U.S. patent application number 12/629740 was filed with the patent office on 2010-06-24 for methods and systems for storing medical implants under sustained vacuum.
This patent application is currently assigned to Alphatech Spine, Inc.. Invention is credited to Markanthony B. Flores, Christian Gabriel Gamboa, Amit Govil, Jeffrey A. Guyer, Sudhansu Somasundar, Neil Irvin Thompson.
Application Number | 20100155282 12/629740 |
Document ID | / |
Family ID | 42237186 |
Filed Date | 2010-06-24 |
United States Patent
Application |
20100155282 |
Kind Code |
A1 |
Govil; Amit ; et
al. |
June 24, 2010 |
METHODS AND SYSTEMS FOR STORING MEDICAL IMPLANTS UNDER SUSTAINED
VACUUM
Abstract
Methods and systems for improving the shelf life of a medical
graft generally comprising a medical implant container having at
least one graft cavity configured to hold at least one graft under
a first vacuum and a needle entry port in fluid communication with
the at least one graft cavity, the needle entry port being
configured to receive and communicate a material to the at least
one graft cavity and an outer chamber configured to hold the
medical implant container under a second vacuum.
Inventors: |
Govil; Amit; (Ladera Ranch,
CA) ; Gamboa; Christian Gabriel; (San Diego, CA)
; Thompson; Neil Irvin; (San Marcos, CA) ; Guyer;
Jeffrey A.; (Boston, MA) ; Flores; Markanthony
B.; (San Diego, CA) ; Somasundar; Sudhansu;
(San Diego, CA) |
Correspondence
Address: |
ALPHATEC SPINE, INC.
5818 EL CAMINO REAL
CARLSBAD
CA
92008
US
|
Assignee: |
Alphatech Spine, Inc.
Carlsbad
CA
|
Family ID: |
42237186 |
Appl. No.: |
12/629740 |
Filed: |
December 2, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12251297 |
Oct 14, 2008 |
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12629740 |
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12130920 |
May 30, 2008 |
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12251297 |
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60932479 |
May 30, 2007 |
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61119688 |
Dec 3, 2008 |
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61138842 |
Dec 18, 2008 |
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Current U.S.
Class: |
206/438 ;
53/432 |
Current CPC
Class: |
A61F 2210/0004 20130101;
A61F 2220/0058 20130101; A61F 2002/30451 20130101; A61K 38/1841
20130101; A61F 2002/4685 20130101; A61F 2310/00365 20130101; A61F
2/28 20130101; A61F 2/4644 20130101; A61F 2/0095 20130101; A61F
2002/2835 20130101; A61F 2002/30062 20130101; A61F 2002/2817
20130101; A61K 38/1875 20130101 |
Class at
Publication: |
206/438 ;
53/432 |
International
Class: |
B65D 81/20 20060101
B65D081/20; B65B 31/04 20060101 B65B031/04 |
Claims
1. A kit for storing medical grafts under vacuum, comprising: a
medical implant container comprising: at least one graft cavity
configured to hold at least one graft under a first vacuum; and a
needle entry port in fluid communication with the at least one
graft cavity, the needle entry port being configured to receive and
communicate a material to the at least one graft cavity; and an
outer chamber configured to hold the medical implant container
under a second vacuum.
2. The kit of claim 1, wherein the first vacuum and second vacuum
are between 1 and 30 inHg.
3. The kit of claim 1, wherein the first vacuum and second vacuum
are substantially the same.
4. The kit of claim 1, wherein the first vacuum and second vacuum
are not substantially the same.
5. The kit of claim 1, wherein the outer chamber is made of a
material selected from the group consisting of SiOx, foil, ACLAR,
EVOH, PVOH. Alox, SiOx-F and PET, metal, glass, plastic, polymers
and ceramics.
6. The kit of claim 1, wherein the outer chamber is compatible with
sterilization techniques selected from the group consisting of
ethylene oxide sterilization, gamma radiation sterilization and
e-beam radiation sterilization.
7. The kit of claim 1, wherein the outer chamber includes a
transparent portion for visualization of the medical implant
container within.
8. The kit of claim 1, further comprising a mechanical insert
configured to engage the medical implant container and reduce
stress imparted on the medical implant container when under the
second vacuum.
9. The kit of claim 8, wherein the mechanical insert is a rigid
material selected from the group consisting of rigid polymer
plastics, polystyrene, polypropylene, metal, acrylonitrile
butadiene styrene and ABS plastic.
10. A medical graft storage system, comprising: at least one
medical graft; a medical implant container comprising: at least one
graft cavity configured to hold at least one graft under a first
vacuum; and a needle entry port in fluid communication with the at
least one graft cavity, the needle entry port being configured to
receive and communicate a material to the at least one graft
cavity; and an outer chamber configured to hold the medical implant
container under a second vacuum.
11. The system of claim 10, wherein the first vacuum and second
vacuum are between 1 and 30 inHg.
12. The system of claim 10, wherein the first vacuum and second
vacuum are substantially the same.
13. The system of claim 10, wherein the first vacuum and second
vacuum are not substantially the same.
14. The system of claim 10, wherein the outer chamber includes a
transparent portion for visualization of the medical implant
container within.
15. The system of claim 10, wherein the outer chamber is made of a
material selected from the group consisting of SiOx, foil, ACLAR,
EVOH, PVOH. Alox, SiOx-F and PET, metal, glass, plastic, polymers
and ceramics.
16. The system of claim 10, further comprising a mechanical insert
configured to engage the medical implant container and reduce
stress imparted on the medical implant container when under the
second vacuum.
17. The system of claim 10, wherein the material is a biological
material.
18. The system of claim 10, wherein at least one medical graft is
selected from the group consisting of freeze-dried bone grafts,
dehydrated bone grafts and synthetic grafts.
19. A method of increasing the shelf life of vacuum imposed on a
medical implant prior to delivery to a patient, comprising:
providing a medical implant; placing the medical implant in a
medical implant container comprising: a medical implant cavity
configured to hold the medical implant under a first vacuum; and a
needle entry port in fluid communication with the a medical implant
cavity, the needle entry port being configured to receive and
communicate a material to the medical implant cavity; placing the
medical implant container in an outer chamber; and applying second
vacuum to said outer chamber.
20. The method of claim 19, wherein the medical implant is a
medical graft.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S.
application Ser. No. 12/251,297, filed on Oct. 14, 2008, entitled
"PROCESSES AND SYSTEMS FOR LOADING MEDICAL IMPLANTS WITH SIMULATIVE
GROWTH AGENTS", which is a continuation-in-part of U.S. application
Ser. No. 12/130,920, filed on May 30, 2008, entitled "PROCESSES AND
SYSTEMS FOR HYDRATING AND SEEDING MEDICAL IMPLANTS WITH BIOLOGICAL
COMPONENTS", which claims priority to U.S. Provisional Application
No. 60/932,479, filed May 30, 2007, entitled "PROCESSES AND SYSTEMS
FOR HYDRATING AND SEEDING MEDICAL IMPLANTS WITH BIOLOGICAL
COMPONENTS", the contents of which are incorporated herein by
reference in their entirety.
[0002] This application also claims priority to U.S. Provisional
Application No. 61/119,688, filed on Dec. 3, 2008, entitled
"PROCESSES AND SYSTEMS FOR LOADING MEDICAL IMPLANTS WITH SIMULATIVE
GROWTH AGENTS" and U.S. Provisional Application No. 61/138,842,
filed on Dec. 18, 2008, entitled "OUTER VACUUM CHAMBER TO INCREASE
EFFICIENCY OF DRUG DELIVERY DEVICE", the contents of which are
incorporated herein by reference in their entirety.
FIELD OF THE INVENTION
[0003] The present invention relates generally to medical implants
and more particularly to methods and systems for storing medical
implants under sustained vacuum.
BACKGROUND
[0004] Bone grafting refers to a wide variety of medical and dental
surgical procedures by which the formation of new bone in a patient
is augmented or stimulated. Bone grafting is used in many types of
orthopedic procedures to treat bone fractures or loss, to repair
injured bone that has not healed, and to fuse together joints to
prevent movement. With particular reference to the spine, grafts
have been used to stabilize the spine and to prevent movement by
selected vertebral segments, which may be a significant cause of
pain in some patients. Grafts have also been used to correct or
stop the progress of spinal deformity, such as scoliosis, and to
provide structural support for fractures of the spine.
[0005] Suitable grafts can be harvested from bones in the patient's
own body (autografts), from bones in members of the same species
(allograft), and from bones in members of other animal species
(xenograft). Alternatively, bone grafts can be created from a wide
variety of natural and/or synthetic materials, such as collagen,
polymers, hydroxyapatite, calcium sulfate, ceramics, and
bioresorbable polymers, among many others. It is understood that
bone grafts can include those which have a predetermined shaped or
which are comprised of smaller particles that can be formed into a
desired shape at the time of implantation.
[0006] Regardless of the source, bone grafts must be adequately
preserved for later implantation in a surgical setting. One common
practice is to dehydrate the grafts by freeze-drying. This not only
extends the shelf-life of the bone grafts, it also inhibits
bacterial growth within the graft. Before implanting the graft into
a recipient, however, the graft must be reconstituted or rehydrated
with a suitable liquid. This can be done by immersing the bone
graft in the liquid. The problem with this approach, however, is
that infusion of the liquid through the pores of the graft is
typically unacceptably slow for a surgical environment and does not
ensure thorough and complete infusion of the liquid throughout the
graft. Moreover, this approach increases the likelihood of exposing
the graft to environmental pathogens.
[0007] It would be desirable to develop a system and process for
extending the shelf-life of vacuum on medical implants or grafts,
particularly bone grafts.
SUMMARY OF THE INVENTION
[0008] Methods and systems are disclosed herein storing medical
implants under sustained vacuum.
[0009] In a first aspect, embodiments of the present invention
provide a kit for storing medical grafts under vacuum, the kit
comprising medical implant container having at least one graft
cavity configured to hold at least one graft under a first vacuum
and a needle entry port in fluid communication with the at least
one graft cavity, the needle entry port being configured to receive
and communicate a material to the at least one graft cavity, and an
outer chamber configured to hold the medical implant container
under a second vacuum.
[0010] In another aspect, embodiments of the present invention
provide a medical graft storage system comprising at least one
medical graft configured for implantation in a body, a medical
implant container having at least one graft cavity configured to
hold at least one graft under a first vacuum and a needle entry
port in fluid communication with the at least one graft cavity, the
needle entry port being configured to receive and communicate a
material to the at least one graft cavity, and an outer chamber
configured to hold the medical implant container under a second
vacuum.
[0011] In another aspect, embodiments of the present invention
provide a medical graft storage system comprising at least one
medical graft configured for implantation in a body, a medical
implant container having at least one graft cavity configured to
hold at least one graft under a first vacuum and a needle entry
port in fluid communication with the at least one graft cavity, the
needle entry port being configured to receive and communicate a
material to the at least one graft cavity, and an outer chamber
configured to hold the medical implant container under a second
vacuum.
[0012] In many embodiments, the first vacuum and second vacuum
between 1 and 30 inHg.
[0013] In many embodiments, the first vacuum and second vacuum are
substantially the same.
[0014] In many embodiments, the first vacuum and second vacuum are
not substantially the same.
[0015] In many embodiments, the outer chamber is made of a material
selected from the group consisting of SiOx, foil, ACLAR, EVOH,
PVOH. Alox, SiOx-F and PET, metal, glass, plastic, polymers and
ceramics.
[0016] In many embodiments, the outer chamber is compatible with
sterilization techniques selected from the group consisting of
ethylene oxide sterilization, gamma radiation sterilization, and
e-beam radiation sterilization.
[0017] In many embodiments, the outer chamber includes a
transparent portion for visualization of the medical implant
container within.
[0018] In many embodiments, the kit further comprising a mechanical
insert configured to engage the medical implant container and
reduce stress imparted on the medical implant container when under
the second vacuum.
[0019] In many embodiments, the mechanical insert is a rigid
material selected from the group consisting of rigid polymer
plastics, polystyrene, polypropylene, metal, acrylonitrile
butadiene styrene and ABS plastic.
[0020] In many embodiments, medical implant is a medical graft.
[0021] Other objects, features and advantages of the present
invention will become apparent to those skilled in the art from the
following detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] FIG. 1A is a top perspective view of an embodiment of a
medical implant container.
[0023] FIG. 1B is a top perspective view of the medical implant
container of FIG. 1 without the lid.
[0024] FIG. 1C is a cross-sectional view of the medical implant
container of FIG. 1A taken along the 1'-1' axis
[0025] FIG. 2A is a front plan view of another embodiment of the
medical implant container.
[0026] FIG. 2B is a rear perspective view of the medical implant
container of FIG. 2A.
[0027] FIG. 3 is a top perspective view of a further embodiment of
the medical implant container alongside a needle syringe.
[0028] FIG. 4A is a top perspective view of yet a further
embodiment of the medical implant container.
[0029] FIG. 4B is a top perspective view of the medical implant
container of FIG. 6A without the lid.
[0030] FIG. 5A is a top perspective view of yet a further
embodiment of the of the medical implant container.
[0031] FIG. 5B is a top perspective view of the medical implant
container of FIG. 5A showing substrate reconstitution using a
syringe.
[0032] FIG. 6 is a data graph showing the relative binding strength
of rhBMP-2 applied to Absorbable Collagen Sponges (ACS) contained
in vacuum sealed package.
[0033] FIG. 7 is a data graph showing the relative binding strength
of rhBMP-2 applied to allograft bone tissue contained in vacuum
sealed package.
[0034] FIG. 8 is a top view of a container disposed within an outer
chamber, wherein the outer chamber is under vacuum.
[0035] FIG. 9A-9D are various views of some embodiments of a
mechanical insert for use with a suitably shaped medical implant
container such as the container shown in FIGS. 1A-C and 5A-B.
[0036] FIG. 10 is a data graph showing the vacuum loss of a
container housed under ambient film packaging.
[0037] FIG. 11 is a data graph showing the vacuum loss of a
container housed under ambient foil packaging.
[0038] FIG. 12 is a data graph comparing the vacuum loss of
containers housed in different outer chambers under vacuum over
time.
[0039] FIG. 13 is a data graph showing the accelerated vacuum
retention observed with various packaging materials at 55 degrees
C.
[0040] Like numerals refer to like parts throughout the several
views of the drawings.
DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION
[0041] The present disclosure is directed to medical graft storage
systems, kits for storing medical grafts under vacuum, and of
increasing the shelf life of vacuum imposed on a medical implant
prior to delivery to a patient. Although the present disclosure
describes the methods and systems for medical grafts, particularly
bone grafts, it is understood that the methods and systems can also
be applied for a wide variety of medical and dental applications
and also soft tissue applications, such as in regenerative medicine
and tissue engineering. Accordingly, the term "graft" as used
herein can be comprised of any naturally occurring tissue including
bone tissue and soft tissues as well as any non-naturally occurring
substance used as a graft, or any combination thereof.
[0042] FIGS. 1A-C depict various views of an embodiment of a
medical implant system 100 that can be used in connection with the
systems and methods disclosed herein. As shown in FIGS. 1A-C, the
medical implant system 100 comprises container 110 that includes an
entry port 120, a needle cavity 130 and a graft cavity 140
containing a medical implant, such as a dehydrated bone graft (not
shown). As shown in FIG. 1A, a needle syringe can be inserted
through the entry port 120 to deliver liquids, biological
components, and/or cells into the needle cavity 130 and to the
graft that is stored in the graft cavity 140 of the container 110.
The needle cavity 130 is disposed adjacent the graft cavity 140 to
receive the needle syringe and the liquids, biological components
and/or cell.
[0043] It is desirable to maintain the entire container 110 under
vacuum and, more preferably, under substantial vacuum. This is
because medical implants, such as bone grafts, are commonly
dehydrated and freeze-dried for storage prior to use or
implantation. The higher the negative pressure or vacuum within the
container, the greater the evacuation of the pores within the graft
and thus the greater infusion of the hydrating solution into the
graft. Thus, it is preferable to have an absolute pressure inside
the container as close to 0 mbar as possible. In a preferred
embodiment, the absolute pressure inside the container is under 100
mbar, more preferably 10 mbar, and most preferably 1-5 mbar.
[0044] Freeze-drying involves a freezing process under negative
pressure that results in a graft having low residual moisture. One
advantage of this process is that it allows for storage of bone
grafts and other biological material at room temperature. It also
provides for increased shelf-life with reduced biochemical changes
to the bone graft. Freeze-dried grafts thus offer the advantage of
providing easy and economical storage prior to use.
[0045] In addition, it is preferable to reduce, if not completely
eliminate, any residual moisture within the graft prior to
packaging it in the container. This is because the negative
pressure or vacuum in the container can cause the residual moisture
to vaporize which, in turn, may cause the negative pressure or
vacuum to decrease within the container. Preferably, the residual
moisture within the graft is less than 6%, more preferably less
than 3%, and most preferably 0%. A desiccant can be included in the
container. The desiccant is preferably non-reactive with the graft
or the solution that is used to hydrate the graft.
[0046] The bone graft is typically rehydrated or reconstituted with
a saline solution prior to implantation in a patient or recipient.
Rehydration of freeze-dried bone grafts typically involves soaking
the grafts in the saline solution until the grafts reach the
desired level of hydration. Depending on the size of the graft,
among other factors, rehydration and reconstitution of a bone graft
can take anywhere from one hour to a few days. Although it is
desirable to achieve uniform penetration of the solution and
homogenous rehydration of bone grafts, it is generally difficult to
achieve these goals in the short period of time typically demanded
in surgical environments.
[0047] The medical implant containers disclosed and described
herein provide a means by which bone grafts, which have been
freeze-dried or otherwise dehydrated, can be expeditiously and
uniformly hydrated and reconstituted prior to implantation. Because
the medical implant containers substantially maintain the vacuum
during the hydration/reconstitution of the graft, the time for
hydration or reconstitution is substantially reduced. The
penetration of solution into the implant is enhanced by the vacuum
induced suction effect. The vacuum produces a pressure differential
that pushes the solution into the interstice or pores of the
implant. Once the solution is distributed into the pores, it can be
further distributed throughout the implant via capillary
action.
[0048] In some embodiments, the medical implant vacuum infused
package container system provides substantial hydration and
reconstitution, along with substantially uniform seeding and
loading of biological components and cells, within one minute to
one hour from infusion.
[0049] In FIGS. 1A-C, since the entire container 110 is maintained
under negative pressure or vacuum, it is desirable to reduce the
internal volume of the container 110 to the extent necessary to
house the bone graft. This is because it is generally more
difficult to maintain negative pressure or vacuum for larger
volumes of space. In a preferred embodiment, the volume of the
container is substantially the same as the volume of the graft. In
accordance with one aspect of this preferred embodiment, the volume
of the container is no greater than approximately 125%, preferably
no greater than approximately 110%, and more preferably no greater
than 105%, of the volume of the graft. In accordance with another
aspect of this preferred embodiment, the volume of the container is
equal to the volume of the graft. As shown in FIGS. 1A-C, the
interior volume of the container 110 is bounded by top 150, side
160 and bottom 170 walls. A septum 190 is coupled to the entry port
120 and disposed externally of the container 110 so as to reduce an
internal volume of the container 110 required to accommodate the
septum. The materials selected for the container are preferably
characterized as having high gas barrier properties to ensure that
the negative pressure or vacuum is effectively maintained over
time. In a preferred embodiment, the container is made from 40
gauge PETG (Pacur.TM. 6763).
[0050] The medical implant system 100 further comprises support
members 180 to support the container 110 in a substantially stable
and upright position. This will permit the surgeon to place the
system 100 on a flat surface and simply insert a needle syringe
into the entry port 120 with a single hand without having to
support the system 100 with the other hand in the desired upright
position. Although FIGS. 1A-C show the support members 180 as a
single peripheral wall that surrounds the container 110, it is
understood that the structure of the support members 180 is not so
limited and can include other structures capable of stabilizing the
container 110 in a sufficiently stable position to permit the
surgeon to perform the injection step into the entry port 120.
[0051] The system 100 is shown to generally comprise a bottom
portion 105 and a lid portion 135. The bottom portion 105 and the
lid portion 135 can be hermetically-sealed by welding the two
portions together so that vacuum can be maintained inside the
container 110. It is preferable to position the weld as close to
the periphery of the container 110 so as to further reduce the
amount of dead airspace that may remain between the bottom portion
105 and the lid portion 135. The resulting weld 125 can surround
the entire periphery of container 110. Although the system 100
depicted in FIGS. 1A-C is shown as a two-part structure comprising
a bottom portion 105 and a lid 135, it is understood that the
container can be constructed as an integral structure, such as an
elastic vacuum package.
[0052] In addition to expeditious and uniform hydrating or
reconstituting bone grafts, the system 100 promotes the efficient
and uniform distribution and seeding of biological components and
cells into the pores of the grafts. Biological components and cells
can be delivered to the grafts in solution via needle syringe
having the appropriate gauge so as to ensure against structural or
cellular damage as they are passed through the needle syringe.
[0053] The interior surface of the container 110 is preferably
configured to help preserve the integrity of the biological
components and the cells during delivery to the bone graft.
Particularly, the needle cavity 130 and the side 160 and bottom 170
walls are configured to promote a laminar flow of the biological
solution received through the entry port. A laminar flow is
characterized either as smooth or non-turbulent fluid flow. It is
preferable to promote a laminar flow, and therefore reduce a
turbulent flow, of the biological solution in the container 110 so
as to preserve the structural and cellular integrity of the
biological components and cells contained in the solution. A
turbulent flow can, for example, cause the cells to become lysed
and clump together. Eliminating, or at least reducing, sharp edges,
corners or angles within the container 110 which the biological
solution can come into contact with in the container can help
promote a laminar flow of the solution. It is noted that because
the liquid is expelled into the needle cavity and towards the
bottom surface 170 of the container 110, the configuration of the
top wall or lid portion 105 of the container 110 or where the side
walls 160 meet the lid portion 105 of the container 110 are not as
critical and therefore do not necessarily need to be curved.
[0054] As can be seen in FIGS. 1B-C, the side 160 and bottom 170
walls of the container 110 converge together as curved surfaces
having radii of curvature greater than zero. Moreover, the internal
surface of the needle cavity 130 is also provided as a curved
surface having a radius of curvature greater than zero.
Additionally, as depicted in FIG. 1C, the bottom wall 170 can be
angled downward from the entry port 120 and the needle cavity 130
so as to ensure that the biological solution flows across and is
distributed along a bottom length of the graft. This not only
ensures the uniform distribution of the solution throughout the
graft, it also prevents the pooling and waste of the solution in
the needle cavity 130. Thus, embodiments of the medical implant
container further provide for substantially precise dosing of a
quantity of biological components or cells to be introduced.
However, it is to be understood that in other embodiments, the
bottom wall 170 need not be angled downward from the entry port 120
and the needle cavity 130.
[0055] Alternate embodiments provide an efficient way to hydrate or
reconstitute more than a single bone graft at the same time. FIGS.
2A-B show an embodiment of the medical graft container 200
comprising a single entry port 220 and a corresponding needle
cavity 230 and a plurality of graft cavities 240A, 240B, 240C, and
240D coupled to and in fluid communication with the needle cavity
230 via channels 235. Once the grafts are loaded into the graft
cavities 240A, 240B, 240C, and 240D, a gas communication is applied
to the container so as to evacuate air remaining in the graft
cavities. The container 200 can comprise a bottom portion and a lid
that is optionally hermetically-sealed by a weld 225. A peripheral
lip area 275 can be provided wherein the lid portion can be pulled
apart from the bottom portion to open the container 200 and remove
the bone grafts.
[0056] FIG. 3 depicts yet another embodiment of the medical graft
container 300 alongside a needle syringe. The container 300 is
designed to disperse the distribution of desired biological
components and cells by providing a plurality of delivery channels
335 along a length of the graft cavity 340. The graft cavity 340 is
preferably molded to the precise dimensions and shape of the
dehydrated bone graft. The biological components and cells can be
delivered via needle syringe through entry port 320 and into the
needle cavity 330. A negative pressure or vacuum is maintained in
the needle cavity 330, the delivery channels 335, and graft cavity
340. A septum 390 can optionally be coupled to the entry port 320
to maintain the negative pressure or vacuum after puncture with the
needle syringe. The container 300 can be hermetically sealed by a
weld 325 peripherally of the needle cavity 330, delivery channels
335 and graft cavity 340.
[0057] Other embodiments of the medical implant containers can be
designed to reduce the internal volume that is maintained under
vacuum. For example, FIGS. 4A-B depicts a medical implant container
400 comprising bone graft chips 402 contained within a graft cavity
410. A lid 450 is hermetically sealed to the peripheral lip 412 of
the graft cavity 410 by a heat weld 425. As can be seen in FIGS.
4A-B, the bone graft chips 402 fill the graft cavity 410 to near
capacity such that the volume of the graft cavity 410 is
substantially the same as the volume of the bone graft chips 402. A
septum 490 is disposed externally of the graft cavity 410.
Preferably, the septum is self-sealing after puncture with a needle
syringe delivering the hydrating solution to the graft chips 402 so
as to sustain the vacuum inside the graft cavity 410.
[0058] FIG. 5A depicts yet another embodiment of a medical graft
container 500. FIG. 5B illustrates how a medical graft disposed
within the medical graft container 500 of FIG. 5A can be infused
with a suitable aqueous composition utilizing needle syringe 510.
The container 500 is designed to disperse the distribution of
desired biological components and cells from a distance closer to
the middle of the medical graft by providing a septum 590 above the
medical graft disposed within the graft cavity. The graft cavity is
sealed under vacuum by a top web 550. This can be especially
desirable for medical grafts that resist diffusion of the aqueous
composition due to small pore size or other factors influencing the
diffusion characteristics of the medical graft, such as viscosity
of the aqueous composition. The medical graft container 500 can
also be used in cases where it is desirable to set up a
concentration gradient of the biological components or cells within
a medical graft having a higher concentration of biological
components and cells closer to the middle of the medical graft and
a lower concentration of biological components and cells further
away from the middle of the medical graft. The needle syringe 510
is inserted into the medical graft during infusion of the aqueous
composition, or the needle syringe is merely placed above or
adjacent to the medical graft during infusion. The graft cavity is
preferably molded to the precise dimensions and shape of the
medical graft. The biological components and cells can be delivered
via needle syringe through entry port 595 of septum 590 to the
medical graft disposed within the graft cavity. The container 500
can be hermetically sealed by a weld 525 peripheral to the graft
cavity and support members 580 can be provided to support the
container 500 in a substantially stable and upright position.
[0059] The aqueous compositions used herein to hydrate or
reconstitute the bone grafts prior to implantation can be
solutions, emulsions, micro-emulsions, suspensions or combinations
thereof. Materials that function as emulsifiers or suspension aids
can also be present in such aqueous compositions
[0060] In some embodiments, the aqueous compositions further
contain water-miscible biocompatible solvents or solvent mixtures.
The biocompatible solvents are preferably organic liquids in which
the grafts are at least partly soluble at mammalian body
temperatures and are substantially non-toxic in the quantities
used.
[0061] Biological components used in connection with the medical
implants disclosed herein include any agent that produces a
biological, therapeutic or pharmacological result in a human. One
group of biological components that are particularly useful in
conjunction with bone grafts are Bone Morphogenetic Proteins
(BMPs). BMPs are a group of growth factors and cytokines known for
their ability to induce the formation of bone and cartilage.
Examples of using BMPs in bone grafts is described in US Patent
Application Publication No. 2004/0230310 A1 entitled, "USE OF
MORPHOGENETIC PROTEINS TO TREAT HUMAN DISC DISEASE," which is
herein incorporated by reference in its entirety.
[0062] The methods and systems disclosed herein can also be
utilized to deliver living cells to desired sites in a recipient.
These cells can be concentrated prior to implantation by methods
such as centrifugation or filtration. Thus, the medical implants
seeded can function as adhesion substrates, anchoring cells to be
transplanted to effect the survival, growth and ultimately,
grafting or anchoring of the transplanted cells to normal cellular
tissue.
[0063] Porous substrates which can be used in connection with the
disclosed methods and systems include autograft, allograft,
xenograft, or other non-human animal-based materials such as
collagen and other peptide comprising implants. Synthetic materials
including ceramics, hydroxyapatite, bioresorbable polymers and the
like can also be used as graft materials. In some embodiments, the
porous substrate is an osteoconductive matrix comprising a
biologically acceptable matrix sponge. The sponge is preferably a
collagen sponge as will be described in greater detail below.
[0064] In some embodiments, the synthetic substrates include
polymers that are biostable, while in other embodiments, the
synthetic substrates include polymers that are bioresorbable.
[0065] In some embodiments, the porous substrate is a bioabsorbable
absorbent matrix. One example of a suitable absorbent matrix is an
Absorbable Collagen Sponge (ACS) as is taught in U.S. Patent
Application Publication No. 2007/0142916 A1 entitled "BONE GRAFT
COMPOSITION, METHOD AND IMPLANT," which is herein incorporated by
reference in its entirety.
[0066] In some embodiments, the absorbent matrix is derived from
Type I bovine tendon collagen. The collagen matrix preferably has
pores of a sufficient size and quantity to permit growing tissue to
infiltrate therein. The collagen matrix can also comprise a
multiplicity of substantially rigid nanofibers dispersed within the
collagen matrix to impart structural integrity to the collagen
matrix with nanofiber ends projecting out of a surface of the
collagen matrix to provide differential load bearing surface
bristles.
[0067] "Nanofiber" includes such structures as nanowires,
nanowhiskers, semi-conducting nanofibers, carbon nanotubes and
composite nanotubes so long as they impart a bristled surface to
the resorbable osteoconductive matrix of the invention.
[0068] Although collagen is a good example of a rigid nanofiber,
other polymers are suitable as well. Derivatives of other
biopolymers that are rod-like, such as tubulin and keratin that can
be manufactured in rigid nanofiber form can be suitable so long as
they retain a fiber structure integrity under conditions of matrix
formation. A preferred nanofiber is a nanometer scale rod-like
polymer that is water compatible and has polar surface groups such
as amino groups.
[0069] Other embodiments of the present invention include use of
the vacuum package container disclosed herein in conjunction with
an INFUSE.RTM. Bone Graft device (Medtronic Sofamor Danek, Memphis,
Tenn.) and can include a Bone Graft/LT-CAGE.RTM. Lumbar Tapered
Fusion Device (Medtronic Sofamor Danek, Memphis, Tenn.) disposed
within the Vacuum Infused Package (VIP) medical container. The
INFUSE.RTM. device comprises two parts: (1) a
genetically-engineered human protein (rhBMP-2) to stimulate bone
healing, and; (2) an absorbable collagen sponge scaffold made from
cow (bovine) collagen that carries the BMP, as described above.
[0070] In yet further embodiments, the vacuum packaging can also
contain other items disposed within it such as mechanical devices
including metal plates, pins, rods, wires, screws, and
Graft/LT-CAGE's.RTM. or any other suitable structural element
either singularly or in combination with a porous substrate.
[0071] Freeze-dried (lyophilized) porous substrate, such as an
absorbent matrix, can be difficult to hydrate and is often
ineffectually hydrated in the operating room (OR) due to the amount
of time it takes to hydrate the porous substrate using conventional
"soaking" methods. The medical container disclosed herein embodies
a novel method for rapidly rehydrating a porous substrate,
decreasing the brittleness of the substrate, and delivering
biological components and cells to the porous substrate in an
effective and efficient manner. The container seals a dehydrated
porous substrate under an extremely strong vacuum by evacuating the
air from the pores of the substrate. During fluid infusion, the
vacuum pulls the fluid into the porous substrate, rapidly infusing
the pores and rehydrating the implant.
[0072] FIG. 8 shows an embodiment of a kit or system having a
medical graft container under vacuum, as described above, disposed
within an outer chamber which is also under vacuum, in either.
Vacuum is applied to the outer chamber such that both the graft
container and the outer chamber are under vacuum. In some
embodiments, the graft container and the outer chamber are under
substantially the same vacuum. In other embodiments, the graft
container and the outer chamber are under different vacuums. For
example the graft container may be under a first vacuum and the
outer chamber may be under a second vacuum.
[0073] In one embodiment, the graft container 800 is sealed under
vacuum of about 10 inHg. Other embodiments have graft containers
sealed under vacuum of between about 1 to about 30 inHg. Other
suitable vacuums are also contemplated. Graft container 800 can be
sealed using a top web comprising, for example, a Perfecseal.RTM.
film (31868-G) top web or a Tolas.RTM. foil film (TCP-0184B) top
web and vacuum sealer (not shown). Perfecseal.RTM. medical
packaging products and specifications can be found at:
http://www.perfecseal.com, and Tolas.RTM. healthcare packaging
products and specifications can be found at: http://www.tolas.com.
The vacuum sealed graft container 800 can then be placed in an
outer chamber 810, such as a SiOx, foil or Alox film pouch and
vacuum is then applied to the outer chamber 810 using a chamber
pouch sealer (not shown) such that both the graft container 800 and
the outer chamber 810 are under vacuum. In one embodiment, the
outer chamber 810 is sealed under vacuum of about 10 inHg. Other
embodiments have outer chambers 810 sealed under vacuum of between
about 1 to about 30 inHg. Other suitable vacuums are also
contemplated.
[0074] The outer chamber is preferably comprised of a high barrier
film to prevent vacuum loss. As will be appreciated by a person
having ordinary skill in the art, any film which possesses the
quality of serving as a barrier to oxygen, water or other
atmospheric substances can be utilized. Suitable films include, for
example, SiOx, foil, ACLAR, EVOH, PVOH. Alox, SiOx-F and PET. In
some embodiments, Rollprint.RTM. packaging products, such as RPP
#37-1021A, can be used for the outer chamber. In other embodiments,
Pacur.TM. packaging products, such as Pacur.TM. 6763 Copolyester
Sheet, can be used for the outer chamber.
[0075] In other embodiments, the outer chamber can be made of one
or more rigid materials suitable for holding vacuum including, but
not limited to: metal, glass, plastic, polymers, ceramics, etc. In
these embodiments, a chamber tray sealer or other vacuum chamber
sealer (not shown) can be used to apply vacuum to the more rigid
outer chambers of these embodiments.
[0076] The outer chamber 810 is constructed of materials compatible
with standard sterilization techniques including, for example,
ethylene oxide sterilization, gamma radiation sterilization, and
e-beam radiation sterilization. In some embodiments, the outer
chamber is constructed as a pouch. In some embodiments, the outer
chamber includes at least one transparent side or portion to allow
for visualization of the graft container within.
[0077] The inclusion of an outer chamber provides many advantages
over the prior art. These advantages include, without limitation,
longer shelf-life due to more reliable and sustained vacuum imposed
on the medical device, an improved sterility barrier, and increased
moisture barrier. In some embodiments, the outer chamber helps
maintain packaging integrity with respect to vacuum retention,
moisture protection, and sterility for at least 3 years. Another
advantage of the use of an outer container in connection with the
medical graft container is the improved and sustained vacuum that
is achieved, resulting in an increased rate and quality of
rehydration of the graft material.
[0078] FIGS. 9A-9D show one embodiment of a mechanical insert for
use with a medical graft container, as described above. The insert
900 includes a plurality of rigid support ribs 920. However, it
will be appreciated by one of skill in the art that any rigid
material in any suitable configuration can also be used, wherein
the insert provides a platform for the medical graft container to
sit. The insert 900 preferably has a graft cavity chamber 930
suitably shaped for receiving the graft cavity portion of a
similarly shaped medical graft container.
[0079] Referring now to FIGS. 9C and 9D, the insert 900 is
configured such that a medical graft container 910 can be seated
over the mechanical insert 900 providing support to the medical
graft container 910 when vacuum is applied by an outer container,
such as outer container 810. Thus, the insert 900 provides
structural support such that the amount of stress imparted to the
medical graft container/medical graft, is reduced when vacuum is
applied. The insert 900 is constructed from any relatively rigid
material which is capable of withstanding vacuum. Some examples of
suitable materials include, without limitation, relatively rigid
polymer plastics such as polystyrene, polypropylene, other standard
plastics, metals, and acrylonitrile butadiene styrene or ABS
plastic.
Experiments
[0080] The following examples teach medical implants and methods
and systems for hydrating and seeding medical implants with
biological components. These examples are illustrative only and are
not intended to limit the scope of the invention disclosed herein.
The treatment methods described below can be optimized using
empirical techniques well known to those of ordinary skill in the
art. Moreover, artisans of skill would be able to use the teachings
described in the following examples to practice the full scope of
the invention disclosed herein.
Experiment 1
[0081] An experiment was conducted using an aqueous solution
containing a known concentration of rhBMP-2 and multiple ACS
sponges. 150 .mu.g of rhBMP-2 (Infuse.RTM., Medtronic, Inc.,
Memphis, Tenn.) per cc of carrier was delivered into absorbable
collagen sponges (ACS, Medtronic, Inc.), using either a drip
(soaking) method or via Vacuum Infused Packaging (VIP). The rhBMP-2
applied by the drip method was allowed to soak for 15 minutes while
the VIP samples were only allowed 1 minute for binding. Unbound
rhBMP-2 was rinsed out of the ACS sponges by being placed in excess
saline on an orbital shaker at 37.degree. C. for 1 hour. An rhBMP-2
ELISA kit (Leinco Technologies, Inc., St. Louis, Mo.) was used to
determine the amount of rhBMP-2 that was bound to the ACS samples
after the 1 hour rinse. Data were then analyzed using a one-way
ANOVA (p<0.05) and Tukey's post-hoc honest significant
difference test for multiple comparisons.
[0082] The amount of rhBMP-2 bound to the dripped ACS after 15
minutes of binding time versus ACS after 1 minute VIP infusion time
is shown in FIG. 6. Some ACS sponges were soaked in rhBMP-2
solution (DRIP) and other ACS sponges were infused (using the same
rhBMP-2 solution) inside of vacuum sealed package. As can be seen
in FIG. 6, the VIP infused ACS exhibited statistically greater
binding of rhBMP-2 as compared to the 15 minute soaked (DRIP) ACS,
even with a substantially lessened binding time of only 1 minute
compared to the 15 minutes allotted to the soaked ACS
(p<0.0035). These surprising and unexpected results indicate
that VIP increases the binding ability of rhBMP-2 to ACS material.
Without being bound to a particular theory, it is believed that the
rhBMP-2 binds better to the ACS using VIP over traditional soaking
methods because VIP facilitates greater binding by exposing the
rhBMP-2 to a greater number of collagen binding sites within the
ACS.
Experiment 2
[0083] A similar experiment was performed using allograft bone
tissue, instead of ACS sponges, to further verify that the
foregoing "surprising and unexpected" results were not unique to
ACS sponges. 150 .mu.g of rhBMP-2 (Infuse.RTM., Medtronic, Inc.,
Memphis, Tenn.) per cc of carrier was delivered to multiple
allograft bone tissue samples using either a drip (soaking) method
or via Vacuum Infused Packaging (VIP). The rhBMP-2 applied by the
drip method was allowed to soak for 15 minutes while the VIP
samples were only allowed 1 minute for binding. Unbound rhBMP-2 was
rinsed out of the allograft bone tissue samples by placing them in
excess saline on an orbital shaker at 37.degree. C. for 1 hour. An
rhBMP-2 ELISA kit (Leinco Technologies, Inc., St. Louis, Mo.) was
used to determine the amount of rhBMP-2 that was bound to the
allograft bone tissue samples after the 1 hour rinse. Data were
then analyzed using a one-way ANOVA (p<0.05) and Tukey's
post-hoc honest significant difference test for multiple
comparisons.
[0084] FIG. 7 shows the relative amounts of rhBMP-2 bound to the
dripped allograft bone tissue samples after 15 minutes of binding
time versus bone samples having a 1 minute VIP infusion time. As is
seen in FIG. 7, the VIP infused allograft bone samples exhibited
statistically greater binding of rhBMP-2 as compared to the 15
minute soaked (DRIP) allograft bone samples, even with a
substantially lessened binding time of only 1 minute compared to
the 15 minutes allotted to the soaked bone samples. These
surprising and unexpected results further indicate that VIP
increases the binding ability of rhBMP-2 in multiple absorbent
matrix materials, not just in ACS sponges.
[0085] In some embodiments, the medical implant vacuum infused
package container system provides greater than 50% binding of
biological components to a bioabsorbable absorbent matrix in less
than 15 minutes from infusion. In other embodiments, the medical
implant vacuum infused package container system provides greater
than 50% binding of biological components to a bioabsorbable
absorbent matrix in less than 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4,
3 or 2 minutes from infusion, and preferably in less than or equal
to 1 minute from infusion.
[0086] In other embodiments, the medical implant vacuum infused
package container system provides greater than 75% binding of
biological components to a bioabsorbable absorbent matrix in less
than 15 minutes from infusion. In other embodiments, the medical
implant vacuum infused package container system provides greater
than 75% binding of biological components to a bioabsorbable
absorbent matrix in less than 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4,
3 or 2 minutes from infusion, and preferably in less than or equal
to 1 minute from infusion.
[0087] The benefits of increased binding between rhBMP-2 and ACS in
a VIP environment are immediate and identifiable. Strong binding of
rhBMP-2 to ACS is very desirable because this lessens premature
precipitation of rhBMP-2 out of absorbent matrix grafts and into
surrounding tissue inside the patient's body. As discussed
previously, premature or excessive precipitation of BMPs has been
known to stimulate ectopic bone growth in muscle tissue and in more
serious cases, involving implants in the cervical spinal area,
ectopic bone growth has been known to completely surround the
subject's trachea closing off their air passage and causing
suffocation.
Experiment 3
[0088] Referring to FIGS. 10 and 11, an experiment was performed
comparing the vacuum loss of two medical graft containers under
vacuum without any additional vacuum seal outer packaging.
Accordingly, FIGS. 10 and 11 graphically depict the transmission of
oxygen or vacuum loss in a container sealed with a top web only,
where no additional vacuum seal outer packaging was utilized. One
medical graft container was sealed with a Perfecseal.RTM. top web,
while the other medical container was sealed with a Tolas.RTM. foil
top web. The medical containers were then exposed to conditions of
40 degrees C., 85% RH, and 760 mm HG pressure. Vacuum loss was
measured over a period of about 250 days. The results of the
experiment are shown in FIGS. 10 and 11. Vacuum loss models
revealed that the Perfecseal.RTM. film top web sealed container
gained an average of 0.205.+-.0.016 cc of air per day, whereas the
Tolas.RTM. foil film top web sealed container gained an average of
0.044.+-.0.001 cc of air per day. Accordingly, the Tolas.RTM. foil
film top web was evidently better at holding vacuum than the
Perfecseal.RTM. top web.
[0089] Referring now to FIG. 12, an experiment was performed
comparing the vacuum loss of multiple medical graft containers
which were first sealed under vacuum using Perfecseal.RTM. film top
webs and then sealed again under vacuum in differing outer
chambers. One outer chamber comprised an Alox film pouch and the
other was a SiOx or foil pouch. The sealed medical graft containers
were then stored at 55.degree. C. and vacuum infusion was measured
periodically by weighing the sealed medical graft containers. FIG.
12 illustrates the reduction of vacuum loss observed for the
medical graft containers housed in the different outer chambers.
The loss in vacuum was measured over a period of about 250 days and
vacuum loss model was extrapolated from this data as can be seen in
FIG. 12. The results of this experiment show generally that the
addition of an outer vacuum chamber will lengthen vacuum life. More
specifically, the results of this experiment show that different
outer chamber materials can lengthen vacuum life better than
others, depending on the specific material(s) used to construct the
outer chamber.
[0090] FIG. 13 illustrates the results of an experiment in a data
graph showing the accelerated vacuum retention observed with
various outer chamber packaging materials. An experiment was
performed comparing the vacuum loss of three medical graft
containers which were first sealed under vacuum using top webs and
then sealed again under vacuum in three different outer chambers.
One outer chamber was an Tyvek.RTM. film pouch, another was a SiOx
pouch and the other was foil pouch. The vacuum sealed containers
were then stored at 55.degree. C. and their infused weight (as a
percentage of baseline) was then measured over a period of about 30
days. FIG. 13 illustrates the reduction of vacuum loss observed for
all of theses medical graft containers housed in their different
outer chambers. More specifically, the results of this experiment
show that different outer chamber materials can lengthen vacuum
life better than others. For example, the container stored in a
foil pouch outer chamber retained its vacuum better than the
containers stored in the SiOx and Tyvek outer chambers.
[0091] It is to be understood that the detailed description and
specific examples, while indicating preferred embodiments of the
present invention, are given by way of illustration and not
limitation. Many changes and modifications within the scope of the
present invention can be made without departing from the spirit
thereof, and the invention includes all such modifications.
* * * * *
References