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Short-term in vitro and in vivo biocompatibility of a biodegradable polyurethane foam based on 1,4-butanediisocyanate.

In this study short-term in vitro and in vivo biocompatibility apects of a biodegradable polyurethane (PU) foam were evaluated. The PU consists of hard urethane segments and amorphous soft segments based on a copolyester of dl-lactide and epsilon-caprolactone. The urethane segments are of uniform length and synthesized with 1,4-butanediisocyanate. The foam has good mechanical properties and will be used for tissue regeneration applications. Degradation tests were carried out in a buffer solution for twelve weeks. Cytotoxicity was determined using extract and direct contact test methods with incubation periods varying form 24 to 72 h. The foam was implanted subcutaneously for one, four and twelve weeks and the tissue response to the material was histologically evaluated. In vitro, the mass loss was 3.4% after twelve weeks. In the cytotoxicity tests the PU caused no abnormal growth behaviour, nor morphological changes or inhibition in metabolic activity. The in vivo studies showed no toxic tissue response to the PU. Connective tissue ingrowth, accompanied by vascular ingrowth was complete at twelve weeks. In vivo degradation had started within four to twelve weeks. In conclusion, the PU shows a good in vitro and in vivo biocompatibility in these short-term experiments.

Absorbable Implants↗

Preparation and characterization of novel biocompatible cryogels of poly (vinyl alcohol) and egg-albumin and their water sorption study.

Polyvinyl alcohol (PVA) and egg albumin are water-soluble, biocompatible and biodegradable polymers and have been widely employed in biomedical fields. In this paper, novel physically cross-linked hydrogels composed of poly (vinyl alcohol) and egg albumin were prepared by cyclic freezing/thawing processes of aqueous solutions containing PVA and egg albumin. The FTIR analysis of prepared cryogels indicated that egg albumin was successfully introduced into the formed hydrogel possibly via hydrogen bonds among hydroxyl groups, amide groups and amino groups present in PVA and egg albumin. The gels were also characterized thermally and morphologically by DSC and SEM-techniques, respectively. The prepared so called 'cryogels' were evaluated for their water uptake potential and influence of various factors such as chemical architecture of the spongy hydrogels, pH and temperature of the swelling bath were investigated on the degree of water sorption by the cryogels. The effect of salt solution and various simulated biological fluids on the swelling of cryogel was also studied. The in vitro biocompatibility of the prepared cryogel was also judged by methods such as protein (BSA) adsorption, blood clot formation and percentage hemolysis measurements.

Albumins↗

Nafamostat mesilate reduces blood-foreign surface reactions similar to biocompatible materials.

BACKGROUND: Nafamostat mesilate (FUT-175) is a synthetic serine protease inhibitor that inactivates coagulation, fibrinolysis, and platelet aggregation. Nafamostat mesilate may suppress the blood-foreign surface reaction similar to biocompatible materials by blocking factor XIIa. METHODS: We performed an in vitro study of cardiopulmonary bypass (CPB) with fresh human blood among the following three groups: standard CPB sets (C), biocompatible CPB sets (B), and standard CPB sets with FUT-175 (10 mg/L) (F). A clinical study using these same CPB groups also was performed in 45 patients undergoing aortocoronary bypass operations (15 patients each). We injected FUT-175 at 40 mg/h during CPB. RESULTS: In the in vitro study, both groups B and F showed significantly lower levels of coagulation factors, thrombin-antithrombin III complex, fibrinopeptide A, beta-thromboglobulin, complement C3a, granulocyte elastase, and free hemoglobin than group C at the conclusion of the study. Thrombin-antithrombin III complex and free hemoglobin in group F also were lower than in group B. The platelet count remained at a higher level in group F than in the other groups. Separation of bradykinin was suppressed most significantly in group F. In the clinical study, group F also showed significantly lower levels of alpha 2-plasmin inhibitor plasmin complex and C3a than both groups C and B. There were minimal levels of free hemoglobin in group F. CONCLUSIONS: Nafamostat mesilate may contribute major beneficial effects toward conservation of blood during CPB and prevention of coagulopathy after CPB.

Benzamidines↗

Biocompatibility: its future in prosthodontic research.

The future of prosthodontic research will involve replacing lost tissues by using scientific methods that evaluate biomaterials and treatment designs based on desired biologic outcomes. The present concept of a biocompatible material is one that elicits an appropriate host response in a specific application. To design optimal biomaterials, three interactive components should be considered: the chemical nature of the surface, the mediating pellicle layer, and microbial and host response. Surface chemistry determines which molecules are selectively absorbed onto a surface from oral fluids. The pellicle-coated surface should be designed to elicit a more desirable host response. Pellicle composition can be altered by chemically changing the surface, precoating surfaces with biological molecules, or using synthetic materials designed to mimic natural tissues. Several surface-sensitive techniques are available to assess these modifications, including vibrational spectroscopy, electron microscopy for chemical analysis, and bioanalytical methods. To develop more biocompatible materials, a further understanding of pellicle formation as a function of surface composition, microbial adhesion to biomaterials, and cellular reaction to implant biomaterials is necessary. This knowledge will facilitate development of new biologically based rationales for treatment modalities in restorative dentistry.

Biocompatible Materials↗

In vivo comparison of the biocompatibility of two root canal sealers implanted into the mandibular bone of rabbits.

The purpose of this study was to evaluate the in vivo biocompatibility of two zinc oxide-eugenol-based sealers, Sealite and Pulp Canal Sealer, after implantation into the mandibular bone of rabbits. Thirty female New-Zealand rabbits were randomly divided into three groups on the basis of the material to be implanted in each side of the mandible: six rabbits received a positive control implant (silicone tubes filled with asbestos) in both sides of the mandible; 12 rabbits received a Sealite implant in the left side and a negative control implant (silicone tubes filled with silicone adhesive) in the right side of the mandible; and 12 rabbits received a silicone tube filled with Pulp Canal Sealer in the left side and a negative control implant in the right side of the mandible. The sealers were implanted in a freshly mixed, unset state. The rabbits were killed 4 or 12 weeks after implantation and the implants and surrounding bone were sectioned and treated in accord with standard histologic procedures. The tissue reactions were scored and rated as none, very slight, slight, moderate, severe, and very severe. The statistical analysis of the data showed that the two sealers had similar, good biocompatibility, and that the reactions observed at the 12-week period were better than those observed at the 4-week period. Both sealers may be used indifferently in routine endodontic practice.

Alveolar Process↗

New matrix material for potential use in "reversible" vasectomy. Preliminary animal biocompatibility studies.

The biocompatibility of a new elastomeric-hydrogel matrix biomaterial for use as an intravasal occlusive device was assessed by inserting it into the vas deferens of dogs. The vas was removed and examined histologically after varying periods of time. The biomaterial resulted in total occlusion of the vas. Epithelial changes were limited to squamous metaplasia in areas adjacent to the implant. Changes in the subepithelium were minimal. This new material is biocompatible with the dog vas, and it has potential as an occlusive device for "reversible" vasectomy in men. Semen analysis studies are needed to assess the completeness and reversibility of the vasal occlusion achieved with this implant.

Animals↗

Polymer implant materials with improved X-ray opacity and biocompatibility.

Poly(methyl methacrylate) samples containing 28 wt% inorganic fillers such as zirconium oxide, barium sulphate, zinc oxide, magnesium oxide and tricalcium phosphate were prepared and studied for their suitability as implant materials by physical property tests, X-ray opacity measurement, cell culture, and animal implantations. Addition of inorganic fillers to poly(methyl methacrylate) increased the compressive strength but decreased the transverse strength. Zirconium oxide was found to be most suitable as an X-ray opaque filler, and tricalcium phosphate showed superior biocompatibility when added to poly(methyl methacrylate) in cell culture experiments. The zirconium oxide and tricalcium phosphate composites evoked no greater unfavourable tissue reaction in rats than pure poly(methyl methacrylate). From the physical and biological standpoints zirconium oxide is the radiopaque filler of choice to be incorporated in poly(methyl methacrylate) implant material and addition of tricalcium phosphate could improve it's biocompatibility.

Animals↗

Biocompatibility testing of prosthetic implant materials by cell cultures.

The main aspects of biocompatibility are discussed first then the methodology used and the results obtained. The cells used included epithelial cells, lymphocytes, fibroblasts, and macrophages. The most commonly used methods were morphological observation, radioactive tracer uptake, and chemotactic migration analysis. It is concluded that cell cultures are a reliable and sensitive method for initial screening in testing the biocompatibility of the materials used in the construction of prosthetic implants.

Animals↗

Biocompatibility of particles of GORE-TEX cruciate ligament prosthesis: an investigation both in vitro and in vivo.

This research was to determine the biocompatibility of simulated wear particles from a GORE-TEX cruciate ligament prosthesis using in vitro and in vivo techniques. Exposure of normal human synovial fibroblasts and primary mouse peritoneal macrophages to the particles revealed no cytotoxicity, as determined by lactate dehydrogenase release, but beta-N-acetyl-D-glucosaminidase was released from macrophages at high concentrations, showing inflammatory potential. This was not seen when the particles were injected into mouse knees, where no adverse reactions were observed. These simulated wear particles were shown to be biocompatible using these in vitro and in vivo systems.

Acetylglucosaminidase↗

Immune response in biocompatibility.

Biocompatibility is concerned with the interactions that occur between biomaterials and host tissues. As foreign objects in that host tissue these materials may initiate several types of response. It has often been postulated that the immune response, by which the host normally defends itself against invasion by foreign organisms, can be involved in the response to biomaterials. This review discusses the mechanisms by which this could occur and the evidence that suggests the immune response is indeed of significance in biocompatibility.

Animals↗

Biocompatibility of the Vascugraft: evaluation of a novel polyester urethane vascular substitute by an organotypic culture technique.

To evaluate the biocompatibility of chemically and structurally modified polyurethane elastomers for use as blood vessel replacements, small squares of vascular prostheses were cultured in direct contact with endothelium from chick embryo aorta using an organotypic culture assay. The polyurethane materials tested were: Vascugraft (fibrous, open pore structure); commercial Hydrophilic Mitrathane prosthesis (high porosity, smooth surface, non-permeable, closed pore structure); experimental hydrophobic Mitrathane (less porosity but a fibrous, open pore structure, similar to Vascugraft). The commercial expanded polytetrafluoroethylene prostheses Impra and reinforced GORETEX were included as controls on account of their extensive clinical application in the femoropopliteal position. After 5 d incubation at 37 degrees C biocompatibility was assessed in terms of average area of migrating cells on the biomaterial, total number of cells surrounding the explant and level of adhesion between the cells and the biomaterial. The Vascugraft prosthesis promoted the growth of a continuous monolayer of cells on its surface. This behaviour was equivalent to Impra and reinforced GORETEX materials in terms of cell density and area of cell migration but appeared to be superior for cell adhesion. From a second series of cell culture tests, in which the extractables leached from the biomaterials were added to the nutrient medium, it was concluded that none of the biomaterials tested released cytotoxic contaminants.

Animals↗

Poly(ethylene oxide)-graft-poly(L-lysine) copolymers to enhance the biocompatibility of poly(L-lysine)-alginate microcapsule membranes.

A graft copolymer having poly(L-lysine) (PLL) as the backbone and monomethoxy poly(ethylene glycol) (MPEG) as pendent chains was synthesized. This polycationic copolymer was used to form microcapsules with sodium alginate, a polyanion. Microcapsules and model surfaces formed with PLL-graft-MPEG demonstrated reduced protein adsorption, complement binding and cell adhesion in vitro compared to materials with unmodified PLL. Microcapsules with PLL-g-MPEG on the surface were seen to be much more biocompatible than the widely used alginate/PLL/alginate microcapsule in a mouse intraperitoneal implant model. The graft copolymers demonstrated a lower affinity for alginate and increased microcapsule permeability more than PLL. To correct this, pentalayered alginate/PLL/alginate/PLL-g-MPEG/alginate microcapsules were fabricated, and these demonstrated both appropriate permselectivity and enhanced biocompatibility.

Adsorption↗

Biocompatibility of tetracalcium phosphate cement when used as a bone substitute.

We evaluated the biocompatibility of tetracalcium phosphate (4CP) cement, made of 4CP powder and 40 wt% copolymer of polyacrylic acid/itaconic acid and 10 wt% citric acid solution. Light and electron microscopic characteristics were studied 3, 10 and 30 d after implantation. Neither inflammation nor foreign-body giant cell reaction was observed in the tissue adjacent to the implanted material. After 30 d, this material was surrounded with newly formed bone. Ultrastructural examination showed that osteogenesis occurred directly on the surface of the material. These findings suggest that this 4CP cement is biocompatible and possesses osteoconductive properties.

Animals↗

In vivo degradation and biocompatibility study of in vitro pre-degraded as-polymerized polyactide particles.

The degradation of high molecular weight as-polymerized poly(L-lactide) (PLLA) is very slow; it takes more than 5.6 yr for total resorption. Moreover, the degradation products of as-polymerized PLLA bone plates, consisting of numerous stable particles of high crystallinity, are related with a subcutaneous swelling in patients 3 yr postoperatively. In order to avoid these complications, polymers were developed that are anticipated to have comparable mechanical properties but a higher degradation rate and do not degrade into highly stable particles that can induce a subcutaneous swelling. On chemical grounds it can be expected that copolymerization of PLLA with 4% D-lactide (PLA96) or by modifying PLLA through cross-linking (CL-PLLA) will lead to less stable particles and a higher degradation rate. To evaluate the long-term suitability of these as-polymerized polymers, the biocompatibility of the degradation products should be studied. Considering the very slow degradation rate of as-polymerized PLLA, in vitro pre-degradation at elevated temperatures was used to shorten the in vivo follow-up periods. In this study, the biocompatibility and degradation of as-polymerized PLLA, PLA96 and CL-PLLA were investigated by implanting pre-degraded particulate materials subcutaneously in rats. Animals were killed after a postoperative period varying from 3 to 80 wk. Light and electron microscopical analysis and quantitative measurements were performed. The histological response of all three pre-degraded materials showed a good similarity with in vivo implanted material. Pre-degraded PLLA induced a mild foreign body reaction and showed a slow degradation rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Biocompatibility of membranes used in the treatment of renal failure.

Haemodialysis membranes with a wide range of solute and hydraulic permeabilities are used clinically. Such membranes are manufactured from either cellulose or synthetic co-polymers and their biocompatibility is commonly characterized by the complement activation and white cell changes observed during their use. The cellobiosic unit may be modified by the partial or total replacement of the hydroxyl groups by diethylaminoethyl (Hemophan), acetate (cellulose acetate), triacetate (cellulose triacetate) or 2,5-acetate (Diaphan). We have undertaken a prospective study in which such renal membranes have been studied in terms of the complement activation and neutropenia produced with the aim of investigating the relationship between modification of the cellobiosic unit and the magnitude of neutropenia and complement activation, and the extent to which membrane base material influences these parameters, by comparing the changes observed in modified cellulose membranes with that for a synthetic membrane (polysulphone). Our findings show that, while the degree of substitution varies between < 1% and total substitution, there is no correlation between the numbers of hydroxyl groups replaced and alteration of complement activation and neutropenia. However, by modification of the cellobiosic unit it is possible to produce a membrane whose biocompatibility is similar to that of a membrane manufactured from a synthetic co-polymer such as polysulphone.

Biocompatible Materials↗

Photo-crosslinked copolymers of 2-hydroxyethyl methacrylate, poly(ethylene glycol) tetra-acrylate and ethylene dimethacrylate for improving biocompatibility of biosensors.

A copolymer containing 88% 2-hydroxyethyl methacrylate (HEMA), 9% poly(ethylene glycol) (MW 18.5 kDa) tetra-acrylate and 3% ethylene dimethacrylate was prepared and evaluated for use as a biocompatible interface between glucose biosensors and tissue in the rat. The glucose sensor utilizes glucose oxidase that is electrically 'wired' to a gold current collector by a reduction-oxidation polymer. Coatings of the copolymer were crosslinked in situ on the sensors using long wavelength ultraviolet light and 2,2-dimethoxy-2-phenyl-acetophenone as the initiator. The effect these films had on the current response to glucose was measured. Over a glucose concentration range of 0-30 mM, the average percentage decrease in response was 45 +/- 28% (mean +/- 95% confidence interval) at 37 degrees C for films that were about 0.1 mm thick, an acceptable value. Copolymer-treated and control electrodes were implanted in the intrascapular subcutaneous tissue of male Sprague-Dawley rats for three days. The explanted samples were evaluated using scanning electron microscopy. The control electrodes were highly encapsulated with fibrous material, while the copolymer-treated electrodes induced much less encapsulation. The results show this copolymer to be a candidate as a biocompatible coating for electrically wired oxidoreductase-based subcutaneous biosensors.

Acrylates↗

Antioxidant N-acetyl-cysteine increasing cell adhesion capability could facilitate the biocompatibility processes.

Cell adhesion plays an important role in several cell processes and functions, including differentiation, proliferation and death. An important role for cell attachment to medical devices in biocompatibility studies has also been hypothesized. In this paper we report that the use of the antioxidant drug N-acetyl-cysteine is capable of increasing the adhesion properties of epithelial cells in culture. This is associated with a modification of specific cytoskeletal element assembly, such as microfilament system molecules. In contrast, no quantitative alterations in the expression of certain surface receptors for extracellular matrix molecules, such as VLA2, VLA3 and VLA6, are found. These data seem to indicate that intracellular oxidative balance, in particular of thiol groups, could play a key role in the cell adhesion properties and that N-acetyl-cysteine treatment, acting as 'thiol supply', could be of importance in several circumstances, including biocompatibility of medical devices.

Acetylcysteine↗

Sterilization, toxicity, biocompatibility and clinical applications of polylactic acid/polyglycolic acid copolymers.

This is a review of salient studies of sterilization, toxicity, biocompatibility, clinical applications and current work in the field of orthopaedics, using implants made of polylactic acid (PLA), polyglycolic acid (PGA) and their copolymers. The intrinsic nature of these biomaterials renders them suitable for applications where temporally slow releases of bioactive agents in situ may be required. They are also desirable as fixation devices of bone, because they can virtually eliminate osteopenia associated with stress shielding or additional surgery. The majority of currently available sterilization techniques are not suitable for these thermoplastic materials and it may be desirable to develop new sterilization standards, which can account for the special character of PLA-PGA materials. Biocompatibility and toxicity studies suggest that, overall, PLA-PGA biomaterials may be suitable for orthopaedic applications, although certain problems, especially pertaining to reduction in cell proliferation, have been reported. Clinical applications are also promising, albeit not without problems usually associated with transient tissue inflammation. The future of these materials appears bright, especially in soft tissues. They may be used to address the exceedingly complex problem of osteochondral repair, but also as a means to enhance fixation and repair processes in tendons and ligaments.

Animals↗