U.S. patent application number 11/192743 was filed with the patent office on 2007-02-01 for composite self-cohered web materials.
Invention is credited to Paul D. Drumheller, Ted R. Farnsworth, Charles Flynn, Byron K. Hayes, Charles F. White.
Application Number | 20070026039 11/192743 |
Document ID | / |
Family ID | 37694589 |
Filed Date | 2007-02-01 |
United States Patent
Application |
20070026039 |
Kind Code |
A1 |
Drumheller; Paul D. ; et
al. |
February 1, 2007 |
Composite self-cohered web materials
Abstract
The present invention is directed to implantable bioabsorbable
non-woven self-cohered web materials having a high degree of
porosity. The web materials are very supple and soft, while
exhibiting proportionally increased mechanical strength in one or
more directions. The web materials often possess a high degree of
loft. The web materials can be formed into a variety of shapes and
forms suitable for use as implantable medical devices or components
thereof.
Inventors: |
Drumheller; Paul D.;
(Flagstaff, AZ) ; Farnsworth; Ted R.; (Flagstaff,
AZ) ; Flynn; Charles; (Flagstaff, AZ) ; Hayes;
Byron K.; (Flagstaff, AZ) ; White; Charles F.;
(Camp Verde, AZ) |
Correspondence
Address: |
GORE ENTERPRISE HOLDINGS, INC.
551 PAPER MILL ROAD
P. O. BOX 9206
NEWARK
DE
19714-9206
US
|
Family ID: |
37694589 |
Appl. No.: |
11/192743 |
Filed: |
July 29, 2005 |
Current U.S.
Class: |
424/424 |
Current CPC
Class: |
A61L 27/18 20130101;
A61L 2300/606 20130101; Y10T 428/1376 20150115; A61L 27/56
20130101; C08L 67/04 20130101; C08L 67/04 20130101; A61B 17/07292
20130101; Y10T 428/1317 20150115; Y10T 442/10 20150401; A61P 29/00
20180101; A61L 31/06 20130101; A61L 31/16 20130101; A61L 31/146
20130101; A61L 27/18 20130101; A61L 31/129 20130101; A61L 27/54
20130101; A61L 27/48 20130101; A61L 31/06 20130101 |
Class at
Publication: |
424/424 |
International
Class: |
A61F 2/00 20060101
A61F002/00 |
Claims
1. An implantable article comprising melt-formed continuous
filaments intermingled to form a porous web wherein said filaments
are self-cohered to each other at multiple contact points, wherein
said filaments comprise at least one semi-crystalline polymeric
component covalently bonded to or blended with at least one
amorphous polymeric component, wherein the filaments possess
partial to full polymeric component phase immiscibility when in a
crystalline state, and a hydrogel material placed on at least one
of said filaments.
2. The implantable article of claim 1 wherein the hydrogel is
cross-linked.
3. The implantable article of claim 1 wherein said hydrogel
material fills at least part of at least one void space present
between said filaments.
4. The implantable article of claim 3 wherein the hydrogel is
cross-linked
5. The implantable article of claim 1 wherein said implantable
article has a percent porosity greater than ninety in the absence
of additional components.
6. The implantable article of claim 1 wherein said implantable
article has a percent porosity greater than ninety in the absence
of additional components.
7. The implantable article of claim 1 wherein said hydrogel
material comprises polyvinyl alcohol.
8. The implantable article of claim 1 wherein said hydrogel
material comprises carboxymethylcellulose.
9. The implantable article of claim 1 wherein said hydrogel
material comprises a co-polymer of polyethylene glycol and
polypropylene glycol.
10. The implantable article of claim 2 wherein said hydrogel
material comprises polyvinyl alcohol.
11. The implantable article of claim 2 wherein said hydrogel
material comprises carboxymethylcellulose.
12. The implantable article of claim 2 wherein said hydrogel
material comprises a co-polymer of polyethylene glycol and
polypropylene glycol.
13. The implantable article of claim 3 wherein said hydrogel
material comprises polyvinyl alcohol.
14. The implantable article of claim 3 wherein said hydrogel
material comprises carboxymethylcellulose.
15. The implantable article of claim 3 wherein said hydrogel
material comprises a co-polymer of polyethylene glycol and
polypropylene glycol.
16. The implantable article of claim 1 further comprising a
bioactive species in combination with the hydrogel material.
17. The implantable article of claim 16 wherein the bioactive
species comprises an anti-inflammatory.
18. The implantable article of claim 17 wherein the
anti-inflammatory is dexamethasone.
19. The implantable article of claim 2 further comprising a
bioactive species in combination with the cross-linked hydrogel
material.
20. The implantable article of claim 19 wherein the bioactive
species comprises an anti-inflammatory.
21. The implantable article of claim 20 wherein the
anti-inflammatory is dexamethasone.
22. The implantable article of claim 3 further comprising a
bioactive species in combination with the hydrogel material.
23. The implantable article of claim 22 wherein the bioactive
species comprises an anti-inflammatory.
24. The implantable article of claim 23 wherein the
anti-inflammatory is dexamethasone.
25. The implantable article of claim 4 wherein said hydrogel
material comprises polyvinyl alcohol.
26. The implantable article of claim 4 wherein said hydrogel
material comprises carboxymethylcellulose.
27. The implantable article of claim 4 wherein said hydrogel
material comprises a co-polymer of polyethylene glycol and
polypropylene glycol.
28. The implantable article of claim 4 further comprising a
bioactive species in combination with the cross-linked hydrogel
material.
29. The implantable article of claim 28 wherein the bioactive
species comprises an anti-inflammatory.
30. The implantable article of claim 29 wherein the
anti-inflammatory is dexamethasone.
31. An implantable article comprising melt-formed continuous
filaments intermingled to form a porous web wherein said filaments
are self-cohered to each other at multiple contact points, wherein
said filaments comprise a first semi-crystalline polymeric
component covalently bonded to or blended with at least one
additional semi-crystalline polymeric component, wherein the
filaments possess partial to full polymeric component phase
immiscibility when in a crystalline state, and a hydrogel material
placed on at least one of said filaments.
32. The implantable article of claim 31 wherein the hydrogel
material is cross-linked.
33. The implantable article of claim 31 wherein said hydrogel
material fills at-least part of at least one void space present
between said filaments.
34. The implantable article of claim 33 wherein the hydrogel
material is cross-linked.
35. The implantable article of claim 31 wherein said implantable
article has a percent porosity greater than ninety in the absence
of additional components.
36. The implantable article of claim 31 wherein the percent
porosity is greater than ninety-one in the absence of additional
components.
37. The implantable article of claim 31 wherein said hydrogel
material comprises polyvinyl alcohol.
38. The implantable article of claim 31 wherein said hydrogel
material comprises carboxymethylcellulose.
39. The implantable article of claim 31 wherein said hydrogel
material comprises a co-polymer of polyethylene glycol and
polypropylene glycol.
40. The implantable article of claim 32 wherein said hydrogel
material comprises polyvinyl alcohol.
41. The implantable article of claim 32 wherein said hydrogel
material comprises carboxymethylcellulose.
42. The implantable article of claim 32 wherein said hydrogel
material comprises a co-polymer of polyethylene glycol and
polypropylene glycol.
43. The implantable article of claim 33 wherein said hydrogel
material comprises polyvinyl alcohol.
44. The implantable article of claim 33 wherein said hydrogel
material comprises carboxymethylcellulose.
45. The implantable article of claim 33 wherein said hydrogel
material comprises a co-polymer of polyethylene glycol and
polypropylene glycol.
46. The implantable article of claim 31 further comprising a
bioactive species in combination with the hydrogel material.
47. The implantable article of claim 46 wherein the bioactive
species comprises an anti-inflammatory.
48. The implantable article of claim 47 wherein the
anti-inflammatory is dexamethasone.
49. The implantable article of claim 42 further comprising a
bioactive species in combination with the cross-linked hydrogel
material.
50. The implantable article of claim 49 wherein the bioactive
species comprises an anti-inflammatory.
51. The implantable article of claim 50 wherein the
anti-inflammatory is dexamethasone.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to implantable medical
materials and devices. More particularly, the present invention is
directed to implantable medical materials and devices made with
bioabsorbable polymeric materials in the form of non-woven,
self-cohered, filamentous webs having a high degree of
porosity.
BACKGROUND OF THE INVENTION
[0002] A variety of bioabsorbable polymeric compounds have been
developed for use in medical applications. Materials made from
these compounds can be used to construct implantable devices that
do not remain permanently in the body of an implant recipient.
Bioabsorbable materials are removed from the body of an implant
recipient by inherent physiological process of the implant
recipient. These processes can include simple dissolution of all or
part of the bioabsorbable compound, hydrolysis of labile chemical
bonds in the bioabsorbable compound, enzymatic action, and/or
surface erosion of the material. The breakdown products of these
processes are usually eliminated from the implant recipient through
action of the lungs, liver, and/or kidneys. It is recognized that
in the literature "bioresorbable," "resorbable," "bioabsorbable,"
and "biodegradable" are terms frequently used interchangeably.
"Bioabsorbable" is the preferred term herein.
[0003] Bioabsorbable polymeric compounds have been used in wound
closure and reconstruction applications for many decades. Sutures
are the most notable examples. Molded articles, films, foams,
laminates, woven, and non-woven materials have also been produced
with bioabsorbable polymeric compounds. Biologically active
compositions have been releasably combined with some of these
bioabsorbable compounds.
[0004] The components of the bioabsorbable compounds can be chosen
to impart a variety of characteristics to the final material used
to construct an implantable medical device. In addition, many
bioabsorbable compounds can be processed in ways that also impart
particular characteristics to the implantable device. For example,
U.S. Pat. No. 6,025,458, issued to Lipinsky et al., and U.S. Pat.
No. 6,093,792, issued to Gross et al., both describe stretching
films made of their respective bioabsorbable materials in one
direction to allow for alignment and ordering of the polymer
molecules along the direction of stretching. Stretching of the film
occurs while the polymeric molecules are in an amorphous condition
at a temperature between the component polymer's glass transition
temperature (T.sub.g) and its melting temperature (T.sub.m).
Optionally, these uniaxially oriented polymer films can be
stretched a second time in a direction substantially perpendicular
to the first direction to form biaxially oriented films. This
second stretching also occurs while the material is in an amorphous
condition at a temperature between the component polymer's T.sub.g
and its T.sub.m. Following axial orientation and suitable restraint
of the material, the positioning of the molecules of these
compounds can be firmly established by the application of heat
above the T.sub.g and below its melting point (T.sub.m) of the
bioabsorbable film. Once annealed, the now "heat-set" films are
ready for use.
[0005] In addition to films, Lipinsky et al. and Gross et al.
disclose their respective bioabsorbable polymers can be made into
several other material forms. Among these forms are spun-bonded
non-woven materials. Neither Lipinsky et al. or Gross et al.
indicate their spun-bond materials have fibers that self-bond, or
self-cohere, to one another without the requisite for added
adhesive binders, adjuncts, or post extrusion melt processing.
Indeed, Gross et al. explicitly cites the need for additives to
bind their fibers together. Accordingly, neither Lipinsky et al.
nor Gross et al. disclose their spun-bonded non-woven materials can
be captured and collected in a quenched amorphous state. Nor do
they disclose such an un-self-cohered material can be stretched in
an unannealed state to either reduce component fiber diameter or to
induce, or increase, porosity in the finished material. If a
spun-bonded non-woven material of Lipinsky et al. or Gross et al.
was stretched, inherent mechanical stresses would be expected to
create distortion of the material through disruption of the
component filaments, the adjunctive bonding present between fibers,
or a combination thereof. The percent porosity of the material
would not be increased with a stretching process. The only
materials in Lipinsky et al. or Gross et al. that lend themselves
to a stretching process are films.
[0006] Absent adhesive binders, adjuncts, or post extrusion melt
processing, only non-woven materials with self-cohered filaments
that can be captured in a quenched amorphous condition have the
requisite intra-fibrillar structure to be considered viable
candidates for a stretching process that increases the porosity of
the final non-woven web material. A suitable precursor nonwoven web
material for stretching below the melting point (T.sub.m) of the
foundational bioabsorbable polymer is taught by Hayes in U.S. Pat.
No. 6,165,217.
[0007] U.S. Pat. No. 6,165,217, issued to Hayes, discloses a
bioabsorbable material in the form of a non-woven self-cohered web
(FIGS. 1 and 1A, herein). A self-cohered non-woven web material is
a spun web of continuous filaments made of at least one
semi-crystalline polymeric component covalently bonded as a linear
block copolymer with or blended with one or more semi-crystalline
or amorphous polymeric components.
[0008] The continuous filaments are produced by selecting spinning
conditions that provide a tackiness to the emerging filaments and
allows them to self-cohere as solid filaments as the filaments are
collected in a cohesive random pile, or web, on a collecting
surface. The spun filaments are intermingled together as they are
collected in the form of a porous web of self-cohered filaments.
The self-cohered filaments have multiple contact points with each
other within the web. The self-cohered filaments bond at the
contact points without need for requisite addition of supplementary
adhesives, binders, adhesive adjuncts (e.g., solvents, tackifier
resins, softening agents), or post extrusion melt processing. The
self-cohered filaments of the preferred embodiment
polyglycolide:trimethylene carbonate (PGA:TMC) non-woven web are
between 20 microns and 50 microns in diameter. According to Hayes,
these self-cohered non-woven webs possess volume densities (also
reported as apparent densities) that indicate percent porosity to
be in a range between approximately forty (40) and eighty (80). If
the potentially semi-crystalline web is preserved in a
thermodynamically unstable (metastable), homogeneous (microphase
disordered), substantially phase miscible, amorphous state of
limited crystallinity, the web is malleable and can be ready
conformed or molded into a desired shape. That shaped form can then
be preserved through its conversion into a more ordered,
thermodynamically stable, at least partially phase immiscible
semi-crystalline state. This irreversible (short of complete
remelting and reformation of the formed web structures) conversion
from a prolonged amorphous (i.e., disordered state of miscibility)
condition into an ordered semi-crystalline state is typically
provided by the chain mobility present in the rubbery state
existing between the melt temperature and that of the
order-disorder transition temperature (T.sub.odt), the temperature
above which the transition from disorder to order can proceed.
Alternatively, solvents, lubricants, or plasticizing agents, with
or without their combination with heat, can be used to facilitate
chain mobility,and rearrangement of the constituent polymer chains
into a more ordered condition. The chemical composition of the
self-cohered filaments can be chosen so the resultant web is
implantable and bioabsorbable.
[0009] Hayes describes the self-cohered non-woven web material as
possessing a degree of porosity variable based on fiber deposition
density and any subsequent compression. Hayes also describes the
ability of the planar web in the malleable unstable amorphous
condition to be shaped into a virtually unlimited array of forms,
the shapes of which can be retained through subsequent
crystallization. However, Hayes does not indicate an unset web of
the self-cohered filaments which can serve as a precursor web
material for additional stretch processing to increase web porosity
prior to annealing. Nor does Hayes teach a self-cohered non-woven
web material having a significant population of continuous
filaments with a cross-sectional diameter less than twenty (20)
microns. In the absence of additional processing of a precursor web
material according to the present invention, the self-cohered
non-woven web material of Hayes would not have increased molecular
orientation in the self-cohered filaments of the web sufficient to
provide a birefringence value greater than 0.050.
[0010] A non-woven self-cohered web material having high porosity
and small filament diameter would have proportionally increased
mechanical strength in one or more directions. Despite increased
mechanical strength, such a high porosity non-woven self-cohered
web material would deliver more loft, suppleness, drapability,
conformability, and tissue compliance than a web material made
according to Hayes.
[0011] For non-implantable applications, a non-woven self-cohered
web having a high degree of porosity could be used to releasably
attach implantable devices and materials to a delivery apparatus.
Combining a population of oriented filaments with an increased
internal void volume within which the oriented filament can move
would imbue such a material with a degree of elasticity or
resiliency.
[0012] In addition to these and other improvements in such a web
material, a more porous bioabsorbable web material would provide
opportunities to combine other components with the web. The
components could be placed on surfaces of the filaments. The
components could also be placed within void spaces, or pores,
between the filaments. The components could be bioabsorbable or
non-bioabsorbable. The components, in turn, could releasably
contain useful substances.
[0013] There is a need, therefore, for a synthetic bioabsorbable,
non-woven, self-cohered polymeric web material having a high degree
of porosity with increased mechanical strength, loft, suppleness,
drapability, comformability, and tissue compliance.
SUMMARY OF THE INVENTION
[0014] The present invention is directed to synthetic
bioabsorbable, non-woven, self-cohered polymeric web materials
having a high degree of porosity. The highly porous web materials
are mechanically strong and have a high degree of loft, suppleness,
drapability, conformability, and tissue compliance. In some
embodiments, the present invention exhibits elastic properties. The
invention is suitable for use as an implantable medical device or a
component of a medical device. The invention is also suitable for
use in many instances as a thrombogenic agent at a site of bleeding
or aneurysm formation.
[0015] These properties are imparted to the present invention by
drawing, or stretching, an unannealed, self-cohered, precursor web
material in at least one direction at a particular rate and stretch
ratio under defined conditions. Stretching is followed
preferentially by heat-setting and cooling under full or partial
restraint.
[0016] Self-cohered, precursor web materials have filaments
attached to one another at multiple contact points (FIGS. 1 and
1A). During processing, the filaments are kept secured together by
the self-cohering contact points. As the self-cohered filaments are
stretched, the filaments elongate and become smaller in
cross-sectional diameter (FIGS. 2-4A, and 6-7). As the filaments
become finer, increased void space is formed between the filaments
(Table 12). The as-stretched structure is then "set" or annealed,
either completely or partially under restraint, to induce at least
partial phase immiscibility and subsequent crystallization. The
finer filaments and increased void space generated within the web
material are responsible for many of the improved characteristics
of the present invention.
[0017] A convenient metric for quantifying the void space of a
porous web material is the percent porosity of the finished web
material. The percent porosity compares the density of an
unprocessed starting compound with the density of a finished porous
web material. The stretched, self-cohered, continuous filament
nonwoven web materials of the present invention are greater than
ninety percent (90%) porous. In the present invention, the
increased porosity imparted to the web is defined as the void space
provided within the external boundaries of the stretched
self-cohering web, absent the inclusion of any fillers or other
added components that may effectively reduce the available
porosity.
[0018] The present invention can include additional compositions
placed on and/or within the polymeric components of the web
material. Additional compositions can also be placed in void
spaces, or pores, of the web material. The compositions can include
useful substances releasably contained thereby. Preferred
compositions for placement in void spaces and surfaces of the
present invention are hydrogel-based materials.
[0019] In one embodiment, the present invention is an implantable
article comprising melt-formed continuous filaments intermingled to
form a porous web wherein said filaments are self-cohered to each
other at multiple contact points, wherein said filaments comprise
at least one semi-crystalline polymeric component covalently bonded
to or blended with at least one amorphous polymeric component,
wherein the filaments possess partial to full polymeric component
phase immiscibility when in a crystalline state, and a hydrogel
material placed on at least one of said filaments.
[0020] In another embodiment, the present invention is an
implantable article comprising melt-formed continuous filaments
intermingled to form a porous web wherein said filaments are
self-cohered to each other at multiple contact points, wherein said
filaments comprise a first semi-crystalline polymeric component
covalently bonded to or blended with at least one additional
semi-crystalline polymeric component, wherein the filaments possess
partial to full polymeric component phase immiscibility when in a
crystalline state, and a hydrogel material placed on at least one
of said filaments.
[0021] These and other features of the present invention, as well
as the invention itself, will be more fully appreciated from the
drawings and detailed description of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] FIG. 1 is a scanning electron micrograph (SEM) of a
self-cohered web material of the prior art.
[0023] FIG. 1A is a scanning electron micrograph (SEM) of a
self-cohered web material of the prior art.
[0024] FIG. 2 is a 50.times. scanning electron micrograph (SEM) of
an embodiment of the present invention having been stretched in a
single direction.
[0025] FIG. 2A is a 100.times. scanning electron micrograph (SEM)
of an embodiment of the present invention having been stretched in
a single direction and constructed from 50-50 PGA:TMC.
[0026] FIG. 3 is a scanning electron micrograph (SEM) of an
embodiment of the present invention having been stretched in two
directions substantially perpendicular to each other.
[0027] FIG. 4 is a scanning electron micrograph (SEM) of an
embodiment of the present invention having a form referred to
herein as fleece.
[0028] FIG. 4A is a scanning electron micrograph (SEM) of an
embodiment of the present invention having been stretched in all
directions outwardly from the center of the material.
[0029] FIG. 5 is a schematic illustration of an apparatus suitable
to produce a precursor web material for use in the present
invention.
[0030] FIG. 6 is a graph showing the effect of different stretching
ratios on the diameter of the filaments in the finish web material
of the present invention.
[0031] FIG. 7 is a graph showing the percentage of filaments having
a diameter less than twenty (20) microns for a given stretching
ratio.
[0032] FIG. 8 is a graph showing the relationship of birefringence
to filament diameter in a finished web material of the present
invention.
[0033] FIG. 9 in an illustration of a web material of the present
invention having at least one additional material placed on
surfaces and in void spaces of the web material.
[0034] FIG. 9A is an illustration of a web material of the present
invention having at least two additional materials placed on
surfaces and in void spaces of the web material.
[0035] FIG. 10 is an illustration of a web material of the present
invention attached to a pledget material.
[0036] FIG. 10A is an illustration of a web material of the present
invention attached to a pledget material and placed on a stapling
apparatus.
[0037] FIG. 10B is an illustration of a web material of the present
invention attached to a pledget material and placed on a stapling
apparatus.
[0038] FIG. 11 is an illustration of a web material of the present
invention in the form of an anastomotic wrap.
[0039] FIG. 12 is an illustration of a web material of the present
invention placed between a second material having openings therein
through which the web material is exposed.
[0040] FIG. 13 is an illustration of a web material of the present
invention having a tubular form.
[0041] FIG. 14 is an illustration of a web material of the present
invention having a cylindrical form.
[0042] FIG. 15 is an illustration of a web material of the present
invention and a non-bioabsorbable material.
[0043] FIG. 16 is an illustration of a web material of the present
invention in a tubular form with at least one structural element
included therewith.
[0044] FIG. 17 is an illustration of a web material of the present
invention in a tubular form having an ability to change dimension
radially and longitudinally.
[0045] FIG. 18 is an Illustration of a whole blood coagulation time
assay.
[0046] FIG. 19 is a photograph of a web material of the present
invention having a very high degree of porosity.
[0047] FIG. 19A is a photograph of a web material of the present
invention having a very high degree of porosity and a metallic band
attached thereto.
[0048] FIG. 19B is a photograph of a web material of the present
invention having a very high degree of porosity with multiple
metallic bands attached thereto.
[0049] FIG. 19C is a scanning electron micrograph (SEM) of an
embodiment of the present invention having a very high degree of
porosity.
[0050] FIG. 20 is an illustration of the web material of FIG. 19
placed inside a delivery device.
[0051] FIG. 21 is an illustration of a composite material having a
stretched self-cohered web material layered on a non-bioabsorbable
material.
[0052] FIG. 21A is an illustration of a composite material having a
stretched self-cohered web material having a bioactive species
releasably contained therein layered on a non-bioabsorbable
material.
DETAILED DESCRIPTION OF THE INVENTION
[0053] The present invention is directed to bioabsorbable
non-woven, self-cohered, polymeric web materials having a high
degree of porosity. The high degree of porosity imparts many
desirable features to the invention. These features include loft,
suppleness, drapability, conformability, and tissue compliance.
Many of these highly porous materials exhibit substantial
mechanical strength. The highly porous web materials of the present
invention can be used as implantable medical devices or components
thereof. When implanted, the highly porous bioabsorbable web
materials of the present invention are removed from the body of an
implant recipient by inherent physiological processes of the
implant recipient.
[0054] The highly porous web materials of the present invention are
made by stretching an unannealed, non-woven, self-cohered,
unstretched precursor web material in one or more directions,
sequentially or simultaneously, followed by annealing of the
polymeric constituents of the stretched web material with heat
and/or appropriate solvents. The precursor web material is made of
continuous filaments formed from semi-crystalline multi-component
polymeric systems which, upon the achievement of an equilibrium
state, possess some evidence of phase immiscibility of the system's
constituent polymeric components. The ability of the precursor web
material to initially self-cohere after solidification from the
melt is believed to be the result of a comparatively reduced rate
of crystallization. The reduced rate of crystallization preserves
the melt's substantially homogenous amorphous non-crystalline phase
mixed condition within the solidified quenched filamentous web
until such a time that it can come into physical contact with other
portions of the continuous filament sustained in a similar
amorphous condition of limited crystallization. As portions of the
continuous filaments contact each other at multiple points in the
precursor web material, the filaments are bonded together at the
contact points in a solidified state without requisite for added
adhesive binders, adjuncts, or post extrusion melt processing.
Continuous or discontinuous filaments connected in such a manner
are considered to be "self-cohered."
[0055] Blend and copolymeric systems that exist in a state of full
component miscibility within their amorphous phase, be it in a
metastable or equilibrium state, are expected to display a single
T.sub.g or T.sub.odt occurring at a temperature that is a function
of the systems' composition and substantially predictable when
utilizing the Fox equation. Conversely, fully immiscible multiphase
amorphous systems are expected to display distinct T.sub.g's which
correlate with the homopolymer analogs for each separated
immiscible phase. In a partially miscible system, some
crystallizable or other constituents remain miscible within the
existing amorphous phase due to reasons such as steric constraints
or segment inclusions. As a result, the respective T.sub.g would be
shifted away from that of its non-crystallizing homopolymer analog
toward a temperature reflective of the constituent ratio existing
within the amorphous phase, a value which could be interpreted
utilizing the Fox equation.
[0056] Similarly, non-crystallizing or amorphous inclusions within
the crystalline regions of such partially miscible systems, when
present in sufficient concentrations, can be expected to produce a
diluent or colligative effect resulting in a depression of the
melting temperature from that expected of a crystallized
homopolymer analog. Such partially miscible systems would result in
the depression of the observed T.sub.m while a fully phase
separated system would retain a T.sub.m similar to that of the
homopolymer analog.
[0057] In the present invention, the self-cohered precursor web
material can be suspended in a substantially homogenous amorphous
non-crystalline metastable phase mixed condition that enables the
precursor web material to be stretched in one or more directions,
either sequentially or simultaneously, to cause elongation and
thinning of the self-cohered filaments. Stretching a precursor web
material increases void space between the intermingled filaments in
the web material. Though Hayes describes materials with a porosity
between approximately forty and eighty percent for a finished
self-cohered web made according to the teachings of U.S. Pat. No.
6,165,217, the present inventors have discovered the precursor web
material can have void spaces amounting to ninety-percent (90%) of
the total volume of material. This metric is expressed herein as a
percent porosity, or simply "porosity." Porosity is determined as
described in Example 3, herein. Finished web materials of the
present invention have porosity values greater than ninety percent
(90%) (Table 12).
[0058] The prolonged amorphous state present in the precursor web
material during processing is attainable through the preferential
selection and utilization of at least partially phase immiscible
blends or block copolymers combined with a sufficiently rapid rate
of cooling that substantially inhibits both full or partial
microphase separation, as well as subsequent crystallization. At
least partially phase immiscible blends of polymers or copolymers
can be utilized, provided the polymeric mixture possesses
sufficient melt miscibility to allow for its extrusion into
filaments. The present invention preferentially utilizes block
copolymers that can be described as diblock, triblock, or
multiblock copolymers that possess at least partially phase
immiscible segmental components when in a thermodynamically stable
state. Phase immiscibility in the context of block copolymers is
intended to refer to segmental components which, if a part of a
blend of the correlating homopolymers, would be expected to phase
separate within the melt.
[0059] More particularly, the current invention preferentially
utilizes an ABA triblock copolymer system synthesized through a
sequential addition ring opening polymerization and composed of
poly(glycolide), also known as PGA, and poly(trimethylene
carbonate), also known as TMC, to form a highly porous, stretched,
self-cohered, non-woven bioabsorbable web material; wherein A
comprises between 40 and 85 weight percent of the total weight, and
wherein A is comprised of glycolide recurring units; and B
comprises the remainder of the total weight and is comprised of
trimethylene carbonate recurring units said material being
bioabsorbable and implantable. Preferred precursor web materials
are made with PGA:TMC triblock copolymers having ratios of PGA to
TMC of sixty-seven percent (67%) to thirty three percent (33%)
(67:33-PGA:TMC) and fifty percent (50%) PGA to fifty percent (50%)
TMC (50:50-PGA:TMC). The inherent viscosity of these polymers at
30.degree. C. in hexafluoroisopropanol (HFIP), can range from an
average of 0.5 dl/g to over 1.5 dl/g, and for preferred use can
range from 1.0 dl/g to 1.2 dl/g . The acceptable melting point for
this particular range of copolymer compositions as determined
through a DSC melt peak can range from approximately 1 70.degree. C
to 220.degree. C. These copolymers' cumulative thermal exposure
over time, be it from extrusion or other processing, needs to be
minimized sufficiently to prevent transesterification reactions
that can result in degradation of the copolymers' block structure
and their correlating crystallinity and phase immiscibility
characteristics.
[0060] Once a self-cohered, continuous filament precursor web
material has been prepared as described herein, the web material is
restrained and pre-heated above its order-disorder transition
temperature (T.sub.odt) and below its melting temperature (T.sub.m)
for a period of time sufficient to soften the material without
inducing significant crystallization. The softened precursor web
material is then subjected to stretching in one or more directions
(FIGS. 2-4A). Stretching the web material in multiple directions
can be performed sequentially or in a single operation. The
precursor web material is stretched at a particular rate and at a
particular ratio of initial dimension to final dimension.
[0061] In most uni-axially stretched embodiments (FIG. 2 and 2A),
the precursor web material is stretched at rates preferably ten to
fifty percent (10-50%) of the precursor web initial dimensions per
second. For a given stretch rate, a precursor web material can be
stretched at a ratio between two to one (2:1) and eleven to one
(11:1). Preferred ratios are four to one (4:1), five to one (5:1),
six to one (6:1), seven to one (7:1), eight to one (8:1), nine to
one (9:1), and ten to one (10:1). Following stretching, the
precursor web material is subjected to a heating step to anneal the
polymeric material to induce partial to full phase separation and
subsequent crytallization. The annealing step can be preformed by
one of two methods.
[0062] The first annealing method requires the web be maintained at
the maximum stretch at annealing conditions until the web is nearly
or fully annealed. Preferred annealing conditions are 110.degree.
C. to 130.degree. C. for 0.5 to 3 minutes, although temperatures
above the order-disorder temperature (T.sub.odt) and below the melt
temperature (T.sub.m), with the appropriate time adjustments, could
be used.
[0063] The second annealing method is referred to herein as
"partially restrained." In the method, the stretched self-cohered
web material is first partially annealed while restrained at the
maximum stretch. The annealing step is then completed with the
restraint on the stretched web material reduced or eliminated.
Preferred conditions for this method are 70.degree. C. for 0.5
minutes for the first step (full restraint) and 120.degree. C. for
1 to 2 minutes for the final step (reduced or no restraint).
[0064] Once annealed, the highly porous self-cohered web material
is removed from the processing apparatus and prepared for use as an
implantable medical device or component thereof. The advantage of
the partially restrained annealing method is that it allows the
stretched web to retract, typically ten to sixty percent, without
an increase in fiber diameter or a reduction in porosity (see e.g.,
Example 9, infra) resulting in is a softer web. This softness is
imparted by the curling of the fibers in the web as they retract
during the final annealing step.
[0065] In most biaxially stretched embodiments (FIG. 3), the
precursor web material is stretched at an approximate rate of
twenty percent (20%) or thirty percent (30%) per second at
25.degree. C. to 75.degree. C. One preferred method is to stretch a
precursor web material of 40 to 50 mg/cm.sup.2 area weight at
70.degree. C. to a stretch ratio of 3.5:1 along the x-axis
(down-web) and 6.0:1 along the y-axis (transverse). By multiplying
the stretch ratios of the x and y axis, this gives an area ratio of
21:1. The stretched web is partially annealed at 70.degree. C. for
2 minutes, then released from restraints and fully annealed at
120.degree. C. for 2 minutes. Either annealing method described
above may be used for annealing biaxially stretched webs.
[0066] Similar conditions are used for radially stretched precursor
web materials (FIG. 4A). A radial stretch ratio of 3.75:1 (area
ratio of 14:1) is preferred, although a stretch ration of 4.5:1
(area ratio of 20:1) works well. As in uniaxial and biaxial
stretched webs, either annealing method described above may be
employed.
[0067] Highly porous stretched self-cohered web materials of the
present invention can be combined with one another to form layered
or laminated materials. Optionally, the materials can be further
processed with heat, binders, adhesives and/or solvents to attach
the individual layers together. Alternatively, portions of one or
more of the layers can remain unattached and separated to form a
space between the layers.
[0068] In some embodiments, highly porous stretched self-cohered
web materials can be made in the form of a rod, cylinder (FIG. 14),
rope, or tube (FIG. 13). The tubular form can be made in a
"stretchy" form that can elongate and/or increase in diameter (FIG.
17). These and other forms can be adapted for use with a particular
anatomical structure or surgical procedure. For example, a highly
porous stretched self-cohered web material in the form of a sheet
can be adapted for placement around an anastomotic junction and
sutured or stapled in place (FIG. 11). In another embodiment (FIG.
10), a pledget material (14) is combined with a "stretchy" form of
the present invention (12) to effect a substantially tubular
structure (10) adapted to facilitate temporary placement of the
pledget component onto a stapling apparatus cartridge (FIGS.
10A-10B). Alternatively, the present invention can additionally
serve as the pledget component.
[0069] In addition, a highly porous stretched self-cohered web
material of the present invention can be combined with other
materials to form composite devices (FIG. 15). In one embodiment, a
sheet of stretched self-cohered bioabsorbable web material (28) is
provided with a planar non-bioabsorbable material (26) surrounding
the web material to form a dental implant (25). When implanted,
bone or other tissue is encouraged to grow in a space defined by
the implant. With time, the bioabsorbable web material is removed
from the implantation site by natural physiological processes of
the implant recipient while bone or other tissue ingrows and fills
the space. Once the bioabsorbable portion of the implant has
disappeared, another dental implant can be placed at the
regenerated bone or tissue present at the site exposed by the
bioabsorbed web material of the present invention. An alternative
embodiment is illustrated in FIG. 12.
[0070] In another embodiment, a highly porous stretched
self-cohered web material (22) of the present invention is layered,
and optionally laminated, to a sheet of non-bioabsorbable material
(24). This composite material (21) is particularly suited for use
as a dura substitute in cranial surgery (FIG. 21). Preferred
non-bioabsorbable materials are fluoropolymeric in composition,
with porous expanded polytetrafluoroethylene (ePTFE) and/or
fluorinated ethylene propylene (FEP) being most preferred.
Bioactive substances (27) can be placed in or on the highly porous
stretched self-cohered web material of the present invention (FIG.
21A).
[0071] In other embodiments (FIG. 16), structural elements (39) are
combined with a highly porous stretched self-cohered web material
(38) to form a composite construction (36). The structural elements
can be made of non-bioabsorbable and/or bioabsorbable materials.
The structural elements can be placed on one or both sides of the
stretched self-cohered web material. The structural elements can
also be placed within the web material.
[0072] The high porosity of stretched self-cohered web materials of
the present invention can be increased further by subjecting the
web material to a procedure that pulls the filaments apart to an
even greater extent (FIG. 19C). The procedure may also fracture the
continuous filaments of the stretched web material into pieces.
These very porous stretched self-cohered web materials of the
present invention have been shown to have highly thrombogenic
properties. In a preferred form, the web material (49) has the
appearance of a "cotton ball" (FIG. 19). One or more of these
reversibly compressible "thrombogenic cotton balls" (49) can be
combined with a delivery system (48), such as a catheter, for
implantation at a site of bleeding or aneurysm formation (FIG. 20).
Additional elements, such as metallic bands (FIGS. 19A-B), can be
added to the very highly porous stretched self-cohered web material
as visualization aids or mechanical supports. When used as a
component for a medical device, these very highly porous,
thrombogenic web materials can provide a seal between the device
and surrounding anatomical structures and tissues.
[0073] Various chemical components (23) can be combined with the
highly porous web stretched self-cohered web materials (20) of the
present invention (FIG. 9). The chemical components can be placed
on surfaces of the polymeric material comprising the highly porous
web material. The chemical components can also be placed in void
spaces, or pores, of the web material. The chemical compositions
can be suitably viscous chemical compositions, such as a hydrogel
material. Biologically active substances (27) can be combined with
the additional chemical component (FIG. 9A). With hydrogel
materials, for example, the biologically active substances can be
released directly from the hydrogel material or released as the
hydrogel material and the underlying web material are bioabsorbed
by the body of an implant recipient. Preferred chemical components
are in the form of hydrogel materials.
[0074] Suitable hydrogel materials include, but are not limited to,
polyvinyl alcohol, polyethylene glycol, polypropylene glycol,
dextran, agarose, alginate, carboxymethylcellulose, hyaluronic
acid, polyacrylamide, polyglycidol, poly(vinyl
alcohol-co-ethylene), poly(ethyleneglycol-co-propyleneglycol),
poly(vinyl acetate-co-vinyl alcohol),
poly(tetrafluoroethylene-co-vinyl alcohol),
poly(acrylonitrile-co-acrylamide), poly(acrylonitrile-co-acrylic
acid-acrylamidine), poly(acrylonitrile-co-acrylic
acid-co-acrylamidine), polyacrylic acid, poly-lysine,
polyethyleneimine, polyvinyl pyrrolidone,
polyhydroxyethylmethacrylate, polysulfone, mercaptosilane,
aminosilane, hydroxylsilane, polyallylamine,
polyaminoethylmethacrylate, polyornithine, polyaminoacrylamide,
polyacrolein, acryloxysuccinimide, or their copolymers, either
alone or in combination. Suitable solvents for dissolving the
hydrophilic polymers include, but are not limited to, water,
alcohols, dioxane, dimethylformamide, tetrahydrofuran, and
acetonitrile, etc.
[0075] Optionally, the compositions can be chemically altered after
being combined with the web material. These chemical alterations
can be chemically reactive groups that interact with polymeric
constituents of the web material or with chemically reactive groups
on the compositions themselves. The chemical alterations to these
compositions can serve as attachment sites for chemically bonding
yet other chemical compositions, such as biologically active
substances (27). These "bioactive substances" include enzymes,
organic catalysts, ribozymes, organometallics, proteins,
glycoproteins, peptides, polyamino acids, antibodies, nucleic
acids, steroidal molecules, antibiotics, antimycotics, cytokines,
carbohydrates, oleophobics, lipids, extracellular matrix material
and/or its individual components, pharmaceuticals, and
therapeutics. A preferred chemically-based bioactive substance is
dexamethasone. Cells, such as, mammalian cells, reptilian cells,
amphibian cells, avian cells, insect cells, planktonic cells, cells
from non-mammalian marine vertebrates and invertebrates, plant
cells, microbial cells, protists, genetically engineered cells, and
organelles, such as mitochondria, are also bioactive substances. In
addition, non-cellular biological entities, such as viruses,
virenos, and prions are considered bioactive substances.
[0076] The following examples are included for purposes of
illustrating certain aspects of the present invention and should
not be construed as limiting.
EXAMPLES
Example 1
[0077] This example describes formation of an article of the
present invention. Initially, an unannealed, non-woven,
self-cohered polymeric precursor web was formed. The precursor web
material was heated slightly and subjected to stretching in a
single, or uniaxial, direction to increase the porosity of the web
material. The highly porous self-cohered web material was then set
with heat.
[0078] The precursor web material was formed from a 67%
poly(glycolide) and 33% poly(trimethylenecarbonate) (w/w) segmented
triblock copolymer (67% PGA:33% TMC). The copolymer is available in
resin form from United States Surgical (Norwalk, Conn., US), a unit
of Tyco Healthcare Group LP. This polymer is commonly referred to
as polyglyconate and has historically been available through the
former Davis & Geck (Danbury, Conn.). A typical 67% PGA:33% TMC
resin lot was characterized previously by Hayes in U.S. Pat. No.
6,165,217, which is incorporated herein by reference. The process
of characterizing the "67:33-PGA:TMC" resin material is reiterated
herein.
[0079] Approximately 25 mg of the acquired copolymer was dissolved
in 25 ml of hexafluoroisopropanol (HFIP). The dilute solution thus
produced had an inherent viscosity (IV) of 1.53 dl/g as measured
with a Cannon-Ubelodde viscometer immersed in a water bath set at
30.degree. C. (.+-.0.05.degree. C.).
[0080] Approximately 10 mg of the acquired copolymer was placed
into an aluminum differential scanning calorimetry (DSC) sample
pan, covered, and analyzed utilizing a Perkin-Elmer DSC 7 equipped
with an Intracooler II cooling unit able to provide sample cooling
to temperatures as low as minus forty degrees centigrade
(-40.degree. C.). After preconditioning of the sample at
180.degree. C. for 2 minutes, the sample was cooled at the maximum
rate provided by the instrument (-500.degree. C./min setting) and
scanned from minus forty degrees centigrade (-40.degree. C.) to two
hundred fifty degree centigrade (250.degree. C.) at a scanning rate
of 10.degree. C./min. After completion of this initial scan, the
sample was immediately cooled at the maximum rate provided by the
instrument (-500.degree. C./min setting). A second similar scan was
undertaken on the same sample over the same temperature range.
After scan completion and thermal maintenance at 250.degree. C. for
5 minutes, the sample was again cooled at the maximum rate provided
by the instrument and a third scan undertaken.
[0081] Each scan was analyzed for the observed glass transition
temperature (T.sub.g), order-disorder transition temperature
(T.sub.odt), crystallization exotherm, and melt endotherm. The
results are summarized in Table 1. TABLE-US-00001 TABLE 1 Exotherm
Exotherm T.sub.g/T.sub.odt T.sub.g/T.sub.odt Peak Enthalpy Melt
Peak Melt Enthalpy Heat 1 0.2.degree. C. 0.26 J/g * .degree. C.
None None 213.7.degree. C. 44.7 J/g Heat 2 17.0.degree. C. 0.59 J/g
* .degree. C. 113.7.degree. C. -34.2 J/g 211.4.degree. C. 41.2 J/g
Heat 3 17.0.degree. C. 0.51 J/g * .degree. C. 121.4.degree. C.
-35.3 J/g 204.2.degree. C. 38.5 J/g
[0082] To prepare the copolymeric resin for processing into a
precursor web material, approximately 100 grams of the copolymer
was heated overnight under vacuum (<40 mm Hg) between
115.degree. C. and 135.degree. C. The resin was pelletized by
grinding the copolymer through a granulator equipped with a screen
having four (4) mm holes (Model 611-SR, Rapid Granulator, Rockford,
Ill., USA).
[0083] A one-half inch screw extruder (Model RCP-0500, Randcastle
Extrusion Systems, Inc., Cedar Grove, N.J., USA) with an attached
fiber spin pack assembly (J. J. Jenkins, Inc., Matthews, N.C., USA)
was obtained. The bottom portion of the spin pack assembly had a
seven (7) orifice spinnerette (see "Spin Pack" in FIG. 5)
consisting of 0.33 mm (0.013 inches) diameter die openings arranged
in a 2.06 cm (0.812 inches) diameter circular configuration. The
spin pack was set to a temperature of between 250.degree. C. and
270.degree. C. The particular temperature was dependent on inherent
viscosity characteristics of the resin.
[0084] An adjustable arm holding a Vortec Model 902
TRANSVECTOR.RTM. (Vortec Corporation--Cincinnati, Ohio USA) was
attached to the spin pack and positioned in alignment with the
travel direction of a screen fabric collector belt and below the
base of the spinnerette (FIG. 5). The top of the TRANSVECTOR.RTM.
inlet was centered below the die openings at an adjusted distance
"A" (FIG. 5) of approximately 2.5 to 3.8 cm (1.0 to 1.5 inches).
The arm was mounted on a mechanical apparatus that caused the
TRANSVECTOR.RTM. to oscillate across the fabric collector in the
same direction as a moving take-up belt. The arm oscillated between
angles approximately five (5) degrees off center at a frequency of
rate of approximately 0.58 full sweep cycles per second
(approximately 35 full cycles per minute). The TRANSVECTOR.RTM. was
connected to a pressurized air source of approximately 50 to 55 psi
(0.34-0.38 MPa). The pressurized air was at room temperature
(20-25.degree. C.), a temperature in excess of the polymer's
T.sub.odt. When operating, the pressurized air was introduced and
accelerated within the TRANSVECTOR.RTM.'s throat. The accelerated
air stream drew additional air into the inlet from the area of the
multiple orifice die.
[0085] The vacuum dried pelletized copolymer was then fed into the
screw extruder (101) and through the crosshead of the spinneret
(102) as illustrated in FIG. 5. The melted copolymer exited the
spinnerette in the form of seven (7) individual filaments (105). As
the filaments became influenced by the air current entering the
TRANSVECTOR.RTM. inlet (103), the filaments were accelerated
through the TRANSVECTOR.RTM. at a significantly higher velocity
than without the air entrainment. The accelerated filaments were
then accumulated on a screen fabric collector belt (106) located at
a distance "107" 66 cm (26 inches) from the outlet of the
TRANSVECTOR.RTM. and moving at the speed of approximately 20.4
cm/min (0.67 feet per minute) to form a precursor web material
(108). Increasing the belt speed produced a thinner web material,
while slowing the belt speed produced a thicker web material.
[0086] The resulting unannealed, unstretched, non-woven,
filamentous, self-cohered precursor web material that accumulated
on the collector belt possessed a relatively consistent loft along
the direction of belt movement and possessed approximately 3.2
inches of "usable width." "Usable width" refers to an inner portion
of the precursor web material having the greatest consistency at a
gross, visual level, and a fine, microscopic, level. Portions of
precursor web material outside the "usable width" have filaments
that accumulate in such a way that the overall web diminishes in
relative height and density on either side of the centerline when
observed in line with the direction of belt movement. Area
densities reported herein were obtained from representative samples
acquired from a region of the web having a "usable width."
[0087] After more than 10 seconds of cooling at ambient
temperature, the precursor web was removed from the fabric belt.
Upon examination, the material was a tactilely supple, cohesive
fibrous web, with individual component fibers that did not appear
to fray or separate from the web when subjected to moderate
handling. The filaments were intermingled and bonded at contact
points to form an un-annealed (i.e. minimally crystallized or
"unset"), unstretched, non-woven, self-cohered precursor web
material.
[0088] Precursor webs produced in this manner typically possess
inherent viscosity (IV) values and crystallization exotherm peaks
similar to those described in Example 2 of U.S. Pat. No. 6,165,217,
issued to Hayes, and incorporated herein by reference. Particularly
pertinent portions of the example are reproduced herein as
follows.
Inherent Viscosity
[0089] Approximately 29 mg of the above-described precursor web was
dissolved in 25 ml of hexafluoroisopropanol (HFIP) to produce a
dilute solution. The solution possessed an inherent viscosity (IV)
of 0.97 dl/g when measured using a Canon-Ubbelohde viscometer
immersed in a 30.degree. C. (.+-.0.05.degree. C.) water bath.
Consequently, the IV was observed to have dropped during processing
from the initial value of 1.53 dl/g in the pelletized copolymer to
a value of 0.97 dl/g in the precursor web.
Thermal Properties
[0090] An appropriately sized sample was obtained from the
above-described precursor web to allow for its thermal analysis
utilizing a Perkin Elmer DSC7 Differential Scanning Calorimeter
(DSC). Scanning was conducted at 1 O.degree. C./minute and the
instrument's temperature was moderated with an Intracooler II
refrigeration unit. A single scan between minus twenty degrees
centigrade (-20.degree. C.) and 250.degree. C. was performed with
the following results (TABLE 2). TABLE-US-00002 TABLE 2
T.sub.g/T.sub.odt Exotherm Exotherm T.sub.g/T.sub.odt Capacity Peak
Enthalpy Melt Peak Melt Enthalpy Heat 1 16.32.degree. C. 0.54 J/g *
.degree. C. 88.16.degree. C. -31.68 J/g 209.70.degree. C. 45.49
J/g
[0091] The order-disorder transition temperature (T.sub.odt)
reported herein occurs at the inflection point between the
differing levels of heat capacity as indicated by a deflection of
greater than 0.1 joule per gram-degree Celsius (J/g*.degree. C.) in
the baseline of the scan. This T.sub.odt occurs at a temperature
between the glass transition temperatures (T.sub.g) of the
respective homopolymers and is roughly approximated by the Fox
equation. In this particular example, the precursor web sample
displayed an order-disorder transition at approximately 16.degree.
C. and a crystallization exotherm beginning at approximately
70.degree. C. Full specimen crystallinity is considered
proportional to the area under the melt endotherm, quantified by
enthalpy in Joules/gram (J/g). The general characteristics of a
thermal scan of this precursor web can be observed in FIG. 3 of the
above-referenced '217 Patent.
[0092] Assuring that the web was not exposed to combinations of
heat or time that would lead to a substantial reduction of the
precursor web's crystallization exotherm enthalpy, as measured
through the aforementioned evaluation with a power compensation
based DSC system, opposite ends of rectangular segments of the
precursor web were then placed under restraint and stretched in a
single, or uniaxial, transverse direction (i.e., in a direction
approximately 90 degrees from the longer length of the precursor
web).
[0093] The highly porous stretched self-cohered web materials of
the present invention were made with a transverse
expansion/stretching machine equipped with pin grips and three
electric heating zones. Such a machine is also known as an
adjustable tenter or stenter frame with the capability to expand
transversely across the surface of a supporting metal sheet while
moving in a longitudinal direction. Due to broad adjustability,
various machines able to fulfill the functions described herein are
available from numerous suppliers, one of which is: Monforts, A
Textilmaschinen GmbH & Co KG, Moechengladbach, Germany.
[0094] This particular unit was equipped with three (3) sequential
conjunct heated platens measuring 24, 6, and 24 inches (61, 15.2,
and 61 cm) in length, respectively. The heated platens created
heated zones through which the web material was passed. The leading
edge of a 13 inch (33 cm) long stretching-transition region began
11 inches (27.9 cm) from the leading edge of the first heated zone.
The initial feed rate was one (1) foot (30.48 cm) per minute.
[0095] In the initial stretching operation, only the third, or last
downstream, zone of the stretching machine was heated to a
temperature of 120.degree. C. However, it was serendipitously
discovered that heat from the third zone progressively invaded the
adjoining second and first zones in such a way that the precursor
web was warmed before it was stretched. Inter alla, this resulted
in progressively improving uniformity of the final highly porous
web material. Precursor web materials were stretched at ratios of
2:1, 3:1, 4:1, 5:1 and 6:1. Preferred materials were formed when
zone one (1) of the transverse stretching apparatus was set at a
temperature of 50.degree. C. and the precursor web material
stretched at a ratio of 6:1.
[0096] After thermosetting the stretched web at a temperature of
about 120.degree. C. for about one (1) minute, a highly porous
self-cohered web material of the present invention was formed and
allowed to cool to room temperature. Each piece of inventive
material was found to be more porous, supple, lofty, compliant, and
uniform in appearance than a similar non-woven self-cohering web
made without pre-heating and stretching of the similar web in an
un-annealed state.
[0097] Additional rectangular sections of precursor web materials
were stretched at ratios of 8:1 and 10:1 using preheated platens
set to approximately 50.degree. C., 75.degree. C., and 125.degree.
C. for each successive heated zone in the stretching apparatus. The
first two heat zone settings provided a reliable "pre-warming" of
the precursor web material. The temperatures, in excess of the
T.sub.odt reported in the '217 Patent, were sufficient to
facilitate mobility of the co-polymeric molecules of the precursor
web material and provide a more consistent final product. The third
heated zone was set to a temperature that at least approximated and
likely exceeded the temperature of the crystallization Exotherm
Peak (T.sub.cr) described within the '217 Patent, to anneal, or
heat-set, the final web material.
Example 2
[0098] In this example, precursor webs produced using the various
belt speeds and transverse expansion ratios described in Example 1
were obtained for a variety of web densities and stretch, or draw,
ratios. Following processing, scanning electron micrographs (SEM)
were generated of representative areas of this embodiment of the
present invention. Some characteristics of the stretched web of the
present invention and the filaments comprising the web were
quantified as follows.
[0099] The cross-sectional diameter of the stretched filaments in
each web material of the present invention was determined by
visually examining the SEMs. In each SEM, fifty (50) stretched
filaments were randomly chosen and the diameter of a cross-section
of each filament was measured. The cumulative results of these
filament cross-sectional diameters is contained in Table 3 and
summarized in FIGS. 6 and 7. The stretch ratios are expressed as
multiples of "X." For example, "
[0100] 0X" refers to unstretched precursor web material. "4X"
refers to a 4:1 stretch ratio. Tabulated features of the web were
the mean, median, maximum, and minimum fiber diameter. In addition,
both the number and percent of the fifty (50) fibers found to be
less than twenty (20) microns in cross-sectional diameter were
tabulated. TABLE-US-00003 TABLE 3 Fiber Dimensional Characteristics
at Varying Stretch Ratios 0X 4X 5X 6X 8X 10X Mean 31.3 19.3 19.2
20.2 19.0 16.0 Median 30.3 18.6 17.6 18.4 18.6 15.0 Web Sample 6 2
2 10 2 2 Count Fiber Count 2.8 32.0 34.0 30.5 35.0 40.5 (<20 um)
% <20 um 5.7% 64.0% 68.0% 61.0% 70.0% 81.0% % >20 um 94.3%
36.0% 32.0% 39.0% 30.0% 19.0% % >50 um 1.3% 0.0% 0.0% 0.6% 0.0%
0.0% Minimum (um) 17.0 7.6 9.6 10.6 9.7 7.3 Maximum (um) 59.4 37.3
38.9 41.9 38.2 39.1
[0101] When evaluated with this method, all the fiber
cross-sectional diameters in the unannealed, unstretched, precursor
web (0X) were observed to be between seventeen (17) and fifty-nine
(59) microns. Further, over ninety percent (90%) of the fibers had
cross-sectional diameters within the twenty (20) and fifty (50)
micron range described in the above-referenced '217 Patent. The
effect of stretching on the fiber diameter is readily seen from
this data. Filaments of unstretched precursor webs can be reduced
in diameter when subjected to the stretching process of the present
invention. The reduction in fiber diameter is readily seen by
contrasting the number of fibers in an unstretched web having
diameters below twenty (20) microns (e.g., 5.7%) with the number of
fibers of stretched webs having diameters below twenty (20)
microns. The number of fibers with diameters less than twenty (20)
microns in a stretched material of the present invention range from
an average of sixty four percent (64%) to eighty one percent (81%).
Accordingly, substantial stretching of a precursor web causes a
significant reduction in fiber diameter in a substantial number of
the fibers in the final stretched web material of the present
invention.
[0102] Since these webs were stretched, or drawn, in a single
direction, or "uniaxial" manner, it is notable from this same data
that twenty (20) to forty (40) percent of the fibers in the
stretched web have diameters larger than 20 microns. This mix of
fiber diameters within the stretched web resulted in an increase in
the web material's overall loft. The Increased the loft of the
stretched web material correlates with a reduction in both the
web's area density and the volume density. Volume density is
directly related to porosity. Web materials of the present
invention have increased porosity compared to similar unstretched
web materials. Increasing porosity and correspondingly reducing
volume density maximizes interstitial space within the web
structure. These features increase the opportunity for infiltration
of host cells into the web material. The number and type of cell
inhabiting a web material of the present invention have a direct
effect on the bioabsorption of the web material.
[0103] To quantify the actual molecular orientation imparted by the
stretching process of the present invention, birefringence values
were determined for a variety of filaments from webs of the present
invention made with different stretch ratios. Birefringence values
were obtained by utilizing a sliding quartz wedge capable
polarizing microscope possessing both an optical grid and a
circular rotating stage (e.g. Nikon Optiphot2-POL). Both filament
cross-sectional diameter and birefringence values were determined
from a sampling of filaments that were either actively or passively
isolated from the optical influences of the surrounding web.
[0104] Assuring no physical distortion artifacts occurred during
filament isolation, cross-sectional diameter values were determined
using convention light microscopy and birefringence values. The
values were acquired through utilization of a Michel-Levy chart.
Such optical equipment is available from various suppliers (e.g.,
Nikon America, Melville, N.Y.). Michel-Levy charts are also
available from various suppliers (e.g., The McCrone Institute
(Chicago, Ill.).
[0105] The birefringence values thus obtained were analyzed for a
correlation with filament diameter. It was found the relationship
appeared to follow a power function that could be approximated by
the equation: Y=0.4726 X.sup.-0.9979 with an R2 value of 0.8211
(see FIG. 8). Using this relationship and referring to FIG. 8, it
was determined that a filament with a twenty (20) micron
cross-sectional diameter could be expected to possess a
birefringence value of approximately 0.024. Thus, filaments having
cross-sectional diameters less than twenty (20) microns could be
reasonably expected to possess birefringence values in excess of
0.025.
Example 3
[0106] As a result of stretching the material described in Example
1, both the amount of polymeric material per unit area (area
density) and amount of polymeric material per unit volume (volume
density) were reduced. A precursor web (produced at a belt speed of
0.67 feet/minute (20.4 cm/minute)) was further processed in an oven
set at 100.degree. C. for 25 minutes to completely anneal, or
"heat-set," the web material.
[0107] The unannealed, unstretched, self-cohered precursor web
material was substantially similar to the web material disclosed in
the '217 Patent. A heat-set version of the precursor web material
was determined to have an area density of approximate 23
mg/cm.sup.2 and a volume density of approximately 0.16 g/cc.
Commercially forms of this type of web are available from W. L.
Gore & Associates, Inc., Flagstaff, Ariz., under the tradenames
GORE Bioabsorbable SeamGuard and GORE Resolut Adapt LT. Each of
these unstretched web materials has an area density of 9.7
mg/cm.sup.2 and 8.4 mg/cm.sup.2, respectively. Each web material
also had a volume density of 0.57 g/cc and 0.74 g/cc, respectively.
This corresponded to a percent porosity of fifty-six (56) and
forty-three (43), respectively.
[0108] After uniaxial stretching of a precursor web material of
Example 1 at a ratio of 6:1, the material was determined to have an
area density of approximately 5.3 mg/cm.sup.2. This represents a
change in area density of approximately seventy-five percent (75%).
The unstretched precursor web material of Example 1 had a volume
density of 0.16 g/cc. In contrast, the stretched web material of
Example 1 had a volume density of 0.083 g/cc. This represents a
reduction in volume density of approximately fifty (50)
percent.
[0109] The specific gravity of full density, unstretched, 67%
PGA:33% TMC (w/w) polymer (.rho..sub.polymer) has been reported to
be 1.30 grams/cc (Mukherjee, D, et al; Evaluation Of A
Bioabsorbable PGA: TMC Scaffold For Growth Of Chondrocytes,
Abstract #12, Proceedings of the Society for Biomaterials, May
2005). By comparing this reported polymeric density value with the
volume density of a web material of the present invention
(.rho..sub.saffold), overall percentage porosity in the absence of
additional components can be determined through the relationship:
(.rho..sub.polymer-.rho..sub.scaffold)/.rho..sub.polymer.times.100
[0110] As used herein, the term "percent porosity" or simply
"porosity" is defined as the void space provided within the
external boundaries of the stretched self-cohering web, absent the
inclusion of any fillers or other added components that may
effectively reduce the available porosity.
[0111] This evaluation showed that stretching the precursor web
material of Example 1 increased the percent porosity of the PGA:TMC
precursor web material from eighty-eight percent (88%) in the
absence of additional components to approximately ninety-four
percent (94%) in the absence of additional components. The
resulting percent porosity in the absence of additional components
of both the precursor and aforementioned 6:1 stretched web is
provided in Table 4. Table 4 also provides a summary of the area
density, the volume density, and the percent porosity of the web
material before and after stretching. TABLE-US-00004 TABLE 4
Physical Property Comparison of 6:1 Stretched Web Precursor 6:1 Web
@ 0.67 Stretched Percent (%) Observation feet/minute Web Change
Density PGA:TMC = 1.30 g/cc Area Density 23 5.3 -77% (in
mg/cm.sup.2) Volume Density 0.158 0.083 -47% (in g/cm.sup.3)
Percent Porosity 88% 94% 7% in the absence of additional
components
Example 4
[0112] This example describes generation of tensile stress-strain
data for uniaxially stretched (6:1 stretch ratio) web materials of
the present invention. The web materials were produced according to
Example 1 with the exception that the belt speed was 0.26
feet/minute (7.9 cm/sec).
[0113] Samples of stretched web materials of the present invention
were cut into shapes having a central strip and enlarged ends, much
like that of a "dog bone." The dog bone-shaped specimens were
approximately half the size of those described for ASTM D638 Type
IV (i.e., with a narrow distance length of 18 mm and a narrow width
of 3 mm). Testing was conducted using an INSTRON.RTM. Tensile
Tester Model No. 5564 equipped with an extensometer and 500 Newton
load cell. The software package used to operate the tester was
Merlin, Version 4.42 (Instron Corporation, Norwood, Mass.). The
gauge length was 15.0 mm. The cross-head rate (XHR) was 250
mm/minute. Data was acquired every 0.1 second.
[0114] The percentage (%) elongation and matrix tensile stress of
the stretched web, as measured from test specimens oriented in
their length to be in line with in the stronger cross-web
direction, was found to be 32.0% and 60 MPa, respectively. The
percentage (%) elongation and matrix tensile stress of the
stretched web, as measured from test specimens oriented in their
length as measured in the weaker down-web direction, was found to
be 84.7% and 3.4 MPa, respectively. Tensile stress results for
these 67:33-PGA:TMC webs are summarized in Table 5 For comparative
purposes, the mechanical characterization of a thinner web of
67:33-PGA:TMC as described in the '217 Patent is included in Table
5.
[0115] Matrix tensile stress is utilized as a means to normalize
tensile stress in samples where measurement of thickness can be
problematic, such as materials of the present invention possessing
a high degree of porosity and easily deformed loft. Through
utilization of the test material's area density and the specific
gravity of its component polymer, the matrix tensile stress
approach converts a difficult to measure porous loft into an
equivalent thickness of full density component polymer. The
reduction is proportional to the volume density of the web divided
by the specific gravity of the component polymer. This equivalent
polymeric thickness was then utilized for cross-sectional area
determinations in the calculation of tensile stress. Such use of
matrix tensile stress has been described in both U.S. Pat. No.
3,953,566, issued to Gore, and U.S. Pat. No. 4,482,516, issued to
Bowman, et al. for utilization in determining the strength of
porous expanded polytetrafluoroethylene (ePTFE) materials.
[0116] To obtain matrix tensile strength, the equivalent thickness
of a tensile specimen is determined by dividing the porous
structure's area density by the specific gravity of the component
polymer. This value is then substituted instead of the specimen's
actual thickness in determining stress. Thus: Equivalent
thickness=area density/specific gravity of polymer
[0117] Provided both the area density and the specific gravity of
the component polymer are known, this equivalent thickness value
can also be utilized to convert the tensile stress of a porous
sample into a matrix tensile stress value. In Example 2 of the '217
Patent, both maximum tensile stress of the 67:33-PGA:TMC web
material was reported along with the area density of the test
specimen and were found to be 4.9 MPa and 28.1 mg/mm.sup.2,
respectively.
[0118] Thus, matrix tensile stress can be calculated as follows:
TABLE-US-00005 TABLE 5 4.9 .times. .times. N mm 2 .times. mm 2 [ (
28.1 .times. .times. mg .times. / .times. 100 .times. .times. mm 2
) .times. / .times. 1.3 .times. .times. mg .times. / .times. mm 3 ]
.times. 1 .times. .times. mm = 22.7 .times. .times. MPa ##EQU1##
Tensile Max Matrix Density Max Force Stress Stress % Area Volume
Sample Description (N) (MPa) (MPa) Elongation (mg/cm.sup.2)
(g/cm.sup.3) Unstretched Precursor n.a. n.a. n.a. n.a. 44 .17 Web
US Patent 6,165,217 Not 4.9 22.7 Not 28.1 0.29 (Example 2; provided
(saline) (calc'd) provided orientation not specified) 6:1
Transverse Stretched 14.3 3.6 60 32.0 9.6 .065 Cross-Web Sample 6:1
Transverse Stretched 1.0 0.34 3.4 84.7 11.5 .078 Down-Web Sample
n.a. = not acquired
[0119] As can be seen for the data, the web material of the present
invention was found to be highly anisotropic and possessed reduced
strength and significant elongation in the "down web" direction.
Conversely, the strength was highest in the direction of stretching
and cross-web matrix tensile stress was found to be significantly
higher than the fully crystallized unstretched web material
described in the '217 Patent. This result provided evidence of
increased molecular orientation of the PGA:TMC block
copolymers.
Example 5
[0120] This example describes the formation of an article of the
present invention using an ABA triblock copolymer of PGA:TMC having
a ratio of poly(glycolide) to poly(trimethylenecarbonate) (w/w) of
50:50.
[0121] Synthesis of a typical 50% PGA:50% TMC resin lot has been
previously described in the '217 Patent and is reiterated herein as
follows.
[0122] A 4CV Helicone Mixer (Design Integrated Technologies,
Warrenton, Va., USA) located within a Class 10,000 clean room and
connected to a Sterling brand hot oil system (Model #S9016,
Sterling, Inc., Milwaukee, Wis., USA) able to maintain temperatures
up to 230.degree. C. was pre-cleaned to remove any polymeric or
other residues and then thoroughly air dried for 2 hours before
reattachment of the mixer bowl. The dry mixer was then preheated to
140.degree. C. followed by a purge and then blanketing with
anhydrous nitrogen a minimum flow during the course of the
experiment. A foil package containing 740.7 grams of trimethylene
carbonate was opened and the contents introduced followed by mixing
at a speed setting of "6.5." After 10 minutes, stirring was stopped
and 2.73 grams of a combination of 0.228 grams of
SnCl.sub.2.2H.sub.2O catalyst and 15.71 grams of diethylene glycol
initiator was then added directly to the melted TMC. Mixing was
recommended and after 10 minutes the temperature was raised to
160.degree. C. which was then followed by an increase to
180.degree. C. after 30 minutes. After an additional 30 minutes, 75
grams of glycolide monomer was added followed by an increase of the
temperature to 200.degree. C. After 15 minutes, 675 grams of
glycolide were added and the temperature setting immediately
changed to 220.degree. C. After 40 minutes, the polymerized product
was discharged at the 220.degree. C. onto a clean release surface
where it solidified as it cooled down to room temperature. The
light brown polymer thus obtained was then packaged in a pyrogen
free plastic bag and then mechanically granulated through a 4.0 mm
screen prior to further analysis and processing.
[0123] In the '217 Patent, Hayes additionally reported the inherent
viscosity (IV) of this particular 50% PGA:50% TMC resin lot to be
0.99 dl/g.
[0124] A 50% PGA:50% TMC triblock co-polymer synthesized as
described was then granulated as described in Example 1 and
subsequently vacuum dried for at least 15 hours at 120.degree. C.
to 130.degree. C. Approximately 250 grams of ground polymer was
placed into the extruder described in Example 1 and heated to a die
temperature of approximately 230.degree. C. to 250.degree. C. A
random continuous precursor web material, approximately 3.2 inches
(5.08 cm) in width, was acquired at a belt speed of approximately
20.4 cm/min (0.67 feet per minute). The precursor web material was
morphologically similar to the unstretched 67:33-PGA:TMC precursor
web material described in Example 1. The individual filaments
formed cohesive bonds at contact points to form a self-cohered web.
The filament diameter for web materials produced through this
process ranged from twenty-five (25) microns to forty (40) microns.
As noted in the '217 Patent, these web materials typically have
inherent viscosity values of 0.9 dl/g. Typical DSC values for these
web materials are listed in Table 6. TABLE-US-00006 TABLE 6 Typical
DSC Values for Unset PGA:TMC (50:50) Precursor Web
T.sub.g/T.sub.odt Exotherm Melt T.sub.g/T.sub.odt Capacity Exotherm
Peak Enthalpy Peak Melt Enthalpy Heat 1 5.degree. C. 0.5 J/g *
.degree. C. 110.degree. C. -33 J/g 203.degree. C. 37 J/g
[0125] Stretching of the unannealed, non-woven, self-cohered,
precursor web material was conducted with the same equipment and
uniaxial stretch rate as described in Example 1 for the
67:33-PGA:TMC triblock co-polymeric non-woven, self-cohered
precursor web material. Care was taken that the unstretched
precursor web was not exposed to combinations of heat or time that
would lead to a substantial reduction of the web's crystallization
exotherm enthalpy prior to stretching.
[0126] In addition to the uniaxial stretch ratios described in
Example 1, additional uniaxial stretch ratios from 7:1 through 10:1
were performed. The oven temperature for zone one (1) was set at
forty degrees centigrade (40.degree. C.) and zone three (3) was set
at eighty-five degree centigrade (85.degree. C.). Thermal setting
of the stretched web was accomplished after approximately one (1)
minute in zone three (3) at eighty-five degrees centigrade
(85.degree. C.).
[0127] For webs of the present invention made with a 50:50 PGA:TMC
triblock copolymer starting material, uniaxial stretch ratios of
7:1 through 10:1 produced webs with the most suppleness and uniform
appearance.
Example 6
[0128] This example describes the formation of an article of the
present invention using multiple layers of precursor web material
and stretching the layered material sequentially in perpendicular
directions.
[0129] A starting material was obtained by layering together nine
sheets of unannealed, unstretched, precursor web material made
according to Example 1. Each of the nine precursor sheets was
produced at a belt speed of 1.58 minute (48 cm/min). Each precursor
sheet was found to have an area density of approximately 9.0
mg/cm.sup.2 and a volume density of approximately 0.27 g/cc.
Accordingly, nine layers of precursor sheet material would be
expected to have an area density of approximately 81 mg/cm.sup.2
and a volume density of approximately 0.27 g/cc.
[0130] The nine unannealed, unstretched, precursor web sheets were
initially oriented so their width was generally in the same
"machine direction" as the moving belt used to take up the web as
it was formed. The similarly oriented layered sheets were stretched
transversely (i.e., in a direction approximately 90 degrees from
the direction of initial orientation of the unannealed web) in an
oven with each of three heated zones set at ambient temperature,
50.degree. C., and 120.degree. C., respectively. The stretch ratio
was 6:1 and the stretch rate was one foot per minute (30.5
cm/min).
[0131] The result was an article of the present invention having an
area density of 18 mg/cm.sup.2. This represents nearly a
seventy-six (76) percent reduction in area density from the
precursor web material. The article had a volume density of 0.11
g/cc. This represents nearly a sixty (60) percent reduction in
volume density from the precursor web material (0.27 g/cc). The
percent porosity of this web material was seventy-nine (79).
[0132] The percentage of elongation of the precursor web and the
matrix tensile stress of the finished laminated web material was
measured in the stronger cross-web direction and found to be
sixty-four percent (64%) and 48 MPa, respectively. The percent
elongation and matrix tensile stress of the finished laminated web
material of the present invention, as measured in the weaker
down-web direction, was found to be one hundred thirty-three
percent (133%) and 5.2 MPa, respectively. Theses values are greater
than those observed with the single layer uniaxially distended web
of Example 1. Matrix tensile stress in the cross-web direction were
also higher than the 22.7 MPa values reported in the '217
Patent.
[0133] The layered web material of this example possessed increased
suppleness and uniform appearance compared to a non-stretched,
non-woven, self-cohered layered web material.
Example 7
[0134] This example describes materials produced from a first
longitudinal web stretching procedure, followed by a subsequent
transverse stretching procedure of the same web. This web material
is referred to herein as a "Longitudinal-Transverse Stretched Web."
Unannealed, unstretched, self-cohered precursor web material was
prepared in accordance with Example 1 and processed as follows to
form a material of the present invention. The precursor web
material had an area density of approximately 45 mg/cm.sup.2.
[0135] When evaluated using DSC parameters as described in Example
1, the thermal characteristics of both the utilized 67:33-PGA:TMC
resin and the resulting unannealed precursor web were those
summarized in Table 7. TABLE-US-00007 TABLE 7 DSC Values for Unset
67:33 PGA:TMC Precursor Web T.sub.g/T.sub.odt Exotherm Exotherm 1
scan T.sub.g/T.sub.odt Capacity Peak Enthalpy Melt Peak Melt
Enthalpy Resin 13.5.degree. C. 0.33 J/g * .degree. C. none none
193.degree. C. 40.5 J/g Web 18.4.degree. C. 0.57 J/g * .degree. C.
82.9.degree. C. -30.1 J/g 196.degree. C. 39.5 J/g
[0136] Five (5) varieties of stretched web material of the present
invention were produced in this example based primarily on stretch
ratio. Using a longitudinal stretching machine able to draw
precursor web of suitable length across the surface of a supporting
three zone heated metal sheet while moving in a longitudinal
direction between dissimilar speed adjusted feed and take-up
rollers, each unannealed, unstretched, precursor web material was
first longitudinally stretched at a ratio of 1.5:1 at a temperature
of twenty degrees centigrade (20.degree. C.) in a direction
substantially the same as the direction of the collector belt used
for retrieval of the unstretched precursor web. This longitudinal
direction (e.g., x-axis direction) is referred to herein as the
"down-web" (DW) direction.
[0137] The longitudinally stretched unannealed, self-cohered, web
material was then transferred to the heated platen transverse
stretching machine described in Example 1. Each of these down-web
stretched materials was subsequently stretched a second time in a
"cross direction" (y-axis) perpendicular to the direction of the
first longitudinal stretching procedure. This "cross-direction"
stretching is referred to herein as "cross-web" (CW) stretching.
The first sample (designated "1B") was stretched cross-web at a
ratio of 2:1. The next sample ("2A") was stretched cross-web at a
ratio of 3:1. Each remaining sample (2B, 2C, and 2D) was stretched
cross-web at a ratio of 3.5:1, 4:1, and 4.5:1, respectively. The
first and third heated zones in the oven were set to fifty degrees
centigrade (50.degree. C.) and one hundred twenty degrees
centigrade (120.degree. C.), respectively. The temperature in zone
three was sufficient to completely heat-set the final stretched web
material of the present invention. The resulting material was a
fully annealed web, as is evidenced by the thermal characteristics
displayed in Table 8 that displayed substantial DW extendibility.
TABLE-US-00008 TABLE 8 DSC Values for Longitudinal-Transverse 67%
PGA:33% TMC Web T.sub.g/T.sub.odt Exotherm Exotherm 1 scan
T.sub.g/T.sub.odt Capacity Peak Enthalpy Melt Peak Melt Enthalpy 1B
11.8.degree. C. 0.39 J/g * .degree. C. none none 193.degree. C.
38.6 J/g 2A 11.4.degree. C. 0.35 J/g * .degree. C. none none
192.degree. C. 38.9 J/g 2B 11.6.degree. C. 0.33 J/g * .degree. C.
none none 194.degree. C. 41.0 J/g 2C 11.1.degree. C. 0.30 J/g *
.degree. C. none none 192.degree. C. 38.8 J/g 2D 11.3.degree. C.
0.32 J/g * .degree. C. none none 192.degree. C. 38.2 J/g
[0138] The physical and tensile stress-strain properties of the
(1.5:1) longitudinal--(4.5:1) transverse stretched web (2D), along
with a fully set precursor web, are summarized in Table 9.
TABLE-US-00009 TABLE 9 Physical & Mechanical Properties of
Longitudinal-Transverse 67:33 PGA:TMC Web Tensile Max Max Matrix
Density Force Stress Stress Area Volume Sample Description (N)
(MPa) (MPa) (mg/cm.sup.2) (g/cm.sup.3) Unstretched Precursor 9.0
3.6 16.9 22.5 0.28 Web Down Web Sample 1.3 2.3 10.3 5.2 2D - DW
(3:2 DW by 5:1 CW) Cross Web Sample 4.8 5.0 23.1 8.4 2D - CW (3:2
DW by 5:1 CW)
Example 8
[0139] This example describes formation of two stretched
self-cohered web materials of the present invention. The web
materials were simultaneously stretched bi-axially in two
directions (x-axis and y-axis) during processing.
[0140] An unstretched precursor web material was made according to
Example 1. The TRANSVECTOR.RTM. apparatus was set at a spinneret
angle of 8.5 degrees and a sweep rate of approximately 0.46 full
cycles per second. The resulting unannealed, unstretched, precursor
web material had a "usable width" of five (5) to six (6) inches
(12.7 cm to 15.2 cm) with a web density of forty (40) to fifty (50)
mg/cm.sup.2 produced at a belt speed of approximately 8 cm/min. The
unannealed, unstretched, precursor web material was not exposed to
interim combinations of heat or time that would lead to a
substantial reduction of the web's crystallization exotherm
enthalpy.
[0141] A pantograph was used to biaxially stretch the unannealed
precursor web material to form a first bi-axially stretched web
material. A pantograph is a machine capable of stretching the
precursor web material biaxially or uniaxially over a range of
rates and temperatures (e.g., 50.degree. C. to 300.degree. C.). The
pantograph used in this example was capable of stretching a piece
of precursor web material from a four inch by four inch
(4''.times.4'') square piece to piece twenty-five inches by
twenty-five inches (25''.times.25''). This represented a 6.1:1
stretch ratio in both x and y axes. To retain the precursor web
material while stretching, the last half-inch of each arm on the
pantograph was equipped with a pin array. There were a total of
thirty-two (32) arms on the pantograph--seven on each side, plus
one in each corner. The pantograph was also equipped with heated
clamshell platens, which permitted control of the temperature of
the precursor web material during processing.
[0142] The first bi-axially stretched web material was made by
fixing a five (5) inch (12.7 cm) square piece of unannealed,
unstretched, precursor web material (45 mg/cm.sup.2) onto the
pantograph pin-frame at an initial setting of four inches by four
inches (4''.times.4''). The clamshell platens were set at fifty
degrees centigrade (50.degree. C.) and were positioned over the
unannealed web for two minutes to pre-heat the precursor web
material in excess of the polymer's T.sub.odt prior to stretching.
The pre-heated precursor web material was stretched sequentially at
a ratio of 3.6:1 along the x-axis (down-web) and a ratio of 6.0:1
along the y-axis (transverse), both at a rate of 20 percent per
second (20%/sec). Upon completion of the stretching process, the
platens were retracted from the bi-axially stretched web
material.
[0143] A pin frame, twelve (12) inches long by eight (8) inches
wide, was inserted into the bi-axially stretched web material of
the present invention to restrain a portion of it after it was
removed from the pantograph pins. The bi-axially stretched web
material was then heat-set, while restrained in the eight (8) inch
by twelve (12) inch pin-frame, in an oven set at one hundred twenty
degrees centigrade (120.degree. C.) for about three (3) minutes.
The resulting first biaxially stretched web material was removed
from the pin-frame and the unrestrained portion trimmed away.
[0144] The first biaxially stretched web material was tested for
area weight and thickness. From these measurements the volume
density and porosity was calculated, as taught in Example 3. The
area weight was measured as described in Example 1. The thickness
was measured per the procedure in Example 1, except that a glass
slide, 25 mm.times.25 mm.times.1 mm thick, was placed on the top of
the web in order to clearly distinguish the upper surface of the
web on the optical comparator. The area weight was 2.61
mg/cm.sup.2, which represents about a ninety-four percent (94%)
reduction of the unannealed precursor web material area weight. The
thickness was 0.44 mm. These values give a volume density of 0.059
g/cm.sup.3 and a percent porosity of ninety-five (95). This percent
porosity value is two-fold greater in void to solids ratio (void
volume/solids volume) than the highest porosity disclosed in the
'217 Patent.
[0145] A second bi-axially stretched web material was made as
described above except for modifications in several process
parameter settings. For this second stretched web material, the
preheat temperature was set to 70.degree. C. and the unannealed web
was pre-heated for about 30 seconds. The web was simultaneously
stretched at a ratio of 3.6:1 along the x-axis and a ratio of 6.0:1
along the y-axis at the same stretch rate of thirty percent per
second (30%/sec). The second bi-axially stretched web material was
restrained and heatset on a pin-frame in an oven as described above
for the first stretched web material.
[0146] The properties of the second bi-axially stretched web
material were measured as described for the first stretched web
material. The area weight was 3.37 mg/cm.sup.2 and the thickness
was 0.94 mm. This gave a volume density and porosity value of 0.036
g/cm.sup.3 and 97%, respectively. The void to solids ratio of the
second bi-axially stretched web material is about 50% greater than
the that of the first bi-axially stretched web material and about
3-fold greater than that disclosed in the '217 Patent.
Example 9
[0147] This example describes formation of a stretched web material
of the present invention. The stretched web material has increased
loft and suppleness and substantially resumes its original shape
when an applied deforming force is removed.
[0148] A biaxially-stretched web material was made according to
Example 8 except that a pin-frame was not used to restrain the web
material as it was heat-set in the oven. Rather, the bi-axially
stretched web material was suspended loosely in the oven from a
rack as it was set. The bi-axially stretched web material was
observed to contract after removal from the pantograph. The
bi-axially stretched web material contracted further in the oven.
The area of the fully stretched starting web material was reduced
by about fifty percent (50%) with this process.
[0149] The resulting highly porous, bi-axially stretched and
contracted, web material was thicker, softer, loftier, and more
flexible than either similarly-produced stretched web material of
Example 8. In addition, this bi-axially stretched and contracted
web material resumed its original shape when an applied deforming
force was removed. This resilient property was found in all
portions of the bi-axially stretched and contracted web material.
Microscopic examination (50X) of the resilient bi-axially stretched
and contracted web material revealed highly curved self-cohered
filaments of the material oriented in all directions, including the
z-axis (i.e., perpendicular to the planar x and y axes). The
diameter of these "z-axis oriented fibers" was similar to those of
the "x-axis" and "y-axis" oriented fibers. The resulting highly
porous, resilient, bi-axially stretched and contracted,
self-cohered, bioabsorbable, polymeric web material of the present
invention possessed physical and handling characteristics similar
to fabrics commonly referred to as "fleece."
[0150] The properties of the bi-axially stretched and contracted
fleece web material were determined per the methods described in
Example 9 and are compared to the second biaxially stretched web of
Example 8 in Table 10 below: TABLE-US-00010 TABLE 10 Property
Example 9 Example 8 Area Weight (mg/cm.sup.2) 5.13 3.37 Thickness
(mm) 2.11 0.94 Volume Density (g/cm.sup.3) 0.024 0.036 Porosity
(%)in the 98 97 absence of additional components Void/Solids Ratio
49 32
[0151] FIG. 4 is a scanning electron micrograph (SEM) showing
filaments of these materials oriented in multiple directions
following the stretching process. Under ten-times (10X)
magnification, a number of the filaments appeared to be oriented in
a direction perpendicular (z-axis) to the other filaments oriented
along the x and y axes of the material. On visual inspection, the
thicker articles of the present invention had a fleece-like
appearance having a deep pile, high degree of loft, and very high
percent porosity.
Example 10
[0152] This example describes the formation of articles of the
present invention by stretching precursor web material radially in
all directions simultaneously. Both single and multiple layered
precursor web materials were radially stretched in this example. In
some embodiments, these multiple layered precursor web materials
became laminated together in the finished web material.
[0153] In each embodiment, at least one piece of a 67:33-PGA:TMC
precursor web material made according to Example 1 was cut into
circular pieces having an initial diameter of six (6) inches (15.24
cm). Embodiments utilizing multiple layers of precursor web
material were formed by placing several layers of the precursor web
material together prior to cutting. For each embodiment, the
circular material was restrained in a clamping apparatus capable of
stretching the precursor web material in all directions at an equal
rate within a temperature controlled environment.
[0154] In each embodiment, eight clamps were placed equidistant
around the periphery of the particular precursor web material
approximately one-half (0.5) inch in from the edge of the web
material. This effectively reduced the initial diameter of the
precursor web material from six (6) inches to five (5) inches (12.7
cm). The clamped precursor web material was preheated at a
temperature of 50.degree. C. for approximately two (2) minutes to
raise the precursor web material above the order-disorder
temperature (T.sub.odt) of the particular polymer system used to
make the precursor web material. The softened precursor web
material was then stretched at a rate of 0.25 inches/second until
the web had a diameter of twelve (12) inches (30.48 cm). The
four-layered material was stretched to a final diameter of 14
inches (35.56 cm) at the same stretch rate. While retained in the
stretched configuration, the stretched web material was heated to
120.degree. C. for two (2) to three (3) minutes to heat-set the
stretched web material.
[0155] The parameters of layers, precursor web material area
weights, and stretch ratios (final diameter/initial diameter) of
each article are listed in Table 11, below. The total area weight
of the precursor web material is the product of the precursor layer
area weight and the number of layers. For example, the gross
precursor area weight of article 10-2 was about 90 mg/cm.sup.2 (2
layers.times.45 mg/cm.sup.2). Article 10-6 was produced to a
uniform appearance, but was not quantitatively tested. Also listed
in the table is the area weight of the finished stretched web.
TABLE-US-00011 TABLE 11 Area Weight Precursor Layer Area Stretch of
Stretched Article ID Layers Weight (mg/cm.sup.2) Ratio Web
(mg/cm.sup.2) 10-1 1 45 2.8 3.68 10-2 2 45 2.4 9.43 10-3 2 22 2.8
5.87 10-4 2 10 2.8 2.75 10-5 4 10 2.8 5.40 10-6 6 45 2.4 Not
measured
[0156] FIG. 4A is a scanning electron micrograph (SEM) showing
filaments of a radially stretched self-cohered web material of the
present invention. The image, which depicts filaments oriented
radially in multiple directions following the stretching process,
is of an alternative embodiment fabricated from 50% PGA:50% TMC
copolymer.
Example 11
[0157] This example provides a compilation of porosity values
observed in various embodiments of the present invention.
Initially, precursor web materials as described in Example 1 were
prepared at belt speeds of 7.9, 14.0, 20.4, and 48.0 cm/min,
annealed under restraint, and then evaluated for volume density and
percent porosity. The percent porosity values were determined by
controlling the height of the finished web material with a glass
microscope slide and an optical comparator as described in Example
8. Stretched web materials of the present invention having the
highest percent porosity values were obtained with a belt speed of
48.0 cm/min.
[0158] Appropriately sized samples of precursor web materials were
either transversely stretched as described within Example 1 or
bi-axially stretched as described in either Example 8 or 9. The
precursor web material and several finished stretched web materials
were then evaluated for average percent porosity. The percent
porosity results and accompanying processing parameters are
presented in Table 12. As seen from Table 11, the highest percent
porosity possessed by the precursor web material was 89.7%.
Accordingly, all stretched, self-cohered, web materials of the
present invention have percent porosity values of at least ninety
percent (90%). TABLE-US-00012 TABLE 12 Porosity of Various
Precursor and Stretched Web Structures Percent porosity in Belt
Stretch Ratio the absence Fabrication Speed Transverse of
additional Method BS (cm/min) or y-axis x-axis components (Example
#) Precursor 48 n.a. n.a. 89.7 1 Biaxial 7.9 6:1 3.6:1 97.3 8
Biaxial 20.4 6:1 3.6:1 96.8 8 Biaxial - 7.9 6:1 3.6:1 98.1 9 Fleece
Uniaxial 7.9 5:1 89.8 1 Uniaxial 7.9 6:1 90.7 1 Uniaxial 7.9 7:1
91.8 1 Uniaxial 13 5:1 92.5 1 Uniaxial 13 6:1 92.7 1 Uniaxial 13
7:1 90.9 1 Uniaxial 14 6:1 94.0 1 Uniaxial 20 4:1 90.7 1 Uniaxial
20 5:1 92.2 1 Uniaxial 20 6:1 93.2 1 Uniaxial 20 8:1 94.4 1
Uniaxial 48 5:1 94.6 1
[0159] As seen in Table 12, the percent porosity increased for all
embodiments of the stretched web material of the present when
compared to precursor web materials made by the present inventors
to have as high a percent porosity as possible with currently
available technology.
Example 12
[0160] This example describes the formation of an article of the
present invention in a tubular form (FIG. 13).
[0161] In this example, a tubular article able to stretch in a
radial direction was formed utilizing a mandrel combination
equipped with means for longitudinal extension of a wrapped tube
formed from an unset precursor web. The utilized combination is
composed of a smaller rigid rod or tube ("mandrel") that can be at
least partially contained within the inside diameter of a
circumferential means for affixing the ends of the wrapped tube. At
least one end of the tube is then slid by manual or mechanical
means along the axis of the mandrel to effect the desired
longitudinal expansion ratio. Alternatively, once the tube is
formed and attached to the circumferential fixation, the mandrel
can be removed and expansion accomplished through tensile
extension.
[0162] Articles were formed by wrapping an approximately five inch
(12.7 cm) length of an unannealed precursor web material (.about.9
mg/cm.sup.2) made as described within Example 1 around both a
three-eighths inch (0.953 cm) diameter metal mandrel and a portion
of the circumferential fixation sufficient to allow later physical
attachment. Wrapping was achieved by slightly overlapping the
opposing edges to form a "cigarette wrap." This step was repeated
with offset seams to produce a multi-layered (i.e., 2-10 layers (5
layers preferred)) tube of unannealed precursor web material.
[0163] Attachment of the tube to the fixation means was
accomplished by affixing the overlying ends of the tube against the
circumferential ridge with a copper wire. The combination was then
placed in a preheated oven set at a temperature of 50.degree. C.
for approximately two (2) minutes to soften the unset polymeric
material. The softened material was then stretched longitudinally
at a ratio of approximately 5:1. This was followed by fixing the
sliding mandrel in place heating the combination to 100C for five
(5) minutes to set (i.e., anneal or fully crystallize) the final
article.
[0164] This tubular form of the present invention displayed an
ability to change from an initial first diameter to a larger second
diameter when exposed to radial expansion forces. The tube formed
in this example was found to be readily distensible from a first
diameter to a second diameter approximately two times larger than
the first diameter.
Example 13
[0165] This example describes the formation of an article of the
present invention in a tubular form having an ability to increase
in diameter from a first initial diameter to a second larger
diameter, combined with an ability to change axial length (FIG.
17).
[0166] As in the prior example, this article was formed by
cigarette wrapping multiple layers of unannealed web around both a
three-eighths inch (0.953 cm) diameter metal mandrel and
circumferential fixation. The wrapped combination was then placed
in an oven preheated at a set temperature of 50.degree. C. for
approximately two (2) minutes to soften the unannealed polymeric
material. The softened material was then stretched longitudinally
at a ratio of 5:1, the sliding fixation immobilized, and the
combination heated for 1 minute in an oven set to 100.degree. C.
The combination was removed and opposite ends of the now stretched
tubular form were urged toward each other to a length approximately
half that if the original extension distance so as to compact the
material along its-length in an "accordion-like" fashion. The
combination containing this "corrugated" tubular material was then
heated to 130.degree. C. for five (5) minutes to impart a complete
set to the final article. Upon completion and removal of the
article from the fixation, the article was observed to retain the
corrugated structure, evidencing partial crystallization at the
100.degree. C. treatment conditions.
[0167] In addition to having the ready ability to change diameter
when exposed to radial expansion forces, the article described in
this example was also able to change in length. In addition, this
article was more flexible and exhibited greater resistance to
kinking when bent into a curved conformation than the article
described in the previous Example, supra.
Example 14
[0168] This example describes the formation of an article of the
present invention in a tubular form having at least one framework
component incorporated into the article (FIG. 16).
[0169] A two layered fully set first tubular form was constructed
as described in Example 12, trimmed to approximately four inches in
length, and then left on the mandrel without overlapping onto the
circumferential fixation. A 0.020 inch (0.051 cm) diameter copper
wire was then wound in a helical manner around the outer surface of
the tubular form with approximately 0.25 inch (0.635 cm) spacing
between windings. A second tubular form made of precursor web
material approximately 5 inches (12.7 cm) wide was then closely
wrapped over both the wire-wound first tubular form and a portion
of the circumferential fixation sufficient to allow its physical
attachment. The combination was then wrapped with an overlying
sacrificial polytetrafluoroethylene (ePTFE) pipe-tape style film.
Longitudinal stretching of the tubular form was then undertaken as
previously described at a 5:1 stretch ratio to effect tube
extension simultaneous with a reduction of the tubes inner
diameter. This process effectively compressed the outer tube into
intimate contact with the underlying metallic coil and inner tube.
This wrapped construct was then heated to 100.degree. C. for five
(5) minutes to heatset the article. The sacrificial PTFE film was
removed from the finished article.
[0170] The article thus produced was a metallic coil encased within
both overlying and underlying layers of a flexible stretched,
non-woven, self-cohered PGA:TMC tube. This construction could serve
as an implantable intravascular medical device, such as a stent or
stent graft.
Example 15
[0171] This example describes the formation of a stretched
self-cohered web material of the present invention in the form of a
rope or flexible rod (FIG. 14).
[0172] In this example, a stretched rope or flexible rod
self-cohered filamentous form was formed by longitudinally pulling
and axially twisting a length (2.54 cm wide.times.25.4 cm long) of
unannealed, unstretched, precursor web material (9 mg/cm.sup.2) to
a point of tactile resistance. The length of precursor material was
extended approximately 15.25 cm (6 inches) and twisted
approximately ten (10) times. The material was then stretched along
its longitudinal axis at a stretch ratio greater than 2:1. In this
example the precursor web material was both twisted and stretched
by manual means, but mechanical methods may be also be used.
[0173] The article was then restrained in its twisted form and
heated in an oven set to a temperature of 50.degree. C. for 1
minute, removed, and then promptly stretched along its longitudinal
axis to a distance twice that of its original length. The article
was then restrained in its stretched form and then heated in an
oven set to 100.degree. C. for 5 minutes to heatset (i.e., anneal
or fully crystallize) the final article.
[0174] The finished article appeared to be a highly flexible rod or
rope that visually appeared to possess a continuous pore structure
through its cross section.
Example 16
[0175] This example describes the formation of a web material of
the present invention having a very low volume density and very
high percent porosity (FIG. 19).
[0176] While a porous stretched web material from any of the
above-described examples is suitable for use as a starting material
for this very high percent porosity material, a web material made
according to Example 1 at a 6:1 stretch ratio and an area density
of 40-50 mg/cm.sup.2 was obtained and used as the starting web
material in this example.
[0177] The starting web material was subjected to a carding
procedure by laying the web material flat onto a granite surface
plate, restraining the web material by hand, and repeatedly
abrading the filaments of the web material in a random fashion with
a wire brush. As the filaments of the web material were abraded, at
least some of the filaments of the web were engaged and separated
by the wires of the brush. As the filaments were separated, the
percent porosity of the web material increased and the volume
density decreased. The visual appearance of the finished carded web
material was similar to a "cotton ball."
[0178] In another embodiment, at least one metallic band is
attached to the web material (FIGS. 19A and 19B). The metallic
bands can serve as radio-opaque markers to aid in visualizing the
web material during and after implantation.
[0179] As described in Example 17, this material has been shown to
be thrombogenic and provide hemostasis in a variety of
circumstances. For example, the carded web material of the present
invention can stop, or significantly reduce, bleeding at an
incision site in a major blood vessel, such as a femoral artery.
Bleeding can also be stopped or significantly reduced in puncture
wounds, lacerations, or other traumatic injuries. The carded web
material described in this example can also be used to fill an
aneurysm or occlude a blood vessel or other opening in the body of
an implant recipient.
[0180] The highly porous web material described herein can be
combined with a delivery system (FIG. 20), such as a catheter, to
aid in placement of the web material at an indirectly accessible
anatomical site.
[0181] This web material can also be used as a component of an
implantable medical device to assist in providing a liquid seal for
the device against an anatomical structure or tissue.
Example 17
[0182] This example describes the use of a very highly porous web
material of the present invention to stop bleeding in an artery of
an implant recipient.
[0183] Using a domestic porcine model that had previously been
heparinized, an eight French (8F) guiding catheter was used to
selectively access the cranial branch of the left renal artery. An
angiogram was performed for baseline imaging and the guide wire
removed. A 6F guide catheter containing a combination of an
approximately 7 mm diameter by 20 mm long piece of web material
made according to Example 16 was then introduced into the
vasculature of the implant recipient through the length of the 8F
catheter. The web material of Example 16 contained a radio-opaque
marker band to assist in remotely visualizing the present invention
during and after implantation (FIG. 20).
[0184] The marked web material of Example 16 was then deployed into
the cranial branch of the above-mentioned left renal artery from
the 6F catheter. Following implantation of the marked web material
in the renal artery, partial occlusion of the blood vessel was
observed, via angiogram, within thirty seconds. Full occlusion of
the blood vessel was observed at three (3) minutes post deployment.
Occlusion was interpreted to be caused by coagulation of blood in
the vessel at the implantation site, despite the presence of the
heparin.
[0185] A second procedure was performed on this implant recipient
to demonstrate the ability of the web material of Example 16 to
stop blood flow at an arterial incision site. A femoral laceration
was created with a partial transaction of the femoral artery. The
artery was occluded proximally, so only retrograde flow was
present. Despite this condition bleeding at the incision site was
profuse. Two cotton ball size pieces of the web material of Example
16 were then applied to the arteriotomy and held under digital
pressure for approximately 30 seconds. Though there was some
initial seeping of blood through the ball, the bleeding was
completely stopped at two minutes.
Example 18
[0186] Swine and canine with normal activated clot times (ACT) used
for other acute vascular patency studies were used in this Example
for a model of an organ laceration-injury. In order to induce organ
laceration, a 13 mm diameter puncture was made in the liver or
spleen of the implant recipient with a modified trephine. The
puncture was allowed to bleed freely for forty-five (45) seconds.
Approximately 1 gram of the highly porous web material described in
Example 16 was applied by hand into the puncture with compression
for one (1) minute. Pressure was then released and the wound
evaluated for bleeding. If bleeding did not cease, pressure was
re-applied for another minute and the evaluation repeated.
[0187] As a comparison, a commercially available chitosan-based
haemostatic material (HEMCON; HemCon Inc., Portland, Oreg.) was
examined in the same organ laceration model. Both the highly porous
web material described in Example 16 and the HEMCON material
successfully produced haamostasis after 1 minute compression. The
ease of handling and implantation of the present invention was
considered superior to the HEMCON product.
[0188] Though the web material of Example 16 is in a "cotton
ball-like" form, other forms of the highly porous web material can
be used for hemostasis and other medical circumstances requiring
thrombogenic results. These forms include, but are not limited to,
rolls or wads of the web material. The high compressibility of the
present invention allows for efficient packaging of the
invention.
Example 19
[0189] This example demonstrates the thrombogenic properties of the
present invention through the use of a comparative in vitro blood
clotting test providing results expressed in terms of relative clot
time (RCT).
[0190] To determine an in vitro whole blood clot time for samples
of different thrombogenic materials, approximately two (2) mg of
each test sample material was obtained and individually placed in a
polypropylene microcentrifuge tube. The sample materials used in
this test were porous web materials made according to Examples 1
and 16, and two commercially available hemostatic materials,
HEMCON.RTM. chitosan bandage (HemCon Inc., Portland, Oreg.) and
HEMABLOCK.RTM. hemostatic agent microporous polysaccharide beads
(Abbott Laboratories, Abbott Park, Ill.).
[0191] FIG. 18 illustrates the steps followed for the Relative Clot
Time test. In the test, fresh unheparinized arterial blood was
collected from domestic swine and immediately mixed with sodium
citrate to a final citrate concentration of 0.0105 M. One (1) ml of
the fresh citrated blood was added to each sample tube. To
facilitate the clotting cascade, 100 .mu.l of 0.1M calcium chloride
was added to each sample tube. The tubes were immediately capped
and inverted 3 times. At each 30 second interval, the tubes were
inverted for 1 second and returned to their upright positions. The
time was recorded when blood ceased to flow in a sample tube. Each
test included a positive control (calcium+citrated blood only) and
negative control (citrated blood only). For every test, clot time
was normalized to the calcium control, with the smaller value
indicating a faster overall time to clot.
[0192] The web materials made according to both Example 1 and
Example 16 each reduced the Relative Clot Time (RCT) to a value of
approximately 0.7 when compared to the positive citrated calcium
control value of 1.0. These materials also displayed superior
results to the commercially available hemostatic products HEMCON,
with an experimentally observed RCT of 1.0. With the HEMABLOCK.RTM.
hemostatic agent powder an RCT of 0.9 was observed.
Example 20
[0193] This example describes the formation of an article of the
present invention to include a second bioabsorbable polymeric
material (FIG. 9).
[0194] In this Example, a finished 6:1 web material according to
Example 1 was obtained and imbibed with a film made of
carboxymethylcellulose (CMC). The CMC utilized was of the high
viscosity (1500-3000 cps at one percent (1%) at twenty-five degrees
centigrade (25.degree. C.)) variety available from Sigma-Aldrich
(St. Louis, Mo., USA), Catalog #C-5013. A CMC film was formed from
a gel concentration of 8 g CMC/100 ml distilled water (8% w/v). The
film had a thickness approximately equal to the thickness of the
web material to be imbibed. The film was produced by rolling a bead
of 8% CMC gel onto a flat metal plate and allowing the film to
consolidate. The CMC gel film was then placed in contact with a
similarly sized piece of web material from Example 1 and tactilely
pressed together between two suitable release surfaces for
approximately one (1) minute at room temperature. The CMC-imbibed
web material was then dried under vacuum at 40.degree. C., with an
occasional purge with air.
[0195] This process was repeated with CMC gel film placed on both
sides of the web material in a "sandwich" relationship.
[0196] When wetted with saline, water, or blood, the material
described in this example generated a concentrated gel that
displayed significant adherence that made the web readily
conformable to the topography of many physical features. Such
adherence was recognized as carrying potential to assist a surgeon,
interventionalist, or other healthcare professional in temporarily
maintaining the present invention at a particular anatomical
location, implantation site, or in approximation to a surgical
instrument or other implantable device. The CMC coating in either
dry or gel form may affect the permeation rate of various
physiological fluids into or out of the underlying web
material.
Example 21
[0197] This example describes imbibing carboxymethylcellulose (CMC)
into interstitial spaces of a finished 7:1 web material according
to Example 5, supra. To make this construction, high viscosity
sodium carboxymethylcellulose ("CMC"; Sigma Chemical Company, St.
Louis, Mo.) was dissolved in deionized water at a four percent (4%)
concentration (i.e., 4 g/100 ml) using an industrial blender.
Entrapped air was removed by centrifugation. The CMC solution was
imbibed into the finished web material (3.8 cm.times.10.2 cm) using
a roller to completely fill the porosity of the web. The
CMC-imbibed web was air dried at room temperature for sixteen hours
(16 hrs) to produce a CMC-imbibed, self-cohered, stretched PGA:TMC
web material.
[0198] When wetted with saline, water, or blood, the material
described in this example generated a concentrated gel that
displayed significant adherence that made the web material readily
conformable to the topography of many physical features. Such
adherence was recognized as carrying potential to assist a surgeon,
interventionalist, or other healthcare professional in temporarily
maintaining the present invention at a particular anatomical
location, implantation site, or in approximation to a surgical
instrument or other implantable device.
Example 22
[0199] This example describes imbibing carboxymethylcellulose (CMC)
into interstitial spaces of a finished web according to Example 16
and dissolving the imbibed CMC from the web into a phosphate buffer
saline (PBS) solution. To make this construction, 4% CMC was
imbibed into a sample of highly porous web material made according
to Example 16 using a roller to completely fill the void spaces.
The imbibed web was air dried at room temperature for sixteen hours
(16 hrs) to produce a CMC-imbibed high porosity, self-cohered,
PGA:TMC web material. The CMC-imbibed web of Example 16 was then
immersed in a PBS solution. Upon immersion, the CMC swelled to
produce a hydrogel-filled, high porosity, self-cohered PGA:TMC web
material. Upon immersion for an additional ten (10) minutes, the
CMC appeared to dissolve into the PBS and elute from the web
material.
Example 23
[0200] This example describes imbibing a carboxymethylcellulose
(CMC) into interstitial spaces of a web material according to
Example 16. To make this construction, eight percent (8%) CMC
solution was imbibed into a sample of highly porous web material
made according to Example 16 using a roller to completely fill the
void spaces of the highly porous web material. The imbibed web was
then dried under vacuum at 40.degree. C. to produce a CMC-imbibed
high porosity, self-cohered, PGA:TMC web material. Upon immersion
into PBS, the CMC swelled to produce a hydrogel-filled web. Upon
additional immersion for 10 min, the CMC dissolved and eluted from
the web material.
Example 24
[0201] This example describes imbibing carboxymethylcellulose (CMC)
into interstitial spaces of a web material according to Example 21
and cross-linking the CMC to itself within the web material. To
make this construction, a finished material according to Example 21
was obtained and subjected to chemical cross-linking as taught in
U.S. Pat. No. 3,379,720, issued to Reid, and incorporated herein by
reference. In this process, the pH of the four percent (4%) CMC
solution was adjusted to pH 4 with dropwise addition of
thirty-seven percent (37%) HCI. Once the CMC was imbibed and air
dried according to Example 20, the composite was placed in an oven
set at one hundred degrees centigrade (100.degree. C.) for one (1)
hour to induce ester crosslinks between carboxylic acid groups and
alcohol groups present on the CMC chemical backbone. The result was
a high porosity, self-cohered, stretched PGA:TMC web material with
a cross-linked CMC material contained therein.
Example 25
[0202] This example describes swelling the cross-linked CMC web
material of Example 24 in PBS. The material of Example 24 was
immersed into PBS for several minutes. Upon immersion, the CMC
swelled to produce a hydrogel-filled web. Upon additional immersion
for two (2) days, the cross-linked chemical groups of the CMC
material caused the CMC to be retained within the web. Once filled
with a cross-linked hydrogel, the web material did not permit PBS
to flow therethrough. The web material of this embodiment
functioned effectively as a fluid barrier.
Example 26
[0203] This example describes imbibing polyvinyl alcohol (PVA) into
interstitial spaces of a finished 7:1 web according to Example 5.
To make this construction, USP grade polyvinyl alcohol (PVA) was
obtained from Spectrum Chemical Company, (Gardena, Calif.). The PVA
was dissolved in deionized water at a ten percent (10%)
concentration (i.e., 10 g/100 ml) using heat and stirring.
Entrapped air was removed by centrifugation. The PVA solution was
imbibed into a web material (3.8 cm.times.10.2 cm) according to
Example 5 using a roller to completely fill the void spaces of the
highly porous web. The imbibed web was air dried at room
temperature for sixteen hours (16 hrs) to produce a PVA-imbibed,
self-cohered, PGA:TMC web material.
Example 27
[0204] This example describes imbibing polyvinyl alcohol (PVA) into
interstitial spaces of a web according to Example 26 and dissolving
the PVA from the web into a phosphate buffer saline (PBS) solution.
The PVA-imbibed web material of Example 26 was immersed in a PBS
solution. Upon immersion, the PVA swelled to produce a
hydrogel-filled, self-cohered, stretched PGA:TMC web material. Upon
immersion for an additional ten (10) minutes, the PVA dissolved
into the PBS and eluted from the web material.
Example 28
[0205] This example describes cross-linking a PVA-imbibed material
according to Example 26 with succinic acid. Once PVA was imbibed
into a web material according to Example 26, the PVA was chemically
cross-linked with succinic acid, a dicarboxylic acid, according to
the teachings of U.S. Pat. No. 2,169,250, issued to Izard, and
incorporated herein by reference.
[0206] PVA was dissolved in deionized water at a 10% concentration
(i.e., 10 g/100 ml) using heat and stirring. Succinic acid (Sigma)
was also dissolved in the PVA solution at a concentration of 2 g
per 100 ml. Entrapped air was removed by centrifugation. The
PVA-succinic acid solution was imbibed into a 7:1 web material (3.8
cm.times.10.2 cm) according to Example 5 using a roller to
completely fill the void spaces of the highly porous web. The web
material was air dried at room temperature for sixteen hours (16
hrs). The composite was placed in an oven set at one hundred forty
degrees centigrade (140.degree. C.) for fifteen (15) minutes to
induce ester crosslinks between carboxylic acid groups present on
the succinic acid and alcohol groups present on the PVA.
Example 29
[0207] This example describes cross-linking a PVA-imbibed material
according to Example 26 with citric acid. Once PVA was imbibed into
a web according to Example 26, the PVA was chemically crosslinked
with citric acid, a tricarboxylic acid, according to the teachings
of U.S. Pat. No. 2,169,250, issued to Izard, and incorporated
herein by reference.
[0208] PVA was dissolved in deionized water at a 10% concentration
(i.e., 10 g per 100 ml) using heat and stirring. Citric acid
(Sigma) was also dissolved in the PVA solution at a concentration
of 2 g per 100 ml. Entrapped air was removed by centrifugation. The
PVA-citric acid solution was imbibed into a 7:1 web material (3.8
cm.times.10.2 cm) according to Example 5 using a roller to
completely fill the void spaces of the highly porous web material.
The web material was air dried at room temperature for sixteen
hours (16 hrs). The composite was placed in an oven set to one
hundred forty degrees centigrade (140.degree. C.) for fifteen (15)
minutes to induce ester crosslinks between carboxylic acid groups
present on the citric acid and alcohol groups present on the
PVA.
Example 30
[0209] This example describes cross-linking a PVA-imbibed material
according to Example 26 with aspartic acid. Once PVA was imbibed
into a web according to Example 26, the PVA was chemically
crosslinked with aspartic acid, a dicarboxylic amino acid.
[0210] PVA was dissolved in deionized water at a 10% concentration
(i.e., 10 g/100 ml) using heat and stirring. Aspartic acid (free
acid, Sigma) was also dissolved in the PVA solution at a
concentration of 1 g per 100 ml. Entrapped air was removed by
centrifugation. The PVA-aspartic acid solution was imbibed into a
7:1 web material (3.8 cm.times.10.2 cm) according to Example 5
using a roller to completely fill the void spaces of the highly
porous web material. The web material was air dried at room
temperature for sixteen hours (16 hrs). The composite was placed in
an oven set to one hundred forty degrees centigrade (140.degree.
C.) for fifteen (15) minutes to induce ester crosslinks between
carboxylic acid groups present on the aspartic acid and alcohol
groups present on the PVA.
Example 31
[0211] This example describes cross-linking a PVA-imbibed material
according to Example 26 with carboxymethylcellulose (CMC). Once PVA
was imbibed into a web according to Example 26, the PVA was
chemically crosslinked with CMC, a polycarboxylic acid.
[0212] PVA was dissolved in deionized water at a 10% concentration
(i.e., 10 g/100 ml) using heat and stirring. CMC was also dissolved
in the PVA solution at a concentration of 1 g per 100 ml. In this
process, the pH of the one percent (1%) CMC solution was adjusted
to pH 1.5 with dropwise addition of thirty-seven percent (37%) HCIl
Entrapped air was removed by centrifugation. The PVA-CMC acid
solution was imbibed into a 7:1 web material (3.8 cm.times.10.2 cm)
according to Example 5 using a roller to completely fill the void
spaces of the highly porous web material. The web material was air
dried at room temperature for sixteen hours (16hrs). The composite
was placed in an oven set to one hundred forty degrees centigrade
(140.degree. C.) for fifteen (15) minutes to induce ester
crosslinks between carboxylic acid groups present on the CMC and
alcohol groups present on the PVA.
Example 32
[0213] This example describes swelling the hydrogel component of
the constructions of Examples 28-31 in PBS. Upon immersion of each
of these constructions in a PBS solution, the PVA swelled to
produce hydrogel-filled web materials of the present invention.
Upon additional immersion for two (2) days, the PVA was intact
within all web materials due to the presence of the above-mentioned
chemical cross-linkages. Each hydrogel-filled web material was
observed to prevent movement of PBS across the web material.
Example 33
[0214] This example describes imbibing PLURONIC.RTM. surfactant
into interstitial spaces of a web material according to Example 5.
PLURONIC.RTM. surfactant is a copolymer of polyethylene glycol and
polypropylene glycol, available from BASF (Florham Park, N.J.).
Certain grades of PLURONIC.RTM. surfactant form gels when immersed
in warm biological fluids, such as grade F-127, as taught in U.S.
Pat. No.5,366,735, issued to Henry and incorporated herein by
reference. Grade F-127 PLURONIC.RTM. surfactant was dissolved in
dichloromethane at a concentration of 5 g per 5 ml.
[0215] The F-127 solution was imbibed into a 7:1 web material (3.8
cm.times.10.2 cm) according to Example 5 using a roller to
completely fill the void spaces of the highly porous web material.
The imbibed web material was dried at sixty degrees centigrade
(60.degree. C.) for five (5) minutes. The imbibed web material was
immersed in PBS, prewarmed to 37.degree. C. Upon immersion, the
F-127 swelled to produce a hydrogel-filled web material. Upon
immersion for an additional 1 day at 37.degree. C., the F-127
dissolved and eluted from the web material.
Example 34
[0216] This example describes the incorporation of a bioactive
species into the hydrogel material of a web material according to
Example 21 (FIG. 9A). Dexamethasone (Sigma, St. Louis) was
dissolved at a concentration of 10 mg/100 ml in deionized water.
Four grams of high viscosity CMC was added to the solution using an
industrial blender. Entrapped air was removed by centrifugation.
The CMC/dexamethasone solution was imbibed into the finished web
using a roller, and was air dried at room temperature for 16 hrs.
Upon immersion into PBS, the CMC swells and the dexamethasone was
observed to elute from the hydrogel.
Example 35
[0217] This example describes the incorporation, with physical
crosslinking, of a bioactive species into the hydrogel material of
a web material according to Example 21. Dexamethasone phosphate
(Sigma, St. Louis) was dissolved at a concentration of 10 mg/100 ml
in deionized water. Four grams of high viscosity CMC was added to
the solution using an industrial blender. Entrapped air was removed
by centrifugation. The CMC/dexamethasone phosphate solution was
imbibed into the finished web using a roller, and was air dried at
room temperature for 16 hrs. Upon immersion into PBS, the CMC
swells and the dexamethasone phosphate was observed to elute from
the hydrogel, at a rate slower than in Example 34, due to physical
acid/base complexation between the basic dexamethasone phosphate
and the acidic CMC.
Example 36
[0218] This example describes the incorporation, with chemical
crosslinking, of a bioactive species into the hydrogel material of
a web material according to Example 24. Dexamethasone (Sigma, St.
Louis) was dissolved at a concentration of 10 mg/100 ml in
deionized water. Four grams of CMC was added to the solution using
an industrial blender. The pH of the dexamethasone/CMC solution was
adjusted to pH 4 with dropwise addition of thirty-seven percent
(37%) HCl. Once the dexamethasone/CMC solution was imbibed and air
dried according to Example 20, the composite was placed in an oven
set at one hundred degrees centigrade (100.degree. C.) for one (1)
hour to induce ester crosslinks between carboxylic acid groups and
alcohol groups present on the CMC chemical backbone, and between
carboxylic acid groups present on the CMC and alcohol groups
present on the dexamethasone. Upon immersion into PBS, the CMC
swells and the dexamethasone was observed to elute from the
hydrogel, at a rate slower than in Example 35, due to chemical
ester-bond formation between the dexamethasone and the CMC.
Example 37
[0219] This example describes the incorporation, with chemical
crosslinking, of a bioactive species into the hydrogel material of
a web material according to Example 28. Dexamethasone (Sigma, St.
Louis) was dissolved at a concentration of 10 mg/100 ml in
deionized water.
[0220] PVA was dissolved in the deionized water at a 10%
concentration (i.e., 10 g/100 ml) using heat and stirring. Succinic
acid (Sigma) was also dissolved in the PVA solution at a
concentration of 2 g per 100 ml. Entrapped air was removed by
centrifugation. The dexamethasone-PVA-succinic acid solution was
then imbibed into a 7:1 web material (3.8 cm.times.10.2 cm)
according to Example 5 using a roller to completely fill the void
spaces of the highly porous web. The web material was air dried at
room temperature for sixteen hours (16 hrs). The composite was
placed in an oven set at one hundred forty degrees centigrade
(140.degree. C.) for fifteen (15) minutes to induce ester
crosslinks between carboxylic acid groups present on the succinic
acid and alcohol groups present on the PVA, and between carboxylic
acid groups present on the succinic acid and alcohol groups present
on the dexamethasone. In this manner, the dexamethasone was
chemically linked via ester bonds to the succinic acid, which in
turn was chemically linked via ester bonds to the PVA. Upon
immersion into PBS, the PVA swelled and the dexamethasone was
observed to elute from the hydrogel at a slow rate, due to ester
bond formation between the dexamethasone and the succinic
acid/PVA.
Example 38
[0221] This example describes the formation of an article of the
present invention to include an added material in combination with
a stretched bioabsorbable web. (FIG. 12).
[0222] A series of holes (0.5 cm) were cut in two rectangular
pieces of solvent cast film composed of 85% d,I-PLA-co-15% PGA
copolymer (available from Absorbable Polymers, Pelham, Ala., USA).
A similarly sized rectangular piece of finished 6:1 web material
according to Example 1 was obtained and placed between the two
pieces of the film material and pressed together at elevated
temperature and time sufficient to provide for both the softening
and penetration of the PLA:PGA copolymer into the interstices of
the Example 1 web. The resulting laminate composite possessed areas
where the enclosed web material was regionally exposed by the film
holes. Dependent on the applied pressure, temperature, and utilized
film and web thicknesses, the porosity of the web between the
opposing film layers may or may not become filled. Alternatively,
the film, with or without holes, may be applied to a single surface
of the provided web. When exposed to aqueous conditions at
37.degree. C., the film component imparts a malleable stiffness
that facilitates the web construct's tactile manipulation and
maintenance in a desired non-planar form prior to implantation.
[0223] The composition of the described laminate component or
components may be selected from either absorbable or non-absorbable
natural or synthetic materials with desirable properties that may
additionally act as carriers for bioactive agents, and may
alternatively act as a media providing a controlled rate of release
of the contained bioactive substance or substances. The described
laminate composite may alternatively be affixed by various
available means to other absorbable or non-absorbable natural or
synthetic materials to elicit a biological response (e.g.,
hwmostasis, inflammation), to provide for mechanical support,
and/or as a vehicle for delivery of bioactive agents.
Example 39
[0224] This example describes the construction of a composite
material comprising a material of the present invention in
combination with a pledget material (FIG. 10). The material of the
present invention aids in holding the pledget material in place on
a stapling apparatus during a surgical procedure (FIGS. 10A and
10B).
[0225] Two finished porous 6:1 stretched self-cohered web materials
according to Example 1 were obtained, cut into similarly sized
rectangular shapes with a pattern-following laser, and layered
together to form a pouch between the layers. A pattern-following
laser was also used to cut a rectangular-shaped bioabsorbable
pledget material made of a block co-polymer of PGA:TMC (67:33
weight percent) obtained from W. L. Gore & Associates, Inc.,
Flagstaff, Ariz. The laser pattern controlled the exact dimensions
of the three pieces of web material. The laser pattern also
provided for four small alignment holes in the three pieces of web
material. The alignment holes were used to locate the individual
pieces on a mandrel and assist in welding the web materials
together. The mandrel had a square cross-sectional shape.
[0226] To construct the device, the two layered piece of porous
stretched web material was wrapped around three of the four sides
of the mandrel and held in place with locating pins placed through
the laser-cut holes. The pledget material was placed on the fourth
side of the mandrel and held in place with locating pins placed
through the laser-cut holes. Once the pieces were properly
juxtaposed, the combination was inserted onto an ultrasonic welder
and hot compression welds formed along the two long edges of the
rectangular web materials to attach the porous stretched web
material to the pledget material. The welds were approximately
0.025 cm in width. The final form of the construction was generally
tubular in shape with a substantially square cross-section. The
ultrasonic weld was sufficiently strong to hold the pledget
material on the stapling apparatus during manipulation of the
pledget material, while remaining sufficiently frangible to allow
the pledget material and the porous stretched web material to
separate when a pulling force is-applied to-the -porous stretched
web material.
[0227] To aid in separating the pledget material from the porous
stretched web material, a pull cord made of polyethylene
terephthalate (PET) was attached to the porous stretched web
material prior to the above-recited ultrasonic welding process. A
pull-tab was provided to the free end of the pull cord. Following
construction of the composite material, the attached pull cord was
coiled and stored in the pouch with the pull tab exposed.
[0228] In a similar embodiment, perforations were made in the
pledget material adjacent to the ultrasonic welds to aid in
separating the pledget material from the porous stretched web
material.
Example 40
[0229] This example describes the construction of a composite
material comprising a material of the present invention in
combination with a non-bioabsorbable material (FIG. 15). In this
embodiment, the bioabsorbable material occupies an area distinct
from the non-bioabsorbable material of the composite. In
particular, this composite material of the present invention is
useful as an implantable dental device where the non-bioabsorbable
portion of the device can remain in the body of an implant
recipient, while the bioabsorbable portion disappears from the body
of the implant recipient in a foreseeable time period. In this
embodiment, a second implantable dental device can be placed in the
area of the present invention originally occupied by the
bioabsorbable portion of the invention.
[0230] A finished 6:1 web material according to Example 1 was
obtained and cut into an oval shape approximately 0.5 cm
wide.times.0.75 cm long. A rectangular piece of medical grade
porous expanded polytetrafluoroethylene (ePTFE) with rounded
corners was obtained from W. L. Gore & Associates, Inc.,
Flagstaff, Ariz. The ePTFE material was 0.75 cm wide and 1.0 cm
long. A hole was cut in the ePTFE slightly smaller than the outer
dimensions of the material of Example 1. The material of Example 1
was placed over the hole and solvent bonded in place using a small
amount of a PLA:TMC/acetone solution applied along the edge of the
hole sufficient to dissolve and flow some of the Example 1 material
into the porous structure of ePTFE material. The utilized acetone
solution was composed of an approximately 20% (w/v) poly(70%
lactide-co-30% trimethylene carbonate), a copolymer commercially
available from Boehringer-lngelheim, (Ingelheim, Germany and
Petersburg, Va., USA). The composite material was briefly placed in
a heated oven below the melting point of the material of Example 1
and under reduced pressure to fully remove the acetone solvent from
the implantable medical device.
[0231] The device of this example is particularly suited for
medical situations requiring regrowth, or regeneration, of tissue
at the site of defect or injury. For example, in some dental
applications, a space is created or enlarged in jawbone as part of
a repair procedure. Unless surrounding gingival tissue is prevented
from ingrowing the space, bone will not regrow in the space as
desired. The device of this example is placed over the space in the
bone to prevent unwanted tissues from ingrowing the space, while
regrowth of desired bone tissue is fostered. With conventional
devices made of ePTFE alone, the ePTFE remains permanently at the
implantation site. In some situations, it may be desirable to place
a second implantable dental device, such as a metallic stud, in the
newly regrown bone tissue. Providing an ePTFE tissue barrier
material with a bioabsorbable material according to the present
invention would allow the bioabsorbable portion of the device to
disappear from the implantation site and leave an unobstructed path
through the ePTFE material to place a second dental implant.
Example 41
[0232] This example describes the construction of a composite
material of the present invention having a non-bioabsorbable
component combined with a bioabsorbable component (FIG. 21). In
this example, a finished 6:1 bioabsorbable web material as
described in Example 1 is bonded to a porous expanded
polytetrafluoroethylene material to form an implantable sheet. The
sheet can be used as a replacement, or substitute, for a variety of
anatomical membranes. In particular, these membranes are useful as
substitutes for dura and other membranes of the nervous system.
[0233] A bioabsorbable material according to Example 1 was obtained
and overlaid on a thin ePTFE sheet material having delicate fibrils
and spacious pore volumes. The ePTFE material was made according to
U.S. Pat. No. 5,476,589 issued to Bacino, which is incorporated
herein by reference.
[0234] The two sheets of material were solvent bonded together
using the previously described PLA:TMC/acetone solution. Once
bonded, the acetone was removed under heat and vacuum. The result
was a composite sheet material suitable for use as an implantable
medical device.
Example 42
[0235] This example describes the use of a porous, self-cohered,
stretched web material of the present invention as an external
supportive wrap for an anatomical structure or organ (FIG. 11). The
wrap can also be used at an anastomotic site to minimize leakage
and tissue adhesions.
[0236] In this example, a tissue compatibility study was performed
in a group of animals. In the study, a piece of a porous,
self-cohered, stretched web material made according to Example 1
was cut into a rectangular piece 2 cm.times.5 cm. The finished
uni-axially 6:1 stretched web material of Example 1 exhibited an
ability to elongate in the longer dimension of the web (i.e., 10
cm). A control material made from non-bioabsorbable materials was
obtained from W. L. Gore & Associates, Inc., Flagstaff, Ariz.
under the tradename PRECLUDE.RTM. Dura Substitute (PDS).
[0237] Two sites on each colon of eight (8) New Zealand White
rabbits were used for the tests. At a distal site approximately 5
cm from the anus, a piece of one of the test materials was wrapped
around the colon. Five centimeters further up the colon, more
proximal, another piece of test material, different from the first
piece, was wrapped around the colon. The materials formed sleeves
around the serosa of the colon and were tacked in place with
GORE-TEX.RTM. Sutures.
[0238] At the end of seven (7) days and thirty (30) days, all of
the animals were sacrificed and the various materials retrieved
intact. The particular segment of the wrapped colon with any
accompanying adhesions were immersed in 10% neutral buffered
formalin for paraffin histology. Adhesions to the materials were
scored.
[0239] Upon gross evaluation and histologic analysis of the web
material of the present invention showed incorporation of the web
material in the serosa at seven (7) days. The web material of the
present invention was well incorporated to the serosa of the colon
as well as to the surrounding adhesions day thirty-one (31). The
web material of the present invention was seen to be highly
vascularized at both seven (7) and thirty-one (31) days. The PDS
was not incorporated into the serosa at seven (7) or thirty-one
(31) days nor had the material become vascularized.
[0240] The use of a web material of the present invention in
combination with a coating of a bioabsorbable adhesion barrier
material such as partially crosslinked polyvinyl alcohol (PVA),
carboxymethylcellulose or hyaluronic acid biomaterial might be
advantageous.
* * * * *