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Influence of two blood conservation techniques (cardiotomy reservoir versus cell-saver) on biocompatibility of the heparin coated cardiopulmonary bypass circuit during coronary revascularization surgery.

Blood conservation during cardiac surgery is critically important because of the inherent risks in homologous blood transfusions. Two techniques for the intraoperative conservation of blood--retransfusion of the red cells using a cell-saver (CS), or retransfusion of the blood using a cardiotomy suction (CTR) system--were compared using biocompatibility markers, granulocyte activation, and production of oxygen-free radicals (OFR). In the CTR group, heparin coated circuits with an uncoated cardiotomy reservoir were used. For the CS group, identical heparin coated cardiopulmonary bypass (CPB) sets, without a cardiotomy reservoir but with a CS, were used. In each group, eight patients had coronary artery bypass grafting performed. The capacity of the whole blood and the granulocytes to produce OFR was estimated by a chemiluminescence, and granulocyte activation was measured as release of the granulocyte granule proteins myeloperoxidase (MPO) and lactoferrin. A significantly reduced capacity to produce OFR by the whole blood was noted at 45 minutes of CPB in the CTR group (68% +/- 17% vs 94% +/- 16% in the CS group). MPO release was higher after 3 hours (p = 0.05) and 20 hours (p < 0.05), postoperatively, in the CTR group (417 +/- 77 micrograms/L and 257 +/- 31 micrograms/L vs 246 +/- 25 micrograms/L and 164 +/- 12 micrograms/L, respectively, in the CS group). We conclude that the heparin coated CPB circuit with the uncoated cardiotomy reservoir may be less biocompatible than the identical CPB set used together with the CS.

Biocompatible Materials↗

Light and electron microscopic evaluation of biocompatibility, resorption and penetration characteristics of human collagen graft material.

This study was initiated to test the biocompatibility, resorption and penetration characteristics of human collagen graft material in vitro and in vivo using light (LM) and electron microscopy (EM). To study this relationship, pieces of glutaraldehyde cross-linked collagen sponges (1 x 1 x 0.5 cm), were: (1) cultured in sterile Petri dishes with human gingival fibroblasts and human periodontal ligament fibroblasts for 2 weeks; (2) implanted in subcutaneous pockets made in both thighs (total 20 sites) of 10 Sprague-Dawley rats for 7-56 days. The behaviour of the growth of the fibroblasts was studied by inverted light microscopy (LM), then tissue culture specimens were studied from without and within using low-temperature scanning electron microscopy (LTSEM). Blocks obtained from the graft sites of the rat were processed for LM and transmission EM. Long-term LM observations showed attachment and random orientation of cells on and around the collagen sponge in culture during the first 48 h. Between 7 and 14 days, the majority of the cells adjacent to the sponge were orientated at right angles to its margin with their long axes approximately parallel to each other. The LTSEM revealed that large numbers of HGF and HPLF grew onto the collagen sponges, but no cellular penetration to the middle of the sponge was seen. LM and TEM of the rat specimens showed a cellular reaction to the collagen graft, as well as slow resorption, and fibroblast invasion of the graft at 6-8 weeks. It was concluded that the human collagen graft was biocompatible with HGF and HPLF, with penetration first observed at 42 days post-implantation. In the in vivo study, the collagen underwent slow resorption over a period of 8 weeks.

Animals↗

Biocompatibility of wound management products: a study of the effects of various polysaccharides on murine L929 fibroblast proliferation and macrophage respiratory burst.

An in-vitro screening method to examine the biocompatibility of materials used in wound management has been evaluated. This involved the use of a macrophage respiratory-burst assay and a fibroblast proliferation assay to represent respectively the inflammatory and the granulation phases in wound healing. Standard polysaccharides (calcium and sodium alginates, l-carrageenan, chitin, chitosan lactate, chondroitin sulphate and pectic acid) were used as test compounds. None of the polysaccharide samples caused a significant increase in L929 fibroblast cell numbers relative to control after 6 days incubation. The overall effect of exposure of the fibroblast cultures to the alginates, carrageenan and chondroitin sulphate was an extension of lag phase followed by an enhanced rate of cell proliferation in the logarithmic phase. Only calcium and sodium alginates and chondroitin sulphate enhanced the respiratory burst activity of murine macrophages; l-carrageenan and chitosan lactate were markedly inhibitory. The results suggest that a macrophage activity assay should be included as part of an in-vitro screening program to evaluate the biocompatibility of wound management materials and to detect intrinsic biological activity.

Alginates↗

Recording properties and biocompatibility of chronically implanted polymer-based intrafascicular electrodes.

We implanted polymer-based longitudinal intrafascicular electrodes (polyLIFEs) in feline dorsal rootlets acutely and for periods of two to six months to evaluate their electrical properties and biocompatibility. A total of 38 implanted electrodes were analyzed. Some 25 of the 38 electrodes were implanted with an insulative flexible polymer cuff, which was required for recording of afferent activity in situ. Electrode impedances remained stable for the duration of the experiments. The distributions of axons were measured at three levels of the implanted rootlets: the implant level, 1-2 mm proximal to the implant with respect to the cell body, and 1-2 mm distal to the implant with respect to the cell body. Similar measurements were made in five samples of fascicles neighboring an implant and six samples of control tissue from animals in which no implants were placed. The polyLIFEs demonstrated a high degree of biocompatibility, as no adverse effects on axon size were observed in either the implanted fascicle or neighboring neural tissue. However, the insulative cuffs were found to be a source of compression, resulting in necrosis of the neural tissue.

Animals↗

Evaluation of in vivo biocompatibility of different devices for interventional closure of the patent ductus arteriosus in an animal model.

OBJECTIVE: To evaluate the in vivo biocompatibility of three different devices following interventional closure of a patent ductus arteriosus (PDA) in an animal model. MATERIALS AND METHODS: A medical grade stainless steel coil (n = 8), a nickel/titanium coil (n = 10), and a polyvinylalcohol foam plug knitted on a titanium wire frame (n = 11) were used for interventional closure of PDA in a neonatal lamb model. The PDA had been maintained by repetitive angioplasty. Between one and 278 days after implantation the animals were killed and the ductal block removed. In addition to standard histology and scanning electron microscopy, immunohistochemical staining for biocompatibility screening was also undertaken. RESULTS: Electron microscopy revealed the growth of a cellular layer in a cobblestone pattern on the implant surfaces with blood contact, which was completed as early as five weeks after implantation of all devices. Immunohistochemical staining of these superficial cells showed an endothelial cell phenotype. After initial thrombus formation causing occlusion of the PDA after implantation there was ingrowth of fibromuscular cells resembling smooth muscle cells. Transformation of thrombotic material was completed within six weeks in the polyvinylalcohol plug and around the nickel/titanium coil, and within six months after implantation of the stainless steel coil. An implant related foreign body reaction was seen in only one of the stainless steel coil specimens and in two of the nickel/titanium coil specimens. CONCLUSION: After implantation, organisation of thrombotic material with ingrowth of fibromuscular cells was demonstrated in a material dependent time pattern. The time it took for endothelium to cover the implants was independent of the type of implant. Little or no inflammatory reaction of the surrounding tissue was seen nine months after implantation.

Animals↗

Biocompatibility of glass-encapsulated electronic chips (transponders) used for the identification of pigs.

The biocompatibility of electronic transponders encapsulated in two different types of glass was studied after they had been implanted subcutaneously into pigs for the purpose of identification. Rods of white crystal glass or green iron-containing glass were screened for superficial impurities by scanning electron microscopy and X-ray analysis, revealing a few crystalline and plaque impurities which were similar for both types of glass, and no differences in elemental composition. In vitro cytotoxicity tests using cell cultures of human dermal fibroblasts and haemolysis and clot formation tests in human blood after contact with the rods, showed that both types of glass were biocompatible. When implanted subcutaneously at the base of the ears of pigs for from three to 150 days, both types of transponder appeared to induce a similar connective tissue capsule, on average less than 0.2 mm in thickness, surrounding the rods. A classic foreign body reaction did not occur. It is concluded that the fibrous capsules were due to scar tissue formed around the glass rods as a result of the tissue being damaged when they were implanted. There were no significant differences between the reactions to the two types of glass. The subcutaneous implantation of glass-encapsulated transponders appears to be a good method for identifying pigs.

Animal Identification Systems↗

Dacron-covered stent-grafts for the percutaneous treatment of carotid aneurysms: effectiveness and biocompatibility--experimental study in swine.

PURPOSE: To evaluate the short-term effectiveness and biocompatibility of Dacron-covered stent-grafts for percutaneous treatment of carotid aneurysms. MATERIALS AND METHODS: In eight swine, nine aneurysms were created surgically in the common carotid artery. Percutaneous treatment was performed with Dacron-covered stent-grafts. Seven of eight swine underwent follow-up angiography at 2, 3, 4, and 5 weeks after stent implantation. Histologic examinations of tissue from the site of stent implantation were performed at the same intervals. RESULTS: Initial closing off of the aneurysm was possible in all swine. Angiographic follow-up revealed patency of only one Dacron-covered stent-graft after 2 weeks. In six of seven swine, the stent was occluded on the follow-up angiogram. One of the swine died of unclear cause after 1 week. The stent-graft of this swine was not occluded. In all Dacron-covered stent-grafts, inflammatory reaction with granulocyte infiltration was found next to the Dacron material. CONCLUSION: Primary treatment of carotid aneurysms with Dacron-covered stent-grafts is effective. However, the short-term patency rate is poor, which probably can be attributed to the limited biocompatibility of the Dacron cover. An acute inflammatory reaction against Dacron seems responsible for the poor patency rate.

Angiography, Digital Subtraction↗

The biocompatibility of silicone, fluorosilicone and perfluorocarbon liquids as vitreous tamponades. an ultrastructural and immunohistochemical study.

PURPOSE: To investigate the interactions occurring at the interface between some currently used vitreous tamponading substances and the ocular tissues, in an early follow-up after surgery. METHODS: Adult albino rabbit eyes underwent vitrectomy and were injected intravitreally with silicone oils at 1,000 or 3,000 cSt, fluorosilicone oil and perfluorodecalin. Different morphological techniques (light microscopy, scanning and electron microscopy, immunohistochemistry) were applied. RESULTS: All the tested materials, although non-toxic, penetrate the ocular tissues also at the anterior segment level, and in the long-term follow-up this can yield functional impairment. No massive inflammation has been detected in the zones in contact with the materials, but immunoglobulins and complement fractions are anyway present in the stroma of various tissues and around the droplets of emulsified materials, suggesting a local immune reaction. CONCLUSIONS: Data from this study confirmed that a permanent vitreous substitute, showing a perfect biocompatibility, still does not exist. The indication to remove the tamponading substance within 2 months after the surgery emerges from this investigation, confirming previous studies. Despite some negative features, silicone oil still appears the most biocompatible material for vitreous replacement.

Animals↗

Membrane biocompatibility does not affect whole body protein metabolism during dialysis.

BACKGROUND: Protein-calorie malnutrition is present in 30-50% of dialysis patients. The lack of biocompatibility of the dialysis membrane, which results in low-grade inflammation, could be responsible for this malnutrition. We investigated whether protein-energy malnutrition could be partly due to incompatibility of the dialyzer during the dialysis session. METHODS: Five patients were dialyzed during 2 periods of 3 weeks (cross-over) with either a single-use low-flux polysulfone or cellulose triacetate (biocompatible) or a single-use cuprophan (bio-incompatible) membrane. As a measure of whole body protein metabolism, a primed constant infusion of L-[1-(13)C]-valine was used during a 4-hour dialysis session. RESULTS: Cuprophan was a more powerful activator of the complement system than other membranes. Protein metabolism parameters during both study protocols were not different and resulted in the same protein balance during polysulfone/cellulose triacetate (-15 +/- 3) and cuprophan (-13 +/- 2 micromol/kg/h) dialysis. CONCLUSION: In stable hemodialysis patients with no apparent complications, protein metabolism during dialysis is not affected by the compatibility of the dialysis membrane.

Amino Acids↗

Comparative cell culture effects of shape memory metal (Nitinol), nickel and titanium: a biocompatibility estimation.

Nitinol is an equiatomic alloy of nickel and titanium which has been attracting increasing interest in the field of biomedical engineering. To quantify toxicity as a preliminary evaluation of biocompatibility, inhibition of mitosis in human fibroblasts in tissue cultures exposed to test materials is an accepted screening method, although a dose-effect relationship had never been investigated. In this experiment, the effect of an increasing dose exposure to Nitinol, nickel or titanium on human fibroblasts in cell cultures was tested in subgroups in comparison with a control group. The results showed that nickel induces a significant (p < or = 0.05) inhibition of mitosis in human fibroblasts, whereas no significant effects of this kind were found for titanium or Nitinol. According to the results of these studies, Nitinol is to be considered in this respect biocompatible and comparable to titanium, which would seem to justify application as a surgical implant.

Alloys↗

Interleukin 8 and biocompatibility of dialysis membranes.

To determine whether interleukin 8 (IL-8) can be used as an index of biocompatibility of dialysis membranes, the effects of hemodialysis (HD) on plasma IL-8 levels and the expression of IL-8 mRNA in peripheral blood mononuclear cell (PBMC) were compared among regenerated cellulose (RC), polyacrylonitrile (PAN) and polymethylmethacrylate (PMMA) dialyzers. HD using RC dialysers significantly increased plasma IL-8 levels and induced abundant expression of IL-8 mRNA in PBMC. HD using PMMA dialyzers also increased plasma IL-8 levels and induced slight expression of IL-8 mRNA. In contrast, HD using PAN dialyzers neither increased plasma IL-8 levels nor induced the expression of IL-8 mRNA. In vitro studies demonstrated that IL-8 was considerably adsorbed by PAN membranes and not at all by RC and PMMA. These studies indicate that plasma IL-8 level and expression of PBMC IL-8 mRNA can be used as indices of biocompatibility of dialysis membranes.

Acrylic Resins↗

Biocompatibility aspects of cellophane, cellulose acetate, polyacrylonitrile, polysulfone and polycarbonate hemodialyzers.

The biocompatibility of cuprammonium rayon (Cu), cellulose acetate, polysulfone (Ps) and polyacrylonitrile hollow-fiber dialyzers and a polycarbonate-polyether flat plate dialyzer has been investigated. The Cu dialyzer resulted in more complement activation and a greater degree of leukopenia than the others, while the Ps hollow-fiber dialyzer appeared to be the most biocompatible of the membrane equipment in this study. These results were confirmed by in vitro evaluations and microscopic examinations of the different dialyzers.

Acrylic Resins↗

Biocompatibility and hemodynamic studies during polycarbonate versus cuprophane membrane dialysis.

A new noncellulosic membrane (polycarbonate) has been tested in terms of biocompatibility and hemodynamic tolerance. The following results were obtained: The polycarbonate membrane manufactured by Gambro Hechingen induces activation of the complement system (slight decrease of CH50 and C3, no increase of C5a) to lower extent and causes a less severe leukopenia than the cuprophane membrane. During dialysis with the polycarbonate membrane hypoxemia does not occur and the pulmonary vascular resistances and pulmonary arterial pressure remain stable. The good biocompatibility of the polycarbonate membrane allows a better outcome of hemodialysis treatments.

Acetates↗

Performance and biocompatibility of the FD 100 Gambrane hollow-fiber dialyzer.

In order to obtain performance data and biocompatibility characteristics of the two new Gambrane FD 100 polycarbonate hollow-fiber dialyzers (y-sterilized, dry or prefilled with isotonic saline) a paired in vivo evaluation was carried out. The measured data indicate that residual blood volume and small molecular weight clearances of Gambrane hollow-fiber dialyzers are not significantly different from comparable Cuprophan dialyzers. Small molecular clearance values are not affected by the significantly different ultrafiltration coefficients of the two tested FD 100 dialyzers. Biocompatibility of Gambrane as reflected by white blood cell count, platelet count and C3d is superior to Cuprophan.

Biocompatible Materials↗

Biocompatibility of different hemodialysis and plasmapheresis membranes.

The biocompatibility of different membranes was assessed by measuring changes in different white blood cell counts, PGE2 concentrations, thromboplastin activity, production of anaphylatoxins and clinical parameters during treatment. The in vivo recorded complement activation was compared with in vitro experiments. Hemodialysis (HD) treatment was performed with 5 different membranes. Plasmapheresis was run with cellulose diacetate membranes in single (SMF) and double (DMF) membrane filtration and with a new polycarbonate membrane in SMF. The polysulfone membrane was found to be the most, and the cuprophane membrane the least biocompatible membrane in HD. However, large individual differences from one HD patient to the other were found. In contrast to the cellulose diacetate membrane, the polycarbonate membrane apparently activated no complement along the blood-membrane interface during plasmapheresis, but activated large amounts within the membrane matrix. High blood concentrations of C5a were promptly cleared in the body, while high concentrations of C3a seemed to block the removal of this substance from the blood compartment. Even when the patients had high blood concentrations of anaphylatoxins throughout the plasmapheresis treatments using cellulose diacetate membranes and when a significant activation of PGE2 was found in patient plasma, no activation of thromboplastin was recorded on the surface circulating monocytes.

Biocompatible Materials↗

Isocyanate-terminated urethane prepolymer as bioadhesive material: evaluation of bioadhesion and biocompatibility, in vitro and in vivo assays.

Attempts have been made to evaluate the degree of bioadhesion and biocompatibility of a synthesized urethane prepolymer with specially tailored microstructure. Wetting behaviour and extent of interfacial adhesion of the prepared prepolymer towards biological substrates were examined by in vitro methods. The former was carried out by measuring the contact angle between drops of the prepolymer liquid and a biological surface, while the latter was determined from the force between the prepolymer and tissue model or mucus. The obtained results exhibited good tissue wettability and bioadhesion by the prepolymer. Preliminary evaluation of biocompatibility for the uncatalytically cured prepolymer films was performed by cytotoxicity and histotoxicity experiments. Results showed a significant growth for the adhered L929 fibroblast cells within a period of 5 days incubation. Also, no severe inflammatory tissue response towards the samples implanted in rabbit for 16 weeks was seen. These observations can support the potentiality of the designed urethane prepolymer to be applied as hemostatic agent.

Adhesiveness↗

Biocompatibility of platinum-metallized silicone rubber: in vivo and in vitro evaluation.

Silicone rubber is commonly used for biomedical applications, including implanted cuff electrodes for both recording and stimulation of peripheral nerves. This study was undertaken to evaluate the consequences of a new platinum metallization method on the biocompatibility of silicone rubber cuff electrodes. This method was introduced in order to allow the manufacture of spiral nerve cuff electrodes with a large number of contacts. The metallization process, implying silicone coating with poly(methyl methacrylate) (PMMA), its activation by an excimer laser and subsequent electroless metal deposition, led to a new surface microtexture. The neutral red cytotoxicity assay procedure was first applied in vitro on BALB/c 3T3 fibroblasts in order to analyze the cellular response elicited by the studied material. An in vivo assay was then performed to investigate the tissue reaction after chronic subcutaneous implantation of the metallized material. Results demonstrate that silicone rubber biocompatibility is not altered by the new platinum metallization method.

Animals↗

Assembly of multilayer microcapsules on CacO3 particles from biocompatible polysaccharides.

Multilayer microcapsules were fabricated by layer-by-layer (LbL) assembly of natural polysaccharides onto CaCO3 particles, following with core removal. The micron-sized CaCO3 particles were synthesized by reaction between Ca(NO3)2 and Na2CO3 solutions in the existence of carboxylmethyl cellulose (CMC). The incorporated amount of CMC in the CaCO3 particles was found to be 5.3 wt% by thermogravimetric analysis. Two biocompatible polysaccharides, chitosan and sodium alginate were alternately deposited onto the CaCO3(CMC) templates to obtain hollow microcapsules. Regular oscillation of surface charge as detected by zeta potential demonstrated that the assembly proceeded surely in a LbL manner. The stability of the microcapsules was effectively improved by cross-linking of chitosan with glutaraldehyde. The chemical reaction was verified by infrared spectroscopy. The microcapsules thus fabricated could be spontaneously filled with positively charged low molecular weight substances such as rhodamine 6G and showed good biocompatibility, as detected by in vitro cell culture.

Alginates↗