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[C-reactive protein (CRP) as a marker of of hemodialysis biocompatibility].

Haemodialysis leads to monocytes activation and secretion of cytokines, which stimulates hepatic production of CRP. To assess the biocompatibility of haemodialysis the CRP serum levels were measured. CRP serum levels during haemodialysis with the use of cuprophane membranes increased from 4743.3 +/- 3251.6 ng/ml to 5231.8 +/- 3458.4 ng/ml just after haemodialysis and 5865.4 +/- 3684.8 ng/ml 22 hours after haemodialysis (p < 0.001). During haemodialysis using polysulfone membranes CRP from the initial value of 4819.4 +/- 4328.2 ng/ml decreased to 3316.9 +/- 3882.7 ng/ml just after haemodialysis (p < 0.01) and increased to 5086.9 +/- 4193.0 ng/ml 22 hours after haemodialysis (p < 0.05). Re-counted CRP values, according to changes in total blood protein, increased significantly (p < 0.02) 22 hours after haemodialysis with the use of cuprophane membranes. During haemodialysis using polysulfone membranes above mentioned levels were significantly decreased just after haemodialysis (p < 0.001). The cuprophane membranes surface area and reutilization of dialyzers did not affect the changes of CRP serum levels. No correlation was observed between CRP level changes and dialysis neutropenia and complement activation. Our results indicate, that CRP serum level measurement may be feasible to assess the biocompatibility of dialysis membranes.

Adult↗

Immobilization of L-asparaginase into a biocompatible poly(ethylene glycol)-albumin hydrogel: evaluation of performance in vivo.

The L-asparaginase of Escherichia coli (ASNase) is currently used in combination with antineoplastic drugs to treat various lymphoblastic leukaemias. However, its use is limited by severe immunological reactions and the short serum half-life associated with the enzyme. Immobilization of ASNase into a biocompatible matrix can greatly decrease the immunogenicity of the enzyme, increase its half-life in vivo and its therapeutic index. Thus the E. coli ASNase was immobilized in a biocompatible hydrogel made of rat serum albumin and poly(ethylene glycol) (PEG; molecular mass 10 kDa). The effectiveness of this enzymic bioreactor to deplete serum L-asparagine was evaluated after its peritoneal implantation in rats. Seven units of immobilized ASNase/rat depleted serum asparagine to an undetectable level (< 1 microM) during 6 days, while 5 units of immobilized ASNase/rat decreased the level of serum asparagine by 85-90% during at least 2 days. Under both conditions asparagine levels returned to normal about 10 days after surgery, and hydrogels still retained 80% of their enzymic activity when assayed in vitro. After 10-14 days in vivo, hydrogels became opaque and surrounded by a fibrotic capsule with a few inflammatory sites. Nevertheless, the enzymic hydrogel showed great stability in vivo, and, after 4 months of implantation, 12% of the initial ASNase activity was still present. At 6 months, histological analysis showed stabilization of the fibrotic capsule thickness. Assays on the levels of ASNase and asparagine synthetase indicated an induction of the latter activity, mainly in the pancreas when compared with the level observed in spleen or liver. ELISA tests at 28 days and 120 days showed the presence of anti-ASNase (and, in lower amounts, anti-PEG) antibodies in sera of implanted rats. As observed with other enzyme-immobilization systems used in vivo, the formation of fibroblast-like cell layers around the implant, which block the translocation of the substrate into the enzymic matrix, is the major factor affecting the performance and longevity of the bioreactor.

Albumins↗

Biocompatibility of dentine-bonding agents. 2. Pulpal considerations.

The paper reviews the literature concerning the biocompatibility of dentine-bonding agents. The literature review indicates that two main hypotheses are presented to explain pulpal inflammation following the placement of materials such as dentine-bonding agents, namely material toxicity and bacterial infection. The paper discusses the role of such factors as microbial microleakage, remaining dentine thickness and the smear layer as factors in determining material toxicity and summarises the reported biocompatibility studies. From this it is concluded that most bonding agents contain constituents which have a potential irritant or toxic effect on the pulpo-dentinal complex. The irritant effect may be due to constituents of the bonding agents, or to poor or lost bonding, or to a combination of all these factors. The recently favoured total-etch technique may cause an increase in dentine permeability by removal of the smear layer and thereby increase the irritant effect of some materials.

Animals↗

Biocompatibility and degradation of collagen bone anchors in a rabbit model.

Bone anchors are used to fasten tendons and ligaments to bone during reconstructive surgery. Although metal anchors are often used, an anchor that could resorb and permit normal bone regeneration would be advantageous. The objective of the study was to evaluate the biocompatibility and degradation of bone anchors that consist of collagen-based bodies, ceramic washers, and polyester sutures. Eighteen rabbits underwent bilateral implantations in the distal femoral condyles. Nine animals received glutaraldehyde-crosslinked fibrillar collagen bone anchors (FC) and nine received glutaraldehyde-crosslinked fibrillar collagen bone anchors containing tricalcium phosphate (FC-TCP). Three animals per group were sacrificed at postimplantation weeks 1, 6, and 12. One femur from each rabbit was evaluated histologically, and the contralateral side underwent biomechanical pull-out testing. Histological evaluation of the implant site indicated that the FC and FC-TCP bone anchors were both biocompatible. The FC-TCP formulation degraded earlier than the FC formulation, and FC-TCP showed significant degradation at 6 weeks; the FC and FC-TCP formulations both showed similar amounts of degradation at 12 weeks. The degrading anchor bodies appeared to be osteoconductive as evidenced by new bone ingrowth into the degrading collagen matrices without a fibrous interface. These results suggest that collagen-based bone anchors have potential as bioresorbable orthopedic implants.

Animals↗

Mechanical properties, phase stability, and biocompatibility of (Y, Nb)-TZP/Al(2)O(3) composite abutments for dental implant.

ZrO(2)/Al(2)O(3) composites were prepared by mixing a tetragonal ZrO(2), stabilized by 5.31 mol% Y(2)O(3) and 4.45 mol% Nb(2)O(5), and various amounts of Al(2)O(3). Influence of the amount of Al(2)O(3) on strength and toughness and tetragonal phase stability in the composites under autoclave conditions was investigated. In addition, in vitro and in vivo biocompatibility of the composites was examined. The composite, prepared with addition of 20 vol% Al(2)O(3), exhibited the highest strength of 700 MPa and toughness of 8.1 MPa. m(1/2) and showed no hydrothermal degradation while aging in an autoclave. The biocompatibility of the composite exhibited no cytotoxicity and no significant adverse soft-tissue response for up to 3 months implant period in guinea pigs.

Aluminum Oxide↗

Suitability of cellulose molecular dialysis membrane for bioartificial pancreas: in vitro biocompatibility studies.

The success of immunoisolation devices for islet transplantation depends on the properties and biocompatibility of semipermeable immunobarrier membranes. In the present study, we have evaluated the in vitro biocompatibility of the cellulose membrane Spectra/Por 2 (MW no larger than 12- 14,000) for its possible application in islet immunoisolation. The membrane was found to be hydrophilic (octane contact angle: 153.2+/-0.66 degrees) and exhibited decreased protein adsorption. It showed mechanical stability after 1 month of storage in PBS (pH 7.4) with tensile strength, percent elongation, and Young's modulus of 88.88 MPa, 36.22, and 291.8 MPa, respectively. It allowed regulated transport of glucose and insulin in an in vitro diffusion assay. The high viability of NIH3T3 fibroblasts and the inability of lymphocytes to proliferate in vitro on exposure to the membrane leach-out products suggested its noncytotoxic and nonimmunogenic nature. Macrophages, when cultured on membranes, did not show increased expression of inflammatory surface marker such as CD11b/CD18, CD45, CD14, and B 7.2. Image analysis studies showed integrity and intact morphology of mouse islets cultured on and inside the membranes with high viability (91%, 89.7%). These islets also retained their functionality, as judged by insulin secretion. The present study provides sufficient documentation to consider cellulose molecular dialysis membrane Spectra/Por 2 (MW no larger than 12-14,000) as a potential candidate for immunoisolation of islets.

3T3 Cells↗

Water-soluble carbosilane dendrimers: synthesis biocompatibility and complexation with oligonucleotides; evaluation for medical applications.

Novel amine- or ammonium-terminated carbosilane dendrimers of type nG-[Si{OCH2(C6H3)-3,5-(OCH2CH2NMe2)2}]x, nG-[Si{O(CH2)2N(Me)(CH2)2NMe2}]x and nG-[Si{(CH2)3NH2}]x or nG-[Si{OCH2(C6H3)-3,5-(OCH2CH2NMe3 +I-)2}]x, nG-[Si{O(CH2)2N(Me)(CH2)2NMe3 +I-}]x, and nG-[Si{(CH2)3NH3 +Cl-}]x have been synthesized and characterized up to the third generation by two strategies: 1) alcoholysis of Si--Cl bonds with amino alcohols and subsequent quaternization with MeI, and 2) hydrosilylation of allylamine with Si--H bonds of the dendritic systems and subsequent quaternization with HCl. Quaternized carbosilane dendrimers are soluble in water, although degradation is apparent due to hydrolysis of Si--O bonds. However, dendrimers containing Si--C bonds are water-stable. The biocompatibility of the second-generation dendrimers in primary cell cultures of peripheral blood mononuclear cells (PBMCs) and erythrocytes have been analyzed, and they show good toxicity profiles over extended periods. In addition, we describe a study on the interactions between the different carbosilane dendrimers and DNA oligodeoxynucleotides (ODNs) and plasmids along with a comparative analysis of their toxicity. They can form complexes with DNA ODNs and plasmids at biocompatible doses via electrostatic interaction. Also a preliminary transfection assay has been accomplished. These results demonstrate that the new ammonium-terminated carbosilane dendrimers are good base molecules to be considered for biomedical applications.

Cell Survival↗

Preliminary biocompatibility screening of several biodegradable phosphate fiber reinforced polymers.

This article describes preliminary biocompatibility screening of three degradable phosphate fibers containing K +, Ca +2/Na + and Na +/Ca +2/Al +3 ions in the polymer chain, and of several different degradable polymers reinforced with these fibers. Biodegradable phosphate fibers of calcium-sodium-metaphosphate (CSM) and sodium-calcium-aluminum-polyphosphate (NCAP) were acutely nontoxic in cellular, tissue, and whole animal evaluations, as determined by standard acute toxicity tests. Histological studies of bone implants sites fabricated from composites of copolymers of poly(E-caprolactone/L-lactide) and poly(ortho ester) reinforced with either CSM or NCAP fibers showed these composite materials to be nontoxic, with no abnormal inflammatory response. However, histological evaluation of muscle implants sites revealed the appearance of necrotic foci associated with implant sites in 12 of 22 NCAP containing composite specimens (p less than 0.05). Results of this preliminary biocompatibility screening suggest CSM fibers may be useful in reinforcing degradable polymers for production of completely biodegradable composites for implant use.

Animals↗

In vivo biocompatibility of an acrylic, fluoride-releasing, anion-exchange resin.

This study evaluated the biocompatibility of an unfilled, fluoride-releasing acrylic resin by subcutaneous implantation in guinea pigs. The experimental fluoride resin was compared to a nonfluoride, dental pit and fissure sealant (DELTON) of similar composition. Thirty-four male albino guinea pigs received four Teflon tubes each, implanted in the dorsal area. The tubes were open at both ends, three contained the experimental fluoride resin and one held the nonfluoride resin. The tubes and surrounding tissue were excised in 1-2 cm blocks, by necropsy, at 14 and 84 days. Histological evaluation showed that inflammatory response was none-to-slight at 14 days for 95% of the fluoride and 100% of the nonfluoride specimens. Five percent of the fluoride specimens produced a moderate tissue response. At 84 days, inflammatory response was none-to-slight for 82.5% of the fluoride and 61.5% of the commercial nonfluoride specimens, while 17.5% of the fluoride and 38.5% of the nonfluoride specimens produced moderate tissue responses. Chi-squared analysis and Fisher's Exact test revealed no statistically significant difference (p less than or equal to 0.05) in tissue response between the two resins at either 14 or 84 days. Hence it is concluded that the experimental, fluoride-releasing resin produces a very mild subcutaneous tissue response and that its biocompatibility is comparable to that of a widely used nonfluoride dental resin. It can, therefore, be considered as having a high potential for biological safety as a dental restorative resin or adhesive, or for other biomedical applications.

Acrylic Resins↗

Ion-selective membranes with low plasticizer content: electroanalytical characterization and biocompatibility studies.

High molecular weight poly(vinyl chloride) and aliphatic polyurethane (Tecoflex)-based ion selective membranes, with normal and reduced amounts of plasticizer, as well as without plasticizer, were tested with respect to their analytical properties, their biocompatibility, and cellular responses. The analytical properties of the membranes did not change significantly within a wide range of polymer to plasticizer ratios. However, the membranes with reduced plasticizer content had better adhesive properties, less anion interference, extended life time, and better biocompatibility. Using the cage implant system, the results showed that an increase of plasticizer weight percent in Tecoflex membranes correlated positively with the increase in host inflammatory response up to 14 days of implantation. The results also demonstrated that both PVC and Tecoflex-based ion-selective membranes with the most common membrane composition (1:2 polymer to plasticizer ratio) exhibited a similar acute inflammatory response, but the PVC-based membrane elicited a reduced chronic inflammatory response when compared with the Tecoflex-based membrane.

Adhesiveness↗

The biocompatibility and osteoconductivity of a cement containing beta-TCP for use in vertebroplasty.

A new composite bone cement designated "G2B1" was developed for percutaneous transpedicular vertebroplasty. G2B1 contains beta tricalcium phosphate particles and methylmethacrylate-methylacrylate copolymer as the powder components, and methylmethacrylate, urethane dimethacrylate, and tetrahydrofurfuryl methacrylate as the liquid components. Biocompatibility and osteoconductivity were evaluated using scanning electron microscopy, contact microradiography, and Giemsa surface staining 4, 8, 12, 26, and 52 weeks after implantation into rat tibiae. To evaluate osteoconductivity, affinity indices (%) were calculated. Scanning electron microscopy and contact microradiography revealed that bone contact with G2B1 was attained within 4 weeks (affinity index: 50.2 +/- 11.8 at 4 weeks) and at most of the margin within 26 weeks (affinity index: 87.4 +/- 7.2 at 26 weeks). Specifically, G2B1 contacted bone via a wide calcium-phosphate-rich layer, and its degradation started within 8 weeks, mainly in the marginal area. Giemsa surface staining showed that there was almost no inflammatory reaction around the G2B1. These results indicate that G2B1 is a biocompatible and osteoconductive bone cement.

Animals↗

Biocompatibility of a new radiopaque iodine-containing acrylic bone cement.

Radiopacity in the vast majority of the commercially available acrylic bone cements that are used clinically is provided by particles of either BaSO(4) or ZrO(2). Literature reports have shown these agents to have a detrimental effect on some mechanical properties of the cements as well as on its biological response. We, therefore, have developed a new type of bone cement, for which radiopacity results from the presence of an iodine-containing methacrylic copolymer. The focus of the present work was the comparison of the biocompatibility of this new cement and a commercially available cement that contains barium sulfate. In vitro experiments show that both cements are cytocompatible materials, for which no toxic leachables are found. Implantation of the cements in a rabbit for three months resulted in the occasional presence of a thin fibrous tissue at the cement-bone interface, which is common for acrylic bone cements. Consideration of all the results led to the conclusion that the new cement is as biocompatible as the BaSO(4)-containing one.

Animals↗

Mechanical and biocompatible influences of chitosan fiber and gelatin on calcium phosphate cement.

Calcium phosphate cement (CPC) is a widely used bone substitute in the clinic; however, the low strength of CPC limits its utilization. In this study, we investigated mechanical influences of chitosan fiber combined with gelatin on CPC, and examined the biocompatibility of the new composite with rat bone marrow stromal cells. Compared to the fiber impregnated in phosphate buffered saline (80.5 MPa), our study showed that tensile strength of chitosan fiber increased 106 and 114% with the impregnation of gelatin at the mass fraction 5 and 10%, although this increase was not statistically significant. It was demonstrated by Fourier transform infrared spectroscopy that the characteristic absorption bands of chitosan were changed with the addition of gelatin. The optimal flexural strength enhancement was obtained when CPC was reinforced with fiber at volume fraction of 30% and gelatin at mass fraction of 5% (maximum: 12.31 MPa). The fiber morphology was more compact when the chitosan fibers impregnated with gelatin at mass fraction of 5 or 10% than chitosan alone. The fracture analysis showed that the new CPC-chitosan fiber-gelatin composite presented many remnants of CPC adhered to fibers. Short minimum essential medium extract test showed no cell growth inhibition after the addition of the new composite. Rat bone marrow stromal cells retain the ability to spread and grow on the composite. Our studies demonstrated that the flexural strength is greatly increased by using CPC incorporated with proper ratio of CF and gelatin. More over, the new composite demonstrated biocompatibility in vitro.

Animals↗

[Biocompatibility of flexible intraocular lenses in vivo].

PURPOSE: One aspect of biocompatibility of IOLs can be tested using specular microscopy of the anterior and posterior surface of the lens in vivo. METHODS: We examined 45 patients after implantation of a "Memory lens" and 31 patients after the implantation of an "Acrysof" lens 3-6 months after surgery. RESULTS: Typical deposits (Lens epithelial cells, spindle-shaped macrophages, giant cells, pigment, Wolter membrane) were rarely seen on both types of lenses. There were fewer lens epithelial cells on the posterior capsule and less secondary cataract after implantation of the "Acrysof" lens. CONCLUSIONS: We did not find any indication of reduced biocompatibility in any of the lenses examined. The reduced rate of secondary cataract after implantation of the "memory lens" may be explained by the fact that this lens type sticks to the posterior capsule better.

Aged↗

[Histological studies of retinal degeneration and biocompatibility of subretinal implants].

Two basic biological premises determine the success of replacement of degenerated photoreceptors by a technical implant. First, the neuronal network in the residual retina of patients selected for implantation must still be capable of processing technically generated signals. Secondly, the implant itself must be biocompatible with tissue, i.e. it may not itself induce further degeneration. Our studies in animal models with advanced retinal degeneration and with donor retinas of retinitis pigmentosa patients have shown that even after complete destruction of the photoreceptors and long periods of blindness, the inner retina in the macular area remains for the most part histologically intact, and that all neurons are demonstrably still present and capable of successfully transmitting and processing signals. Biocompatibility of subretinal implants was studied in pigs. After 14 months of implantation, histological examination of tissue covering the implant showed that the inner retina was completely intact. There were no signs of histopathologic changes.

Animals↗

Biocompatibility testing of novel multifunctional polymeric biomaterials for tissue engineering applications in head and neck surgery: an overview.

Biomaterial research and tissue engineering are rapidly growing scientific fields that need an interdisciplinary approach where clinicians should be included from the onset. Biocompatibility testing in vitro and in vivo comprise the agarose-overlay test, the MTT test, direct cell seeding tests and the chorioallantoic membrane test for angiogenic effects, among others. Molecular biology techniques such as real-time polymerase chain reaction and microarray technology facilitate the investigation of tissue integration into biomaterials on a cellular and molecular level. The physicochemical characterization of biomaterials is conducted using such methods as X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Excellent biocompatibility and biofunctionality were demonstrated for a series of recently developed multifunctional biodegradable, polymeric biomaterials both in vitro and in vivo. Novel, multifunctional polymeric biomaterials offer a highly specific adjustment to the physiological, anatomical and surgical requirements and can thereby facilitate new therapeutic options in head and neck surgery.

Absorbable Implants↗

Preliminary in vivo biocompatibility studies on perfluorosulphonic acid polymer membranes for biosensor applications.

The first biocompatibility studies on the DuPont perfluorosulphonic acid polymer (Nafion) are presented. Presterilized samples of commercially cast and solution cast Nafion membranes were implanted subcutaneously, intraperitoneally and intravenously in male Sprague-Dawley rats. Scanning electron microscopy and histological examination of explanted samples and surrounding tissues reveal little, if any, evidence of acute or chronic foreign body inflammatory response. The fibrous capsules surrounding the implant remain nominally thin (less than 100 microns) after more than 3 months in situ, while the surrounding tissue remains well vascularized. Nafion polymer exhibits sufficient biocompatibility to make it a viable candidate for some implantable biosensor applications. It may, however, be necessary to compensate for the effect of the progression of fibrous encapsulation on sensor performance, particularly during the acute response stage.

Abdominal Muscles↗

Biocompatibility of surfaces for antibody microarrays: design of macroporous silicon substrates.

Major efforts to develop antibody microarray technology to enable global proteome analysis to be performed in a facile manner are under way. In this process, the design and the properties of the substrate will play crucial roles. In the present study, we have developed novel, highly biocompatible solid supports for microarrays, using adsorbed recombinant human single-framework antibody fragments as probes. Several silicon-based supports, including planar silicon, micro- and macroporous silicon, and nitrocellulose-coated variants thereof, were designed and evaluated in a stepwise procedure. The surfaces were scored based on biocompatibility and probe binding capacity as judged by spot morphology, signal intensities, signal to noise ratios, dynamic range, sensitivity, and reproducibility. A set of five commercially available substrates, selected to represent a set of supports providing different surface and coupling chemistries, was used as reference surfaces. The results showed that several well-performing silicon-based supports could be designed; in particular, a nitrocellulose-coated macroporous variant, MAP3-NC7, received the highest scores. In comparison, MAP3-NC7 displayed properties equal to or better than those of the reference substrates. Taken together, designed surfaces based on silicon can undoubtedly meet the requirements of the next generation of solid supports for antibody microarrays.

Antibodies↗