A new modified silicone was obtained by physical entrapment of a hydrophobic lipoid, isopropyl myristate ( IPM ) , to better encapsulation belongingss and corrosion opposition for medical electronic implants. It was demonstrated that IPM loaded silicone movies were stable in an aqueous environment with no leaching from the silicone matrix, though little initial leaching was observed in buffered BSA. An unexpected difference between H2O conveyance for movies in contact with H2O vapor V those in contact with liquid H2O was identified, demoing increased permeableness to H2O vapor, perchance the consequence of differences in H2O administration at the hydrophobic movie interface. An betterment in the mechanical belongingss of the modified stuff was besides achieved including enhanced abrasion opposition and adhesion.
Incorporation of IPM farther resulted in important betterment of cell biocompatibility compared with the unmodified polymer proposing that the IPM combination could be a feasible footing for implant device packaging.
Keywords: silicone coating, isopropyl myristate, H2O vapor conveyance, liquid H2O conveyance, biocompatibility
Silicone elastomers are widely used as biomaterials for coating of medical devices and implants due to their well known, and normally accepted, biocompatibility and bioinertness. Nevertheless, basic stuffs belongingss could still be further optimised[ 1 ]. The generic advantage of these elastomers, nevertheless, is that they can severally work as lasting dielectric dielectrics, a barrier against matrix induced taint and as emphasis alleviating shock/vibration adsorbers over a broad scope of humidness and temperature[ 2 ]. The production of catheters, stents, cardiac leads, tracheal intubators[ 3 ]soft contact lenses[ 4 ]and plastic surgery implants[ 5 ]is normally silicone based, and now silicones have become the industry criterion for encapsulating implantable electronic devices[ 6 ]. However, the major concern in these applications is opposition to H2O conveyance, peculiarly through comparatively thin barrier beds, taking to device dependability issues through hydration, corrosion and debasement procedures compounded by possible delamination[ 7 ]. Therefore, it was reported that the chief failure of a ocular prosthetic device was attributable to the immersion of wet ; such wet could arise as H2O vapor every bit good as condensed H2O[ 8 ]caused by the failure of adhesion between encapsulant and microelectronic device, so making nothingnesss within which condensation can happen[ 9 ]. Finally, when adequate H2O diffuses through an encapsulant to make a uninterrupted H2O way at the device interface, the presence of entrained ions and any electrical prejudice promotes electrocorrosion[ 10 ]. This accelerates the surface debasement that puts at hazard device functionality over the longer term.
Several solutions at molecular degree exist to cut down H2O permeableness through polymeric membranes. First and the most of import is control through alteration of chemical construction of polymer influencing for illustration concatenation mutual opposition and hydrophobicity[ 11 ],[ 12 ],[ 13 ]. The permeableness of polymers towards gases lessenings with increasing polymer mutual opposition, mostly due to the higher activation energy for diffusion in a polar polymer[ 14 ]. Conversely, polar polymers are hapless H2O barriers because H2O is soluble in such polymer stages[ 15 ].
Polymer symmetricalness promotes closer concatenation wadding and crystallinity, both of which besides decrease permeableness[ 16 ],[ 17 ]. The orientation of polymer molecules has a farther consequence on permeability17, the extent depending on the type of polymer and the grade of orientation ; this can besides take to anisotropic permeableness behavior. Inter-chain crosslinking can besides cut down permeableness[ 18 ], particularly where the original non-crosslinked stage can be swollen by the penetrant. Finally, the add-on of plasticizer to a polymer causes increased segmental mobility, efficaciously take downing the TAg value and so doing a decrease in barrier belongingss[ 19 ].
Entrapment of an extra hydrophobic agent, a man-made lipoid as portion of a silicone membrane to mime human tegument[ 20 ]has proved a utile agencies of proving drug conveyance. In peculiar it appears that for tegument it is intercellular lipid matrix that is indispensable to the barrier belongingss of tegument, and drug pervasion is radically altered after extraction of tegument lipoid[ 21 ].
It was considered, nevertheless, that incorporation of the extremely hydrophobic isopropyl myristate into a silicone matrix would non merely cut down surface H2O repellency, but through decreased H2O solubility in the majority stage, cut down H2O conveyance.
A farther possible benefit of lipid incorporation into silicone was a slower ripening of the stuff in vivo. One cause of ageing of silicone chest implants, for illustration, is identified to be lipid infiltration from tissue ensuing in loss of mechanical belongingss and failure of the elastomer[ 22 ]. Pre-entrapment of man-made lipoid should saturate the matrix with a defined, controlled agent and aid cut down the farther impact of organic structure lipid immersion, so decelerating down any consequence on ripening.
A farther concern sing development of new stuffs for biomedical applications is the regulative blessing procedure.[ 23 ]Although man-made polymer chemical science is a powerful and convenient stuffs alteration tool, this leads to major regulative challenges when any new chemical science is applied. Concerns would be, for illustration, sing residuary man-made side merchandises, their bioeffects and the length of service of any facile surface chemical alteration in the face of a chronic tissue degradative response at the implant venue. Both medical class silicones and IPM have the advantage that they are already approved for clinical usage, and usage of physical entrapment eliminates the jobs of covalent binding, with the uncertainness of unknown reaction side merchandises. Such a modified stuff should therefore see a shorter blessing tract.
II. Materials and methods
Medical class unrestricted usage ( for & gt ; 30 yearss in vivo ) silicone gum elastic ( MED-4211 or MED6215 ) . Nusil Technology Ltd, USA ) portion A was dissolved in heptane ( VWR Int. , UK ) at a concentration of 20 % w/v and stirred until solution homogeneousness was obtained ( 2-3h ) . Following, isopropyl myristate ( Fluka, UK ) was added ( with stirring ) in changing sums as required ( specified under consequences ) . For preliminary surveies, the undermentioned lipoids were added: cholesterin, behenyl oleate, 4-methylumbelliferyl stearate, all purchased from SigmaAldrich and used without farther purification. Finally, silicone portion B of the was added in the ratio 1:10 ( A: Bacillus ) to portion A was added and stirred. After 1h the stuff was ready for usage for sample readying. 4ml was cast on to a polystyrene Petri dish followed by 65A°C incubation for 4h. After that, silicone movies were gently removed from the Perti dish and placed on a glass home base for farther heat intervention at 100A°C for 2h and so at 150A°C for 45min.
Contact angle measurings were performed by a contact angle rig ( CAM 200, KSV Instruments Ltd. , Finland ) set up with at least five readings for each sample, utilizing H2O as a wetting agent by the sessile bead method.
Visual image of IPM
Lipid soluble dye Sudan Red ( SR ) , purchased from Fluka, UK, was used to track IPM in silicone and to visualize any leaching. SR was dissolved in IPM ( 50mg/ml ) which was so assorted with the silicone gum elastic as a ocular marker and the combination taken through the standard process for silicone membrane production. After plunging the membranes in H2O for 14 yearss they were analysed by optical microscopy.
Water vapour conveyance
Water vapour transmittal was determined by repairing a silicone membrane over the unfastened oral cavity of a 50ml glass conelike flask incorporating a known sum of H2O ( ~10ml ) . Membranes were to boot sealed at the sides with Parafilmi?’ . Measurements of H2O vapor conveyance, based on hydrometric finding – vaporised H2O[ 24 ], were taken after one hebdomad exposure to ambient air.
Liquid H2O conveyance measuring
A specially designed device was used to find H2O transmittal from liquid H2O through the silicone membranes. It consisted of two parts: a screwed, unfastened handbill ( r=22.5 millimeter ) upper clinch and a lower constituent of a known sum of hygroscopic agent ( anhydrous CuSO4, ~2g, Fluka, UK ) in a weighting boat. A silicone membrane was mounted between the two parts with paste sealer to guarantee a leak-proof seal. After one hebdomad of submergence of the concept in distilled H2O at temperature 37i‚°C, the weight of CuSO4 was remeasured to find hydrate formation and hence H2O conveyance through the membrane.
Membranes both for H2O vapor and liquid H2O conveyance measurings were vacuum dried at 60i‚°C for 4h to take any residuary H2O prior to surveies.
A Si wafer coated with a individual bed of Nusil MED 6215 silicone ( used as a control sample ) was coated with extra beds of either unmodified or 1 % IPM modified silicones ( MED4211 or instead MED 6215 ) . The abrasion opposition of such laminates was so determined by the undermentioned experimental apparatus: 1 ) a wafer was attached to a steel home base by dual side adhesive tape 2 ) a specially designed device with a bevelled chromium steel steel acerate leaf was mounted on a tensile examiner such that the acerate leaf pushed into the wafer with a changeless force 3 ) the device was moved with a changeless perpendicular speed of 25mm/min to do a abrasion. Scratch opposition was determined by measurings of the breadth of the created crevice utilizing an optical microscope.
The same samples as described in the abrasion trial were cut into 50×10 mm squares and so a silicone bed strip was removed up to ~20mm and clamped on the upper portion of a tensile examiner, while the staying Si adherent sample was clamped to the lower surface. Once the sample was mounted, increasing force was applied and measured at the minute when the extra silicone flap started to delaminate. The value of this force was a direct index of the strength of adhesion. Each sample was measured in triplicate.
The trial chosen was the direct cell contact check, carried out in conformance with ISO10993-5:1999 utilizing 3T3 mouse fibroblasts. Since the end-point of the standard trial is a comparatively subjective observation of cell morphology, it has become common pattern to supplement this with a quantitative rating of cell proliferation. Here we used the rezazurin-based AlamarBlueA® dye decrease check.
Samples of 10 ten 10 millimeters were cut for proving. Both positive and negative toxicity polymer samples were included in the trial. The negative toxicity controls were 13 millimeters Thermanox coverslips ( Nalgene Nunc, USA, type 174950, lot 551810 ) . ISO 10993-5 criterion organo-tin plasticised PVC ( Portex UK, type 499/400/000 batch 30375 ) was used for positive toxicity controls. Cell growing in the presence of trial and control stuffs was compared to growing in standard multi-well tissue civilization plates.
The Swiss albino murine fibroblast cell line 3T3 ( ECACC Ref No: 93061524 ) was obtained from mycoplasma-free stocks held within the Institute of Cell and Molecular Biology. Cells were cultured in Eagle minimum indispensable medium ( EMEM, D5546, Sigma, UK ) supplemented with 1 % penicillin/sterptomycin solution ( 10,000 U/ml of each antibiotic, Gibco Invitrogen, type 15140-122, batch 1268409 ) and 10 % heat-inactivated calf serum ( Biosera, South America beginning, cat. No. S 1810/500 ) .
The trial stuffs were immersed overnight in 100 % ethyl alcohol ( Analytic reagent class, Fisher Scientific, codification: E/0605 DF/17, Batch 0613664 ) in a petri dish and kept overnight within a category II laminar flow cabinet. The stuffs were so washed three times in phosphate buffered saline and later washed with EMEM incorporating 3 % ( w/v ) penicillin/streptomycin.
The trial and control stuffs were placed into 24 good home bases ; each incorporating three replicates of three of the trial stuffs, and negative and positive controls. Each trial stuff was used in two replicate cell civilization plates, so that a sum of 6 replicate findings were carried out for each stuff. Once the trial and control stuffs had been positioned in the home base, 1 milliliter of cell civilization medium incorporating 3T3 cells at a denseness of 1 ten 104 cells ml-1 was added to the Wellss. The trials for this group of stuffs were carried out in two parts, with extra cell civilization plates used in each portion.
1ml of a 10 % solution of AlamarBlue ( Biosource, type DAL1100, lot 146581SA ) in cell civilization medium was added to each well. The home bases were placed back into the brooder for 4 hours at 37A°C to let decrease of the dye. A sample of the medium was so removed from each well and its optical denseness measured utilizing a fluorescence home base reader ( Bio-TEK Synergy HT ) with excitement filters at 530-560 nanometer and emanation at 590 nanometer. The ensuing fluorescence signal is relative to the sum the AlamarBlue dye that had been converted to the reduced signifier by the metabolic action of the cells and so is a step of the figure of metabolically active cells.
At the terminal of each dye incubation period, the dye incorporating medium was removed, the cells washed one time, and so 1 milliliters of fresh cell civilization medium was added. The cells were so returned to the brooder until the following measuring point.
III. Results and treatment
Preliminary lipoid showing
The scheme for making a new stuff with possible use as a coating for implantable microdevices was centred here on a modified commercially available silicone. Lipids were selected as qualifiers with a possibility for making a H2O impermeable barrier through a displacement to hydrophobic belongingss, with the purpose of widening coated implant life clip.
Four lipoids: isopropyl myristate ( IPM ) , cholesterin ( CH ) , behenyl oleate ( BO ) and 4-methylumbelliferyl stearate ( 4MB ) were investigated.
Contact angle measuring was used for a preliminary appraisal of modified stuff H2O repellency[ 25 ].
Contact angle measurings for Nusil MED-4211 silicone modified with assorted w/v lipoids at 1 % w/v are shown in Figure 1. None of the compounds gave a important addition in contact angle and cholesterin really reduced contact angle, presumptively because of the surface exposure of its hydrophilic hydroxyl group.
Among investigated lipoids, IPM was attractive because of its anterior usage in biomedicine. Therefore, it was reported non to do important inflammatory alteration to outer human stratum horny layer in a comparative survey with rat tegument[ 26 ]. Besides, it is besides widely used in deeper corium beds to heighten drug flux through the tegument, eg of estradiol[ 27 ]. The hydrophobicity of the stuff gives a good footing for cut downing device surface wetting through its interior surface contact with the device ; liquid H2O tracking along the silicone/substrate interface would be less likely to happen.
Figure 1. Water / polymer surface contact angle measurings of lipid ( 1 % w/v ) modified MED 4211 silicone membranes with H2O. Abbreviations: IPM- isopropyl myristate, 4MB- 4-methylumbelliferyl stearate BO- behenyl oleate, CH- cholesterin.
IPM as a feasible hydrophobic qualifier was confirmed by a important concentration dependent addition in contact angle up to at least 5 % w/v IPM ( Fig 2 ) . At 10 % IPM, likely surface inhomogenity may hold led to an anomalous lessening in contact angle, a consequence of the surface migration of IPM as its scattering in silicone becomes less stable at high concentration.
Figure 2. Consequence of IPM concentration on the H2O / polymer surface contact angle of modified silicones.
After readying, IPM modified silicone membranes were rinsed and so immersed in distilled H2O for 24h. Subsequently, they were dried with tissue and weighed. Consequences reflecting weight alteration are summarized in Table 1.
IPM 0.5 %
IPM 1 %
IPM 2 %
IPM 5 %
IPM 10 %
Mean % weight loss [ n=5 ]
Table 1. Percentage weight loss after plunging in distilled H2O for 1day with subsequent vacuity drying. Silicone deposited on a glass slide
Consequences show important experimental variableness and no dependance of IPM concentration. However, the confirmed loss in weight for silicone entirely suggests that some of the loss in weight with IPM alteration is the consequence of residuary stuff losingss in the silicone itself instead than due merely to IPM leaching ; perchance IPM loss was from hints on the surface and non from the majority. The consequences besides indicate that silicone polymerisation went to near completion transcending 99.4 % ( the upper limit average weight loss seen in Table 1 ) .
After the above preliminary lavation phase, in order to look into the aging consequence of silicone movies they were immersed in H2O and reweighed sporadically. There was no extra weight loss seen over a 3 hebdomad period ( informations non shown ) , bespeaking that IPM did non leach out from the silicone matrix and so was efficaciously retained even though merely physically dispersed in the silicone.
Another trial of IPM keeping stableness was a microscopy comparing of trial membranes before and after plunging in a inactive H2O bath. Based on images in Figure 3, where Sudan ruddy is the IPM marker, it is clear that hive awaying membranes in H2O did non do IPM leaching nor to important intra-membrane diffusing alteration. The images taken from matched membrane locations show small or no alteration in distribution or morphological characteristics for the IPM after 14 yearss. It is besides deserving observing that at low concentration ( 0.5 % w/v ) IPM is dispersed uniformly, whereas at higher concentrations it created big sums and bunchs.
Dye merely 0.5 % w/v IPM
1 % w/v IPM
2 % w/ V IPM
Before plunging in H2O solution
After 14 yearss of plunging in H2O solution
Figure 3. Detection of IPM leaching utilizing lipid soluble dye – Sudan Red, at light microscope, rapid climb 10X.
Modified silicone membranes were besides exposed to phosphate buffer saline ( pH 7.4 ) and bovid serum albumen ( BSA ) ( 40mg/ml ) solution at 37a-¦C for 30 yearss to measure any protein influence on IPM stableness. Figure 4 shows that with increasing of IPM concentration, the weight loss of silicone membranes immersed in BSA increased. It can be concluded that BSA has an extra consequence and that as an amphiphile it appears to solvate the IPM helping its release from the silicone matrix. It is known both that BSA has surfactant belongingss and that it can perforate a polymer matrix, peculiarly a slackly jammed polymer bed, irrespective of its thickness provided there is polymer sufficient concatenation flexibleness.[ 28 ]
Figure 4. IPM modified silicones membrane immersed in phosphate buffer with BSA solution for 30 yearss, at pH 7.0.
The most of import characteristic of an encapsulating stuff, and the primary purpose of the silicone IPM alteration, is H2O opposition. One facet to this is H2O consumption, ie H2O shacking within the polymer at concentrated equilibrium, the other is H2O conveyance through the silicone membrane stage ; a more direct index of membrane barrier belongings. A farther subscriber of H2O opposition is the strength of adhesion to the substrate8 ; adhesion should be strong plenty to avoid condensed H2O tracking entirely between surfacing and device following delamination.
Water vapour conveyance
Permeation of a gas or vapor through a polymer movie is thought to affect the undermentioned phases: surface assimilation of the permeating species onto the polymer surface ; solubilisation in the polymer matrix ; diffusion through the movie down a concentration gradient ; and desorption from the opposite surface10.
Unusually, an upward tendency of increased H2O vapor conveyance was seen with increased IPM concentration can be observed with the exclusion of at IPM 1 % w/v concentration ( Fig 5 ) . A statistical analysis was performed utilizing one-way ANNOVA coupled with Dunnett ‘s Multiple Comparison Test to measure differences between H2O vapour permeableness of stuffs ( GraphPad Prism Version 5.01 ) . Assurance taken at degrees 0.05, 0.1, 0.01 showed that the increased H2O vapor conveyance through IPM modified membranes was statistically important and correlated with an addition in IPM concentration.
Equally far as H2O vapor conveyance through a membrane is concerned, two phenomena: nucleation and constellating on the hydrophobic surface contribute to the diffusion procedure[ 29 ].
In this instance nucleation can likely be neglected since the handiness of any hydrophilic sites for H2O molecules nucleation is highly low, given that polymer and lipoid are hydrophobic and the likeliness of hydrophilic drosss, eg in the signifier of ionic salts is practically zero.
Clustering on the other manus, can happen when common penetrant-penetrant interactions at a surface are stronger than those of the penetrant-polymer, which surely appears the instance for the hydrophobic polydimethyl siloxane ( PDMS )[ 30 ]. Hence, H2O bunchs are likely to hold been created on the present hydrophobic surface. However, from a modeling survey[ 31 ], the opportunities of important incursion of H2O bunchs from surface to bulk PDMS, every bit good as bunch formation within the PDMS, is extremely unlikely.
Therefore, it would look sensible to reason that conveyance involves non-aggregated H2O conveyance through the membrane.
Figure 5. Consequence of IPM concentration on H2O vapor conveyance through modified silicone membranes during 7 yearss.
Liquid H2O conveyance through modified silicones
Compared with a mention aluminum foil movie the silicones allowed significant H2O conveyance. The nominal sum seen for the aluminum indicated the experimental mistake during measuring due to transient CuSO4 exposure to ambient air during setup assembly. Improved H2O opposition can be observed ( Figure 6 ) with increasing of IPM concentration up to 1 % w/v and so a farther addition of IPM concentration had no evident consequence on H2O transmittal through membranes, nevertheless, any consequence is little in any instance. Again, a statistical analysis performed utilizing one-way ANNOVA coupled with Dunnett ‘s Multiple Comparison Test to measure differences between H2O permeableness of stuffs ( GraphPad Prism Version 5.01 ) shows the consequences to be important with a assurance taken at 0.05. However, consequences were non statistically important at a assurance 0.1 and 0.01. Overall, informations can be interpreted as demoing that IPM modified stuffs do cut down liquid H2O permeableness when compared with unmodified silicone to a grade that reaches statistical significance[ 32 ].
These consequences are rather the contrary of the H2O vapor tendencies ; this may be because with liquid H2O interfacial bunch, known to be prevailing at such membranes[ 33 ], included initial H2O consumption. Therefore, on a silicone membrane liquid H2O is exposed to the driving action of IPM molecules across all of the available surface country. However, whilst IPM at the membrane surface might drive H2O sums in the liquid province, it does non sufficiently suspend the flux of monomeric H2O vapor.
Figure 6. Liquid H2O conveyance through IPM modified silicone membranes – IPM concentration dependance.
Introduction of any extra overlaying silicone bed significantly improved the abrasion opposition of the substrate as reflected in ascertained lower abrasion breadth ( Table 2 ) . It is besides deserving observing that alteration of the MED-4211 silicone with IPM had the greatest consequence on abrasion opposition. Improved abrasion opposition accompanies, with some advantage, the snap addition of a modified material20. A more elastic stuff would besides conform more readily to natural tissue mechanics and follow the abnormality of any device surface. Another advantage of increased snap is that such stuffs are less vulnerable to mechanical harm during the nidation procedure itself, e.g. rubing by surgical instruments or during managing.
Average width [ millimeter ]
Master of education 4211
MED 4212+1 % IPM
Master of education 6215
MED 6215+1 % IPM
Table 2. Rub trial consequences of assorted dual silicone beds measured as an mean value of created crevices
Consequences of the adhesion strength finding between silicone base MED 4211 stuff and either unmodified, or 1 % w/v IPM modified, extra silicone beds are shown in Figure 7. Alteration for both sorts of silicone consequences in a lower strength of adhesion but when a dual coating is used ( silicone foremost bed ) adhesion was at least every bit good as that with a control individual silicone disciple bed, the criterion coating. Therefore, a dual bed has advantages, and if delamination does happen it will take topographic point at the silicon-silicone interface instead than between two silicone beds.
Figure 7. Adhesion trial consequences of assorted dual silicone beds measured as minimal force required to get down a individual bed pealing procedure.
A quantitative appraisal of cell growing in each well as a whole is provided by the AlamarBlue dye decrease trial. The trial produces a fluorescence signal of arbitrary units that is relative to the figure of feasible cells in each well. The average AlamarBlue fluorescence from six replicate trials for each stuff and the clip points is shown in Figure 8. All the trial stuffs and the biocompatible stuff control displayed less cell growing at 48 hours incubation than the cell-only control, and increasing sums of IPM appeared to be associated with increasing sums of cell growing up to 5 % IPM.
Figure 8. Cell Growth as measured by AlamarBlue fluorescence for the two parts of the experiment.Points show the average A± sem for 12 ( controls ) or 6 ( trial samples ) replicate incubations.
The comparative consequence of these stuffs on cell growing is best assessed if growing is normalised to that in the negative toxicity ( no stuff nowadays ) control. From this, the mean background fluorescence without cells ( coefficient of fluctuation & lt ; 5 % ) was subtracted from all other measurings and cell growing expressed as a proportion of the duplicate cell-only control in the subsequent analysis.
The comparative cell growing at 96 hours is shown in Figure 9, and efficaciously summarises the findings. An declarative statistical analysis was performed for the 96 hr incubations utilizing one-way ANNOVA coupled with Bonferroni ‘s Multiple Comparison Test[ 34 ]to measure differences between the stuffs ( GraphPad Prism Version 4.02 ) . Significance was taken at p= & lt ; 0.05. The cell merely control showed significantly greater cell growing than all other incubations except the MED 4211 with 5 % IPM. However, there was no statistical difference between the biocompatible stuff control and all trial incubations other than the MED 4211 with 10 % IPM, which had significantly less growing than all other incubations.
In decision, the consequences show the unmodified MED 4211 used in this survey, as prepared, had a well lower biocompatibility than the biocompatible control, but the incorporation of IPM resulted in a dose-dependent addition in cell growing on the stuff up to a concentration of 5 % . Inclusion of 10 % IPM resulted in much less cell growing than on the unmodified stuff. Therefore, it appears that IPM up to 5 % can increase the short-run biocompatibility of this silicone gum elastic to a important grade.
Figure 9. Relative cell growing at 96 hours. Mean A± 95 % CI ( n=12 for controls and 6 for trial stuffs ) .
A potentially utile campaigner stuff was established as possible packaging stuff and laminate for inactive microelectronic device surfaces. Preliminary coating of a scope of microelectronic devices with IPM modified silicone showed promising consequences for its functionality and in vitro compatibility35. Furthermore, some decrease in H2O permeableness for the modified stuff, though non apparent to a major grade, offers an improved protection barrier against H2O immersion that may be of cumulative importance over drawn-out periods of nidation. In combination with the better biocompatibity, the stuff of would be of possible usage for in vivo devices.