Biomaterials, artificial cells, and immobilization biotechnology : official journal of the International Society for Artificial Cells and Immobilization Biotechnology最新文献

Applications of alginate polylysine (APL) microcapsules in cell culture engineering and hybrid artificial organs require strict control of membrane permeability. For example, hybrid artificial organs must permit the diffusion of smaller molecules including peptides and proteins and the exclusion of leucocytes and immunoglobulins (MW > 150,000). Single molecular weight solutes such as proteins have been used to study the molecular weight cut-off of the membrane. A new approach that uses a heterogenous mixture of dextrans of different molecular weights: -MW 10,000-500,000 as a test solute in diffusion experiments is described. Intra/extra capsular changes in concentration and molecular weight distribution of the heterogenous dextran mixture are monitored and determined by high performance gel chromatography. MW can then be related to diffusional Stokes radius, a more useful parameter when comparing permeability of cell membrane to different test solutes.

Poly(D,L-lactide-co-glycolide) (PLG, 90:10) microspheres containing 20% norethisterone (NET) were prepared by solvent evaporation method. Microspheres in the size ranges of 65 to 100 microns were sterilized by irradiation and used for further study. In vitro release showed fairly constant release of NET from the above microspheres over more than 90 days. However, in vivo drug release determined by residual NET analysis after i.m. injection in rats indicated a faster release rate. About 95% of NET was released in a period of 45 days. At the dose of 80 mg of microspheres, vaginal estrus cycles were inhibited for 45 days compared to 27 days for the same dose of NET crystals in rats. Biodegradation of the microspheres was tested by direct measurement of molecular weight losses and SEM observation of morphological changes of the microspheres, which showed continuous erosion in the internal matrix of microspheres with the decrease of molecular weight of PLG until total collapse of microspheres, and biodegradation was faster in rats than in human serum at 37 degrees C in vitro. Total degradation of 90:10 PLG microspheres was less than 7 months in rats and more than 9 months in vitro.

After first adventurous attempts to apply perfusion techniques to the treatment of liver diseases, more extensive experiences have been acquired in the last twenty years, not only in acute hepatic failure but also in some chronic liver diseases (mainly in CAH:chronic active hepatitis, and in primary biliary cirrhosis) and in a severe complication of them, that is cryoglobulinemia. Some experiences on this field that are found in literature, using both plasma exchange and hemoperfusion, are reviewed and some personal data are reported: 15 patients with acute viral liver failure (survival rate: 33%) and 5 patients with a CAH-linked (3 viral and 2 autoimmune) cryoglobulinemia, in whom a good control of the disease parameters was obtained.

A preliminary, comparative biological evaluation of two new families of non-ionic telomeric surfactants derived from Tris(hydroxymethyl)acrylaminomethane (THAM) is reported. These trisacryl conjugates, or TAC, were designed with the purpose of improving the stability and biocompatibility of fluorocarbon emulsions to be used in injectable oxygen-delivering systems. Their amphiphilic character arises from the simultaneous presence in the same molecule of several hydrophilic THAM residues and of a hydrophobic tail consisting in either a hydrocarbon (H-TAC family) or a fluorocarbon (F-TAC family) chain. The acute toxicity in mice after intravenous injection is low (LD50 in the 625 to 1250 mg/kg body weight range for the H-TAC compared to 630 to 4500 mg/kg body weight range for F-TAC) and increases with the length of the hydrophobic chain. No hemolytic activity was detected for the F-TAC at concentrations up to 200 g/l, while hemolysis is found for the H-TAC at a concentration of 5 g/l or less and increases with the alkyl chain length. The impact of the new surfactants on the growth and viability of Namalva cell cultures also increases with the length of the hydrophobic chain, with again a better tolerance for the F-TAC. Altogether the fluorinated amphiphiles display better tolerance than their hydrocarbon analogs in spite of their significantly increased surface activity. Both families of compounds appear to have potential as strongly hydrophilic surfactants for biomedical applications.

Rat islets encapsulated in the immuno-isolated membrane were transplanted intraperitoneally into 11 streptozotocin induced diabetic mice. The effective rate was 91% while all rejected in the 11 nonencapsulated xenograft group. 4 mice showed complete remission and longest normoglycemic period in those mice was 360 days. The pathological changes of islets of the long-term successful xenograft group were studied and showed atrophy. It proved that the immuno-isolated membrane can protect rejection during xeno-transplantation.

Little is known about the microvascular effects of blood replacement solutions. This study was undertaken to develop an animal model suitable for studies of the microcirculatory effects of such solutions and to investigate microvascular responses to isovolemic transfusion with stroma-free hemoglobin (SFH), whole donor blood, or a new potential blood substitute solution containing oxypolyhemoglobin (OPH) as an oxygen carrier. Hamster livers were exposed and the microcirculation studied using intravital epifluorescent video microscopy. 33% blood volume replacement with SFH elevated systemic blood pressure by 25 Torr. Accompanying this increase in pressure was a 36% decrease in sinusoidal blood flow velocity and a 10% decrease in terminal hepatic venular diameters. Terminal portal venular diameters did not change. Decrease in liver sinusoidal perfusion was not due to neutrophil mediated injury, as myeloperoxidase activity in jejunum, liver, kidney, and lung remained unchanged. The reduction in perfusion was likely due to systemic vasoconstriction produced by SFH. In contrast, transfusion with whole blood did not change any of the measured parameters showing the excellent stability of the model. OPH transfused animals exhibited only a small 10 Torr transient increase in MAP 15 min post-transfusion. By 30 min MAP returned to the pre-infusion value. No significant changes were observed in either venular diameters or sinusoidal velocities in this group of animals. These results demonstrate suitability of this model for studies of the microcirculatory and hemodynamic effects of blood replacement solutions. Furthermore, OPH solution produced only minor transient disturbances in microvascular and systemic parameters.

Polyacrylate based microbeads were prepared by copolymerization of four different acrylate monomers, namely 2-hydroxyethylmethacrylate (HEMA), ethyleneglycoldimethacrylate (EGDMA), methylmethacrylate (MMA) and dimethylaminoethylmethacrylate (DMEAMA). These beads were further activated with CNBr at alkaline pH. The extend of nonspecific adsorption and covalent coupling of heparin on these beads were investigated in a batch reactors at different temperatures. The effects of initial concentrations of activation agent and heparin were also studied. Nonspecific heparin adsorption on the microbeads containing DMAEMA was significantly higher than the others. Nonspecific adsorption decreased with increasing temperature. Heparin was covalently coupled on CNBr activated microbeads. The amount of coupled heparin increased by increasing concentration of CNBr.

The complexity of platelet mediated hemostasis has hindered development of a platelet substitute for transfusion therapy. In the current study, the hemostatic efficacy of a liposome based modality, the plateletsome, is demonstrated. A deoxycholate extract of a platelet membrane fraction, with a minimum of 15 proteins including GPIb, GPIIb-IIIa and GPIV/III, was incorporated into sphingomyelin: phosphatidylcholine: monosialylganglioside or egg phosphatide small unilamellar vesicles by reverse-phase/sonication and French press extrusion. These plateletsomes decreased bleeding by 67% in the tail bleeding time in rats made thrombocytopenic (platelets < 30,000/microliters) with external irradiation (7-9Gy) by Cesium source. Efficacy was also demonstrated in the thrombocytopathic, Fawn-Hooded rat, but to a lesser extent than in the thrombocytopenic animals. Direct plateletsome infusion to the tail wound was more effective than systemic administration for all effective preparations. On post-mortem examination, no pathologic thrombi were detected by gross and histopathologic examination of the lungs, livers, kidneys, or spleens of thrombocytopenic or normal animals after plateletsome infusion. No evidence of intravascular coagulation, monitored by levels of circulating fibrinogen and platelet counts, was observed when plateletsomes were administered intravenously to rabbits. No deleterious effect, either inhibition or hyperaggregability, on platelet aggregation studies in vitro was observed. While further refinements are clearly required, this study indicates that liposomes bearing specific platelet proteins may provide a basis for a clinically applicable platelet substitute.

One of the criteria for the Dental Restorative Material is to not to evoke sensitization reaction when used clinically. The newly synthesized BIS-GMA based Chitra's Dental Material intended for such application was tested for skin sensitization as per the international protocol of test i.e. skin Maximization test in G.Pig. Result of this test showed conclusively that the material is devoid of sensitization potential and fit for clinical application.