Patent Publication Number: US-2010114274-A1

Title: Surface modification of implantable article

Description:
FIELD OF THE INVENTION 
     This invention relates to modification of the surface characteristics of at least one surface of an elastomeric article, for example tubing, composed of polymeric materials such as silicone rubber, polypropylene, polyethylene, polyvinylchloride, fluoropolymers and the like or other dielectric materials and to an improved method for effecting such modifications. The invention also concerns a method of assembly of an implantable electrode lead. 
     BACKGROUND OF THE INVENTION 
     Polymeric plastic tubing, particularly that of small diameter, and most especially that of silicone rubber, is used in many medical applications and devices. Actually, silicone rubber (especially peroxide cross linked silicone elastomer with silica filling) is the polymer of choice for tubing in many medical applications involving implantation. In many instances this tubing is less than about 2 mm in inner diameter (ID). 
     Although this invention is applicable to other polymeric materials and dielectric materials, it will be described herein with particular reference to silicone rubber, the preferred embodiment. For example, the so called “screw-in” pacing leads make use of very small diameter tubing such as less than 1.4 mm outer diameter (OD) with an ID of 0.9 mm. In this type of lead, an elongate wire core (usually in the form of a coil) having a helical screw-in electrode at its distal end is placed inside an elongate silicone tube to provide a catheter-like device. The core wire is manipulated at the proximal end of this arrangement by the physician during implantation to screw the helical electrode into heart tissue and fix the lead in place. 
     Unfortunately, silicone rubber has a tacky surface with high surface friction making assembly of internal components into silicone lumens during manufacture of pacemaker and cardiac leads difficult. For example, inserting the spiral conductor into the tubing is difficult because it tends to fasten to the silicone tubing. Also, this surface adherence impedes motion of parts making the extension of a helix in active-fix leads more difficult. Torque transfer through the tubing is difficult making difficult the turning of the core wire to screw the helical electrode into tissue. Further, due to sticking of the core wire to the inside of the tubing, flex life is shortened. 
     Previous practices to ameliorate these friction characteristics have involved; 1) the use of harder materials which are more slippery but less bio stable and less suitable for implantation e.g., polyurethane, 2) coating, 3) hardening, 4) swelling and, even 5) the use of environmentally unfriendly materials such as chlorofluorocarbons (CFC). Also, plasma discharge has been used on tubing with some degree of success. However, none of these practices have been satisfactory with respect to long lengths of narrow tubing and the provision of a uniform surface therein. 
     Another problem of implantable articles is how to obtain surface characteristics promoting growth of tissue on the surface to securely fastened the article after implantation. 
     U.S. Pat. No. 5,830,329 describes a process of reducing the friction inside a small diameter tubing by placing the tubing in a close fitting glow discharge chamber with the plasma discharge gas inside the tubing and submitting the inner surface to glow discharge. 
     U.S. Pat. No. 6,438,425 concerns another solution to the problem of reducing the coefficient of friction. In this case a tubular lead body is extruded to define a plurality of small parallel longitudinally extending grooves on the inner or outer surface of the lead body. The grooves may be formed by means of a die having inwardly or outwardly directed projections. 
     Presently, the assembly of silicone insulated leads is facilitated by using solvents such as isopropyl alcohol as lubricant or n-heptane in order to temporarily swell the tubing to larger dimensions. Also, the silicone lumens are over-dimensioned to provide some extra mobility of internal parts. However, shrinkage after heptane-swelling is non-uniform and the tubing fastens to the conductors in localized places leaving tensions in the materials which are not easy to relax because of the adherence of silicone to the internal parts. Alternatively, relaxation after evaporation of isopropyl alcohol is impeded. Helix extension is also adversely affected by this adherence. 
     Another way to deal with the problems of assembly of silicone insulated leads is to over-dimension the silicone lumens to provide some extra mobility of internal parts. However, a general goal is to reduce dimensions, not to increase them. 
     The present methods do not provide adequate solutions to achieve easy assembly of pacemaker and cardiac leads. 
     OBJECTS OF THE INVENTION 
     An object of the invention is to enable easy assembly of pacemaker and cardiac leads. 
     Another object is to provide an implantable elastomeric tubing having reduced surface friction on the inner or outer surface or on both surfaces. 
     A further object is to provide an implantable elastomeric article having a surface which promotes growth of tissue on the article after implantation. 
     An additional object is to provide an implantable elastomeric article having a surface roughness on at least one surface. 
     A further object is to provide a method of modifying at least one surface of implantable articles, such as tubing. 
     BRIEF DESCRIPTION OF THE INVENTION 
     The invention concerns an implantable elastomeric article such as tubing with modified surface characteristics on at least one surface obtained by treatment with an acid. 
     The invention also concerns a method of treating at least one surface on an implantable elastomeric article with an acid to modified surface characteristics. 
     Further the invention concerns a method of assembly of an implantable electrode lead made of silicone tubing and a spiral conductor, comprising treating the tubing with an acid before inserting the conductor into the tubing. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows attenuated total reflection-fourier transform infrared (ATR-FTIR) spectra for surface of untreated tubing and differently treated tubings. 
         FIG. 2  shows optical microscope picture of untreated tubing. 
         FIGS. 3-5  show optical microscope pictures of treated tubings. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     It was surprisingly found that the treatment of a surface of an implantable article of elastomeric material such as silicone provides a surface roughness which decreases the surface friction. The contact area between the spiral conductor and the silicone tubing during assembly of a pacemaker or cardiac lead is reduced owing to surface roughness obtained by treating the inside of the tubing with an acid. Thereby adherence between the spiral conductor and the lead is avoided and the insertion of the conductor facilitated. Further, it is possible to move the conductor inside the tubing and thus easier screw the electrode tip into heart tissue. A treatment of the outer surface of the silicone tubing may also result in the lead being more easily inserted into a blood vessel. 
     Thus, the surface roughness obtained by the treatment of an implantable article of elastomeric material with an acid gives a reduced friction between the article and another object. However, such surface roughness on an implantable article may also be of advantage to provide for growth of tissue on the article to fasten the implanted article. 
     Thus, the invention concerns an implantable elastomeric article having modified surface characteristics on at least one surface obtained by application of an acid on said at least one surface and after a predetermined treatment time removing the acid by rinsing. 
     Further, the invention concerns a method of modifying surface characteristics of at least one surface on an implantable elastomeric article, comprising application of an acid on said at least one surface and after a predetermined treatment time removing the acid by rinsing. 
     The invention also concerns a method of assembly of an implantable electrode lead including a spiral conductor inside a silicone tube having an inner surface and an outer surface, comprising application of an acid on said inner surface and after a predetermined treatment time removing the acid by rinsing with water followed by inserting the conductor into the tube. 
     The implantable elastomeric article of the invention may have a surface roughness of 0.1-50 μm on the treated surface. 
     The surface roughness is the medium depth of depressions in the surface or the height of the corresponding protrusions, from the base to the peak. The protrusions are formed in the surface of the elastomeric article by the treatment with an acid. 
     The height or depth may be evaluated optically with a visual microscope. A precision measurement may be made with an atomic force microscope, e.g. by Pacific Nanotechnology, Inc, Santa Clara, Calif. or Surface Science Laboratories, Sunnyvale, Calif. A measurement may also be made using a laser beam to create a “Glitter Effect” as described by Bryan Beckingham and Professor Gregory Campbell, Department of Chemical Engineering, Clarkson University. Other methods comprise optical profilers, scatterometry and electron/ion beam methods. 
     The preferred implantable elastomeric material is silicone. The preferred acid for the treatment is hydrofluoric acid, HF. The following more detailed description is made in relation to silicone and treatment with hydrofluoric acid. However, this should not be interpreted as a limitation of the invention to these two materials. 
     The treatment with HF may be performed with a HF concentration of 0.02N-20N. Preferably the concentration is between 0.1N and 10N and especially between 0.5 and 2N. 
     An appropriate treatment time would be at most 2 hours, corresponding to a minimum concentration of 0.1N. Rapid process less than 30 sec may be difficult to control. This gives a practical useful upper limit of 10N HF. A higher concentration could work faster if desired for a particular process. However, more rapid treatment leads to deeper and larger pitting before the entire surface is treated uniformly. Therefore, an optimum treatment is in the range of 0.5N-2N HF for periods between 2.5 minutes and 5.5 minutes, giving the most uniform and finest grain surface roughness structures. Rougher structure may be desirable in some uses, though. 
     Treatment times and HF concentration are inversely proportional, to a fairly good approximation over the range of 0.02N-20N HF. 
     The surface roughness can vary from 0.1 um (width and depth) to 50 μm depending on treatment conditions. The surface roughness is suitably 0.2 to 20 μM, preferably 0.3 to 10 μm. Fine structures in the 0.5-2 μm range uniformly distributed over entire surface is optimum for effect in an implantable lead. A greater surface roughness may be used to achieve growth of tissue. 
     Examples 
     Treatment of silicone tubing is carried out by contacting the silicone surfaces to be treated with 1.0 N (aq) hydrofluoric acid for 5.5 minutes. Contacting the inside of the lumen is facilitated by the use of a syringe to apply vacuum and suck the acid solution into the tubing. External surfaces are treated by immersion. Both internal and external surfaces can be treated simultaneously. Following the contact with acid, the silicone is flushed with distilled water. Then drying of the tubing (optional) is facilitated by an additional flush with isopropyl alcohol followed by blow-drying with pressurized (room temperature) air. The resulting treated surfaces have greater roughness (on microscopic scale), leading to less contact area with other components of the leads. There may or may not be some chemical modification of the surface as well, perhaps fluorination of the silicone polymer or deposition of lower-molecular weight silicone oils, which may contribute to the reduced adherence. In tubing with wall thickness as low as 0.12 mm treatment on both inside and outside of lumen gave a permanent (as far as we can tell at this time) improvement in handling and only reduced mechanical strength by about 5%. 
     Practical Treatment Time Limits and Min/Max HF Concentration: 
     HF of concentrations of 0.02N-20N were tested. Process time should be under 2 hrs to be most practical. Then 0.1N HF is minimum concentration. A rapid process less than 30 sec may also be difficult to control. Then 10N HF would be the practical useful upper limit—but higher concentration could work faster if desired for a particular process. However, more rapid treatment leads to deeper and larger pitting before entire surface is treated uniformly. Therefore, an optimum treatment is in the range of 0.5N-2N HF for periods between 2.5 minutes and 5.5 minutes, giving the most uniform and finest grain surface roughness structures. Rougher structure may be desirable in some uses, though. 
     Treatment times and HF concentration are inversely proportional, to a fairly good approximation over the range of 0.02N-20N HF. 
     Size, Topography and Necessary Wall Thickness: 
     Visual microscope was used. The modified surface has roughness imparted by the HF treatment. This roughness can vary from 0.1 μm (width and depth) to 50 μm depending on treatment conditions (fine structures in the 0.5-2 μm range uniformly distributed over entire surface is optimum for effect in device). Should avoid so thin tubing that 50 μm is more than 20% of wall thickness. Above 50 μm surface feature size, the surface of the tubing obtains a wet feel, due to macroscopic amounts of unfilled silicone (PDMS) polymer at the surface—unfilled PDMS has the undesirable feel and properties of a gel instead of a rubber. 
       FIG. 2  shows an optical microscope picture (400 μm×500 μm) of untreated tubing (0.072″ ID×0.098″ OD) MED4759 silicone rubber (extrusion lines clearly visible). 
     The result of different treatments are shown in  FIGS. 3-5 .  FIG. 3  being a microscope picture (400 μm×500 μm): 20N HF for 44 sec (0.072″ ID×0.098″ OD) MED4759 silicone rubber (deeper larger pitting).  FIG. 4  is an optical Microscope picture (400 μm×500 μm): 2N HF for 2.5 min (0.072″ ID×0.098″ OD) MED4759 silicone rubber (within optimum range).  FIG. 5  is an optical Microscope picture (400 μm×500 μm): 2N HF for 54 min (0.072″ ID×0.098″ OD) MED4759 silicone rubber (wet surface feel, exceeded optimum). 
     Is F Present After Washing: 
     ATR-FTIR (surface measurement of infrared spectroscopy) shows that there is no chemical alteration of the PDMS polymer; no detectable fluorination occurs. The Si—O—Si stretching at 1020 cm−1 decreases in intensity in relation to the Si—CH 3  bending at 1259 cm −1 , indicating that the filler to polymer ratio at the surface is decreased in the HF-treated tubing. The decrease in filler content in the surface of treated tubing is greater for harsher treatments: for longer treatments at the same concentration or for more concentrated HF for a fixed time. This is consistent with what is known about HF that it is capable of corroding silicates (glass). 
     The result is shown on  FIG. 1  comprising ATR-FTIR spectra for surface of untreated tubing, optimal treated tubing, and excessively treated tubing (superimposed). This shows that no chemical modification such as fluorination or oxidation is occurring, and indicates that the HF treatment reduces the filler:polymer ratio at the surface. 
     Number of Turns/Torque Reduction: 
     A silicone tubing with surface modification according to the invention gives a 25% reduction in the amount of torque required to extend a helix on an active fixation lead from 0.8 mNm to 0.6 mNm. 
     The treated tubing also shows 12% reduction in moment (number of turns) from 8 to 7 on helix extension and 33% reduction in moment (number of turns) from 9 to 6 on helix retraction. 
     The invention is described above in the examples with reference to an implantable silicone tube. However, this should not be interpreted as a limitation of the scope of the invention. Modifications of both the material in the implantable article, the form of the article and the acid will be obvious to a person skilled in the art. The scope of the invention is defined in the enclosed claims.