U.S. patent application number 17/110446 was filed with the patent office on 2021-03-25 for three dimensional tissue printing device, three dimensional tissue printing method and artificial skin.
The applicant listed for this patent is INDUSTRIAL TECHNOLOGY RESEARCH INSTITUTE. Invention is credited to Chih-Yu Ke, Li-Wen Lai, Chang-Chou Li, Yang-Cheng Lin, Chin-Lung Liu, Teng-Yen Wang.
Application Number | 20210085447 17/110446 |
Document ID | / |
Family ID | 1000005252035 |
Filed Date | 2021-03-25 |
View All Diagrams
United States Patent
Application |
20210085447 |
Kind Code |
A1 |
Li; Chang-Chou ; et
al. |
March 25, 2021 |
THREE DIMENSIONAL TISSUE PRINTING DEVICE, THREE DIMENSIONAL TISSUE
PRINTING METHOD AND ARTIFICIAL SKIN
Abstract
A three dimensional tissue printing method is disclosed. The
three dimensional tissue printing method includes the following
steps: performing large support stand printing to form a first
printing body; performing small support stand printing to form
second printing body on the first printing body and forming a
tissue structure by crossly connecting in between the first
printing body and the second printing body. Besides, a three
dimensional tissue printing device and artificial skin are also
presented.
Inventors: |
Li; Chang-Chou; (Tainan,
TW) ; Lai; Li-Wen; (Taichung, TW) ; Lin;
Yang-Cheng; (Chiayi, TW) ; Liu; Chin-Lung;
(Kaohsiung, TW) ; Ke; Chih-Yu; (Pingtung City,
TW) ; Wang; Teng-Yen; (Yunlin County, TW) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
INDUSTRIAL TECHNOLOGY RESEARCH INSTITUTE |
Hsin-chu |
|
TW |
|
|
Family ID: |
1000005252035 |
Appl. No.: |
17/110446 |
Filed: |
December 3, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
14971211 |
Dec 16, 2015 |
10888416 |
|
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17110446 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B29L 2031/7532 20130101;
B33Y 30/00 20141201; B29C 64/314 20170801; C12N 5/0698 20130101;
A61L 27/60 20130101; B29C 64/112 20170801; A61F 2/105 20130101;
B29K 2105/251 20130101; A61L 27/3839 20130101; B29C 64/364
20170801; B33Y 80/00 20141201; B29K 2995/006 20130101; B29C 64/245
20170801; B29C 64/106 20170801; B29C 64/295 20170801; A61L 2430/34
20130101; B33Y 10/00 20141201; A61L 27/18 20130101; B29K 2105/0058
20130101; B29K 2995/0012 20130101; A61L 27/24 20130101; B29C 64/209
20170801 |
International
Class: |
A61F 2/10 20060101
A61F002/10; B29C 64/112 20060101 B29C064/112; B29C 64/245 20060101
B29C064/245; B29C 64/295 20060101 B29C064/295; B29C 64/314 20060101
B29C064/314; B29C 64/364 20060101 B29C064/364; B29C 64/106 20060101
B29C064/106; A61L 27/18 20060101 A61L027/18; A61L 27/24 20060101
A61L027/24; A61L 27/38 20060101 A61L027/38; A61L 27/60 20060101
A61L027/60; C12N 5/071 20060101 C12N005/071 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 13, 2015 |
TW |
104137567 |
Claims
1. A three dimensional tissue printing method, comprising the
following steps: performing a large support stand printing to form
a first printing body; and performing small support stand printing
to form a second printing body on the first printing body; wherein,
a tissue structure is formed by crossly connecting in between the
first printing body and the second printing body.
2. The three dimensional tissue printing method as claimed in claim
1, further comprising: performing a cell printing to instill a
plurality of cells on the tissue structure formed by crossly
connecting in between the first printing body and the second
printing body.
3. The three dimensional tissue printing method as claimed in claim
2, wherein the step of performing cell printing further comprising
stirring the plurality of cells.
4. The three dimensional tissue printing method as claimed in claim
2, wherein the plurality of cells are the human-body fiber mother
cell.
5. The three dimensional tissue printing method as claimed in claim
1, wherein the step of performing the large support stand printing
further comprising the following steps: providing a
temperature-reaction type material; cooling the
temperature-reaction type material; squeezing out the
temperature-reaction type material; and curing the
temperature-reaction type material.
6. The three dimensional tissue printing method as claimed in claim
5, wherein the temperature-reaction type material can be a
collagen, a melt-state material, a flow-state polylactide (PLA)
with dissolved-solution added, or a polycaprolactone (PCL).
7. The three dimensional tissue printing method as claimed in claim
5, wherein the step of cooling the temperature-reaction type
material includes making the temperature-reaction type material
appear flow-state.
8. The three dimensional tissue printing method as claimed in claim
5, wherein in the step of curing the temperature-reaction type
material includes making the temperature-reaction type material
appear quasi-plastic state.
9. The three dimensional tissue printing method as claimed in claim
1, wherein performing the small support stand printing further
comprising the following steps: exerting an electric voltage;
making a material of the small support stand printing generate
static charge accumulation; and forming a micro jet stream under
the traction of the static charge.
10. The three dimensional tissue printing method as claimed in
claim 9, wherein the material is a volatile macromolecule material,
the flow-state polylactide (PLA) with dissolved-solution added or
polycaprolactone (PCA).
11. The three dimensional tissue printing method as claimed in
claim 9, wherein the material is a solid state drawing snag,
powders, or granular state, and through the process of stirring,
melting, or heat melting.
12. An artificial skin, comprising: a first printing body,
constituted by a temperature-reaction type material; a second
printing body, forming a tissue structure by crossly connecting in
between the first printing body and the second printing body; and a
plurality of human-body fiber mother cells positioned at the tissue
structure formed by crossly connecting in between the first
printing body and the second printing body.
13. The artificial skin as claimed in claim 12, wherein the
temperature-reaction type material is a collagen, a melt-state
material, a flow-state polylactide (PLA) with dissolved-solution
added, or a polycaprolactone (PCL).
14. The artificial skin as claimed in claim 12, wherein the
material of the second printing body is a volatile macromolecule
material, a flow-state polylactide (PLA) with dissolved-solution
added or polycaprolactone (PCL).
15. The artificial skin as claimed in claim 12, wherein the
material of the second printing body is a flow-state material
processed by having a solid state drawing snag, powders, or
granular state, process by stirring, melting, or heat melting.
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application is a divisional application of U.S. patent
application Ser. No. 14/971,211, filed on Dec. 16, 2015, now
pending, which itself claims priority to and the benefit of Taiwan
Patent Application No. 104137567 filed in the Taiwan Patent Office
on Nov. 13, 2015. The disclosure of each of the above-identified
applications is incorporated herein by reference in its
entirety.
TECHNICAL FIELD
[0002] The disclosure relates to a printing device, printing method
and artificial skin, and more particularly, to a three dimensional
tissue printing device, three dimensional tissue printing method
and artificial skin.
BACKGROUND
[0003] Following the progress of computer-aided manufacturing
(CAM), the manufacturers develop a technology of three dimensional
printing capable of rapidly manufacturing the original conceptual
design.
[0004] Additive manufacturing is a rapid prototyping technology and
its manufacturing process is to establish a three dimensional model
through the computer-aided design, and then to have the model
segment horizontally into cross-sections by tiny intervals,
afterward, making use of the manufacturing facilities to have the
liquid, powder, strip-shaped or flake-shaped material to be printed
layer by layer according to the shape of the cross-section, cure
and join, and then pack up to become entity. Conventional cutting
working employs "subtraction" to have a lump of material remove the
unwanted parts while the additive manufacturing employs "addition"
to have the needed parts deposited into three dimensional structure
by the way similar to the printing, thereby, is called three
dimensional printing technology.
[0005] The above-mentioned three dimensional printing technology
can not only overcome the difficulty that the machine tool is
unable to accomplish complicated geometric shape but is also
capable of rapidly forming the prototype without being limited to
their shapes, thereby, is favored in the market. Through years of
progressing, from mainly manufacturing the prototype of polymer
material to the development of industrial goods and tool, the
biomedical material, and the required biomedical products such as
medical aided appliance, scaffold used for tissue working frame
etc. are also able to be working and fabricated. Among them, the
successful medical programs of tissue regeneration and
reconstruction technology are the most challenging directions of
development, and the maximum efficacy and benefit for human
being.
[0006] Although the period of the technological development of
tissue engineering has been over twenty one years, a big break
through has not been able to accomplish. The main reason is that
the existing technology is unable to manufacture and produce
complicated tissue structure that possesses required functions.
Recently, the three dimensional tissue printing technology makes
the development of tissue engineering technology a new beam of
hope. Conceptually, the three dimensional tissue printing
technology can appears the correct positions of the cells in the
tissue, cell interstitial and active molecules at each point in the
three dimensional space, and can fabricate the products of
different appearances, different cells or active molecular density.
For the idea of tissue printing, although the overall concept have
been formed, as far as the existing machine of printing tissue as
concerned, the printed out product is merely a macromolecule tissue
prosthesis possessing the tissue appearance. How to provide a
tissue structure of appropriate growth environment for the cell
still needs breakthroughs for the bottlenecks.
SUMMARY
[0007] The disclosure provides a three dimensional tissue printing
device capable of providing the integrity and mechanical strength
of the three dimensional tissue structure, also capable of having
the precision of "printing the micro structure" improve up to
20.about.200 micron, and further capable of maintaining the cell
function after printing to avoid gene mutation and functional
variation of the cell.
[0008] The disclosure provides a three dimensional tissue printing
method capable of establishing a three dimensional tissue structure
for providing sufficient mechanical strength for the tissue and
having the precision of "printing the micro structure" improve up
to 20.about.200 micron, and further establish a three dimensional
tissue structure suitable for the conditions of cell growth.
[0009] The disclosure provides an artificial skin formed by
printing through the use of the above-mentioned three dimensional
tissue printing device and method. These facilities and methods is
capable of performing customized printing. What is more, as the
artificial skin contains growth factors, it can promotes the growth
of the skin.
[0010] An embodiment of the disclosure provides a three dimensional
tissue printing device which includes a three dimensional moving
platform, an instillation unit, and a carrier unit. The
instillation unit, being connected to the three dimensional moving
platform, further comprising a large support stand printing device
and a small support stand printing device. Among them, the large
support stand printing device being used for filling a
temperature-reaction type material further comprising a
temperature-controlled modulation module, while the small support
stand printing device is used for filling a material. The carrier
unit, being connected to the three dimensional moving platform and
positioned opposite to the instillation unit further comprising a
heating element, wherein, the temperature-controlled modulation
module is used for cooling the temperature-reaction type material
contained in the large support stand printing device; the three
dimensional moving platform moves the large support stand printing
device which has the temperature-reaction type material, after
being cooled down, squeezes out to the carrier unit; the heating
element, heats the temperature-reaction type material, after being
cooled, to form a first printing body; the small support stand
printing device, after being exerted electric voltage, generates
voltage difference with the carrier unit making the material
contained in the small support stand printing device form a micro
jet stream; the three dimensional moving platform moves the small
support stand printing device to make the micro jet stream print on
the first printing body to form a second printing body; and a
tissue structure is formed by crossly connecting between the first
printing body and the second printing body.
[0011] An embodiment of the disclosure provides a three dimensional
tissue printing method which includes the following steps:
performing a large support stand printing to form a first printing
body, and performing a small support stand printing to form a
second printing body on the first printing body, wherein, a tissue
structure is formed by crossly connecting in between the first
printing body and the second printing body.
[0012] An embodiment of the disclosure provides an artificial skin
which includes a first printing body, a second printing body, and a
plurality of human-body fiber mother cells. The first printing body
is constituted by a temperature-reaction type material, and through
the process of cooling the temperature-reaction type material and
curing, the material form a micro jet stream that prints on the
first printing body to form a second printing body, and a tissue
structure is formed by crossly connecting in between the first
printing body and the second printing body, and the plurality of
human-body fiber mother cells are positioned at the tissue
structure formed by crossly connecting in between the first
printing body and the second printing body.
[0013] Based on the above statements, in the three dimensional
tissue printing device, the three dimensional tissue printing
method, and the artificial skin of the disclosure, the first
printing body is constituted by the temperature-reaction type
material. The temperature-reaction type material appears flow-state
through the cooling process. The flow-state temperature-reaction
type material is performed moving-and-printing on the bearing plate
and formed the first printing body through heating and curing
process for providing a main support stand that possesses
mechanical strength. Subsequently, through exerting electric
voltage to make the material form micro jet stream, the micro jet
stream will be printed on the first printing body to form a second
printing body which provides cell connection, and since the line
width of small support stand printing device is relatively smaller,
making them capable of being established between the first printing
bodies and is formed a tissue structure in between with the second
printing body for providing sufficient mechanical strength.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] The accomplishment of this and other objects of the
disclosure will become apparent from the following description and
its accompanying drawings of which:
[0015] FIG. 1 is a schematic drawing of the three dimensional
tissue printing device of the disclosure;
[0016] FIG. 2 is a partial schematic drawing of the infusion unit
and the Z-axis driving element of the disclosure;
[0017] FIG. 3 is a schematic drawing of the infusion unit of the
disclosure;
[0018] FIG. 4 is a schematic drawing of the partial structural
members of the infusion unit in FIG. 3 of the disclosure;
[0019] FIG. 5 is a schematic drawing of the partial structural
members of the quick-released platen assembly in FIG. 3 of the
disclosure;
[0020] FIG. 6 is a schematic drawing of the temperature-controlled
modulation module and syringe platen in FIG. 3 of the
disclosure;
[0021] FIG. 7 is a schematic cross-sectional drawing of the
temperature-controlled modulation module and injection device in
FIG. 3 of the disclosure;
[0022] FIG. 8 is a schematic drawing of the injection device of the
small support stand printing device of the disclosure;
[0023] FIG. 9 is a schematic drawing showing when the small support
stand printing device is performing printing in FIG. 8 of the
disclosure;
[0024] FIG. 10 is a schematic drawing showing the printing
performance of the three dimensional tissue of the disclosure;
[0025] FIG. 11 is the flow chart of the printing method of the
three dimensional tissue of the disclosure;
[0026] FIG. 12 is the schematic drawing of the further flow chart
of the large support stand printing of the disclosure;
[0027] FIG. 13 is the schematic drawing of the further flow chart
of the small support stand printing of the disclosure;
[0028] FIG. 14A through FIG. 14D are schematic drawings showing the
observation of the printing growth of the cell of the small support
stand of the disclosure;
[0029] FIG. 15 is a schematic drawing showing the cells positioned
at the support stand additive of the disclosure;
[0030] FIG. 16 is the cell tissue crystallographic of the real
electric field test of the disclosure;
[0031] FIG. 17 is a simulated schematic drawing of the small
support stand printing device of the disclosure.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0032] The following descriptions are embodiments of the disclosure
employing some particular concrete examples. Those people skilled
in the art are capable of easily realizing the advantages and
efficacies of the disclosure through the content disclosed by the
patent specification of the disclosure.
[0033] FIG. 1 is a schematic drawing of the three dimensional
tissue printing device of the disclosure while FIG. 2 is a partial
schematic drawing of the infusion unit and the Z-axis driving
element of the disclosure. Firstly, as shown in FIG. 1, in the
present embodiment, the three dimensional tissue printing device
(100) includes a instillation unit (110), a three dimensional
moving platform (120) and a carrier unit (130) wherein both the
instillation unit (110) and the carrier unit (130) are connected to
the three dimensional moving platform (120) and the carrier unit
(130) and the instillation unit (110) are mutually opposite.
[0034] The three dimensional moving platform (120) includes a base
seat (150), an X-axis driving element (122), a Y-axis driving
element and a Z-axis driving element (126) wherein the X-axis
driving element (122), the Y-axis driving element and the Z-axis
driving element (126) are furnished on the base seat (150)
respectively.
[0035] To depict in detail, the base seat (150) includes a bottom
part (152), a left support stand (154), a right support stand (156)
and a base seat back plate (158) wherein the left support stand
(154) and the right support stand (156) are furnished on the bottom
part (152) while the base seat back plate (158) is securely clipped
by the left support stand (154) and the right support stand
(156).
[0036] The Y-axis driving element (124) being positioned on the
bottom part (152) includes a Y-axis cable protecting tube (124a)
and a Y-axis trunking box (124b) wherein the Y-axis cable
protecting tube (124a) is positioned between the Y-axis driving
element (124) and the Y-axis trunking box (124b).
[0037] The carrier unit (130), being positioned on the Y-axis
driving element (124) which is capable of driving the carrier unit
(130) to move along the Y-axis direction, includes a heating
element (140) and a cultivation dish (50).
[0038] The X-axis driving element (122) and the Z-axis driving
element (126) are installed at the left support stand (154) and the
right support stand (156) respectively where the X-axis driving
element (122) includes an X-axis cable protecting tube (122a).
[0039] It should be noted that the Z-axis driving element (126),
whose inner structure can be seen in FIG. 2, shown in FIG. 1 is
covered and shielded by a sheet metal part. The instillation unit
(110), being furnished in the Z-axis driving element (126) that is
capable of driving the instillation unit (110) to move in Z-axis
direction, includes a large support stand printing device (110a), a
small support stand printing device (110b) and a cell printing
device (110c). It should be also noted that the small support stand
printing device (110b) shown in FIG. 1 is arranged between the
large support stand printing device (110a) and cell printing device
(110c), but this is not limited in the present embodiment, it all
depends on the real situation that the arrangement order of the
large support stand printing device (110a), the small support stand
printing device (110b) and the cell printing device (110c) can be
adjusted.
[0040] FIG. 3 is a schematic drawing of the infusion unit of the
disclosure; FIG. 4 is a schematic drawing of the partial structural
members of the infusion unit in FIG. 3 of the disclosure; FIG. 5 is
a schematic drawing of the partial structural members of the
quick-released platen assembly in FIG. 3 of the disclosure; while
FIG. 6 is a schematic drawing of the temperature-controlled
modulation module and syringe platen in FIG. 3 of the
disclosure.
[0041] As shown in FIG. 2 through FIG. 6, the instillation unit
(110) includes a driving motor (112), a driving-sliding platform
(114), a rapidly releasing platen assembly (116), a syringe platen
(117), a temperature-controlled modulation module (118) and an
injection device (119).
[0042] The driving motor (112) being connected to the
driving-sliding platform (114) includes a reducer (112a). The
rapidly releasing platen assembly (116) is furnished on the
driving-sliding platform (114).
[0043] The injection device (119) includes an injection push rod
(119a), an injection barrel (119b) and a pinhead (119c) wherein the
injection barrel (119b) is furnished through the
temperature-controlled modulation module (118), and the syringe
platen (117) is inserted into the temperature-controlled modulation
module (118) for withholding the injection barrel (119b), and the
pinhead (119c) is positioned at an end of the injection barrel
(119b) while an end of the injection push rod (119a) is movably
inserted in the injection barrel (119b) with another end of the
injection push rod (119a) connected to the driving-sliding platform
(114) through the rapidly releasing platen assembly (116).
[0044] As shown in FIG. 3 through FIG. 5, in the present
embodiment, the driving-sliding platform (114) includes a top plate
(114d), a side plate (114e), a bottom plate (1140, a bearing plate
(114m), two guided rods (114c), a ball screw (114b), a securing
member (114a), a connecting member (114g), two linear bushings
(114j), a ball screw nut (114i), an indentation (114h) and two
magnetic elements (114k).
[0045] As shown in FIG. 3 and FIG. 4, the top end and the bottom
end of the side plate (114e) are perpendicularly connected to the
top plate (114d) and the bottom plate (1140 respectively to form a
containing space. The reducer (112a) of the driving motor (112) is
positioned on the top plate (114d) while the bearing plate (114m)
is positioned beneath the top plate (114d). The securing member
(114a), the ball screw (114b), the two guided rods (114c), the two
linear bushings (114j) and a ball screw nut (114i) (see FIG. 5) are
all positioned in this containing space.
[0046] To state in detail, the two guided rods (114c) are
positioned on both sides of the ball screw (114b), the two linear
bushings (114j) are positioned on both sides of the ball screw
(114i). The two guided rods (114c) are sleeved into the two linear
bushings (114j) while the ball screw (114b) is sleeved into the
ball screw nut (114i). The connecting member (114g) is connected to
the securing member (114a). the indentation (114h) is formed at the
connecting member (114g) while the two first magnetic elements
(114k) are positioned within the indentation (114h).
[0047] The rapidly releasing platen assembly (116) includes a
platen (116a), two embossment added nuts (116b), a push rod screw
(116c), a trench (116d), two salient parts (116e) and the second
magnetic element (1160.
[0048] The two embossed nuts (116b) are furnished on both sides of
the platen (116a) respectively. The push rod screw (116c) being
penetrated through the two embossed nuts (116b) and platen (116a)
has an end connected to injection push rod (119a).
[0049] In the present embodiment, the platen (116a) being
structurally a horseshoe-shape itself has an end thereof possess
the two salient parts (116e). The trench (116d) is formed between
the two salient parts (116e) of the platen (116a). The two second
magnetic elements (1160 being furnished on the platen (116) are
positioned on both sides of the trench (116d) respectively. Based
on this, the two first magnetic elements (114k) and the two second
magnetic elements (1160 are mutually attracted making the platen
(116a) connect to the connecting member (114g).
[0050] Under this disposition, the driving motor (112) drives the
ball screw (114b) making the ball screw (114b) and the ball screw
nut (114i) perform relative rotation. Since both ends of the ball
screw (114b) are pivotally supported, it makes the ball screw nut
(114i) be driven by the ball screw (114b) to rotate and perform,
together with the securing member (114a), up-and-down linear motion
in Z-direction on the two guided rods (114c) so as to push the
injection push rod (119a) to move along inside the injection barrel
(119b). In other embodiments not shown in the Figures, a guidance
mode of linear sliding rail and slider can be employed or a
pneumatic pushing mode can also be employed to push the injection
push rod to be moved within the injection barrel, but the present
embodiment is not limited to these.
[0051] FIG. 7 is a schematic cross-sectional drawing of the
temperature-controlled modulation module and injection device in
FIG. 3 of the disclosure. Please refer to FIG. 2, FIG. 3, FIG. 6
and FIG. 7.
[0052] In the present embodiment, the temperature-controlled
modulation module (118) includes cooling water ring jacket (118a),
a containing part (118b), a cool-guidance washer (118c), a cooling
inner ring (118d), an O-ring (118e), a heat-exchange area (1180, a
first temperature modulation pipeline (118g), a second temperature
modulation pipeline (1180.
[0053] As shown in FIG. 2, the first temperature modulation
pipeline (118g) and the second temperature modulation pipeline
(1180 are communicated to the inner part of the cooling water ring
jacket (118a) such that the first temperature modulation pipeline
(118g) and the second temperature modulation pipeline (1180 are
able to outwardly connected to a water source supply device (not
shown in the Figure). In the present embodiment, the water source
supply device, for instance, can be a chiller which is capable of
providing ice water by the way of performing heat exchanging with
refrigerant.
[0054] Referring again to FIG. 3, FIG. 6 and FIG. 7, the cooling
inner ring being furnished in the cooling water ring jacket (118a)
forms the heat-exchange area (1180 there between, while the first
temperature modulation pipeline (118g) and the second temperature
modulation pipeline (1180 are communicated within the heat-exchange
area (1180. The O-ring (118e) is positioned between the cooling
water ring jacket (118a) and the cooling inner ring (118d) for
preventing the liquid from leaking from the junction between
cooling water ring jacket (118a) and cooling inner ring (118d). The
cool-guidance washer (118c) being positioned between the front end
of the injection barrel (119b) and the cooling water ring jacket
(118a) have the heat at low-temperature therein transfer by
conduction to the pinhead (119c) to maintain the pinhead (119c) at
low temperature as within the injection barrel (119b) to enhance
the cool-maintaining effect of the temperature-reaction mode of
material.
[0055] The injection barrel (119b) being positioned within the
containing part (118b) formed by the cooling inner ring (118d)
possesses a material feeding area (119d). In the present
embodiment, the material feeding area (119d) is capable of filling
the corresponding material depending on the what kind of printing
device it is. In an embodiment, the collagen of the
temperature-reaction type material is filled in the material
feeding area (119d) in the large support stand printing device
(110a) as shown in FIG. 1. In other embodiment, the biodegradable
materials such as the volatile macromolecule material, the
flow-state Polylactide (PLA) with dissolved-solution added or
Polycaprolactone etc. is filled in the material feeding area (119d)
in the small support stand printing device (110b) as shown in FIG.
1. In another embodiment, the human-body fiber mother cell is
filled in the material feeding area (119d) in the cell printing
device (110c) as shown in FIG. 1.
[0056] Under this disposition, through the chiller (not shown in
the Figure), having the ice water at 4-degree C. from the first
temperature modulation pipeline (118g) enter the heat-exchange area
(1180 and through second temperature modulation pipeline (118h) to
carry the ice water away from the heat-exchange area (1180, it is
capable of having the 4-degree ice water perform circulation with
the heat-exchange area to make the temperature-controlled
modulation module (118) maintain at the state of low temperature.
However, it is not limited in the present embodiment, in the other
embodiment, the temperature-controlled modulation module is capable
of having different fluid pass through according to the temperature
control requirements, for instance, ice water under the room
temperature, hot water above the room temperature, refrigerant,
coal-burning oil, various fluids that is capable of performing heat
exchange reaction. In another embodiment, the
temperature-controlled modulation module is also capable of
performing cooling and heating control through refrigerating chip
or electric heating.
[0057] FIG. 10 is a schematic drawing showing the printing
performance of the three dimensional tissue of the disclosure. As
shown in FIG. 10, after completing the introduction of the
structure of the above-mentioned three dimensional tissue printing
device, subsequently, the large support stand printing device
(110a), small support stand printing device (110b) and cell
printing device (110c) are introduced as follows: As far as the
large support stand printing device (110a) is concerned, it is used
for filling a temperature-reaction type material which is mainly a
collagen. The characteristics of the collagen are as follows: (a)
The collagen is capable of appearing flow-state if it is maintained
below 4.degree. C. temperature; (b) The collagen is capable of
appearing quasi-plastic-state if it is heated to 37.degree. C.
temperature; (c) The collagen is capable of performing reversible
reaction if it is maintained between 4.degree. C. and 37.degree. C.
temperature. In other embodiment, the temperature-reaction type
material can be melt-state material, the biodegradable materials
such as a flow-state Polylactide (PLA) with dissolved-solution
added, or a polycaprolactone (PCL) etc.
[0058] Under this disposition, temperature-controlled modulation
module (118) is employed to cool down the temperature-reaction type
material, the three dimensional moving platform (120) moves the
large support stand printing device (110a) which has the
temperature-reaction type material, after being cooled, squeeze out
to the carrier unit (130), the heating element (140) has the
temperature-reaction type material, after being cooled down, to be
heated to form the first printing body (60) as shown in FIG.
10.
[0059] To explain in detail, in the process that the large support
stand printing device (110a) prints the first printing body (60),
the temperature-reaction type material is contained in the material
feeding area (119d) (e.g. FIG. 7) of the injection barrel (119b).
In the present embodiment, the temperature-reaction type material
is collagen for example, and the injection barrel (119b) is
penetrated in the temperature-controlled modulation module (118)
which, employs the above-mentioned cooling mode and is capable of
maintaining a low temperature of below 4.degree. C. temperature,
makes the temperature-reaction type material in the injection
barrel (119b) appear flow-state while the way of cooling has been
mentioned above and is not going to repeat here.
[0060] Subsequently, pushing the injection push rod (119a) to make
the temperature-reaction type material, after being cooled down,
squeeze out from the pinhead (119c) to the carrier unit (130)
while, through the cool-guidance washer (118c), make the pinhead
(119b) capable of maintaining a low temperature of below 4.degree.
C. temperature and enhancing the cool-maintaining effect of the
temperature-reaction type material contained in the injection
barrel (119b). Besides, by making use of the movement of the three
dimensional moving platform (120) to let the pinhead (119c) and
carrier unit (130) generate relative movement and, also through the
heating action of the heating element (140) for curing the
temperature-reaction type material after being cooled to form the
first printing body (60), and the first printing body (60), after
being cured, is capable of providing a main support stand that
possesses strength.
[0061] FIG. 8 is a schematic drawing of the injection device of the
small support stand printing device of the disclosure while FIG. 9
is a schematic drawing showing when the small support stand
printing device is performing printing in FIG. 8 of the disclosure.
As shown in FIG. 1, FIG. 8, and FIG. 9, as far as the small support
stand printing device (110b) is concerned, the three dimensional
tissue printing device (100) further includes an electric field
auxiliary system (20) which is coupled to the injection device
(119) and the carrier unit (130).
[0062] The electric field auxiliary system (20) includes a power
supply (21) and a voltage controller (22).
[0063] The small support stand printing device (110b) is used for
filling a material which, for example, is the biodegradable
materials such as a volatile macromolecule material, a flow-state
Polylactide (PLA) with dissolved-solution added, or a
polycaprolactone (PCL), and so forth. In other embodiment, the
material can also be the one possessing flow-state by the use of a
solid state drawing snag, powders, or granular state, and through
the process of stirring, melting, or heat melting.
[0064] Under this disposition, having the small support stand
printing device (110b) be activated by voltage, a voltage
difference is generated between the an injection device (119) of
the small support stand printing device (110b) and the carrier unit
(130) making the material in the small support stand printing
device (110b) form a micro jet stream, while the three dimensional
moving platform (120) moves the small support stand printing device
(110b) making the micro jet stream print on the first printing body
(60) and form a second printing body (70) and making a tissue
structure (e.g. as shown in FIG. 10) crossly-connected form between
the first printing body (60) and second printing body (70).
[0065] To state in detail, while the small support stand printing
device (110b) is printing the second printing body (70), the
material is contained in the material feeding area (119d) (as shown
in FIG. 7) of the injection barrel (119b), by means of moving the
an injection device (119) by the three dimensional moving platform
(120), the pinhead (119c) is made to maintain a distance H with the
carrier unit (130) where the distance H is between 0.2 mm through 5
mm.
[0066] The voltage controller (22) being used for providing a
voltage condition is output to the pinhead (119c) through the power
supply (21), wherein the voltage condition is the relative voltage
difference provided in the range of 10 through 30 kv between the
pinhead (119c) and the carrier unit (130). In the present
embodiment, the pinhead (119c) is connected to positive voltage,
however, the present embodiment is not limited to this, the pinhead
(119c) can be either connected to negative voltage or to the ground
in other embodiments.
[0067] Subsequently, pushing the injection push rod (119a) to make
the material flow out from the pinhead (119c). As the surface of
the material being subjected to traction generates electric charge
polarity and accumulate near the tip of the pinhead (119c). These
accumulated electric charges makes the material form a Taylor cone
(32) (as shown in FIG. 9) at the tip of the pinhead (119c) and
generate a micro jet stream (34) spraying out from the Taylor cone
(32). Besides, by making use of the movement of the three
dimensional moving platform (120) to let the pinhead (119c) and
carrier unit (130) generate relative movement, the micro jet stream
(34) is printed on the first printing body (60) forming the second
printing body (70) (as shown in FIG. 10) which is capable of
providing cell connection.
[0068] Comparing with the first printing body (60), since the line
width of the second printing body (70) printed by the small support
stand printing device (110b) is relatively small, they can be
constructed between the previous first printing bodies (60). As
shown in FIG. 10, the second printing body (70) includes a
multiplicity of long strips that are perpendicular and connected to
the ones on the first printing body (60) and are contained thereof
for providing sufficient mechanical strength. Moreover, the long
strip structures of the second printing body (70) are crossly
connected with the ones in the first printing body (60) to form a
plurality of cell-disposed spaces for providing the cultivation and
proliferation for the cells with stable growth environment.
[0069] As far as the cell printing device (110c) is concerned, the
cell printing device (110c) is used for filling the human-body
fiber mother cells (80) which are contained in the material feeding
area (119d) (as shown in FIG. 7) of the injection barrel (119b).
Under this disposition, the three dimensional moving platform (120)
moves the cell printing device (110c) making the human-body fiber
mother cells (80) instill into the tissue structure formed by
crossly connecting between the first printing body (60) and the
second printing body (70). Moreover, by means of the Z-axis driving
element (126) of the three dimensional moving platform (120), the
cell printing device (110c) is made to perform reciprocating
movement (e.g. make the cell printing device 110c perform
up-and-down linear motion in Z-axis direction) making the
human-body fiber mother cells (80) perform stirring action to
improve the density uniformity of the cell instillation.
[0070] FIG. 11 is the flow chart of the printing method of the
three dimensional tissue of the disclosure. As shown in FIG. 11,
the three dimensional tissue printing method S200 in the present
embodiment includes the following step S210 through step S230:
[0071] What is needed to explain that the three dimensional tissue
printing method S200 includes a pre-operating flow chart.
[0072] Firstly, Providing the three dimensional tissue printing
device (100) as shown in FIG. 1.
[0073] Subsequently, printing the parameter set-up, for instance,
the parameters of the set-up of cooling temperature, printing path,
printing speed, voltage strength, the distance between the pinhead
(119c) and the carrier unit (130) etc.
[0074] Afterward, Feeding the printing material: take the large
support stand printing device (110a) for example, as shown in FIG.
7, having the temperature-reaction type material feed into the
material feeding area (119d). In this way, the pre-operating flow
chart is substantially completed.
[0075] Performing Step S210, Performing a large support stand
printing to form a first printing body.
[0076] The Step S210 further includes the following steps: FIG. 12
is the schematic drawing of the further flow chart of the large
support stand printing of the disclosure, as shown is FIG. 12 which
is a further schematic flow chart drawing of the large support
stand printing of FIG. 11.
[0077] Performing Step S212, provides a temperature-reaction type
material.
[0078] The temperature-reaction type material is a collagen. In
other embodiments, the temperature-reaction type material can be
biodegradable materials such as a melt-state material, Polylactide
(PLA) of added dissolved-solution or polycaprolactone (PCL)
etc.
[0079] Subsequently, Step S214 is performed, cooling
temperature-reaction type material.
[0080] The step for cooling the temperature-reaction type material
includes making the temperature-reaction type material appear
flow-state. As far as the present embodiment is concerned, cooling
the temperature-reaction type material till below 4.degree. C.
temperature and maintaining below 4.degree. C. temperature makes
the temperature-reaction type material appear flow-state.
[0081] Subsequently, performing the Step S216 to squeeze out the
temperature-reaction type material.
[0082] As far as the present embodiment is concerned, the driving
motor (112) drives the driving-sliding platform (114) making the
ball screw (114b) and the ball screw nut (114i) relatively rotate.
Since both ends of the ball screw (114b) are pivotally supported,
the ball screw nut (114i) is driven to rotate by the ball screw
(114b), and together with the securing member (114a) and the two
linear bushings (114j) to perform up-and-down linear motion in
Z-direction so as to push the injection push rod (119a) to move
along inside the injection barrel (119b) so as to squeeze out the
temperature-reaction type material in the injection barrel (119b).
In other embodiments not shown in the Figures, a guidance mode of
linear sliding rail and slider can be employed or a pneumatic
pushing mode can also be employed to push the injection push rod
(119a) to be moved within the injection barrel (119B), but the
present embodiment is not limited to these.
[0083] Besides, in the process of squeezing out the
temperature-reaction type material, the three dimensional moving
platform (120) is employed to make the pinhead (119c) move, and the
moving path can be various modes of shapes such as zigzag,
dendritic, mesh structure, concentric circle and helical etc. to
form through required printing framework, however, the present
embodiment is not limited to these, it all depends on the real
requirements to adjust the printing framework.
[0084] Subsequently, the Step S218 is performed to cure the
temperature-reaction type material.
[0085] In the Step S218 of curing the temperature-reaction type
material includes heating the temperature-reaction type material to
make it appear a quasi-plastic state to form the first printing
body for providing the main support stand which possesses
strength.
[0086] Referring again to FIG. 11 to perform the Step S220,
performing a small support stand printing to form a second printing
body on the first printing body, wherein a tissue structure is
crossly-connected formed between the first printing body and the
second printing body.
[0087] What is needed to depict is that after completing the Step
S210, the process will come back to the pre-operating flow chart.
At this moment, in the process of setting up the printing
parameter, the set-up of the printing path, printing speed, voltage
strength, the distance H between the pinhead (119c) and the carrier
unit (130) wherein the distance H is between 0.2 mm through 5
mm.
[0088] When it comes to filling the material, taking the small
support stand printing device (110b) for example, having the
biodegradable materials such as a volatile macromolecule material,
a flow-state Polylactide (PLA) with dissolved-solution added, or a
polycaprolactone (PCL), and so forth or the one possessing
flow-state by the use of a solid state drawing snag, powders, or
granular state, and through the process of stirring, melting, or
heat melting fill in the material feeding area (119d) (e.g. FIG. 7)
of the injection barrel (119b).
[0089] FIG. 13 is the schematic drawing of the further flow chart
of the small support stand printing of the disclosure. As shown in
FIG. 11, the Step S220 further includes the following steps:
[0090] First of all, performing the Step S2223, exerting an
electric voltage and subsequently, performing Step S224 to make a
material printed by the small support stand printing device
generate static charge accumulation. Step S226: a micro jet stream
is formed under the traction function of the electric charge.
[0091] As far as the present embodiment is concerned, by exerting
electric voltage, a voltage difference is formed between the small
support stand printing device (110b) and carrier unit (130) making
the material contained in the small support stand printing device
(110b) form a micro jet stream while the three dimensional moving
platform (120) moves the small support stand printing device (110b)
making the micro jet stream print on the first printing body (60)
to form the second printing body (70) as shown in FIG. 10. This
second printing body provides cell connection while a tissue
structure is formed between the first printing body (60) and the
second printing body (70).
[0092] What is needed to explain is that after completing the Step
S220, it will conducting-through member (140) back to a
pre-operating flow chart. At this moment, the following parameter
set-up needs to be readjusted: printing path, printing speed,
voltage strength, the distance between the pinhead (119c) and the
carrier unit (130), and so forth.
[0093] Referring again to FIG. 11 to perform Step S230, performing
cell printing, infusing a plurality of cell at the tissue framework
formed by crossly connecting in between the second printing body
and the first printing body.
[0094] The steps for performing the cell printing includes:
Stirring the plurality of cells which are the human-body fiber
mother cells, as shown in FIG. 11, the human-body fiber mother
cells (80) are the tissue structure crossly-connected formed
between the first printing body (60) and the second printing body
(70).
[0095] In this way, repeating the step S210 through the step S230
to repeat the printing procedure to be able to form a three
dimensional tissue structure.
[0096] Referring again to FIG. 10, in the present embodiment, the
first printing body (60) is constituted by temperature-reaction
type material which being mainly a collagen becomes the first
printing body (60) through the process of cooling and curing the
temperature-reaction type material.
[0097] The second printing body (70) is constituted by materials,
e.g. the biodegradable materials such as a volatile macromolecule
material, a flow-state Polylactide (PLA) with dissolved-solution
added, or a polycaprolactone (PCL) etc. Therefore, the materials
form micro jet stream through exerting electric voltage. The micro
jet stream is sprayed to print on the first printing body (60) to
form a second printing body (70). Besides, a tissue structure is
formed by crossly connecting in between the first printing body
(60) and the second printing body (70).
[0098] The plurality of human-body fiber mother cell (80) is
positioned in a tissue structure formed by crossly connecting in
between the first printing body (60) and the second printing body
(70).
[0099] FIG. 14A through FIG. 14D are schematic drawings showing the
observation of the printing growth of the cell of the small support
stand of the disclosure. As shown in FIG. 14A through FIG. 14D, in
an embodiment, this three dimensional tissue structure is capable
of applying in the three dimensional skin tissue printing to form
an artificial skin. Take the above-mentioned FIG. 10 for example,
the first printing body (60) employs collagen, the second printing
body (70) employs biodegradable material, while the cell employs
human-body fiber mother cell having the cell cultivation liquid
employ fetal bovine serum.
[0100] Through the substantial printing testing, FIG. 14A
represents the printing, by small support stand printing, to become
grid with line width being 50.about.95 .mu.m. FIG. 14B shows that
the fiber mother cells, being appear in spherical shapes, are just
instilled. As shown in FIG. 14C, the fiber mother cells stickers
cover appears slender strips in shape while the fiber mother cells
shown in FIG. 14D shows that the fiber mother cells is successfully
duplicated and proliferated and connected. As can be seen from FIG.
14B through FIG. 14D, the cells can be maintained printing cell
function and also can be successfully proliferated. This is
sufficient to prove that the tissue structure made by employing the
three dimensional tissue printing device and the three dimensional
tissue printing method is capable of providing cell cultivation and
the proliferated and stable growth environment. When it comes to
applying the three dimensional tissue printing to form artificial
skin, since the human-body fiber mother cell that contains growth
factors is employed, the human-body fiber mother cell can promote
the skin growth without exclusivity. Besides, FIG. 15 is a
schematic drawing showing the cells positioned at the support stand
additive of the disclosure.
[0101] FIG. 16 is the cell tissue crystallographic of the real
electric field test of the disclosure. Please refer to in FIG. 5
and FIG. 16.
[0102] As shown in FIG. 9, if the simulated condition will be
affected by the pinhead length L, the aperture D of the pinhead,
and the surface tension .gamma. of the liquid, the electric voltage
of the micro jet stream (34) generated from spraying from the tip
of the Taylor cone (32) is called critical voltage V.sub.c and this
critical voltage divided by the distance H between the pinhead
(119c) and the carrier unit (130) is called critical electric field
E.sub.c, the calculation formula is as follows:
E c 2 = 2 L 2 ( ln 2 D - 3 2 ) ( 0.117 .pi..gamma. D ) ( 1 )
##EQU00001##
[0103] FIG. 17 is a simulated schematic drawing of the small
support stand printing device of the disclosure. As shown in FIG.
17, it shows the relationship between the ratio of Z/D and the
electric field, where Z is the distance between the cultivation
dish (50) and the tip of the pinhead (119c), D is the aperture of
pinhead. In the present embodiment, if the length of the fixed
pinhead is 3 mm, the influence of the pinhead aperture to the jet
printing is discussed. The smaller the aperture of the pinhead,
through the simulation, the greater the gained electric field and
the smaller the sprayed line width of the micro jet stream they
are, and the experimental result shows the same trend. Considering
the degree of difficulty of manufacturing the pinhead, if the sizes
of the pinhead (119c) are that the aperture D=0.6 mm, length of the
pinhead L=3 mm, the received area electric field of the carrier
unit (130) is around 200 kV/m, then the optimum ratio of Z/D is
between 1 through 10 according to the results of the analysis. FIG.
16 is the cell tissue crystallographic of the real electric field
test of the disclosure. As shown in FIG. 16, as for the effect of
the influence of the high voltage electric field with respect to
the cell, the titration of the human-body fiber mother cell is
performed, under the pinhead of the small support stand printing
device, the cell is substantially scanned by 200 kV/m of electric
field for 10 minutes and cultivated for 48 hours, the cell is still
capable of performing proliferation through observation without
being affected by the high voltage electric field. However, the
small support stand printing device needs to be exerted by electric
voltage only while it is performing printing, but the cell printing
device (110c) does not need to be exerted by electric voltage while
it is performing printing.
[0104] To summarize the above statements, in the three dimensional
tissue printing device, three dimensional tissue printing method
and artificial skin of the disclosure, the first printing body is
constituted by the temperature-reaction type material which appears
flow-state through the cooling process. The flow-state
temperature-reaction type material performs movingly printing to
become first printing body through heating-to-cure process for
providing a main support stand that possesses mechanical
strength.
[0105] Then, by exerting electric voltage, the material forms micro
jet stream which prints on a first printing body to form second
printing body that provides cell connection. Since the line width
of the second printing body is relatively small, they can be
constructed between the first printing bodies and the second
printing body includes a multiplicity of long strips that are
perpendicular and connected to the ones on the first printing body
and are contained thereof for providing sufficient mechanical
strength and a plurality of cell-disposed spaces are formed for
providing the cultivation and proliferation for the cells with
stable growth environment.
[0106] Moreover, the human-body fiber mother cell instills in
between the first printing body and the second printing body and
are crossly connected to form a tissue structure, and the printing
process is repeated to form a three dimensional tissue structure so
as to provide the integrity and mechanical strength of the three
dimensional tissue structure. Besides, the precision of printed
microstructure is improved down to 20.about.200 micrometer
structure. It is capable of further maintaining the cell function
after printing, establishing a three dimensional tissue structure
to avoid the gene mutation and functional variation of the
cell.
[0107] What is more, when it comes to applying in the three
dimensional skin tissue printing and forming artificial skin, as
the human-body fiber mother cells employed to make the artificial
skin contain growth factors, the artificial skin, formed by the
above-mentioned three dimensional tissue printing device and the
printing method, can promote the skin growth without exclusivity by
the growth factors. Besides, as the three dimensional tissue
printing device of the disclosure can set the moving path of the
three dimensional moving platform to form the required printing
framework according to the requirements (e.g. the range of wound
part) of the user, thereby, can accomplish the customer-made
printing skin tissue so as to completely stick on the wound part
and reduce the risk of wound infection.
[0108] It will become apparent to those people skilled in the art
that various modifications and variations can be made to the
structure of the disclosure without departing from the scope or
spirit of the disclosure. In view of the foregoing description, it
is intended that all the modifications and variation fall within
the scope of the following appended claims and their
equivalents.
* * * * *