Modulation of bone ingrowth of rabbit femur titanium implants by in vivo axial micromechanical loading.

Titanium implants commonly used in orthopedics and dentistry integrate into host bone by a complex and coordinated process. Despite increasingly well illustrated molecular healing processes, mechanical modulation of implant bone ingrowth is poorly understood. The objective of the present study was to determine whether micromechanical forces applied axially to titanium implants modulate bone ingrowth surrounding intraosseous titanium implants. We hypothesized that small doses of micromechanical forces delivered daily to the bone-implant interface enhance implant bone ingrowth. Small titanium implants were placed transcortically in the lateral aspect of the proximal femur in 15 New Zealand White rabbits under general anesthesia and allowed to integrate with the surrounding bone for 6 wk. Micromechanical forces at 200 mN and 1 Hz were delivered axially to the right femur implants for 10 min/day over 12 consecutive days, whereas the left femur implants served as controls. The average bone volume 1 mm from mechanically loaded implants (n = 15) was 73 +/- 12%, which was significantly greater than the average bone volume (52 +/- 21%) of the contralateral controls (n = 15) (P < 0.01). The average number of osteoblast-like cells per endocortical bone surface was 55 +/- 8 cells/mm(2) for mechanically loaded implants, which was significantly greater than the contralateral controls (35 +/- 6 cells/mm(2)) (P < 0.01). Dynamic histomorphometry showed a significant increase in mineral apposition rate and bone-formation rate of mechanically stressed implants (3.8 +/- 1.2 microm/day and 2.4 +/- 1.0 microm(3).microm(-2).day(-1), respectively) than contralateral controls (2.2 +/- 0.92 microm/day and 1.2 +/- 0.60 microm(3).microm(-2).day(-1), respectively; P < 0.01). Collectively, these data suggest that micromechanical forces delivered axially on intraosseous titanium implants may have anabolic effects on implant bone ingrowth.     

A paradigm for the development and evaluation of novel implant topologies for bone fixation: Implant design and fabrication

The future development of bio-integrated devices will improve the functionality of robotic prosthetic limbs. A critical step in the advancement of bio-integrated prostheses will be establishing long-term, secure fixation to the remnant bone. To overcome limitations associated with contemporary bone-anchored prosthetic limbs, we established a paradigm for developing and fabricating novel orthopedic implants undergoing specified loading. A topology optimization scheme was utilized to generate optimal implant macrostructures that minimize deformations near the bone-implant interface. Variations in implant characteristics and interfacial connectivity were investigated to examine how these variables influence the layout of the optimized implant. For enhanced tissue integration, the optimally designed macroscopic geometry of a titanium (Ti)-alloy implant was further modified by introducing optimized microstructures. The complex geometries of selected implants were successfully fabricated using selective laser sintering (SLS) technology. Fabrication accuracy was assessed by comparing volumes and cross-sectional areas of fabricated implants to CAD data. The error of fabricated volume to CAD design volume was less than 8% and differences in cross sectional areas between SEM images of fabricated implants and corresponding cross sections from CAD design were on average less than 9%. We have demonstrated that this computational design method, combined with solid freeform fabrication techniques, provides a versatile way to develop novel orthopedic implants.     

A low noise multichannel integrated circuit for recording neuronal signals using microelectrode arrays

This paper reports on the development of a fully integrated 32-channel integrated circuit (IC) for recording neuronal signals in neurophysiological experiments using microelectrode arrays. The IC consists of 32 channels of low-noise preamplifiers and bandpass filters, and an output analog multiplexer. The continuous-time RC active filters have a typical passband of 20-2000 Hz; the low and the high cut-off frequencies can be separately controlled by external reference currents. This chip provides a satisfactory signal-to-noise ratio for neuronal signals with amplitudes greater than 50 microV. For the nominal passband setting, an equivalent input noise of 3 microV rms has been achieved. A single channel occupies 0.35 mm(2) of silicon area and dissipates 1.7 mW of power. The chip was fabricated in a 0.7 microm CMOS process.     

Bone-implant interface shear modulus and ultimate stress in a transcortical rabbit model of open-pore Ti6Al4V implants

This experimental study on laser-textured implants aimed to evaluate periimplant bone elasticity and ultimate stress of the bone-implant interface in a rabbit femur model. After randomization, two cylindrical Ti6Al4V samples (3.5 mm wide, 5.5 mm long) were transcortically implanted in each femur of 15 female New Zealand White Rabbits. Polished implants had been laser-textured with 100, 200, and 300 microm diameter pores, and another corundum blasted implant was additionally textured with 200 microm pores. Twelve weeks into the experiment, a modified push-out test was performed. The median shear modulus indicating the elasticity of the periimplant bone was 41.12 MPa for the proximal implant location and 25.38 MPa for the distal, without evidence for significant differences between implant types. Taking into account the median ultimate shear stress for 200 microm implants with and without corundum blasting, no significant difference could be demonstrated. However, for blasted 200 microm implants a statistically significant (p<0.025) relative gain in ultimate shear stress of 41% and 17% was proven in comparison with 100 and 300 microm implants, respectively. Non-blasted 200 microm implants reached 48% relative gain in respect of 100 microm samples.     

Multichannel thin-film electrode for intramuscular electromyographic recordings.

It is currently not possible to record electromyographic (EMG) signals from many locations concurrently inside the muscle in a single wire electrode system. We developed a thin-film wire electrode system for multichannel intramuscular EMG recordings. The system was fabricated using a micromachining process, with a silicon wafer as production platform for polyimide-based electrodes. In the current prototype, the flexible polymer structure is 220 microm wide, 10 microm thick, and 1.5 cm long, and it has eight circular platinum-platinum chloride recording sites of 40-microm diameter distributed along the front and back surfaces with 1,500-microm intersite spacing. The system prototype was tested in six experiments where the electrode was implanted into the medial head of the gastrocnemius muscle of rabbits, perpendicular to the pennation angle of the muscle fibers. Asynchronous motor unit activity was induced by eliciting the withdrawal reflex or sequential crushes of the sciatic nerve using a pair of forceps. Sixty-seven motor units were identified from these recordings. In the bandwidth 200 Hz to 5 kHz, the peak-to-peak amplitude of the action potentials of the detected motor units was 75 +/- 12 muV and the root mean square of the noise was 1.6 +/- 0.4 muV. The noise level and amplitude of the action potentials were similar for measures separated by up to 40 min. The experimental tests demonstrated that thin film is a promising technology for a new type of flexible-wire intramuscular EMG recording system with multiple detection sites.     

Selection of developmentally competent buffalo oocytes by brilliant cresyl blue staining before IVM

The brilliant cresyl blue (BCB) test determines the activity of glucose-6-phosphate dehydrogenase (G6PDH); the activity of this enzyme is greatest in growing oocytes, but it declines as oocytes mature. The objective was to develop and evaluate this test for assessing development of buffalo oocytes (to select developmentally competent oocytes for increased in vitro embryo production). Oocytes were exposed to BCB stain diluted in mDPBS (DPBS with 0.4% BSA) for 90 min at 38.5 degrees C in a humidified air atmosphere; those with or without blue coloration of the cytoplasm were designated as BCB+ and BCB-, respectively. In Experiment 1, oocytes were exposed to 13, 26, or 39 microM BCB. There were fewer BCB+ oocytes after exposure to 13 microM BCB (10%) than after exposure to 26 or 39 microM BCB (57.2 and 61.8%; P<0.05), but there was no significant difference among treatments for blastocyst production rate. In Experiment 2, the diameter of BCB+ oocytes (144.4+/-4.2 microm; mean+/-S.E.M.) was higher (P<0.05) than that of BCB- oocytes (136.8+/-4.6 microm). In Experiment 3, oocytes were allocated into three groups: control (immediately cultured); holding-control (kept in mDPBS for 90 min before cultured); and treatment-incubation (incubated with 26 microM BCB). After IVM, oocytes were fertilized in vitro and cultured on an oviductal monolayer. The nuclear maturation rate was higher (P<0.05) in BCB+ (86.2%), control (83.4%) and holding-control (82.6%) oocytes than BCB- (59.2%) oocytes. The BCB+ oocytes yielded more blastocysts than control or holding-control oocytes (33.4, 20.2, and 21.0%, P<0.05); blastocyst development was lowest in BCB- oocytes (5.2%). In conclusion, staining of buffalo oocytes with BCB before IVM may be used to select developmentally competent oocytes for increased in vitro embryo production.     

Preliminary fabrication and characterization of electron beam melted Ti–6Al–4V customized dental implant

The current study was aimed to fabricate customized root form dental implant using additive manufacturing technique for the replacement of missing teeth. The root form dental implant was designed using Geomagic™ and Magics™, the designed implant was directly manufactured by layering technique using ARCAM A2™ electron beam melting system by employing medical grade Ti–6Al–4V alloy powder. Furthermore, the fabricated implant was characterized in terms of certain clinically important parameters such as surface microstructure, surface topography, chemical purity and internal porosity. Results confirmed that, fabrication of customized dental implants using additive rapid manufacturing technology offers an attractive method to produce extremely pure form of customized titanium dental implants, the rough and porous surface texture obtained is expected to provide better initial implant stabilization and superior osseointegration.     

Gold nanograin microelectrodes for neuroelectronic interfaces

Neuroelectronic interfaces are imperative in investigating neural tissues as electrical signals are the main information carriers in the nervous system and metal microelectrodes have been widely used for recording and stimulation of nerve cells. For high performance microelectrodes, low tissue-electrode interfacial impedance and high charge injection limits are essential and nanoscale surface engineering has been utilized to meet the requirements for microelectrodes. We report a single-cell sized microelectrode, which has unique gold nanograin structures, using a simple electrochemical deposition method. The fabricated microelectrode had a sunflower shape with 1–5 (m of micropetals along the circumference of the microelectrode and 500 nm nanograins at the center. The nanograin electrodes had 69-fold decrease of impedance and 10-fold increase in electrical stimulation capability compared to unmodified flat gold microelectrodes. The recording and stimulation performance of nanograin electrodes was tested using dissociated rat hippocampal neuronal cultures. Noise levels were extremely low (2.89 μV_rms) resulting in high signal-to-noise ratio for low-amplitude action potentials (18.6–315 μV). Small biphasic current pulses (20–60 μA) could evoke action potentials from neurons nearby electrodes. This new nanostructured neural electrode may be applicable for the development of cell-based biosensors or clinical neural prosthetic devices.     

Influence of the stiffness of bone defect implants on the mechanical conditions at the interface--a finite element analysis with contact

The study focused on the influence of the implant material stiffness on stress distribution and micromotion at the interface of bone defect implants. We hypothesized that a low-stiffness implant with a modulus closer to that of the surrounding trabecular bone would yield a more homogeneous stress distribution and less micromotion at the interface with the bony bed. To prove this hypothesis we generated a three-dimensional, non-linear, anisotropic finite element (FE) model. The FE model corresponded to a previously developed animal model in sheep. A prismatic implant filled a standardized defect in the load-bearing area of the trabecular bone beneath the tibial plateau. The interface was described by face-to-face contact elements, which allow press fits, friction, sliding, and gapping. We assumed a physiological load condition and calculated contact pressures, shear stresses, and shear movements at the interface for two implants of different stiffness (titanium: E=110GPa; composite: E=2.2GPa). The FE model showed that the stress distribution was more homogeneous for the low-stiffness implant. The maximum pressure for the composite implant (2.1 MPa) was lower than for the titanium implant (5.6 MPa). Contrary to our hypothesis, we found more micromotion for the composite (up to 6 microm) than for the titanium implant (up to 4.5 microm). However, for both implants peak stresses and micromotion were in a range that predicts adequate conditions for the osseointegration. This was confirmed by the histological results from the animal studies.     

Temperature-modulated diversity of TRPV4 channel gating: activation by physical stresses and phorbol ester derivatives through protein kinase C-dependent and -independent pathways

The TRPV4 calcium-permeable channel was cloned from mouse kidney M-1 cells, and the effect of temperature modulation on channel gating/activation by physical and chemical signals was evaluated. A TRPV4 cDNA construct with a C-terminal V5 epitope was stably transfected into human embryonic kidney (HEK) 293 and Chinese hamster ovary cells resulting in high levels of expression at the plasma membrane. Channel activation was assessed from changes in calcium influx (fura-2 fluorescence measurements) or whole cell currents (patch clamp analysis). At room temperature (22-24 degrees C), exposure of TRPV4-transfected cells to hypotonic medium (225 mOsm/liter) or a non-protein kinase C (PKC)-activating phorbol ester derivative, 4alpha-phorbol 12,13-decanoate (100 nm), induces modest channel activation, whereas phorbol 12-myristate 13-acetate (100 nm), a PKC-activating phorbol ester, and shear stress (3-20 dyne/cm2) had minimal or no effect on channel activation. In contrast, at elevated temperatures (37 degrees C) the channel was rapidly activated by all stimuli. Inhibition of PKC by calphostin C (50 nm) or staurosporine (500 nm) abolished phorbol 12-myristate 13-acetate-induced activation of the channel without affecting the response to other stimuli. Ruthenium red (1 microm) effectively blocked the channel activity by all stimuli. It is concluded that temperature is a critical modulator of TRPV4 channel gating, leading to activation of the channel by a diverse range of microenvironmental chemical and physical signals utilizing a least two transduction pathways, one PKC-dependent and one PKC-independent. The convergence of multiple signals and transduction pathways on the same channel indicate that the channel functions as a molecular integrator of microenvironmental chemical and physical signals.     

Selection of prepubertal goat oocytes using the brilliant cresyl blue test

Brilliant cresyl blue stain allows us to determine the activity of glucose-6-phosphate dehydrogenase (G6PD), an enzyme synthesized in growing oocytes but with decreased activity in oocytes that have finished their growth phase. The objective of this study was to evaluate the utility of the brilliant cresyl blue (BCB) test as an indirect measure of oocyte growth, in order to select competent prepubertal goat oocytes for in vitro embryo production. Oocytes were exposed to BCB diluted in PBS and were classified according to their cytoplasm coloration: oocytes with a blue cytoplasm or grown oocytes (BCB+) and oocytes without a blue cytoplasm or growing oocytes (BCB-). After exposure to different BCB concentrations, we evaluated in vitro maturation (IVM), in vitro fertilization (IVF) and embryo development parameters. We defined matured oocytes as those oocytes that reached the metaphase II (MII) stage after being cultured for 27 h. Oocytes showing two pronuclei at 20 h post-insemination were classified as normally fertilized oocytes. We assessed embryo development 8 days post-insemination and recorded the percentage of total embryos, morale and blastocysts. The mean percentage of BCB+ oocytes was 29.4%. Mean diameter of BCB+ oocytes (136.6+/-6.3 microm) was higher (P < 0.001) than that of BCB- oocytes (125.5+/-10.2 microm). The percentage of BCB+ oocytes reaching the MII stage (81.4%) was higher (P < 0.05) than that of BCB- (52.5%) and control oocytes (72.4%). Normal fertilization rate of BCB+ oocytes was also higher (23.5%) than that of BCB- (8.2%; P < 0.0001) and control oocytes (11.9%; P < 0.05). The percentages of total embryos undergoing development to >8-cell and the morula plus blastocyst stages were higher (P < 0.05) in the group of BCB+ (41.3 and 12.0%, respectively) than in BCB- oocytes (21.3 and 3.6%, respectively). In conclusion, the BCB test is a useful way to select more competent prepubertal goat oocytes for in vitro embryo production.     

Effects of different-shaped tissue expanders on transluminal pressure, oxygen tension, histopathologic changes, and skin expansion in pigs

This study, performed on domestic pigs, was designed to show whether the shape and size of a tissue expander influences the amount of surface area increase. When a defect is irregular, a larger custom-fitted implant is more efficient than several smaller expanders. Oval implants gained 5 percent more skin using 50 percent less time and almost 20 percent less intraluminal pressure, while U-shaped implants yield 2.2 percent more skin in 10 percent less time with 35 to 50 percent less pressure when compared with several smaller implants covering the same surface area. Transcutaneous TpO2 measurements and histologic evaluation revealed no significant difference between all implant shapes. These results show that less time, pressure, and volume are needed in a larger implant to gain the same surface area as would be attained from several smaller implants, thus sparing the patient more discomfort, trauma, and risk of infection by reducing the number of filling domes and hence the number of fillings.     

Developmental competence of heifer oocytes selected using the brilliant cresyl blue (BCB) test

The aim of this study was to evaluate the usefulness of the brilliant cresyl blue (BCB) test in the selection of more competent heifer oocytes for in vitro embryo production (IVEP). IVEP from selected BCB heifer oocytes was compared to IVEP from morphologically selected heifer (control group) and cow oocytes. BCB staining determines the activity of glucose-6-phosphate dehydrogenase (G6PD), an enzyme synthesized in growing oocytes but with less activity in grown oocytes. Six hundred and fifty seven heifer cumulus-oocyte complexes (COC) were classified morphologically as Grade 1-3 and exposed to 26 microM of BCB and classified as: blue (or grown) oocytes (BCB+) or unstained oocytes or growing oocytes (BCB-). Grade 1-3 heifer oocytes showed significantly different percentages of BCB+ oocytes (78.6, 66.2, and 51.1%, respectively; P<0.05). The diameter of BCB+ oocytes was significantly higher than BCB- oocytes (152.6+/-5.8 microm and 147+/-5.9 microm, respectively; P<0.001). The percentage of BCB+ oocytes reaching the blastocyst stage was significantly higher than those of BCB- and control heifer oocytes (12.3, 1.6, and 5.2%, respectively; P<0.05), but lower than those of cow oocytes (30.0%; P<0.05). In conclusion, heifer oocytes selected by the BCB test (BCB+) are larger and more competent for IVEP than control heifer oocytes. However, fewer heifer oocytes selected using the BCB test develop to blastocyst stage compared to cow oocytes.     

Enlarged gold-tipped silicon microprobe arrays and signal compensation for multi-site electroretinogram recordings in the isolated carp retina

In order to record multi-site electroretinogram (ERG) responses in isolated carp retinae, we utilized three-dimensional (3D), extracellular, 3.5-μm-diameter silicon (Si) probe arrays fabricated by the selective vapor-liquid-solid (VLS) growth method. Neural recordings with the Si microprobe exhibit low signal-to-noise (S/N) ratios of recorded responses due to the high-electrical-impedance characteristics of the small recording area at the probe tip. To increase the S/N ratio, we designed and fabricated enlarged gold (Au) tipped Si microprobes (10-μm-diameter Au tip and 3.5-μm-diameter probe body). In addition, we demonstrated that the signal attenuation and phase delay of ERG responses recorded via the Si probe can be compensated by the inverse filtering method. We conclude that the reduction of probe impedance and the compensation of recorded signals are useful approaches to obtain distortion-free recording of neural signals with high-impedance microelectrodes.     

Histomorphometric evaluation of bone ingrowth of porous titanium by a computer-assisted analyzing system]

The objective of this study was to evaluate the bone ingrowth of a new vacuum plasma sprayed titanium surface (vps-ti) in comparison to cs-titanium implants in a g?ttinger minipig model. Fifteen g?ttinger minipigs each received the two implants, vacuum plasma sprayed titanium with a porosity of 50% and a pore size of 200 microm (vps-ti) and an implant with a similar porosity but a different pore size 500 microm (cs-ti), at the proximal femur metaphysis by press-fit technique. The pigs were euthanized at three different postsurgical periods: 4, 8 and 12 weeks. Each femur was harvested and qualitative (macroscopic and microscopic) and quantitative (histomorphometric) histological analysis was done on histological slides. The results indicated that there was a difference in bone ingrowth between the two implants, whereas the bone ingrowth of vps-ti was superior to cs-ti after 4 and 8 weeks healing time. 12 weeks post implantationem no statistiscal difference was evident. The pore size of 200 microm seemed superior to a pore size of 500 microm. Whether or not these effects lead to a better mechanical stability remains unanswered.     

Engineered bone culture in a perfusion bioreactor: a 2D computational study of stationary mass and momentum transport

Successful bone cell culture in large implants still is a challenge to biologists and requires a strict control of the physicochemical and mechanical environments. This study analyses from the transport phenomena viewpoint the limiting factors of a perfusion bioreactor for bone cell culture within fibrous and porous large implants (2.5 cm in length, a few cubic centimetres in volume, 250 microm in fibre diameter with approximately 60% porosity). A two-dimensional mathematical model, based upon stationary mass and momentum transport in these implants is proposed and numerically solved. Cell oxygen consumption, in accordance theoretically with the Michaelis-Menten law, generates non linearity in the boundary conditions of the convection diffusion equation. Numerical solutions are obtained with a commercial code (Femlab 3.1; Comsol AB, Stockholm, Sweden). Moreover, based on the simplification of transport equations, a simple formula is given for estimating the length of the oxygen penetration within the implant. Results show that within a few hours of culture process and for a perfusion velocity of the order of 10(-4) m s(-1), the local oxygen concentration is everywhere sufficiently high to ensure a suitable cell metabolism. But shear stresses induced by the fluid flow with such a perfusion velocity are found to be locally too large (higher than 10(-3) Pa). Suitable shear stresses are obtained by decreasing the velocity at the inlet to around 2 x 10(-5) m s(-1). But consequently hypoxic regions (low oxygen concentrations) appear at the downstream part of the implant. Thus, it is suggested here that in the determination of the perfusion flow rate within a large implant, a compromise between oxygen supply and shear stress effects must be found in order to obtain a successful cell culture.     

Ion permeation of AQP6 water channel protein. Single channel recordings after Hg2+ activation

Aquaporin-6 (AQP6) has recently been identified as an intracellular vesicle water channel with anion permeability that is activated by low pH or HgCl2. Here we present direct evidence of AQP6 channel gating using patch clamp techniques. Cell-attached patch recordings of AQP6 expressed in Xenopus laevis oocytes indicated that AQP6 is a gated channel with intermediate conductance (49 picosiemens in 100 mm NaCl) induced by 10 microm HgCl2. Current-voltage relationships were linear, and open probability was fairly constant at any given voltage, indicating that Hg2+-induced AQP6 conductance is voltage-independent. The excised outside-out patch recording revealed rapid activation of AQP6 channels immediately after application of 10 microm HgCl2. Reduction of both Na+ and Cl- concentrations from 100 to 30 mm did not shift the reversal potential of the Hg2+-induced AQP6 current, suggesting that Na+ is as permeable as Cl-. The Na+ permeability of Hg2+-induced AQP6 current was further demonstrated by 22Na+ influx measurements. Site-directed mutagenesis identified Cys-155 and Cys-190 residues as the sites of Hg2+ activation both for water permeability and ion conductance. The Hill coefficient from the concentration-response curve for Hg2+-induced conductance was 1.1 +/- 0.3. These data provide the first evidence of AQP6 channel gating at a single-channel level and suggest that each monomer contains the pore region for ions based on the number of Hg2+-binding sites and the kinetics of Hg2+-activation of the channel.     

Long-term results of MISTI gold breast implants: a retrospective study

MISTI Gold breast implants (Bioplasty, St. Paul, Minn.) filled with polyvinylpyrrolidone-hydrogel were developed as a promising alternative to silicone-filled implants. Some studies have reported on the positive effects of the implant, such as improved radiolucency and biocompatibility of the gel; however, there are also reports that such implants increased in volume and were subject to capsular contracture in the human body, resulting in demands for their removal. The purpose of this retrospective study was to analyze the long-term results of a series of patients with MISTI Gold breast implants. Between 1991 and 1993, the authors inserted 83 MISTI Gold implants in 61 patients with an average age of 46 years (range, 16 to 69). The authors were able to follow up 48 patients with 71 MISTI Gold implants. The average follow-up was 68 months (range, 10 to 108 months). The retrospective study found that 59 percent of all MISTI Gold implants were removed after an average period of 4.14 years. The main reason for implant removal was an increase in volume of 38 percent, followed by capsular contracture in 14 percent of all 71 MISTI Gold implants. The average increase in volume of all removed MISTI Gold implants was 43 percent. Capsular contracture was graded as Baker I and II in 63 percent and as Baker III and IV in 37 percent. In conclusion, the authors believe that MISTI Gold implants do not fulfill the criteria of safe breast implants, and they agree with the December of 2000 opinion of the Medical Devices Agency of the Department of Health in London that the hydrogel-filled breast implants should not be used until more information about the filler material and its metabolic fate is available.     

The effectiveness of sodium 2-mercaptoethane sulfonate (mesna) in reducing capsular formation around implants in a rabbit model

The development of capsular contracture is the most common complication associated with the insertion of breast implants. The authors studied the role of sodium 2-mercaptoethane sulfonate (mesna) in reduction of capsular formation in a rabbit model. Two 40-cc textured saline implants were placed dorsally into each of the 20 rabbits in the study. At the time of insertion of the implants, 10 ml of a 10% solution of mesna was instilled into one of the pockets and normal saline was instilled into the other. The implants were removed and a capsulectomy was performed at 5 months. The capsules were examined histologically for qualitative differences between the two groups. Quantitative analysis of the thickness of the capsule and the myofibroblast populations was also performed and compared between the two groups. The mean total thickness of the capsule around the implants was 496.8 microm in the mesna-treated group compared with 973.7 microm in the saline-treated group (p < 0.001). Likewise, the thickness of the myofibroblast layer was reduced in the mesna-treated group at 283.2 microm versus 555 microm in the saline-treated group (p < 0.0001). The capsules were also relatively less vascular in the mesna-treated group. Because of its ability to reduce the extent of capsular formation and to diminish development of myofibroblasts in the capsules, mesna would appear to be a useful adjunct in the prevention of capsular contracture formation.     

Flexible polyimide probes with microelectrodes and embedded microfluidic channels for simultaneous drug delivery and multi-channel monitoring of bioelectric activity

The study of intracellular communication requires devices that can not only monitor the bioelectric activity, but also control and observe the biochemical environment at the cellular level. This paper reports on the development and characterisation of implantable polyimide microprobes that allow simultaneous, selective chemical delivery/probing and multi-channel recording/stimulation of bioelectric activity. The key component of the system is a flexible polyimide substrate with embedded microchannels that is batch-fabricated combining polyimide micromachining and a lamination technique. The devices provide platinum microelectrodes on both sides of the polyimide substrate with an active surface between 20 microm x 20 microm and 50 microm x 50 microm. The embedded microchannels permit highly localised drug delivery or probing at the tip of the device via channel outlets adjacent to the microelectrodes. The microelectrodes were characterised by electrical impedance spectroscopy and the microchannels were studied in microflow experiments. Two different fluid delivery schemes were explored in two different designs. The first device type consists of a simple combination of microchannels and microelectrodes on one substrate. Liquids are ejected at the tip of the device by pressure injection techniques. The second device was inspired by the so-called U-tube concept allowing for highly localised delivery of controlled amounts of liquids in the picoliters range. Thus, the influence of chemical compounds on the electrical activity of cells can be studied with high temporal and spatial resolution. The flexible, implantable devices can be used for studying the chemical and electrical information exchange and communication of cells in in vivo and in vitro experiments.