Abstract:
A biocompatible implantable portal is provided that has a wall defining a communicative passage through an interior bore. The exterior of the portal has a neck region adapted to promote autologous cell growth on the neck region. A series of channels are provided on the exterior neck region to facilitate autologous cell growth while disfavoring fluid pooling and bacterial growth. Typical channel widths are from 20 to 300 microns, with adjacent channels being separated by plateaus having a width of between 0 and 600 microns. Providing the portal exterior neck region with a texture varying on a nanometer length scale facilitates autologous cell growth. Applying a coating such as a tissue scaffolding matrix to the neck region prior to implantation also facilitates cell growth. A coupling or a manifold encompassing the neck region facilitates the draw of vacuum and/or mechanical protection for the growing cells.

Description:
RELATED APPLICATION  
       [0001]     This application claims priority of U.S. Provisional Patent Application Ser. No. 60/703,661 filed Jul. 29, 2005, which is incorporated herein by reference. 
     
    
     FIELD OF THE INVENTION  
       [0002]     The present invention in general relates to percutaneous access devices and in particular to a percutaneous access device amenable to skin growth around the device periphery so as to form a biologically stable seal.  
       BACKGROUND OF THE INVENTION  
       [0003]     A common problem associated with implantation of a percutaneous access device (PAD) is skin regeneration about the periphery of the device to form an immunoprotective seal against infection. New cell growth and maintenance is typically frustrated by the considerable mechanical forces exerted on the interfacial layer of cells. In order to facilitate skin regeneration about the exterior of a PAD, subject cells are often harvested and grown in culture onto PAD surfaces for several days prior to implantation in order to allow an interfacial cell layer to colonize PAD surfaces in advance of implantation. Unfortunately, cell culturing has met with limited acceptance owing to the need for a cell harvesting surgical procedure preceding the implantation procedure. Additionally, maintaining tissue culture integrity is also a complex and time-consuming task.  
         [0004]     As an alternative to cell culturing on a percutaneous access device, vacuum assisted wound treatment about a percutaneous access device has been attempted. While Dacron based random felt meshes have been used to promote cell regrowth in the vicinity of a wound, such felts have uncontrolled pore sizes that harbor bacterial growth pockets.  
         [0005]     Thus, there exists a need for a percutaneous access device surface and processes to enhance autologous cell growth into a stable long term relation to the device.  
       SUMMARY OF THE INVENTION  
       [0006]     A biocompatible implantable portal is provided that has a wall defining a communicative passage through an interior bore. The exterior of the portal has a neck region adapted to promote autologous cell growth on the neck region. A series of channels are provided on the exterior neck region to facilitate autologous cell growth while disfavoring fluid pooling and bacterial growth. Typical channel widths are from 20 to 300 microns, with adjacent channels being separated by plateaus having a width of between 0 and 600 microns. Providing the portal exterior neck region with a texture varying on a nanometer length scale facilitates autologous cell growth. Applying a coating such as a tissue scaffolding matrix to the neck region prior to implantation also facilitates cell growth. A coupling or a manifold encompassing the neck region facilitates the draw of vacuum and/or mechanical protection for the growing cells.  
         [0007]     By forming a seal between a manifold encompassing the neck region of a portal to form a seal and providing a route of fluid communication between the manifold inlet and channels associated with the portal exterior, various gaseous or liquid fluids are provided to enhance cell growth after implantation of a percutaneous access device is facilitated.  
         [0008]     A process is provided for producing a biocompatible implantable portal having a nanoporous surface. The process includes dispersing nanocrystals in a polymer to yield a polymer dispersion. The polymer dispersion is applied onto the surface of a portal. Exposing the polymer dispersion on the surface to a solution selectively dissolves the nanocrystals from the surface to create the nanoporous surface. An alternative process includes forming a dual domain coating having a first domain type and a second domain type dispersed through the coating on the portal. Selectively removing the first domain type leaves the material of the second domain type in place to yield the porous surface. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0009]      FIG. 1  is a composite perspective view depicting two exemplary cell growth channel pattern halves to an inventive percutaneous access device joined together where the cell growth channels are not depicted to scale for visual clarity;  
         [0010]      FIG. 2  is a plan view of the percutaneous access device depicted in  FIG. 1  with a cross-sectional view along with a cross-sectional view of a vacuum manifold coupled thereto; and  
         [0011]      FIG. 3  is a perspective view of a cell growth channel according to the present invention. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0012]     The present invention has utility as a protective assembly for a portal for the coupling of a permanent or semi-permanent medical intervention, the portal having an interior bore through which communication is maintained between the portal recipient and external medical equipment. As a result, the conveyance of electrical signals, pneumatic drive power, or biological fluids is facilitated. Such portals are routinely used in conjunction with mechanical auxiliary ventricles, chronic ambulatory peritoneal dialysis, prosthetic limb anchorage to an amputation stump, cochlear or other neurological stimulators, drainage tubes, and vascular access lines as exemplary of instances in which such a portal is used. Exemplary of such portals are those detailed in U.S. Pat. Nos. 4,634,422; 4,668,222; 5,059,186; 5,120,313; 5,250,025; 5,814,058; 5,997,524; and 6,503,228. Such devices are collectively defined herein as percutaneous access devices CPADs).  
         [0013]     The stabilization of a PAD within the skin to form a germ-free barrier requires subject cells to grow onto the neck surfaces of the PAD adjacent to the subject&#39;s epidermis. The present invention uses alone, or in combination cell channeling contours, porous biodegradable polymers and the application of vacuum to promote cellular growth towards the surface the neck of a PAD. The present invention in facilitating rapid cellular colonization of a PAD neck allows the subject to act as their own cell culture facility and as such affords more rapid stabilization of the PAD, and lower incidence of separation and infection.  
         [0014]     Referring now to the figures, an inventive portal is shown generally at  10 . The portal  10  has an opening  12  defined by a sidewall  14 , the exterior side of the wall  14  defining a neck region  16  adapted to promote growth of autologous fibroblast cells thereon. A suitable exterior side surface substrate for fibroblast growth is a nanotextured polycarbonate (LEXAN) as detailed as a sleeve in U.S. Pat. No. 4,634,422. Unfortunately, the process of fission product bombardment followed by etching in a base solution detailed yields a range of pits and pores that vary in size to an extent that some of the pores are large enough to harbor pools of extracellular fluid and bacteria. A preferred method of generating a nanotextured neck surface yields pore sizes that are uniformly less than 500 to provide an anchor point for a fibroblast podocyte, while having dimensions that disfavor bacterial colonization. More preferably, a nanotextured surface as used herein has a uniform distribution of 50 to 500 nanometer median dimension indentations. Most preferably, the indentations have a median dimension of between 100 and 300 nanometers.  
         [0015]     A method of forming such pores in a ceramic or metal neck involves impregnating a porous polymer such as a polyurethane with particulate and combusting the polymer under conditions that allow the particles to sinter to form a porous surface with the desired properties. U.S. Pat. No. 4,004,933 details such a process. An analogous porous polymeric neck is formed by forming an interpenetrating polymer network in which the two networks are not cross linked, Exposing the resultant structure to a condition such as a solvent digestive towards only one type of interpenetrating polymer network domain yields a porous surface. It is appreciated that the domain need not be uniform in dimension. By way of example, the second domain type remaining after digestion or dissolution of the first domain type is formed as globular, spherical or other shape that is present at or above the percolation threshold such that these second domains are cross linked, sintered or otherwise adhered to yield a porous surface coating. Representative second domain types operative herein illustratively include metals, ceramics, and polymeric beads.  
         [0016]     Alternatively, combustion of a polymer containing metal or ceramic ions or inclusions yields a porous coating of the second domain type of the metal, the metal oxide or ceramic. Polyacrylic acid and polycarbonate are representative of water soluble and organic solvent polymers, respectively.  
         [0017]     Alternatively, an acid etchable, biocompatible nanocrystal such as silver or silica is dispersed in a polymer melt such as polycarbonate and a neck either formed directly therefrom or the nanocrystal-doped polymer is coated onto a neck substrate. Through subjecting the nanocrystal-doped polymer to an acid or base solution, depending on the solubility of the nanocrystal, voids are formed in the polymer reflective of the original nanocrystal dopant, For instance, silver is readily dissolved in 6 N hydrochloric acid while silica is dissolved in concentrated hydrofluoric acid. Dissolution in the presence of sonication is appreciated to facilitate the process. Silver represents a preferred nanocrystal as nanocrystal leachant not dissolved imparts antimicrobial properties to the resulting neck. Nanocrystal loading of 1 to 10 percent by weight, depending on the specific nanocrystal dimensions, is sufficient to achieve the desired uniformity and density of pores.  
         [0018]     Beneath the neck region  16  lies an implanted region  18  terminating in an inward portal face  20 , that is communicative with the opening  12  to form a passage through which fluids, electrical signals, gases or a combination thereof are communicated. The neck region  16  has a pattern of contoured autologous cell-conveying channels  22  or  22 ′.  
         [0019]     It is appreciated that the channels can take a variety of forms. In the figures, a linear channel  24  and a chrysanthemum-pattern channel  26  are depicted in composite halves as defined by the dashed plane. It is appreciated that an operative device typically would have a pattern  24  or  26  circumferentially decorating the device surface. Other channel patterns operative herein include any pattern that disfavors bacterial pocket formation. Specific patterns operative herein are those associated with vehicle tire treads with the proviso that sharp angular interactions between channel and intermediate plateaus are disfavored. Representative of these patterns are those found in U.S. Pat. No. 5,896,905. The channel  22  is formed by methods such as imprinting, embossing, molding or machining into the portal  10 . Preferably, the portal  10  is a nanotextured surface as detailed in regard to the sleeve in U.S. Pat. No. 4,634,422. As a portal  10  is formed of a conventional biocompatible material, one of skill in the art will appreciate the relative merits of impressing, embossing, machining, or molding based on whether the portal  10  is formed of a metal such as stainless steel, or titanium; a thermoplastic such as a fluoropolymer (TEFLON), a polyoxymethylene (DELRIN), or polycarbonate (LEXAN); or composite material. A channel  22  according to the present invention preferably has dimensions on the order of two to ten times the diameter of a plasma-borne fibroblast that is equivalent to  20  to 300 microns since a fibroblast has a diameter from 10 to 15 microns. More preferably, an inventive channel  22  has a width of between 30 and 120 microns. Most preferably, channel  22  is devoid of discontinuities and acute angles that disfavor cellular planarization and adhesion. A parabolic cross section is exemplary of a channel facilitating fibroblast growth. Typically, the plateau region between adjacent channels  22  has a width ranging from 0 to 600 microns. Preferably, the transition between the channel  22  and the plateau  30  is devoid of discontinuities and acute angles that disfavor cellular planarization and adhesion. A non-existent zero micron width plateau  30  corresponds to the instance where the cross section between channels corresponds to a sinusoidal pattern or the edges of adjacent parabolic channels intersect. Preferably, a plateau  30  has a width relative to an adjacent channel width that defines a ratio between 0.5 and 3:1. The alternation of channels  22  and plateaus  30  according to the present invention facilitates capillary draw of fibroblasts up into the neck region  16  of the inventive device  10 .  
         [0020]     Optionally, the neck region  16  is coated with a substance to facilitate cellular infiltration and growth on the neck region  16 . Such coating substances include cell growth scaffolding matrices as detailed in U.S. Pat. Nos. 5,874,500; 6,056,970; and 6,656,496; and Norman et al.  Tissue Eng.  3/2005, 11(3-4) pp. 375-386. Preferably, autologous plasma from the subject receiving an inventive portal  10  is applied to the neck region  16  as part of a scaffold matrix or independent thereof. More preferably, the coating  32  is porous in order to enhance capillary draw. More preferably, the coating  32  is porous and biodegradable. The coating has pores typically of an average size of between 10 and 500 microns, and preferably, of an average size of between 30 and 50 microns.  
         [0021]     Optionally, a vacuum is drawn toward an upward region of the neck region  16  in order to actively draw blood plasma and fibroblasts contained therein along the channels  22  to further facilitate autologous cell growth on the neck region  16 . Preferably, vacuum is applied intermittently for the first days or weeks after PAD implantation. The length of time for which vacuum is applied is dependent upon variables illustratively including vacuum strength, linear dimension of the neck region to be colonized, channel pattern, porosity characteristics of any coating present, subject wound fluid production, and subject serum fibroblast concentration.  
         [0022]     Referring now to  FIG. 2 , a vacuum manifold  40  is secured to an inventive portal  10  by way of a fastener  42 . The fastener  42  extends into a temporary seating pin (not shown) to fit within the opening  12 . A spacer  44  assures a uniform gap between the manifold  40  and the neck region  16 . An inlet  46  is provided for the coupling of the manifold  40  to a vacuum source. Manifold  40  has an extending lip  48  that terminates proximal to a surface of the neck portion  16  at at least one point amenable to form a seal  50  with the surrounding subject skin or a gel applied to the user skin. It is appreciated that a retaining groove  54  is defined on a lip surface in opposition to the portal neck portion  16 , the retaining groove  54  amenable to seat a vacuum gasket between the manifold  40  and the neck portion  16 . A gasket used herein is formed of conventional materials illustratively including neoprene. While the skin seal  50  is suitable to draw a vacuum around the periphery of the neck portion  16 , cells that are drawn within the portal portion under vacuum tend to be drawn to a surface of the neck portion  16  as opposed to intercalating within a channel or a matrix coating. As such, it is appreciated that while drawing a vacuum at the interface between the neck portion  16  and lip terminus  52  is suitable to urge an initial population of cells into the channels  22 , drawing of cells to the uppermost reaches of channels  22  preferably occurs by forming a vacuum seal between the manifold  40  and the neck portion  16  that includes only the uppermost terminus of the channels  22 . It is appreciated that once cells  31  begin to adhere to a surface defining a portion of a channel  22  or plateau  30 , abrasion and indeed contact with that surface is preferably avoided. It is further appreciated that a retaining groove  54  and the ensuing vacuum seal formed between the manifold  40  and the neck portion  16  is readily moved relative to the neck portion  16  by varying the thickness of the spacer  44 . While the manifold  40  is beneficial in drawing serum and the fibroblasts contained therein through the channels  22  in the neck portion  16 , it is also appreciated that independent of vacuum, the manifold  40  also serves to provide a mechanical guard to protect growing cells on the neck portion  16 . To this end, it is appreciated that an inlet  46  can be connected to a gas supply such as air or oxygen to promote autologous cell growth and granulation about the neck portion  16 ; or liquid solutions fostering cell growth are also provided and illustratively include autologous plasma, fibroblast growth enhancing solutions, and antimicrobials.  
         [0023]     A vacuum source suitable for coupling to the inlet  46  includes conventional vacuum sources such as a mechanical pump, aspirator, peristaltic pump, and the pneumatic system of a left ventricular assist device of a system such as the Kantrowitz CARDIOVAD drive unit as detailed at lvadtech.com. Optionally, a fibroblast compatible dye (not shown) is placed in proximity to channel termini nearest the implanted region  18 , the dye serving as a marker to indicate the extent of capillary draw of cells  31  into channels  22  and the optionally present coating  32 .  
         [0024]     Patent documents and publications mentioned in the specification are indicative of the levels of those skilled in the art to which the invention pertains. These documents and publications are incorporated herein by reference to the same extent as if each individual document or publication was specifically and individually incorporated herein by reference.  
         [0025]     The foregoing description is illustrative of particular embodiments of the invention, but is not meant to be a limitation upon the practice thereof. The following claims, including all equivalents thereof, are intended to define the scope of the invention.