U.S. patent application number 13/309504 was filed with the patent office on 2012-03-29 for post-biopsy cavity treatment implants and methods.
Invention is credited to Ary S. Chernomorsky, Simon Chernomorsky, James W. Vetter.
Application Number | 20120076733 13/309504 |
Document ID | / |
Family ID | 34521136 |
Filed Date | 2012-03-29 |
United States Patent
Application |
20120076733 |
Kind Code |
A1 |
Chernomorsky; Ary S. ; et
al. |
March 29, 2012 |
POST-BIOPSY CAVITY TREATMENT IMPLANTS AND METHODS
Abstract
A post-biopsy cavity treatment implant includes a radiopaque
element, a core portion and a shell portion. The core portion is
coupled to the radiopaque element, and includes a first porous
matrix defining a first controlled pore architecture. The shell
portion is coupled to the core portion and includes a second porous
matrix defining a second controlled pore architecture that is
different from the first controlled pore architecture.
Inventors: |
Chernomorsky; Ary S.;
(Walnut Creek, CA) ; Vetter; James W.; (Portola
Valley, CA) ; Chernomorsky; Simon; (Orinda,
CA) |
Family ID: |
34521136 |
Appl. No.: |
13/309504 |
Filed: |
December 1, 2011 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
12806890 |
Aug 23, 2010 |
8092779 |
|
|
13309504 |
|
|
|
|
12256619 |
Oct 23, 2008 |
7780948 |
|
|
12806890 |
|
|
|
|
12018170 |
Jan 22, 2008 |
7534452 |
|
|
12256619 |
|
|
|
|
10688289 |
Oct 16, 2003 |
7537788 |
|
|
12018170 |
|
|
|
|
10627960 |
Jul 25, 2003 |
|
|
|
10688289 |
|
|
|
|
Current U.S.
Class: |
424/9.3 ;
424/400; 424/423; 424/484; 424/9.1; 623/23.72 |
Current CPC
Class: |
A61P 17/02 20180101;
A61B 2090/3908 20160201; A61B 2017/00654 20130101; A61K 49/04
20130101; A61B 2090/3925 20160201; A61L 31/146 20130101; A61B 90/39
20160201; A61B 2090/3987 20160201; A61B 17/0057 20130101; A61L
31/18 20130101 |
Class at
Publication: |
424/9.3 ;
424/400; 424/9.1; 424/423; 424/484; 623/23.72 |
International
Class: |
A61K 49/18 20060101
A61K049/18; A61K 49/00 20060101 A61K049/00; A61F 2/02 20060101
A61F002/02; A61K 9/00 20060101 A61K009/00 |
Claims
1. A post-biopsy cavity treatment implant, comprising: a radiopaque
element; a core portion coupled to the radiopaque element, the core
portion including a first porous matrix defining a first controlled
pore architecture, and a shell portion coupled to the core portion,
the shell portion including a second porous matrix defining a
second controlled pore architecture that is different from the
first controlled pore architecture.
2. The post-biopsy cavity treatment implant of claim 1, wherein the
core portion surrounds the radiopaque element.
3. The post-biopsy cavity treatment implant of claim 1, wherein the
shell portion surrounds the core portion.
4. The post-biopsy cavity treatment implant of claim 1, wherein the
core portion surrounds the radiopaque element and the shell portion
surrounds the core portion.
5. The post-biopsy cavity treatment implant of claim 1, wherein the
shell portion swells faster than the core portion when the implant
is placed in a biological fluid environment.
6. The post-biopsy cavity treatment implant of claim 1, wherein the
shell portion swells to a greater extent than the core portion when
the implant is placed in the biological fluid environment.
7. The post-biopsy cavity treatment implant of claim 1, wherein the
first controlled pore architecture differs from the second
controlled pore architecture with respect to at least one of: pore
density, pore shape, pore orientation and pore dimensions.
8. The post-biopsy cavity treatment implant of claim 1, wherein the
radiopaque element includes a portion having a paramagnetic
property.
9. The post-biopsy cavity treatment implant of claim 1, wherein at
least one of the core and shell portions includes a dye disposed
therein.
10. The post-biopsy cavity treatment implant of claim 1, wherein at
least one of the core and shell portions includes a pigment
disposed therein.
11. The post-biopsy cavity treatment implant of claim 1, wherein at
least one of the core and shell portions includes a contrast medium
disposed therein.
12. The post-biopsy cavity treatment implant of claim 1, wherein at
least one of the core and shell portions includes a therapeutic
agent disposed therein.
13. The post-biopsy cavity treatment implant of claim 1, wherein at
least one of the core and shell portions is biodegradable.
14. The post-biopsy cavity treatment implant of claim 1, wherein at
least the shell portion includes collagen.
15. The post-biopsy cavity treatment implant of claim 1, wherein
the core portion includes at least one of a polylactide (PLA), a
polyglycolide (PGA), a poly(lactide-co-glycolide) (PLGA), a
polyglyconate, a polyanhydride, PEG, cellulose, a gelatin, a lipid,
a polysaccharide, a starch and a polyorthoester.
16. The post-biopsy cavity treatment implant of claim 1, wherein
the core and shell portions are configured so as to form a laminar
structure.
17. The post-biopsy cavity treatment implant of claim 1, wherein at
least one of the core and shell portions is echogenic.
18. The post-biopsy cavity treatment implant of claim 1, wherein at
least the shell portion includes a plurality of fibers.
19. The post-biopsy cavity treatment implant of claim 1, wherein at
least one of the core and shell portions includes an internal
reservoir configured to contain at least one of a dye, a pigment
and a therapeutic agent.
20. The post-biopsy cavity treatment implant of claim 19, wherein
the internal reservoir is configured to deliver the at least one of
dye, pigment and therapeutic agent through elution when the implant
is placed in a biological fluid environment.
21. The post-biopsy cavity treatment implant of claim 19, wherein
the internal reservoir is configured to deliver the at least one of
dye, pigment and therapeutic agent at a first rate when the
reservoir is breached and at a second rate that is lower than the
first rate when the reservoir is not breached.
22. The post-biopsy cavity treatment implant of claim 1, wherein
the shell portion is configured to swell to a greater degree than
the core portion when the implant is placed in the biological fluid
environment.
23. The post-biopsy cavity treatment implant of claim 1, wherein
the shell portion includes collagen and wherein a crosslinking
density of the shell portion is controlled through adding a
selected amount of a bifunctional reagent to the collagen.
24. The post-biopsy cavity treatment implant of claim 23, wherein
the bifunctional reagent includes at least one of an aldehyde and a
cyanamide.
25. The post-biopsy cavity treatment implant of claim 24, wherein
the aldehyde includes a glutaraldehyde.
26. The post-biopsy cavity treatment implant of claim 1, wherein
the shell portion include collagen and wherein a crosslinking
density of the shell portion is controlled by an application of
energy to the collagen.
27. The post-biopsy cavity treatment implant of claim 26, wherein
the application of energy includes at least one of dehydrothermal
processing, exposure to UV light and radiation.
28. The post-biopsy cavity treatment implant of claim 1, wherein
the shell portion includes collagen and wherein a crosslinking
density of the shell portion is controlled by a combination of
dehydrothermal processing and exposure to cyanamide.
29. The post-biopsy cavity treatment implant of claim 1, wherein
the implant, in a state prior to being placed in a biological fluid
environment, is generally wedge-shaped.
30. The post-biopsy cavity treatment implant of claim 1, wherein
the implant, in a state prior to being placed in a biological fluid
environment, has a shape of a disk that has been folded multiple
times.
31. The post-biopsy cavity treatment implant of claim 1, wherein
the implant, in a state prior to being placed in a biological fluid
environment, has a rectangular shape.
32. The post-biopsy cavity treatment implant of claim 1, wherein
the shell portion defines a center portion and a peripheral portion
and wherein the peripheral portion defines a plurality of
independently movable free ends.
33-62. (canceled)
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to post-biopsy cavity
treatment methods and implants. More particularly, the present
inventions relates to post-biopsy cavity treatment implants
inserted into cavities formed in soft tissue that may be created
during a biopsy or therapeutic excisional procedure.
[0003] 2. Description of the Related Art
[0004] Breast biopsies are routinely performed in the United States
following a detection of abnormalities discovered through
mammographic visualization, manual palpation or ultrasound
examination. There are a number of traditional methods to obtain
breast biopsy tissue samples, including surgical excisional
biopsies and stereotactic and ultrasound guided needle breast
biopsies. Recently, methodologies have emerged that are based upon
percutaneous minimally invasive large intact tissue sample
collection. The use of these devices results in a unique cavity
connected to the skin by a narrow neck. For example, such cavities
may generally resemble an igloo. It is becoming apparent that the
post-biopsy cavities left within the patient by such procedures may
benefit from different post procedure treatment methods and
implants, as compared to the post-procedure treatment methods and
implants (if any) conventionally employed to treat cavities left by
needle, core biopsy procedures or open surgical procedures. In
part, this need for new post-procedure methods and implants is
driven by the different nature, size and shape of the cavity
created by such emerging percutaneous minimally invasive large
intact tissue sample collection methods and devices.
[0005] In certain cases, locating a previously biopsied area is
highly desirable. Therefore, to mark the biopsy site, a variety of
biopsy site markers and identifiers have been developed, ranging
from metal clips to pellets and sponges placed during or right
after the biopsy procedure. Usually, these markers contain
radiopaque and/or echogenic articles and include features such as
metal clips and air or gas bubbles incorporated in a biodegradable
matrix. However, existing markers are believed to be unsuited to
the unique size and shape of some cavities, in that they do not
adequately fill the cavity, do not adequately promote tissue
ingrowth, and are not easily visualizable, among other
disadvantages. It has become apparent, therefore, that new
post-biopsy and post-procedure cavity implants and treatment
methods are needed that are better suited to the percutaneous
minimally invasive large intact tissue sample collection methods
and devices that are currently gaining favor in the medical
community.
SUMMARY
[0006] The present invention, according to an embodiment thereof,
is a post-biopsy cavity treatment implant. The post-biopsy cavity
treatment implant, according to an embodiment thereof, may include
a radiopaque element; a core portion coupled to the radiopaque
element, the core portion including a first porous matrix defining
a first controlled pore architecture, and a shell portion coupled
to the core portion, the shell portion including a second porous
matrix defining a second controlled pore architecture that is
different from the first controlled pore architecture.
[0007] The core portion may surround the radiopaque element. The
shell portion may surround the core portion. Alternatively still,
the core portion may surround the radiopaque element and the shell
portion may surround the core portion. The shell portion may swell
faster than the core portion when the implant is placed in a
biological fluid environment (or other aqueous environment). The
shell portion may swell to a greater extent than the core portion
when the implant is placed in the biological fluid environment. The
first controlled pore architecture may differ from the second
controlled pore architecture with respect to at least one of: pore
density, pore shape, pore orientation and/or pore dimensions. The
radiopaque element may include a portion having a paramagnetic
property. The core and/or shell portions may include a dye disposed
therein. The core and/or shell portions may include a pigment
disposed therein. The core and/or shell portions may include a
contrast medium disposed therein. The core and/or shell portions
may include a therapeutic agent disposed therein. The core and/or
shell portions may be biodegradable. At least the shell portion may
include collagen. The core portion may include a polylactide (PLA),
a polyglycolide (PGA), a poly(lactide-co-glycolide) (PLGA), a
polyglyconate, a polyanhydride, PEG, cellulose, a gelatin, a lipid,
a polysaccharide, a starch and/or a polyorthoester, for example.
The core and shell portions may be configured so as to form a
laminar structure. The core or the shell portion may be echogenic.
At least the shell portion may include a plurality of fibers. The
core and/or shell portions may include an internal reservoir
configured to contain a dye, a pigment and/or a therapeutic agent,
for example. The internal reservoir may be configured to deliver
the dye, pigment and/or therapeutic agent through elution when the
implant is placed (e.g., implanted) in a biological fluid
environment. The internal reservoir may be configured to deliver
the dye, pigment and/or therapeutic agent at a first rate when the
reservoir is breached and at a second rate that is lower than the
first rate when the reservoir is not breached. The shell portion
may be configured to swell to a greater degree than the core
portion when the implant is placed in the biological fluid
environment. The shell portion may include collagen and a
crosslinking density of the shell portion may be controlled through
adding a selected amount of a bifunctional reagent to the collagen.
The bifunctional reagent may include, for example, an aldehyde
and/or a cyanamide. The aldehyde may include a glutaraldehyde, for
example. The shell portion may include collagen and a crosslinking
density of the shell portion may be controlled by an application of
energy to the collagen. The application of energy may include
dehydrothermal processing, exposure to UV light and/or radiation,
for example. The shell portion may include collagen and a
crosslinking density of the shell portion may be controlled by a
combination of dehydrothermal processing and exposure to cyanamide,
for example. The implant, in a state prior to being placed in a
biological fluid environment, may be generally wedge-shaped. The
implant, in a state prior to being placed in a biological fluid
environment (e.g., in a pre-implantation state), may have a
rectangular shape or the shape of a disk that may have been folded
multiple times. The shell portion may define a center portion and a
peripheral portion and the peripheral portion may be configured to
define a plurality of independently movable free ends.
[0008] According to another embodiment thereof, the present
invention is also a post-biopsy cavity treatment implant that may
include one or more radiopaque elements, a core portion coupled to
the radiopaque element(s), the core portion(s) including a first
porous matrix defining a first controlled pore architecture, the
core portion including a polylactide (PLA), a polyglycolide (PGA),
a poly(lactide-co-glycolide) (PLGA) and/or a polyglyconate (for
example), and a collagenous shell portion coupled to the core
portion, the collagenous shell portion including a second porous
matrix defining a second controlled pore architecture that is
different from the first controlled pore architecture.
[0009] The core portion may surround the radiopaque element. The
shell portion may surround the core portion. Alternatively still,
the core portion may surround the radiopaque element and the shell
portion may surround the core portion. The core portion may be
configured to biodegrade at a first controlled rate and the
collagenous shell portion may be configured to biodegrade at a
second controlled rate that is higher than the first controlled
rate when the implant is placed in the biological fluid environment
(e.g., implanted). The radiopaque element(s) may include a portion
having a paramagnetic property. The core and/or collagenous shell
portions may include a dye, a pigment, a contrast medium or media
and/or a therapeutic agent disposed therein. The core portion
further may include a polyanhydride, PEG, cellulose, a gelatin, a
lipid, a polysaccharide, a starch and/or a polyorthoester, for
example. The core and collagenous shell portions may be configured
so as to form a laminar structure. The core or the shell portion
may be echogenic. At least the collagenous shell portion may
include a plurality of fibers. The core and/or collagenous shell
portions may include an internal reservoir configured to contain at
least one of a dye, a pigment and a therapeutic agent, for example.
The internal reservoir may be configured to deliver the dye,
pigment and/or therapeutic agent through elution when the implant
is placed in a biological fluid environment. The internal reservoir
may be configured to deliver the dye, pigment and/or therapeutic
agent at a first rate when the reservoir is breached and at a
second rate that is lower than the first rate when the reservoir is
not breached. The collagenous shell portion may be configured to
swell to a greater degree than the core portion when the implant is
placed in a biological fluid environment. A crosslinking density of
the collagenous shell portion may be controlled through adding, for
example, a selected amount of a bifunctional reagent to the
collagen. The bifunctional reagent may include an aldehyde and/or a
cyanamide, for example. The aldehyde may include a glutaraldehyde,
for example. A crosslinking density of the collagenous shell
portion may be controlled by an application of energy to the
collagen, for example. The application of energy may include
dehydrothermal processing, exposure to UV light and radiation, for
example. A crosslinking density of the shell portion may be
controlled by a combination of dehydrothermal processing and
exposure to cyanamide. The implant, in a state prior to being
placed in a biological fluid environment (e.g., prior to
implantation in a patient), may be generally wedge-shaped. The
implant, in a state prior to being placed in a biological fluid
environment, may have a rectangular shape or the shape of a disk
that has been folded multiple times. The shell portion may define a
center portion and a peripheral portion and the peripheral portion
may define a plurality of independently movable free ends.
[0010] The present invention, according to yet another embodiment
thereof is also a method of treating a cavity created by a
percutaneous excisional procedure carried out through an incision.
The method may include steps of providing a post-procedure cavity
implant, the post-procedure cavity implant including a radiopaque
element; a core portion coupled to the radiopaque element, the core
portion including a first porous matrix defining a first controlled
pore architecture, and a shell portion coupled to the core portion,
the shell portion including a second porous matrix defining a
second controlled pore architecture that is different from the
first controlled pore architecture; implanting the post-procedure
cavity implant into the cavity, and closing the incision.
[0011] According to yet another embodiment, the present invention
may be viewed as a method of treating a cavity created by an
excisional procedure that includes steps of selecting a first
biodegradation rate range; selecting a second biodegradation rate
range that is different from the first biodegradation rate range;
providing a post-procedure cavity implant, the post-procedure
cavity implant including a radiopaque element; a core portion
coupled to the radiopaque element, the core portion being
configured to biodegrade at a first effective rate within the first
biodegradation rate range, and a shell portion coupled to the core
portion, the shell portion being configured to biodegrade at a
second effective rate within the second biodegradation rate range,
and implanting the post-procedure cavity implant within the
cavity.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] For a further understanding of the objects and advantages of
the present invention, reference should be made to the following
detailed description, taken in conjunction with the accompanying
figures, in which:
[0013] FIG. 1 shows an exemplary large intact specimen percutaneous
biopsy device in operation.
[0014] FIG. 2 shows further aspects of the exemplary large intact
specimen percutaneous biopsy device of FIG. 1 in operation.
[0015] FIG. 3 shows further aspects of the exemplary large intact
specimen percutaneous biopsy device of FIG. 1 in operation.
[0016] FIG. 4 shows still further aspects of the exemplary large
intact specimen percutaneous biopsy device of FIG. 1 in
operation.
[0017] FIG. 5 shows further aspects of the exemplary large intact
specimen percutaneous biopsy device of FIG. 1 in operation.
[0018] FIG. 6A shows further aspects of the exemplary large intact
specimen percutaneous biopsy device of FIG. 1 in operation, and
illustrates the creation of a cavity within the soft tissue from
which the excised specimen was taken.
[0019] 6B is a cross sectional view of the post treatment cavity of
FIG. 6A, taken along cross-sectional line II'.
[0020] FIG. 7 shows further aspects of the exemplary large intact
specimen percutaneous biopsy device of FIG. 1 in operation, and
further illustrates the creation of a cavity within the soft tissue
from which the specimen was taken, with the aforementioned narrow
neck or access path connecting the cavity to the skin.
[0021] FIG. 8 shows an exemplary delivery device for a post-biopsy
cavity treatment implant, according to an embodiment of the present
invention.
[0022] FIG. 9 shows the delivery device of FIG. 8 in operation,
delivering a post-biopsy cavity treatment implant according to an
embodiment of the present invention within the cavity of FIG.
7.
[0023] FIG. 10A shows the cavity of FIG. 7, after the implantation
of the post-biopsy cavity treatment implant shown in FIGS. 8 and 9,
with the percutaneous incision closed.
[0024] FIG. 10B shows the cavity of FIG. 7, after the implantation
of the post-biopsy cavity treatment implant shown in FIGS. 8 and 9
in another orientation, with the percutaneous incision closed.
[0025] FIG. 10C shows the cavity of FIG. 7, after the implantation
of a post-biopsy cavity treatment implant according to another
embodiment of the present invention, with the percutaneous incision
closed.
[0026] FIG. 11 shows a post-biopsy cavity treatment implant having
a predetermined pore architecture, according to an embodiment of
the present invention.
[0027] FIG. 12 shows another post-biopsy cavity treatment implant
having another predetermined pore architecture, according to
another embodiment of the present invention.
[0028] FIG. 13A shows a post-biopsy cavity treatment implant that
includes a plurality of fibers, according to another embodiment of
the present invention.
[0029] FIG. 13B shows a cross-section of a post-biopsy cavity
treatment implant, according to another embodiment of the present
invention.
[0030] FIG. 13C shows a portion of another post-biopsy cavity
treatment implant, according to a further embodiment of the present
invention.
[0031] FIG. 13D shows another post-biopsy cavity treatment implant,
according to still another embodiment of the present invention.
[0032] FIG. 13E shows another post-biopsy cavity treatment implant,
according to still another embodiment of the present invention.
[0033] FIG. 14A shows a post-biopsy cavity treatment implant that
includes a plurality of fibers having predetermined pore
architectures, according to another embodiment of the present
invention.
[0034] FIG. 14B shows a front view of a post-biopsy cavity
treatment implant, according to another embodiment of the present
invention.
[0035] FIG. 14C shows a portion of another post-biopsy cavity
treatment implant, according to a further embodiment of the present
invention.
[0036] FIG. 14D illustrates the stacked structure of a post-biopsy
cavity treatment implant, according to a further embodiment of the
present invention.
[0037] FIG. 14E illustrates the stacked structure of another
post-biopsy cavity treatment implant, according to a further
embodiment of the present invention.
[0038] FIG. 14F illustrates the stacked structure of a post-biopsy
cavity treatment implant, according to a further embodiment of the
present invention.
[0039] FIG. 14G illustrates the stacked structure of another
post-biopsy cavity treatment implant, according to a further
embodiment of the present invention.
[0040] FIG. 15A shows a post-biopsy cavity treatment implant that
includes a radiopaque and/or echogenic member around which one or
more fibers are wound, according to another embodiment of the
present invention.
[0041] FIG. 15B shows a post-biopsy cavity treatment implant that
includes a core portion surrounded by an outer shell portion, each
of the core and shell portions having a predetermine core
architecture, according to another embodiment of the present
invention.
[0042] FIG. 15C is a cross-sectional representation of the implant
of FIG. 15B, taken along cross-sectional line II-II'.
[0043] FIG. 15D shows a post-biopsy cavity treatment implant that
includes a core portion having a first predetermine core
architecture surrounded by an outer shell portion formed by a
plurality of wound collagenous fibers having a second predetermined
pore architecture, according to another embodiment of the present
invention.
[0044] FIG. 15E shows a post-biopsy cavity treatment implant that
includes a core portion having a first predetermine core
architecture surrounded by an outer shell portion formed by a
plurality of collagenous fibers having a second predetermined pore
architecture, according to another embodiment of the present
invention.
[0045] FIG. 15F is a cross-sectional view of the embodiment of FIG.
15D, taken along cross-sectional line I-I'.
[0046] FIG. 16 is a photomicrograph of a collagen matrix having a
predetermined pore architecture with post-biopsy cavity treatment
implants according to embodiments of the present invention may be
constructed.
[0047] FIG. 16 is a photomicrograph of a collagen matrix having a
predetermined pore architecture with post-biopsy cavity treatment
implants according to embodiments of the present invention may be
constructed.
[0048] FIG. 17 is a photomicrograph of a collagen matrix having
another predetermined pore architecture with post-biopsy cavity
treatment implants according to embodiments of the present
invention may be constructed.
[0049] FIG. 18 is a photomicrograph of a collagen matrix having
still another predetermined pore architecture with post-biopsy
cavity treatment implants according to embodiments of the present
invention may be constructed.
[0050] FIG. 19 is a photomicrograph of a collagen matrix having a
still further predetermined pore architecture with post-biopsy
cavity treatment implants according to embodiments of the present
invention may be constructed.
[0051] FIG. 20 is a photomicrograph of a collagen matrix having yet
another predetermined pore architecture with post-biopsy cavity
treatment implants according to embodiments of the present
invention may be constructed.
[0052] FIG. 21 combination of photomicrographs of collagen matrices
illustrating the formation of a stacked laminate structure
including a first layer having a first predetermined pore
architecture and a second layer having a second predetermined pore
structure, according to an embodiment of the present invention.
[0053] FIG. 22 is a combination of photomicrographs of collagen
matrices that collectively illustrate a post-biopsy cavity
treatment implant having a predetermined pore density gradient
and/or predetermined graduated crosslinking gradient, according to
a further embodiment of the present invention.
[0054] FIG. 23 is a combination of photomicrographs of collagen
matrices that collectively illustrate a post-biopsy cavity
treatment implant according to another embodiment of the present
invention.
[0055] FIG. 24 shows a post-biopsy cavity treatment implant that
includes a core portion surrounded by an outer shell portion, the
core portion including a radiopaque element and the core and shell
portions having mutually different and predetermined pore
architectures, according to another embodiment of the present
invention.
[0056] FIG. 25 shows the post-biopsy cavity treatment implant of
FIG. 24 loaded into an exemplary delivery device, according to an
embodiment of the present invention.
[0057] FIG. 26 shows a post-biopsy cavity treatment implant
according to a still further embodiment of the present invention,
in various stages of manufacture.
[0058] FIG. 27 shows the post-biopsy cavity treatment implant of
FIG. 26 loaded into an exemplary delivery device, according to an
embodiment of the present invention.
[0059] FIG. 28 shows the post-biopsy cavity treatment implant of
FIGS. 26 and 27 during implantation, according to an embodiment of
the present invention.
[0060] FIG. 29 shows the post-biopsy cavity treatment implant of
FIG. 28 after implantation, illustrating the manner in which the
implant may expand and/or unfold within the cavity after
implantation, according to an embodiment of the present
invention.
[0061] FIG. 30 shows a post-biopsy cavity treatment implant
according to another embodiment of the present invention, in
various stages of manufacture.
[0062] FIG. 31 shows the post-biopsy cavity treatment implant of
FIG. 30 loaded into an exemplary delivery device, according to an
embodiment of the present invention.
[0063] FIG. 32 shows a post-biopsy cavity treatment implant
according to yet another embodiment of the present invention, in a
configuration prior to folding and/or compression.
[0064] FIG. 33 shows the post-biopsy cavity treatment implant of
FIG. 32 in one of many possible folded configurations, according to
still another embodiment of the present invention.
[0065] FIG. 34 shows a core portion suitable for use in conjunction
with the present post-biopsy cavity treatment implant, according to
another embodiment of the present invention.
[0066] FIG. 35 shows a post-biopsy cavity treatment implant
incorporating the core portion of FIG. 34, according to yet another
embodiment of the present invention, in a configuration prior to
folding and/or compression.
[0067] FIG. 36 shows further core portions suitable for use in
conjunction with the present post-biopsy cavity treatment implant,
according to another embodiment of the present invention.
[0068] FIG. 37 shows a post-biopsy cavity treatment implant
incorporating the core portions of FIG. 36, according to a further
embodiment of the present invention, in a configuration prior to
folding and/or compression.
[0069] FIG. 38 shows another core portion suitable for use in
conjunction with the present post-biopsy cavity treatment implant,
according to another embodiment of the present invention.
[0070] FIG. 39 shows an exemplary radiopaque element suitable for
use in conjunction with the present post-biopsy cavity treatment
implant, according to a still further embodiment of the present
invention.
[0071] FIG. 40 shows another radiopaque element suitable for use in
conjunction with the present post-biopsy cavity treatment implant,
according to yet another embodiment of the present invention.
[0072] FIG. 41 shows a post-biopsy cavity treatment implant,
according to a further embodiment of the present invention, in a
configuration prior to folding and/or compression.
[0073] FIG. 42 shows a post-biopsy cavity treatment implant,
according to another embodiment of the present invention, in a
configuration prior to folding and/or compression.
DESCRIPTION OF EMBODIMENTS OF THE INVENTION
[0074] FIGS. 1-7 show aspects of a percutaneous method for cutting,
collecting and isolating a tissue specimen and the subsequent
creation of a cavity within which embodiments of the present
inventions may be implanted. The excisional device shown in FIGS.
1-7 is described in commonly assigned U.S. Pat. No. 6,022,362 and
in copending and commonly assigned patent application Ser. No.
10/189,277 filed on Jul. 3, 2002, the disclosure of each being
incorporated herein in its entirety. Although embodiments of the
present invention are described relative to a cavity created by the
excisional device shown in FIGS. 1-7, it is to be understood that
the present inventions are not to be limited thereby. Indeed,
embodiments of the present invention may be advantageously utilized
to treat cavities of various shapes and sizes created by other
devices, including devices that obtain tissue specimen through
coring or ablation techniques, for example.
[0075] As shown in FIG. 1, the excisional device 100 is introduced
into a mass of tissue 110 through the skin 102, with the integrated
cut and collect assembly 112 thereof in a retracted position. The
device 100 is then advanced such that the assembly 112 is adjacent
to the target lesion 108. The assembly 112 may then be energized
and expanded as shown in FIG. 2 by acting upon the actuator 118. As
the assembly 112 is RF energized and expanded, it cuts the tissue
through which it travels. As shown at FIG. 3, the excisional device
100 may then be rotated, while the assembly 112 remains energized,
causing the leading edge thereof to cut through the tissue,
preferably with clean margins. The expanded integrated cut and
collect assembly 112 deploys the membrane 114 and the cut specimen
108 is collected in the open bag formed by the close-ended deployed
flexible membrane 114. As shown in FIGS. 4 and 5, the rotation of
the device 100 may then be continued as needed, preferably under
ultrasonic guidance. To fully sever the specimen 108 from the
surrounding tissue 110, the assembly 112, while still energized, is
retracted to capture, encapsulate and isolate the specimen 108
within the flexible membrane 114. As shown in FIG. 6A, the specimen
108 may then be recovered by retracting the device 100 through the
retraction path 127, stretching it as necessary. FIG. 7 shows a
fully retracted device 100, containing a collected and isolated
specimen 108.
[0076] As shown in FIGS. 6A-7, after the procedure described above
or after any procedure in which a substantial volume of tissue
specimen is taken, a void or cavity 126 is created where the tissue
specimen 108 used to be. Cavities as shown at 126 may require
different post procedural treatments, as compared to procedures
such as needle biopsies due to the different nature, size and shape
created by the biopsy device. As shown in FIGS. 6A and 6B, the
exemplary cavity 126 is characterized by a relatively narrow access
path 127 that emerges into a larger cavity chamber 128 formed by
the extension and rotation of the cut and collect assembly 112
during the above-described procedure. After the device 100 is
withdrawn from the patient as shown in FIG. 7, portions of the
cavity 126 and/or access path 127 may settle and collapse somewhat,
as the interior tissue walls defining the cavity 126 are no longer
supported by the tissue previously occupying that space.
[0077] Treating the post-biopsy cavity 126 is desirable for a
variety of reasons. One such reason is to accommodate the unique
size and shape of the cavity 126 created by the device 100. It is
desirable to influence and/or promote the healing process of the
cavity, and to do so in a predictable manner. One aspect of
influencing the healing process of the cavity 126 is promoting the
growth of new connective tissue within the cavity 126 in a
predictable manner. Indeed, it is desirable to influence and
promote both tissue ingrowth within the cavity and to influence the
formation of hematomas and seromas. Another reason for treating the
post-biopsy cavity 126 is to modify it in such a manner as to
render it recognizable immediately and preferably long after the
procedure that created the cavity 126. The cavity 126, left
untreated, may be visible under ultrasound. However, that may not
be the case and it is believed to be desirable to at least
partially fill the cavity 126 with a cavity treatment implant that
will render the cavity 126 clearly visible under various imaging
modalities, including modalities such as ultrasound, X-ray, MRI,
elastography, microwave and the unaided eye, for example. Such
visibility may be due to the structure of a cavity treatment
implant or devices implanted within the cavity and/or a
recognizable pattern of tissue ingrowth caused or influenced by the
continuing or past presence of post-biopsy cavity treatment
implants disclosed herein. Other desirable attributes of
embodiments of the implantable post-biopsy cavity treatment implant
of the present invention include hemostasis, and the ability to
deliver one or more therapeutic agents to the patient at the
post-biopsy cavity treatment implant site such as, for example,
lido/epi, Non-Steroidal Anti-Inflammatory Drugs (NSAIDS), tissue
growth factors, anti-neoplastic medications (to name a few) or
combinations of the above and/or others. Filling the cavity 126 may
have other benefits, including cosmetic. Indeed, filling the cavity
and promoting a smooth, gradual, recognizable and orderly tissue
ingrowth pattern may prevent dimpling, skin depressions and the
like sometimes associated with the removal of a large intact
specimen during the biopsy procedure. Embodiments of the present
invention may also find utility in augmentation or reconstructive
procedures for the breast or other soft tissue.
[0078] According to an embodiment of the present invention, the
post-biopsy cavity treatment implant may have a size and a shape
that at least partially fills the cavity. Advantageously, the
present post-biopsy cavity treatment implant, after insertion, may
have a characteristic shape that is readily perceptible and
recognizable through various modalities, including, for example,
ultrasound, X-ray or MRI. The shape of the present post-biopsy
cavity treatment implant may also influence the manner in which
tissue growths therein. Preferably, embodiments of the present
post-biopsy cavity treatment implant should be shaped and
dimensioned so as to uniquely accommodate the size and shape of the
cavity 126 created by the device 100 of FIGS. 1-7. However,
embodiments of the present invention may be readily sized and
shaped to specifically accommodate cavities of any shape and size
created by other devices and/or biopsy or therapeutic surgical
procedures.
[0079] According to an embodiment thereof, the present invention
may include an implantable post-biopsy cavity treatment implant
having one or more of the structures, characteristic and properties
described herein. As shown in FIG. 8, the implantable post-biopsy
cavity treatment implant 802, in a pre-implanted state, may be
loaded into an introducer, an illustrative example of which is
shown at reference numeral 804. The introducer 804 may then be
inserted into the tissue 110 through the access path 127 and at
least partially into the cavity chamber 128 of the cavity 126. The
post-biopsy cavity treatment implant 802 may then be delivered to
the cavity 126 and thereafter be left in place and the introducer
804 withdrawn. The pre-implanted state of the post-biopsy cavity
treatment implant 802 is preferably a state in which the
post-biopsy cavity treatment implant occupies its minimum volume.
According to an embodiment of the present invention, the
pre-implanted state of the post-biopsy cavity treatment implant 802
is an at least partially lyophilized (e.g., at least partially
dehydrated) state and the post-biopsy cavity treatment implant may
be configured to swell when placed within a biological fluid
environment such as the cavity 126. The post-biopsy cavity
treatment implant 802 may define a proximal portion 806 that is
closest to the access path 127 and a distal portion 808 that is
relatively further away from the access path 127 than is the
proximal portion 806.
[0080] Whereas FIG. 9 shows the present post-biopsy cavity
treatment implant 802 immediately after implantation in tissue
(i.e., still in a state in which it occupies its minimum volume),
FIG. 10A shows the state of the present post-biopsy cavity
treatment implant 802 a short period of time after implantation. As
shown, the post-biopsy cavity treatment implant 802 is no longer in
its pre-implanted state. Indeed, the post-biopsy cavity treatment
implant 802, having been placed in a biological fluid environment
(such as the patient's tissue), begins to swell. According to an
embodiment of the present invention, the post-cavity treatment
implant 802 may be configured to swell in a uniform manner. In
another example, the surgeon may inject fluids after placing the
device with the intent to "wet" the present post-cavity treatment
implant. Substances such as saline, fibrin solution or other
catalyst or activator may be used for that purpose. The activator
or swelling fluid could be injected preferentially at the proximal
portion 806 or selectively at points in the post-cavity treatment
implant to cause it to secure itself in position inside the cavity
126. Alternatively, as part of the insertion device (such as, for
example, the introducer 804), an integral vial may be crushed by
the surgeon to release the activating fluid (for example, an
aqueous solution, dye/pigment) in the area of the proximal portion
806 for example, thus causing rapid swelling of that region.
Alternately, the introducer 804 may define an internal lumen 811
over its length and may include a fluid injection port 812 at the
proximal end of the device. Fluids such as the aforementioned
saline or fibrin may then be introduced into the cavity 126 through
the fluid injection port 812 and the internal lumen 811 to cause
the rapid swelling of the implant or for any other reason.
Delivering such fluids can be especially useful if the field within
the cavity is relatively dry as can occur in the ideal case.
According to another embodiment of the present invention, the
post-biopsy cavity treatment implant 802 may be configured to swell
non-uniformly. Such non-uniform swelling rates may be advantageous
in insuring that the post-biopsy cavity treatment implant 802 stays
where it is placed during the implantation procedure. In the
embodiment shown in FIG. 10A, the post-biopsy cavity treatment
implant 802 is structured such that the rate at which the proximal
portion 806 swells faster than the rate at which the distal portion
808 swells. When implanted in a cavity 126 such as shown in FIGS.
6A, 6B, 7, 9 and 10, the proximal portion 806 swells faster than
the distal portion 808, thereby serving to maintain the post-biopsy
cavity treatment implant 802 within the cavity chamber 128 of the
cavity 126. This may be achieved by, for example, controlling the
crosslinking densities or creating a gradient of crosslinking
densities within the post-biopsy cavity treatment implant 802,
where certain regions of the post-biopsy cavity treatment implant
802 are controlled to have a greater crosslinking density than
other regions, resulting in a non-uniform swelling pattern over the
extent of the device 802. For example, the distal portion 808 may
be configured to be relatively more crosslinked than the proximal
portion 806 thereof, resulting in the proximal portion 806 swelling
more and/or faster than the distal portion 808. As the proximal
portion 806 of the post-biopsy cavity treatment implant 802 swells,
it preferably swells from a shape in which it is easily implantable
through the access path 127 to a shape and size wherein at least
the proximal portion 806 thereof no longer fits through the access
path 127. As this swelling occurs rapidly after the post-biopsy
cavity treatment implant 802 comes into contact with the fluids
present within the cavity 126, the surgeon may retract the
introducer 804 from the cavity 126, close the initial incision and
be confident that the post-biopsy cavity treatment implant 802 has
remain in its intended position, squarely within the cavity chamber
128 of the cavity 126, and has not migrated back into the access
path 127.
[0081] The post-biopsy cavity treatment implant 802 may
alternatively be structured such that its distal 808 portion swells
faster than its proximal portion 806 such as shown in FIG. 10B,
such that both the proximal and distal portions 8f the post-biopsy
cavity treatment implant swell relatively faster than the portion
thereof between the proximal and distal portions or such that the
proximal and distal portions 852, 856 of the implant 850 swell
relatively slower than a middle portion 854, as shown in FIG. 10C.
Alternatively still, the post-biopsy cavity treatment implant 802
may not have well defined proximal and distal portions and the
post-biopsy cavity treatment implant 802 may be structured such
that one portion thereof swells at a different rate than another
portion thereof, for the purpose outlined above or for different
purposes altogether--such as cavity shaping, for example. As
suggested in FIGS. 9 and 10A, 10B, the post-biopsy cavity treatment
implant 802 may be formed from a tightly rolled up sheet of
swellable material. Alternatively, the post-biopsy cavity treatment
implant 802 may be formed of stacked layers of swellable material
as shown in FIG. 10C. Alternatively still, the post-biopsy cavity
treatment implant 802 may be formed as a single unitary and
homogeneous mass of swellable material and molded or cut (stamped)
into the desired shape. Other embodiments include post-biopsy
cavity treatment implants formed of or including fibers, fibrils
and/or bundles of fibers and/or fibrils.
[0082] According to embodiments of the present invention, the
present post-biopsy cavity treatment implant may include or be
formed of biocompatible and water swellable material, such as
collagen, for example. The collagen molecule is rod-shaped triple
helix and consists of a three polypeptide chains coiled about each
other. Besides the central triple helical region of the collagen
molecule, there are terminal peptides regions known as
telopeptides. These telopeptides are non-helical and are subdivided
into two groups; namely, amino terminals and carboxyl terminals.
Intermolecular crosslinking between triple helical molecules of
collagen occurs in the telopeptides regions. Crosslinking may also
occur within the central triple helical region of the collagen
molecule, and is known as intramolecular crosslinking. It is the
control of the formation and density of such crosslinks that is
responsible for some of the mechanical, physicochemical and
biological properties of the embodiments of the present post-biopsy
cavity treatment implant disclosed herein.
[0083] The embodiments of the present post-biopsy cavity treatment
implant may be selectively biodegradable and/or bio-absorbable such
that it degrades and/or is absorbed after its predetermined useful
lifetime is over. An effective way of controlling rate of
biodegradation of embodiments of the present post-biopsy cavity
treatment implant is to control and selectively vary the number and
nature (e.g., intermolecular and/or intramolecular) of crosslinks
in the implant material. Control of the number and nature of such
collagen crosslinks may be achieved by chemical and/or physical
means. Chemical means include the use of such bifunctional reagents
such as aldehyde or cyanamide, for example. Physical means include
the application of energy through dehydrothermal processing,
exposure to UV light and/or limited radiation, for example. Also, a
combination of both the chemical and the physical means of
controlling and manipulating crosslinks may be carried out.
Aldehydes such as glutaraldehydes, for example, are effective
reagents of collagenous biomaterials. The control and manipulation
of crosslinks within the collagenous matrix of the present
post-surgery cavity treatment implant may also be achieved, for
example, through a combination of dehydrothermal crosslinking and
exposure to cyanamide. For example, the present post-surgery cavity
treatment implant may, through proper control of the crosslinking
density within the collagen matrix thereof, be designed and
implemented to remain long term in situ at the implant site within
the cavity 126. Crosslinking density may be indirectly measured,
for example, via measurement of the swelling ratio where identical
dry and wetted samples are weighted and weight is compared.
[0084] According to further embodiments of the present invention,
the post-biopsy cavity treatment implant may be formed of or
include other biomaterials such as, for example, bioresorbable
poly(ester)s such as polylactide (PLA), polyglycolide (PGA),
poly(lactide-co-glycolides) (PLGA), polyglyconate, polyanhydrides
and their co-polymers, PEG, cellulose, gelatins, lipids,
polysaccharides, starches and/or polyorthoesters and the like.
According to an embodiment of the present invention, the present
post-biopsy cavity treatment implant may be formed of or include
collagen having a predetermined structure. Such predetermined
structure refers not only to the overall shape of the implant, but
also to the structure of its internal collagen matrix. Indeed,
embodiments of the present invention include a macroporous
cross-linked polymer matrix having a predetermined pore
architecture. A "pore", as the term is used herein, includes a
localized volume of the present post-biopsy cavity treatment
implant that is free of the material from which the post-biopsy
cavity treatment implant is formed. Pores may define a closed and
bounded volume free of the material from which the post-biopsy
cavity treatment implant is formed. Alternatively, pores may not be
bounded and many pores may communicate with one another throughout
the internal matrix of the present post-biopsy cavity treatment
implant. The pore architecture, therefore, may include closed and
bounded voids as well as unbounded and interconnecting pores and
channels. The internal structure of the post-biopsy cavity
treatment implant according to embodiment of the present invention
defines pores whose dimensions, shape, orientation and density (and
ranges and distributions thereof), among other possible
characteristics are tailored so as to maximize the visibility of
the resultant post-biopsy cavity treatment implant 802 under
various modalities, notably ultrasound and X-ray, for example.
Unlike polymeric matrices that contain bubbles of gas through a
process in which gas is forced through a dispersion in a hydrated
state, embodiments of the present post-biopsy cavity treatment
implant have an internal structure that defines internal voids
without requiring such gas to be forced therethrough. There are
numerous methods and technologies available for the formation
collagenous matrices of different pore architectures and
porosities. By tailoring the dimensions, shape, orientation and
density of the pores of the present implant, a recognizable pattern
of post-biopsy cavity treatment implant material may be formed that
may be readily visualized under, for example, ultrasound, X-ray,
elastography or microwave radiation. This recognizable pattern may
then influence the pattern of tissue ingrowth within the cavity
126, forming a porous scaffold on and within which tissue may
infiltrate and grow. In turn, this pattern of tissue ingrowth may
be readily recognizable under ultrasound and/or other imaging
modalities discussed above long after the post-biopsy cavity
treatment implant has been absorbed by the body or has
degraded.
[0085] According to an embodiment of the present invention, the
post-biopsy cavity treatment implant may be formed of or include a
collagen matrix having a predetermined pore architecture. For
example, the post-biopsy cavity treatment implant may include one
or more sponges of lyophilized collagen having a predetermined pore
architecture. Suitable collagen material for the post-biopsy cavity
treatment implant may be available from, for example, DEVRO,
Integra Life Sciences, Collagen Matrix and Kensey Nash, among
others. The present post-biopsy cavity treatment implant, after
implantation in the cavity 126, swells on contact with various body
fluids therein and substantially fills a predetermined portion or
the entire biopsied cavity, and does so in predictable manner.
[0086] Such a post-biopsy cavity treatment implant may be
configured to have a hemostatic functionality to stop bleeding
within the cavity 126 through a biochemical interaction with blood
(such as coagulation) and/or other bodily fluids. The post-biopsy
cavity treatment implant may, according to further embodiments,
also be used to medically treat the patient. That is, the porous
matrix of the present post-biopsy cavity treatment implant may be
imbibed or loaded with a therapeutic agent to deliver the agent
through elution at the cavity 126. Such a therapeutic agent may
include, for example, an antibiotic agent, an analgesic agent, a
chemotherapy agent, an anti-angiogenesis agent or a steroidal
agent, to name but a few of the possibilities.
[0087] The post-biopsy cavity treatment implant 802 shown in FIGS.
9 and 10 may be formed of one or more thin sheets of collagen
material having a predetermined (and controlled) pore architecture
that has been rolled up into a cylinder shape. As the post-biopsy
cavity treatment implant 802 swells with water from the cavity 126,
it may unroll partially or entirely, and at least partially fill
the cavity 126, including at least a portion of the cavity chamber
128. Some of the access path 127 may also be filled as the
post-biopsy cavity treatment implant 802 swells. The post-biopsy
cavity treatment implant 802, according to embodiments of the
present invention, has a predetermined pore architecture or a
combination of predetermined pore architectures, as will be
described hereunder with reference to the drawings. The description
of the figures below assumes that the post-biopsy cavity treatment
implant is formed of or contains collagen, it being understood that
the embodiments of the present invention disclosed herein are not
limited to collagen and that aspects of the present inventions may
readily be applied to such non-collagen containing post-biopsy
cavity treatment implants.
[0088] FIG. 11 shows a post-biopsy cavity treatment implant 1100
having predetermined pore architectures, according to an embodiment
of the present invention. As shown therein, the post-biopsy cavity
treatment implant 1100 may include a first portion 1102 and a
second portion 1104. The collagen matrix of the first portion 1102
of the device 1100 defines a plurality of pores 1106 having a first
predetermined pore architecture and the collagen matrix of the
second portion 1104 of the device 1100 defines a plurality of pores
1108 having a second predetermined pore architecture. The
dimensions of the layers or portions may be selected at will,
preferably accounting for the dimensions of the cavity into which
the device is to be inserted. As shown, the first pore architecture
features pores 1106 that are relatively small, have a narrow pore
size distribution and are substantially randomly oriented. In
contrast, the second pore architecture features pores 1108 that
have a relatively larger size, have a wider pore size distribution,
are predominantly oriented along the axis indicated by
double-headed arrow 1110 and are less densely distributed than the
pores 1106 of the first portion 1102 of the post-biopsy cavity
treatment implant 1100. Between the first and second portions 1102
and 1104 lies the interface 1103. As shown, the post-biopsy cavity
treatment implant 1100 may be formed of a first collagen matrix
having a first predetermined pore architecture and a second
collagen matrix having a second pore architecture. The two collagen
matrices may each be formed from separate collagen dispersions,
each of which may be caused to form pores having predetermined
characteristics and may each be at least partially lyophilized and
formed (e.g., molded, cut or stamped) into the desired shape (in
the illustrative case of FIG. 11, a substantially cylindrical
shape). The two collagen plugs formed thereby may then be stacked
one on the other, re-wetted and again lyophilized through a
lyophilization process in a specifically shaped mold (for example)
to form the stacked laminate structure shown in FIG. 11. Other
methods of making the post-biopsy cavity treatment implant 1100 may
occur to those of skill in this art. Not only may the predetermined
pore architectures of the first portion 1102 and of the second
portion 1104 cause these portions to be visible under, for example,
ultrasound, but the interface 1103 therebetween may also be
visualizable and recognizable under, for example, ultrasound as the
boundary between two regions having a pronounced density
differential. As can be seen, the post-biopsy cavity treatment
implant 1100 is not formed of a rolled up sheet of material, as is
the post-biopsy cavity treatment implant 802 in FIGS. 9 and 10.
Instead, the post-biopsy cavity treatment implant 1100 is formed of
solid matrices of collagenous material. It is to be understood that
the pore architecture of the first and second portions 1102, 1104
may be varied at will by, for example, changing the porosity and/or
crosslinking of the collagen chains, the pore density, the
distribution of pore size, the orientation of the pores and the
shape of the pores, to mention a few of the possible pore
parameters. By judiciously choosing the pore architectures of the
first and second portions 1102, 1104, one end of the post-biopsy
cavity treatment implant 1100 may be caused to swell at a faster
rate than the other end thereof. This is the case illustrated in
FIG. 10.
[0089] Moreover, the cross-sectional characteristics of the
post-biopsy cavity treatment implant 1100 may be changed. For
example, the first portion 1102 may form a cylindrical inner core
of collagenous material having a first predetermined pore
architecture and the second portion 1104 may form a cylindrical
outer shell around the inner core and may define a second pore
architecture. In this manner, the outer surface of the post-biopsy
cavity treatment implant 1100 may swell at a different rate (e.g.,
faster) than the rate at which the inner core swells. Moreover, the
pore architectures may be chosen to maximize not only water
absorption, but also to promote tissue ingrowth, to facilitate
imaging and/or may be tailored to contain and release a
pharmaceutical agent at a controllable rate and/or under
predetermined conditions. Alternatively, the inner core may be
formed of or include a non-collagenous material (such as a
polylactic or polyglycolic material, for example) and the outer
shell may include a collagenous material, for example. The outer
shell may include a solid matrix of collagenous material having a
predetermined pore architecture and/or may include wound fibers of
collagenous material having a predetermined pore architecture, for
example.
[0090] FIG. 12 shows a post-biopsy cavity treatment implant 1200
having predetermined pore architectures, according to another
embodiment of the present invention. As shown, the post-biopsy
cavity treatment implant 1200 includes a first portion 1202 and a
second portion 1204, each of which has a predetermined pore
architecture. It is to be noted that the present post-biopsy cavity
treatment implants may have more than the two portions shown in
both FIGS. 11 and 12 (or may define only a single portion). As
shown, the post-biopsy cavity treatment implant 1200 is shaped as a
substantially rectangular sponge. The first portion 1202 is stacked
on the second portion 1204. As with the embodiment shown in FIG.
11, the first and second portions may have pore architectures that
facilitates tissue ingrowth, wound healing and are readily
visualizable and/or recognizable under one or more imaging
modalities. The different pore architectures of post-biopsy cavity
treatment implants according to embodiments of the present
invention may also be chosen so as to maximize the visibility of
the interface (such as reference numeral 1203 in FIG. 12)
therebetween under the desired imaging modality such as, for
example, ultrasound.
[0091] Post-biopsy cavity treatment implants according to
embodiments of the present invention need not be formed as a solid
mass of collagen (FIGS. 11, 12) or as a rolled up sheet of collagen
(FIGS. 9, 10). FIGS. 13A, 13B and 13C show various other
configurations for the present implant. As shown therein,
embodiments of the present invention may include or be formed of a
bundle of fibers or fibrils 1302 of (for example) collagenous
material having one or more predetermined pore architectures. The
pores defined within the collagen matrix of all or some of the
fibers are not shown in FIGS. 13A-13C, but are nevertheless
present. The bundle 1300 of fibers shown in FIG. 13A may be used to
form post-biopsy cavity treatment implants by, for example, forming
them into a rope-like structure as shown in FIG. 13B. In the
cross-sectional representation of FIG. 13B, the longitudinal axis
of the individual constituent fibers is perpendicular to the plane
of the page on which they are printed. Post-biopsy cavity treatment
implants may also be formed from the bundle 1300 of FIG. 13A by
cutting (at 1304, for example) the bundle 1300 into a plurality of
sections at an angle that is (for example) perpendicular to the
longitudinal axis of the fibers 1302, so as to form a post-biopsy
cavity treatment implant whose constituent fibers run from one end
of the post-biopsy cavity treatment implant to the other end
thereof, as shown in the detail representation of FIG. 13C.
According to an embodiment of the present invention, a post-biopsy
cavity treatment implant may be formed of a volume of collagenous
material having a predetermined pore architecture or a combination
of several bounded volumes of collagenous materials, each with a
predetermined pore architecture. For example, several sponges
having the structure shown in FIG. 13C may be stacked onto each
other to define a laminate structure having a layered, composite
pore architecture.
[0092] FIG. 13D shows another embodiment of the present post-biopsy
cavity treatment implant. As shown, the implant 1306 includes a
first portion 1308 and a second portion 1310. According to an
embodiment of the present invention, the first portion 1308 may
include a solid matrix of collagenous material 1312 having a first
predetermined pore architecture. The second portion 1310 may
include a plurality of fibers or fibrils 1314. The plurality of
fibers may also be formed of or include collagenous material, and
this collagenous material may have the same pore architecture as
the first portion 1308 or a different pore architecture. The
plurality of fibers may be formed or include non-collagenous
material, such as polylactic or polyglycolic acid, for example. In
the case wherein the plurality of fibers 1314 are formed of a
collagenous material, after implantation in a biological fluid
environment such as a cavity within a patient, the second portion
1310 may swell at a faster rate than the first portion 1310, as the
constituent fibers 1314 thereof may be exposed to the biological
fluid environment of the cavity over their entire surface. This
swelling rate differential between the first and second portions
1308, 1310 may serve to further secure the implant 1306 within the
cavity. In the case wherein the cavity is relatively dry, the
physician may choose to introduce a volume of an aqueous solution,
such as saline, into the cavity to speed the swelling of the
implant 1306. The implant 1306 may be formed from a collagen
dispersion in a mold configured to form the first portion 1308 and
the second portion 1310 and lyophilized. Alternatively, the fibers
1314 may be formed after lyophilization by cutting the implant 1306
so as to form the plurality of fibers 1314. Alternatively still,
the first and second portions 1308, 1310 may be formed by
superimposition of the first and second portions 1310, 1310, as
discussed above. Other means of forming the first and second
portions 1310, 1312 may occur to those of skill in this art.
[0093] FIG. 13E shows another embodiment of the present post-biopsy
cavity treatment implant. As shown therein, the implant 1316 is
similar to the embodiment of FIG. 13D, but for the addition of a
third portion 1318 on another surface of the first portion 1308.
The third portion 1318 may be formed as detailed above relative to
second portion 1310. The pore architecture of the third portion
1318 may be the same as that of the first portion 1308 and the
second portion 1310, or may be different therefrom. It should be
noted that various modifications to the embodiments of FIGS. 13D
and 13E may be envisaged. For example, the embodiment of the
implant 1316 of FIG. 13E may be modified to include additional
fibers or fibrils projecting from other surfaces of the first
portion 1308. Other modifications may occur to those of skill in
this art, and all such modifications are deemed to fall within the
scope of the present invention.
[0094] FIG. 14A through 14E show other illustrative embodiments of
the post-biopsy cavity treatment implants according to the present
invention. As shown in FIG. 14A, two or more bundles of fibers of
collagenous material (for example--the fibers may be made of or
include other materials) may be used in the formation of
post-biopsy cavity treatment implants according to embodiments of
the present invention. As shown, the pores within the fibers of the
first bundle 1402 may collectively define a first pore
architecture, whereas the pores within the fibers of a second
bundle 1404 may collectively define a second pore architecture that
is different from the first pore architecture. The two bundles
1402, 1404 may then be joined together, for example, by re-wetting
the bundles, stacking them and lyophilizing the composite
structure. The length and diameter of the fibers may be selected
and varied at will. The fibers or bundles thereof may even be woven
together. From this composite structure, post-biopsy cavity
treatment implants may be formed. As shown in FIG. 14B, the bundles
of fibers may be arranged in a cylindrical shape, for example. Such
a cylindrical shape may include an inner core 1406 of fibers having
a first pore architecture and an outer shell 1408 surrounding the
inner core 1406. The outer shell may include fibers having a second
pore architecture that is different from the pore architecture of
the inner core 1406. FIG. 14C shows a detail of a post-biopsy
cavity treatment implant having a first portion 1402 of fibers
having a first pore architecture and a second portion 1404 having a
second pore architecture, formed, for example, by cutting the
composite structure of FIG. 14A at 1410. Alternatively still, the
fibers may be arranged such that the constituent fibers thereof
closer to the center of the post-biopsy cavity treatment implant
conform to a first pore architecture whereas the outside
constituent fibers thereof conform to a second pore architecture
that is different from the first pore architecture. As shown in the
exploded views of FIGS. 14D and 14E, the post-biopsy cavity
treatment implant may be have a layered laminate structure in which
sheets formed of fibers (or woven fibers) having a first pore
architecture are stacked onto sheets formed of fibers having a
second pore architecture. As shown in FIG. 14E, many variations on
this theme are possible. As shown therein, the orientation of the
fibers (and thus of the pores defined by the collagenous matrix
thereof) may be varied. For instance, whereas the fibers of the
first (top or outer, for example) portion of the post-biopsy cavity
treatment implant may be oriented in a first direction, whereas the
fibers of the second (bottom or inner, for example) portion of the
post-biopsy cavity treatment implant may be oriented along a
direction that is different from the first direction (perpendicular
thereto, for example). Imaging such post-biopsy cavity treatment
implants within a cavity (such as shown at 126 in FIGS. 9 and 10,
for example) using sonography may yield an image in which any
fluids contained in the cavity 126 may appear substantially black,
because the sound waves travel directly through such anechoic
media, and a gradation of visible structures defined by
comparatively hypoechoic layers or portions of the post-biopsy
cavity treatment implant whose echogenicity is lower than the
surrounding area and defined by hyperechoic layers or portions of
the post-biopsy cavity treatment implant whose echogenicity is
higher than the surrounding area.
[0095] FIGS. 14F and 14G illustrate the stacked structure of a
post-biopsy cavity treatment implant, according to further
embodiments of the present invention. The embodiments of FIGS. 14F
and 14G are similar to the embodiments shown in FIGS. 14D and 14E,
but for the structure of the stacked sheets of collagenous
material. In FIGS. 14F and 14G, the stacked sheets of collagenous
material are not formed of fibers or fibrils, but instead are each
formed of a solid mass of collagenous material. The sheets may have
the same or different pore architectures. Moreover, the sheets of
collagenous material may define pore architectures in which the
predominant orientation of the pores is varied. For example, some
of the sheets may have a pore architecture in which the pores are
predominantly oriented along the y-axis (FIG. 14F) or along the
x-axis (FIG. 14G), for example. Alternatively, the constituent
sheets of collagenous materials may define pore architectures in
which other pore characteristics (size, shape, density, for
example) are varied according to a predetermined pattern to
influence tissue growth, visualization, etc. The resulting laminate
structure may be formed (e.g., molded or cut) in the desired shape
of the implant. For example, the resulting laminate structure may
then be rolled into a cylindrical shape, as suggested in FIGS. 8
and 9, for example.
[0096] FIG. 15A shows a post-biopsy cavity treatment implant
according to another embodiment of the present invention. As shown,
the post-biopsy cavity treatment implant 1500 includes an inner
portion 1502 and an outer portion 1504. The inner portion 1502 may
be radiopaque. For example, the inner portion 1502 may be or
include a metallic element. The metallic element may have a simple
bar shape as shown, or may have a more complex shape such as, for
example, a ring. The inner portion 1502 may have other structures
to, for example, adhere or hook onto the walls of the cavity 126.
Wound around the inner portion 1502 is one or more fibers 1504 of
swellable (collagenous, for example) material having one or more
predetermined pore architectures and/or one or more controlled
crosslinking densities. The inner portion may be completely encased
within the wound bundles of fibers or fibrils 1504 or may be only
partially encased, as shown in FIG. 15A. The inner element 1502,
rather than being radiopaque, may have a predetermined echogenicity
so as to be immediately recognizable under ultrasound. The inner
element 1502, moreover, may include an inner reservoir configured
to contain a volume of therapeutic agent. For example, the inner
element 1502 may be bioabsorbable and may be configured to release
the contained pharmaceutical agent at a controlled rate. A
plurality of fibers 1504 (having the same or different pore
architectures) may be wound about the inner element 1502, the
windings thereof being oriented at a given inclination or mutually
different inclinations. Moreover, the embodiments of FIGS. 11
through 14E may advantageously be provided with an inner element as
shown at 1502 and/or as described immediately above.
[0097] FIG. 15B and the cross-sectional representation of FIG. 15C
show another embodiment of the present post-biopsy cavity treatment
implant. As shown therein, the implant 1506 may include a first
inner portion 1508 forming an inner core and a second outer portion
1510 forming an outer shell around the first inner portion 1508.
Both the first and second portions may be formed of or include a
collagenous material. The first portion 1508 may have a first
predetermined pore architecture and the second portion 1510 may
have a second predetermined pore architecture that is different
from pore architecture of the first portion 1508. For example, the
first portion 1508 may have a greater pore density (number of pores
per unit volume) than the second portion 1510. In the exemplary
implant 1506 shown in FIGS. 15B and 15C, the pore architecture of
the first portion 1508 is such that the collagenous material
thereof defines pores that are both smaller and more densely packed
than those defined by the collagenous material of the second
portion 1510. Although FIGS. 15B and 15C show the implant 1506 as
shaped as a right cylinder, the implant 1506 may be molded into
most any shape, to accommodate most any cavity shape. In this
manner, the implant may be configured such that its ultimate size
and shape after implantation and swelling, substantially matches
the size and shape of the cavity in which it is implanted. As shown
in the cross-sectional representation of FIG. 15C, the first
portion 1508 of the implant 1506 may define an inner reservoir 1512
(created as a void within the first portion 1508 or as a discrete
biocompatible reservoir or pouch having a predetermined
biodegradability rate). The inner reservoir 1512 may be pre-loaded
with a dye/pigment and/or a pharmaceutical agent, as indicated at
1514 in FIG. 15C. The pharmaceutical agent may be configured to
slowly release into the cavity 126 as soon as the implant is
inserted therein and/or may be configured to require a physician or
a RN to pinch or squeeze (or otherwise breach) the implant 1506 to
rupture the reservoir 1512 to release the dye/pigment and/or
pharmaceutical agent 1514 contained therein.
[0098] FIG. 15D shows another embodiment of the implant according
to the present invention. The implant 1516 includes a first portion
1508 defining a first pore architecture, such as described above
relative to FIGS. 15B and 15C. The implant 1516 may include a
reservoir 1512, and the reservoir 1512 may contain a volume of
dye/pigment and/or one or more therapeutic agents. Wound around the
first portion 1508 is one or more fibers or fibrils of collagenous
material defining a second pore architecture that may be different
from the first pore architecture. The fibers or fibrils 1520 may
completely encase the first portion 1508 or may do so only
partially, as shown in FIG. 15D. FIGS. 15E and 15F show another
embodiment of the present invention. In this embodiment, the
implant 1518 also includes a first portion 1508 defining a first
pore architecture, as described relative to FIGS. 15B-15D above. At
least partially surrounding the first portion 1508 are a plurality
of fibers or fibrils 1508 that define a second pore architecture
that may be different from the first pore architecture. Several
layers of such fibers or fibrils 1508 may be disposed around the
first portion 1508, as suggested by the cross-sectional view of
FIG. 15F.
[0099] Most any of the portions or layers of the embodiments
disclosed herein may be configured to contain one or more
dyes/pigments and/or pharmaceutical agents. The post-biopsy cavity
treatment implants discussed herein may be rendered selectively
radiopaque by the selective mechanical, chemical or physical
incorporation of a radiopaque articles or particles into the
collagenous matrix of embodiments of the present post-biopsy cavity
treatment implant. For example, the post-biopsy cavity treatment
implant may define pores having a predetermined and recognizable
architecture and may incorporate some radiopaque compound or
particles such as, for example barium sulfate or other commonly
used radiopaque or radioactive materials.
[0100] Embodiments of the present invention may also include
recognizable articles or substances within the collagenous matrix
such as, for example, dyes and/or pigments (i.e., including both
synthetic dyes and natural pigments). The dyes/pigments may be
incorporated within the collagenous dispersion that forms the
constituent layers or portions of the embodiments of the
post-biopsy cavity treatment implants disclosed herein. Such
dyes/pigments may form mapping compounds that may be gradually
released into the body upon implantation of the present
post-surgery cavity treatment implant and may form the basis of
lymphatic mapping in the future. In this manner, lymphatic mapping
may be carried out immediately after a biopsy procedure via elution
of the mapping compound (e.g., dyes/pigments and/or radioactive
agent) deposited into the collagenous matrix of the implant. In the
case wherein a cancer is detected or suspected in the tissue
specimen retrieved by the biopsy procedure, this elution of mapping
compound from the post-biopsy cavity treatment implant may enable
the physician to skip the conventional step of injecting
dyes/pigments into the patient, which dye/pigment injection step is
conventionally carried out prior to a (sentinel) lymph node status
evaluation procedure. Embodiments of the post-biopsy cavity
treatment implant according to present invention may include
metal-less dyes/pigments as well radiopaque, radioactive or
paramagnetic metal-containing dyes/pigments such as, for example,
porphyrins and/or porphyrin derivatives (such as chlorophyll and/or
chlorophyll derivatives, for example) that are bound to the
collagenous matrix. The porphyrins and/or porphyrin derivatives may
be tailored, for example, to enhance crosslinking and enhance wound
healing and/or to control biodegradation, among other reasons. A
metal with paramagnetic properties (such as Mn, for example) may be
placed within the porphyrins or porphyrin derivatives so that
another mode of recognition may be achieved. Impregnation of the
present post-biopsy cavity treatment implant with porphyrins or
porphyrin derivatives (for example, copper chlorophyllin) gives the
post-biopsy cavity treatment implant a lymphatic mapping
functionality due to the elution of the porphyrins or porphyrin
derivatives into the surrounding tissue lymphatic drainage
system.
[0101] According to other embodiments of the present invention, the
present post-biopsy cavity treatment implants may define or include
an internal reservoir configured to contain a volume of a mapping
compound and/or a beneficial therapeutic agent. Following the
biopsy procedure and the subsequent implantation of the present
post-biopsy cavity treatment implant having a predetermined pore
architecture into the biopsy cavity and following a histopathology
report on the excised biopsy specimen, the physician or RN may
pinch or squeeze the post-biopsy cavity treatment implant to
express the mapping compound(s) and/or agent(s) into the
surrounding tissue via lymphatic system to the sentinel node and
other lymphatics. In the absence of such squeezing or pinching, the
mapping compound and/or therapeutic agent may much more gradually
find its way into the surrounding tissue through elution following
a gradual biodegradation of the reservoir.
[0102] FIGS. 16-20 are photomicrographs of collagenous matrices
having various pore architectures. As shown, the porosity of the
collagenous material is not formed by bubbles forced through the
collagen dispersion prior to lyophilization thereof. Indeed, it is
the structure of the collagen material itself that creates and
defines the voids or pores (anechoic regions that appear black in
the photomicrographs) within the material. FIGS. 17 and 19 show
relatively round pores having a wide size distribution, whereas
FIGS. 16 and 18 show a relatively denser collagen matrix having a
smaller pore size distribution. FIG. 20 shows an example of a
collagenous matrix that is relatively less dense than, for example,
the matrix shown in FIG. 18.
[0103] FIGS. 21-23 are combinations of photomicrographs to
illustrate further embodiments of the post-biopsy cavity treatment
implants according to the present invention. FIG. 21 shows a
post-biopsy cavity treatment implant 2100 that includes a first
portion 2102 having a first pore architecture and, stacked thereon,
a second portion 2104 having a second pore architecture. As shown,
the pore architecture of the first portion 2102 may be
characterized as being relatively denser than the pore architecture
of the second portion 2104. Alternatively, the post-biopsy cavity
treatment implant 2100 may be structured such that the first
portion has a higher porosity (is less dense) than that of the
second portion 2104. The thicknesses of the first and second
portions 2102, 2104 may be varied at will. More than two layers of
collagenous material may be provided.
[0104] FIG. 22 shows a post-biopsy cavity treatment implant 2200
having a graduated porosity profile. Such a post-biopsy cavity
treatment implant 2200 may be formed by lining up a plurality of
collagen matrices having of progressively lower densities. That is,
matrix 2002 has the highest density (amount of collagen per unit
volume), matrix 2204 has the next highest density, matrix 2206 has
the next to lowest porosity and matrix 2208 has the lowest porosity
of the entire post-biopsy cavity treatment implant 2200.
Alternatively, the degree to which each matrix is crosslinked may
be varied and controlled. For example, each matrix may be
crosslinked to a different degree through the use of, for example,
gluteraldehyde. For example, matrix 2202 may be configured to have
about 0.0085% gluteraldehyde, matrix 2204 may be configured with
about 0.0075% gluteraldehyde, matrix 2206 may be configured with
about 0.0065% gluteraldehyde and matrix 2208 may be configured with
about 0.0055% gluteraldehyde, for example. Other concentrations are
possible, as are different reagents. After superimposing all four
such matrices 2202, 2204, 2206 and 2208, a (in this case,
piece-wise linear) cross-linking and/or porosity gradient may be
achieved across the embodiment of the present post-biopsy cavity
treatment implant shown at 2200.
[0105] FIG. 23 shows a composite post-biopsy cavity treatment
implant 2300 having a more complex structure, according to another
embodiment of the present invention. The post-biopsy cavity
treatment implant 2300 includes three distinct collagen matrices,
as shown at 2302, 2306 and 2308. As shown, each of the matrices
2302, 2306 and 2308 has a unique pore architecture. Indeed, the
portion of the post-biopsy cavity treatment implant referenced at
numeral 2302 has a dense appearance, in which the pores have a high
aspect ration and are aligned substantially parallel to the length
of the device 2300. The post-biopsy cavity treatment implant 2300
also includes a second portion 2304 that includes two unique
collagenous matrices referenced at 2306 and 2308, each having
different pore architectures. Whereas matrix 2306 features a wide
distribution of pore shapes and sizes, matrix 2308 features
comparatively larger, generally rounder pores than those of matrix
2306. Each of these matrices 2302, 2306 and 2308 may have a unique
ultrasonic or X-ray signature and/or contain dyes/pigments or
radiopaque materials or compounds. Moreover, not only may the
various matrices be visible under selected modalities, the
interfaces therebetween may also provide the physician with
position and orientation information of the post-biopsy cavity
treatment implant within the cavity. Indeed, there are distinct
interfaces between dissimilar materials between matrices 2302 and
2306, between matrices 2302 and 2308 as well as a distinct
interface between adjoining matrices 2306 and 2308, each of which
may be readily visible under, for example, ultrasound. It is to be
noted that the interfaces between the external surfaces of all
three matrices 2302, 2306 and 2308 with the surrounding tissue may
also provide the physician with additional visual clues are to the
position and orientation of the post-biopsy cavity treatment
implant 2300 within the cavity in which it is implanted. The
interfaces described herein, as well as the different rates of
swelling may be achieved through control of the porosity and/or as
through the control of crosslinking. A single post-biopsy cavity
treatment implant may include constituent portions controlled to
have a predetermined pore architecture and/or predetermined
portions having controlled crosslinking. Although the irregular
closed features within the drawings are intended to suggest pores
of various configurations and densities, they are alternatively
intended to indicate crosslinking. Therefore, illustrated
differences in these irregular closed features between adjacent
portions of an implant may also be interpreted as being differences
in crosslinking densities between adjacent portions in the
implant.
[0106] Use of the post-biopsy cavity treatment implants disclosed
herein is not limited to filling post biopsy cavities. Indeed, the
present post-biopsy cavity treatment implants also find utility in
the correction of defects caused by poorly healed cavities,
whatever their origin or cause. The present post-biopsy cavity
treatment implants may be placed in cavities in which it is desired
that the collagen matrices be replaced, over time, with (human or
animal) autogenous tissue. Hence, the embodiments of the present
invention may be used for the repair of tissue that has been
damaged due to tissue removal, thereby providing a favorable tissue
scaffold in which autogenous tissue may infiltrate and grow. In
addition, embodiments of the post-biopsy cavity treatment implants
according to the present invention may serve to absorb exudates
within the cavity, thereby further facilitating the healing
process.
[0107] FIG. 24 shows a post-biopsy cavity treatment implant 2400,
according to another embodiment of the present invention. The
post-biopsy (or, more generally, post-excisional) implant 2400
includes a radiopaque element 2402. The radiopaque element may be
formed as a clip, a staple, or may have other shapes, as discussed
herein below with reference to FIGS. 34, 36 and 38-40. The
radiopaque element 2402 may also exhibit other characteristics,
besides its visibility under X-Ray. For example, the element 2402
may have paramagnetic characteristics, to enable the implant 2400
to be visible under electron paramagnetic
resonance-spectroscopy.
[0108] Coupled to the radiopaque element 2402 is a core portion
2404. The core portion 2404 may include a first porous matrix that
defines a controlled pore architecture. The pore architecture of
the core portion 2404 may be controlled in a manner similar to that
described above. According to an embodiment of the present
invention, the core portion 2404 may include or be formed of, for
example, a polylactide (PLA), a polyglycolide (PGA), a
poly(lactide-co-glycolide) (PLGA), a polyglyconate, a
polyanhydride, PEG, cellulose, a gelatin, a lipid, a
polysaccharide, a starch and/or a polyorthoester.
[0109] Coupled to the core portion 2404 is a shell portion 2406
that includes a second porous matrix defining a second controlled
pore architecture that is different from the pore architecture of
the core portion 2404. According to an embodiment of the present
invention, the shell portion 2406 includes collagen. Such a
collagenous shell portion 2406 may be selectively configured to
have a predetermined pore density, pore shapes, pore sizes and pore
orientation, for example. Such controlled pore architecture may
influence the degree and the manner in which the collagenous shell
portion 2406 swells when the implant 2400 is placed, immersed or
implanted in a biological fluid environment, such as a cavity
within a patient's body. Such controlled pore architecture also
influences tissue ingrowth, by providing a scaffolding support
structure on and within which new tissue may develop. The rate at
which the shell portion 2406 degrades within the body may also be
influenced by controlling the crosslinking of the collagenous
matrix of the shell portion 2406. By controlling the formation and
the density of crosslinks, it is possible to control and/or
influence some of the mechanical, physicochemical and biological
properties of the collagenous shell portion 2406.
[0110] Visualization of the post-biopsy cavity treatment implant
2400 is facilitated not only by the presence of the radiopaque
element 2402 within the core portion 2404, but also by means of the
echogenic nature of the core portion 2404 and of the shell portion
2406. Such dissimilar pore architectures in the core portion 2404
and shell portion 2406 may also influence the relative elasticity
of the two portions 2404 and 2406 further enabling the implant to
be visible under elastography.
[0111] More than one radiopaque element 2402 may be present in the
core portion 2404. Moreover, another element exhibiting
radiopacity, having paramagnetic characteristics and/or visible
under other modalities (such as ultrasound, for example), may be
present in the core portion 2404 and/or the shell portion 2406. At
least the shell portion 2406 may include a dye, a pigment, a
contrast medium and/or a beneficial therapeutic agent (for example)
disposed therein. Such dye, a pigment, a contrast medium and/or a
beneficial therapeutic agent may be held sponge-like within the
porous matrix of the shell portion 2406 and delivered through
elution over time, but may also be contained within an internal
reservoir (a voided space) defined within the core portion 2404
and/or the shell portion 2406. For example, the internal reservoir
may be configured to deliver the dye, pigment, contrast medium
and/or therapeutic agent at a first rate when the reservoir is
breached and at a second rate that is lower than the first rate
when the reservoir is not breached.
[0112] FIG. 25 shows the post-biopsy cavity treatment implant 2400
of FIG. 24 loaded into an exemplary introducer 804, according to an
embodiment of the present invention. The post-biopsy cavity
treatment implant 2400, in a pre-implanted state, may be loaded
into the introducer 804, which may then be inserted into the tissue
110 through the access path 127 and at least partially into the
cavity chamber 128 of the cavity 126, in the manner illustrated in
FIG. 8. The post-biopsy cavity treatment implant 2400 may then be
delivered to the cavity 126 and thereafter be left in place and the
introducer 804 withdrawn. The pre-implanted state of the
post-biopsy cavity treatment implant 2400 is preferably in a state
in which it occupies its minimum volume. According to an embodiment
of the present invention, the pre-implanted state of the
post-biopsy cavity treatment implant 2400 is a lyophilized (e.g.,
dehydrated) state and the post-biopsy cavity treatment implant may
be configured to swell when placed within a biological fluid
environment such as the cavity 126.
[0113] FIG. 26 shows a post-biopsy cavity treatment implant 2600
according to a still further embodiment of the present invention,
in various stages of manufacture. Embodiments of the present
post-biopsy cavity treatment device may assume most any shape that
is suited to the shape and size of the cavity into which it is
designed to be placed. One such shape is the generally right
cylindrical shape (e.g., a disc) shown in FIG. 26. The implant
2600, at the top left hand of FIG. 26 is shown in an intermediate
manufacturing shape; i.e., prior to assuming its final
pre-implantation shape. The implant 2600 includes a radiopaque
element 2602 that may be coupled with a core portion 2604. The core
portion 2404, in FIG. 24, is shaped as a cylinder. However, the
shape of the core portion may be freely selected. In FIGS. 26-27,
the core portion 2604 has a generally rectangular cross-section. To
couple the core portion 2604 with the shell portion 2606, the core
portion 2604 may be placed on a pedestal within a mold. In the case
wherein the shell portion 2606 includes collagen, a collagenous
slurry may be poured into the mold and thereafter lyophilized.
Other means and methods for manufacturing the implant 2600 may
occur to those of skill in this art.
[0114] The implant 2600, according to one embodiment of the present
invention, may be folded along a diameter thereof, in such a manner
as to form the implant 2600 shown in the plan view shown in the
lower left hand side of FIG. 26. Thereafter, the implant 2600 may
again be folded along fold line 2611, in the manner suggested by
arrow 2610 to create the implant 2600 shown in the lower right hand
side of FIG. 26. Additional folding may then be carried out along
fold lines 2612, 2614 and 2616 to create an implant 2600 having
several layers and a generally wedge shape. The core portion 2604,
depending upon how the folding has been carried out, may be
sandwiched within several layers of the folded shell portion 2606.
In this state, the implant 2600 may be further compressed and
disposed in an introducer, an example of which is shown in FIG. 27
at 804 for eventual implantation within a post-biopsy cavity. It
should be noted that the folding need not take place as illustrated
in FIG. 26, but may be carried out in a different manner, to
achieve a different ultimate shape for the implant 2600. In
addition or in place of folding, the implant may also be rolled or
crumpled (for example) into its intended pre-implantation
shape.
[0115] FIG. 28 shows the post-biopsy cavity treatment implant 2600
of FIGS. 26 and 27 during implantation, according to an embodiment
of the present invention. FIG. 29 shows the post-biopsy cavity
treatment implant 2600 of FIG. 28 after implantation, illustrating
the manner in which the implant 2600 may expand and/or unfold
within the cavity 126 after implantation, according to an
embodiment of the present invention. As shown, the introducer 804
may be inserted into the tissue through the access path 127 and at
least partially into the cavity chamber 128 of the cavity 126. The
post-biopsy cavity treatment implant 2600 may then be delivered to
the cavity 126 and thereafter be left in place and the introducer
804 withdrawn. The pre-implanted state of the post-biopsy cavity
treatment implant 2600 is preferably in a state in which the
post-biopsy cavity treatment implant 2600 occupies its minimum
volume. According to an embodiment of the present invention, the
pre-implanted state of the post-biopsy cavity treatment implant
2600 is a lyophilized (e.g., dehydrated) state and the post-biopsy
cavity treatment implant 2600 may be configured to swell when
placed within a biological fluid environment such as the cavity
126. Whereas FIG. 28 shows the present post-biopsy cavity treatment
implant 2600 immediately after implantation in tissue (i.e., still
in a state in which it occupies its minimum volume), FIG. 29 shows
the state of the present post-biopsy cavity treatment implant 2600
a period of time after implantation. As shown, the post-biopsy
cavity treatment implant 2600 is no longer in its pre-implanted
state. Indeed, the post-biopsy cavity treatment implant 2600 having
been placed in a biological fluid environment (such as the
patient's tissue), begins to swell. To accelerate the swelling, the
surgeon may inject fluids after placing the device with the intent
to "wet" the present post-cavity treatment implant 2600. Substances
such as saline, fibrin solution or other catalyst or activator may
be used for that purpose. For example, as part of the insertion
device (such as, for example, the introducer 804), an integral vial
may be crushed by the surgeon to release the activating fluid (for
example, an aqueous solution, dye/pigment) within the cavity 126,
thus causing rapid swelling of the implant 2600. Alternately, and
as shown in FIG. 9, the introducer 804 may define an internal lumen
811 over its length and may include a fluid injection port 812 at
the proximal end of the device. Fluids such as the aforementioned
saline or fibrin may then be introduced into the cavity 126 through
the fluid injection port 812 and the internal lumen 811 to cause
the rapid swelling of the implant 2600 or for any other reason.
Delivering such fluids can be especially useful if the field within
the cavity 126 is relatively dry as can occur in the ideal
case.
[0116] As the post-biopsy cavity treatment implant 2600 swells, it
preferably swells from a shape in which it is easily implantable
through the access path 127 to a shape and size wherein it no
longer fits through the access path 127. As this swelling occurs
rapidly after the post-biopsy cavity treatment implant 2600 comes
into contact with the fluids present within the cavity 126, the
surgeon may retract the introducer 804 from the cavity 126, close
the initial incision and be confident that the post-biopsy cavity
treatment implant 2600 has remain in its intended position,
squarely within the cavity chamber 128 of the cavity 126, and has
not migrated back into the access path 127.
[0117] As shown in FIG. 29, the release of the implant 2600 from
compression at it is ejected from the introducer 804, combined with
the hydration and subsequent swelling of the post-biopsy cavity
treatment implant 2600 within the cavity 126 causes the implant
2600 to at least partially unfold (and/or unroll), thereby causing
the volume that it occupies to increase. This unfolding and
swelling may enable the implant 2600 to occupy a significant
portion of the internal volume of the cavity 126. This, in turn,
aids in promoting tissue ingrowth by providing scaffolding upon and
within which new tissue may develop. Moreover, the now at least
partially filled cavity 126 is readily visible under a variety of
imaging modalities. As the ranges at which the core and shell
portions may biodegrade may be controlled as detailed above, it is
possible to manufacture the implant 2600 to have a predictable rate
of biodegradation. After the core and shell portions of the implant
have substantially degraded within the cavity, the radiopaque
element will remain in the newly formed tissue within the cavity,
providing a ready positional reference of the cavity 126, should
that be subsequently necessary. More that one such implant 2600 may
be placed within the cavity 126.
[0118] FIG. 30 shows a post-biopsy cavity treatment implant 3000
according to another embodiment of the present invention, in
various stages of manufacture. The implant 3000 is similar to that
shown in FIGS. 26-29, but for the presence of two core portions
3004, 3008 within the shell portion 3010. Each of the core portions
3004, 3008 surrounds a radiopaque element 3002, 3306, respectively.
To form the implant 3000 in its ultimate pre-implantation shape
(i.e., its shape prior to being placed in a biological fluid
environment), the implant 3000 may first be folded along a diameter
thereof, to achieve the shape thereof shown in the plan view in the
lower left hand of FIG. 30. Thereafter, the implant 3000 may be
sequentially folded along the direction indicated by arrows 3010
along the fold lines 3014, 3016, 3018 and 3020 to achieve a
generally wedge shape.
[0119] It is to be noted that embodiments of the present
post-biopsy cavity treatment devices are not limited to the shapes
described and illustrated herein. Moreover, the present implants
may be folded differently than shown, as they may be irregularly
folded, rolled or otherwise caused to assume as small a volume as
practicable. A greater number of core portions may be accommodated
within the shell portion 3010. Other variations may occur to those
of skill in this area, and all such variations are believed to fall
within the scope of the present invention. FIG. 31 shows the
post-biopsy cavity treatment implant 3000 of FIG. 30 loaded into an
exemplary introducer 3022, according to another embodiment of the
present invention.
[0120] FIG. 32 shows a post-biopsy cavity treatment implant 3000
according to yet another embodiment of the present invention, in a
configuration prior to folding and/or compression. As shown, the
post-biopsy cavity treatment implant 3000 may be shaped, for
example, such that the shell portion 3010 is shaped as a
rectangular sheet. The embodiment shown in FIG. 32 includes two
radiopaque elements 3002 and 3006, although a lesser or greater
number of such radiopaque elements may be present. Coupled to the
radiopaque element 3002 is a core portion 3004 and coupled to the
radiopaque element 3006 is another core portion 3008. In the
illustrated embodiment, the core portion 3004 surrounds the
radiopaque element 3002, the core portion 3008 surrounds the
radiopaque element 3006 and the shell portion 3010 surrounds both
core portions 3004 and 3008. Other arrangements of the constituent
elements of the post-biopsy cavity treatment implant 3000 are
possible.
[0121] According to one embodiment, the post-biopsy cavity
treatment implant 3000 of FIG. 32 may be folded and/or rolled or
otherwise arranged into any desired shape. FIG. 33 shows the
post-biopsy cavity treatment implant 3200 of FIG. 32 in one such
many possible folded configurations, according to still another
embodiment of the present invention. After lyophilization, the
implant 3200 may be folded two or more times (for example) and
compressed into an introducer, such as shown in FIG. 27 or 31. Any
folding pattern may be used. Some of the goals of such folding,
rolling and/or compression include reducing the dimensions of the
implant 3200, fitting the shape of the implant 3200 to the shape
and dimensions of the cavity into which the implant is to be
placed, and to influence the manner in which the implant unfolds
and/or unrolls within the cavity, upon being released from the
introducer, decompressing and swelling with biological fluids
within the environment of use within the patient. FIG. 33 is to be
considered only as illustrative of one of many possible
configurations for the implant 3200.
[0122] FIG. 34 shows a core portion 3400 suitable for use in
conjunction with the present post-biopsy cavity treatment implant,
according to another embodiment of the present invention. As shown,
the core portion of the present post-biopsy cavity treatment
implant need not be rectangular or cylindrical. In the embodiment
of FIG. 34, although the core portion 3404 has a uniform
cylindrical cross-section, it may exhibit a more complex geometry.
For example, the center portion of the core portion 3403 may be
locally thinner than the ends thereof. This locally thinner portion
facilitates any folding or rolling that may be carried out to bring
the implant into its final (pre-implantation) shape and
configuration. The core portion 3404 may be coupled to (or
surround, as shown in FIG. 34) one or more radiopaque elements
3402. FIG. 35 shows a post-biopsy cavity treatment implant 3500
incorporating the core portion 3404 of FIG. 34, according to yet
another embodiment of the present invention, in a configuration
prior to folding and/or compression. The shell portion 3406 is
coupled to the core portion 3403. As shown in FIG. 35, the shell
portion 3406 may surround the core portion 3404. The implant 3500
may then be folded, rolled and/or compressed, as described
above.
[0123] FIG. 36 shows further core portions 3604, 3608 suitable for
use in conjunction with the present post-biopsy cavity treatment
implant, according to another embodiment of the present invention.
FIG. 37 shows a post-biopsy cavity treatment implant 3700
incorporating the core portions 3604, 3608 of FIG. 36, according to
a further embodiment of the present invention, in a configuration
prior to folding and/or compression. As shown in FIGS. 36 and 37,
more than one core portion may be coupled to the shell portion 3406
and each (or only one) of such core portions 3604, 3608 may be
coupled to (or surround) a radiopaque element, as shown at
reference numerals 3602 and 3606. The core portion or portions of a
post-biopsy cavity treatment implant according to an embodiment of
the present invention may be fabricated in most any shape that is
consistent with the cavity treatment goals. FIG. 38 shows a core
portion 3804 having yet another possible shape. As with the core
portions discussed herein, the core portion 3804 is coupled to or
surrounds a radiopaque element 3802. The core portions shown in
FIGS. 34-38 may be stamped from a sheet of core material. The core
material, according to an embodiment of the present invention, may
be formed of or include one or more of the following materials: a
polylactide (PLA), a polyglycolide (PGA), a
poly(lactide-co-glycolide) (PLGA), a polyglyconate, a
polyanhydride, PEG, cellulose, a gelatin, a lipid, a
polysaccharide, a starch and a polyorthoesters, for example.
[0124] FIGS. 39 and 40 shows exemplary radiopaque elements 3900 and
4000 suitable for use in conjunction with the present post-biopsy
cavity treatment implant, according to still further embodiments of
the present invention. The radiopaque element may be shaped as a
staple or the letter "C" as shown in FIG. 38 or in another shape,
such as shown in FIG. 39, in which the radiopaque element 400 has
the general shape of the letter "R". Other shapes and
configurations are possible.
[0125] FIG. 41 shows a post-biopsy cavity treatment implant 4100,
according to a further embodiment of the present invention, in a
configuration prior to folding and/or compression. A radiopaque
element 4102 is coupled to (or surrounded by) a core portion 4104.
In turn, the core portion 4104 is coupled to (or surrounded by) a
shell portion 4106. This embodiment is similar to that shown in
FIG. 26, but for the radial cuts 4108 in the shell portion 4106.
The radial cuts 4108 may enable the implant 4100 to better
accommodate and fill irregularly shaped cavities when the implant
is placed in a biological fluid environment and the implant 4100
decompresses, unfolds or unrolls and swells. Such radial cuts
define a plurality of independently movable free ends 4110 in the
peripheral portion of the implant 4100.
[0126] FIG. 42 shows a post-biopsy cavity treatment implant 4200,
according to another embodiment of the present invention, in a
configuration prior to folding and/or compression. A radiopaque
element 4202 is coupled to (or surrounded by) a core portion 4204,
as shown in the cutout (the purpose of the cutout is only to show
the internal structure of the implant 4200 and is not present in
the actual implant). In turn, the core portion 4204 is coupled to
(or surrounded by) a shell portion 4206. This embodiment is similar
to that shown in FIG. 13E. The implant 4200 includes a radiopaque
element 4202 coupled to or surrounded by a core portion 4204 that
is, in turn, coupled to or surrounded by a shell portion 4206. The
core portion 4204 and the radiopaque element may be configured
and/or have any of the characteristics discussed above and shown in
the corresponding figures. The shell portion 4206, as shown,
defines a center portion 4208 and a peripheral portion and wherein
the peripheral portion defines a plurality of independently movable
free ends 4210.
[0127] While the foregoing detailed description has described
preferred embodiments of the present invention, it is to be
understood that the above description is illustrative only and not
limiting of the disclosed invention. For example, the post-biopsy
cavity treatment implants disclosed herein may be configured to
have a unique "signaturing" capability, in which a specific code
appears under a given imaging modality. The specific code may be
formed within or molded into the structure of the collagen matrix
or matrices. For example, a combination of the elements with
different crosslinking patterns (e.g., bundles of cylindrical
fibers or layers of collagen sponges) may be used for both pattern
recognition and predictable filling of the post biopsy procedure
cavity. Alternatively, the code may be embodied as a discrete
echogenic or radiopaque constituent element of the implant. The
codes may confer information to the radiologist or treating
physician when viewed under X-ray or ultrasound. Alternatively
still, the post-biopsy cavity treatment implants having
predetermined pore architectures and/or controlled crosslinking
densities according to the disclosed embodiments may include a
biocompatibly-sealed integrated circuit that may be interrogated
electronically to convey information to the physician. Those of
skill in this art may recognize other alternative embodiments and
all such alternative embodiments are deemed to fall within the
scope of the present invention.
* * * * *