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Biomedical subjects

J A Jansen

Publications and source records attributed to J A Jansen.

At least 109 records · Page 6Linked to original sources

Performance of subcutaneously implanted glucose sensors for continuous monitoring.

Despite a considerable amount of research attributed to the development of an implantable glucose sensor, to date there is no clinically applicable concept for continuous glucose monitoring. Investigations to validate the subcutaneous tissue for continuous glucose sensing mostly comprised short-term implantations of glucose sensors. Most implanted glucose sensors showed a significant drift in sensitivity over the implantation period. This bioinstability was not to be expected from the in vitro performance of the sensors. In this paper, the influence of possible failure mechanisms on the poor in vivo performance of subcutaneously implanted glucose sensors is reviewed.

Animals↗

In vitro dentine hardness following gamma-irradiation and freezing.

OBJECTIVES: To investigate the short term effects of gamma-irradiation and conventional freezing on the hardness of human dentine. METHODS: Twenty-one dentine disks were produced by transverse sectioning 21 sound extracted human permanent molar teeth. The 2.1 mm thick disks were wet polished using 4000 grit polishing paper. Three lines were drawn dividing each disk into six symmetrical areas. Seven disks were randomly assigned for freezing in water at -18 degrees C for 12 days; seven were exposed to a single dose of 25.2 kGy gamma radiation in water; seven were kept in water at 20 degrees C for 12 days (control). Before treatment, three Vicker's indentations at a load of 30 kg and a dwelling time of 20 s were made in one half of each disk, at equal distances from its edge and centre. Using light microscopy and image analysis software, the indentation diagonals were measured 4 h after preparation. Vicker's hardness values (VHN = kg/mm2) were calculated for each indentation. Following the treatment, VHNs were calculated again, for three symmetrical indentations in the second half of each disk. A statistical analysis was performed using the Wilcoxon rank sum test. RESULTS: The frozen group showed no changes following the treatment (VHN = 58 +/- 6 before vs. 57 +/- 6 after). The irradiation and control groups showed some hardening (VHN = 53 +/- 7 vs. 59 +/- 8; 57 +/- 3 vs. 63 +/- 6, respectively), however all values were within the normal variation. CONCLUSION: Both conventional freezing at -18 degrees C for 12 days in water, and a single gamma-irradiation dose of 25.2 kGy in water, appeared to have no short term effects on the hardness of human coronal dentine.

Dentin↗

Soft tissue and epithelial models.

The applicability of a biomaterial for the manufacturing of oral implants is determined by its physicochemical and geometric surface properties. Research, therefore, is concerned with the cellular reactions that occur when an implant material comes into contact with body tissues. For permucosal oral implants, this involves both the reaction of bone and gingival cells. In vitro cell culturing--including the use of various analytical techniques like light microscopy, scanning and transmission electron microscopy, confocal laser scanning microscopy, and digital image analysis--is a good tool whereby investigators can obtain more insight into the relevant components of implant-tissue adhesion. In the current overview, the role of cell models in oral implant research is discussed, specifically with reference to responses of epithelial cells and fibroblasts.

Alveolar Process↗

Microgrooved subcutaneous implants in the goat.

We investigated the behavior of microgrooved implants in soft tissue using polystyrene implantable disks, either smooth or microgrooved (1-10 microm) on both sides. The implants were placed subcutaneously in a goat for 1, 4, or 12 weeks. Light and transmission electron microscopy showed that fibrous capsule formation around the implants was fairly uniform. After 1 week the implants were covered with a fibrous capsule about 80 microm thick. The collagen matrix was loose, and many inflammatory cells were present. After 4 weeks the matrix was more dense and contained many newly formed blood vessels. At the implant surface a layer of inflammatory cells about 10 microm thick had accumulated. Finally, after 12 weeks the matrix had densified. One cellular layer of inflammatory cells was present at the implant surface. We carried out histomorphometric measurements of capsule thickness, inflammatory layer thickness, and the number of blood vessels. Capsule thickness appeared not to decrease with time. Further, these measurements showed that there were no differences in tissue reaction between smooth and microgrooved implants. On the basis of our observations, we suggest that 1 microm deep and 1-10 microm wide microgrooves do not influence tissue response around polystyrene implants in soft tissue.

Animals↗

Measurement and control of interface strength of RF magnetron-sputtered Ca-PO coating on Ti-6Al-4V substrates using a laser spallation technique.

In previous studies, an RF magnetron sputter technique was developed for the production of thin calcium phosphate coating. Several deposition parameters were found to influence the growth rate and the stoichiometry of the coatings. For instance, deposition with additional oxygen pressure decreased the Ca to P ratio of the coatings to 1.67. For application of these coatings on actual Ti implants, it is important to know their adhesive tensile strength with the implant surface and how it varies with the deposition parameters. Motivated by these goals, the aim of this study was to measure the adhesive tensile strength of these coatings with Ti substrates and to study its variation with the deposition parameters. Since most mechanical characterization methods are incapable of providing a direct measure of the interface's fundamental strength, a novel laser spallation experiment was used to accomplish this task. In this experiment, a compressive stress pulse is generated on the back side of a substrate by impinging a 3-ns long Nd:YAG laser pulse. The stress pulse propagates through the substrate and is reflected into a tensile stress wave from the free surface of the coating deposited on its front surface. The returning tensile pulse pries off the coating if its amplitude is high enough. The peak interface tensile stress is computed by using the optically recorded free surface displacement of the coating. Because interface decohesion is accomplished at a strain rate of almost 10(7) s-1, all inelastic processes essentially are suppressed and the measured value essentially is the intrinsic tensile strength of the interface. Tensile strength values in the range of 500-900 MPa were recorded for the interfaces between sputter-deposited calcium-phosphate coatings and Ti substrates. To confirm the locus of failure, the spalled spots were examined using SEM and EDS. The variation in the measured values was related to the changes in the deposition conditions.

Alloys↗

Scanning electron microscopic, transmission electron microscopic, and confocal laser scanning microscopic observation of fibroblasts cultured on microgrooved surfaces of bulk titanium substrata.

During this study, microtechnology and plasma etching were used to produce gratings 1.0 (TiD01), 2.0 (TiD02), 5.0 (TiD05), and 10.0 microns wide (TiD10) into commercially pure titanium wafers. After incubation of rat dermal fibroblast (RDFs) on these surfaces for 3 days, the cells were observed with scanning electron (SEM), transmission electron (TEM), and confocal laser scanning microscopy (CLSM). Results showed that the RDFs as a whole and their stress fibers oriented strictly parallel to the surface pattern on the TiD01 and TiD02 surfaces. On the TiD05 and TiD10 surfaces, this orientation was not observed. In addition, TEM and CLSM demonstrated that the focal adhesion points (FAP) were located mainly on the surface pattern ridges. TEM revealed that FAP were wrapped occasionally around the edges of the ridges. Only the RDFs on both the TiD05 and TiD10 surfaces protruded into the grooves and possessed FAP on the walls of the grooves. Attachment to the groove floor was observed only on the TiD10 textures. Comparison of these results with earlier observations on microtextured silicone rubber substrata suggests that material-specific properties do not influence the orientational effect of the surface texture on the observed RDF cellular behavior. The proliferation rate of the RDFs, however, seems to be much higher on titanium than on silicone rubber substrata.

Animals↗

Interfacial phenomena: an in vitro study of the effect of calcium phosphate (Ca-P) ceramic on bone formation.

In previous studies we developed a RF magnetron sputter technique for the production of thin Ca-P coatings. With this technique coatings can be produced that vary in Ca/P ratio as well as in structural appearance. The aim of this investigation was to obtain more understanding of the biological behavior of these coatings by way of in vitro experiments. The effect of noncoated titanium (Ti) and three different Ca-P-sputtered surfaces on the proliferation and differentiation (morphology and matrix production) of osteoblast-like cells was studied. Proliferation was determined using counting procedures; morphology was studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Fluorescent markers and energy-dispersive X-ray microanalysis (EDX) were used to obtain quantitative and compositional information about the resultant calcified extracellular matrix (ECM). Results demonstrated that proliferation of the osteoblast-like cells was significantly (p < 0.05) higher on noncoated than on Ca-P-coated samples. On the other hand, more mineralized ECM was formed on the coated surfaces. In addition, TEM confirmed that the cells on the coated substrates were surrounded by ECM with collagen fibers embedded in crystallized, needle-shaped structures. On the basis of these findings, we concluded that: (1) the investigated Ca-P sputter coatings possess the capacity to activate the differentiation and expression of osteogenic cells, and (2) bone formation proceeds faster on Ca-P surfaces than on Ti substrates. Further, this bone-inductive effect appeared to be dependent on the Ca-P ratio of the deposited coatings.

Animals↗

In vivo dissolution behavior of various RF magnetron sputtered Ca-P coatings.

Radiofrequency magnetron sputter deposition was used to deposit Ca-P sputter coatings on titanium discs, and these coatings were implanted subcutaneously into the backs of rabbits. Half of the as-sputtered coatings were subjected to additional heat treatment for 2 h at 500 degrees C. X-ray diffraction (XRD) demonstrated that annealing at 500 degrees C changed the amorphous sputtered coating into an amorphous-crystalline apatite structure. Scanning electron microscopic (SEM) examination of the sputtered coatings showed excellent coverage of the substrate surface. Annealing of the 4-microm-thick coatings resulted in the appearance of small cracks. SEM demonstrated that until 4 weeks of implantation, all heat-treated coatings were present and all amorphous coatings were completely or mostly dissolved. Fourier transform infrared spectroscopy showed the formation of carbonate apatite (CO3-AP) on these specimens. Furthermore, XRD analysis showed that these CO3-AP precipitated coatings disappeared after 8 weeks of implantation. On the other hand, SEM inspection of these specimens revealed that the 4-microm heat-treated coating was still partially maintained and that small Ca-P crystals were present on the titanium substrate. On the basis of these results, we conclude that apparently 0.1 microm heat-treated Ca-P sputter coating is of sufficient thicknesses to stimulate carbonate apatite deposition under in vivo conditions.

Animals↗

Orientation of ECM protein deposition, fibroblast cytoskeleton, and attachment complex components on silicone microgrooved surfaces.

The microfilaments and vinculin-containing attachment complexes of rat dermal fibroblasts (RDF) incubated on microtextured surfaces were investigated with confocal laser scanning microscopy (CLSM) and digital image analysis (DIA). In addition, depositions of bovine and endogenous fibronectin and vitronectin were studied. Smooth and microtextured silicone substrata were produced that possessed parallel surface grooves with a groove and ridge width of 2.0, 5.0, and 10.0 microns. The groove depth was approximately 0.5 micron. CLSM and DIA make it possible to visualize and analyze intracellular and extracellular proteins and the underlying surface simultaneously. It was observed that the microfilaments and vinculin aggregates of the RDFs on the 2.0 microns grooved substrata were oriented along the surface grooves after 1, 3, 5, and 7 days of incubation while these proteins were significantly less oriented on the 5.0 and 10.0 microns grooved surfaces. Vinculin was located mainly on the surface ridges on all textured surfaces. In contrast, bovine and endogenous fibronectin and vitronectin were oriented along the surface grooves on all textured surfaces. These proteins did not seem to be hindered by the surface grooves since many groove-spanning filaments were found on all the microgrooved surfaces. In conclusion, it can be said that microtextured surfaces influence the orientation of intracellular and extracellular proteins. Although results corroborate three earlier published hypotheses, they do not justify a specific choice of any one of these hypotheses.

Animals↗

Histomorphometrical and mechanical evaluation of titanium plasma-spray-coated implants placed in the cortical bone of goats.

The aim of this study was to investigate the biological and mechanical response of bone to titanium plasma-sprayed implants of different roughnesses. Three types of titanium plasma-spray coating were applied to beam-shaped implants: Ti2, Ti3, and Ti4, with a Ra of 16.5, 21.4, and 37.9 microm, respectively. An Al2O3 grit-blasted implant (Ti-un) with a Ra of 4.7 microm was used as a control. In total, 72 implants were inserted in the tibial cortical bone of nine adult female goats. These implants were evaluated histologically and mechanically 3 months after implantation. At the end of the experiment, of the 72 inserted implants, two implants (one Ti2 and one Ti4) were lost. Histological evaluation of the other retrieved implants revealed a uniform bone reaction for all implants. The unloaded plasma-spray coatings showed no signs of delamination at the implant-coating interface. Occasionally, particles of the Ti4 coating broke free and were found near the implant. Histomorphometry revealed no difference in bone contact for the different implants (P > 0.05). Furthermore, the push-out test showed no significant difference (P > 0.05). Linear regression showed no interaction between the push-out values and the roughness values (r = 0.5). On the basis of these results, it may be concluded that the used surface roughnesses did not lead to differences in bone response or mechanical attachment strength in goat cortical bone.

Animals↗

A complete characterization of Ca5(PO4)3OH sputter-deposited films by ion beam analysis: RBS and ERD.

RF magnetron sputter deposition was used to deposit thin calcium phosphate (hydroxyapatite) layers on titanium alloy substrate material. We determined the precise amount of calcium, phosphorus, oxygen, and hydrogen in these films by combining two ion-beam analysis techniques: Rutherford backscattering spectrometry (RBS) and elastic recoil detection (ERD). Variables were power level, partial oxygen pressure, or additional water vapor. Also examined was the influence of additional bias power to the substrates during deposition and the effect of annealing on the final composition of the deposited layers. Measurements showed that the Ca/P ratio decreased with increasing oxygen pressure or decreasing sputtering power. In addition, the Ca/P ratio increased when a bias was applied to the substrates. The O/P ratio of the films decreased with additional oxygen pressure but increased when additional water vapor was applied during deposition. All as-deposited films showed a higher hydrogen content than stoichiometric HA. The hydrogen content in the films deposited with water vapor was more than 7 times higher than in the films deposited under pure argon conditions. After annealing, the hydrogen content decreased to about 3.5 at % whereas in stoichiometric HA the hydrogen content amounts to 4.5 at %. After annealing, the oxygen concentration in the film also decreased. We assume that hydrogen disappears out of the film as H2O during annealing. For the targets used in these experiments, sputter deposition at 400 W, with additional water vapor and annealing at 500 degrees C, produced films with a stoichiometry closest to that of hydroxyapatite.

Biocompatible Materials↗

Subperiosteal implantation of various RF magnetron sputtered Ca-P coatings in goats.

The aim of this study was to obtain more information about the initial biological events around RF magnetron sputtered calcium phosphate (Ca-P) coatings. Therefore, uncoated and coated disks were inserted subperiosteal into the tibia of a goat. The coatings were deposited on commercially pure titanium. The thickness of the coating was 0.1 or 2.0 microm. All the as-sputtered coatings were subjected to an additional heat treatment for 2 h at 500 degrees C. After 1 and 3 weeks of implantation the experimental disks were retrieved and prepared for histological and physicochemical analysis. The histological results demonstrated that the periosteum covered the specimens after both implantation periods. In between the periosteum and implant an acellular layer and a collagen matrix was observed. Energy dispersive spectrometry revealed that the acellular layer consisted of C, Ca, and P ions for the 0.1 microm thick Ca-P coatings. The 2 microm thick Ca-P coatings also showed the presence of sulfate ions in this layer. Only organic material was found on the titanium disks. Further, SEM showed that even after 3-week implantation, a substantial thickness of both coatings was still maintained. Thin film X-ray diffraction demonstrated that after both implantation periods, the CaP-0.1 coating was still present. FTIR of the retrieved specimens demonstrated on the coated disks the formation of additional carbonate apatite (CO3-AP) associated with an organic phase (NH2 groups). On basis of these findings we conclude that our experimental approach is very suitable for the investigation of the healing process around Ca-P coatings. Further, we again demonstrated that the initial interfacial response to Ca-P materials differs from titanium.

Animals↗

Tiagabine, a novel antiepileptic agent: lack of pharmacokinetic interaction with digoxin.

OBJECTIVE: To assess the possibility of any clinically relevant pharmacokinetic interactions between tiagabine, a novel antiepileptic drug, and digoxin. METHODS: Potential pharmacokinetic interactions between tiagabine and digoxin were investigated in an open-label, two-period cross-over study in healthy male volunteers. Thirteen volunteers, aged between 18 and 43 years, were randomised to receive digoxin (0.5 mg twice a day for 1 day, then 0.25 mg once a day for 8 days) either alone or co-administered with tiagabine (4 mg three times daily for 9 days). Following a 7-day washout period, volunteers crossed over to the other dosing regimen. Peak serum concentration, time to maximum serum, concentration, area under the serum concentration-time curve from zero to 24 h and steady state serum concentration were calculated for digoxin and compared between treatment groups. RESULTS: No statistically significant differences between treatment groups were observed for any of the derived digoxin pharmacokinetic parameters. The most common adverse events reported during digoxin alone and in combination with tiagabine were somnolence and headache; an overall greater frequency of adverse events was reported during combined treatment. Adverse events were generally mild in nature; no serious adverse events were reported. CONCLUSIONS: At the doses administered, there is no evidence of a pharmacokinetic interaction between digoxin and tiagabine in healthy male volunteers.

Adult↗

The effect of titanium plasma-sprayed implants on trabecular bone healing in the goat.

The bone response to different titanium plasma-sprayed implants was evaluated in a goat model. Therefore, beam-shaped implants were installed into the trabecular femoral condyles of 10 goats. These implants were provided with three different titanium plasma-sprayed coatings (Ti2, Ti3 and Ti4) with a Ra of 16.5, 21.4 and 37.9 microm, respectively. An Al2O3 grit-blasted implant (Ti-un) with a Ra of 4.7 microm was used as control. After an implantation period of 3 months, the implants were evaluated histologically and histomorphometrically. Only one implant (Ti3) was not recovered after the evaluation period. Light microscopy showed a limited amount of bone for the various implants. Most of the implants showed a different degree of fibrous tissue alternating with direct bone contact. Complete fibrous encapsulation of the implants was observed in some of the sections. No signs of delamination of the plasma-sprayed coating was visible. No significant difference in bone contact were measured between the different types of implants (P > 0.05). Histomorphometrical analysis revealed significantly higher bone mass close to the implant (0-500 microm) for the Ti3, Ti4 and Ti-un implants placed in the medial femoral condyle and the Ti4 implants placed in the lateral condyle. At distance (500-1500 microm), no difference in bone mass measurements between the different implants was observed (P > 0.05).

Aluminum Oxide↗

Growth behavior of fibroblasts on microgrooved polystyrene.

We investigated the contact guidance phenomenon of rat dermal fibroblasts (RDF) on microgrooved polystyrene substrates. Grooves were 1 microm deep, and between 1 and 10 microm wide. Light microscopy and digital image analysis (DIA) showed that RDF were oriented on all microgrooved substrates. Scanning electron microscopy showed that RDF cultured on 1 or 2 microm wide grooves were positioned on top of the ridges. On the wider 5 and 10 microm grooves, the cells were able to descend into the grooves. In confocal laser scanning microscopy, focal adhesions were lying in the same direction as the actin filament where they attached to. DIA confirmed an orientational behavior of focal adhesions and actin filaments on microgrooves. There were no differences in the measured orientation between the different grooves. Besides, no obvious preference was found for focal adhesions to lie along edges of the surface ridges. Transmission electron microscopy showed that focal adhesions were able to bend along the edges of ridges. On the basis of our observations, we suggest that the breakdown and formation of fibrous cellular components, especially in the filopodium, is influenced by the microgrooves. The microgrooves create a pattern of mechanical stress, which influences cell spreading and cause the cell to be aligned with surface microgrooves.

Animals↗

Evaluation of the tissue reaction to a percutaneous access device using titanium fibre mesh anchorage in goats.

The tissue reaction to a percutaneous access device, applicable as a carrier for an implantable glucose sensor, was evaluated in goats. Titanium fibre mesh structures were used for anchorage of the device in superficial as well as deeper soft-tissue locations. The percutaneous part was subcutaneously anchored with a fibre mesh sheet. The distal part was placed intraperitoneally and anchored in deeper soft-tissue layers using a fibre mesh cuff. All implants showed good healing with the surrounding tissue. Histological evaluation showed that the subcutaneous fibre mesh sheets and peritoneal fibre mesh cuffs were filled with immature connective tissue, generally free of inflammation. Problems concerning disconnection of the silicone catheter from the titanium holding element and filling of part of the peritoneal fibre mesh cuff with silicone glue have to be overcome by more appropriate preclinical testing and improved implant design. Our results demonstrate that titanium fibre mesh structures can be used effectively for soft-tissue anchorage of percutaneous access devices. A sufficient ingrowth of connective tissue was obtained in superficial as well as in deeper soft-tissue layers. The access device could have application as a carrier for an implantable glucose sensor for glucose monitoring in different tissue compartments.

Journal Article↗

Bone healing capacity of titanium plasma-sprayed and hydroxylapatite-coated oral implants.

The influence of surface quality, in particular surface topography and implant material, was evaluated by inserting titanium- and hydroxylapatite plasma-sprayed coated implants into the maxilla of 10 goats. Three types of plasma-spray coatings were applied to tapered, screw shaped implants; titanium plasma-spray coating (TPS), titanium plasma-spray coating with additional acid passivation (TPSA) and a bilayered coating (TPS/HA) consisting of titanium plasma-spray coating (TPS) and a hydroxylapatite part (HA). In addition, as-machined implants (TiM) were used as control. A total of 40 implants were inserted according a balanced split plot design. At the end of a 3-month healing period, it appeared that 5 implants (2 TPS, 1 TPSA, 1 TPS/HA and 1 TiM) were lost. Histological examination revealed a stronger bone response to TPS/HA coated implants. Even the TPS/HA coated implants induced bone formation on the part of the implant inserted into the sinus. No signs of delamination of the TPS coatings were visible. The HA part of the dual coating showed signs of degradation. Histomorphometrical analysis confirmed these findings. A significant difference in bone contact (P < 0.05) was measured between the TPS/HA coated implants and the other types of implants. Linear regression (r = 0.27) showed no correlation between the inscrew values at the base line and the bone contact measurements 3 months after healing. On the basis of these results, we can conclude that the chemical composition of the HA coating has a positive influence on the bone reaction. The influence of roughness is less evident.

Alveolar Process↗

Calcium phosphate coatings for medical implants.

In surgical disciplines where bone has to be repaired, augmented or improved, bone substitutes are essential. Although bone banks, such as Eurotransplant, are founded to supply such substitutes, natural bone is not always adequate. For example, frequently these so-called bone grafts resorb after implantation (1). Further, they cannot be used for joint and tooth replacement, and recently worries have been raised about the transfer of infectious diseases. Therefore, interest has dramatically increased in the use of synthetic materials for replacement of lost or damaged bone tissue. The generic name of these tissue alternatives is biomaterials. A special class of these biomaterials is composed of metallic devices with coatings to improve bone bonding. These specialized coatings used to improve the metallic implant are the topic of this paper.

Adhesiveness↗