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[Assays of cytotoxicity of the Nickel-Titanium shape memory alloy].

The equiatomic Nickel-Titanium (NiTi) alloy has exceptional mechanical properties such as shape memory and superelasticity. It already has applications in orthodontics and is a promising orthopaedic biomaterial. Cytocompatibility studies must therefore be undertaken. The objective of this study is to determine the biological response that NiTi elicits compared to other orthopaedic metals currently used in orthopaedic surgery. Cytotoxicity tests constitute an efficient first step in a biocompatibility study and contribute to reduce animal use in laboratory. Direct contact and agar diffusion cytotoxicity assays were performed following ASTM standards #F813-83 and #F895-84 respectively. Confluent L-929 fibroblasts culture plates were incubated (directly or under an agar bed) in presence of NiTi, titanium (Ti), vitallium (Co-Cr-Mo) and 316L stainless steel discs. Following exposition to specimens, a vital dye was added to the plates. All cultures were evaluated for cytotoxic reactions, under light microscopy. Direct contact and agar diffusion assays indicated that all metals tested induced a mild biological reaction. Specimens were ranked according to an index of biological response, they are enumerated here in decreasing order of cytotoxicity: NiTi approximately Co-Cr-Mo >> pure grade 4 Ti approximately pure grade 1 Ti approximately Ti 6A1 4V approximately 316L stainless steel. Furthermore, plasma surface modification increased the cytocompatibility of NiTi.

Biocompatible Materials↗

Flow intrusion characteristics and fracture properties of titanium-fibre-reinforced bone cement.

Two clinically relevant considerations for a new bone cement are its fracture properties and flow intrusion characteristics. We present data for a titanium-fibre-reinforced poly(methyl methacrylate) (Ti-PMMA). The fracture properties presented are a concise review of previously published material, while the flow intrusion observations are new. We performed fracture toughness and fatigue fracture experiments. Two types of fatigue specimens were designed and tested. A 'smooth' specimen represented the extreme case of minimum surface flaws. The lifetime of a 'smooth' specimen incorporates fatigue crack initiation (FCI) and fatigue crack propagation (FCP). 'Notched' specimens were created by machining a sharp notch into cylindrical specimens. The sharp notch effectively eliminated FCI from a random surface flaw and thus we made the assumption that the lifetime of the notched specimen was a function of FCP only. Fatigue testing was performed on rotating-bending fatigue machines until failure. Fibre addition resulted in a significant increase in fracture toughness over the control bone cement. Fibre addition and the combination of fibre addition and centrifugation increased the fatigue crack initiation and propagation resistance of the bone cement. For the intrusion studies, eight femurs were obtained from four dogs. The femurs were prepared following a procedure similar to that in human hip replacement surgery. One of the pair of femurs from each dog was filled with non-reinforced bone cement and the other was filled with Ti-PMMA. A stainless-steel rod was inserted into the cement to simulate the insertion of a prosthesis stem. The cemented bones were sectioned and then stained with Alizarin Red S to distinguish the bone from the PMMA or Ti-PMMA. Because of the irregular bone morphology, it was not practical to quantify intrusion depth, but instead to make general observations on the intrusion characteristics. The Ti fibres did not generally flow into the small openings; however, fibre addition did not hinder the bone cement's ability to penetrate into bone interstices.

Animals↗

Comparison of the electrochemical properties of various orthopedic porous metals.

The electrochemical properties of various porous metal coatings used in reconstructive orthopedic prosthetics were examined. Potentiodynamic corrosion testing was used to evaluate the behavior of the following porous metals; CSTi on Cast CoCr, CSTi on Ti-6Al-4V, CoCr beads on Cast CoCr, CoCr beads on Ti-6Al-4V, CP Ti beads on Cast CoCr, and CP Ti beads on Ti-6Al-4V. Analysis of the resultant corrosion scans showed that these materials behave similarly to one another. No corrosion-related anomalies were noted.

Corrosion↗

Aligned bioactive mesoporous silica coatings for implants.

Ongoing research is reported aimed at preparing mesoporous silica coatings on various substrates for medical applications by a biomimetic approach (self-assembling of organic/inorganic sol-gel systems into ordered structures). Tetraethylorthosilicate (TEOS) was selected as the silica precursor, and amphiphilic triblock copolymers poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), and the cationic surfactant cetyltrimethyl ammonium chloride (CTAC), as structure-directing agents. The mesochannels diameter could be adjusted by changing the directing agent, and a preferred alignment of the mesostructure was observed independently of the used substrate (glass, silicon, Ti or Ti6Al4V). Three different treatments (thermocalcination, photocalcination, and solvent extraction) have been also studied to remove the organic templates, of which photocalcination showed to be the most versatile. When soaked in a simulated body fluid, mesoporous silica coatings induced apatite formation after seven days.

Journal Article↗

Tricuspid valve annuloplasty using a partial flexible ring: mid-term follow-up.

BACKGROUND: Tricuspid valve annuloplasty (TVA) using a complete or partial rigid or flexible ring is becoming common practice in the surgical treatment of tricuspid insufficiency (TI). This study evaluates the immediate outcome and the mid-term clinical and echocardiographic follow-up after TVA performed using the Cosgrove-Edwards partial flexible ring. METHODS: From June 1998 to March 2002, 35 consecutive adult patients with TI > 2+ underwent TVA using this annuloplasty ring. TI was secondary to right ventricular dilation and/or dysfunction (functional TI) in 32 (91.4%) patients, and due to anatomic anomalies of the tricuspid valve (organic TI) in 3 (8.6%). Pulmonary hypertension was present in 34.4% of the patients with functional TI. Thirty-two (91.4%) patients were in preoperative NYHA functional class III or IV. The mean follow-up was 28.3 +/- 14.6 months. RESULTS: There were three (8.6%) in-hospital non-valve-related cardiac deaths, and one (3.1%) non-cardiac death during follow-up. The 3-year actuarial survival was 96.5%. TI was well controlled within grade 1+ in 30 (96.8%) survivors, but one presented residual grade 2+ TI. The NYHA functional class improved to 1.3 +/- 0.5 (p = 0.035). CONCLUSIONS: TVA performed using the Cosgrove-Edwards ring is a valid option for the surgical treatment of both functional and organic TI, even in case of pulmonary hypertension and at mid-term follow-up.

Adult↗

Long-term treatment with estradiol induces reversible alterations in tuberoinfundibular dopaminergic neurons: a decreased responsiveness to prolactin.

Previous studies have demonstrated that short-term (3-5 days) treatment with estradiol increases the rate of turnover and synthesis of dopamine (DA) in terminals of tuberoinfundibular (TI) neurons in the median eminence by virtue of the ability of this hormone to increase circulating concentrations of prolactin. The present studies were undertaken to examine the long-term effects of estradiol on serum prolactin concentrations and TIDA neuronal activity (estimated by the rate of DOPA accumulation in the median eminence after the administration of a decarboxylase inhibitor). Female rats, ovariectomized for 2 weeks, were implanted subcutaneously with silastic capsules containing estradiol benzoate and sacrificed 6, 12 and 18 days after capsule implantation. Serum prolactin concentrations were markedly increased at 6, 12 and 18 days whereas the rate of DOPA accumulation was increased at 6 days but not at 12 days, and was decreased at 18 days. The concentration of DA in the median eminence was reduced at 6 days and further reduced at 12 and 18 days. The low rate of DOPA accumulation in the median eminence despite the high circulating concentrations of prolactin suggests that long-term estradiol treatment reduces the ability of TIDA neurons to respond to prolactin. This was confirmed by the finding that direct intracerebroventricular (icv) injections of prolactin increased the rate of DOPA accumulation in the median eminence of sham-implanted rats but not in 18 day estradiol-treated rats. To determine if the effects of estradiol were reversible, ovariectomized rats were implanted with estradiol-containing capsules for 18 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Strengthening mechanisms in Ti-Nb-Zr-Ta and Ti-Mo-Zr-Fe orthopaedic alloys.

The microstructural evolution and attendant strengthening mechanisms in two novel orthopaedic alloy systems, Ti-Nb-Zr-Ta and Ti-Mo-Zr-Fe, have been compared and contrasted in this paper. Specifically, the alloy compositions considered are Ti-34Nb-9Zr-8Ta and Ti-13Mo-7Zr-3Fe. In the homogenized condition, both alloys exhibited a microstructure consisting primarily of a beta matrix with grain boundary alpha precipitates and a low-volume fraction of intra-granular alpha precipitates. On ageing the homogenized alloys at 600 degrees C for 4 hr, both alloys exhibited the precipitation of refined scale secondary alpha precipitates homogeneously in the beta matrix. However, while the hardness of the Ti-Mo-Zr-Fe alloy marginally increased, that of the Ti-Nb-Zr-Ta alloy decreased substantially as a result of the ageing treatment. In order to understand this difference in the mechanical properties after ageing, TEM studies have been carried out on both alloys prior to and post the ageing treatment. The results indicate the existence of a metastable B2 ordering in the Ti-Nb-Zr-Ta alloy in the homogenized condition which is destroyed by the ageing treatment, consequently leading to a decrease in the hardness.

Alloys↗

Porous single-phase NiTi processed under Ca reducing vapor for use as a bone graft substitute.

Porous nickel-titanium alloys (NiTi, nitinol) have recently attracted attention in clinical surgery because they are a very interesting alternative to the more brittle and less machinable conventional porous Ca-based ceramics. The main remaining limitations come from the chemical homogeneity of the as-processed porous nickel-titanium alloys, which always contain undesired secondary Ti- and Ni-rich phases. These are known to weaken the NiTi products, to favor their cavitation corrosion and to decrease their biocompatibility. Elemental nickel must also be avoided because it could give rise to several adverse tissue reactions. Therefore, the synthesis of porous single-phase NiTi alloys by using a basic single-step sintering procedure is an important step towards the processing of safe implant materials. The sintering process used in this work is based on a vapor phase calciothermic reduction operating during the NiTi compound formation. The as-processed porous nickel-titanium microstructure is single-phase and shows a uniformly open pore distribution with porosity of about 53% and pore diameters in the range 20-100 microm. Furthermore, due to the process, fine CaO layers grow on the NiTi outer and inner surfaces, acting as possible promoting agents for the ingrowth of bone cells at the implantation site.

Alloys↗

Time course of the effect of a bolus dose of intrathecal baclofen on severe cerebral spasticity.

Continuous intrathecal administration of baclofen with implanted programmable pump systems is recommended in the treatment of severe spasticity of cerebral origin. Prior to pump implantation, a baclofen bolus test (BBT) is used to assess the effectiveness of intrathecal baclofen using clinical scales such as the Modified Ashworth Scale (MAS). In the literature, the time and period of maximum effect of a bolus dose of intrathecally administered baclofen in patients with cerebral spasticity is variously reported. The aim of the study was, therefore, to reveal the time course of the effect of a BBT on severe cerebral spasticity by the use of a recently described spasticity measurement method. Spasticity in knee joints of 13 patients with severe cerebral spasticity was repeatedly assessed using the MAS and also continuously recorded by the measurement of force under circular fibreglass casts. Force was recorded as nettorque by multiplying the force by the distance between sensor and joint axis, thus allowing inter-individual comparison. Half-hour time integrals (TI) of net-torque were determined 9 hours before and 22 hours after intrathecal baclofen administration. Post-BBT half-hour time integrals (TI(+0), TI(+0.5), to TI(+22)) were compared with the mean of 17 pre-BBT half-hour time integrals. Significantly lower post-BBT half-hour time integrals compared with were found between TI(+2) and TI(+8) (Dunnett adjusted p < 0.05). The median lowest TI after BBT of the 13 patients was TI(+4). The lowest mean MAS scores were found 4 hours after BBT. The findings suggest that the greatest effect of BBT on cerebral spasticity occurs between 2 and 8.5 hours, with a maximal effect at 4 hours after intrathecal baclofen injection. Clinical scales used to determine the effect of BBT should thus be carried out during this period-ideally at 4 hours after baclofen injection.

Adult↗

Physico-chemical considerations of titanium as a biomaterial.

Physico-chemical properties of titanium are discussed. Special attention is paid to those of amorphous TiO 2 that contact tissues in vivo. In aqueous environments TiO 2. (aq) has low ion-formation tendency and low reactivity with macromolecules. This is accompanied by low toxicity. Titanium does not facilitate reactive oxygen radical generation during inflammatory conditions as observed in in-vitro experiments. The outermost layers of the oxide are in the Ti(IV) oxidation state, although using electron spin resonance (ESR) techniques, formation of Ti(III) is observed at atmospheric conditions. The impact of similarities between water and TiO 2 is speculated upon, and the physico-chemical properties of titanium are tentatively linked to some in-vivo consequences.

Biocompatible Materials↗

The role of whole blood in thrombin generation in contact with various titanium surfaces.

Understanding of the thrombotic response (activation of the intrinsic coagulation system followed by platelet activation) from blood components upon contact with a titanium dental implant is important and not fully understood. The aims of this study were to evaluate: (1) the thrombogenic response of whole blood, platelet-rich plasma (PRP) and platelet-poor plasma (PPP) in contact with a highly thrombogenic surface as titanium, (2) the thrombogenic response of clinically used surfaces as hydroxyapatite (HA), machined titanium (mTi), TiO2 grit-blasted titanium (TiOB) and fluoride ion-modified grit-blasted titanium (TiOB-F). An in vitro slide chamber model, furnished with heparin, was used in which whole blood, PRP or PPP came in contact with slides of the test surfaces. After incubation (60 min rotation at 22 rpm in a 37 degrees C water bath), blood/plasma was mixed with EDTA or citrate, further centrifuged at +4 degrees C (2200 g at 10 min). Finally, plasma was collected pending analysis. Whole blood in contact with Ti alloy resulted in the binding of platelets to the material surface and in the generation of thrombin-antithrombin (TAT) complexes. With whole blood TAT levels increased 1000-fold compared with PRP and PPP, in which both almost no increase of TAT could be detected. In addition, the platelet activation showed a similar pattern with a 15-fold higher release of beta-TG in whole blood. In the in vitro chamber model with the clinically relevant materials, the fluoride-modified surface (TiOB-F) showed pronounced TAT generation compared with TiOB, mTi and HA. Similar results were achieved for platelet consumption and activation markers of the intrinsic coagulation system. Taken together these results implicate first that whole blood is necessary for sufficient thrombin generation and platelet activation during placement of implants. Second, a fluoride ion modification seems to augment the thrombogenic properties of titanium.

Biocompatible Materials↗

In vivo study on biocompatibility and bonding strength of hydroxyapatite-20vol%Ti composite with bone tissues in the rabbit.

Biocompatibility and bonding strength of hydroxyapatite-20vol%Ti composite fabricated by hot-pressing technique with bone tissues in the rabbit were investigated by in vivo studies in comparison with those of Ti metal and dense HA ceramic. Although fibrous tissues formed at the interface between the composite and bone tissues at 3 weeks in vivo, bonding strength of the composite increases faster than that of dense HA after 4 weeks. At 3 months in vivo, bonding strength of the composite is higher than that of dense HA and exceeds 6.5 MPa. Moreover, as compared with the visible bonding interfaces between dense HA and new bones, the bonding interfaces for the composite cannot already be distinguished and the composite was osseointegrated fully with bone tissues into one bony body. The shear fracture of bonding strength test for the composite occurred in new bone zones near the interface, which indicates that bonding strength of the composite could even exceed the shear strength of new bones after 3 months in vivo. In conclusion, HA-Ti composite has better osteoconduction and osseointegration abilities than Ti metal and dense HA ceramic after 3 months in vivo and is a promising biomaterial for hard tissue replacement.

Adhesiveness↗

Biocompatibility and charge injection property of iridium film formed by ion beam assisted deposition.

Iridium thin film formed by electron-beam evaporation with simultaneous bombardment of Ar ion beam was evaluated for a stimulating neural electrode. The electrochemical behavior of as-deposited Ir film on Ni-Ti sample was almost identical to bulk Ir by producing much higher open-circuit corrosion potential and much lower anodic current density than the uncoated Ni-Ti in both 1N sulfuric acid and saline solution. The charge injection capability of Ir film was compared with that of Pt electrode currently used mostly as a stimulating neural electrode. The charge density of Pt was small and unchanged with increasing number of activating cycles in 0.1M H(2)SO(4), whilst the Ir film continuously produced increases in charge density. The charge injection density of Ir film in physiological solution was higher for the more activated sample under the identical stimulating condition. Attachment and proliferation with PC12 cells on Ir-coated CP Ti without applying electrical stimulation was similar to the polished CP Ti. A network of neurons and extending axons were formed on Ir film.

Animals↗

Electrochemically assisted co-precipitation of protein with calcium phosphate coatings on titanium alloy.

A bovine serum albumin protein-containing calcium phosphate coating (BSA/brushite) was prepared by electrochemically assisted co-precipitation onto a hydroxyapatite (HA) coated Ti-6Al-4V surface. Electrochemically assisted co-precipitation of BSA/brushite coatings onto HA resulted in a 70-fold increase in BSA inclusion compared to simple adsorption, and was subsequently released by a slower mechanism (15% loss over 70 h). Thus, this electrochemically assisted co-precipitation technique provides an efficient method of protein incorporation at physiological temperature, with a potential for sustained release of therapeutic agents as may be required for metallic implant fixation.

Adsorption↗

TiN: a suitable coating for defibrillator electrodes?

The electrochemical behavior of porous TiN coating for defibrillator electrodes was investigated by in vitro studies. A commercially available Ti patch was compared with a Ti patch coated with a layer of porous TiN. Similarly, the influence of the TiN coating on a Pt/Ir intracardial electrode was tested. Porous TiN coatings were made by reactive sputtering on the plain electrodes. Electrode potential measurements were performed during monophasic anodic and cathodic defibrillator shocks delivering energies between 1 J and 49 J. Porous TiN coating of Pt/Ir coils was found suitable to deliver cathodal pulses, while a plain coil remains recommended for anodic shocks. TiN coating was of benefit for conventional Ti patches. Particularly, in the case of anodic shocks, the TiN layer protected the Ti-mesh from immediate oxidation. However, above 70 anodic shocks of 49 J, the TiN coating underwent oxidation to an oxynitride. An estimated 180 anodic shocks of 10 J could be delivered before TiN oxidation became measurable by increased polarization.

Biocompatible Materials↗

Role of ceramic implants. Design and clinical success with total hip prosthetic ceramic-to-ceramic bearings.

Ceramic implants have become of great interest because of the increased awareness that wear debris from metal-polyethylene components of total hip prostheses can cause osteolysis around implants. Polyethylene wear rates with the Charnley total hip prosthesis were found to be from 0.1 to 0.2 mm/year in the elderly, which corresponded to 30 to 80 mm3 of polyethylene debris being released to the joint tissues. This in turn can be related to 40 million to 40 billion particles being released into the joint every year. This polyethylene particulate is heavily implicated in the osteolytic destruction of periarticular tissues. The ceramic ball, ceramic cup combination of total hip prostheses may have promise of wear rates that could be thousands of times smaller than polyethylene alone. Such alumina ceramic prosthetic concepts were introduced in Europe from 1970 to 1973. Under Food and Drug Administration regulations at that time, the only U.S. introductions allowed circa 1980 were the Autophor and Xenophor types of ceramic prostheses. However, this particular prosthetic design was not successful in the United States because of pain, neck-socket impingement, ceramic fracture, and component loosening. This did not therefore appear to be a successful compromise in the hands of U.S. surgeons. Ceramic innovations from Europe now include cemented ceramic cups of "matching" tolerances with the femoral ball, and press-fit Ti-alloy acetabular shells with modular ceramic inserts. In addition, alumina and zirconia ceramic balls are now in routine clinical use in Europe. The objectives of this Symposium are to highlight these ceramic ball, ceramic cup innovations with their long-term clinical results from Europe. Then one can evaluate which of these innovations in material and design selections offers the best possible alternatives in the 1990s.

Alloys↗

Interleukin (IL)-1beta regulation of IL-1beta and IL-1 receptor antagonist expression in cultured human endometrial stromal cells.

The interleukin (IL)-1 system is a major regulator of local cellular interactions during embryonic implantation. Because IL-1beta and IL receptor antagonist (IL-1ra) are both expressed in human endometrium, we hypothesized that an appropriate ratio of IL-1beta to IL-1ra might favor the process of embryo implantation. Therefore, we investigated IL-1 regulation of the quantitative ratio of IL-1beta/IL-1ra messenger RNA (mRNA) expression in human endometrial stromal cells using quantitative competitive PCR, as well as intracellular protein expression after stromal cell solubilization. Confluent stromal cell cultures were stimulated with human IL-1beta (0-1000 IU/mL) for 24 h. After 24 h, total RNA was extracted, reverse transcribed, and coamplified by PCR with a defined amount of internal standard. The quantitative ratio was determined by the density of target to the internal standard. After culture with IL-1beta for 24 and 48 h, stromal cells were solubilized, and the intracellular protein levels of IL-1beta and IL-1ra were measured by enzyme-linked immunosorbent assay. The IL-1beta and IL-1ra mRNA were both up-regulated, and IL-1R tI mRNA was down-regulated, by IL-1beta in a dose-dependent manner. The quantitative ratio of IL-1beta to IL-1ra mRNA was constant with the presence of increasing concentrations of IL-1beta (1-1000 IU/mL). IL-1beta and IL-1ra protein was not detected in conditioned media of cultures before addition of IL-1beta. IL-1beta and IL-1ra protein levels increased with increasing amounts of IL-1beta after solubilization of stromal cells. The IL-1beta was detectable after 12 h of culture, in comparison with IL-1ra, which was detectable after 24 h of IL-1beta stimulation. These results suggest that IL-1 may play a crucial role in embryo-maternal interaction by regulating stromal cell expression of IL-1beta and IL-1ra, resulting in an appropriate ratio during the process of embryonic implantation.

Binding, Competitive↗

Monocyte activation on titanium-sputtered polystyrene surfaces in vitro: the effect of culture conditions on interleukin-1 release.

The release of interleukin-1 alpha (IL-1 alpha) by human peripheral blood monocytes cultured for 24 and 48 h on polystyrene (PS) and titanium-sputtered polystyrene (Ti) was evaluated. Magnetron sputtering of the PS surfaces resulted in a formation of a 50-nm-thick coat, consisting of an outer layer of TiO2. Monocytes released IL-1 alpha without the addition of exogenous stimuli. A doubling of the culture time from 24 to 48 h did not have a major effect on the amount of IL-1 alpha released. The IL-1 alpha levels were increased by addition of lipopolysaccharide (LPS). High concentrations of PS particles (1 and 3 microns diameter) were equally effective stimuli for IL-1 alpha release as LPS. Preadsorption of fibronectin to culture plates augmented LPS-stimulated IL-1 alpha secretion, whereas preadsorbed fibrinogen had an inhibitory effect. Our observation indicate a direct activation of monocytes by PS and Ti, resulting in IL-1 alpha secretion, which is modified by protein adsorption and exogenous stimuli.

Adsorption↗