U.S. patent application number 12/066628 was filed with the patent office on 2009-08-27 for soft tissue implants and methods for making same.
Invention is credited to Peter Gingras, Dean King.
Application Number | 20090216338 12/066628 |
Document ID | / |
Family ID | 37496856 |
Filed Date | 2009-08-27 |
United States Patent
Application |
20090216338 |
Kind Code |
A1 |
Gingras; Peter ; et
al. |
August 27, 2009 |
SOFT TISSUE IMPLANTS AND METHODS FOR MAKING SAME
Abstract
The present invention features soft tissue implants comprising
major (34) and minor struts (36) and methods for making same. The
implants can include biocompatible film (30) that is rendered
porous due to the inclusion of uniformly or non-uniformly patterned
cells (32), and the film has a thickness of less than about (0.015
inches) in the event the starting material is non-porous and less
than about (0.035 inches) in the event the starting material is a
microporous film. Multi-film implants can also be made.
Inventors: |
Gingras; Peter; (Galway,
IE) ; King; Dean; (Galway, IE) |
Correspondence
Address: |
FISH & RICHARDSON PC
P.O. BOX 1022
MINNEAPOLIS
MN
55440-1022
US
|
Family ID: |
37496856 |
Appl. No.: |
12/066628 |
Filed: |
September 12, 2006 |
PCT Filed: |
September 12, 2006 |
PCT NO: |
PCT/US06/35518 |
371 Date: |
February 20, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60716438 |
Sep 12, 2005 |
|
|
|
Current U.S.
Class: |
623/23.72 ;
606/151 |
Current CPC
Class: |
A61F 2/0077 20130101;
A61F 2/0063 20130101 |
Class at
Publication: |
623/23.72 ;
606/151 |
International
Class: |
A61F 2/02 20060101
A61F002/02; A61B 17/08 20060101 A61B017/08 |
Claims
1. A non-woven soft tissue implant comprising a porous
biocompatible film having a plurality of cells, a thickness of less
than about 0.015 inches, a plurality of major struts having a width
of about 0.020 inches to about 0.100 inches and a plurality of
minor struts having a width of about 0.001 inches to about 0.024
inches.
2. The non-woven soft tissue implant of claim 1, wherein the porous
biocompatible film comprises a non-absorbable polymer or
copolymer.
3. The non-woven soft tissue implant of claim 2, wherein the
non-absorbable polymer or copolymer comprises polypropylene,
polyethylene terephthalate, polytetrafluoroethylene,
polyaryletherketone, nylon, fluorinated ethylene propylene,
polybutester, or silicone.
4. The non-woven soft tissue implant of claim 1, wherein the porous
biocompatible film comprises an absorbable polymer or
copolymer.
5. The non-woven soft tissue implant of claim 4, wherein the
absorbable polymer or copolymer comprises polyglycolic acid (PGA),
polylactic acid (PLA), polycaprolactone, or
polyhydroxyalkanoate.
6. The non-woven soft tissue implant of claim 1, wherein the porous
biocompatible film comprises a biological material.
7. The non-woven soft tissue implant of claim 6, wherein the
biological material is collagen.
8. The non-woven soft tissue implant of claim 1, wherein the major
strut is about 0.050 inches wide.
9. The non-woven soft tissue implant of claim 1, wherein one or
more of the cells in the plurality of cells has a diameter,
measured along the longest axis of the cell, of about 10.mu. to
about 10,000.mu..
10. The non-woven soft tissue implant of claim 9, wherein one or
more of the cells in the plurality of cells has a diameter,
measured along the longest axis of the cell, of about 1,500.mu. to
about 5,000.mu..
11. The non-woven soft tissue implant of claim 9, wherein one or
more of the cells in the plurality of cells has a diameter,
measured along the longest axis of the cell, of about 50.mu. to
about 100.mu..
12. The non-woven soft tissue implant of claim 1, wherein each of
the plurality of cells is essentially square, rectangular, or
diamond-shaped.
13. The non-woven soft tissue implant of claim 1, wherein each of
the plurality of cells is essentially round or oval-shaped.
14. The non-woven soft tissue implant of claim 1, wherein one or
more of the cells of the plurality have essentially the same shape
as the cell shown in Mesh2, Mesh2C, Mesh3, or Mesh4.
15. The non-woven soft tissue implant of claim 1, wherein the
thickness of the porous biocompatible film is or is less than about
0.014 inches, is or is less than about 0.013 inches, is or is less
than about 0.012 inches, is or is less than about 0.011 inches, is
or is less than about 0.010 inches, is or is less than about 0.009
inches, is or is less than about 0.008 inches, is or is less than
about 0.007 inches, is or is less than about 0.006 inches, is or is
less than about 0.005 inches, is or is less than about 0.004
inches, is or is less than about 0.003 inches, is or is less than
about 0.002 inches, or is about 0.001 inch.
16. The non-woven soft tissue implant of claim 1, wherein the
porous biocompatible film has atraumatic edges.
17. The non-woven soft tissue implant of claim 1, wherein the
porous biocompatible film is at least about 2.5 cm long along a
first side and no more than about 45.0 cm long along a second
side.
18. The non-woven soft tissue implant of claim 1, wherein the
implant is flexible along two axes.
19. The non-woven soft tissue implant of claim 18, wherein the
plurality of cells comprises a cell pattern containing undulating
elements comprising a sinusoidal element.
20. The non-woven soft tissue implant of claim 18, wherein each of
the cells in the plurality of cells has a plurality of undulating
elements in the form of a repeating pattern.
21-49. (canceled)
Description
TECHNICAL FIELD
[0001] This document describes medical devices and relates more
specifically to soft tissue implants that can be used to improve
injured or otherwise defective tissue within a body.
BACKGROUND
[0002] Soft tissue implants are used to reinforce or replace areas
of the human body that have acquired defects. The inclusion of
biomaterials, which can work either by creating a mechanical
closure or by inducing scar formation, has improved the results
obtained with soft tissue implants. However, implanting large
amounts of synthetic material increases the rate of local wound
complications such as seromas (30-50%), paraesthesia (10-20%), and
restriction of mobility (25%) (see Klinge et al., Eur. J. Surg.
164: 951-960, 1998). Loss of mobility can occur, for example, when
soft tissue implants are used in abdominal wall closures. Following
implantation, current biomaterials with initially low bending
stiffness may turn into hard sheets that cannot be displaced to the
same extent as the abdominal wall (i.e., the sheets do not exhibit
25% strain under forces of 16 N/cm (see Junge et al., Hernia
5:113-118, 2001)). As a consequence, excessive scar tissue can
form, which will decrease mobility in the abdominal wall. In
addition, implants can cause inflammation and connective tissue
formation. These events appear to be closely related to the amount
of material implanted, the type of filament, and the proportion of
pores, which define the surface or contact area between the foreign
material and the recipient tissues. In particular, large amounts of
polypropylene, especially that where the surface has been greatly
enlarged by processing multifilaments, induce a strong inflammatory
response (see Klosterhalfen et al., Biomaterials 19:2235-2246,
1998). Histological analysis of explanted biomaterials has revealed
persistent inflammation at the interface, even after several years
of implantation. The persistent foreign body reaction is
independent of the inflammation time, but considerably affected by
the type of biomaterial (see Welty et al., Hernia 5:142-147, 2001,
and Klinge et al., Eur. J Surg., 165:665-673, 1999). The
persistence of this reaction at the biomaterial-tissue interface
might cause severe problems, particularly in young patients, in
whom the biomaterial is expected to hold for prolonged periods of
time.
[0003] There are currently several known soft tissue implants. Bard
Mesh.TM. is a non-absorbable implant that is made from monofilament
polypropylene fibers using a knitting process (C. R. Bard, Inc.,
Cranston, R.I.; see also U.S. Pat. No. 3,054,406; U.S. Pat. No.
3,124,136; and Chu et al., J. Bio. Mat. Res. 19:903-916, 1985).
Additional non-absorbable meshes are described in, for example,
U.S. Pat. Nos. 2,671,444; 4,347,847; 4,452,245; 5,292,328;
5,569,273; 6,042,593; 6,090,116; 6,287,316 (this patent describes
the mesh marketed as Prolene.TM.); and 6,408,656.
[0004] The meshes described above are made using synthetic fiber
technology. Different knit patterns impart unique mechanical
properties to each configuration. The implant surface area ratio
has also been calculated for prior art knit biomaterials. The
following formulas were used to calculate the surface area
ratio:
[0005] V.sub.mat=W.sub.mat/D.sub.mat where V.sub.mat is the
material volume, W.sub.mat is the material weight, and D.sub.mat is
the material density which is 0.904 g/cm.sup.3 for
polypropylene;
[0006] L.sub.fiber=V.sub.mat/((.pi.)(R.sub.fiber).sup.2) where
R.sub.fiber is the radius of the fiber and L.sub.fiber is the
length of the fiber;
[0007] A.sub.surface=(.pi.)(D.sub.fiber)(L.sub.fiber) where
A.sub.surface is the surface area of the fiber used to construct
the material and D.sub.fiber is the diameter of the fiber; and
[0008] Surface Area Ratio=A.sub.surface/F.sub.area where F.sub.area
is the area of the biomaterial fabric used to obtain W.sub.mat.
TABLE-US-00001 Fiber Weight Diameter Surface Product Construction
(g/cm2) (cm) Area Ratio Bard Mesh Monofilament Knit 0.0096 0.017
2.52 Trelex Mesh Monofilament Knit 0.0112 0.017 2.85 Prolene Mesh
Monofilament Knit 0.0096 0.015 2.91
[0009] The Gore-Tex Soft Tissue Patch.TM. is another non-absorbable
implant (W.L. Gore & Associates, Inc., Flagstaff, Ariz.; see
also U.S. Pat. Nos. 3,953,566; 4,187,390; 5,641,566; and 5,645,915)
made from expanded polytetrafluoroethylene (ePTFE). This product is
microporous, having pores of approximately 20 microns in diameter.
The porosity of the Gore-Tex material may, however, be insufficient
to allow incorporation into surrounding tissues; a minimum pore
size of approximately 60 microns may be required for fibrous or
collagenous material to grow into the patch (Simmermacher et al.,
J. Am. Coll. Surg. 178:613-616, 1994). Methods to improve tissue
ingrowth are described in U.S. Pat. Nos. 5,433,996 and 5,614,284,
and a method of laminating a layer of mesh-type material to the
ePTFE has also been described. In addition, U.S. Pat. No. 5,858,505
describes a macroscopically perforated ePTFE material with
perforations having a minimum diameter of about 100 microns, and
methods for producing high strength multiple component articles
made from ePTFE are described in U.S. Pat. Nos. 4,385,093 and
4,478,655. Biomaterials made from ePTFE, however, do not have
displacement elasticity properties that would prevent injury at the
biomaterial-tissue junction. The ePTFE has a relatively low
displacement elasticity, which prevents the biomaterial from
extending when physiological force is applied.
[0010] Another type of implant, referred to as a "reinforcing
plate" has been developed for treating damaged tissues (WO
01/80774). It contains a non-woven material based on polypropylene
and forms a plate with small circular perforations (non-woven films
may also be described in the art as "biaxially-oriented" films).
The plate is preformed in a circular shape for treating damaged
tissues of the abdominal wall.
[0011] Absorbable soft tissue implants are also known. For example,
there are devices composed of polyglycolic acid and non-absorbable
filaments (see U.S. Pat. No. 3,463,158; see also U.S. Pat. No.
4,520,821). Absorbable fibers can be used to create a knit mesh
(see U.S. Pat. Nos. 4,633,873 and 4,838,884), and a warp knit mesh
has been developed to prevent adhesions composed of regenerated
cellulose (U.S. Pat. No. 5,002,551). A non-woven mesh made from
biodegradable fibers has also been described (U.S. Pat. No.
6,045,908), as has a mesh having two layers that degrade at
different rates (U.S. Pat. No. 6,319,264).
[0012] The thickness for the commercially available implants
disclosed above is provided in the table below. As indicated, the
thinnest material available has a thickness of 0.016 inches.
TABLE-US-00002 Thickness Material Company Code No. (inches) Bard
Mesh C. R. Bard/Davol 112660 0.026 Prolene Mesh J&J/Ethicon PML
0.020 Gore-Tex Soft Tissue Patch W. L. Gore 1415020010 0.039
Gore-Tex Soft Tissue Patch W. L. Gore 1315020020 0.079 ProLite
Atrium Medical 1001212-00 0.019 ProLite Ultra Atrium Medical 30721
0.016
[0013] Each of the implants presently in use has one or more
deficiencies. For example, their construction can result in
characteristics (e.g., wall thickness and surface area) that
increase the risk of an inflammatory response or of infection;
seromas can form postoperatively within the space between the
prosthesis and the host tissues; due to material content, width,
and wall thickness, surgeons must make large incisions for
implantation (the present implants can be difficult to deploy in
less invasive surgical methods); rough implant surfaces can
irritate tissues and lead to the erosion of adjacent tissue
structures; adhesions to the bowel can form when the implant comes
in direct contact with the intestinal tract; where pore size is
reduced, there can be inadequate tissue ingrowth and incorporation;
and the pore size and configuration of the implants does not permit
adequate visualization through the implant during laparoscopic
procedures. Implants with increased thickness, surface area, and
void area can lead to excessive scar tissue formation and implant
encapsulation, which results in shrinkage and stiffness to the
implant and surrounding tissue region. Accordingly, there remains a
need for implants for repairing soft tissue and methods of making
those implants.
SUMMARY
[0014] The present invention features a strong and flexible soft
tissue implant that includes a biocompatible film that is rendered
porous due to the inclusion of uniformly and/or non-uniformly
patterned cells (i.e., the film can contain a plurality of cells);
the film can have a thickness of less than about 0.015 inches in
the event the starting material is non-porous and less than about
0.035 inches in the event the starting material is a microporous
film. The terms "porous," "non-porous," and "microporous" are used
herein in a manner consistent with their usual meaning in the art
(as noted above, the ePTFE material described in U.S. Pat. No.
5,858,505 is a microporous material having perforations with a
minimum diameter of about 100.mu.; the Gore-Tex Soft Tissue
Patch.TM. is made from ePTFE and has pores that are approximately
20.mu. in diameter). The methods used to make an implant from a
non-porous material can be applied to make an implant from a porous
or microporous material (and vice-versa), and implants made from
these types of starting material can be similarly used to treat
patients.
[0015] The overall thickness of the implant can remain within the
parameters given for the thickness of the individual films (i.e.,
the soft tissue implant can be less than about 0.015 inches when
constructed from one or more non-porous films and less than about
0.035 inches when constructed from one or more microporous films)
or it can be a multiple of the individual film's thickness (e.g.,
where two 0.008'' films are laminated, the implant can be about
0.016'' thick; where three such films are laminated, the implant
can be about 0.024'' thick, and so forth). Thus, a given implant
can include more than one film (e.g., more than one biocompatible
film, regardless of whether the starting material is non-porous or
microporous; one or more additional films of different content, as
described further below, can also be included).
[0016] In one embodiment, the invention features a soft tissue
implant that includes a first porous biocompatible film and a
second porous biocompatible film, the thickness of the implant
being less than about 0.015 inches (e.g., about 0.014'', 0.013'',
0.012'', 0.011'', 0.010'', 0.009'', 0.008'', 0.007'', 0.006'',
0.005'', 0.004'', 0.003'', 0.002'', 0.001'') (as noted above, the
thickness of the implant can be less than about 0.035'' when
microporous films are used (e.g., about 0.033, 0.030, 0.027, 0.025,
0.023, 0.020, 0.018, or 0.015''), and implants containing laminated
films will be about as thick as the combined thickness of the
incorporated films). The implants, including the materials from
which they are made and the cell patterns they can contain are
described further below. We note here that, regardless of the
number, size, or pattern of the cells within the implants, one or
more (and up to all) of the edges of the cells can be atraumatic
(i.e., the implant can have cells with smooth, tapered, or rounded
edges). The term "cell(s)" may be used interchangeably below with
the term "pore(s)."
[0017] The soft tissue implants are made up of a repeating pattern
of cells. The cells have dimensions along the longest axis being
less than about 0.500 inches (e.g., about 0.400'', 0.300'', 0.200,
0.100'', 0.090'', 0.080'', 0.070'', 0.060'', 0.050'', 0.040'',
0.030'', 0.020'', 0.010'', 0.009'', 0.008'', 0.007'', 0.006'',
0.005'', 0.004'', 0.003'', 0.002'', 0.001''). The distance between
cells can include or consist of biocompatible film material in the
form of struts. Strut distances can vary, as described further
below, and are dependent on the cell pattern. Where a first
plurality of cells is separated from a second plurality of cells,
the distances between cells within each plurality may be referred
to as minor struts, and the distances between the first and second
pluralities may be referred to as major struts. Where the cell
pattern is a regular, repeating pattern, the cells may appear as
blocks (or other shapes, as described further below), the minor
struts being within the blocks, and the major struts being between
the blocks. The width of the struts (e.g., the major struts) can
vary from, for example, about 0.001'' to at least, or about,
0.500'' (e.g., 0.001'', 0.005'', 0.010'', 0.012'', 0.014'',
0.015'', 0.020'', 0.025'', 0.030'', 0.035'', 0.040'', 0.045'',
0.050'', 0.055'', 0.060'', 0.065'', 0.070'', 0.075'', 0.080'',
0.085'', 0.090'', 0.095'', 0.100'', 0.125'', 0.150'', 0.200'',
0.250'', 0.300'', 0.350'', 0.400'', 0.450'', or 0.500'').
[0018] The soft tissue implants can also have one or more of the
material characteristics described below. For example, a soft
tissue implant can have a surface area ratio of about 1.5 or less
(e.g., of about 1.00 (e.g., 0.90-0.99 (e.g., 0.94 or 0.97)) of
about 0.80 (e.g., 0.75-0.79 (e.g., 0.79)) or of about 0.50 (e.g.,
of 0.45-0.55 (e.g., 0.54))). In addition, or alternatively, the
soft tissue implant can be defined by the extent to which it can be
distended when placed on or within a body. For example, in some
embodiments, the implants can be distended by about 25% or more
(e.g., 20%, 30%, 33%, 35%, 40%, 50% or more) at a force borne by a
tissue (e.g., a muscle or muscle group) by which they are placed.
For example, the implants can be distended by about 25% at 16
N/cm.
[0019] The films can be made from a variety of polymers (including
absorbable and non-absorbable polymers, such as those set out
below) or copolymers thereof. For example, the implants of the
invention can include films of non-absorbable polymers such as
polypropylene, polyethylene terephthalate, polytetrafluoroethylene,
polyaryletherketone, nylon, fluorinated ethylene propylene,
polybutester, or silicone. Where absorbable polymers are used, they
can be, for example, a polyglycolic acid (PGA), a polylactic acid
(PLA), polycaprolactone, or polyhydroxyalkanoate.
[0020] The invention also features implants containing biological
materials rather than, or in addition to, the polymer-based films
described herein. These biological materials may or may not be
polymeric. For example, one or more of the films in the implants of
the invention can include collagen (which is generally considered
to be a repetitive, polymeric substance) or tissue-based products
(which are generally not considered to be polymeric). For example,
the implants of the invention can be made from films consisting of,
or that include, mucosal tissue (e.g., the mucosa and/or submucosa
of an organ such as the large or small intestine (the mucosa and/or
submucosa can be from a human (as might be obtained from a cadaver)
or non-human animal (such as a pig, sheep, cow, goat, horse, or
other such animal)). For example, the implants of the invention can
be made from porcine submucosa (such as is sold by Cook Surgical
(Bloomington, Ind.) as Surgisis.TM.). Films of biological material,
such as the mucosal/submucosal preparations described here, can be
layered to produce an implant of the invention. As few as two, or
as many as 5, 10, 15, 20, or 25 biological films can be adhered to
one another and then rendered porous by the same methods (e.g.,
laser ablation, die punching or other physical intervention) used
to introduce a cellular pattern into the conventional polymeric
films described herein. As with any of the implants of the
invention, the cellular pattern can be regular or irregular and can
be repeated in a regular or irregular pattern, an edge of the pores
can be smooth, and one or more portions of the periphery of the
implant can be reinforced (e.g., can be made thicker or more dense)
to facilitate implantation.
[0021] The invention also features methods for producing soft
tissue implants and methods of using those implants to treat a
patient who has an injured or otherwise defective tissue. These
methods can include the steps of extruding a biocompatible polymer
into a film and forming pores in the film. In alternative
embodiments, the film can be stretched or otherwise manipulated
(e.g., trimmed, shaped, washed or otherwise treated) before or
after forming pores in the film. For example, in one embodiment,
the invention features a method having one or more of the following
steps: (a) providing a polymeric film or a film of a biological
tissue or extruding a polymer into a film; (b) stretching the film
(this may be done along one axis or, to the same, similar, or
dissimilar extents, along two axes (i.e., biaxially) (stretching
the film is less likely to be necessary where the film comprises
non-polymeric biological tissue, such as submucosal tissue); (c)
laminating one or more films (this is an optional step that can be
done by, for example, applying heat, pressure, or an adhesive to
two or more films); (d) producing a plurality of cells within the
film or laminated films; (e) cleaning the porous implant; and (f)
packaging the porous implant. The implant can be sterilized
(according to methods known in the art as effective in sterilizing
implants and medical devices), before or after it is packaged. The
packaged implants, provided, optionally, with instructions for
their use are also within the scope of the invention. More
specifically, where an implant contains more than one film, the
methods of the invention can be carried out by, for example,
extruding a first biocompatible polymer to form a first film,
extruding a second biocompatible polymer to form a second film,
attaching the first film to the second film to produce a soft
tissue implant, and forming pores in the soft tissue implant.
Alternatively, the pores can be formed before the two films (or any
of the multiple films) are adhered to one another. In that
instance, the method of making the soft tissue implant can be
carried out by, for example: extruding a first biocompatible
polymer to form a first film; forming pores in the first film;
extruding a second biocompatible polymer to form a second film;
forming pores in the second film; and attaching the first film to
the second film to produce a soft tissue implant. Implants having
two or more films (which may or may not consist of the same
material(s)), including those made by the methods described herein,
are within the scope of the invention. Thus, the invention features
a soft tissue implant made by a method described herein.
[0022] Where more than two films (e.g., three, four, five, six, or
more) are present, the extruding step can be repeated for each
film, and pores can be formed in each film before or after it is
incorporated in the implant or adhered to another film. The films
in a multi-film implant may be substantially identical or
non-identical. For example, they can vary in thickness, length, or
width, or in any combination of thickness, length, and width, from
one another. The films can also vary in their material content and
in the size, number, or arrangement of their pores (e.g., an
implant can include a tear resistant substrate and the polymers
used to construct the film(s) can be compounded with impact
modifiers).
[0023] As indicated above, as an alternative to forming a film by
polymer extrusion, one may simply obtain the film(s). Such films
may have substantially final overall dimensions (e.g.,
substantially final length, width, and thickness) or they may be
modified to attain the desired form.
[0024] Where a film is obtained, rather than made, the methods of
making the soft tissue implant can simply require providing a given
film that is then attached (e.g., reversibly or irreversibly bound
by mechanical or chemical forces)), if desired, to another film
and/or processing the film to alter its outer dimensions (e.g., to
decrease, in a regular or irregular way, the length or width of the
film; this can be achieved by stretching the film, which may also
alter its thickness). The method can continue by processing the
film to include one or more pores (or cells) of a given size and
arrangement. For example, the single provided film (or adherent
multiple films) can then be subjected to a process (e.g., laser
ablation, die punching, or the like) that forms pores within the
film(s). Accordingly, any of the methods of the invention can be
carried out by providing a given biocompatible film, rather than by
producing it by an extrusion or extrusion-like process.
[0025] The film(s) can be further modified so that the edges, or
selected points along the edges, have different features than the
remainder of the implant. For example, the implant can be denser
along its outer periphery, or at one or more points around the
periphery, in order to facilitate suture (or similar fastener)
retention (as loss of attachment can cause the implant to
fail).
[0026] The soft tissue implants of the invention may be referred to
herein as "non-woven." The term "non-woven" indicates that the
implant is made, at least in part, from a material or materials
that are processed into sheets or films using traditional melt or
paste extrusion methods. After extrusion, the sheet or film can be
cut, stretched, annealed, or sintered to change its material
properties (preferably in a way that improves the performance of
the implant in the body). Before it is machined (by, for example, a
laser or other device capable of forming pores within the sheet or
film) the material (i.e., the intact sheet or film) is
substantially impermeable (thus, by way of the methods of the
invention, non-porous or microporous films can be made into porous
implants).
[0027] As noted above, the soft tissue implants of the invention
can include (or consist of) a film that has a low profile (or
reduced wall thickness) and that is biocompatible. A biocompatible
film is one that can, for example, reside next to biological tissue
without harming the tissue to any appreciable extent. As noted
above, the film(s) used in the soft tissue implants of the
invention can have pores or cells (e.g., open passages from one
surface of a film to another) that permit tissue ingrowth and/or
cellular infiltration.
[0028] The overall shape of the implants can vary dramatically
depending on the indication or intended use. The overall length and
width of the implants of the present invention can be the same as,
or similar to, those of presently available implants (although, of
course, other parameters or characteristics, as described herein,
will vary). The implants of the invention can be, for example,
rectangular in shape. For example, the implants can have a length
that is approximately, 2, 3, 4, or more times greater than their
width. For example, implants having a length that is approximately
four times greater than their width can be, for example, about 0.5
cm.times.2.0 cm (or 0.5''.times.2.0''); about 1.0 cm.times.4.0 cm
(or 1.0''.times.4.0''); about 2.0 cm.times.8.0 cm (or
2.0''.times.8.0''); about 2.5 cm.times.10.0 cm (or about
2.5''.times.10.0''); about 3.0 cm.times.9.0 cm (or
3.0''.times.9.0''); etc. Alternatively, the implants can be square
(e.g., they can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 cm, or
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 inches square). Larger
implants can be readily made and used if required. For example,
implants that are about 15.0 cm.times.15.0 cm; about
20.0.times.20.0 cm; about 30.0.times.30.0 cm; or about
45.0.times.45.0 cm can be made by the methods described herein and
are within the scope of the present invention. Of course, round,
oval, or irregularly shaped implants may be made as well.
[0029] The implants of the present invention offer a combination of
high porosity, high strength, low stiffness, and low material
content, and they may have one or more of the following advantages.
They can include pores or porous structures that stimulate fibrosis
and reduce inflammation; they can reduce the risk of erosion and
formation of adhesions with adjacent tissue (this is especially
true with implants having a smooth surface and atraumatic (e.g.,
smooth, tapered, or rounded) edges; their displacement elasticity
can reduce the damage that may occur with other implants at the
tissue-biomaterial interface; they can simulate the physical
properties of the tissue being repaired or replaced, which is
expected to promote more complete healing and minimize patient
discomfort; their surface areas can be reduced relative to prior
art devices (having a reduced amount of material may decrease the
likelihood of an immune or inflammatory response). Moreover,
implants with a reduced profile can be introduced and/or implanted
in a minimally invasive fashion; as they are pliable, they can be
placed or implanted through smaller surgical incisions. The methods
of the invention may also produce implants with improved optical
properties (e.g., implants through which the surgeon can visualize
underlying tissue). Practically, the micromachining techniques that
can be used to produce the implants of the present invention are
efficient and reproducible. The soft tissue implants described
herein should provide enhanced biocompatibility in a low profile
configuration while maintaining the requisite strength to repair
tissue.
[0030] The details of one or more embodiments of the invention are
set forth in the accompanying drawings and the description below.
Other features, objects, and advantages of the invention will be
apparent from the description and drawings, and from the
claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0031] FIGS. 1A-1C are micrographs of commercially available
meshes. FIG. 1A is of a poly-propylene mesh (Bard Mesh.TM.); FIG.
1B is of Prolene.TM. Mesh; and FIG. 1C is of Trelex.TM. Mesh.
[0032] FIGS. 2A-2C are perspective views of materials that can be
machined to produce implants of the invention.
[0033] FIGS. 3A and 3B are perspective views of diamond-like cell
patterns machined in films.
[0034] FIGS. 4A and 4B are photomicrographs of an exemplary cell
(FIG. 4A; this cell-shape was incorporated in Mesh4) and of the
edge of that cell (FIG. 4B).
[0035] FIG. 5 is a flow chart illustrating some of the steps in a
method of producing a soft tissue implant of the invention.
[0036] FIGS. 6A and 6B relate to a non-woven soft tissue implant
designated Mesh2. FIG. 6A is a diagram of an exemplary pore;
structures and areas that can be measured are shown. FIG. 6B is a
Table assigning values to various measured parameters within Mesh2
and the equations used to calculate the surface area ratio.
[0037] FIGS. 7A and 7B are photomicrographs. FIG. 7A shows a
histological preparation of Mesh2 stained with hematoxylin and
eosin, following a 14-day implantation. FIG. 7B shows a
histological preparation of Mesh2, Masson's trichrome-stained,
following a 14-day implantation.
[0038] FIGS. 8A and 8B relate to a non-woven soft tissue implant
designated Mesh2C. FIG. 8A is a diagram of an exemplary pore. FIG.
8B is a display of various measured parameters within Mesh 2C and
the equations used to calculate the surface area ratio.
[0039] FIGS. 9A and 9B relate to a non-woven soft tissue implant
designated Mesh4. FIG. 9A is a diagram of an exemplary pore. FIG.
9B is a display of various measured parameters within Mesh4 and the
equations used to calculate the surface area ratio.
[0040] FIGS. 10A and 10B relate to a non-woven soft tissue implant
designated Mesh3. FIG. 10A is a diagram of an exemplary pore. FIG.
10B is a display of various measured parameters within Mesh3 and
the equations used to calculate the surface area ratio.
[0041] FIG. 11 is an illustration of a cell.
[0042] FIG. 12 is a graph showing the percentage strain (x-axis) on
various soft tissue implants including Marlex.TM., Prolene.TM.,
Trelex.TM., Mesh2, and ePTFE.
[0043] FIGS. 13A-13I illustrate soft tissue implants within the
scope of the present invention. FIG. 13A illustrates a cell pattern
and provides measurements obtained of a variety of the features
related to the pattern. FIGS. 13B-13I illustrate soft tissue
implants of varying sizes and shapes.
[0044] FIG. 14 relates to a nonwoven soft tissue implant.
[0045] FIG. 15 relates to a nonwoven soft tissue implant.
DETAILED DESCRIPTION
[0046] Commercially available, woven materials that have been used
to help repair soft tissue are illustrated in FIGS. 1A-1C. The
polypropylene mesh shown in the micrograph of FIG. 1A is Bard Mesh,
a non-absorbable, knitted material produced by C. R. Bard, Inc.
(Murray Hill, N.J.); and the material shown in the micrograph of
FIG. 1B is Prolene.TM. Mesh (Ethicon, Inc., Somerville, N.J.); and
the material shown in the micrograph of FIG. 1C is Trelex
Natural.RTM. Mesh, a non-absorbable, knitted material produced by
Boston Scientific Corporation (Natick, Mass.);
[0047] FIGS. 2A-2C are perspective views of materials that can be
machined to produce a non-woven soft tissue implant of the present
invention. FIG. 2A is a perspective view of non-woven biocompatible
film 14. Film 14 has known or discernable dimensions (width,
length, and thickness), which can be modified or left intact in the
manufacture of a soft tissue implant. Film 14 is a single-layer,
smooth-edged film. As shown in FIG. 2B, film 14 can be laminated to
produce film 16, which can also be used, with or without further
modification, to manufacture the implants of the present invention.
Multiple layers of biocompatible film 14 can be added together to
improve the mechanical properties (e.g., tear resistance or burst
strength) of the implant. A first film 14 can be thermally bonded
to a second film 14 using hydraulic presses such as those
manufactured by OEM Press Systems (Orange, Calif.).
[0048] As shown in FIG. 2C, an implant can include laminated film
16, that includes two pieces of film 14 and tear resistant
substrate 18. Tear resistant substrate 18 is placed between a first
film 14 and a second film 14. Where tear resistant substrate 18 is
thermally compatible with film 14, tear resistant substrate 18 and
film 14 can be bonded using heat and/or pressure. If necessary, an
adhesive or thermal attachment layer can be used between film 14
and tear resistant substrate 18. This may include a layer of
material with a lower melting point, which can be achieved by
reducing the crystallinity of a like material or by selecting a
different material composition. Alternatively, tear resistant
substrate 18 can be mechanically bonded to film 14 by sutures,
clips, or the like.
[0049] Biocompatible materials useful in film 14 or laminated film
16 can include non-absorbable polymers such as polypropylene,
polyethylene, polyethylene terephthalate, polytetrafluoroethylene,
polyaryletherketone, nylon, fluorinated ethylene propylene,
polybutester, and silicone, or copolymers thereof (e.g., a
copolymer of polypropylene and polyethylene); absorbable polymers
such as polyglycolic acid (PGA), polylactic acid (PLA),
polycaprolactone, and polyhydroxyalkanoate, or copolymers thereof
(e.g., a copolymer of PGA and PLA); or tissue based materials
(e.g., collagen or other biological material or tissue (e.g.,
mucosal or submucosal tissue) obtained from the patient who is to
receive the implant or obtained from another person (e.g., a
recently deceased person) or an animal (i.e., the implant can
constitute a xenograft)). The polymers can be of the D-isoform, the
L-isoform, or a mixture of both. An example of a biocompatible film
14 suitable for producing the laminated film structure 16 is
biaxially oriented polypropylene. AET Films (Peabody, Mass.)
manufactures biaxially oriented films (AQS and OPB).
[0050] Tear resistant substrate 18 can be spunbonded polypropylene,
ePTFE, or a polymeric film compounded with impact modifiers.
[0051] FIGS. 3A and 3B are perspective views of machined films 20
and 21, respectively. Referring to FIG. 3A, diamond-like cell
pattern 22 has been machined into film 20 to impart porosity, which
can support tissue ingrowth on high strength thin film substrates.
Radius 24 has been applied to each cell pattern 22 corner to
improve tear strength. Changing the dimensions of cell member 26
can alter the configuration of cell pattern 22. Different physical
properties can be imparted along each axis of the film. Referring
to FIG. 3B, a perspective view of a machined film 21, tapered cell
pattern 22 has been machined into the film to impart porosity,
which can support tissue ingrowth. The ability to alter mechanical
properties with tapered cell pattern 22 geometry is demonstrated.
Manufacturing methods to impart patterns such as cell pattern 22
include, but are not limited to, laser machining, die punching,
water jet cutting, and chemical etching. The lasers preferred for
creating smooth edges on plastic films include, but are not limited
to, CO.sub.2, diode ultraviolet, or excimer lasers. An implant
having cell pattern 22 is expected to confer benefit to a patient
in which it is implanted because of the substantially smooth edges
of cell pattern 22.
[0052] Referring to FIGS. 4A and 4B, cell member 27 was created in
biocompatible film 28. Atraumatic edge 29 lies at the interface
between cell member 27 and biocompatible film 28. Cell member 27
was created using a 3.0-Watt Avia Q-switched Ultraviolet Laser
(Coherent, Inc., Santa Clara, Calif.).
[0053] Referring to FIG. 5, a block diagram shows manufacturing
steps for creating a non-woven soft tissue implant. The polymer
used to construct the film is extruded using melt or paste
extrusion techniques (as noted herein, in alternative methods of
the invention, the film can be obtained, rather than made). After
extrusion, the mechanical properties (e.g., tensile strength) can
be improved through a biaxial stretching process (this is an
optional step). Equipment that can be used to carry out this
process can be purchased from Bruckner GmbH (Siegsdorf, Germany).
If desired, the film can be laminated using heat, pressure, or
adhesives to further improve the mechanical properties of the
implant. Films with properties that may improve an implant (e.g.,
films with increased tear strength) can be added at this step. A
cell pattern (such as one described or illustrated herein) is
machined into the film. The film can be annealed at elevated
temperatures (e.g., above the glass transition temperature for the
polymer within the film) to relieve stresses caused by film
stretching and the machining process. The material can then be
cleaned, packaged, and sterilized. The packaging material can
include instructions for use (i.e., instructions can be printed on
the packaging material); similarly, instructions can be provided on
a separate material.
[0054] Referring to FIGS. 6A, 8A, 9A, and 10A, unit cells of Mesh2,
Mesh2C, Mesh4, and Mesh3, respectively, are diagrammed. As shown in
the legends,
[0055] Ap=Area of pore;
[0056] Pp=perimeter of pore;
[0057] t=thickness;
[0058] Ac=Area of space in unit cell;
[0059] Atop=Ac-As
[0060] Abot=Bottom surface area;
[0061] Abot=Atop
[0062] A5=Area of thickness
[0063] At=t(Pg+4(Pp/4))=2tPp
[0064] Asu=Surface area of a unit cell
[0065] Asu=Atop+Abot+At; and
[0066] Asurf=Total 3D surface area per 2D area of mesh.
[0067] Referring to FIGS. 6B, 8B, 9B, and 10B, methods for
calculating the surface area ratio of Mesh2, Mesh2C, Mesh4, and
Mesh3 are provided in tabular form. A summary of the four nonwoven
films, their thickness and surface area ratio are shown in the
following Table:
TABLE-US-00003 Product Thickness (cm) Surface Area Ratio Mesh2
0.020 0.79 Mesh2C 0.020 0.97 Mesh3 0.020 0.94 Mesh4 0.020 0.54
[0068] Referring to FIG. 11, an exemplary pore having an opening of
0.100'' and a wall thickness of 0.025 inches is shown.
[0069] Referring to FIG. 12, a graph illustrates the percentage
strain .alpha.-axis) on various soft tissue implants including
Marlex.TM., Prolene.TM., Trelex.TM., Mesh2, and ePTFE.
[0070] Referring to FIGS. 13A-13I, uniformly patterned implants
including cell blocks divided by a material grid (e.g., a grid of
non-porous material) are shown. This pattern can be employed in any
of the implants described herein and regardless of the precise end
use (e.g. the precise medical indication).
[0071] FIG. 13A is a perspective view of machined film 30 with an
undulating cell pattern 32. A combination of major struts 34 and
minor struts 36 result from the repeating cell pattern. The major
struts 34 provide added strength and stability while the minor
struts 36 provide tissue support and coverage without imparting
excessive amounts of stiffness to the implant. Compositions that
consist of, or that include, this cell pattern (e.g., a non-woven
mesh made into a soft tissue implant by a method described herein)
are easy to handle yet of sufficient strength for applications such
as tissue repair. The combined ease of handling and strength can be
advantageous and should improve the desirability of these
compositions. Handling properties can be assessed by, for example,
assessing flexibility, and mechanical strength can be assessed by
any method known in the art (e.g., tensile strength, burst
strength, tear resistance).
[0072] The major strut pattern in FIG. 13A is substantially square.
Alternative major strut patterns could be employed to provide load
bearing potential along different axes (e.g. circular, triangular,
hexagonal, undulating). In addition, alternative minor strut
patterns could be employed to provide different levels of support
within the major strut patterns (e.g. circular, triangular,
hexagonal, undulating). These sizes and shapes are exemplary;
essentially any other size or shape can be made and used. Moreover,
more than one strut pattern can be present in a given implant.
[0073] The dimensions of the cell patterns shown in FIGS. 13A-13I,
like others shown or described herein, can be reduced or enlarged.
For example, the dimensions shown in FIG. 13A can be 1-20% smaller
or larger. The size of the pores and the material separating the
cell blocks can be changed in a way that allows their proportions,
relative to one another, to stay the same or substantially the
same. FIGS. 13B-13I illustrate grid-patterned cell blocks in
implants having a variety of sizes and shapes. These sizes and
shapes are exemplary; essentially any other size or shape can be
made and used. Moreover, the cells within the cell blocks can have
any of the shapes described and illustrated herein. For example,
the cells illustrated in any of FIG. 7A, 7B, 8A, 8B, 9A, 9B, 10A,
10B, or 11 can be arranged in blocks and separated by a material
grid as shown in FIG. 13A. In other embodiments, the sizes and
shapes of the cell blocks can vary. The cell blocks of FIG. 13A are
blocks of 16 cells (4.times.4). Alternatively, the blocks could
include 4 cells (2.times.2); 9 cells (3.times.3), 25 cells
(5.times.5), 36 cells (6.times.6), and so forth. The cell blocks
need not be square. For example, the cell blocks could include 16
cells in a 2.times.8 arrangement; 20 cells in a 2.times.10
arrangement; 44 cells in a 4.times.11 arrangement; and so
forth.
[0074] Referring to FIG. 14, a uniformly patterned implant is
shown. This pattern can be employed in any of the implants
described herein and regardless of the precise end use (e.g., the
precise medical indication). FIG. 14 is a perspective view of
machined film 40 with an undulating cell pattern 42.
[0075] Referring to FIG. 15, a uniformly patterned implant is
shown. This pattern can be employed in any of the implants
described herein and regardless of the precise end use (e.g., the
precise medical indication). FIG. 15 is a perspective view of
machined film 50 with an undulating cell pattern 52.
[0076] As illustrated by FIG. 3A and FIG. 6A, the cells within a
soft tissue implant can be regularly shaped (as are the rectangular
cells of FIG. 3A) or irregularly shaped (i.e., they can have an
irregularly shaped perimeter, as shown in FIG. 6A, which may or may
not be symmetrical). For example, the cell can be of a "regular"
shape when it is essentially square, rectangular, or
diamond-shaped, or essentially round or oval; the cell(s) can be of
an "irregular" shape when at least one of the cell walls contains a
sinusoidal element. Moreover, each of the cells in the implant can
have a plurality of undulating elements that form a repeating
pattern (e.g., the undulations can be in phase with one another).
The shape of the cells, their pattern, number, size, etc. can vary
as described herein regardless of the film from which the implant
is constructed (i.e., the cells can vary as described herein
regardless of whether the film is non-porous or microporous;
whether the implant contains a single film or multiple films;
whether the film contains an absorbable or non-absorbable polymer;
whether the implant contains a film to increase tear resistance;
etc.).
[0077] In any event (regardless of the cellular shape), the length
of an opening (i.e., the distance between one part of the cell wall
and another (e.g., the distance along the longest axis, the
shortest axis, an intermediate axis; or the distance between two
points that do not define an axis)) can be between about 10 and
about 10,000 microns (e.g., about 50-100 (e.g., about 75); about
10-1,000 (e.g., about 500); about 10-2,000 (e.g., about 1,200);
about 10-5,000 (e.g., about 2,500); about 10-7,500 (e.g., about
4,500); about 100-1,000 (e.g., about 750); about 500-2,000 (e.g.,
about 1,750); about 1,000-3,000 (e.g., about 2,100); about
1,000-5,000 (e.g., about 3,500); about 1,500-5,000 (e.g., about
3,750) about 4,000-6,000 (e.g., about 4,750); about 5,000-7,500
(e.g., about 6,500); about 6,000-8,000 (e.g., about 7,200); or
about 7,500-10,000 (e.g., about 9,000 microns). In one embodiment,
the cells of a soft tissue implant will be about 10-10,000.mu.;
about 1,500-5,000.mu.; or about 50-100.mu. (i.e., the length across
the longest axis of the cell can be about 100.mu., 250.mu.,
500.mu., 1,000.mu. or 2,000.mu.. Such implants (e.g., implants in
which the longest length of a cellular opening is about 2,000
microns) can be porous enough to permit tissue ingrowth while
having good mechanical properties (e.g., sufficient strength and
flexibility (e.g., an implant flexible along two axes)). One or
more of the cells in the plurality within an implant can have
essentially the same shape as the cell shown herein as that of
Mesh2, Mesh2C, Mesh3, or Mesh4.
[0078] Finite element analysis can be used to design a cell or cell
pattern that, when incorporated in a soft tissue implant, provides
the implant with properties that approximate one or more of the
properties of the soft tissue being repaired or replaced. Human
skeletal muscle can exert 3-4 kg of tension per square centimeter
of cross sectional area. Since many muscles in humans (or other
animals, which may also be treated with a soft tissue implant
described herein) have a relatively large cross-sectional area, the
tension they develop is quite large. The gluteus maximus can exert
a tension of 1200 kg, and the quadriceps can exert a tension of 360
kg. This difference is due to varying cross sectional areas.
Because areas of the body contain different muscle groups, the
non-woven soft tissue implants of the invention can be constructed
so that their characteristics (e.g., their strength
characteristics) match those of the tissue(s) being replaced or
repaired. For example, the soft tissue implant can have force
displacement characteristics that do not restrict tissue movement
(e.g., that do not restrict the contraction or stretching of a
muscle to which the implant is attached) or that restrict such
movement to a limited extent. For example, a soft tissue implant
can restrict tissue movement by less than 5%, less than 10%, less
than 25%, or less than 50%. The force displacement character of a
given implant can be calculated by measuring the percentage by
which the implant is displaced (e.g., the amount by which it
"gives" relative to a resting configuration) under a given force.
For example, a soft tissue implant can be distended by about 25%
(or more (e.g., 30, 35, 40, 45, 50% or more)) at 16 N/cm (see FIG.
12). The number, shape, and arrangement of the plurality of cells
and the thickness of the implant can be varied to impart force
displacement characteristics that approximate those of the
structure being repaired.
[0079] As noted above, the films can be made from a variety of
polymers, including absorbable polymers. Where the implant contains
more than one absorbable (e.g., bioresorbable) film, the rate at
which one film (e.g., a first film) is resorbed within a body can
be different from the rate at which another film (e.g., a second
film) is resorbed. As with other bi-layer or multi-layer implants
of the invention, a surface of the first film can adhere to a
surface of the second film, and multi-layer implants can include a
film that increases tear resistance (e.g., a porous biocompatible
film).
[0080] A soft tissue implant can also be defined by measured
parameters such as the area of a cell (or pore; Ap (see the size
ranges above), its perimeter (Pp), the area of a cell "unit" (Ac),
and the surface area ratio (Asurf), which is preferably less than
1.5. A method for calculating Asurf is shown in FIG. 6B, for
example. Asurf is calculated by dividing Asu (the 3D surface area
of a unit cell) by the area of the unit cell (Ac). Asu is
determined by adding the top surface area (Atop), the bottom
surface area (Abot; which can equal the top surface area), and the
area of thickness (At). These values, in turn, can be found as
follows: Atop is the difference between the area of a unit cell
(Ac) and the area of space in a unit cell (As); Abot can equal
Atop; and At equals the thickness of the film multiplied by
(Pp+4(Pp/4)). Lastly, As is equal to Ap plus 4(Ap/4) (which is
equal to 2Ap).
[0081] The methods of making a soft tissue implant include those
described above as well as the following. An implant can be made by
a method that includes the steps of extruding a biocompatible
polymer into a film and forming a plurality of cells in the film.
The film can be of a thickness described above and have the
material content described above, and the cells can have the
characteristics of any of those described above. As noted, the
extrusion process can be, for example, a melt or paste extrusion
process, and the cells can be formed by, for example, laser
ablation or machining (e.g., die punching). A soft tissue implant
having more than one layer can be made by a method that includes
the steps of (a) extruding a first biocompatible polymer to form a
first film; (b) extruding a second biocompatible polymer to form a
second film; (c) attaching the first film to the second film to
produce a soft tissue implant and (d) forming pores in the soft
tissue implant. Alternatively, a multi-layer implant can be made by
a method including the steps of (a) extruding a first biocompatible
polymer to form a first film; (b) forming pores or cell patterns in
the first film; (c) extruding a second biocompatible polymer to
form a second film; (d) forming pores in the second film; and (e)
attaching the first film to the second film to produce a soft
tissue implant. As for single-layer implants, the films can be of a
thickness described above and have the material content described
above, and the cells can have the characteristics of any of those
described above. Any of the soft tissue implants made by these
methods can be further processed (e.g., their edges can be modified
to facilitate tissue placement and/or their shape can be changed
(by, for example, stretching)). The implants can also be cleaned
and/or sterilized and packaged, with or without instructions for
use. Any of the soft tissue implants made by these methods can be
used to repair, or in the course of repairing, a damaged tissue in
a body (including, but not limited to, a human body).
[0082] Medical implant applications for the soft tissue implant
technology described above may include, but are not limited to,
plastic reconstruction, urinary stress incontinence, hernia repair,
gastric banding, and chest wall reconstruction. Accordingly, the
methods of the invention include methods of treating a patient who
has sustained an injury to a tissue, independent of the source of
the injury (i.e., the injury could arise from a traumatic injury,
including an accidental injury or a surgical incision, or the
injury may be associated with a disease, disorder, or condition).
The method can include exposing, preferably under sterile
conditions, the injured tissue (e.g., a muscle, muscle group, or
other tissue such as the intestine, liver, or kidney), and
administering a soft tissue implant to the tissue. The implant can
be further secured to the tissue by one or more sutures, staples,
or other fasteners. Alternatively, or in addition, the implant can
be secured by an adhesive. The surgical incision through which the
implant was inserted can then be closed. The physician or surgeon
performing the operative procedure can select an appropriate
implant. For example, it will be readily apparent what size implant
is required (generally, the implant should be large enough to cover
the affected part of a tissue). Similarly, the physician or surgeon
can choose a non-absorbable implant when appropriate. For example,
one may select a non-absorbable soft tissue implant for indications
such as hernia repair that require long-term durability and
strength. Alternatively, one may select an absorbable soft tissue
implant for indications such as tissue augmentation during plastic
reconstruction when one wants to avoid the potential complications
associated with a permanent implant. Tissue-based materials are
best suited for indications such as pelvic slings that require
materials less prone to erosion into adjacent tissue
structures.
[0083] In other methods, the soft tissue implant can be produced in
more three-dimensional forms for certain indications, such as the
plug and patch procedure for inguinal hernia repair. A three
dimensional structure can be machined using a laser system
incorporating a third axis for micromachining. Alternatively, the
nonwoven soft tissue implant could be thermoformed into a
three-dimensional shape after machining.
[0084] The product designs may also be suitable for non-medical
device applications. Non-medical applications may include
diagnostic testing, in biotechnology or other research, in
automotive, electronics, aerospace, and home and commercial
appliances.
[0085] A number of embodiments of the invention have been
described. Nevertheless, it will be understood that various
modifications may be made without departing from the spirit and
scope of the invention.
EXAMPLES
Example 1
[0086] A non-woven soft tissue implant was constructed using
biaxially-oriented polymer films. The film is stretched in both the
machine and transverse directions (relative to the extrusion
direction) to orient the polymer chains. The stretching process can
take place simultaneously or sequentially depending on the
equipment that is available. The base film was Syncarta.TM. (AET
Films, Peabody, Mass.). The base film was machined into Mesh Design
2 ("Mesh2") using a 3.0-Watt Avia Q-switched Ultraviolet Laser
produced by Coherent, Inc. (Santa Clara, Calif.). The design of a
cell of the non-woven soft tissue implant is shown in FIG. 6A. The
finished product was implanted, using standard surgical techniques,
in the subcutaneous tissue of rats for 7, 14, and 28 days.
Following sacrifice and retrieval of the specimens, histological
evaluation was carried out to evaluate the inflammatory and wound
healing response. Histology sections were obtained and stained with
Haematoxylin and Eosin for cellularity of the implant site and
Masson's Trichrome stain was used to evaluate the extent of fibrous
capsule formation. The findings over a 28-day period indicate that
the nonwoven soft tissue implant is biocompatible and undergoes a
normal resolution of the inflammatory response, secondary to
surgical injury, and development of a normal foreign body reaction
at the material/tissue interface with fibrous capsule formation
surrounding the entire implant and within the holes of the
material. The results of histological analyses are shown in FIGS.
7A and 7B.
Example 2
[0087] A non-woven soft tissue implant was constructed using
biaxially-oriented polymer films. Two base films were used. The
first film was a two-side sealable material OPB 95 (AET Films,
Peabody, Mass.). The second film was a one-side sealable material
AQS 90 (AET Films). Six sheets of the first film were placed
between two sheets of the second film with the sealable side of the
second in contact with the first film set. The sheet assembly was
brought to 145.degree. C. at 400 PSI of constant pressure for 60
minutes under vacuum. The laminated assembly was machined into
designs Mesh2 and Mesh4 (see FIGS. 6A and 9A, respectively) using a
3.0-Watt Avia Q-switched Ultraviolet Laser produced by Coherent,
Inc. (Santa Clara, Calif.).
Example 3
[0088] A non-woven soft tissue implant was constructed using
biaxially-oriented polymer films. Two base films were produced. The
first film comprised a three-layer extrusion in an A-B-A form. The
"A" layer was made up from PKS409 resin (Solvay Polyolefins Europe,
Brussels, Belgium) and the "B" layer was made up from HC312BF resin
(Borealis Group, Kongens Lyngby, Denmark). The layers were melt
extruded and oriented using a stenter film process. The film was
oriented in the machine direction at a 5:1 ratio and in the
transverse direction at a 10:1 ratio. The thickness of the film
after stretching was 24 .mu.l. The second film included a
three-layer extrusion in an A-A-B form. The "A" layer was made up
from HC312BF and the "B" layer was made from PKS409. The layers
were melt extruded and oriented using a stenter film process. The
film was oriented in the machine direction at a 5:1 ratio and in
the transverse direction at a 10:1 ratio. The thickness of the film
after stretching was 23.mu.. Six sheets of the first film were
placed between two sheets of the second film with the "B" side in
contact with the first film set. The sheet assembly was brought to
145.degree. C. at 400 PSI of constant pressure for 60 minutes under
vacuum. The laminated assembly was machined into the design Mesh2C
(see FIG. 8A) using a 3.0-Watt Avia Q-switched Ultraviolet Laser
produced by Coherent, Inc. (Santa Clara, Calif.). In addition, cell
patterns of design Mesh4 were created in the same assembly using a
die punch produced by Elite Tool & Die (Smithstown, Ireland).
Surface area ratios for the cell patterns in the produced films
were calculated and are shown in the Table above.
Example 4
[0089] Polyaryletherketone (PEEK; Invibio Inc., Lancashire, UK) is
a polymer that has properties making it useful as an implant
material for devices such as spine cages, bone screws, orthopedic
stems, and dental implants. PEEK exhibits a desirable combination
of strength, stiffness, and toughness, and it is biocompatible.
Accordingly, a soft tissue implant was constructed using PEEK
material. Westlake Plastics (Lenni, Pa.) supplies PEEK polymer
films that range from about 0.001 to about 0.029 inches thick.
These films can be used to fabricate biocompatible implants with
lower profiles than commercially available textile based products.
A film made of 0.005 inch PEEK polymer was machined using an
ultraviolet laser (more specifically, a 3.0-Watt Avia Q-switched
Ultraviolet Laser (Coherent, Inc., Santa Clara, Calif.)) into the
pattern shown in FIG. 6A using a CAD-CAM process. FIG. 4B shows a
highly magnified image of a cell pattern edge created using the
laser machining process. This soft tissue implant has an implant
surface area ratio of 0.79, which reduces the amount of material
available to provoke a foreign body reaction. In addition, the
implant had a smooth surface with a low coefficient of
friction.
Example 5
[0090] Polytetrafluoroethylene (PTFE; Bard Vascular Systems (Tempe,
Ariz.)) polymer also has properties that allow it to be used, as
described herein, as an implant material for, for example, vascular
grafts and patches. PTFE can be processed into a microporous form
using an expansion procedure. Like PEEK, expanded PTFE is strong,
flexible, and biocompatible.
Example 6
[0091] Yet another non-woven soft tissue implant was constructed
using a biaxially-oriented polymer film. The film is stretched in
both the machine and transverse directions (relative to the
extrusion direction) to orient the polymer chains. As noted above,
the stretching process can take place simultaneously or
sequentially depending on the equipment that is available. The base
film was Syncarta.TM. (AET Films, Peabody, Mass.). The base film
was machined into Mesh Design 3 ("Mesh3") using a 3.0-Watt Avia
Q-switched Ultraviolet Laser produced by Coherent, Inc. (Santa
Clara, Calif.). The design of a cell of the non-woven soft tissue
implant is shown in FIG. 10A.
Example 7
[0092] A non-woven soft tissue implant was constructed using
biaxially-oriented polymer films. The film is stretched in both the
machine and transverse directions (relative to the extrusion
direction) to orient the polymer chains. The stretching process can
take place simultaneously or sequentially depending on the
equipment that is available. The base film was expanded
polytetrafluoroethylene. Sixteen layers of film were laminated and
the film laminate had a thickness of 0.006 inches. The film
laminate was machined using a 100 watt CO.sub.2 laser produced by
Coherent, Inc. (Santa Clara, Calif.). The design of the non-woven
soft tissue implant comprised major and minor struts as shown in
FIG. 13A. The major strut width was 0.048 inches and the minor
strut width was 0.024 inches.
Example 8
[0093] A non-woven soft tissue implant was constructed using
biaxially-oriented polymer films. The film is stretched in both the
machine and transverse directions (relative to the extrusion
direction) to orient the polymer chains. The stretching process can
take place simultaneously or sequentially depending on the
equipment that is available. The base film was expanded
polytetrafluoroethylene. Sixteen layers of film were laminated and
the film laminate had a thickness of 0.006 inches. The film
laminate was machined using a 100 watt CO.sub.2 laser produced by
Coherent, Inc. (Santa Clara, Calif.). The design of the non-woven
soft tissue implant comprised minor struts as shown in FIG. 14A.
The minor strut width was 0.024 inches.
Example 9
[0094] A non-woven soft tissue implant was constructed using
biaxially-oriented polymer films. The film is stretched in both the
machine and transverse directions (relative to the extrusion
direction) to orient the polymer chains. The stretching process can
take place simultaneously or sequentially depending on the
equipment that is available. The base film was expanded
polytetrafluoroethylene. Sixteen layers of film were laminated and
the film laminate had a thickness of 0.006 inches. The film
laminate was machined using a 100 watt CO.sub.2 laser produced by
Coherent, Inc. (Santa Clara, Calif.). The design of the non-woven
soft tissue implant comprised minor struts as shown in FIG. 15A.
The minor strut width was 0.048 inches.
[0095] The non-woven soft tissue implants described in Examples 7,
8, and 9 were physically tested. Tensile tests were performed
according to the ASTM D882-02 standard to measure the strength of
the non-woven implants in the normal and parallel directions.
Flexural rigidity tests were performed according to the ASTM
D4032-94 standard to measure the stiffness of the non-woven
implants. Five samples for each implant sample were tested and the
results from the tests are summarized in the table below. The
non-woven implant described in Example 7 comprising relatively
large major and relatively small minor struts provided a high level
of strength while maintaining a low level of stiffness. Example 8
comprising relatively small minor struts provided a low level of
strength and low level of stiffness. Example 9 comprising
relatively large minor struts provided a high level of strength and
a high level of stiffness.
TABLE-US-00004 Implant Design Tensile Strength (N/cm) Flexural
Rigidity (Fmax N) Example 7 38.7 3.8 Example 8 18.0 2.2 Example 9
44.5 6.3
[0096] Accordingly, the implants of the invention can have tensile
strengths encompassing the strengths exemplified (e.g., at least or
about 10-100 N/cm (e.g., at least or about 10, 20, 25, 30, 35, 40,
45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 or 100 N/cm). Similarly,
flexural rigidity can vary from at least, or about, 1.0-12.0 Fmx
N). The strength to flexibility ratios exemplified can be
maintained or can vary in the implants of the invention (e.g. the
ratios can vary by at least or about 10%, 25%, 50%, 75%, 100%,
150%, or 200%). Further embodiments are within the scope of the
following claims.
* * * * *