U.S. patent application number 13/014737 was filed with the patent office on 2012-08-02 for devices for generating and transferring micrografts and methods of use thereof.
This patent application is currently assigned to MOMELAN TECHNOLOGIES, INC.. Invention is credited to Denis LoBombard, Brian Newkirk, Sameer Sabir, Andrew Ziegler.
Application Number | 20120197267 13/014737 |
Document ID | / |
Family ID | 46577954 |
Filed Date | 2012-08-02 |
United States Patent
Application |
20120197267 |
Kind Code |
A1 |
Sabir; Sameer ; et
al. |
August 2, 2012 |
DEVICES FOR GENERATING AND TRANSFERRING MICROGRAFTS AND METHODS OF
USE THEREOF
Abstract
The invention generally relates to devices for generating and
transferring micrografts and methods of use thereof. In certain
embodiments, devices of the invention include a housing having an
open configuration and a closed configuration, a micrograft
generating station, and a micrograft transferring station.
Inventors: |
Sabir; Sameer; (Cambridge,
MA) ; Newkirk; Brian; (London, GB) ; Ziegler;
Andrew; (Arlington, MA) ; LoBombard; Denis;
(Georgetown, MA) |
Assignee: |
MOMELAN TECHNOLOGIES, INC.
Cambridge
MA
|
Family ID: |
46577954 |
Appl. No.: |
13/014737 |
Filed: |
January 27, 2011 |
Current U.S.
Class: |
606/132 |
Current CPC
Class: |
A61B 2017/306 20130101;
A61B 17/322 20130101 |
Class at
Publication: |
606/132 |
International
Class: |
A61B 17/00 20060101
A61B017/00 |
Claims
1. A device for generating and transferring micrografts, the device
comprising: a housing comprising an open configuration and a closed
configuration; a micrograft generating station; and a micrograft
transferring station.
2. The device according to claim 1, wherein the housing comprises a
bottom portion hingedly connected to a top portion.
3. The device according to claim 2, wherein the top portion of the
housing is movable in a vertical direction.
4. The device according to claim 3, wherein the micrograft
generating station comprises: an first member connected to the top
portion of the housing; and a second member connected to the bottom
portion of the housing, wherein the first member is aligned with
the second member.
5. The device according to claim 4, wherein the second member
comprises a spring loaded base.
6. The device according to claim 3, wherein the micrograft
transferring station comprises: a transfer pusher comprising a
plurality of prongs, wherein the pusher is connected to the top
portion of the housing; and a transfer stage connected to the
bottom portion of the housing, wherein the pusher and the stage are
aligned with each other.
7. The device according to claim 6, wherein the transfer stage
comprises a compressible material.
8. The device according to claim 6, wherein the transfer stage
comprises a spring loaded base.
9. The device according to claim 3, wherein the housing further
comprises a cartridge receiving portion that is located between the
top portion and the bottom portion of the housing.
10. The device according to claim 9, wherein the cartridge
receiving portion comprises a first slot and a second slot, wherein
the first slot is aligned with the micrograft generating station
and the second slot is aligned with the micrograft transferring
station.
11. The device according to claim 9, wherein the cartridge
receiving portion comprises a single slot and components of the
micrograft generating station and the micrograft transferring
station are removable from the top and bottom portions of the
housing, thereby providing for the micrograft generating station
and the micrograft transferring station to be located at a same
place in the device.
12. The device according to claim 10, further comprising a
cartridge that is compatible with the first slot and second slots
of the cartridge receiving portion and is removable from the first
and second slots of the cartridge receiving portion.
13. The device according to claim 12, wherein the cartridge is
configured to hold a skin graft.
14. The device according to claim 12, wherein the cartridge
comprises: a frame comprising a hollow inner portion; a removable
first plate comprising a mesh grid; a removable second plate
comprising a mesh grid; wherein in an assembled configuration, the
mesh grid of the first plate and the mesh grid of the second plate
are aligned with the hollow portion of the frame, and the grid of
the first plate is aligned with the grid of the second plate.
15. The device according to claim 14, wherein holes of the grids of
the first and second plates are larger than prongs of the transfer
pusher.
16. A method for generating and transferring micrografts, the
method comprising: providing a device comprising a housing having
an open configuration and a closed configuration; a micrograft
generating station; and a micrograft transferring station;
inserting a skin graft into the device, engaging the micrograft
generating station, thereby generating a plurality of micrografts;
and engaging the micrograft transferring station, thereby
transferring the plurality of micrografts to a substrate.
17. The method according to claim 16, wherein inserting comprises:
obtaining a cartridge comprising: a frame comprising a hollow inner
portion; a removable first plate comprising a mesh grid; a
removable second plate comprising a mesh grid; wherein in an
assembled configuration, the grid of the first plate and the grid
of the second plate are aligned with the hollow portion of the
frame, and the grid of the first plate is aligned with the grid of
the second plate; and inserting the skin graft between the first
and second plates such that the graft is aligned with the grids in
the first and second plates.
18. The method according to claim 17, wherein engaging the
micrograft generating station comprises: inserting the cartridge
into the micrograft generating station of the device while the
housing is in the open configuration; and transforming the housing
from the open configuration to the closed configuration, thereby
generating a plurality of micrograft.
19. The method according to claim 17, wherein engaging the
micrograft transferring station comprises: inserting the cartridge
into the micrograft transferring station of the device while the
housing is in the open configuration; inserting a substrate below
the cartridge; and transforming the housing from the open
configuration to the closed configuration, thereby transferring the
plurality of micrografts to the substrate.
20. The method according to claim 19, wherein the substrate is a
medical dressing.
21. The method according to claim 16, wherein the graft is an
autograft.
22. The method according to claim 16, further comprising prior to
the providing step: harvesting the skin graft.
23. The method according to claim 22, wherein harvesting comprises:
raising a blister; and cutting the blister to obtain the skin
graft.
24. The method according to claim 22, wherein raising comprises:
contacting a device having a hole to skin; and applying heat and/or
vacuum pressure, thereby raising the blister.
25. The method according to claim 16, wherein the skin graft is
selected from the group consisting of: an epidermal skin graft, a
split thickness graft, and a full thickness graft.
26. The method according to claim 16, further comprising: expanding
the micro grafts; and applying the expanded grafts to a patient
recipient site.
27. The method according to claim 26, wherein the recipient site is
an area of depigmented skin that has been prepared to receive a
skin graft.
28. A device for generating and transferring micrografts, the
device comprising: a base member; a micrograft generating station
integrated with the base member; and a micrograft transferring
station integrated with the base member.
29. The device according to claim 28, wherein the micrograft
generating station comprises: a frame comprising an open
configuration and a closed configuration; a first member connected
to a top portion of the frame; and a second member connected to a
bottom portion of the frame, wherein the first member is aligned
with the second member.
30. The device according to claim 29, wherein the second member
comprises a spring loaded base.
31. The device according to claim 29, wherein the frame further
comprises a cartridge receiving portion that is located between the
top portion and the bottom portion of the frame.
32. The device according to claim 31, wherein the cartridge
receiving portion comprises a slot that is aligned with the first
and second members of the micrograft generating station.
33. The device according to claim 28, wherein the micrograft
transferring station comprises: a frame comprising an open
configuration and a closed configuration; a transfer pusher
comprising a plurality of prongs, wherein the pusher is connected
to a top portion of the frame; and a transfer stage connected to a
bottom portion of the frame, wherein the pusher and the stage are
aligned with each other.
34. The device according to claim 33, wherein the transfer stage
comprises a compressible material.
35. The device according to claim 33, wherein the transfer stage
comprises a spring loaded base.
36. The device according to claim 33, wherein the frame further
comprises a cartridge receiving portion that is located between the
top portion and the bottom portion of the frame.
37. The device according to claim 36, wherein the cartridge
receiving portion comprises a slot that is aligned with the pusher
and the stage of the micrograft generating station.
38. The device according to claim 37, wherein the top portion of
the frame further comprises a latch that allows for the top portion
of the frame to lock with the cartridge receiving portion.
39. The device according to claim 36, wherein the frame further
comprises a stripper plate that comprises a hollow inner portion
such that the cartridge receiving portion, the pusher, and the
stage can fit within the hollow inner portion of the stripper
plate.
40. The device according to claim 28, further comprising a
cartridge that is compatible with the cartridge receiving portions
of the micrograft generating station and the micrograft
transferring station.
41. The device according to claim 40, wherein the cartridge is
configured to hold a skin graft.
42. The device according to claim 40, wherein the cartridge
comprises: a frame comprising a hollow inner portion; a removable
first plate comprising a mesh grid; a removable second plate
comprising a mesh grid; wherein in an assembled configuration, the
mesh grid of the first plate and the mesh grid of the second plate
are aligned with the hollow portion of the frame, and the grid of
the first plate is aligned with the grid of the second plate.
42. The device according to claim 42, wherein holes of the grids of
the first and second plates are larger than prongs of the transfer
pusher.
43. A method for generating and transferring micrografts, the
method comprising: providing a device comprising a base member; a
micrograft generating station integrated with the base member; and
a micrograft transferring station integrated with the base member;
inserting a skin graft into the device, engaging the micrograft
generating station, thereby generating a plurality of micrografts;
and engaging the micrograft transferring station, thereby
transferring the plurality of micrografts to a substrate.
44. The method according to claim 43, wherein inserting comprises:
obtaining a cartridge comprising: a frame comprising a hollow inner
portion; a removable first plate comprising a mesh grid; a
removable second plate comprising a mesh grid; wherein in an
assembled configuration, the grid of the first plate and the grid
of the second plate are aligned with the hollow portion of the
frame, and the grid of the first plate is aligned with the grid of
the second plate; and inserting the skin graft between the first
and second plates such that the graft is aligned with the grids in
the first and second plates.
45. The method according to claim 44, wherein engaging the
micrograft generating station comprises: inserting the cartridge
into the micrograft generating station while a frame of the station
is in an open configuration; and transforming the frame from the
open configuration to a closed configuration, thereby generating a
plurality of micrograft.
46. The method according to claim 44, wherein engaging the
micrograft transferring station comprises: inserting the cartridge
into the micrograft transferring station while a frame is in an
open configuration; inserting a substrate below the cartridge; and
transforming the frame from the open configuration to a closed
configuration, thereby transferring the plurality of micrografts to
the substrate.
47. The method according to claim 46, wherein the substrate is a
medical dressing.
48. The method according to claim 43, wherein the graft is an
autograft.
49. The method according to claim 43, further comprising prior to
the providing step: harvesting the skin graft.
50. The method according to claim 49, wherein harvesting comprises:
raising a blister; and cutting the blister to obtain the skin
graft.
51. The method according to claim 50, wherein raising comprises:
contacting a device having a hole to skin; and applying heat and/or
vacuum pressure, thereby raising the blister.
52. The method according to claim 43, wherein the skin graft is
selected from the group consisting of: an epidermal skin graft, a
split thickness graft, and a full thickness graft.
53. The method according to claim 43, further comprising: expanding
the micro grafts; and applying the expanded grafts to a patient
recipient site.
54. The method according to claim 53, wherein the recipient site is
an area of depigmented skin that has been prepared to receive a
skin graft.
55. A device for generating and transferring micrografts, the
device comprising: a base member; a micrograft generating station
integrated with the base member; a micrograft transferring station
integrated with the base member; and a micrograft expansion station
integrated with the base member.
Description
FIELD OF THE INVENTION
[0001] The invention generally relates to devices for generating
and transferring micrografts and methods of use thereof.
BACKGROUND
[0002] Skin is the largest organ of the human body, representing
approximately 16% of a person's total body weight. Because it
interfaces with the environment, skin has an important function in
body defense, acting as an anatomical barrier from pathogens and
other environmental substances. Skin also provides a semi-permeable
barrier that prevents excessive fluid loss while ensuring that
essential nutrients are not washed out of the body. Other functions
of skin include insulation, temperature regulation, and sensation.
Skin tissue may be subject to many forms of damage, including
burns, trauma, disease, and depigmentation (e.g., vitiligo).
[0003] Skin grafts are often used to repair such skin damage. Skin
grafting is a surgical procedure in which a section of skin is
removed from one area of a person's body (autograft), removed from
another human source (allograft), or removed from another animal
(xenograft), and transplanted to a recipient site of a patient,
such as a wound site. As with any surgical procedure, skin grafting
includes certain risks. Complications may include: graft failure;
rejection of the skin graft; infections at donor or recipient
sites; or autograft donor sites oozing fluid and blood as they
heal. Certain of these complications (e.g., graft failure and
rejection of the skin graft) may be mitigated by using an autograft
instead of an allograft or a xenograft.
[0004] A problem encountered when using an autograft is that skin
is taken from another area of a person's body to produce the graft,
resulting in trauma and wound generation at the donor site.
Generally, the size of the graft matches the size of the recipient
site, and thus a large recipient site requires removal of a large
section of skin from a donor site. As the size of the section of
skin removed from the donor site increases, so does the probability
that the donor site will not heal properly, requiring additional
treatment and intervention. Additionally, as the size of the
section of skin removed from the donor site increases, so does the
possibility of infection. There is also increased healing time
associated with removal of larger sections of skin because a larger
wound is produced.
[0005] To address those problems, techniques have been developed
that allow for expansion of a skin graft so that a harvested graft
can treat a recipient site that is larger than a donor site. Such
methods involve cutting a skin graft into many smaller micrografts,
transferring the micrografts onto a substrate, expanding the
micrografts on the substrate, and applying the expanded substrate
having the expanded micrografts to a recipient site. Producing
micrografts and transferring micrografts is typically accomplished
using two devices, one device to cut the skin graft into the many
smaller micrografts, and a second device to transfer the
micrografts from the cutting surface to a substrate for expansion.
The need for two devices slows the grafting process and increases
the risk of graft failure. Further, the need for separate devices
has prevented development of an automated system for producing a
skin graft.
SUMMARY
[0006] The present invention provides a micrograft generating
device integrated with a micrograft transferring device. The
invention thus provides a single device that can generate a
plurality of micrografts and transfer the micrografts to a
substrate.
[0007] In certain embodiments, devices of the invention include a
housing having an open configuration and a closed configuration, a
micrograft generating station, and a micrograft transferring
station. The housing may include a bottom portion hingedly
connected to a top portion. Generally, the top portion of the
housing is movable in a vertical direction.
[0008] In certain embodiments, the micrograft generating station
includes a first member connected to the top portion of the
housing, and a second member connected to the bottom portion of the
housing, in which the first member is aligned with the second
member. In certain embodiments, the micrograft transferring station
includes a transfer pusher including a plurality of prongs, in
which the pusher is connected to the top portion of the housing,
and a transfer stage connected to the bottom portion of the
housing, in which the pusher and the stage are aligned with each
other. The transfer stage may be made of any material that is
softer than that of the transfer pusher. In certain embodiments,
the transfer stage is composed of a compressible material. In other
embodiments, the transfer stage includes a spring loaded base. The
spring loaded base may further include a ball to focus the force on
the center of the stage.
[0009] The housing may further include a cartridge receiving
portion, in which the cartridge receiving portion is located
between the top portion and the bottom portion of the housing. The
cartridge receiving portion may include a first slot and a second
slot, in which the first slot is aligned with the micrograft
generating station and the second slot is aligned with the
micrograft transferring station. Alternatively, the cartridge
receiving portion may include a single slot and components of the
micrograft generating station and the micrograft transferring
station are removable from the top and bottom portions of the
housing, thereby providing for the micrograft generating station
and the micrograft transferring station to be located at a same
place in the device.
[0010] Devices of the invention may further include a cartridge
that is compatible with the first slot and the second slot of the
cartridge receiving portion. Further, the cartridge may be
removable from the first and second slots of the cartridge
receiving portion. The cartridge is configured to hold a skin
graft. In certain embodiments, the cartridge includes a frame
having a hollow inner portion, a removable first plate including a
mesh grid, and a removable second plate including a mesh grid, in
which, in an assembled configuration, the grid of the first plate
and the grid of the second plate are aligned with the hollow
portion of the frame, and the grid of the first plate is aligned
with the grid of the second plate. In certain embodiments, holes in
the grids of the first and second plates are generally larger than
the prongs of the transfer pusher.
[0011] Another aspect of the invention provides methods for
generating and transferring micrografts, including providing a
device having a housing having an open configuration and a closed
configuration, a micrograft generating station, and a micrograft
transferring station, inserting a skin graft into the device,
engaging the micrograft generating station, thereby generating a
plurality of micrografts, and engaging the micrograft transferring
station, thereby transferring the plurality of micrografts to a
substrate.
[0012] In certain embodiments, inserting includes obtaining a
cartridge having a frame including a hollow inner portion, a
removable first plate having a mesh grid, and a removable second
plate having a mesh grid, in which in an assembled configuration,
the grid of the first plate and the grid of the second plate are
aligned with the hollow portion of the frame, and the grid of the
first plate is aligned with the grid of the second plate, and
inserting the skin graft between the first and second plates such
that the graft is aligned with the grids in the first and second
plates.
[0013] In certain embodiments, engaging the micrograft generating
station includes inserting the cartridge into the micrograft
generating station of the device while the housing is in the open
configuration, and transforming the housing from the open
configuration to the closed configuration, thereby generating a
plurality of micrografts. In certain embodiments, engaging the
micrograft transferring station includes inserting the cartridge
into the micrograft transferring station of the device while the
housing is in the open configuration, inserting a substrate below
the cartridge, and transforming the housing from the open
configuration to the closed configuration, thereby transferring the
plurality of micrografts to the substrate. The substrate may be any
biocompatible material. An exemplary substrate is a medical
dressing.
[0014] Methods of the invention are used with any type of skin
graft, such as an epidermal skin graft, a split thickness graft, or
a full thickness graft. In particular embodiments, methods of the
invention are used with skin grafts including only or substantially
only the epidermal layer of skin. Methods of the invention can be
used with autografts, allografts, or xenografts. In preferred
embodiments, the grafts are autografts.
[0015] Methods of the invention may also include harvesting the
skin graft. Harvesting of skin grafts can occur by any method known
in the art. In certain embodiments, harvesting involves raising a
blister, and cutting the blister to obtain the skin graft. In
certain embodiments, raising involves contacting a device having a
hole to skin, and applying heat and/or vacuum pressure, thereby
raising the blister.
[0016] Methods of the invention may further include expanding the
micrografts, and applying the expanded grafts to a patient
recipient site. Methods of the invention are used to prepare skin
grafts for any recipient site of damaged skin. Exemplary types of
skin damage include burns (e.g., thermal or chemical), infections,
wounds, or depigmentation. In particular embodiments, the recipient
site is an area of depigmented skin that has been prepared to
receive a skin graft.
BRIEF DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 is a drawing showing the anatomy of skin.
[0018] FIG. 2A shows an embodiment of devices of the invention.
This figure shows the device in an open configuration. FIG. 2B is
an enlarged view of the transfer pusher. This figure shows the
plurality of prongs of the pusher.
[0019] FIG. 3 shows the device of FIG. 2A in a closed
configuration.
[0020] FIGS. 4A and 4B show a cartridge that is compatible with
devices of the invention. FIG. 4A shows an exploded view of the
cartridge. FIG. 4B shows a view of a fully assembled cartridge.
[0021] FIGS. 5A-5B show the process of generating the plurality of
micrografts using devices of the invention.
[0022] FIGS. 6A-6B show the process of transferring the plurality
of micrografts to a substrate using devices of the invention.
[0023] FIG. 7 shows another embodiment of devices of the
invention.
[0024] FIG. 8 shows the spring loaded base member of devices of the
invention.
[0025] FIG. 9 shows a latch that links a top portion of a frame to
a cartridge receiving portion of devices of the invention.
DETAILED DESCRIPTION
[0026] The skin consists of 2 layers. The outer layer, or
epidermis, is derived from ectoderm, and the thicker inner layer,
or dermis, is derived from mesoderm. The epidermis constitutes
about 5% of the skin, and the remaining 95% is dermis. FIG. 1
provides a diagram showing the anatomy of skin. The skin varies in
thickness depending on anatomic location, gender, and age of the
individual. The epidermis, the more external of the two layers, is
a stratified squamous epithelium consisting primarily of
melanocytes and keratinocytes in progressive stages of
differentiation from deeper to more superficial layers. The
epidermis has no blood vessels; thus, it must receive nutrients by
diffusion from the underlying dermis through the basement membrane,
which separates the 2 layers.
[0027] The dermis is a more complex structure. It is composed of 2
layers, the more superficial papillary dermis and the deeper
reticular dermis. The papillary dermis is thinner, including loose
connective tissue that contains capillaries, elastic fibers,
reticular fibers, and some collagen. The reticular dermis includes
a thicker layer of dense connective tissue containing larger blood
vessels, closely interlaced elastic fibers, and coarse, branching
collagen fibers arranged in layers parallel to the surface. The
reticular layer also contains fibroblasts, mast cells, nerve
endings, lymphatics, and some epidermal appendages. Surrounding the
components of the dermis is the gel-like ground substance composed
of mucopolysaccharides (primarily hyaluronic acid), chondroitin
sulfates, and glycoproteins.
[0028] In a graft, the characteristics of the donor site are more
likely to be maintained after grafting to a recipient site as a
function of the thickness of the dermal component of the graft.
However, thicker grafts require more favorable conditions for
survival due to the requirement for increased revascularization. It
has been discovered, however, that a substantially epidermal graft
according to the invention is more likely to adapt to the
characteristics of the recipient site.
[0029] The invention generally relates to devices for generating
and transferring micrografts and methods of use thereof. Reference
is now made to FIG. 2A, which shows a device 100 of the invention.
Device 100 includes a housing 101. The housing has a top portion
101a and a bottom portion 101b. The top portion 101a is hingedly
connected to the bottom portion 101b. The housing 101 has an open
configuration and a closed configuration. FIG. 2A shows the housing
101 in the open configuration. FIG. 3 shows the housing 101 in a
closed configuration. The hinges are connected to device 100 by
bolts 118.
[0030] Device 100 further includes a micrograft generating station
104 and a micrograft transferring station 105. The micrograft
generating station 104 includes a first member 106 connected to the
top portion 101a of the housing 101, and a second member 107
connected to the bottom portion 101b of the housing 101. The first
member 106 is aligned with the second member 107. The second member
may be a spring loaded base that includes a stage 401, coupled to a
spring 402 (FIG. 8). The spring loaded base may further include a
ball 403 to focus the force on the center of the stage 401.
[0031] The micrograft transferring station 105 includes a transfer
pusher 108 including a plurality of prongs 109 (FIG. 2B). The
transfer pusher 108 is connected to the top portion 101a of the
housing 101 such that the prongs 109 are oriented downward toward
the bottom portion 101b of the housing 101. The micrograft
transferring station 105 further includes a transfer stage 110,
which is connected to the bottom portion 101b of the housing 101.
The transfer pusher 108 and the transfer stage 110 are aligned with
each other. The transfer stage 110 may be made of any material that
is softer than that of the transfer pusher 108. In certain
embodiments, the transfer stage 110 is composed of a compressible
material. In other embodiments, the second member 107 includes a
spring loaded base (FIG. 8). The spring loaded base includes a
stage 401, coupled to a spring 402. The spring loaded base may
further include a ball 403 to focus the force on the center of the
stage 401. The base is generally has a flat top and is made of a
relatively hard material, i.e., not easily deformable or
compressible.
[0032] Housing 101 further includes a cartridge receiving portion
111. The cartridge receiving portion 111 is located between the top
portion 101a and the bottom portion 101b of the housing 101, and is
also hingedly connected with the top portion 101a and the bottom
portion 101b of the housing 101. The cartridge receiving portion
111 includes a first slot 112 and a second slot 113. The first slot
112 is aligned with the micrograft generating station 104 and the
second slot 113 is aligned with the micrograft transferring station
105.
[0033] The housing 101 may further include members 102 and 103 that
connect to the top portion 101a, the cartridge receiving portion
111, and the bottom portion 101b. Members 102 and 103 are movable
and help control the position of the cartridge receiving portion
111 as device 100 is transformed from the open configuration to the
closed configuration.
[0034] Device 100 also includes a lever 114 and linkage arms 115
and 116. The lever 114 is connected to the top portion 101a of the
housing 101. The lever 114 may include a handle 117 that may be
used to transform the device 100 from the open configuration to the
closed configuration and back to the open configuration. Linkage
arms 115 and 116 are connected to the lever 114, the top portion
101a of the housing 101, and bottom portion 101b of the housing
101. The linkage arms 115 and 116 act as force multipliers, such
that upon engagement of the lever 114, an exponential amount of
force is transferred to the micrograft generating station 104 and
the micrograft transferring station 105 as an operator transforms
device 100 from the open configuration to the closed configuration.
The exponential amount of force transferred may be varied by
varying the length of the lever 114 or the length of the linkage
arms 115 and 116. In certain embodiments, the device 100 is
configured to provide for at least about a 50.times., e.g. about
100.times., increase in force transferred to the micrograft
generating station 104 as compared to the amount of force applied
to the lever 114 by an operator to transform the device from the
open configuration to the closed configuration.
[0035] Reference is now made to FIGS. 4A and 4B, which show a
cartridge 119. FIG. 4A shows an exploded view of the cartridge 119.
FIG. 4B shows a fully assembled cartridge 119. The cartridge 119 is
compatible with the first slot 112 and second slot 113 of the
cartridge receiving portion 111 of the device 100, and is removable
from the first and second slots 112 and 113 of the cartridge
receiving portion 111 of the device 100. The cartridge 119 is
configured to hold a skin graft 120.
[0036] The cartridge 119 includes a frame 121. It is noted that
FIG. 4B shows the frame 121 of the cartridge 119 in the orientation
in which it is inserted into the device 100. FIG. 4A shows the
frame upside down. The frame 121 includes a beveled edge 122. The
beveled edge 122 aligns with beveled edges of the first slot 112
and second slot 113 of the cartridge receiving portion 111 of the
device 100, ensuring that the cartridge 119 is inserted into first
slot 112 and second slot 113 with the proper orientation. The frame
121 also includes a hollow portion 123. Upon insertion of the
cartridge 119 into the first and second slots 112 and 113, the
hollow portion 123 is aligned with the first and second members 106
and 107 of the micrograft generating station 104 and is also
aligned with the transfer pusher 108 and the transfer stage 110 of
the micrograft transferring station 105.
[0037] Cartridge 119 further includes a first plate 126 and a
second plate 127. The first plate 126 includes a mesh grid 128, and
the second plate 127 includes a mesh grid 129. Once assembled, the
mesh grid 128 of the first plate 126 and the mesh grid 129 of the
second plate 127 are aligned with the hollow portion 123 of the
frame 121, and holes of the mesh grid 128 of the first plate 126
are aligned with holes of the mesh grid 129 of the second plate
127. The holes in the grids 128 and 129 of the first and second
plates 126 and 127 are sized to provide an array of micrografts of
a desired size, such as lateral sizes between about 100 microns and
about 1000 microns or about 300 microns to about 500 microns.
[0038] For example, for repigmenting skin tissue, the micrografts
used may have a presence of melanocytes. Accordingly, a lateral
dimension of such micrografts can be between less than about 1 mm,
e.g., 200 to 1000 microns. Other exemplary sizes are between 400
and 800 microns. The area of the micrografts can be between about
0.04 mm.sup.2 and about 1 mm.sup.2. The exemplary sizes can provide
micrografts large enough such that each micrograft is likely to
contain some melanocytes, yet small enough to provide a large
number of micrografts from a particular piece of graft tissue,
which can facilitate a significant degree of expansion on the graft
site.
[0039] For treating burns or ulcers, where presence and
proliferation of keratinocytes is important, the micrograft sizes
may be smaller. For example, a lateral dimension of micrografts
containing keratinocytes can be between about 50 microns and about
1000 microns, or between 100 microns and about 800 microns. The
area of such micrografts can be between about 0.0025 mm.sup.2 and
about 1 mm.sup.2. The exemplary size ranges provide micrografts
large enough to contain viable and undamaged keratinocytes, and
small enough to facilitate repair of a larger area of damaged
skin.
[0040] To ensure proper alignment, frame 121 includes plate
retaining pins 124 and plate locating pins 125. First plate 126
includes plate retaining holes 130 and plate locating holes 131,
and second plate 127 includes plate retaining holes 132 and plate
locating holes 133. The plate retaining holes 130 and plate
locating holes 131 of the first plate 126 are aligned with plate
retaining pins 124 and plate locating pins 125 of frame 121.
Similarly, plate retaining holes 132 and plate locating holes 133
of the second plate 127 are aligned with plate retaining pins 124
and plate locating pins 125 of frame 121. The alignment of the
plate retaining holes 130 and plate locating holes 131 of the first
plate 126, the plate retaining holes 132 and plate locating holes
133 of the second plate 127, and the plate retaining pins 124 and
plate locating pins 125 of frame 121 ensures that once assembled,
the mesh grid 128 of the first plate 126 and the mesh grid 129 of
the second plate 128 are aligned with the hollow portion 123 of the
frame 121, and the mesh grid 128 of the first plate 126 is aligned
with the mesh grid 129 of the second plate 127.
[0041] The first plate 126 and the second plate 127 are removable
from the frame 121. Removability allows for re-use of the frame
121. The skin graft 120 is inserted such that at least a portion of
the graft 120 is aligned with the mesh grid 128 of the first plate
126 and the mesh grid 129 of the second plate 127.
[0042] In an alternative embodiment, cartridge retaining portion
111 of housing 101 includes only a single slot. In this embodiment,
components of the micrograft generating station 104 (first and
second members 105 and 106) and components of the micrograft
transferring station 105 (transfer pusher 108 and transfer stage
110) are removable from housing 101. Thus, instead of transferring
the cartridge 119 between first and second slots 112 and 113 that
are aligned with a dedicated micrograft generating station 104 and
a dedicated micrograft transferring station 105, the cartridge 119
remains in a single slot for the generating and transferring
process, and it is the components of the micrograft generating
station 104 and the micrograft transferring station 105 that are
interchanged within the housing 101 depending on the whether an
operator is generating micrografts or transferring micrografts.
[0043] Devices of the invention as described herein may be used to
prepare skin grafts for any recipient site of damaged skin.
Exemplary types of skin damage include burns (e.g., thermal or
chemical), infections, wounds, or depigmentation. In particular
embodiments, the recipient site is an area of depigmented skin that
has been prepared to receive a skin graft.
[0044] General methods for preparing skin grafts are described in
co-owned and co-pending U.S. patent application Ser. No.
12/851,621, the content of which is incorporated by reference
herein in its entirety. In certain embodiments, methods of the
invention generally involve harvesting a skin graft from a donor
site, such as an epidermal graft, generating an array of
micrografts from the single graft, placing the graft on a first
substrate, expanding a distance between the micrografts on a first
substrate, optionally transferring the micrografts from the first
substrate to a second substrate, and applying the micrografts to a
recipient site.
[0045] Harvesting of the skin grafts may be accomplished by any
technique known in the art, and the technique employed will depend
on the type of graft required (e.g., epidermal graft, split
thickness graft, or full thickness graft). An epidermal graft
refers to a graft that consists of substantially epidermal skin and
does not include any substantial portion of the dermal layer. A
split thickness graft refers to a graft that includes sheets of
superficial (epithelial) and some deep layers (dermal) of skin. A
full-thickness graft refers to a graft that includes all of the
layers of the skin including blood vessels.
[0046] In certain embodiments, harvesting a skin graft involves
raising a blister and cutting the blister. In certain embodiments,
the blister may be a fluid-filled blister (e.g. a suction blister).
In other embodiments, the blister is not fluid-filled. Any type of
raised blister may be used with methods of the invention.
[0047] In certain embodiments, suction blister grafting is used.
Suction blister grafting involves raising a blister, and then
cutting off the raised blister. An exemplary suction blister
grafting technique is shown in Awad, (Dermatol Surg,
34(9):1186-1193, 2008), the content of which is incorporated by
reference herein in its entirety. This article also shows various
devices used to form suction blisters. A suction blister device is
also described in Kennedy et al. (U.S. Pat. No. 6,071,247), the
content of which is incorporated by reference herein in its
entirety. An exemplary device is commercially available from
Electronic Diversities (Finksburg, Md.).
[0048] A device for raising a suction blister typically operates by
use of suction chambers that are attached to a patient's skin. An
instrument typically contains a power source, a vacuum pump,
temperature controls and all related controls to operate multiple
suction chambers. The suction chambers are connected to the console
by a flexible connection. Each of the chambers is controlled by a
preset temperature control to provide an optimal skin warming
temperature. Both chambers share an adjustable common vacuum source
that affects all chambers equally.
[0049] Blister formation is accomplished by attaching the suction
blister device to a patient's skin. Typically hook & loop
fastener straps are used to keep the device in place. The chamber
heating system provides a slight warming of an orifice plate of the
device, which is in direct contact with the patient's skin surface.
The application of a moderate negative pressure from the instrument
console, to the chamber interior, causes the patients skin to be
gently drawn through the opening(s) in the orifice plate. The
results are typical suction blisters, approximately the size of the
opening(s) in the orifice plate. The skin and blister area is
generally not damaged and patient discomfort is minimal.
[0050] The negative pressure chamber is fabricated of mostly
plastic components, with two removable threaded caps. The upper cap
is fitted with a clear viewing lens so that the actual blister
formation can be observed. The opposite end of the chamber is
fitted with a removable orifice plate that is placed on the
patient's skin. Since this plate is simply threaded onto the
chamber end, multiple plates with different opening patterns can be
interchanged as desired.
[0051] The interior of the device is warmed and illuminated by an
array of low voltage incandescent lamps. This lamp array is
controlled from the instrument console temperature controller,
cycling as needed, to maintain the set point temperature. The heat
from these lamps is radiated and conducted to the orifice plate,
which then warms the patient's skin. The chamber is connected to
the console via a composite vacuum and low voltage electrical
system. Quick connections are used for the vacuum and electrical
system to facilitate removal and storage.
[0052] The Negative Pressure Instrument console is a self-contained
fan cooled unit which is designed to operate on 120 VAC 60 Hz
power. Vacuum is supplied by an industrial quality diaphragm type
vacuum pump, capable of a typical vacuum of 20 in Hg (0-65 kpa) at
0 CFM. An analog controller that is preset to 40.degree. C.
provides the temperature control for each suction chamber. This
provides accurate control of the orifice plate temperature. The
instrument console has internal adjustments that allow the user to
recalibrate the temperature setting if desired. Other temperatures
can be preset if desired. The front panel includes a vacuum gauge
and vacuum bleeder adjustment to regulate the vacuum to both
chambers. The console front panel also contains the connections for
the chamber assemblies.
[0053] Once the suction blister is raised, it is cut by methods
known in the art (see e.g., Awad, Dermatol Surg, 34(9):1186-1193,
2008). The skin graft 120 is then inserted into cartridge 119.
Frame 121 is turned upside down, as is shown in FIG. 4A. First
plate 126 is placed over frame 121. The plate retaining holes 130
and plate locating holes 131 of the first plate 126 are aligned
with the plate retaining pins 124 and the plate locating holes 125
of the frame 121. Once aligned, the first plate 126 is placed onto
the frame 121 such that the plate retaining pins 124 and the plate
locating holes 125 of the frame 121 go through the plate retaining
holes 130 and plate locating holes 131 of the first plate 126. Once
placed on the frame 121, the mesh grid 128 is aligned with the
hollow portion 123 of the frame 121.
[0054] The skin graft 120 is then placed on the mesh grid 128 of
the first plate 126. The graft should be roughly centered on the
mesh grid 128 (FIG. 4A). In certain embodiments, the graft 120 is
placed on the grid such that a basal layer of the graft 120 is
facing up. Epidermal skin includes a stratum corneum layer and a
basal layer. The stratum corneum refers to the outermost layer of
the epidermis, composed of large, flat, polyhedral, plate-like
envelopes filled with keratin, which is made up of dead cells that
have migrated up from the stratum granulosum. This layer is
composed mainly of dead cells that lack nuclei. The thickness of
the stratum corneum varies according to the amount of protection
and/or grip required by a region of the body. In general, the
stratum corneum contains 15 to 20 layers of dead cells, and has a
thickness between 10 and 40 .mu.m.
[0055] The basal layer (or stratum germinativum or stratum basale)
refers to the deepest layer of the 5 layers of the epidermis. The
basal layer is a continuous layer of live cells and can be
considered the stem cells of the epidermis. These cells are
undifferentiated and proliferative, i.e., they create daughter
cells that migrate superficially, differentiating during migration.
Keratinocytes and melanocytes are found in the basal layer.
[0056] For a graft to become integrated at a recipient site, the
graft must be able to receive nutrients. Since the cells of the
basal layer are live cells, orienting an epidermal graft such that
the basal layer interacts with the recipient site allows the graft
to receive nutrients, and thus remain viable. In contrast, since
the cells of the stratum corneum are dead cells, orienting an
epidermal graft such that the stratum corneum layer interacts with
the recipient site prevents the graft from receiving nutrients,
resulting in death of the graft tissue and graft failure. By
placing the graft 120 on the cartridge 119 with the basal layer
facing up, proper orientation of the graft 120 is maintained,
ensuring that once applied to the skin, it is the basal layer of
the graft 120 that interacts with the tissue of the recipient site.
Thus, methods of the invention ensure that during the grafting
process, the basal layer of a graft interacts with the recipient
site of a patient, allowing for the graft to receive nutrients and
thus remain viable.
[0057] Once the graft 120 has been placed on the first plate 126,
the second plate 127 is placed on top of the graft 120, sandwiching
the graft 120 between the first and second plates 126 and 127 (FIG.
4A). Second plate 127 is placed over frame 121. The plate retaining
holes 132 and plate locating holes 133 of the second plate 127 are
aligned with the plate retaining pins 124 and the plate locating
holes 125 of the frame 121. Once aligned, the second plate 127 is
placed onto the frame 121 such that the plate retaining pins 124
and the plate locating holes 125 of the frame 121 go through the
plate retaining holes 132 and plate locating holes 133 of the
second plate 127. Once placed on the frame 121, the mesh grid 129
is aligned with the hollow portion 123 of the frame 121, and the
mesh grid 129 of the second plate 127 is aligned with the mesh grid
128 of the first plate 126. Additionally, the skin graft 120 is now
sandwiched between the first and second plates 126 and 127. The
mesh grid 128 of the first plate 126 and the mesh grid 129 of the
second plate 127 are only separated by the thickness of the graft
120.
[0058] Now loaded into the cartridge, a plurality of micrografts
may be generated from the single skin graft 120. To generate the
micrografts, the cartridge 119 is flipped right side up and loaded
into the micrograft generating station 104 of device 100. Reference
is now made to FIGS. 5A-5B which show the process of generating the
plurality of micrografts. Cartridge 119 is oriented such that bevel
122 on frame 121 of cartridge 119 is aligned with a bevel in first
slot 112 of cartridge receiving portion 111 of housing 101. Once
aligned, the cartridge 119 is slid into first slot 112. Once in
slot 112, the hollow portion 123 of the frame 121 of the cartridge
119 is aligned with the first member 106 and the second member 107
of the micrograft generating station 104.
[0059] The device 100 is then transformed from the open
configuration to the closed configuration by engaging lever 114,
and moving the lever 114 from an open configuration to a closed
configuration. Such movement causes the top portion 101a and the
cartridge receiving portion 111 of the housing 101 to move
vertically downward toward the bottom portion 101b of the housing
101. With such movement, the mesh grid 129 of the second plate 127
of the cartridge 119 come in contact with the second member 107 of
the micrograft generating station 104. Additionally, the first
member 106 of the micrograft generating station 104 passes into the
hollow portion 123 of the frame 121 of cartridge 119 and contacts
the mesh grid 128 of first plate 126 of the cartridge 119. The
first and second members 106 and 107 compress the mesh grids 128
and 129 of first and second plates 126 and 127 of the cartridge
119. The compressive force results in the mesh grids 128 and 129
cutting the skin graft 120 that is sandwiched between plates 126
and 127, thereby generating the plurality of micrografts. The cuts
may pass partially or completely through the graft tissue. The
plurality of micrografts reside in the holes of the mesh grids 128
and 129.
[0060] Once the micrografts are generated, the lever 114 is moved
from the closed configuration to the open configuration,
transforming device 100 from the closed configuration to the open
configuration. Cartridge 119 is removed from first slot 112 of
cartridge receiving portion 111 of housing 101. The cartridge is
now ready to be transferred to the micrograft transferring station
105.
[0061] Reference is now made to FIGS. 6A-6D which show the process
of transferring the plurality of micrografts to a substrate. The
cartridge 119 is inserted into the second slot 113 of cartridge
receiving portion 111 of housing 101. Cartridge 119 is oriented
such that bevel 122 on frame 121 of cartridge 119 is aligned with a
bevel in second slot 113 of cartridge receiving portion 111 of
housing 101. Once aligned, the cartridge 119 is slid into second
slot 113. Once in slot 113, the hollow portion 123 of the frame 121
of the cartridge 119 is aligned with the transfer pusher 108 and
the transfer stage 110 of the micrograft transferring station
105.
[0062] A substrate 134 is placed on top of transfer stage 110.
Generally, the substrate 134 will have an adhesive side and the
substrate 134 should be placed onto the transfer stage 110 such
that the adhesive side of the substrate 134 is facing up. The
substrate may be made from any material that is biocompatible. In
certain embodiments, the substrate is biocompatible and made from a
material that is capable of being stretched upon application of a
moderate tensile force. Exemplary materials include medical
dressings, such as TEGADERM (medical dressing, commercially
available from 3M, St. Paul, Minn.) or DUODERM (medical dressing,
commercially available from 3M, St. Paul, Minn.). The substrate may
also be gas permeable.
[0063] In certain embodiments, substrate 134 includes an adhesive
on one side that facilitates attachment of the micrografts to the
substrates. The substrate material may have intrinsic adhesive
properties, or alternatively, a side of the substrate may be
treated with an adhesive material, e.g., an adhesive spray such as
LEUKOSPRAY (Beiersdoerf GmbH, Germany).
[0064] In certain embodiments, the material of the substrate 134 is
a deformable non-resilient material. A deformable non-resilient
material refers to a material that may be manipulated, e.g.,
stretched or expanded, from a first configuration to a second
configuration, and once in the second configuration, there is no
residual stress on the substrate. Such materials may be stretched
to an expanded configuration without returning to their original
size. Such deformable non-resilient materials tend to be soft,
stiff or both soft and stiff. Softness is measured on the durometer
scale. An example of such a material is a soft polyurethane. A soft
polyurethane is produced as follows. Polyurethanes in general
usually have soft and hard segments. The hard segments are due to
the presence of phenyl bridges. In a soft polyurethane, the phenyl
bridge is switched out for an aliphatic, which is more flexible as
its 6 carbon ring has no double bonds. Therefore, all the segments
are soft. On the Durometer Scale, a soft polyethylene is rated
about Shore 80A. Other materials suitable for use with methods of
the invention include low density polyethylene, linear low density
polyethylene, polyester copolymers, polyamide copolymers, and
certain silicones.
[0065] The device 100 is then transformed from the open
configuration to the closed configuration by engaging lever 114,
and moving the lever 114 from an open configuration to a closed
configuration. Such movement causes the top portion 101a and the
cartridge receiving portion 111 of the housing 101 to move
vertically downward toward the bottom portion 101b of the housing
101. With such movement, the mesh grid 129 of the second plate 127
of the cartridge 119 come in contact with the substrate 134 that is
on top of the transfer stage 110 of the micrograft generating
station 105. Additionally, the plurality of prongs 109 of the
transfer pusher 108 of the micrograft generating station 105 pass
into the hollow portion 123 of the frame 121 of cartridge 119. The
prongs 109 are small than the holes of the mesh grids 128 and 129.
The prongs pass through the holes of the mesh grids 128 and 129 and
push the micrografts 135 residing in the holes of the mesh grids
128 and 129 through the mesh grids 128 and 129 and onto the
substrate 134.
[0066] Once the micrografts 135 are transferred to substrate 134,
the lever 114 is moved from the closed configuration to the open
configuration, transforming device 100 from the closed
configuration to the open configuration. Due to the adhesive layer
of the substrate 134, after contact with the substrate 134, the
plurality of micrografts 135 remain adhered to the substrate
134.
[0067] Once the micrografts 135 have been transferred to the
substrate 134, the substrate is stretched or expanded, resulting in
increased distance between the individual micrografts, moving them
apart and resulting in production of a skin graft that can repair a
recipient site that is larger than the donor site from which the
grafts were obtained. In methods of the invention, the individual
grafts themselves are not expanded, i.e., the graft tissue is not
stretched; rather, stretching of the substrate increases the space
or distance between each individual micrograft. Methods of the
invention thus minimize tissue manipulation. Methods for expanding
micrografts on a substrate are described for example in U.S. patent
application Ser. No. 12/851,621, the content of which is
incorporated by reference herein in its entirety.
[0068] The purpose of such processing is to use tissue from a donor
site to cover a wound area that is larger than the donor site. The
stretching of the substrate may be done manually, i.e., by hand, or
may be done with the help of a machine. The stretching may be
substantially uniform in all directions or may be biased in a
certain direction. In a particular embodiment, the stretching is
substantially uniform in all directions. Stretching of the
substrate may be performed mechanically or may be accomplished by
application of a pressurized fluid or gas. In certain embodiments,
air pressure is used to expand the first substrate. Exemplary
devices and methods are described in Korman (U.S. Pat. No.
5,914,264), the content of which is incorporated by reference
herein in its entirety.
[0069] Any minimum distance can be provided between micrografts
after the first substrate is stretched. The amount of stretching
can be large enough to provide a sufficiently large area of
substrate containing micrografts to allow a larger area of damaged
tissue to be repaired using a particular amount of graft tissue
removed from the donor site, i.e., the area of the stretched first
substrate containing the separated micrografts can be much larger
than the total area of the donor site. For example, the distance
between adjacent micrografts on the stretched first substrate can
be greater than about 0.5 mm, although small separation distances
may also be used. For repigmentation of skin tissue, an amount of
stretching can be applied to the first substrate such that the
distance between adjacent micrografts is less than about 4 mm,
because it is known that melanocytes, when grafted to a depigmented
region, can migrate up to about 2 mm from each micrograft to
repigment regions between the micrografts. This average distance
can be larger if keratinocyte migration is involved with the tissue
being treated because keratinocytes typically migrate greater
distances compared to melanocytes.
[0070] The ratio of the wound area to the donor site area is
referred to as the expansion ratio. A higher expansion ratio is
desirable to minimize the trauma of the donor site, and to aid
patients who have only a small amount of tissue available for
grafting purposes. The amount of area expansion, e.g., the ratio of
an area of damaged tissue that can be repaired compared to an area
of graft tissue removed from a donor site, may be 500.times. or
more. In particular embodiments, the area of expansion may be from
about 10.times. to about 100.times., which provides a more uniform
coverage and/or repigmentation of the recipient site. For repairing
burns or ulcerated tissue, the micrografts may be smaller than
those used to repair other types of damaged tissue, and thus the
distances between adjacent micrografts may be greater after
stretching of the first substrate. In such an exemplary
application, an area expansion of about 1000.times. or more may be
used.
[0071] In other embodiments and depending on the material of the
substrate 134, maintaining the substrate 134 in a stretched
configuration may result in stress on the substrate 134 that is not
optimal. Additionally, the stretched substrate 134 may not retain
the same properties as the unstretched configuration of the
substrate 134, i.e., technological characteristics, such as
physical, environmental and performance characteristics could be
affected by the stretching of the substrate 134. Additionally,
methods used to maintain the substrate 134 in its stretched
condition may be physically cumbersome and prevent uniform
application of the micrografts to uneven skin surfaces. Thus in
certain embodiments, once the substrate 134 has been stretched, the
spaced apart micrografts are transferred to a second substrate. By
transferring the micrografts to a second substrate, methods of the
invention minimize manipulation and stress of the substrate that
holds the graft to the recipient site.
[0072] After stretching the substrate 134, the second substrate is
brought into contact with the grafts on the stretched substrate
134. Transfer is facilitated by the second substrate having greater
affinity or more adhesive force toward the micrografts than the
substrate 134. In certain embodiments, the second substrate is
coated with a hydrocolloid gel. In other embodiments, the substrate
134 is wetted with a fluid such as water or a saline solution.
Wetting the micrografts and the substrate 134 provides lubrication
between the grafts and the substrate 134 and allows for easy
transfer of the grafts from the substrate 134 to the second
substrate. After wetting the substrate 134, the grafts have greater
affinity for the second substrate than the substrate 134. The
wetted substrate 134 is then removed from the second substrate and
the grafts remain attached to the second substrate. The distance
between the micrografts is maintained after transfer of the
micrografts from the stretched substrate 134 to the second
substrate.
[0073] The second substrate may be made from any material known in
the art that is compatible with biological tissue. The second
substrate may also be capable of being stretched upon application
of a moderate tensile force. Exemplary materials for the second
substrates include medical dressings, such as TEGADERM (medical
dressing, commercially available from 3M, St. Paul, Minn.) or
DUODERM (medical dressing, commercially available from 3M, St.
Paul, Minn.). The second substrate may also be gas permeable.
[0074] In certain embodiments, the second substrate includes an
adhesive on one side that facilitates attachment of the grafts to
the second substrate. The second substrate material may have
intrinsic adhesive properties, or alternatively, a side of the
second substrate may be treated with an adhesive material, e.g., an
adhesive spray such as LEUKOSPRAY (Beiersdoerf GmbH, Germany). In
certain embodiments, the substrate 134 and the second substrates
are the same material. In other embodiments, the substrate 134 and
second substrate are different materials. In certain embodiments,
the materials of substrate 134 and the second substrate are chosen
to facilitate transfer of the micrografts from the substrate 134 to
the second substrate. For example, in certain embodiments, the
material chosen for substrate 134 has a weaker adhesive than the
material chosen for the second substrate.
[0075] In certain embodiments, the material of substrate 134 is a
deformable non-resilient material as discussed above. Such
materials may be stretched to an expanded configuration without
returning to their original size, and thus in these embodiments it
is not necessary to transfer the micrografts from substrate 134 to
a second substrate. Instead, the substrate 134 including the
micrografts is applied to a recipient site.
[0076] Ultimately, the grafts and substrate are applied to a
recipient of site of a patient. Prior to applying the grafts to the
recipient site, the site is prepared to receive the grafts using
any technique known in the art. Necrotic, fibrotic or avascular
tissue should be removed. The technique used to prepare the site
will depend on damage to the recipient site. For example, epidermal
tissue, if present at the recipient site, can be removed to prepare
the area for receiving the micrografts. Burned or ulcerated sites
may not need removal of epidermal tissue, although some cleaning of
the site or other preparation of the site may be performed. Wounds
should be debrided and then allowed to granulate for several days
prior to applying the graft. Most of the granulation tissue should
be removed since it has a tendency to harbor bacteria. Applying
silver sulfadiazine to the wound for 10 days prior to grafting
reduces the bacterial count greatly.
[0077] The size of the area at the recipient site can be about the
same size as the area of the stretched substrate 134 having
micrografts 135 adhered thereto. This size generally will be
greater than the area of the original graft tissue that was removed
from the donor site to form the micrografts. The depigmented or
damaged skin can be dermabraded with sandpaper or another rough
material. Alternatively, the epidermal tissue can be removed from
the recipient site by forming one or more blisters over the area to
be treated, e.g., a suction blister or a freezing blister, and the
raised epidermal blister tissue can then be removed by cutting or
another procedure.
[0078] The substrate having the micrografts can be placed over the
area to be treated to form a dressing. A portion of the substrate
having the micrografts can be positioned over the area to be
repaired, e.g., the area from which the epidermal tissue has been
abraded or removed for repigmentation. The substrate can be fixed
in place over the treatment area, e.g., using tape or the like. The
substrate can be removed after sufficient time has elapsed to allow
attachment and growth of the micrografts in the treatment area,
e.g., several days to a few weeks.
[0079] Reference is now made to FIG. 7, which shows a device 200 of
the invention. Device 200 includes a base member 250, a micrograft
generating station 260 integrated with the base member 250, and a
micrograft transferring station 370 integrated with the base member
250. Integration of the micrograft generating station and the
micrograft transferring station with the base member can be as a
single unitary device or can be such that the micrograft
transferring station and the micrograft generating station are
removably coupled to the base member. In certain embodiments, the
micrograft generating station and the micrograft transferring
station are removed from the base member and are used as individual
stand-alone devices.
[0080] The micrograft generating station 260 comprises a frame 201.
The frame has a top portion 201a and a bottom portion 201b. The top
portion 201a is connected to the bottom portion 201b. The frame 201
has an open configuration and a closed configuration. FIG. 7 shows
the frame 201 in the closed configuration. The micrograft
generating station 260 further includes a first member 206
connected to the top portion 201a of the frame 201, and a second
member 207 connected to the bottom portion 201b of the frame 201.
The first member 206 is aligned with the second member 207.
[0081] In certain embodiments, the second member 207 includes a
spring loaded base (FIG. 8). The spring loaded base includes a
stage 401, coupled to a spring 402. The spring loaded base may
further include a ball 403 to focus the force on the center of the
stage 401.
[0082] Frame 201 further includes a cartridge receiving portion
211. The cartridge receiving portion 211 is located between the top
portion 201a and the bottom portion 201b of the frame 201, and is
also connected with the top portion 201a and the bottom portion
201b of the frame 201. The cartridge receiving portion 211 includes
a slot 212. The slot 212 is aligned with the first and second
members of the micrograft generating station 260. In this figure,
slot 212 is shown with a the cartridge 119 loaded into the slot
212.
[0083] The micrograft generating station 260 also includes a lever
214. The lever 214 is connected to the top portion 201a of the
frame 201. The lever 214 is used to transform the micrograft
generating station 260 from the open configuration to the closed
configuration and back to the open configuration. Linkage arms 215
and 216 are connected to the lever 214, the top portion 201a of the
frame 201, and bottom portion 201b of the frame 201. The linkage
arms 215 and 216 act as force multipliers, such that upon
engagement of the lever 214, an exponential amount of force is
transferred to the micrograft generating station 260 as an operator
transforms micrograft generating station 260 from the open
configuration to the closed configuration. The exponential amount
of force transferred may be varied by varying the length of the
lever 214 or the length of the linkage arms 215 and 216. In certain
embodiments, the micrograft generating station 260 is configured to
provide for at least about a 50.times. increase in force
transferred to the micrograft generating station 260 as compared to
the amount of force applied to the lever 214 by an operator to
transform the micrograft generating station 260 from the open
configuration to the closed configuration.
[0084] The micrograft transferring station 370 comprises a frame
301. The frame has a top portion 301a and a bottom portion 301b.
The top portion 301a is connected to the bottom portion 301b. The
frame 301 has an open configuration and a closed configuration.
FIG. 7 shows the frame 301 in the open configuration. The
micrograft transferring station 370 further includes a transfer
pusher 308 including a plurality of prongs 309. The prongs are
similar to those shown in FIG. 2B. The transfer pusher 308 is
connected to the top portion 301a of the frame 301 such that the
prongs 309 are oriented downward toward the bottom portion 301b of
the frame 301. The micrograft transferring station 370 further
includes a transfer stage 310, which is connected to the bottom
portion 301b of the frame 301. The transfer pusher 308 and the
transfer stage 310 are aligned with each other. In certain
embodiments, the transfer stage 310 may be made of any material
that is softer than that of the transfer pusher 308. In certain
embodiments, the transfer stage 310 is composed of a compressible
material. In other embodiments, the transfer stage 310 includes a
spring loaded base (FIG. 8). The spring loaded base includes a
stage 401, coupled to a spring 402. The spring loaded base may
further include a ball 403 to focus the force on the center of the
stage 401.
[0085] Frame 301 further includes a cartridge receiving portion
311. The cartridge receiving portion 311 is located between the top
portion 301a and the bottom portion 301b of the frame 301, and is
also hingedly connected with the top portion 301a and the bottom
portion 301b of the frame 301. The cartridge receiving portion 311
includes a slot 312. The slot 312 is aligned with transfer pusher
and the transfer stage of the micrograft transferring station 370.
In this figure, slot 312 is shown with a the cartridge 119 loaded
into the slot 312.
[0086] Frame 301 further includes a stripper plate 320. The
stripper plate 320 is located above the bottom portion 301b of the
frame 301 and below the cartridge receiving portion 311 and the top
portion 301a of the frame 301. The stripper plate 320 includes an
inner hollow portion 321 such that the cartridge receiving portion
311, the transfer pusher transfer pusher 308 and the transfer stage
310 fit within the inner hollow portion 321 of the stripper plate
320. Such configuration is important for transfer of micrografts
from the cartridge to the substrate, which is described in greater
detail below.
[0087] The micrograft transferring station 370 also includes a
lever 314. The lever 314 runs through the center of frame 301 and
is connected to the top portion 301a, the cartridge receiving
portion 311, the stripper plate 320, and the bottom portion 301b.
The lever 314 is used to transform the micrograft transferring
station 370 from the open configuration to the closed configuration
and back to the open configuration. The lever 314 acts as a force
multiplier, such that upon engagement of the lever 314, an
exponential amount of force is transferred to the micrograft
transferring station 370 as an operator transforms micrograft
transferring station 370 from the open configuration to the closed
configuration. The exponential amount of force transferred may be
varied by varying the length of the lever 314. In certain
embodiments, the lever 314 is configured to provide for at least
about a 50.times. increase in force transferred to the micrograft
transferring station 370 as compared to the amount of force applied
to the lever 314 by an operator to transform the micrograft
transferring station 370 from the open configuration to the closed
configuration.
[0088] Cartridges that may be used with device 200 are the same as
those described above in connection with device 100.
[0089] Device 200 as described herein may be used to prepare skin
grafts for any recipient site of damaged skin. General methods for
preparing skin grafts are described in co-owned and co-pending U.S.
patent application Ser. No. 12/851,621, the content of which is
incorporated by reference herein in its entirety. In certain
embodiments, methods of the invention generally involve harvesting
a skin graft from a donor site, such as an epidermal graft,
generating an array of micrografts from the single graft, placing
the graft on a first substrate, expanding a distance between the
micrografts on a first substrate, optionally transferring the
micrografts from the first substrate to a second substrate, and
applying the micrografts to a recipient site. Harvesting of the
skin grafts and placing of the harvested skin graft into a
cartridge for use with device 200 is described above.
[0090] Now loaded into the cartridge, a plurality of micrografts
may be generated using device 200. To generate the micrografts, the
cartridge 119 is flipped right side up and loaded into the
micrograft generating station 260 of device 200. Cartridge 119 is
oriented such that bevel 122 on frame 121 of cartridge 119 is
aligned with a bevel in slot 212 of cartridge receiving portion 211
of frame 201. Once aligned, the cartridge 119 is slid into slot
212. Once in slot 212, the hollow portion 123 of the frame 121 of
the cartridge 119 is aligned with the first member 206 and the
second member 207 of the micrograft generating station 260.
[0091] The micrograft generating station 260 is then transformed
from the open configuration to the closed configuration by engaging
lever 214. Such movement causes the top portion 201a and the
cartridge receiving portion 211 of the frame 201 to move vertically
downward toward the bottom portion 201b of the frame 201. With such
movement, the mesh grid 129 of the second plate 127 of the
cartridge 119 come in contact with the second member 207 of the
micrograft generating station 260. Additionally, the first member
206 of the micrograft generating station 260 passes into the hollow
portion 123 of the frame 121 of cartridge 119 and contacts the mesh
grid 128 of first plate 126 of the cartridge 119. The first and
second members 206 and 207 compress the mesh grids 128 and 129 of
first and second plates 126 and 127 of the cartridge 119. The
compressive force results in the mesh grids 128 and 129 cutting the
skin graft 120 that is sandwiched between plates 126 and 127,
thereby generating the plurality of micrografts. The cuts may pass
partially or completely through the graft tissue. The plurality of
micrografts reside in the holes of the mesh grids 128 and 129.
[0092] Once the micrografts are generated, the lever 214 is used to
transform the micrograft generating station 260 back to the open
configuration. Cartridge 119 is removed from slot 212 of cartridge
receiving portion 211 of frame 201. The cartridge is now ready to
be transferred to the micrograft transferring station 370.
[0093] Using micrograft transferring station 370, the micrografts
are transferred to a substrate, as described here. The cartridge
119 is inserted into the 312 of cartridge receiving portion 311 of
frame 301. Cartridge 119 is oriented such that bevel 122 on frame
121 of cartridge 119 is aligned with a bevel in slot 313 of
cartridge receiving portion 311 of frame 301. Once aligned, the
cartridge 119 is slid into slot 313. Once in slot 313, the hollow
portion 123 of the frame 121 of the cartridge 119 is aligned with
the transfer pusher 308 and the transfer stage 310 of the
micrograft transferring station 370.
[0094] A substrate 134 is placed on top of transfer stage 310.
Generally, the substrate 134 will have an adhesive side and the
substrate 134 should be placed onto the transfer stage 310 such
that the adhesive side of the substrate 134 is facing up. Further
description of types of substrates to me used with devices of the
invention is provided above.
[0095] The micrograft transferring station 370 is then transformed
from the open configuration to the closed configuration by engaging
lever 314. Engagement of the lever results in movement that causes
the top portion 301a, the cartridge receiving portion 311, and the
stripper plate 320 to move vertically downward toward the bottom
portion 301b of the frame 301. With such movement, the stripper
plate 320 moves downward and contacts the outer perimeter of the
substrate 134. The hollow inner portion 321 surrounds that transfer
stage 310 and leaves the transfer stage 310 accessible to interact
with the cartridge 119. Then, the cartridge receiving portion 311
and the transfer pusher 308 move downward and into the hollow inner
portion 321 of the stripper plate 320, resulting in the mesh grid
129 of the second plate 127 of the cartridge 119 coming in contact
with the substrate 134 that is on top of the transfer stage 310 of
the micrograft transferring station 370.
[0096] As this is occurring, the plurality of prongs 309 of the
transfer pusher 308 of the micrograft transferring station 370 pass
into the hollow portion 123 of the frame 121 of cartridge 119. The
prongs 309 are small than the holes of the mesh grids 128 and 129.
The prongs pass through the holes of the mesh grids 128 and 129 and
push the micrografts 135 residing in the holes of the mesh grids
128 and 129 through the mesh grids 128 and 129 and onto the
substrate 134. Once the micrografts 135 are transferred to
substrate 134, the lever 314 is used to transform micrograft
transferring station 370 back to the open configuration.
[0097] In greater detail, the mesh grid 129 holding the tissue is
the first component to contact the substrate 134 on the transfer
stage 310. The grid 129, the pusher 308, and the transfer stage
move downward together a small amount before the cartridge
receiving portion 311 that is holding the cartridge 119 holding the
mesh grid 129 hits a stop. The prongs 309 of the pusher 308
continue pushing the tissue held in the grid 129 and the transfer
stage 310 downward until the top portion 301a of the frame 301 hits
a second stop. At this point, the micrografts 135 have been pushed
through the grid 129 and onto the substrate 134 and the micrografts
135 are no longer in contact with the grid 129. Just prior to the
pusher 310 hitting the second stop, a latch 340 on the top portion
301a interacts with a hasp 341 on the cartridge receiving portion
311, locking the top portion 301a to the cartridge receiving
portion 311 so that their upward movement is linked (FIGS. 7 and
9). The lever 314 is then reengaged to transform the micrograft
transferring station 370 back to the open configuration. This
results in the pusher top portion 301a and linked cartridge
receiving portion 311 to move upward until there is no longer
contact with the substrate 134, leaving the micrografts fully
transferred to the substrate 134. During this process, the stripper
plate 320 also moves upward, releasing itself from the edges of the
substrate 134.
[0098] Once the micrografts 135 have been transferred to the
substrate 134, the substrate is stretched or expanded, the
micrografts are optionally transferred to a second substrate, and
the expanded micrografts are applied to a recipient site, all of
which is described above.
INCORPORATION BY REFERENCE
[0099] References and citations to other documents, such as
patents, patent applications, patent publications, journals, books,
papers, web contents, have been made throughout this disclosure.
All such documents are hereby incorporated herein by reference in
their entirety for all purposes.
EQUIVALENTS
[0100] The invention may be embodied in other specific forms
without departing from the spirit or essential characteristics
thereof. The foregoing embodiments are therefore to be considered
in all respects illustrative rather than limiting on the invention
described herein. Scope of the invention is thus indicated by the
appended claims rather than by the foregoing description, and all
changes which come within the meaning and range of equivalency of
the claims are therefore intended to be embraced therein.
* * * * *