun nanofiber membranes used as highly efficient bilirubin adsorbents have been applied to remove the extra bilirubin in hemoperfusion for their high surface area and easy functionalized properties. In this work, Lysine (Lys) grafted polyacrylonitrile (PAN) electrospun nanofiber membranes doped with organic Hectorite (OHec) (Lys-HPAN@OHec) have been fabricated via a series of modified process, including pore forming, alkaline hydrolysis and grafting reaction. The obtained Lys-HPAN@OHec nanofiber membranes have been analyzed in detail and investigated the adsorption capacity for bilirubin. Compared with original PNA membranes, Lys-HPAN@OHec nanofiber membranes show an excellent bilirubin adsorption capacity and more stable rejection rate of bovine serum albumin (BSA). The maximum adsorption capacity of Lys-HPAN@OHec membranes for bilirubin is 64 mg/g, the adsorption process of Lys-HPAN@OHec membranes matched the Langmuir model well. In addition, dynamic adsorption reveals that the adsorption equilibrium time of Lys-HPAN@OHec membranes is about 2 h. Significantly, Lys-HPAN@OHec membranes have excellent biocompatibility and hemocompatibility. This study demonstrates that the novel Lys-HPAN@OHec membranes may provide a new way to treat hyperbilirubinemia.

Biocompatible Composite Microspheres of Chitin/Ordered Mesoporous Carbon CMK3 for Bilirubin Adsorption and Cell Microcarrier Culture.

Extra bilirubin in the blood can provoke serious illness in patients with severe liver disease. Hemoperfusion is an effective method to remove the extra bilirubin, but its application is limited by the low adsorption efficiency and poor biocompatibility of available adsorbent materials. In this study, chitin/ordered mesoporous carbon CMK3 (Ch/CMK3) microspheres are successfully prepared. Results of characterization experiments indicated that these composite microspheres possess a multilayered porous nanofibrous structure with an extremely large specific surface area (300.19 m2 g-1 ) and large pore size. Notably, the Ch/CMK3 microspheres demonstrated a high bilirubin adsorption capacity (228.19mg g-1 ) in phosphate buffer solution (PBS), and an outstanding bilirubin removal ratio (76.78% ± 4.40%) in the plasma of rabbits with hyperbilirubinemia without affecting the protein components. More importantly, the Ch/CMK3 microspheres showed no effect on other blood components, no cytotoxicity, and no systemic toxicity to mice. Cell co-culture experiments revealed that the microspheres can provide a 3-dimensional (3D) space to promote cell adhesion, proliferation, and nutrient exchange. These Ch/CMK3 microspheres featuring a strong ability for bilirubin adsorption and good biocompatibility can be a promising candidate in biomedical applications such as hemoperfusion, cell microcarrier, and 3D tissue engineering.

Structure design and performance study on filtration-adsorption bifunctional blood purification membrane

Plasma perfusion is one of the primary therapies for hepatic failure. However, biocompatibility and toxins removal of plasma perfusion adsorbents are mutual constraints. Herein, a novel bifunctional blood purification membrane structure is proposed, which can remove toxins via “filtration-adsorption”. The internal surface of membrane has excellent biocompatibility. Meanwhile, the external surface can adsorb toxins. When blood flows in internal surface, toxins in plasma can be filtrated through membrane and adsorbed on the external surface. Herein, plasma separation membrane with excellent biocompatibility was prepared firstly. Then, the external surface was modified by β-cyclodextrin to construct bilirubin adsorption functional layer. XPS, ATR-FTIR and FE-SEM demonstrated that β-cyclodextrin was grafted on the external surface without modifying the internal surface. The bovine serum albumin sieving coefficient of membrane reached (97.8 ± 1.9)%. The water flux reached (1084 ± 30)L.m2.h−1. Bilirubin adsorption capacity of the external surface reached 12.8 mg/g via “filtration-adsorption”. Bilirubin competitive adsorption coefficient was 9.1. The internal surface was similar to original plasma separation membrane, which had excellent biocompatibility due to low hemolysis and blood cells adsorption. Thus, the bifunctional blood purification membrane can remove bilirubin safely via one-step “filtration-adsorption”. The structure design of membrane provides a new blood purification treatment scheme for clinical hepatic failure.

Engineered liver-inspired collagen matrix as a high-performance hemoperfusion adsorbent for bilirubin removal

Highly efficient removal of bilirubin from blood by hemoperfusion for liver failure therapy remains a great challenge in the clinical field due to the unsatisfied biocompatibility of non-biological materials and the slow adsorption kinetics of currently used bilirubin adsorbents. Here, inspired by the natural collagen-supported multiscale structures of the liver for bilirubin removal, a natural collagen-based artificial liver, named ColAL, was successfully constructed via a biomimetic synthetic strategy. ColAL exhibited a record-high adsorption capacity of 102.32 mg g−1 for bilirubin in the presence of 40.0 g L−1 bovine serum albumin. The ColAL also presented excellent bilirubin adsorption capacity in the complex serum. Importantly, the total bilirubin (TBIL) removal rate was higher than 69.17% and the direct bilirubin (DBIL) removal rate was 75.31% by immersing the ColAL in ex vivo blood samples. No damages were observed in the major organs after the injection of ColAL extract solution subcutaneously in vivo, indicating high biocompatibility and biostability of these natural collagen-based materials. This facile approach provides a new avenue to develop collagen-based high-performance hemoperfusion adsorbent for the removal of bilirubin, showing great promise to the translational therapy of hyperbilirubinemia.

High-strength, blood-compatible, and high-capacity bilirubin adsorbent based on cellulose-assisted high-quality dispersion of carbon nanotubes

Excess bilirubin can accumulate in body organs and has serious effects on human health. In this work, a simple engineering strategy, based on cellulose-assisted high-quality dispersion of carbon nanotubes (CNTs), is proposed to produce high-performance bilirubin adsorbents. By dispersing cellulose and CNTs in NaOH/thiourea aqueous solution, a homogeneous and stable cellulose/CNTs solution is achieved. The obtained cellulose/CNTs solution is applied for the fabrication of cellulose/CNTs microspheres (CCMs), in which cellulose serves as a base material and guarantees the blood compatibility of the composite material, and CNTs contribute to the improved mechanical strength and high adsorption capacity. To further improve blood compatibility and adsorption capacity, lysine is immobilized on the CCMs. The obtained lysine-modified CCMs (LCCMs) exhibit a large surface area (171.31 m2/g) and hierarchically porous structure. Experimental results demonstrate LCCMs have high bilirubin adsorption capacity (204.12 mg/g) that is significantly higher than most of the reported adsorbents. The combination of high strength, blood compatibility, and high adsorption capacity positions the LCCMs as a promising candidate for bilirubin removal.

Fabrication of chitosan/graphene oxide composite aerogel microspheres with high bilirubin removal performance.

Functional chitosan/graphene oxide (CS/GO) composite aerogel microspheres were fabricated via CO2 supercritical drying, which displayed excellent performance for bilirubin removal. The morphology and chemical structure of CS/GO composite aerogel microspheres were characterized, which illustrated a nanoporous structure with a maximum specific surface area of 174.69 m2/g, and a special pore size distribution at 20-40 nm, also a good mechanical property. Importantly, the composite aerogel microspheres (10% GO) revealed a large adsorption capacity (178.25 mg/g) for bilirubin within 2 h. Dynamic adsorption experiment illustrated that the aerogel microspheres adsorbed much more bilirubin with a shorter equilibrium time of about 30 min. Besides, the adsorption mechanism of bilirubin by the CS/GO composite aerogel microspheres was investigated through the relevant model fitting, including adsorption kinetics and adsorption isotherm, which illustrated that the mechanism included both physical and chemical processes, but chemical adsorption was dominated. Adsorption isotherm indicated that bilirubin adsorption by the microspheres was fitted well with Freundlich isotherm, which ascribed to multilayer adsorption. After five adsorption-desorption cycles, the adsorption capacity still maintains large adsorption capacity. In addition, the hemolysis rate and coagulation time tests presented the good blood compatibility for the adsorbents. Therefore, the CS/GO composite aerogel microspheres with rapid, high adsorption capacity and good blood compatibility might be promising for hyperbilirubinemia treatment.

Procion Blue H-5R functionalized cellulose membrane with specific removal of bilirubin

The specific removal of bilirubin is essential to cure hyperbilirubinemia. In this study, cellulose membranes were prepared by a phase inversion technique with surface functionalized Procion Blue H-5R (PB) for bilirubin adsorption. The chemical structures and morphologies of membranes were characterized by FITR, XPS and SEM. The immobilized PB amounts of membranes were investigated. Moreover the effects of immobilized PB amounts, initial concentration of bilirubin, NaCl concentration, pH value, recycle numbers and BSA concentration on adsorption capability of PB-immobilized cellulose membrane to bilirubin. Results showed that PB was immobilized onto the cellulose membrane surfaces and reached a maximum amount of 230 mg/g membrane. The bilirubin adsorption isotherm fitted Langmuir model well. Furthermore, the PB-immobilized membrane could specifically adsorb bilirubin in BSA/bilirubin mixed solution and bilirubin adsorption capacity reached 26 mg/g at pH 9.5. The membrane showed excellent reusability that the adsorption capability of bilirubin decreased 1.3% after 3 adsorption–desorption cycles. This work indicated that the Procion Blue H-5R can be expected as a ligand for specific removal of bilirubin.

Selective adsorption of bilirubin against albumin to alkylamine functionalized PVA microspheres

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.

Construction of blood compatible chitin/graphene oxide composite aerogel beads for the adsorption of bilirubin

Excess bilirubin in blood can provoke hepatic damage and related malfunctions. Hereby we designed and constructed a novel bilirubin adsorbent, called chitin/graphene oxide (Ch/GO) composite aerogel beads, for efficient, fast and safe removal for bilirubin. The Ch/GO aerogel beads were prepared from chitin and GO in a NaOH/urea aqueous solution, followed dried by supercritical carbon dioxide. The morphology, structure and properties of the Ch/GO composite aerogel beads were characterized by scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and compressive strength measurement. The results indicated that GO was successfully bound to chitin matrix with enhanced surface area, thermal stability and mechanical strength. The adsorption capacity of Ch/GO composite aerogel beads for bilirubin was examined by UV–vis spectrophotometry. Moreover, batch adsorption results revealed that the Ch/GO composite aerogel beads showed excellent bilirubin adsorption capacity (484.1 ± 16.9 mg/g) and short adsorption equilibrium time (0.5 h) under optimized condition. Furthermore, the Ch/GO aerogel beads exhibited a lower hemolysis property and improved anticoagulant property. Hence, this work provided a new strategy to develop a novel blood compatible bilirubin adsorbent, which presented good application potential for bilirubin adsorption.

Preparation of chitosan/SiO2-loaded graphene composite beads for efficient removal of bilirubin

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.

Fabrication of chitin/graphene oxide composite sponges with higher bilirubin adsorption capacity.

Chitin/graphene oxide (Ch/GO) composite sponges had been synthesized in 11 wt% NaOH/4 wt% urea aqueous solution by a simple method. The structure, thermal stability and mechanical properties of the composite sponges were investigated by scanning electron microscopy, Fourier-transform infrared spectroscopy, wide-angle X-ray diffraction, thermogravimetric analysis, and compressive strength measurements. The results revealed that chitin and GO were mixed homogeneously. Interestingly, the composite sponges showed meso-macroporous structure, which played an important role in improving their adsorption properties. Besides, thermal stability and mechanical properties were significantly improved compared with pure chitin sponges. Taking advantages of these fantastic characteristics, the maximum adsorption capacity of composite sponges for bilirubin was up to 422.9 mg/g under the optimized condition, which was not only significantly higher than the adsorption capacities of pure chitin sponges, but also superior to those of many reported adsorbents for removal of bilirubin. Furthermore, blood compatibility evaluations confirmed that this blended sponges had negligible hemolysis and coagulation. Therefore, this work provided a potential possibility to offer Ch/GO composite sponges for removal of bilirubin.

Bilirubin detoxification using different phytomaterials: characterization and in vitro studies.

BackgroundActivated carbon (AC) is a common adsorbent that is used in both artificial and bioartificial liver devices.MethodsThree natural materials – date pits of Phoenix dactylifera (fruit), Simmondsia chinensis (jojoba) seeds, and Scenedesmus spp. (microalgae) – were used in the present investigation as precursors for the synthesis of AC using physical activation. The chemical structures and morphology of AC were analyzed. Then, AC’s bilirubin adsorption capacity and its cytotoxicity on normal liver (THLE2) and liver cancer (HepG2) cells were characterized.ResultsCompared with the other raw materials examined, date-pit AC was highly selective and showed the most effective capacity of bilirubin adsorption, as judged by isotherm-modeling analysis. MTT in vitro analysis indicated that date-pit AC had the least effect on the viability of both THLE2 and HepG2 cells compared to jojoba seeds and microalgae. All three biomaterials under investigation were used, along with collagen and Matrigel, to grow cells in 3D culture. Fluorescent microscopy confirmed date-pit AC as the best to preserve liver cell integrity.ConclusionThe findings of this study introduce date-pit-based AC as a novel alternative biomaterial for the removal of protein-bound toxins in bioartificial liver devices.

Poly-l-lysine modified cryogels for efficient bilirubin removal from human plasma.

In this study, poly-l-lysine (PLL) immobilized PHEMA cryogel was designed for the specific bilirubin removal from human plasma. The surface of PHEMA cryogels is surrounded by PLL chains to enhance specific binding of bilirubin molecules via specific complementary electrostatic interactions. The functionalization of the PHEMA cryogel was carried out by direct coupling of PLL to pre-activated OH-group of the HEMA alcohol units via carbodiimide activation. Prior to removal of bilirubin from human plasma, the optimization parameters including, initial bilirubin concentration, flow rate, temperature, ionic strength, and adsorption rates on adsorption of PLL-PHEMA cryogel were investigated from the aqueous medium. According to the elemental analyses results, the incorporation of PLL was 690.0 μmol/g cryogel. The cryogel has highly interconnected supermacroporous structure sized between 20 and 100 μm with a positive surface charge value. The maximum bilirubin adsorption capacity was found as 59.9 mg/g of the dry weight of PLL-PHEMA cryogel. Reusability study explored that PLL-PHEMA could be used with a negligible loss in the bilirubin adsorption capacity after successive ten adsorption-desorption cycles using the same adsorbent. The results of the study demonstrated that the PLL-PHEMA cryogel exhibited high specificity that can be used as an efficient column for removing the bilirubin from the human plasma.