Blood Protein Adsorption Research Articles

Preparation and characterization of infection‐resistant antibiotics‐releasing hydrogels rods of poly[hydroxyethyl methacrylate‐co‐(poly(ethylene glycol)‐methacrylate]: Biomedical application in a novel rabbit penile prosthesis model

In this work, preparation and characterization of novel three different antibiotic loaded penile prosthesis in the rod form were investigated by copolymerization of 2-hydroxyethylmethacrylate (HEMA) with poly(ethylene glycol)-methacrylate, (PEG-MA). To achieve this goal, a series of novel copolymer hydrogels were prepared in rod form using HEMA and PEG-MA monomers via UV initiated photopolymerization. The thermal stability of the copolymer was found to be lowered by increase in the ratio of PEG-MA in the rod structure. Contact angle measurements on the surface of copolymer hydrogel demonstrated that the copolymer gave rise to a significant hydrophilic surface compared with pure poly(HEMA). The blood protein adsorption and platelet adhesion were significantly reduced on the surface of the copolymer hydrogels compared with control pure poly(HEMA). Poly(HEMA:PEG-MA;1:1)-1 formulation containing different antibiotics (20 mg antibiotic/g polymer) released about 90, 91, and 55% of the total loaded cephtriaxon, vancomycin, and gentamicin in 48 h at pH 7.4, respectively. Finally, antibiotics loaded biocompatible poly(HEMA:PEG-MA;1:1)-1 hydrogel compositions was used as a penile prosthesis in preventing cavernous tissue infections in a rabbit prosthesis model. The efficacy of the three different antibiotics loaded hydrogel system was evaluated in four different groups of rabbits, in which various infectious agents were inoculated. The animals were sacrificed after predetermined time periods, and clinical, histological and microbiological assessment on the implant side were carried out to detect infections. Eventually, we concluded that three different antibiotic loaded penile prostheses (i.e. poly(HEMA:PEG-MA;1:1)-1 hydrogel systems) were as effective as parenteral antibiotics applications.

PMMA‐multigraft copolymers derived from linseed oil, soybean oil, and linoleic acid: Protein adsorption and bacterial adherence

AbstractSynthesis of Poly(methyl methacrylate), PMMA‐multigraft copolymers derived from linseed oil, soybean oil, and linoleic acid PMMA‐g‐polymeric oil/oily acid‐g‐poly(3‐hydroxy alkanoate) (PHA), and their protein adsorption and bacterial adherence have been described. Polymeric oil/oily acid peroxides [polymeric soybean oil peroxide (PSB), polymeric linseed oil peroxide (PLO), and polymeric linoleic acid peroxide (PLina)] initiated the copolymerization of MMA and unsaturated PHA‐soya to yield PMMA–PLO–PHA, PMMA–PSB–PHA, and PMMA–PLina–PHA multigraft copolymers. PMMA–PLina–PHA multigraft copolymers were completely soluble while PMMA–PSB–PHA and PMMA–PLO–PHA multigraft copolymers were partially crosslinked. Crosslinked parts of the PLO‐ and PSB‐multigraft copolymers were isolated by the sol gel analysis and characterized by swelling measurements in CHCl3. Soluble part of the PLO‐ and PSB‐multigraft copolymers and completely soluble PLina‐multigraft copolymers were obtained and characterized by spectroscopic, thermal, gel permeation chromatography (GPC), and scanning electron microscopy (SEM) techniques. In the mechanical properties of the PHA–PLina–PMMA, the elongation at break is reduced up to ∼ 9%, more or less preserving the high stress values at its break point (48%) when compared to PLina‐g‐PMMA. The solvent casting film surfaces were studied by means of adsorption of blood proteins and bacterial adhesion. Insertion of the PHA into the multigraft copolymers caused the dramatic increase in bacterial adhesion on the polymer surfaces. PHA insertion into the graft copolymers also increased the protein adsorption. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007

Preparation and characterization of macroporous poly(2‐hydroxyethyl methacrylate)‐based biomaterials: Water sorption property and in vitro blood compatibility

AbstractA semi‐interpenetrating polymer network (IPN) comprising gelatin and poly(2‐hydroxyethyl methacrylate‐co‐acrylamide) was prepared and characterized by FTIR, environmental scanning electron microscopy (ESEM) and differential scanning calorimetry (DSC) techniques. The water sorption potential of the prepared semi‐IPNs was investigated for varying chemical architecture of the IPN, and experimental conditions such as pH, temperature and ionic strength of the swelling media. The semi‐IPNs were also judged for in vitro blood compatibility by performing blood clot, percent hemolysis, protein adsorption and platelet adhesion tests. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 1559–1571, 2007

Plasma‐deposited tetraglyme surfaces greatly reduce total blood protein adsorption, contact activation, platelet adhesion, platelet procoagulant activity, and in vitro thrombus deposition

The ability of tetraethylene glycol dimethyl ether (tetraglyme) plasma deposited coatings exhibiting ultralow fibrinogen adsorption to reduce blood activation was studied with six in vitro methods, namely fibrinogen and von Willebrand's factor adsorption, total protein adsorption, clotting time in recalcified plasma, platelet adhesion and procoagulant activity, and whole blood thrombosis in a disturbed flow catheter model. Surface plasmon resonance results showed that tetraglyme surfaces strongly resisted the adsorption of all proteins from human plasma. The clotting time in the presence of tetraglyme surfaces was lengthened compared with controls, indicating a lower activation of the intrinsic coagulation cascade. Platelet adhesion and thrombin generation by adherent platelets were greatly reduced on tetraglyme-coated materials, compared with uncoated and Biospan-coated glass slides. In the in vitro disturbed blood flow model, tetraglyme plasma coated catheters had 50% less thrombus than did the uncoated catheters. Tetraglyme-coated materials thus had greatly reduced blood interactions as measured with all six methods. The improved blood compatibility of plasma-deposited tetraglyme is thus not only due to their reduced platelet adhesion and activation, but also to a generalized reduction in blood interactions.

Polymeric Linoleic Acid–Polyolefin Conjugates: Cell Adhesion and Biocompatibility

AbstractTo diversify edible‐oil polymer composite, polymeric linoleic acid (PLina) peroxide was obtained by the auto‐oxidation of linoleic acid in a simple way for use as a macroinitiator in free radical polymerization of vinyl monomers. Peroxidation, epoxidation, and/or perepoxidation reactions of linoleic acid under air at room temperature resulted in PLina, having soluble fraction more than 91 weight percent (wt%), with molecular weight ranging from 1,644 to 2,763 Da, and containing up to 1.0 wt% of peroxide. PLina initiated the free radical polymerization of ether styrene (S), methyl methacrylate (MMA), or n‐butyl methacrylate (nBMA) to give PLina‐g‐polystyrene (PS), PLina‐g‐poly‐MMA (PMMA), and PLina‐g‐poly‐ nBMA (PnBMA) graft copolymers. The polymers obtained were characterized by proton nuclear magnetic resonance (1H NMR), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), and gel permeation chromatography (GPC) techniques. Microstructure of the graft copolymers was observed by using scanning electron microscope (SEM). Graft copolymers obtained contained polymeric linoleic acid in a range between 8.5 and 19.3 mol percent (mol%). PLina‐g‐PS, PLina‐g‐PMMA and PLina‐g‐PnBMA graft copolymer samples were also used in cell culture studies. Fibroblast and macrophage cells were strongly adhered and spread on the copolymer film surfaces. These newly synthesized copolymers were tested for their effects on human blood protein adsorption compared with PMMA graft copolymers containing polymeric soybean oil and polymeric linseed oil; interestingly we observed a dramatic decrease in the protein adsorption on the linoleic acid graft copolymer, which is important in tissue engineering.

Blood protein adsorption onto macroporous semi‐interpenetrating polymer networks (IPNs) of poly(ethylene glycol) (PEG) and poly(2‐hydroxyethyl methacrylate) (PHEMA) and assessment of in vitro blood compatibility

AbstractThis work reports a study of the adsorption of fibrinogen (Fgn) onto the surface of semi‐interpenetrating polymer networks (IPNs) of poly(ethylene glycol) (PEG) and poly(2‐hydroxyethyl methacrylate) (PHEMA). The semi‐IPNs were prepared by polymerizing 2‐hydroxyethyl methacrylate with a redox system and in the presence of PEG and crosslinker ethyleneglycol dimethacrylate. The proposed spongy IPNs were characterized by Fourier transform infrared and environmental scanning electron microscopy methods, and network structural parameters, such as molecular weight between crosslinks and crosslink density, were calculated using swelling measurements. The adsorption of Fgn was carried out onto the spongy IPNs and kinetic constants of the adsorption process as well as isotherm constants were evaluated. The adsorption process was also studied under varying pH, ionic strengths, and chemical architecture of the IPNs. The anti‐thrombogenic behaviour of the polymer matrices was judged using in vitro tests. Copyright © 2006 Society of Chemical Industry

Biocompatibility of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolyesters produced byAlcaligenes sp. MT-16

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(3HB-co-3HV), copolyesters, with 3-hydroxyvalerate (3HV) contents ranging from 17 to 60 mol%, were produced byAlcaligenes sp. MT-16, and their biocompatibility evaluated by the growth of Chinese hamster ovary (CHO) cells and the adsorption of blood proteins and platelets onto their film surfaces. The number of CHO cells that adhered to and grew on these films was higher with increasing 3HV content. In contrast, the tendency for blood proteins and platelets to adhere to the copolyester surfaces significantly decreased with increasing 3HV content. Examination of the surface morphology using atomic force microscopy revealed that the surface roughness was an important factor in determining the biocompatibility of theses copolyesters. The results obtained in this study suggest that poly(3HB-co-3HV) copolyesters, with >30 mol% 3HV, may be useful in biocompatible biomedical applications.

Interfacial energetics of globular–blood protein adsorption to a hydrophobic interface from aqueous-buffer solution

Adsorption isotherms of nine globular proteins with molecular weight (MW) spanning 10-1000 kDa confirm that interfacial energetics of protein adsorption to a hydrophobic solid/aqueous-buffer (solid-liquid, SL) interface are not fundamentally different than adsorption to the water-air (liquid-vapour, LV) interface. Adsorption dynamics dampen to a steady-state (equilibrium) within a 1 h observation time and protein adsorption appears to be reversible, following expectations of Gibbs' adsorption isotherm. Adsorption isotherms constructed from concentration-dependent advancing contact angles theta(a) of buffered-protein solutions on methyl-terminated, self-assembled monolayer surfaces show that maximum advancing spreading pressure, Pi(a)max, falls within a relatively narrow 10 < Pi(a)max < 20 mN m(-1) band characteristic of all proteins studied, mirroring results obtained at the LV surface. Furthermore, Pi(a) isotherms exhibited a 'Traube-rule-like' progression in MW similar to the ordering observed at the LV surface wherein molar concentrations required to reach a specified spreading pressure Pi(a) decreased with increasing MW. Finally, neither Gibbs' surface excess quantities [Gamma(sl)-Gamma(sv)] nor Gamma(lv) varied significantly with protein MW. The ratio {[Gamma(sl)-Gamma(sv)]/Gamma(lv)} approximately 1, implying both that Gamma(sv) approximately 0 and chemical activity of protein at SL and LV surfaces was identical. These results are collectively interpreted to mean that water controls protein adsorption to hydrophobic surfaces and that the mechanism of protein adsorption can be understood from this perspective for a diverse set of proteins with very different composition.

Novel Hydrogel Membrane Based on Copoly(hydroxyethyl methacrylate/p‐vinylbenzyl‐poly(ethylene oxide)) for Biomedical Applications: Properties and Drug Release Characteristics

The aim of this study was to synthesize and characterize a novel biocompatible polymeric membrane system and demonstrate its potential use in various biomedical applications. Synthetic hydrogels based on poly(hydroxyethyl methacrylate), poly(HEMA), have been widely studied and used in biomedical fields. A novel copolymer hydrogel was prepared in the membrane form using 2-hydroxyethyl methacrylate monomer (HEMA) and a macromonomer p-vinylbenzyl-poly(ethylene oxide) (V-PEO) via photoinitiated polymerization. A series of poly(HEMA/V-PEO) copolymer membranes with different compositions was prepared. The membranes were characterized using infrared, thermal and SEM analysis. The thermal stabilities of the copolymer membranes were found to be lowered by an increase in the ratio of macromonomer (V-PEO) in the membrane structure. Because of the incorporation of PEO segments, the copolymers exhibited significantly higher hydrophilic surface properties than pure poly(HEMA), as demonstrated by contact angle measurements. Equilibrium swelling studies were conducted to investigate the swelling behavior of the membranes. The equilibrium water uptake was reached in about 4 h. Moreover, the blood protein adsorption and platelet adhesion were significantly reduced on the surface of the PEO containing copolymer membranes compared to control pure poly(HEMA). Drug release experiments were performed in a continuous release system using model drug (vancomycin) loaded copoly(HEMA/V-PEO) membranes. A specific poly(HEMA/V-PEO) membrane formulation possessing the highest PEO content (with a HEMA:V-PEO (mmol:mmol) feed ratio of 112:1 and loaded with 40 mg antibiotic/g polymer) released about 81% of the total loaded drug in 24 h at pH 7.4. This membrane composition provided the best results and can be considered as a potential candidate for a transdermal antibiotic carrier and various biomedical and biotechnological applications.

Porous and Electrically Conductive Polypyrrole−Poly(vinyl alcohol) Composite and Its Applications as a Biomaterial

Bulk modification of polypyrrole (PPY) with poly(vinyl alcohol) (PVA) was carried out by the electropolymerization of pyrrole in the presence of PVA in the reaction solution, with tetraethylammonium perchlorate (TEAP) as the electrolyte. The surface morphology of the as-synthesized PPY-TEAP-PVA film was investigated using scanning electron microscopy, and the film was further characterized using X-ray photoelectron spectroscopy, electrical conductivity, the water contact angle, and BET surface area measurements. The PPY-TEAP-PVA composite is electrically conductive, hydrophilic, and microporous with a high surface area. Its potential as a biomaterial was investigated with respect to its blood compatibility and function as a substrate for biosensor fabrication and cell culture. The presence of PVA in the film attenuates blood protein adsorption, and the porous nature of the PPY-TEAP-PVA film results in a 10-fold increase in the amount of glucose oxidase covalently immobilized on the film over that on a nonporous PPY film. PC12 cell attachment and growth on the PPY-TEAP-PVA film was also shown to be enhanced compared with that on tissue culture polystyrene. The attached cells proliferated and formed a monolayer on the film surface after 48 h of seeding.

Development of an infection‐resistant, bioactive wound dressing surface

Trauma, whether caused by an accident or in an intentional manner, results in significant morbidity and mortality. The goal of this study was to develop a novel biomaterial surface in vitro and ex vivo that provides both localized infection resistance nd hemostatic properties. Our hypothesis is that a combination of specific surface characteristics can be successfully incorporated into a single biomaterial. Functional groups were created with woven Dacron (Cntrl) material via exposure to ethylenediamine (C-EDA). The antibiotic ciprofloxacin (Cipro) was then applied to the C-EDA material using pad/autoclave technique (C-EDA-AB) followed by surface immobilization of the coagulation cascade enzyme thrombin (C-EDA-AB-Thrombin). Antimicrobial activity by the C-EDA-AB surface persisted for 5 days compared with Cntrl and dipped controls, which lasted <1 h. C-EDA-AB-Thrombin surfaces had 2.6- and 105-fold greater surface thrombin activity compared with nonspecifically bound thrombin and Cipro-dyed surfaces, respectively. Surface thrombus formation ex vivo was evident after 1 min of exposure, with thrombus organization evident by 2.5 min. In contrast, C-EDA-AB and Cntrl segments showed only blood protein adsorption on the fibers. Thus, this study demonstrated that Cipro and thrombin can be simultaneously incorporated onto a biomaterial surface while maintaining their respective biological activities.

Biocompatibility of Poly(carbonate urethane)s with Various Degrees of Nanophase Separation

Nanophase separation has been suggested to influence the biological performance of polyurethane. In a previous work, six different 4,4'-diphenylmethane diisocyanate (MDI)-based poly(carbonate urethane)s (PCUs) that exhibited various degrees of nanophase separation were synthesized and characterized. In the present work, these PCUs were used as a model system to study the effect of nanometric structures on the biocompatibility of polyurethane. Human blood platelet activation, monocyte activation, protein adsorption, and bacterial adhesion on PCU were investigated in vitro. It was found that human blood platelets as well as monocytes were less activated on the PCU surfaces with a greater degree of nanophase separation in general. This phenomenon was closely associated with the lower ratio of human fibrinogen/albumin competitively adsorbed on these surfaces. Bacterial adhesion was also inhibited in some nanophase-separated PCUs. [diagram in text].

Surface characteristics and hemocompatibility of PAN/PVDF blend membranes

Polyacrylonitrile (PAN) was blended with polyvinylidine fluoride (PVDF) at various ratios and made into membranes. The hemocompatibility of the resulting membranes was evaluated based on human plasma proteins adsorption, platelet adhesion, thrombus formation, and blood coagulation time. The PAN/PVDF blends exhibited partial miscibility according to the inward shifting of their two glass transition temperatures. The microstructures of blend membranes examined using atomic force microscopy (AFM) indicated that the roughness increased with the PVDF content, and the phase separation was too severe to form a membrane when the PVDF content was more than 30%. The water contact angle of PAN/PVDF blend membranes increased with the PVDF content. By blending with 20wt% apolar PVDF the adsorption of blood proteins could be reduced, and hence the platelet adhesion and thrombus formation was also reduced. However, when the PVDF content was 30wt%, severe thrombogenicity was observed due probably to the more porous structure of blend membrane. These results demonstrated that the hemocompatibility would be improved for PAN/PVDF blend membranes with appropriate hydrophilicity and roughness. Copyright # 2005 John Wiley & Sons, Ltd.

Blood protein adsorption onto a polymeric biomaterial of polyethylene glycol and poly[(2‐hydroxyethyl methacrylate)‐co‐acrylonitrile] and evaluation of in vitro blood compatibility

AbstractA semi‐interpenetrating polymer network (semi‐IPN) of polyethylene glycol (PEG) and crosslinked poly[(2‐hydroxyethyl methacrylate)‐co‐acrylonitrile] was prepared and adsorption of bovine serum albumin (BSA) on the IPN surfaces was investigated. The dynamic nature of the adsorption process was studied, and the effects of various experimental factors such as pH and ionic strength on the adsorption isotherms of BSA were investigated. Various kinetic parameters, such as the adsorption coefficient, rate constant for adsorption and penetration rate constants, were calculated. For assessment of in vitro blood compatibility of the IPN surfaces, water sorption, blood clot formation tests and percent hemolysis measurements were performed. Copyright © 2004 Society of Chemical Industry

Selective protein adsorption and blood compatibility of hydroxy-carbonate apatites.

We examined the blood compatibility and protein adsorption on hydroxyapatite and hydroxy-carbonate apatite. Those apatites were synthesized under a 0, 5, or 15% CO(2)-containing N(2) atmosphere by a wet-chemical method with a strong ammonia alkali solution of calcium nitrate and diammonium hydrogen phosphate (5:3 in molar ratio) and subsequent calcination in the range of 105-700 degrees C. From infrared (IR) analysis, the carbonate ions substituted both phosphate ions and hydroxyl ions in the hydroxyapatite lattice; the intensities of IR bands assignable to phosphate ions and hydroxyl ions were reduced on calcinations. The specific surface areas of synthesized apatites decreased with increasing calcination temperature. Blood-clotting properties were evaluated in terms of active partial thromboplastin time, prothrombin time, and the amount of fibrinogen for the plasma in contact with the apatites, indicating that all the apatites barely influenced the blood clotting system. The apatites were in contact with a solution containing both bovine serum albumin (BSA) and beta(2)-microglobulin (beta(2)-MG), and the amounts of those proteins adsorbed on them were examined: the amount of absorbed BSA and beta(2)-MG gradually increased with the calcination temperature below 500 degrees C, while it showed a sudden increase when more than 600 degrees C. Hydroxy-carbonate apatite synthesized under a 15% CO(2)-containing N(2) atmosphere and calcined below 400 degrees C had the greatest selectivity in adsorbing beta(2)-MG. Thus, a higher selectivity for beta(2)-MG adsorption was empirically correlated to carbonate ions incorporated in the hydroxyapatite lattice.

Staphylococcus aureus adhesion to titanium oxide surfaces coated with non-functionalized and peptide-functionalized poly( l-lysine)- grafted-poly(ethylene glycol) copolymers

Implanted biomaterials are coated immediately with host plasma constituents, including extracellular matrix (ECM); this reaction may be undesirable in some cases. Poly( l-lysine)- grafted-poly(ethylene glycol) (PLL- g-PEG) has been shown to spontaneously adsorb from aqueous solution onto metal oxide surfaces, effectively reducing the degree of non-specific adsorption of blood and ECM proteins, and decreasing the adhesion of fibroblastic and osteoblastic cells to the coated surfaces. Cell adhesion through specific peptide-integrin receptors could be restored on surfaces coated with PLL- g-PEG functionalized with peptides of the RGD (Arg–Asp–Gly) type. To date, no study has examined the effect of surface modifications by PLL- g-PEG-based polymers on bacterial adhesion. The ability of Staphylococcus aureus to adhere to the ECM and plasma proteins deposited on biomaterials is a significant factor in the pathogenesis of medical-device-related infections. This study describes methods for visualizing and quantifying the adhesion of S. aureus to smooth and rough (chemically etched) titanium surfaces without and with monomolecular coatings of PLL- g-PEG, PLL- g-PEG/PEG-RGD and PLL- g-PEG/PEG- R DG . The different surfaces were exposed to S. aureus cultures for 1–24 h and bacteria surface density was evaluated using scanning electron microscopy and fluorescence microscopy. Coating titanium surfaces with any of the three types of copolymers significantly decreased the adhesion of S. aureus to the surfaces by 89–93% for PLL- g-PEG, and 69% for PLL- g-PEG/PEG-RGD. Therefore, surfaces coated with PLL- g-PEG/PEG-RGD have the ability to attach cells such as fibroblasts and osteoblasts while showing reduced S. aureus adhesion, resulting in a selective biointeraction pattern that may be useful for applications in the area of osteosynthesis, orthopaedic and dental implantology.

Competitive adsorption of plasma proteins on polysaccharide-modified silicon surfaces

ABSTRACTThe initial response of blood exposed to an artificial surface is the adsorption of blood proteins that triggers a number of biological reactions such as inflammation and blood coagulation. Competitive protein adsorption plays a key role in the hemocompatibility of the surface. The synthesis of nonfouling surfaces is therefore one of the major prerequisites for devices for biomedical applications. Polysaccharides are the main components of the endothelial cell glycocalyx and have the ability to reduce nonspecific protein adsorption and cell adhesion and, therefore, are generally coupled with a wide variety of surfaces to improve their biocompatibility. We have developed a procedure for covalently binding dextran and sodium hyaluronate (HA) on silicon wafers and we have been able to achieve a high level of control over the surface properties of the coatings. In the present research effort we focus on a detailed investigation of competitive bovine serum albumin (BSA) and bovine fibrinogen (Fg) adsorption on dextran- and HA-modified silicon surfaces. Polysaccharide based biomimetic layers preferentially adsorb BSA and, in general, strongly suppress protein adsorption with respect to bare silicon and APTES-activated silicon surfaces used as control.

Competitive interfacial adsorption of blood proteins

The competitive adsorption of blood proteins is of great importance for the treatment of thrombosis using a colloidal drug delivery system. The aim of this study is to investigate competitive adsorption of albumin (BSA) and human immunoglobulin G (HIgG) against fibrinogen (Fb). The competitive adsorption of blood proteins was investigated using interfacial rheology at physiological pH. The influence of bulk concentration, temperature and pH on the interfacial adsorption of protein molecules was determined at the air/aqueous interface. As expected, the results indicated that increase in bulk concentration enhanced the interfacial adsorption. Structure and molecular weight of the protein molecules under investigation had influence on interfacial adsorption leading to a competition at the interface. HIgG is more flexible and surface active molecule than BSA. Thus, HIgG replaced BSA and Fb at the air/aqueous interface. In the presence of Fb, BSA adsorbed rapidly initially and then, was replaced by Fb at the interface. The kinetics of displacement of albumin at the interface was rather slow. In conclusion, the investigation of competitive adsorption of blood proteins may be useful biotechnologically, as it will provide useful information for the production of an antithrombogenic material, which will adsorb albumin rather than Fb.

Use of ultrathin shell microcapsules of hepatocytes in bioartificial liver-assist device.

We previously encapsulated hepatocytes in ultrathin shell microcapsules and showed them to have enhanced differentiated functions over cells cultured in monolayer. Here we have used these microencapsulated hepatocytes in a bioartificial liver-assisted device (BLAD) with a rat hepatectomy model. Primary rat hepatocytes were encapsulated in 150- to 200-microm microcapsules, using an electrostatic droplet generator. The microencapsulated hepatocytes exhibited good in vitro urea synthesis activity in plasma from rats with fulminant hepatic failure (FHF). The ex vivo hemoperfusion was conducted in FHF rats by perfusing plasma at a rate of 1-2 mL/min through 1.5-2 x 10(8) encapsulated hepatocytes packed into a packed-bed bioreactor. Hemoperfusion with the bioreactor was initiated 5 h after operative induction of liver failure and continued for 7 h. The BLAD-treated rats showed improvements over the control groups in survival time and metabolic indicators, including ammonia and total bilirubin levels. Furthermore, expanded bed adsorption (EBA) detoxification technology using Streamline-SP resin was explored to complement the bioreactor with microencapsulated hepatocytes. In vitro experiments indicated that serum ammonia could be specifically removed in dose-dependent manner, whereas the total serum proteins were unaffected by the resin. In ex vivo experiments, hemoperfusion with the resin was initiated 3 h after operative induction of liver failure and continued for 7 h. The resin-treated rats showed obvious serum ammonia removal with no observable total blood protein and blood cell adsorption. Therefore, Streamline-SP resin can potentially be integrated into a BLAD for improved efficacy.

Poly(ethylene glycol)-grafted poly(3-hydroxyundecenoate) networks for enhanced blood compatibility

Poly(ethylene glycol)-grafted poly(3-hydroxyundecenoate) (PEG- g-PHU) networks were prepared by irradiating homogeneous solutions of poly(3-hydroxyundecenoate) (PHU) and the monoacrylate of poly(ethylene glycol) (PEG) with UV light. The resulting polymer networks were characterized by measuring the water contact angle, water uptake, and mechanical properties and by performing attenuated total reflectance infrared spectroscopy and scanning electron microscopy. These measurements showed that the PEG chains were present in polymer networks. Adsorption of blood proteins and platelets on cross-linked PHU (CLPHU) and PEG- g-PHU were examined using poly( l-lactide) (PLLA) surfaces as control. Blood proteins and platelets had significantly lower tendency of adhesion to surfaces composed of CLPHU and PEG- g-PHU networks than to PLLA. Blood compatibility of polymer networks increased as the fraction of grafted PEG increased. The results of this study suggest that PEG- g-PHU networks might be useful for blood-compatible biomedical applications.