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In vitro biocompatibility evaluation of naturally derived and synthetic biomaterials using normal human bladder smooth muscle cells.

PURPOSE: Tissue engineering of the urinary tract often requires the use of various biomaterials. Adequate biomaterial biocompatibility is necessary for successful urinary reconstruction. In this study using a primary normal human bladder smooth muscle cell culture system we evaluated the in vitro biocompatibility of a number of naturally derived biomaterials, including bladder submucosa, small intestinal submucosa, collagen and alginate, and polymeric biomaterials, including polyglycolic acid, poly(L-lactic acid) and poly(lactic-co-glycolic acid, which have been used for urinary reconstruction experimentally or clinically. MATERIALS AND METHODS: To determine the cytotoxic and bioactive effects of bladder submucosa, small intestinal submucosa, collagen, alginate, polyglycolic acid, poly(L-lactic acid) and poly(lactic-co-glycolic acid) we measured cell viability, metabolic activity, apoptotic properties and DNA synthesis activity with 4 types of assays, namely Neutral Red (Sigma Chemical Co., St. Louis, Missouri), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (Sigma Chemical Co.), apoptotic activity and tritiated thymidine incorporation (Dupont NEN, Boston, Massachusetts) assays. Normal human bladder smooth muscle cells were cultured with the extracts of the biomaterials or cultured in direct contact with the biomaterials. RESULTS: All naturally derived and synthetic biomaterials tested in this study except alginate exhibited nontoxic and bioactive effects on human bladder smooth muscle cells (HBSMCs) in vitro, as indicated by the 4 types of biocompatibility assays using the extract and direct contact methods. Cell viability, apoptotic properties, metabolic activity and DNA synthesis activity of HBSMCs cultured with the extracts of the biomaterials or cultured in direct contact with the biomaterials were not significantly different from those of negative controls (fresh medium with no extracts or tissue culture plates without biomaterials). CONCLUSIONS: All naturally derived and synthetic biomaterials tested in this study except alginate exhibited nontoxic and bioactive effects on HBSMCs in vitro. This normal primary human bladder smooth muscle cell culture model is suitable for in vitro biocompatibility assessment. It provides information on cell-biomaterial interactions and on the ability of biomaterials to support bioactive cell functions.

Biocompatible Materials↗

[The advance of research for biocompatibility of medical polyurethanes].

Polyurethanes are popularly used in cardiovascular and other biomedical fields due to their good biocompatibility as well as mechanical properties. But they are subject to biodegradation in vivo for a long time, and cause inflammation, so improving the biocompatibility of medical polyurethanes is an important subject of biomaterials. Recent researches have focused on biological modelling of biomaterials for improving the biocompatibility of polyurethanes. This paper reviews two main methods for improving biocompatibility of polyurethanes-endothelial cells seeding and mimic biomembrane (phospholipid surface), and summarizes the main procedures and questions of these two methods.

Biocompatible Materials↗

[Membrane biocompatibility in dialysis: the role of absorption].

Membrane biocompatibility is a concept that have gained clinical relevance. How to define a "biocompatible membrane" in hemodialysis is still object of discussion. Intermediate biochemical reactions, measured in the blood are more relevant than clinical events to document membrane's quality. In the absence of prospective studies, it is not possible to document that the constant use of a dialysis membrane governs risk of death in the hemodialyzed patient. Nevertheless, some clinical criteria are relevant, such as hemocompatibility, i.e. clotting of the extracorporeal circuit and heparin consumption, hypersensitivity reactions, denutrition associated with the "microinflammatory" stress induced by the hemodialysis session, occurrence of beta 2 microglobulin-derived amyloidosis. Synthetic membranes are credited of higher biocompatibility than cellulosic membranes. In general, they are highly permeable to peptides and proteins of the middle molecular range that contain some uremic toxins. In addition to be "highly permeable", allowing convective transfert, some synthetic membranes (polymethylmetacrylate, polyacrylonitrile, polyamide) bind proteins. Protein adsorption into synthetic membrane results from electrical charges distribution both at the surface and in the bulk of the membrane. Ionic interactions are the main contribution to protein adsorption, but rheological conditions, surface rugosity, and porosity or gel consistency play also a role. Consequently, some membranes can bind cytokines and oxygen species, other bind endotoxins. Recently, it has been demonstrated that heparin coating was possible with the AN69-ST membrane, resulting in improved hemocompatibility and significant lessening of heparin requirements during the sessions. It appears that adsorption characteristics govern biocompatibility. For clinical practice, a classification of various membranes according to these properties must be taken into account.

Adsorption↗

[Biocompatibility and resistance to corrosion of orthodontic wires].

Various materials are currently used to make orthodontic wires. This article suggests a synthesis on their resistance to corrosion and biocompatibility. In the first part, after a review of some basic notions on the corrosion processes, the authors develop the electrochemical characteristics of the three main groups of alloys used in orthodontics. They study more precisely corrosion resistance of nickel-titanium alloys and, through their own experimental results, they show that this type of alloy is subject to corrosion in acid and fluoridated environment. In the second part, the authors study those alloys biocompatibility. They first mention nickel toxicity and allergy induced by this element. Then, biocompatibility of alloys used in orthodontics is assessed following studies on the release of metallic elements from orthodontic wires, and studies on cell-compatibility when in contact with those wires. It is proved that the state of materials surface has a very high influence on their biocompatibility. As a conclusion, in spite of numerous studies carried out so far, showing a satisfactory biological behaviour of those orthodontic wires, many questions are yet to be answered: long term in vivo performances of those materials have not yet been exactly assessed. Further studies must definitely be carried out.

Biocompatible Materials↗

Histological evaluation of biocompatible orthopaedic polymer.

The biocompatibility of biocompatible orthopaedic polymer implant materials was studied in subcutaneous and bony tissue of rats and rabbits. The tissue response was evaluated by histological techniques. No bone induction capacity of biocompatible orthopaedic polymer could be observed. In rabbits, the presence of plasma cells was significantly higher than in rats. The biomaterial showed some signs of biodegradation and was not very biocompatible.

Animals↗

Biocompatibility of dental amalgams in vitro during 52 week period.

Short term biocompatibility of biomaterials including various dental materials has been elucidated so far. When considering the practical cases of utilization of the biomaterials, it is known that they stay for quite a long period in situ once after brought into the living system. It seems, therefore, essential that long term biocompatibility of the materials should be clarified in order to provide better knowledge on various aspects of biocompatibility. The present paper deals with long term biocompatibility in vitro of common dental materials, dental amalgams.

Biocompatible Materials↗

Orthodontic magnets. A study of force and field pattern, biocompatibility and clinical effects.

Magnetic forces have been incorporated into orthodontic mechanics during recent years. However, the biocompatibility of magnet alloys and the possible risk of harmful or unusual reactions in tissues exposed to static magnetic fields have been characterized as inconsistent and often contradictory. It has also been questioned whether magnetic forces have significant advantages over traditional mechanics. The present series of studies aimed to analyse the force and field properties, the biocompatibility and the clinical effects of rare earth magnets as well as to compare the efficiency of tooth movement between magnets and another force system. Samarium-cobalt magnets for molar distalization were tested in experimental models for force and field properties. The cytotoxicity of different magnet alloys (rare earth types) as well as of clinically used and recycled magnets was assessed by two in vitro methods, the millipore filter method and an extraction method. The effect of static magnetic fields on human gingival tissue and dental pulp was examined histologically for alterations in cell pattern and cell morphology. The effects of using repelling samarium-cobalt magnets for simultaneous distalization of maxillary first and second molars were analysed in individuals with Class II malocclusion. The efficiency of molar distalization was also intra-individually compared between repelling magnets and superelastic NiTi-coils in individuals with Class II malocclusion and deep bite. The magnet forces decreased approximately with the reciprocal square of the separation distance between the magnets. No fatigue of force over time could be seen. The static magnetic fields were weak and had a limited extent and the flux density dropped exponentially in all directions with increased distance from the magnets, implying a small exposure area when the magnets are used clinically. Rare earth magnets showed good biocompatibility, particularly coated magnets. However, uncoated samarium-cobalt magnets showed significant cytotoxicity. It was also found that stainless-steel-coated samarium-cobalt magnets could be recycled with maintained good biocompatibility. After exposure to static magnetic fields, normal clinical and histological conditions in the human gingival tissue and normal histological features in the human dental pulp were found. Repelling magnets were effective in producing maxillary molar distalization but some side effects like anchorage loss and molar tipping were found. The superelastic coils were shown to be even more efficient than the repelling magnets for maxillary molar distalization in individuals with Class II malocclusion and deep bite.

Adolescent↗

[Evaluation of the biocompatibility of medical devices based on European standards].

Several issues concerning the biocompatibility) testing of medical devices as stated in European directive 90/385 and 93/42 are discussed. The authors describe the fundamental characteristics that biomaterials should have to be employed in the human body, the assays useful for testing different aspects of biocompatibility and the harmonized regulations already available or under development. The testing protocol applied by the a. in their Lab covering many issues of biocompatibility is presented: a body of experience was gained over the years and it has been revised under the new regulatory items. In conclusion, the biocompatibility of devices must be assessed following the European harmonized standards, the available. Where proper standards are still lacking, feasible testing methods, even if not officially adopted yet, have to be used.

Biocompatible Materials↗

The use of biocompatible dialysis membranes in acute renal failure.

The interactions between blood and the dialysis membrane, aside from solute clearance, can be referred to as biocompatibility. It has increasingly been recognized that significant side effects may occur as a result of interactions of blood with the dialysis membrane itself. The use of unmodified cellulosic hemodialysis membranes results in potent activation of the alternative pathway of complement, and numerous investigators have now carefully defined the membrane characteristics that contribute to complement activation, adsorption, and clearance. Complement-dependent granulocyte activation during hemodialysis causes neutrophil degranulation and protease release, the production of reactive oxygen species, and modulation of granulocyte cell adhesion molecules. Recently, a number of experimental studies in animal models suggest that complement and granulocyte activation during hemodialysis could contribute to the prolongation of acute renal failure. Based on the hypothesis that hemodialysis with complement and granulocyte-activating membranes could contribute to the prolongation of acute renal failure and increased mortality, several recent prospective randomized clinical trials examining the role of membrane biocompatibility in the treatment of acute renal failure have been reported. Although not unanimous in their conclusions, most studies suggest that hemodialysis with more biocompatible membranes in patients with acute renal failure leads to a more rapid return of renal function and a lower morbidity and mortality. Thus, hemodialysis membrane biocompatibility may be an important contributor to the outcome of patients with acute renal failure who require dialysis.

Acute Kidney Injury↗

[The biocompatibility of catheters and stents used in urology].

Biocompatibility can be interpreted as the optimal combination of a series of interactions occurring at the material-tissue interface as soon as these two systems are in contact. It is a multifactorial interface property which integrates all of the phenomena involved in a biological environment i.e. absence of toxicity of the material for the body and absence of degradation of the material by the body. Biocompatibility can be evaluated in a normative context by using in vivo techniques in animals or in vitro techniques using cell cultures allowing the study of cytotoxicity (related to a concept of safety) and cytocompatibility (related to biological acceptability) of a material. Because of their intimate contact with the urothelium throughout implantation, the biocompatibility of catheters and stents constitutes a major requirement. This review presents the current data reported in the literature concerning the evaluation of the biocompatibility of materials used in urology. The main problems encountered are alterations of the urothelium, such as erosions or, on the contrary, mucosal hyperplasia, and the existence of incrustations developing on these materials.

Animals↗

Biocompatibility, cell adhesion, and degradation of surface-modified biodegradable polymers designed for the upper urinary tract.

OBJECTIVES: The aim of this study was to develop a short bioresorbable ureteric stent and to characterize polymers and their surface modifications with respect to biocompatibility, degradation kinetics, cell adhesion properties, and incorporation of biologically active substances. Poly(D,L-lactide) PDLLA, poly(D,L-lactide-co-glycolide) PDLLA-co-GLY, and poly(D,L-lactide-co-trimethylenecarbonate) PDLLA-co-TMC were chosen as basic polymers. Surface modification was performed by plasma-induced graft polymerization and included grafting with hydroxyethylmethacrylate (HEMA), oligo(ethyleneoxide)-monomethacrylate (OEOMA), and acrylic acid (AAC). Biocompatibility of the polymers was assessed in vitro applying parameters of cell morphology, proliferative activity, and cell adhesion. All polymers were biocompatible and exerted no toxic effect on urothelial cell lines and on primary human urothelial cell cultures. A markedly reduced cell adhesion could be achieved in polymers grafted with HEMA, OEOMA, and AAC. Our results indicate that surface modification of bioresorbable polymers by grafting with HEMA, OEOMA, or AAC is an efficient approach to improve surface properties with respect to biocompatibility and cell adhesion properties.

Absorption↗

Biocompatibility evaluation of dental metal alloys in vitro: expression of extracellular matrix molecules and its relationship to cell proliferation rates.

The biocompatibility in vitro of dental biomaterials has been widely studied, with consideration of cell viability and cell proliferation rates. In the present study we evaluated the biocompatibility in vitro of three single-phase dental metal alloys, all provided by the same manufacturer. To this aim, we considered the percentage of proliferating cells revealed by 5-bromodeoxyuridine incorporation in human fibroblast cultures in the presence of these biomaterials, performing a short time test (72 h). These data were correlated with immunocytochemical expression of four molecules of the extracellular matrix, i.e., fibronectin, type I collagen, beta(1)-integrin subunit, and chondroitin sulfate, because the capability of cells to adhere to substrata is widely related to cell proliferation rates. Alloys presenting higher amounts of noble elements were more biocompatible even when they contained significant amount of both Ag and Cu. As regards the expression of the extracellular matrix molecules, the organization level of fibronectin in fibrils was correlated with higher cell proliferation rates, whereas no difference was detected for the expression of the other antigens. On these bases, we assume that expression of fibronectin could be a useful parameter in evaluation of biocompatibility in addition to cell proliferation capability.

Bromodeoxyuridine↗

In vitro biocompatibility of resorbable experimental glass ceramics for bone substitutes.

Tricalcium phosphate ceramics (TCPs) are increasingly used as bone substitutes. They demonstrate good biocompatibility and degrade relatively slowly. New glass ceramics based on calcium alkali orthophosphates (Ca(2)KNa(PO(4))(2)) were developed that degrade faster than TCP but could have reduced biocompatibility due to their high solubility. Therefore, they were modified by a neutralizing surface treatment. The aim of this study was to evaluate the biocompatibility of some of these ceramics, GB1a, GB9, and GB14, which differ in the amount of added Na, K, Mg, or Si ions, with standard and modified surfaces. The in vitro cytotoxicity of the ceramics GB1a, GB9, and GB14 was determined by the agar diffusion and filter test and the microculture tetrazolium (MTT) assay. In order to investigate the influence of surface modification, these three ceramics were compared to their surface-treated counterparts, GB1aN, GB9N, and GB14N. GB1a, the ceramic with the highest in vitro solubility, showed the strongest toxic influence in all cell culture tests. GB9 and GB14 produced better results. In contrast, the counterparts with modified surfaces exhibited no (GB9N, GB14N) or weak (GB1aN) signs of cytotoxicity. It is concluded that the toxicity of the ceramics GB1a, GB9, and GB14 depends on their solubility. A positive influence of the surface treatment on in vitro biocompatibility was demonstrated. Therefore, the surface-treated glass ceramics could be promising materials for bone replacement.

3T3 Cells↗

Biocompatibility studies on plasma polymerized interface materials encompassing both hydrophobic and hydrophilic surfaces.

The biocompatibility of radiofrequency plasma polymerized films (less than 100 nm thick) deposited on biomedical polymer supports has been characterized by in vitro and in vivo methods. The polymer interface materials covered a wide range of elemental composition and surface properties, and were prepared from N-vinyl-2-pyrrolidone, gamma-butyrolactone, n-hexane, and hexamethyldisilazane (PPHMDSZ). The biocompatibility studies showed that the interface materials were noncytotoxic to mouse and human fibroblasts, as shown by morphologic evaluation, and by determination of extracellular LDH; and they did not stimulate interleukin-1-like production from human monocytes, as indicated by a thymocyte proliferation assay. The human fibroblast proliferation assay showed that three of the polymers supported cell growth at levels comparable to, or greater than, polymer controls, while the hydrophobic PPHMDSZ inhibited both cell attachment and proliferation. The response to subcutaneous implantation for all test materials was indicative of biocompatibility, with rapid resolution of the acute phase response and normal wound healing. The wide range of composition and surface properties for the plasma polymerized films evaluated in this study suggest that this general class of materials is likely to exhibit excellent biocompatibility.

Animals↗

On the in vitro biocompatibility of Elgiloy, a co-based alloy, compared to two titanium alloys.

AIM: The aim of the present investigation was to contribute to an understanding of the effects of surface topography and chemical composition on the corrosion behavior and thus the biocompatibility of Elgiloy (RMO, Denver, CO, USA), a common Co-based alloy. MATERIAL AND METHODS: The results are compared with those obtained for a binary NiTi alloy, Neo Sentalloy (GAC, Central Islip, NY, USA) and a beta-III-Ti alloy, TMA (Ormco, Glendora, CA, USA). In the present study, the surface topography and the chemical composition of two different grades of Elgiloy, Blue Elgiloy (soft) and Yellow Elgiloy (ductile), were examined by means of scanning electron microscopy (SEM) and energy-dispersive spectroscopy analysis (EDS). Their corrosion behavior in half-strength Ringer solution and in an artificial saliva solution according to Barrett [1] was investigated using potentiodynamic corrosion testing (PDC). The photometry-based PAN method was used to quantify the released Ni and Co ions. The in vitro biocompatibility of the two grades of Elgiloy was tested in three different cell cultures: in L929, a commercially available mouse fibroblast cell line, and in primary human epithelial cells and fibroblasts. RESULTS: The results of the corrosion testing showed satisfactorily high pitting corrosion potentials but lower repassivation potentials and a strong increase in current density once pitting had occurred. The photometric results revealed the release of Ni and Co ions in both tested electrolytes. The tested native surfaces exhibited numerous grinding and polishing grooves, inclusions and inhomogeneities of the microstructure. After corrosion testing the same surfaces displayed numerous signs of corrosion, especially in areas with microstructural inhomogeneities. In vitro biocompatibility testing showed a substantially reduced dehydrogenase activity in the presence of Elgiloy. The reduced quality of surface finish resulting from the manufacturing process led in the case of the tested Elgiloy types to decreased corrosion resistance with consequently reduced in vitro biocompatibility. CONCLUSIONS: In this context it is also conceivable that patients with a proven allergy to nickel, cobalt or chromium may react sensitively to the deployment of this alloy, at least in the surface quality tested by us. From this aspect, the introduction of a binding standard for the surface quality of materials used in orthodontic appliances is urgently recommended.

Animals↗

Importance of enzyme and solvent physical properties for the biocompatibility relationship of alpha-amino acid ester hydrolase.

The enzyme alpha-amino acid ester hydrolase was used with a variety of organic solvents to further explore the relationships between biocompatibility and solvent physical properties. Biocompatibility was shown to be system-specific; that is, the infection point of the characteristic log P trend (approximately 1.5) was specific to the enzyme employed, while the biocompatibility of solvents that were exceptions to the trend was dependent on the extent of agitation. In addition, phase toxic solvents all possessed a high interfacial tension with water. Finally, while the source of the enzyme may be significant, the extent of purification does not appear to be a factor in biocompatibility.

Biotransformation↗

Biodegradation and biocompatibility of PLA and PLGA microspheres.

A fundamental understanding of the in vivo biodegradation phenomenon as well as an appreciation of cellular and tissue responses which determine the biocompatibility of biodegradable PLA and PLGA microspheres are important components in the design and development of biodegradable microspheres containing bioactive agents for therapeutic application. This chapter is a critical review of biodegradation, biocompatibility and tissue/material interactions, and selected examples of PLA and PLGA microsphere controlled release systems. Emphasis is placed on polymer and microsphere characteristics which modulate the degradation behaviour and the foreign body reaction to the microspheres. Selected examples presented in the chapter include microspheres incorporating bone morphogenetic protein (BMP) and leuprorelin acetate as well as applications or interactions with the eye, central nervous system, and lymphoid tissue and their relevance to vaccine development. A subsection on nanoparticles and nanospheres is also included. The chapter emphasizes biodegradation and biocompatibility; bioactive agent release characteristics of various systems have not been included except where significant biodegradation and biocompatibility information have been provided.

Journal Article↗

Dependence of in vitro biocompatibility of ionomeric cements on ion release.

The in vitro biocompatibility of a group of ionomeric cements (ICs) was evaluated with respect to their ion release properties. These ICs were made from a defined series of glasses with the general formula 1.5SiO2.0.5P2O5.Al2O3.(1.0-Z)CaO.0.75CaF2 where Z was the mole fraction (ranging from 0-0.1) of an alkali metal oxide, either sodium or potassium or a mixture of both. For these alkali metal ICs, the amount of sodium released was directly related to the sodium content of the constituent glass. Similarly, the amount of potassium released was directly related to the potassium content. There was no correlation between the aluminum content of the glass and the aluminum ion release. Increasing the monovalent cation concentration, however, produced ICs with increased fluoride release. The biocompatibility of the ICs, as assessed by in vitro cell growth and viability measurements, was inversely proportional to aluminum ion release. Fluoride ion release, although important in terms of in vitro biocompatibility, would appear to be less important than aluminum ion release in determining the overall biocompatibility of the ICs studied.

Journal Article↗