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Biocompatibility and fatigue properties of polystyrene-polyisobutylene-polystyrene, an emerging thermoplastic elastomeric biomaterial.

This paper will discuss the biocompatibility and dynamic fatigue properties of polystyrene-b-polyisobutylene-b-polystyrene thermoplastic elastomer with 30 wt % polystyrene (SIBS30), an emerging FDA-approved biomaterial. SIBS30 is a very soft, transparent biomaterial resembling silicone rubber, with superior mechanical properties. Using the hysteresis method adopted for soft biomaterials, the dynamic fatigue properties of SIBS30 were found to be between those of polyurethane and silicone rubber, with fatigue life twice as long as that of silicone. Under single load testing (SLT, 1.25 MPa), SIBS30 displayed less than half the dynamic creep compared to silicone, both in air and in vitro (37 degrees C, simulated body fluid). Hemolysis and 30- and 180-day implantation studies revealed excellent biocompatibility of the new biomaterial. The results presented in this paper indicate that, in comparison with silicone rubber, SIBS30 has similar biocompatibility and superior dynamic fatigue properties.

Animals↗

Facile synthesis of highly biocompatible poly(2-(methacryloyloxy)ethyl phosphorylcholine)-coated gold nanoparticles in aqueous solution.

Diblock copolymers comprising a highly biocompatible poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC) block and a poly(2-(dimethylamino)ethyl methacrylate) (PDMA) block were evaluated for the synthesis of sterically stabilized gold nanoparticles in aqueous solution. The PDMA block becomes partially protonated on addition of HAuCl4, and the remaining nonprotonated tertiary amine groups reduce the AuCl4- counterion to zerovalent gold in situ. This approach results in the adsorption of the PDMA block onto the gold nanoparticle surface while the PMPC chains serve as a stabilizing block, producing highly biocompatible gold sols in aqueous solution at ambient temperature without any external reducing agent. The size and shape of gold nanoparticles could be readily controlled by tuning synthesis parameters such as the block composition and the relative and absolute concentrations of the PMPC-PDMA diblock copolymer and HAuCl4. These highly biocompatible gold sols have potential biomedical applications.

Biocompatible Materials↗

Correlation between the physicochemical properties of organic solvents and their biocompatibility toward epoxide hydrolase activity in whole-cells of a yeast, Rhodotorula sp.

Epoxides are often highly hydrophobic substrates and the presence of an organic co-solvent within an aqueous bioreactor is in such cases indicated. The effect of 40 water-miscible and -immiscible organic solvents on epoxide hydrolase activity in whole-cells of the yeast Rhodotorula sp. UOFS Y-0448 was investigated. No formal correlation between solvent biocompatibility and physicochemical properties was deductible, although the introduction of hydroxyl groups increased biocompatibility. 1-Pentanol, 2-methylcyclohexanol and 1-octanol were the most biocompatible resulting in relatively low activity losses when used at up to 20% (v/v).

Biocompatible Materials↗

Rapid biocompatible micro device fabrication by micro electro-discharge machining.

Fabrication of a biocompatible micro device is predominantly done by silicon micromachining techniques. The lithographic and etching techniques require preparation and the use of masks which are time consuming and costly. Since bio research involves highly complex mechanisms, the modeling and simulation is difficult and experimental study is inevitable. To incorporate frequent design changes and to realize the hardware quickly, fabrication processes, complementary to the silicon micromachining techniques are required. In the present work the feasibility of using micro electro-discharge machining (EDM) for the fabrication of biocompatible microdevice has been studied. Micro channels with feature size as small as 25 microm are realized. The process is further improved by the introduction of ultrasonic vibration of the workpiece and the total time taken for the hardware realization is about 4 hours. The effects of ultrasonic vibration on the roughness of the spark eroded surface has been studied and reported. The potential of using micro EDM for making biocompatible devices for bio experiments is demonstrated and the surface finish achieved is well within the recommended Rz and Ra values of 3.4 and 0.4 microm respectively for biological studies like implant abutment.

Biocompatible Materials↗

Effect of membrane composition and structure on solute removal and biocompatibility in hemodialysis.

Effect of membrane composition and structure on solute removal and biocompatibility in hemodialysis. Significant changes in extracorporeal membranes have occurred over the past five decades in which hemodialysis (HD) has been available as a therapy for both acute renal failure (ARF) and end-stage renal disease (ESRD). For cellulosic membranes, these changes have included a reduction in thickness, hydroxyl group substitution, and an increase in pore size. These modifications have resulted in enhanced efficiency of small solute removal, a broader spectrum of overall solute removal, and an attenuation of complement activation in comparison to the thick, unsubstituted cellulosic membranes of low permeability used in the early days of HD therapy. Synthetic membranes, originally developed specifically for use in high-flux HD and hemofiltration, have also evolved during this same time period. In fact, the initially clear distinction between low-flux regenerated cellulosic and high-flux synthetic membranes has become blurred, as membrane formulators have developed products designed to appeal to enthusiasts for both membrane formats. The purpose of this review is to characterize both the solute removal and biocompatibility characteristics of dialysis membranes according to their composition (that is, polymeric makeup) and structure. In this regard, the manner in which membrane biocompatibility interacts with flux is highlighted.

Biocompatible Materials↗

Increased reduction of dimethylarginines and lowered interdialytic blood pressure by the use of biocompatible membranes.

Hypertension contributes to cardiac and cerebrovascular complications in HD patients. Endogenous inhibitors of nitric oxide synthase accumulate in renal failure and may interfere with the regulation of vascular tone. We investigated the elimination of asymmetric dimethylarginine (ADMA) by using biocompatible Polyamide Strade mark membranes in low-flux (Polyflux 6L) or high-flux (Polyflux 14S) hemodialysis or hemodiafiltration (HDF) compared with hemodialysis with cellulosic membranes. Removal rates for ADMA, symmetric dimethylarginine (SDMA), and beta2-microglobulin significantly increased in HDF. The plasma total amino acid concentration and the arginine/ADMA ratio increased, and the mean 24-hour blood pressure decreased during the study. In a second study, we investigated whether plasma amino acids and interdialytic blood pressure are influenced by the use of a biocompatible membrane and HDF. Seventeen end-stage renal disease patients were treated for six weeks with hemodialysis using cellulosic membranes, six weeks with low-flux hemodialysis using Polyflux 6L, and six weeks with HDF using Polyflux 14S. Only in the diabetic patients were the hemoglobin concentration (from 10.6 +/- 1.5 to 11.9 +/- 0.6 mg/dL) and hematocrit (from 33.6 +/- 1.9 to 36.2 +/- 1.5%) increased significantly, whereas the mean 24-hour systolic blood pressure decreased (from 154 +/- 22 to 129 +/- 18 mm Hg). No significant changes were observed in nondiabetic patients. We conclude that primarily diabetic patients seem to benefit from the use of biocompatible membranes--most in HDF--after a period of six weeks. The regulation of nitric oxide pathways by ADMA removal and changed ADMA/arginine ratio might be contributing factors. Further prospective studies are required to show whether the long-term application of HDF or other changes of dialysis treatment modalities may help to improve well-being, morbidity, and mortality in hemodialysis patients.

Adult↗

Serum neopterin monitoring and vitamin E-modified, regenerated hemodialyzer membrane influence on biocompatibility.

The exposure of blood to hemodialysis membranes results in numerous phenomena and/or complications in hemodialyzed patients, which have an influence on the quality of life (QOL) of those patients. A vitamin E-modified regenerated cellulose membrane (E-membrane) was developed to act as a scavenger for reactive oxygen species causing complications in hemodialysis patients. Neopterin (NEOP) is a metabolite derived from guanosine triphosphate with the production and release of NEOP being induced in monocytes and macrophages by cytokines such as interferon-gamma (IFN-gamma). Serum neopterin levels are shown to be a reactive marker of bioincompatibility of dialysis membranes in hemodialysis patients. The following report evaluates the usefulness of serum NEOP as a marker for the biocompatibility of the E-membrane hemodialyzer in a clinical study. In the clinical study, where extracorporeal ultrafiltration strategies with E-membranes were employed, the serum levels of NEOP were lower than those in patients using cellulose triacetate membranes (C-membranes). In the long-term evaluation of the biocompatibility of E- and C-membranes, the increase of serum neopterin levels in the C-membrane was higher than those in the E-membrane. In conclusion, the evaluation of serum neopterin levels during hemodialysis shows that the E-membrane has a good biocompatibility in hemodialyzed patients.

Adult↗

Biocompatibility of a biodegradable, controlled-release polymer in the rabbit brain.

The biodegradable polyanhydrides are a new class of controlled release polymers developed for the interstitial delivery of drugs to their target site in the brain or other organs over periods ranging from days to years. These polymers can release molecules of any size in a predictable fashion. Their degradation products are non-cytotoxic and biocompatible. The biocompatibility of a biodegradable polyanhydride, the copolymer of poly[bis(p-carboxyphenoxy)propane] anhydride and sebacic acid (PCPP-SA) in a 50:50 formulation, was studied in the rabbit brain. Twenty adult New Zealand White male rabbits underwent implantation of PCPP-SA in a frontal lobe and absorbable gelatin sponge (Gelfoam) in the other frontal lobe. The animals were evaluated daily until the time of sacrifice. Groups of four animals were sacrificed sequentially on post-operative days 1, 3, 7, 21, and 60, and the brains processed for histological evaluation. None of the animals showed behavioral changes or neurological deficits suggestive of toxicity and all that received implants survived to their date of sacrifice. The histological examination showed no significant differences between the tissue reaction from PCPP-SA compared to Gelfoam. The polymers were also tested in the rabbit cornea bioassay and did not induce an inflammatory response. We conclude that PCPP-SA (50:50), a new biodegradable polymeric matrix that can be surgically implanted for the interstitial delivery of drugs in the brain, is biocompatible in the rabbit brain.

Animals↗

In vivo biocompatibility and degradation studies of polyhydroxyoctanoate in the rat: a new sealant for the polyester arterial prosthesis.

The present study examined the biocompatibility and degradation properties of poly (beta-hydroxy octanoate) (PHO) as an impregnation substrate on arterial prostheses. PHO-impregnated polyester grafts sterilized by ethylene oxide (EO) or gamma (gamma) radiation, and polyester Dacron(R) prostheses impregnated with fluoropolymer, gelatin, or albumin were implanted subcutaneously in rats for periods ranging from 2 to 180 days. The biocompatibility was assessed by quantifying the alkaline and acid phosphatase secretion while performing histological studies at the tissue/prosthesis interface. The degradation was determined by chemical analysis of the EO and gamma-sterilized PHO after implantation using differential scanning calorimetry (DSC), wide angle x-ray diffraction (WAXD), and size exclusion chromatography (SEC). Alkaline phosphatase activity by the sterilized PHO and by the gelatin and albumin grafts was significantly elevated early after implantation in contrast to that of the Dacron and fluoropolymer grafts that occurred later, at 7 and 5 days, respectively The peak of acid phosphatase activity for all of the grafts occurred between 5 and 10 days postimplantation, with the gamma-sterilized PHO grafts recording the greatest activity. Histological study revealed that the tissue incorporation into the graft wall was earlier and more complete for the Dacron and fluoropolymer grafts after 6 months than for the gelatin and albumin grafts, because the latter induced important inflammatory reactions during the resorption of the cross-linked protein substrates. The EO and gamma-sterilized PHO grafts exhibited a similar healing sequence characterized by the development of a collagenous tissue surrounding the prostheses. However, no infiltration of tissue into the graft wall was observed after 6 months, mainly because of the presence of the PHO. Degradation of the EO and gamma-sterilized PHO occurred preferentially by a hydrolytic mechanism as shown by a 30% molecular weight decrease after 6 months. In conclusion, PHO showed good biocompatibility in terms of enzyme activity and tissue reaction. Degradation was a slow, in vivo process controlled primarily by a random hydrolytic reaction and by a local enzymatic attack by macrophages and giant cells.

Acid Phosphatase↗

Synthetic modification of PAN membrane: biocompatibility and functional characterization.

A disturbing interaction of PAN membranes and the bradykinin generation system particularly in the presence of angiotensin converting enzyme inhibitors has been described. A modified new membrane, SPAN (special PAN), was produced by varying the polymer components in type and composition, in particular by a reduction in Na-Methallylsulfonate. Although the SPAN membrane successfully averted the bradykinin generating ability of PAN, it was important to determine whether such a modification did not lead to a loss of the satisfactory biocompatibility profile characteristic of the parent membrane. For this purpose, we conducted the present clinical study in nine patients comparing 3 membranes; (i) a polysulphone membrane (F60S); (ii) PAN; and (iii) SPAN, to examine the clinical biocompatibility profile and performance of the new membrane. A small increase in C5a with F60S and SPAN was found which is in the range expected for highly biocompatible synthetic membranes. The three dialysers had a similar inert profile for terminal complement complex arterial values, and had similar venous values. A minimal nonsignificant decline in white cell count was observed at 15 min for all dialysers, but otherwise WBC counts were unchanged. Platelet counts were unchanged throughout treatment for the three dialysers. Arterial and venous thrombin-anti-thrombin complex values were similar for all three dialysers. F60S and SPAN dialysers had similar urea clearances.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of dialyser biocompatibility on recovery from acute renal failure after cadaver renal transplantation.

BACKGROUND: It has been reported that patients with acute renal failure (ARF) requiring haemodialysis show an improved recovery of renal function when the dialysis treatment is performed using a biocompatible membrane rather than a bioincompatible membrane. However, most recent published human trials have not been able to confirm these findings. METHOD: Over a 2-year period, we prospectively studied 53 patients with ARF after cadaver renal transplantation who required haemodialysis and randomized them into two treatment groups. One group underwent dialysis with a cuprophane membrane and the other group underwent haemodialysis with a more biocompatible membrane, polysulfone. All patients received an immunosuppressive regimen which included azathioprine, prednisone and cyclosporine. RESULTS: There was no difference by patient characteristics or immunosuppressive regimen before acute tubular necrosis (ATN) recovery. In both groups the number of haemodialysis sessions required prior to the recovery of renal function (6.57+/-2.79 vs 6.05+/-2.40), the number of oliguric days (16.25+/-5.14 vs 14.40+/-4.67) and the number of hospital days (33.38+/-12.85 vs 30.10+/-11.00), were not statistically different. There was also no difference in long-term allograft outcome. CONCLUSION: Our data demonstrate that the use of a more biocompatible membrane had no influence on the recovery from acute renal failure after renal transplantation.

Acute Kidney Injury↗

Heparins and blood polymorphonuclear stimulation in haemodialysis: an expansion of the biocompatibility concept.

BACKGROUND: At the concentrations used in haemodialysis and in a dose-dependent way, unfractionated heparin (UFH) and, to a lesser degree, a low-molecular-weight heparin (LMWH) stimulate polymorphonuclear cells (PMN) in vitro, and could act in synergy with the stimulatory effect of dialysis membranes in vivo. To examine this hypothesis, we studied the effects of different heparin types and regimens on blood PMNs during haemodialysis sessions. METHODS: Ten haemodialysed patients were studied during regular dialysis sessions on a cellulose triacetate membrane (CT 110 G; 1.10 m(2); Baxter), with four different random heparin protocols: one high-UFH regimen (HHR) at 90 IU/kg body-weight (b.w.) and one low-UFH regimen (LHR) at 50 IU/kg b.w., and with a LMWH (nadroparin calcium) at 85 (HHR) or 45 (LHR) IU/kg b.w. Blood granulocytes, platelet counts, and plasma granulocyte degranulation products (elastase, lactoferrin) were measured serially during 4 h dialysis sessions. RESULTS: After 10 min, the reduction in PMNs with UFH was 29.5% for HHR (P<0.01) and 28.5% for LHR (P<0.01), and only 16.8 and 18.6% with LMWH (NS), significantly higher for HHR with UFH than with LMWH (P<0.01). At 60 min, the elastase increase with HHR was greater, 61% with UFH (P<0.01) and 37.8% with LMWH (P<0.01), significantly higher than LHR for UFH (P<0.05) or LMWH (P<0.05). The overall decrease in platelets (with LMWH P<0.01) and the overall increase in lactoferrin (P<0.001) were not different between heparinization procedures. CONCLUSION: Under a conventional heparin regimen, the PMN variation during the course of the dialysis session suggests a more biocompatible effect of LMWH over UFH. In addition, the variation of elastase favours the lower dose, whatever the type of heparin. Heparin type and dose should therefore be considered in studies addressing biocompatibility in haemodialysis: a low dose of LMWH may be viewed as a better biocompatible treatment with regard to leukocyte stimulation.

Adult↗

Efficiency and biocompatibility of a polyethylene glycol grafted cellulosic membrane during hemodialysis.

Dialytic efficiency and biocompatibility of a new modified cellulose membrane (NMC) were examined in vitro and clinically. NMC was obtained by grafting polyethylene-glycol (PEG) chains to the membrane surface of ordinary cellulose (OC), and it was expected that the random movement of PEG chains would prevent blood cells and large plasma proteins from coming into contact with the membrane surface, resulting in improving the biocompatibility and thrombogenicity of the membrane. Surface characteristics of NMC were rendered anionic and hydrophilic, however, the activations of complement and platelet systems were clearly suppressed in NMC. Minimum heparin requirement for hemodialysis was significantly lower with NMC than with OC dialyzer. No significant difference in solute and water removal was observed between the two dialyzers. These results indicate that NMC can provide increased biocompatibility and antithrombogenic effect while retaining the essential dialysis efficiency of OC.

Biocompatible Materials↗

Nitric oxide gas infusion to the oxygenator enhances the biocompatibility of heparin coated extracorporeal bypass circuits.

Heparin coated bypass circuits have been reported to improve the biocompatibility of extracorporeal circulation, although it is still insufficient and improvable. Nitric oxide (NO) is known to inhibit platelet activation and inflammatory reactions. In this study, the authors evaluated exogenous NO infusion in enhancing the effect of a heparin coated bypass circuit on the biocompatibility of an extracorporeal circuit, especially in view of the attenuation of the inflammatory response. A miniature closed bypass circuit, including an oxygenator (BioActive surface; Carmeda, Stockholm, Sweden) was primed with fresh human heparinized blood and perfused with a centrifugal pump. Either pure N2 gas (control group: n = 7) or NO gas (NO group [100 ppm in N2]: n = 7) was infused to the oxygenator. NO metabolites (nitrite and nitrate), platelet count, thrombin-antithrombin III complex (TAT), alpha2-plasmin-plasminogen inhibitor complex (PIC), beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), serotonin, complement 3 activation products (C3a), granulocyte elastase, and bradykinin were measured at 0, 30, 60, 120, and 180 min after starting perfusion. At every sampling point, platelet counts were significantly higher, and TAT, beta-TG, and bradykinin were lower in the NO group than in the control group. PF4, C3a, and granulocyte elastase were significantly lower in the NO group at 60, 120, and 180 min. These results suggest that NO gas infusion to the oxygenator enhances the biocompatibility of heparin coated extracorporeal circuits.

Biocompatible Materials↗

Biocompatibility of radiolucent breast implants.

Current implants for breast augmentation containing silicone gel, saline, or both are radiopaque on mammographic examination and can totally obscure microcalcifications and soft-tissue masses. The effect of these implants on the detection of early breast cancers in patients who have undergone augmentation mammaplasty remains unproven and controversial. Implants filled with medium-chain triglycerides (peanut oil) are radiolucent on mammographic examination and allow visualization of both soft-tissue masses and microcalcifications. To investigate the biocompatibility of radiolucent implants, 10 cc of sterile, nonpyrogenic peanut oil was injected subcutaneously into rats using silicone gel as a control. Twenty-one rabbits had two 125-cc silicone shell implants inserted on either side of the chest wall. The right-sided shell was filled with 125 cc of sterile saline, and the left-sided shell was filled with 125 cc of sterile, nonpyrogenic peanut oil. Results were determined by both histologic and radiographic examination. Rats injected with peanut oil equivalent to 7 percent of their body weight rapidly absorbed the freely injected oil without detriment. Histologic examination of the lungs, liver, kidneys, and tissues adjacent to the injection sites demonstrated no abnormalities. There was no evidence of allergic, toxic, inflammatory, or neoplastic response. Eighteen of 21 rabbits survived more than 3 months. Radiographs showed the oil-filled implants to be radiolucent, whereas the saline-filled controls obscured the surrounding soft and bony tissues. Histologic examination demonstrated a fibrous capsule surrounding both types of implants. Histologic examination of the lungs, liver, and kidneys showed no significant abnormalities. These and previous studies have shown peanut oil to be biocompatible when freely injected either intramuscularly or subcutaneously. This study demonstrates that a radiolucent, peanut oil-filled implant is biocompatible in animals and that further long-term studies for its use in humans are merited.

Animals↗

Evaluation of artecoll polymethylmethacrylate implant for soft-tissue augmentation: biocompatibility and chemical characterization.

Artecoll polymethylmethacrylate implant (Artecoll) is a combination of polymethylmethacrylate beads suspended in 3.5% atelocollagen and has been designed for use in soft-tissue augmentation applications. The biocompatibility and immunogenicity of Artecoll were evaluated to assess the safety of this product for use in the dermis. To characterize the collagen component, chemical analysis was performed including trypsin sensitivity, differential scanning calorimetry, and pepsin content. Particle size analysis was also performed on the polymethylmethacrylate beads. The ability of this material to elicit an immunologic response was measured in a sensitized and nonsensitized guinea pig intradermal model. In these studies, 24 guinea pigs were injected intradermally with either Artecoll or Zyderm, a bovine collagen product for soft-tissue augmentation. Six sites were evaluated for each material at 3, 7, and 28 days after injection. In the sensitized model, 60 guinea pigs were divided into five groups, and each group received a sensitizing dose (in conjunction with Freund's adjuvant) of Zyderm, Artecoll, or a nonsensitizing dose of the same materials. The fifth group served as a nontreatment control. After the animals were sensitized, they were challenged with intradermal injections of various antigens to evaluate delayed type hypersensitivity reactions. Chemical characterization indicated polymethylmethacrylate beads of varying sizes, including many less than 35 microns, and a vehicle of extensively denatured and impure collagen. In vivo evaluations indicated that Artecoll elicited an immune response in guinea pigs, including delayed type hypersensitivity and antibody reactions. Histological assessment demonstrated particle phagocytosis and transepidermal elimination. Following immunization with Artecoll, guinea pigs were also found to be sensitized to pepsin, an impurity found in the collagen carrier. The biocompatibility of this material was compared with that of bovine dermal collagen (Zyderm collagen implant), which is widely used and accepted as biocompatible. The results of this evaluation indicate that Artecoll polymethylmethacrylate implant has the potential to elicit an immune response in humans, and polymethylmethacrylate beads are susceptible to phagocytosis and elimination.

Adjuvants, Immunologic↗

Biocompatibility in haemodialysis: fact and fiction.

Several of the pro-inflammatory pathways that are activated in patients during dialysis have the potential of producing many side effects. These occur three times a week, accompanying dialysis, and are particularly intense in patients dialysed with so-called 'bioincompatible' membranes. Despite the proven biological superiority of biocompatible membranes, we lack definitive evidence that complement and cell activation three times a week over a period of years is detrimental to patients, because the results of prospective randomized studies are conflicting. Although they do not lead to a decrease in acute clinical symptoms, epidemiological studies suggest that semi-synthetic and synthetic membranes may reduce morbidity and mortality in dialysis patients. Further large scale, prospective and randomized trials with a long follow-up are needed in order to clarify the clinical effects of biocompatibility per se, the increasingly recognized clinical importance of high-flux treatments and the possible interaction between biocompatibility and membrane flux.

Biocompatible Materials↗

In vivo study on the biocompatibility of newly developed calcium phosphate-based root canal sealers.

This study compared the biocompatibility of two new calcium phosphate-based root canal sealers (CAPSEAL I, CAPSEAL II) with another type of commercially available calcium phosphate sealer (Apatite Root Sealer type I, Apatite Root Sealer type II) and a zinc oxide eugenol-based sealer (Pulp Canal Sealer EWT) after implanting them in the subcutaneous tissue of rats. After 1, 2, 4, and 12 weeks, the tubes were removed with the surrounding tissues. The tissue reactions were graded as being mild or 1, moderate or 2, and severe or 3 after a histopathological examination. The results were analyzed statistically with the Kruskal-Wallis test. The biocompatibility of the materials was interpreted according to the Federation Dentaire Internationale criteria (1980). The inflammatory reactions decreased with time. The new sealers showed a lower tissue response than any of the other sealers in all the experimental periods. All the tested sealers showed an acceptable biocompatibility.

Animals↗