RESUMEN
Failure of soft tissue implants has been largely attributed to the influence of biomaterial surface properties on the foreign body response, but some implant complications, e.g. macrophage accumulation and necrosis, are still not effectively addressed with surface treatments to minimize deleterious biomaterial effects. We explored an alternative explanation for implant failure, linking biocompatibility with implant micromotion-induced pressure fluctuations at the tissue-biomaterial interface. For this purpose, we used a custom in vitro system to characterize the effects of pressure fluctuations on the activity of macrophages, the predominant cells at a healing implant site. Initially, we quantified superoxide production by HL60-derived macrophage-like cells under several different pressure regimes with means of 5-40 mmHg, amplitudes of 0-15 mmHg and frequencies of 0-1.5 Hz. All pressure regimes tested elicited significantly (p < 0.05) reduced superoxide production by macrophage-like cells relative to parallel controls. Notably, pressure-sensitive reductions in superoxide release correlated (r(2) = 0.74; p < 0.01) only with pulse pressures. Based on the connection between superoxide production and cell viability, we also explored the influence of cyclic pressure on macrophage numbers and death. Compared to controls, adherent macrophage-like cells exposed to 7.5/2.5 mmHg cyclic pressures for 6 h exhibited significantly (p < 0.01) reduced cell numbers, independent of cell death. A similar effect was observed for cells treated with 10 U/ml superoxide dismutase. Collectively, our results suggest that pressure pulses are a putative regulator of macrophage adhesion via a superoxide-related effect. Pressure fluctuations, e.g. due to implant micromotion, may, therefore, potentially modulate macrophage-dependent wound healing.
Asunto(s)
Macrófagos/metabolismo , Presión , Prótesis e Implantes , Superóxidos/metabolismo , Adhesión Celular , Muerte Celular , Supervivencia Celular , Citosol/metabolismo , Células HL-60 , Humanos , Hidrodinámica , Superóxido Dismutasa/metabolismo , Propiedades de Superficie , Factores de TiempoRESUMEN
Titanium is widely used clinically, yet little is known regarding the effects of modifying its three-dimensional surface geometry at the nanoscale level. In this project we have explored the in vivo response in terms of nitric oxide scavenging and fibrotic capsule formation to nano-modified titanium implant surfaces. We compared titanium dioxide (TiO(2)) nanotubes with 100 nm diameters fabricated by electrochemical anodization with TiO(2) control surfaces. Significantly lower nitric oxide was observed for the nanostructured surface in solution, suggesting that nanotubes break down nitric oxide. To evaluate the soft tissue response in vivo TiO(2) nanotube and TiO(2) control implants were placed in the rat abdominal wall for 1 and 6 weeks. A reduced fibrotic capsule thickness was observed for the nanotube surfaces for both time points. Significantly lower nitric oxide activity, measured as the presence of nitrotyrosine (P<0.05), was observed on the nanotube surface after 1 week, indicating that the reactive nitrogen species interaction is of importance. The differences observed between the titanium surfaces may be due to the catalytic properties of TiO(2), which are increased by the nanotube structure. These findings may be significant for the interaction between titanium implants in soft tissue as well as bone tissue and provide a mechanism by which to improve future clinical implants.
Asunto(s)
Implantes Experimentales , Nanotubos/química , Especificidad de Órganos/efectos de los fármacos , Titanio/farmacología , Animales , Recuento de Células , Fibrosis , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Nanotubos/ultraestructura , Óxido Nítrico/metabolismo , Ratas , Ratas Sprague-Dawley , Dióxido de Silicio/farmacología , Propiedades de Superficie/efectos de los fármacos , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMEN
Implant topography is critical to the clinical success of bone-anchored implants, yet little is known how nano-modified implant topography affects osseointegration. We investigate the in vivo bone bonding of two titanium implant surfaces: titanium dioxide (TiO(2)) nanotubes and TiO(2) gritblasted surfaces. In previous in vitro studies, the topography of the TiO(2) nanotubes improved osteoblast proliferation and adhesion compared with gritblasted titanium surfaces. After four weeks of implantation in rabbit tibias, pull-out testing indicated that TiO(2) nanotubes significantly improved bone bonding strength by as much as nine-fold compared with TiO(2) gritblasted surfaces. Histological analysis confirmed greater bone-implant contact area, new bone formation, and calcium and phosphorus levels on the nanotube surfaces. It is anticipated that further studies will contribute to a better understanding of the effect of implant nanotopography on in vivo bone formation and bonding strength.
Asunto(s)
Huesos , Nanotubos , Titanio , Animales , Microscopía Electrónica de Rastreo , ConejosRESUMEN
The titanium dioxide (TiO(2)) nanotube surface enables significantly accelerated osteoblast adhesion and exhibits strong bonding with bone. We prepared various sizes (30-100 nm diameter) of titanium dioxide (TiO(2)) nanotubes on titanium substrates by anodization and investigated the osteoblast cellular behavior in response to these different nanotube sizes. The unique and striking result of this study is that a change in osteoblast behavior is obtained in a relatively narrow range of nanotube dimensions, with small diameter ( approximately 30 nm) nanotubes promoting the highest degree of osteoblast adhesion, while larger diameter (70-100 nm) nanotubes elicit a lower population of cells with extremely elongated cellular morphology and much higher alkaline phosphatase levels. Increased elongation of nuclei was also observed with larger diameter nanotubes. By controlling the nanotopography, large diameter nanotubes, in the approximately 100 nm regime, induced extremely elongated cellular shapes, with an aspect ratio of 11:1, which resulted in substantially enhanced up-regulation of alkaline phosphatase activity, suggesting greater bone-forming ability than nanotubes with smaller diameters. Such nanotube structures, already being a strongly osseointegrating implant material, offer encouraging implications for the development and optimization of novel orthopedics-related treatments with precise control toward desired cell and bone growth behavior.
Asunto(s)
Sustitutos de Huesos/química , Nanotubos/química , Nanotubos/ultraestructura , Osteoblastos/citología , Osteogénesis/fisiología , Ingeniería de Tejidos/métodos , Titanio/química , Células 3T3 , Animales , Técnicas de Cultivo de Célula/métodos , Tamaño de la Célula , Supervivencia Celular , Cristalización/métodos , Ensayo de Materiales , Ratones , Osteoblastos/fisiología , Propiedades de SuperficieRESUMEN
Neural devices may play an important role in the diagnosis and therapy of several clinical conditions, such as stroke, trauma or neurodegenerative disorders, by facilitating motor and pain control. Such interfaces, chronically implanted in the CNS, need to be biocompatible and have the ability to stimulate and record nerve signals. However, neural devices of today are not fully optimized. Nanostructured surfaces may improve electrical properties and lower evoked tissue responses. Vertical gallium phosphide (GaP) nanowires epitaxially grown from a GaP surface is one way of creating nanostructured electrodes. Thus, we chose to study the soft tissue reactions evoked by GaP surfaces. GaP and the control material titanium (Ti) were implanted in the rat abdominal wall for evaluation of tissue reactions after 1, 6, or 12 weeks. The foreign-body response was evaluated by measuring the reactive capsule thickness and by quantification of ED1-positive macrophages and total cells in the capsule. Furthermore, the concentration of Ga was measured in blood, brain, liver and kidneys. Statistically significant differences were noticed between GaP and Ti at 12 weeks for total and ED1-positive cell densities in the capsule. The chemical analysis showed that the concentration of Ga in brain, liver and kidneys increased during 12 weeks of implantation, indicating loss of Ga from the implant. Taken together, our results show that the biocompatible properties of GaP are worse than those of the well-documented biomaterial Ti.
Asunto(s)
Materiales Biocompatibles , Reacción a Cuerpo Extraño , Galio , Implantes Experimentales , Fosfinas , Prótesis e Implantes , Pared Abdominal/cirugía , Animales , Masculino , Ratas , Ratas Sprague-Dawley , TitanioRESUMEN
We propose that the mechanical property of the interface between an implant and its surrounding tissues is critical for the host response and the performance of the device. The interfacial mechanics depends on several different factors related to the physical shape of the device and its surface as well as properties of the host tissue and the loading conditions of the device and surrounding tissue. It seems plausible that the growth of the fibrotic tissue to support mechanical loads is governed by the same principles as depicted by Wolfs' Law for bone. Of course, biocompatibility will have different implications depending on which vantage point we look at the host-material interface. Another implication is that only limited aspects of biocompatibility is measurable with current in vitro tests and that the elicited host response in vivo models remains crucial for evaluation of medical devices and tissue engineering constructs.
Asunto(s)
Materiales Biocompatibles/metabolismo , Ingeniería de Tejidos , Animales , Humanos , Implantación de Prótesis , Estrés Mecánico , Cicatrización de HeridasRESUMEN
This study describes a new method for the fixation of titanium hip stem prostheses based on interdigitation of irregularly shaped porous titanium granules onto bone tissue. The granules were distributed into the prepared femoral cavity using a vibrating tool, and the stem was vibrated and tapped into the bed of granules. In this pilot study, 5 patients were followed between 9 and 15 years. The clinical results were excellent and the prostheses remained stable. Autopsy (one specimen) and computer tomography (three patients) show that the granules become incorporated by bone ingrowth.
Asunto(s)
Fémur , Prótesis de Cadera , Titanio , Vibración , Anciano , Artroplastia de Reemplazo de Cadera , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Tomografía Computarizada por Rayos XRESUMEN
Prolonged inflammation and reactive oxygen species (ROS) generated around an implanted biosensor are the primary causes of the foreign body response, including encapsulation of biosensor membranes. We have previously demonstrated that TiO2 surfaces reduce ROS. Here we investigated the potential of using the anti-inflammatory properties of TiO2 in the design of biosensor membranes with improved long-term in vivo transport properties. Micropatterned Ti films were sputtered onto quartz surfaces in a series of hexagonally distributed dots with identical coverage area of 23% and dot size ranging from 5 to 100 microm. The antioxidant effect of the surfaces was investigated using a cell-free peroxynitrite donor assay and assays of superoxide released from stimulated surface-adhering neutrophils and macrophages. In all three assays, the amount of ROS was monitored using luminol-amplified chemiluminescence. Patterned surfaces in all experimental models significantly decreased ROS compared to the etched surfaces. In the cell-free experiment, the ROS reduction was only dependent on fractional surface coverage. In the cell experiments, however, a dot-size-dependent ROS reduction was seen, with the largest reduction at the smallest dot-size surfaces. These results indicate that micropatterned surfaces with small dots covering only 23% of the surface area exhibit similar antioxidative effect as fully covered surfaces.
Asunto(s)
Antiinflamatorios/metabolismo , Técnicas Biosensibles , Materiales Biocompatibles Revestidos/metabolismo , Titanio/metabolismo , Animales , Antiinflamatorios/química , Línea Celular , Macrófagos/citología , Macrófagos/metabolismo , Ratones , Molsidomina/análogos & derivados , Molsidomina/metabolismo , Donantes de Óxido Nítrico/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Propiedades de Superficie , Titanio/químicaRESUMEN
To evaluate the predictive value of cytotoxicity testing, the present study compares the in vivo tissue responses to in vitro cytotoxicity before and after implantation. Material toxicity was caused by addition of the toxic substance Zincdiethyldithiocarbamate (ZDEC) that is used as a standard for in vitro cytotoxicity testing. Polyurethane discs with the addition of 0.5% or 1% ZDEC as well as nontoxic discs were inserted in the abdominal wall of rats for 1 day up to 6 weeks. After explantation the foreign body response was analyzed immunohistochemically. An in vitro reanalysis of the explanted reference materials (RMs) revealed remaining high concentrations of toxic compounds after 1-week implantation, whereas no toxicity was seen after 6 weeks implantation. This was reflected in the foreign body response where a significantly thicker capsule and more inflammatory cells were seen at 1 week for the toxic implants. Over time, with decreasing toxicity, these differences disappeared. Test samples that only were subjected to in vitro extraction with water did not elute toxic compounds to the same extent as the in vivo conditions. It is concluded that many clinically useful implant materials may be unnecessarily rejected due to the results of in vitro tests.