Technical field of the invention
[0001] This invention relates to a continuous electrospinning system and process for the
production of three-dimensional matrices of aligned polymeric fibres.
[0002] From the invention applicability, it is possible to obtain three-dimensional matrices
of aligned polymeric fibres, which can present several patterns of fibre alignment
along the matrix thickness, being this thickness dependent on the number of deposited
fibre layers, the fibre thickness and the degree of compaction between layers.
[0003] In this way, the present invention has been applied in various areas, in the manufacture
of products or structures, at the nanometric scale, which depend on the high surface
area, such as biotechnology, pharmaceuticals, research, tissue engineering and medicine,
particularly in regenerative medicine, such as cell therapy, cartilaginous and related
tissue production, especially for the replacement and strengthening of joints.
Prior Art
[0004] Among the main themes of interest in the processing of polymeric materials is the
production of micro or nanostructured polymeric structures, especially nanofibres
or nanowires. The unique properties of nanomaterials associated with the different
possibilities of morphologies and functionalities reveal a series of possibilities
for new fields of application and drive the progress in the processing of these nanostructures.
[0005] In this regard, the electrospinning or electrostatic spinning method is very advantageous,
since the fibres obtained with this technique have a high surface area, combined with
a low production cost and the possibility of being formed from a wide variety of polymers
or composites. This technique is based on the application of high voltage (5-50 KV)
and low current (0.5-1 µA) electric fields for the production of very small diameter
fibres. In this process, the electrostatic forces control the formation and deposition
of these fibres.
[0006] The document
US2349950A describes a basic experimental arrangement, in which the proposed diagram already
presents a configuration formed by a high voltage source, polymeric solution and a
grounding system.
[0007] The documents
US 2013/302595,
US 2013/095252 and
US 2012/301567 are related to materials, coatings and apparatus but don't disclosed any of the features
relates to the system and process of continuous electrospinning for the production
of three-dimensional matrices of aligned polymeric fibres of the present invention
including all of the features claimed in the current application.
[0008] Currently, the key configuration of a generic electroplating process consists of
a syringe, where the molten polymer or polymeric solution is introduced, which is
connected to a capillary tube, a diffuser pump, which controls the flow of the polymeric
solution to be supplied, so that a drop of solution is always maintained at the tip
of the capillary tube, a metal collector, maintained at zero potential (grounded),
where the fibres produced will be collected, a high voltage source, responsible for
producing a difference in potential between the tip of the capillary tube and the
collector. With the application of the electric field between the capillary tube and
the collector the drop of solution is subject to the orientation of loads on its surface.
[0009] As the field intensity increases, the balance of electrostatic charges to which the
droplet is subjected, namely the surface tension force of the solution and the force
exerted by the applied electric field, begins to suffer an imbalance and, from a certain
critical value of electric field, a jet of polymeric material from the capillary tube
is projected and accelerated towards the collector.
[0010] During the trajectory to the collector, the jet with the polymeric solution suffers
evaporation of a large part of its solvent, thus ensuring that the fibres formed have
enough rigidity to support their own weight. In addition, the solvent that remains
in the solution, such as moisture, allows the adhesion of one fibre to another, as
they are deposited in layers, forming a non-woven web. In this basic configuration,
the electrospun fibres form a two-dimensional, randomly oriented blanket or fabric
due to the instability of the jet path.
[0011] Interest in the electrospinning process has grown very rapidly since the 1990s. Multidisciplinary
efforts, both in the area of academic and application-oriented research, have generated
a huge number of scientific publications, patent applications and a significant increase
in the exploitation of the technique by companies of filtration products, regenerative
medicine, protective clothing, catalysis, among others.
[0012] Oriented fibre networks have the possibility of developing anisotropic properties
in materials. These relationships are quite obvious in the field of tissue engineering.
[0013] Typical examples include the production of polymeric meshes, containing aligned fibres,
used as substrates for culture and regeneration of neural cells, due to the inherently
anisotropic nature of nerves and their regenerative mechanisms. In these bioengineering
applications, it is a fundamental requirement that the scaffold material has a three-dimensional
structure of controlled porosity, so that it is possible to develop three-dimensional
cell construction at the full depth of the matrix.
[0014] Many efforts have been concentrated on the production of aligned fibres with controlled
standardization, due to its exceptional potential for development of functional devices,
such as those presented in documents
US20120009292A1,
US20110142806A1 and
US2016004706A1.
[0015] Several approaches have been suggested to promote the alignment of the electrospun
fibre blankets, among which the "air gap electrospinning" process, which foresees
the configuration of spaced parallel electrodes, with the fibres stretched in the
spacing between the plates, has been the most used method to deposit and collect these
fibres.
[0016] The publication of a pioneering work by Dan Li and collaborators (
Li, et al., Nanoletters, 2003, 3:8, 1167) showed that two effects favoured the production and deposition of nanofibres well
aligned between the electrode space parallel to each other, namely the effect of nanofibres
deposition direction, caused by deformation of the electric field between the capillary
tube and the collector, and the accumulation of charges along deposited nanofibres,
which favoured the parallel arrangement between them, due to electrostatic repulsion.
[0017] An interesting variation of this assembly system is the collector for production
of fibre matrices, whose system comprises electrodes arranged in a 90° separated plane.
The operation is based on the connection of the ground terminal to the electrodes
arranged in the same line. The electrospun fibres are collected between the electrodes,
which are connected to ground, and this connection is alternated between the pairs
of electrodes with defined time intervals, allowing the formation of a mesh with layers
of fibres with different arrangements (
Li, et al., Adv. Matter, 2004, 16:4, 361) .
[0018] In this regard, document
US20110018174A1 discloses the production of aligned electrospun fibres, with location and orientation
control of the fibres, using for this purpose a device that provides a voltage depending
on the selected time, whereby that voltage is applied to a collector with multiple
electrodes. However, said document does not disclose a process capable of forming
a three-dimensional matrix of aligned fibres in any desired thickness.
[0019] Other strategies for the formation of three-dimensional matrices of aligned fibres
have been the subject of studies, mainly in the field of regenerative medicine, such
as, for example, the articles:
Sheikh, et.al., Nanomedicine, 2015, 11, and
Li, et.al., Mater. Sci. Eng. C.,2016,68.
[0020] In this regard, the document
US 8580181B1 also discloses a method of forming three-dimensional matrices of nanofibres aligned
with an open and loose structure.
[0021] Although the configurations above consider the formation of multiple fibres layers
aligned one over the other, in the space between the electrodes, there are still some
problems with the formation of three-dimensional matrices. The limitations related
to the current processes of electrospinning the aligned fibres are mainly related
to the fact that, as the aligned and electrically charged fibres are deposited one
over the other, the increasing electric charge tends to repel the new fibres from
being deposited, preventing their correct alignment and limiting their thickness to
a few tenths of a millimetre of the matrix of the formed fibres.
[0022] For certain purposes, such as tissue engineering, the formation of high thickness
fibre matrices in the order of several millimetres is necessary, with control of the
fibre alignment along the thickness and with the possibility to control the degree
of compaction (porosity) between the deposited aligned fibre layers.
[0023] This way, there is a need to develop and implement a process of production of three-dimensional
matrices of aligned polymeric fibres, which allows the production of several patterns
of fibre alignment, along the thickness of the matrix, forming three-dimensional structures
with controlled thicknesses.
[0024] The present invention proposes to solve the problems of the state of the art above
described, through the implementation of a system and process of production of three-dimensional
matrices of aligned polymeric fibres, which can present several patterns of fibre
alignment, along the thickness of the matrix, being this thickness dependent on the
number of layers of deposited fibres, the thickness of fibres and the degree of compaction
between layers.
Summary of the invention
[0025] This invention relates to a continuous electrospinning system and process for the
production of three-dimensional matrices of aligned polymeric fibres.
[0026] The formation of three-dimensional matrices of aligned polymeric fibres occurs when
one or more pairs of electrodes are exposed to the electrospinning capillary tube,
thereby creating a layer of two-dimensional aligned fibres, on which are successively
deposited, other layers formed by exposure of one or more pairs of electrodes to the
capillary tube, accompanied, subsequently, by controlled movement away from the central
collecting table of the capillary tube, after each layer of deposited fibres, in accordance
with the claim 1.
[0027] Thus, the process of the present invention allows the production of three-dimensional
matrices of aligned polymeric fibres, which can present several patterns of fibre
alignment along the thickness of the matrix, being this thickness dependent on the
number of deposited fibre layers, fibre thickness and the degree of compaction between
layers, in accordance with the claim 7.
[0028] The produced matrices are used in various areas, such as biotechnology, pharmaceuticals,
research, tissue engineering and medicine, in particular regenerative medicine, such
as cell therapy and the production of cartilaginous and related tissue, in particular
for joint replacement and strengthening, in accordance with the claim 9.
[0029] Additionally, the process of the present invention, by using the proposed electrospinning
system, has the additional advantage of being versatile, simple, inexpensive and working
in a continuous mode, therefore not being necessary to produce series of layers with
a certain alignment and to proceed to add other layers, with different alignment,
to obtain three-dimensional matrices of polymeric fibres aligned with different patterns
of fibre alignment and different thicknesses.
[0030] The system of the present invention comprises an electrospinning capillary tube,
a set of multi-electrodes, in which each electrode presents a controlled movement
of exposure or retraction- occultation in relation to the electrospinning tube, and
a central collecting table of the electrospun fibres, which comprises holes subject
to vacuum pressure, with the possibility of regulating the distance between the electrospinning
capillary tube and the electrodes in exposure position, and with controlled movement,
towards the capillary tube axis, in accordance with the claim 12.
[0031] The system of the present invention, through the controlled movement of exposure
or retraction-occultation of the electrodes, in relation to the electrospinning tube,
with controlled vacuum production applied to the holes of the central collecting table,
allows to secure the fibres to the table, as well as to achieve a certain degree of
compaction (and consequently porosity in vertical direction) necessary for certain
uses of the fibres. In addition, the controlled downward movement of the table allows
the formation of three-dimensional aligned fibre structures.
Brief description of the drawings
[0032]
Figure 1: Schematic depiction of an embodiment of an electrospinning system, according to the
present invention, with two exposed electrodes, the following numbers representing:
- 1 electrospinning system;
- 2 electrospun fibre;
- 3 electrospinning capillary tube;
- 4 positive polarity connection between the electrospinning capillary tube (3) and
a power supply (not shown);
- 5 capillary tube bracket (3), resting on the mounting base (8) ;
- 6 holes in the peripheral support, where the multi-electrodes are inserted (7,14);
- 7 electrode in exposure position, with respect to the electrospinning capillary tube (3) with negative polarity;
- 8 fixing base for the entire electrospinning system (1);
- 9 computer control unit for the entire electrospinning system (1);
- 10 induction coil for generating the electromagnetic force for the electrospinning
system (1);
- 11 permanent magnet attached to an electrode (7,14);
- 12 linear motion actuator of the central collecting table (17);
- 13 vacuum pump with pressure regulation;
- 14 electrode in retraction-occultation position, with respect to the electrospinning capillary tube (3);
- 15 peripheral support of the collecting table (17), made of insulating material;
- 16 holes in the surface of the central collecting table (17), which connect to the
inside of the chamber (not shown);
- 17 central collecting table; and
- 18 connecting channel between the inner chamber (not shown) of the central collecting
table (17) and the vacuum pump (13) .
Figure 2: Schematic depiction of a longitudinal section of the electrospinning system (1),
according to a preferred embodiment of the present invention, in which:
- The electrospun fibre (2) is located between the two electrodes exposed with negative
polarity (7) and the collecting table (17) with its surface (19) covered with holes
(16) connected to the chamber (21) inside it, which is submitted to vacuum pressure,
in the position closest to the electrospinning capillary tube (3);
- Two electrodes are in exposure position (7) on the surface (20) of the peripheral
support (15), one electrode is in a concealed position (14);
- the actuator (12) of the linear movement (24) of the collecting table (17),
- the senses the electromagnetic forces of attraction (23) and repulsion (22) generated
between the end of the electrodes (7)(14) with permanent magnet (11) and the electromagnetic
coils (10);
Figure 3: Schematic depiction of a longitudinal section of the electrospinning system (1),
according to a preferred embodiment of the present invention, in which:
- the electrospun fibre (2) is deposited between the two exposed electrodes (7) and
the central collecting table (17), covered with holes (16), connected to the chamber
(21), inside it, in a position further away from the electrospinning capillary tube
(3);
- the direction of suction force (25), fixation-compaction of the different fibre layers
(27) (28) (29), generated by the effect of vacuum pressure in the chamber (21), and
the thickness (26) of the fibre matrix formed after the deposition of different layers
(27) (28) (29) of aligned fibres.
Figure 4: Schematic depiction of one of embodiments used in the invention's electrospinning
process, in which:
- a first layer of aligned fibres (30) lies between two exposed electrodes (7) with
negative polarity, belonging to the multi-electrode array, which are in a concealed
position in the holes (6) of the peripheral support (15), with the central collecting
table (17) in the closest operating position to the electrospinning capillary tube
(3) ;
- the central collecting table (17) through its chamber (21) connected to it.
Figure 5: Schematic depiction of the aligned fibres of the first layer (30) fixed to the surface
(19) of the central collecting table (17), by action of the suction force (25) generated
in the holes (16) of the surface (19) of the central collecting table (17), by effect
of the vacuum present in the chamber (21) of the central collecting table (17), which,
after a certain period of time, moved away from the electrospinning capillary tube
(3), by the action of the movement (32) of the actuator (12), and is followed by the deposition of the second layer of aligned fibres (31), between the two exposed electrodes (7) and by the movement away from the table
(32).
Figure 6: Schematic depiction of the aligned fibres of the first layer (30) and second layer
(31) fixed on the surface (19) of the central collecting table (17), by action of
the suction force (25) generated in the holes (16) of the surface (19) of the central
collecting table (17), by the effect of the vacuum present in the chamber (21) of
the central collecting table (17), which, after a certain period of time, moved away
from the electrospinning capillary tube (3), by action of the movement (33) of the
actuator (12), and is followed by the deposition of the third layer of aligned fibres (31), between the two exposed electrodes (7).
Figure 7: Schematic depiction of the aligned fibres of the first layer (30), second layer (31) and third layer (32), fixed on the surface (19) of the central collecting table (17), by the action of
suction force (25) generated in the holes (16) of the surface (19) of the central
collecting table (17), by the effect of vacuum pressure, present in the chamber (21)
of the central collecting table (17), which, after a certain period of time, moved
away from the electrospinning capillary tube (3), by action of the movement (36) of
the actuator (12), and is followed by deposition of the fourth layer of aligned fibres (35) between the two exposed electrodes (7);
Figure 8: Schematic depiction of the top view of the central collecting table (17) and peripheral
electrode support (15) with the representation of nine fibre alignments (301) (302) (303) (304) (305) (306) (307) (308) (309), deposited sequentially in layers, being the alignment (301) obtained by exposing the electrodes (702) and (710), the
alignment (302) obtained by exposing the electrodes (702) and (705), the alignment
(303) obtained by exposing the electrodes (701) and (706), the alignment (304) obtained
by exposing the electrodes (701) and (706), the alignment (305) obtained by exposing
the electrodes (708) and (702), the alignment (306) obtained by exposing the electrodes
(706) and (711), the alignment (307) obtained by exposing the electrodes (710) and
(707), the alignment (308) obtained by exposing the electrodes (709) and (702), the
alignment (309) obtained by exposing the electrodes (710) and (703), in which the
set of these nine layers forms an alignment pattern (200), which is repeated successively,
between the first (203), intermediate (205) and last (206) pattern, thus resulting
in the thickness (26) of the three-dimensional matrix, which is delimited by the dimensions
(202) and (201).
Description of the invention
[0033] This invention relates to a system and a continuous electrospinning process for the
production of three-dimensional matrices of aligned polymeric fibres, in particular
for tissue engineering, with the possibility of producing several patterns of fibre
alignment along the thickness of the matrix forming three-dimensional structures with
controlled thicknesses.
[0034] The system of the present invention comprises a module of fibre formation, which
can consist basically of a syringe to contain a polymeric solution, connected to an
injection pump, connected to a electrospinning capillary tube, which is connected
to a voltage source, configured to provide positive polarity, the referred module
is aligned longitudinally with the peripheral support in insulating material in which
they are inserted longitudinally in holes in its multi-electrode surface, each electrode
being provided with individual movement controlled towards the axis of the electrospinning
capillary tube, with two positions, an exposure position and a retraction-occultation
position with respect to the electrospinning capillary tube, as well as the possibility
of selective activation of the negative polarities of these electrodes, when these
electrodes are in the exposed position with respect to the electrospinning capillary
tube, the alignment and distribution of these electrodes in the peripheral support
delimit the area and shape of the central fibre collecting table.
[0035] The fibre of polymeric material, formed by electrospinning from the capillary tube
with positive polarity, moves by the action of an electric field towards a collector
module, which consists of a peripheral support in insulating material where are inserted
longitudinally multi-electrodes and each electrode equipped with controlled movement
towards the axis of the electrospinning capillary tube allowing its exposure or retraction-occultation
with respect to the electrospinning capillary tube, a central collecting table delimited
by the peripheral support of the multi-electrodes which consists of the region of
accumulation of the electrospun fibres integrating these holes which extend from its
upper surface to the inside of the chamber being this chamber connected to a vacuum
pump with pressure control, this central collecting table has controlled movement
towards the axis of the capillary tube allowing its separation or approach to the
electrospinning capillary tube.
[0036] The peripheral support of the multi-electrodes and the central collecting table are
mounted on a fixed platform where the length-adjustable bracket of the electrospinning
capillary tube is placed, allowing the distance between the electrospinning capillary
tube and the multi-electrodes to be adjusted.
[0037] The exposure and retraction-occultation movement of the electrodes inserted into
holes in the peripheral support to the electrospinning capillary tube results from
a controlled electromagnetic force that develops at the end of the opposite electrode
the upper surface of the peripheral support by the action of magnetic flux between
a permanent magnet attached to the electrode and a fixed induction coil in the lower
region of the peripheral support.
[0038] Fibre flow is deposited and aligned when one or more electrode pairs are held in
the exposure position with respect to the electrospinning capillary tube, and their
respective negative polarities are activated, according to the intended fibre deposition
orientation, thus forming an aligned two-dimensional fibre layer.
[0039] The retraction-occultation movement of the electrodes, with respect to the electrospinning
capillary tube, to the inside of its hole in the peripheral support of the multi-electrodes
allows the deposit of the fibres on the central collecting table followed by the separation
of the fibres from the end of the electrode.
[0040] The controlled movement away from the upper surface of the central collecting table
of the electrospinning capillary tube, after each two-dimensional layer of aligned
fibres has been deposited, allows the accumulation of successive fibre layers on the
central collecting table thus allowing the formation of a three-dimensional fibre
matrix structure in which its thickness is dependent on the number of layers of two-dimensional
deposited fibres, the fibre thickness and the degree of intended compaction between
layers by the vacuum system action.
[0041] The successive two-dimensional layers of deposited fibres in the collector module,
according to the referred electrospinning process, are kept in position in the central
collecting table, between the multi-electrodes, by the action of vacuum generated
in the holes of the upper surface of the central collecting table that communicate
with a chamber connected to the vacuum pump inside it.
[0042] The pressure control in the vacuum pump also has the purpose of controlling the degree
of compaction between the two-dimensional fibre layers formed and so the porosity
in the perpendicular direction to the plane of the deposited fibre layer.
[0043] Control of the distance between the electrospinning capillary tube with positive
polarity and the collector module, control of the exposure and retraction-occultation
movements of the electrodes with negative polarity with regard to the electrospinning
capillary tube, control of the movement of the upper surface of the central collecting
table in reference to the electrospinning capillary tube, control of the negative
polarity applied to the multi-electrodes and the control of the vacuum pump pressure
are carried out by a computerised control unit which, depending on the fibre alignment
intended for each two-dimensional layer deposited and the thickness of the matrix,
program the sequence of all the movements, vacuum pressure and polarity of the necessary
electrodes based on a computer program developed for that purpose.
[0044] This invention has the ability to form matrices of aligned fibres of any thickness
in continuous and with any alignment pattern along that thickness, because it combines
different technical particularities, among them we highlight the use of multi-electrodes
distributed spatially with the possibility of individual and controlled movements
of exposure and retraction-occultation to the electrospinning capillary tube, thus
allowing the possibility of controlling the alignment of deposited fibres, the support
and deposit of the fibres on the central collecting table and the separation of the
fibres from the ends of the electrodes during the retraction movement, the surface
of the collecting table being provided with holes subject to vacuum pressure, which
on one hand allow the fibres to be fixed to the table and also allow the control of
the degree of compaction (porosity) between the different layers of deposited fibres,
this capacity being also associated with the movement of the collecting table away
from the electrospinning capillary tube, thus allowing the successive deposit of aligned
fibre layers to the intended thickness.
1. Electrospinning system for the production of three-dimensional matrices of aligned
polymeric fibres
[0045] The system of the present invention comprises, in a broad sense:
- a fibre-forming module comprising a container for the containment and supply of molten polymer or polymeric
solution, typically a syringe, and an injecting pump, connected to an electrospinning
capillary tube, connected to a voltage source, which is configured to provide positive
polarity;
- a multi-electrode assembly comprising several electrodes with negative polarity;
- a collector module for collecting the produced fibres;
- a power supply to the electrospinning system; and
- a vacuum pump.
[0046] In addition to the aforementioned elements, the system of the present invention also
comprises a permanent magnet, attached to each of the electrodes, to generate the
forces of attraction and repulsion between the ends of the electrodes and the electromagnetic
coils, also present in the system, a computerized control unit and the electronics
necessary for its proper operation, actuators, including the actuator of the linear
movement of the central collecting table, as well as all the electrical wiring for
distribution of energy to the various components of the system.
[0047] More specifically, the system (1) of this invention comprises:
- a fibre-forming module with an electrospinning capillary tube (3);
- a set of multi-electrodes;
- a collector module to collect the produced fibres;
- a vacuum pump (13) for pressure regulation;
Wherein:
- a) The set of multi-electrodes, which is inserted in a peripheral support (15), comprises:
- (i) multiple electrodes (7) (14), each with controlled movement, towards the axis
of the electrospinning capillary tube (3);
- (ii) several magnets (11), each of which is attached to an electrode (7,14) for generating
electromagnetic force (22, 23), together with the induction coil (10), controlled
by the computer unit (9);
- b) The collector module comprises:
- (i) a peripheral support (15), where the electrodes (7) (14) are inserted longitudinally
into holes (6) on its surface (20), with the support (15) mounted on a fixed platform
(8), where the support (5), adjustable in length, of the electrospinning capillary
tube (3) is supported, to adjust the distance between the electrospinning capillary
tube (3) and the electrodes in exposure position (7), with respect to the electrospinning
capillary tube (3) ;
- (ii) a central collecting table (17), bounded by the aforementioned peripheral support
(15), defining a region of accumulation of electrospun fibres, and also having holes
(16), which extend from its surface (19) to a chamber (21);
- (iii) a chamber (21), which is inside the central table (17), this chamber being connected
by a channel (18) to a vacuum pump (13);
wherein:
- each electrode is capable of being independently exposed (7) or retracted/occluded
(14), with respect to the electrospinning capillary tube (3);
- the vacuum pump (13) exerts a controlled vacuum pressure on the holes (16); and
- the central collecting table (17) presents controlled movement, towards the axis of
the capillary tube (3), allowing its movement (24) away from or close to the electrospinning
capillary tube (3).
[0048] The
electrospinning system (1) comprising the fibre (2) of polymeric material formed by electrospinning from
the capillary tube (3) with positive polarity moves by the action of an electric field
towards a collector module, which consists of a peripheral support (15) in insulating
material where they are longitudinally inserted in holes (6) in its surface (20) multi-electrodes
(7) (14) and each electrode (7) (14) equipped with controlled movement towards the
axis of the electrospinning capillary tube (3) allowing its exposure (7) or retraction-occultation
(14) with respect to the electrospinning capillary tube (3), a central collecting
table (17) delimited by the peripheral support (15) of the multi-electrodes which
consists of the region of accumulation of the electrospun fibres integrating this
holes (16) which extend from its surface (19) to a chamber (21) in its interior being
this chamber connected by a channel (18) to a vacuum pump (13) with pressure control,
this central collecting table (17) has controlled movement towards the axis of the
capillary tube (3) allowing its movement (24) away or close to the electrospinning
capillary tube (3).
[0049] In one embodiment, this continuous electrospinning system and process comprises the
peripheral support (15) of the multi-electrodes mounted on a fixed platform (8) on
which the length-adjustable support (5) of the electrospinning capillary tube (3)
is supported, allowing the distance between the electrospinning capillary tube (3)
and the electrodes in exposure position (7) to the electrospinning capillary tube
to be adjusted (3).
[0050] In one embodiment, the movement of exposure (22) and retraction-occultation (23)
of the electrodes (7) and (14) inserted into holes (6) of the peripheral support (15)
to the electrospinning capillary tube (3) results from an electromagnetic force (22)
(23) controlled by the computer control unit (9) which develops at the end of the
electrode (7) (14) opposite the upper surface (20) of the peripheral support (15)
by the action of magnetic flux between a permanent magnet (11) attached to the electrode
(7) (14) and an induction coil (10) positioned in the lower region of the peripheral
support (15).
[0051] In one embodiment, the deposit and alignment of the fibre flow (2) is carried out
when one or more pairs of electrodes (7) are held in the exposed position in relation
to the electrospinning capillary tube (3), and their respective negative polarities
are activated by the computer control unit (8), according to the intended fibre deposition
orientation thus forming successive aligned two-dimensional fibre layers (27) (28)
(29) (30) (31) (34) (35) .
[0052] In one embodiment, the retraction-occultation movement of the electrodes (23), with
respect to the electrospinning capillary tube (3), towards the interior of its hole
(6) in the peripheral support (15) allows the support - deposit of the fibres (27)
(28) (29) (30) (31) (33) (35) on the surface (19) of the central collecting table
(17) followed by the separation - release of the fibres from the end of the electrodes
(7).
[0053] The controlled movement (24) (32) (33) (36) (36) away from the surface (19) of the
central collecting table (17) of the electrospinning capillary tube (3), after each
two-dimensional layer of aligned deposited fibres (27) (28) (29) (30) (31) (33) (35),
allows the accumulation of successive fibre layers (27) (28) (29) (30) (30) (31) (33)
(35) on the central collecting table (17) thus allowing the formation of a three-dimensional
fibre matrix structure (207) in which its thickness (26) is dependent on the number
of two-dimensional fibre layers (27) (28) (29) (30) (31) (33) (35) deposited, the
fibre thickness and the degree of intended compression between layers by vacuum system
action (13).
[0054] The successive two-dimensional fibre layers deposited (27) (28) (29) (30) (31) (33)
(35) on the central collecting table (17) are maintained in position on the central
collecting table (17) by the action of a suction force (25) generated by the vacuum
pressure in the surface holes (19) of the central collecting table (17) that communicate
with a chamber (21) in its interior connected by a channel (18) to the vacuum pump
(13) .
[0055] The pressure control in the vacuum pump (13) is also intended to control the suction
forces (25) on the fibres and the degree of compaction between the formed two-dimensional
fibre layers (27) (28) (29) (30) (31) (33) (35) and then the porosity in the perpendicular
direction of the deposited fibre layer plane.
[0056] Control of the distance between the electrospinning capillary tube (3) with positive
polarity through its holder (5) and the exposed multi-electrodes (7) with negative
charge, control of the exposure movements (22) and retraction-occultation (23) of
the electrodes (7) with negative polarity with respect to the electrospinning capillary
tube (3), control of the surface movement (19) of the central collecting table (17)
with respect to the electrospinning capillary tube (3), the control of the negative
polarity applied to the electrodes (7) and the control of the vacuum pump pressure
(13) are carried out by a computer control unit (8) which, depending on the alignment
(301) (302) (303) (304) (305) (306) (307) (308) (309) of fibres intended for each
two-dimensional layer deposited (27) (28) (29) (30) (31) (33) (35) and the thickness
(26) of the matrix, program the sequence of all movements, vacuum pressure and polarity
of the required electrodes based on a computational program developed for this purpose.
2. Process of obtaining three-dimensional matrices of aligned polymeric fibres
[0057] The process of the present invention is carried out in several steps with the use
of the electrospinning system (1), as described in the previous section.
[0058] The production of three-dimensional matrices of aligned polymeric fibres (2) occurs
when one or more pairs of electrodes (7,14) are exposed to the capillary tube (3),
according to the intended fibre orientation, thus forming a two-dimensional layer
of aligned fibres, which are kept in adequate position on the central collecting table
(17), after the movement of retraction-occultation of the electrodes, by action of
the suction force generated by vacuum pressure in their holes.
[0059] The controlled movement away from the central collecting table (17) of the electrospinning
tube (3), after each deposited fibre layer, allows the accumulation of successive
layers and the formation of a three-dimensional matrix with thickness depending on
the number of deposited fibre layers, the fibre thickness and the degree of compaction
between layers controlled by vacuum pressure.
[0060] This way, the production process of aligned three-dimensional matrices of polymeric
fibres of the present invention comprises the following steps:
- a) exposure of one or more electrode pairs (7) to the capillary tube (3), according
to the desired fibre orientation, to form a first layer of aligned fibres (30) ;
- b) application of vacuum pressure to the aligned fibre layer obtained in (a) through
the holes (16) of the central collecting table (17), after the retraction-occultation
movement of the electrodes (14);
- c) separation of the central collecting table (17) from the electrospinning capillary
tube (3), by action of movement (33) of the actuator (12);
- d) exposure of one or more pairs of electrodes (7) to the capillary tube (3), according
to the intended fibre orientation, to form a second layer (31) of aligned fibres;
- e) application of vacuum pressure to the layer (31) of aligned fibres, obtained in
(d), through the holes (16) of the central collecting table (17), after the movement
of retraction-occultation of the electrodes (14).
[0061] The production of three-dimensional matrices of aligned polymeric fibres, with more
than two layers, is performed by repeating steps (a), (b) and (c), as many times as
the number of desired layers, to the process as described above.
[0062] Therefore, in order to obtain a matrix with three layers, the process of the present
invention comprises the following steps:
- a) exposure of one or more electrode pairs (7) to the capillary tube (3), according
to the intended fibre orientation, to form a first layer of aligned fibres (30) ;
- b) application of vacuum pressure to the aligned fibre layer obtained in (a) through
the holes (16) of the central collecting table (17), after the retraction-occultation
movement of the electrodes (14);
- c) separation of the central collecting table (17) from the electrospinning capillary
tube (3), by action of movement (33) of the actuator (12);
- d) exposure of one or more electrode pairs (7) to the capillary tube (3), according
to the intended fibre orientation, to form a second layer (31) of aligned fibres;
- e) application of vacuum pressure to the layer (32) of aligned fibres, obtained in
(d), through the holes (16) of the central collecting table (17), after the movement
of retraction-occultation of the electrodes (14);
- f) exposure of one or more pairs of electrodes (7) to the capillary tube (3), according
to the intended fibre orientation, to form a third layer (33) of aligned fibres;
- g) application of vacuum pressure to the layer (33) of aligned fibres, obtained in
(f), through the holes (16) of the central collecting table (17), after the movement
of retraction-occultation of the electrodes (14).
[0063] To obtain matrices with multiple layers and alignment patterns one or more pairs
of electrodes are used which are exposed (7) to the capillary tube (3), containing
a certain polymeric solution, where the composition and concentration of the polymer
in solution, as well as the solvents used, vary according to the purpose for which
the matrix is intended.
[0064] To the electrodes, located in superficial holes (16) and radially distributed around
the central collecting table (17), with a certain area, a certain negative voltage
is applied, also selected according to the type of fibre and matrix to produce.
[0065] Each one of the different alignments of the two-dimensional fibre layers is obtained
by the sequential exposure (7), of a number of selected electrodes, to the electrospinning
capillary tube (3) during a certain period, also selected according to the purpose
for which the fibres and the matrices are intended.
[0066] The different layers of deposited two-dimensional fibres thus result from the performance
of consecutive cycles of various types of alignment, which is obtained by combining
the variables or production factors described above.
[0067] It is thus possible to obtain several fibre alignments (301) (302) (303) (304) (305)
(306) (307) (308) (309) sequentially deposited in layers, each one of the alignments
being obtained by exposure (7) of different electrodes to the spinning capillary tube
(3).
[0068] The set of different layers, differently aligned, forms an alignment pattern (200),
which is repeated successively between the first (203), intermediate (205) and last
(206) pattern, thus resulting in the thickness (26) of the three-dimensional matrix,
which is delimited by the dimensions (202) and (201) of the central collecting table
(17).
[0069] The production process of three-dimensional matrices of aligned polymeric fibres
is carried out continuously by successively carrying out the various steps for the
formation of two-dimensional layers of polymeric fibres, according to the above described.
3. Characterization of the three-dimensional matrices of aligned polymeric fibres
[0070] The thickness of the obtained matrices varies therefore, not only in function of
the type and quantity of polymer used, but also in function of the number of deposited
fibre layers, the thickness of these fibres and the degree of compaction between layers,
each one of these aspects being controlled by vacuum pressure exerted on the fibre
layers deposited in the central collecting table.
[0071] On the other hand, the alignment of the fibres in each layer is controlled by the
different movements and number of electrodes exposed and/or concealed in each cycle
of fibre formation.
[0072] In conclusion, through the implementation of the system and the process of the present
invention, it is possible to obtain three-dimensional matrices of aligned polymeric
fibres, which can present several alignment patterns, along the thickness of the matrix,
which can also be variable.
4. Matrix applications
Example: Production of a polymeric matrix of aligned fibres
[0073] This example refers to the production of a matrix composed of 27 layers of aligned
polymeric fibres for cartilage engineering, with a total thickness of 3,24 mm.
[0074] The polymer used to manufacture the matrix was polycaprolactone (PCL) with a molecular
weight of 80,000 Da.
[0075] PCL was dissolved at concentrations of 12% dichloromethane (DCM) and dimethylformamide
(DMF) at a ratio of 1:1 (v:v) after 12 hours of stirring at room temperature.
[0076] Then, the molten polymer was electrospun using a capillary tube (3) with a flow of
2,5 mL/h, a voltage of 25 kV and a working distance of 15 cm to the central collecting
table (17) .
[0077] In this configuration of the electrospinning system (1), the central collecting table
(17) has a diameter of 8mm, and the holes (16) on its surface are subjected to a vacuum
pressure of 3300 Pa.
[0078] Eleven electrodes (701), (702), (703), (704), (705), (706), (707), (708), (709),
(710) and (711) distributed radially around the table (as shown in figure 8) were
used for the formation of each layer of fibres, each electrode having an average diameter
of 1,5 mm.
[0079] In their exposure position (7) to the electrospinning capillary tube (3) the said
electrodes were subjected to a negative voltage of -3kV.
[0080] Each of the different alignments of the two-dimensional fibre layers was obtained
by sequential exposure (7) of pairs of electrodes to the electrospinning capillary
tube (3) for 2.3 min.
[0081] The 27 layers of deposited two-dimensional fibres resulted from the performance of
3 consecutive cycles (3 times) of 9 alignment patterns (301), (302), (303), (304),
(305), (306), (307), (308) and (309) in this order, as follows:
- the alignment (301) obtained by exposure (7) of the electrodes (702) and (710);
- the alignment (302) obtained by exposure (7) of the electrodes (702) and (705);
- the alignment (303) obtained by exposure (7) of the electrodes (701) and (706);
- the alignment (304) obtained by exposure (7) of the electrodes (701) and (706);
- the alignment (305) obtained by exposure (7) of the electrodes (708) and (702);
- the alignment (306) obtained by exposure (7) of the electrodes (706) and (711);
- the alignment (307) obtained by exposure (7) of the electrodes (710) and (707);
- the alignment (308) obtained by exposure (7) of the electrodes (709) and (702); and
- the alignment (309) obtained by exposure (7) of the electrodes (710) and (703).
[0082] At the end of the deposition of each layer of aligned fibres, the central collecting
table (17) has moved away from the electrospinning capillary tube about 0,12 mm, this
being the value corresponding to the average thickness of each layer of deposited
dimensional fibres.
[0083] In total, the central collecting table moved away about 3,24 mm, corresponding to
the thickness of the matrix obtained at the end of the 27 deposited layers.
[0084] The three-dimensional matrix of aligned fibres obtained in this example shows, like
the native cartilage, a preferential alignment of the fibres in its surface area parallel
to the surface, in the intermediate area there is no preferential alignment, and in
the deepest area the fibres are aligned in a vertical manner to the surface.
1. An
electrospinning system (1) comprising (a) a fibre-forming module, (b) a multi-electrode array, (c) a collector
module, for collecting deposited fibres, a power supply, a vacuum pump (13),
characterised in that:
a) The fibre-forming module consists of an electrospinning capillary tube (3) with
positive polarity;
b) The multi-electrode array is inserted in a peripheral support (15) and comprises:
- several electrodes (7) (14), each one being equipped with controlled movement towards
the axis of the electrospinning capillary tube (3);
- several magnets (11), each of which is attached to an electrode (7,14) for generating
electromagnetic force (22, 23), together with the induction coil (10), controlled
by the computer unit (9);
c) The collector module comprises:
- a peripheral support (15), where the electrodes (7) (14) are inserted longitudinally
into holes (6) on its surface (20), the said support (15) being mounted on a fixed
platform (8), where the length adjustable support (5) of the electrospinning capillary
tube (3) is supported, to adjust the distance between the electrospinning capillary
tube (3) and the electrodes in exposure position (7), with regard to the electrospinning
capillary tube (3);
- a central collecting table (17), bounded by the aforementioned peripheral support
(15), defining a region of accumulation of electrospun fibres, and also having holes
(16), which extend from its surface (19) to a chamber (21);
- a chamber (21), which is located inside the central table (17), this chamber being
connected by a channel (18) to a vacuum pump (13);
wherein:
- each electrode is capable of being independently exposed (7) or retracted/occluded
(14), with respect to the electrospinning capillary tube (3);
- the vacuum pump (13) exerts a controlled vacuum pressure on the holes (16); and
- the central collecting table (17) presents controlled movement, towards the axis
of the capillary tube (3), allowing its movement (24) away from or close to the electrospinning
capillary tube (3).
2. Electrospinning system (1) according to the previous claim comprising computer control unit (9) and computer
program.
3. A
process for the production of three-dimensional matrices of continuously aligned polymeric fibres that occurs
in the system of any of claims 1 or 2
characterized by comprising the following steps:
a) exposure of one or more pairs of electrodes (7) to the capillary tube (3) containing
a solution of a certain polymer suitable for the function of the matrix to be produced,
this exposure being made according to the intended fibre orientation, by applying
a negative voltage to the selected electrodes, during a certain time, to form layers
of aligned fibres (30);
b) application of vacuum pressure to the aligned fibre layer obtained in (a) through
the holes (16) of the central collecting table (17), with the movement of retraction-occultation
of the electrodes (14);
c) separation of the central collecting table (17) from the electrospinning capillary
tube (3), by action of movement (33) of the actuator (12);
d) repetition of electrode pair sequential exposure cycles (7) to the electrospinning
capillary tube (3) from (a), application of vacuum pressure to the aligned fibre layer
(b) and separation of the central collecting table (17) from the electrospinning capillary
tube (3) from (c), as many times as necessary to form a two-dimensional fibre layer
matrix (2), with the required alignment;
e) repetition of the cycles, as described in steps (a), (b) and (c), as many times
as necessary, in which at least one of the electrospinning factors is modified from
those defined in step (a), (b) or (c) to form a matrix of two-dimensional fibre layers
(2), with the required alignment, this alignment being different from that obtained
in steps (a), (b), (c) and (d);
f) repetition of exposure cycles from (e) as many times as necessary, in which at
least one of the electrospinning factors is modified from those defined in the previous
cycle to form a matrix of two-dimensional fibre layers (2), with the required alignment,
this alignment being different from that obtained in the previous cycle
wherein:
the controlled movement away from the central collecting table of the electrospinning
tube after each layer of deposited fibres allows the accumulation of successive layers
and the formation of a three-dimensional matrix with thickness depending on the number
of fibre layers deposited, the thickness of the fibres and the degree of compaction
between layers is controlled by vacuum pressure and the vacuum pressure secures the
fibres to the table.
4. Process for the production of three-dimensional matrices of continuously aligned polymeric fibres according
to the previous claim, which occurs in the system of any of the claims 1 or 2 characterised by the peripheral support having a multi-electrode array and each electrode has individual
movement controlled towards the axis of the electrospinning capillary tube, comprising
two positions, one of exposure and another of retraction-occultation with respect
to the electrospinning capillary tube.
5. Process for the production of three-dimensional matrices of continuously aligned polymeric fibres according
to any of the previous claims 3 or 4, which occurs in the system of any of the claims
1 or 2 characterized by the central collecting table being delimited by the peripheral support of the multi-electrodes
consisting of the region of accumulation of electrospun fibres integrating these holes
that extend from its surface to a cavity inside it being this cavity connected to
a vacuum pump with pressure control, in which the central collecting table has controlled
movement towards the axis of the capillary tube allowing its separation or approach
to the electrospinning capillary tube.
6. Process for the production of three-dimensional matrices of continuously aligned polymeric fibres according
to any of the previous claims 3 to 5, which results in the system from any of the
claims 1 or 2 characterised by the exposure and retraction-occultation movement of the electrodes inserted into
holes in the peripheral support to the electrospinning capillary tube resulting from
a controlled electromagnetic force which develops at the end of the electrode opposite
the upper surface of the peripheral support by the action of magnetic flux between
a permanent magnet attached to the electrode and an induction coil positioned in the
lower region of the peripheral support.
7. Process for the production of three-dimensional matrices of continuously aligned polymeric fibres according
to any of the previous claims 3 to 6, which occurs in the system of any of the claims
1 or 2 characterized by the deposit and alignment of the flow of fibres being performed when one or more
pairs of electrodes are held in the exposed position with regard to the electrospinning
capillary tube, and their respective negative polarities are activated, according
to the intended orientation of the fibre deposition thus forming a layer of aligned
two-dimensional fibres.
8. Process for the production of three-dimensional matrices of continuously aligned polymeric fibres according
to any of the previous claims 3 to 7, which occurs in the system of any of the claims
1 or 2 characterized by the movement of retraction-occultation of the electrodes, with regard to the electrospinning
capillary tube, to the inside of its hole in the peripheral support to support and
deposit the fibres on the central collecting table followed by the separation of the
fibres from the ends of the electrodes.
9. Process for the production of three-dimensional matrices of continuously aligned polymeric fibres according
to any of the previous claims 3 to 8, which occurs in the system of any of the claims
1 or 2 characterized by the controlled movement away from the surface of the central collecting table of
the electrospinning capillary tube, after each two-dimensional layer of aligned fibres,
accumulate successive layers of fibres on the central collecting table for the formation
of a three-dimensional fibre matrix structure in which its thickness is dependent
on the number of two-dimensional fibre layers deposited, the fibre thickness and the
degree of compaction between layers required by the system action and vacuum pressure.
10. Process for the production of three-dimensional matrices of continuously aligned polymeric fibres according
to any of the previous claims 3 to 9, which occurs in the system of any of the claims
1 or 2 characterized by the successive layers of deposited fibres in the collector module being kept in position
in the central collecting table, by action of the suction force generated in the holes
of the surface of the central collecting table by action of vacuum pressure generated
in the inner chamber of the central collecting table that communicate with the vacuum
pump.
11. Process for the production of three-dimensional matrices of continuously aligned polymeric fibres according
to any of the previous claims 3 to 10, which occurs in the system of any of the claims
1 or 2 characterized by the pressure control in the vacuum pump controlling the degree of compaction between
the formed two-dimensional fibre layers and the porosity in the perpendicular direction
of the deposited fibre layer plane.
12. Process for the production of three-dimensional arrays of continuously aligned polymeric fibres according to
any of the previous claims 3 to 11, which occurs in the system of any of the claims
1 or 2 characterised by the parameters being controlled by a computer control unit (9) and the movements
of the electrodes being controlled by a computer program.
13. Three-dimensional matrices of aligned polymeric fibres characterized by 27 layers of two-dimensional polymeric fibres, with 9 alignment patterns (301), (302),
(303), (304), (305), (306), (307), (308) and (309), with a total thickness of 3.24
mm.
14. Three-dimensional matrices of aligned polymeric fibres, according to the previous claim, characterised by a preferential alignment of the fibres, (i) in parallel in their surface area, (ii)
without any preferential alignment in the intermediate area, and (iii) the fibres
are aligned in a vertical manner to the surface in the deepest area.
15. Three-dimensional matrices of aligned polymeric fibres, as described in any of the claims 13 or 14, characterized by being applied in medicine, in regenerative medicine and/or in cartilage engineering.
1. Elektrospinnsystem (1), bestehend aus(a) einem faserbildendes Modul, (b) einer Mehrfachelektrodenanordnung,
(c) einem Kollektormodul zum Sammeln der abgeschiedenen Fasern, einer Stromversorgung,
einer Vakuumpumpe (13),
dadurch gekennzeichnet, dass:
a) Das faserbildende Modul besteht aus einem Elektrospinn-Kapillarrohr (3) mit positiver
Polarität;
b) Die Mehrfachelektrodenanordnung wird in einen peripheren Träger (15) eingesetzt und besteht aus:
- mehreren Elektroden (7) (14), von denen jede mit einer kontrollierten Bewegung in
Richtung der Achse des Elektrospinn-Kapillarrohrs (3)ausgestattet ist;
- mehreren Magneten (11), von denen jeder zur Erzeugung einer elektromagnetischen
Kraft (22, 23), zusammen mit der Induktionsspule (10), die von der Rechnereinheit
(9)gesteuert wird an einer Elektrode (7, 14) befestigt ist;
c) Das Kollektormodul besteht aus:
- einem peripheren Träger (15), in den die Elektroden (7) (14) in Längsrichtung in
Löcher (6) auf seiner Oberfläche (20) eingeführt werden, wobei der besagte Träger
(15) auf einer festen Plattform (8) montiert ist, auf der der längenverstellbare Träger
(5) des Elektrospinn-Kapillarrohrs (3) gelagert ist, um den Abstand zwischen dem Elektrospinn-Kapillarrohr
(3) und den Elektroden in der Expositionsposition (7) in Bezug auf die Elektrospinn-Kapillarrohre
(3) einzustellen;
- einem zentralen Sammeltisch (17), der von dem oben erwähnten peripheren Träger (15)
begrenzt wird, einen Bereich zur Ansammlung von elektrogesponnenen Fasern definiert
und ebenfalls Löcher (16) aufweist, die sich von seiner Oberfläche (19) zu einer Kammer
(21) erstrecken;
- einer Kammer (21), die sich im Inneren des zentralen Sammeltisches (17) befindet,
wobei diese Kammer durch einen Kanal (18) mit einer Vakuumpumpe (13) verbunden ist;
wobei:
- jede Elektrode unabhängig von dem Elektrospinn-Kapillarrohr (3) freigelegt (7) oder
eingezogen/verschlossen (14) werden kann;
- die Vakuumpumpe (13) einen kontrollierten Vakuumdruck auf die Löcher (16) ausübt;
und
- der zentrale Sammeltisch (17) eine kontrollierte Bewegung in Richtung der Achse
des Kapillarrohrs (3) aufweist, die seine Bewegung (24) weg von oder in die Nähe des
Elektrospinn-Kapillarrohrs (3) ermöglicht.
2. Elektrospinnsystem (1) nach dem vorhergehenden Anspruch mit einer Computersteuereinheit (9) und einem
Computerprogramm.
3. Ein
Verfahren zur Herstellung von dreidimensionalen Matrizen aus kontinuierlich ausgerichteten Polymerfasern, das
in dem System nach einem der Ansprüche 1 oder 2 abläuft,
dadurch gekennzeichnet, dass es die folgenden Schritte umfasst:
a) Exposition eines oder mehrerer Elektrodenpaare (7) gegenüber des Kapillarrohrs
(3), das eine Lösung eines bestimmten Polymers enthält, das für die Funktion der herzustellenden
Matrix geeignet ist, wobei diese Exposition entsprechend der beabsichtigten Faserausrichtung
erfolgt, durch Anlegen einer negativen Spannung an die ausgewählten Elektroden während
einer bestimmten Zeit, um Schichten von ausgerichteten Fasern (30) zu bilden;
b) Anwendung von Vakuumdruck auf die in (a) erhaltene ausgerichtete Faserschicht durch
die Löcher (16) des zentralen Sammeltisches (17), mit der Bewegung der Rückzugsokkultation
der Elektroden (14);
c) Trennung des zentralen Sammeltisches (17) vom Elektrospinn-Kapillarrohr (3) durch
die Bewegung (33) des Stellglieds (12);
d) Wiederholung der sequentiellen Expositionszyklen des Elektrodenpaares (7) an dem
Elektrospinn-Kapillarrohr (3) von (a), Anlegen von Vakuumdruck an die ausgerichtete
Faserschicht (b) und Trennen des zentralen Sammeltisches (17) von dem Elektrospinn-Kapillarrohr
(3) von (c), so oft wie nötig, um eine zweidimensionale Faserschichtmatrix (2) mit
der erforderlichen Ausrichtung zu bilden;
e) Wiederholung der in den Schritten (a), (b) und (c) beschriebenen Zyklen so oft
wie nötig, wobei mindestens einer der Elektrospinnfaktoren gegenüber denen in den
Schritten (a), (b) oder (c) definierten verändert wird, um eine Matrix aus zweidimensionalen
Faserschichten (2) mit der gewünschten Ausrichtung zu bilden, wobei sich diese Ausrichtung
von der in den Schritten (a), (b), (c) und (d) erhaltenen unterscheidet;
f) Wiederholung der Expositionszyklen von (e) so oft wie nötig, wobei mindestens einer
der Elektrospinnfaktoren gegenüber denen im vorhergehenden Zyklus definierten verändert
wird, um eine Matrix aus zweidimensionalen Faserschichten (2) mit der erforderlichen
Ausrichtung zu bilden, wobei sich diese Ausrichtung von der im vorhergehenden Zyklus
erhaltenen unterscheidet
wobei:
die kontrollierte Bewegung weg vom zentralen Sammeltisch des Elektrospinn-Kapillarrohrs
nach jeder abgelagerten Faserschicht ermöglicht die Anhäufung aufeinanderfolgender
Schichten und die Bildung einer dreidimensionalen Matrix mit einer Dicke, die von
der Anzahl der abgelagerten Faserschichten abhängt, wobei die Dicke der Fasern und
der Grad der Verdichtung zwischen den Schichten durch den Vakuumdruck gesteuert wird
und der Vakuumdruck die Fasern am Tisch festhält.
4. Verfahren zur Herstellung von dreidimensionalen Matrizen aus kontinuierlich ausgerichteten Polymerfasern nach
dem vorhergehenden Anspruch, das in dem System nach einem der Ansprüche 1 oder 2 durchgeführt
wird, dadurch gekennzeichnet, dass der periphere Träger eine Mehrfachelektrodenanordnung aufweist und jede Elektrode
eine individuelle Bewegung hat, die in Richtung der Achse des Elektrospinn-Kapillarrohrs
gesteuert wird, umfassend zwei Positionen, eine der Exposition und eine andere der
Rückzugsokkultation in Bezug auf das Elektrospinn-Kapillarrohr.
5. Verfahren zur Herstellung von dreidimensionalen Matrizen aus kontinuierlich ausgerichteten Polymerfasern nach
einem der vorhergehenden Ansprüche 3 oder 4, das in dem System nach einem der Ansprüche
1 oder 2 durchgeführt wird, dadurch gekennzeichnet, dass der zentrale Sammeltisch durch den peripheren Träger der Mehrfachelektroden begrenzt
wird, der aus dem Bereich der Ansammlung von elektrogesponnenen Fasern besteht, die
diese Löcher integrieren, die sich von seiner Oberfläche zu einem Hohlraum in seinem
Inneren erstrecken, wobei dieser Hohlraum mit einer Vakuumpumpe mit Druckkontrolle
verbunden ist, in dem der zentrale Sammeltisch eine kontrollierte Bewegung in Richtung
der Achse des Kapillarrohrs aufweist, die seine Trennung oder Annäherung an das Elektrospinn-Kapillarrohr
ermöglicht.
6. Verfahren zur Herstellung von dreidimensionalen Matrizen aus kontinuierlich ausgerichteten Polymerfasern nach
einem der vorhergehenden Ansprüche 3 bis 5, das in dem System nach einem der Ansprüche
1 oder 2 durchgeführt wird, gekennzeichnet durch die Rückzugsokkultationsbewegung der in Löcher im peripheren Träger eingeführten
Elektroden zum Elektrospinn-Kapillarrohr, die aus einer kontrollierten elektromagnetischen
Kraft resultiert, die sich an dem der Oberseite des peripheren Trägers gegenüberliegenden
Ende der Elektrode durch die Wirkung des magnetischen Flusses zwischen einem an der
Elektrode befestigten Permanentmagneten und einer im unteren Bereich des peripheren
Trägers angeordneten Induktionsspule entwickelt.
7. Verfahren zur Herstellung von dreidimensionalen Matrizen aus kontinuierlich ausgerichteten Polymerfasern nach
einem der vorhergehenden Ansprüche 3 bis 6, das in dem System nach einem der Ansprüche
1 oder 2 durchgeführt wird, dadurch gekennzeichnet, dass die Ablagerung und Ausrichtung des Faserstroms durchgeführt wird, wenn ein oder mehrere
Elektrodenpaare in der exponierten Position in Bezug auf das Elektrospinn-Kapillarrohr
gehalten werden und ihre jeweiligen negativen Polaritäten aktiviert werden, entsprechend
der beabsichtigten Ausrichtung der Faserablagerung, wodurch eine Schicht aus ausgerichteten
zweidimensionalen Fasern gebildet wird.
8. Verfahren zur Herstellung von dreidimensionalen Matrizen aus kontinuierlich ausgerichteten Polymerfasern nach
einem der vorhergehenden Ansprüche 3 bis 7, das in dem System nach einem der Ansprüche
1 oder 2 durchgeführt wird, gekennzeichnet durch die Bewegung der Rückzugsokkultation der Elektroden in Bezug auf das Elektrospinn-Kapillarrohr
in das Innere seines Lochs in der peripheren Halterung, um die Fasern zu halten und
auf dem zentralen Sammeltisch abzulegen, gefolgt von der Trennung der Fasern von den
Enden der Elektroden.
9. Verfahren zur Herstellung von dreidimensionalen Matrizen aus kontinuierlich ausgerichteten Polymerfasern nach
einem der vorhergehenden Ansprüche 3 bis 8, das in dem System nach einem der Ansprüche
1 oder 2 durchgeführt wird, gekennzeichnet durch die kontrollierte Bewegung weg von der Oberfläche des zentralen Sammeltisches des
Elektrospinn-Kapillarrohrs nach jeder zweidimensionalen Schicht aus ausgerichteten
Fasern, aufeinanderfolgende Schichten von Fasern auf dem zentralen Sammeltisch zur
Bildung einer dreidimensionalen Fasermatrixstruktur ansammeln, deren Dicke von der
Anzahl der abgelagerten zweidimensionalen Faserschichten, der Faserdicke und dem Grad
der durch die Systemwirkung und den Vakuumdruck erforderlichen Verdichtung zwischen
den Schichten abhängt.
10. Verfahren zur Herstellung von dreidimensionalen Matrizen aus kontinuierlich ausgerichteten Polymerfasern nach
einem der vorhergehenden Ansprüche 3 bis 9, das in dem System nach einem der Ansprüche
1 oder 2 durchgeführt wird, dadurch gekennzeichnet, dass die aufeinanderfolgenden Schichten von abgelegten Fasern in dem Kollektormodul in
dem zentralen Sammeltisch durch die Wirkung der Saugkraft in Position gehalten werden,
die in den Löchern der Oberfläche des zentralen Sammeltisches durch die Wirkung des
Vakuumdrucks erzeugt wird, der in der inneren Kammer des zentralen Sammeltisches erzeugt
wird, die mit der Vakuumpumpe in Verbindung steht.
11. Verfahren zur Herstellung von dreidimensionalen Matrizen aus kontinuierlich ausgerichteten Polymerfasern nach
einem der vorhergehenden Ansprüche 3 bis 10, das in dem System nach einem der Ansprüche
1 oder 2 durchgeführt wird, dadurch gekennzeichnet, dass die Drucksteuerung in der Vakuumpumpe den Grad der Verdichtung zwischen den gebildeten
zweidimensionalen Faserschichten und die Porosität in der senkrechten Richtung der
abgelagerten Faserschichtebene steuert.
12. Verfahren zur Herstellung von dreidimensionalen Anordnungen von kontinuierlich ausgerichteten Polymerfasern
nach einem der vorhergehenden Ansprüche 3 bis 11, das in dem System nach einem der
Ansprüche 1 oder 2 durchgeführt wird, dadurch gekennzeichnet, dass die Parameter durch eine Computersteuereinheit (9) gesteuert werden und die Bewegungen
der Elektroden durch ein Computerprogramm gesteuert werden.
13. Dreidimensionale Matrizen aus ausgerichteten Polymerfasern, gekennzeichnet durch 27 Schichten zweidimensionaler Polymerfasern mit 9 Ausrichtungsmustern (301), (302),
(303), (304), (305), (306), (307), (308) und (309), mit einer Gesamtdicke von 3,24
mm.
14. Dreidimensionale Matrizen aus ausgerichteten Polymerfasern nach dem vorhergehenden Anspruch, gekennzeichnet durch eine bevorzugte Ausrichtung der Fasern, (i) parallel in ihrem Oberflächenbereich,
(ii) ohne irgendeine bevorzugte Ausrichtung im Zwischenbereich, und (iii) die Fasern
sind in vertikaler Weise zur Oberfläche im tiefsten Bereich ausgerichtet.
15. Dreidimensionale Matrizen aus ausgerichteten Polymerfasern, wie in einem der Ansprüche 13 oder 14 beschrieben, dadurch gekennzeichnet,
dass sie in der Medizin, in der regenerativen Medizin und/oder in der Knorpelzüchtung eingesetzt
werden.
1. Système d'électrofilage (1) comprenant (a) un module de formation de fibres, (b) un
réseau multi-électrodes, (c) un module collecteur, pour collecter les fibres déposées,
une alimentation électrique, une pompe à vide (13),
caractérisé en ce que :
a) Le module de formation de fibres consiste en un tube capillaire d'électrofilage
(3) de polarité positive ;
b) Le réseau multi-électrodes est inséré dans un support périphérique (15) et comprend
:
- plusieurs électrodes (7) (14), chacune étant équipée d'un mouvement contrôlé vers
l'axe du tube capillaire d'électrofilage (3) ;
- plusieurs aimants (11), chacun desquels étant attaché à une électrode (7, 14) pour
générer une force électromagnétique (22, 23), conjointement avec la bobine d'induction
(10), contrôlés par l'unité informatique (9) ;
c) Le module collecteur comprend :
- un support périphérique (15), où les électrodes (7) (14) sont insérées longitudinalement
dans des trous (6) sur sa surface (20), ledit support (15) étant monté sur une plate-forme
fixe (8), où le support réglable en longueur (5) du tube capillaire d'électrofilage
(3) est supporté, pour ajuster la distance entre le tube capillaire d'électrofilage
(3) et les électrodes en position d'exposition (7), par rapport au tube capillaire
d'électrofilage (3) ;
- une table collectrice centrale (17), délimitée par le support périphérique (15)
précité, définissant une zone d'accumulation de fibres électrofilées, et présentant
également des trous (16), qui s'étendent depuis sa surface (19) jusqu'à une chambre
(21) ;
- une chambre (21), qui est située à l'intérieur de la table centrale (17), cette
chambre étant reliée par un canal (18) à une pompe à vide (13) ;
dans lequel :
- chaque électrode est capable d'être indépendamment exposée (7) ou rétractée/occluse
(14), par rapport au tube capillaire d'électrofilage (3) ;
- la pompe à vide (13) exerce une dépression contrôlée sur les trous (16) ; et
- la table collectrice centrale (17) présente un mouvement contrôlé, vers l'axe du
tube capillaire (3), permettant son déplacement (24) à l'écart ou à proximité du tube
capillaire d'électrofilage (3).
2. Système d'électrofilage (1) selon la revendication précédente comprenant une unité de contrôle informatique
(9) et un programme informatique.
3. Procédé de production de matrices tridimensionnelles de fibres polymères alignées
en continu qui se manifeste dans le système selon l'une quelconque des revendications
1 ou 2
caractérisé en ce qu'il comprend les étapes suivantes :
a) exposition d'une ou plus paires d'électrodes (7) au tube capillaire (3) contenant
une solution d'un certain polymère adapté à la fonction de la matrice à produire,
cette exposition étant réalisée selon l'orientation des fibres visée, en appliquant
une tension négative aux électrodes sélectionnées, pendant un certain temps, pour
former des couches de fibres alignées (30) ;
b) application d'une dépression à la couche de fibres alignées obtenue en (a) à travers
les trous (16) de la table collectrice centrale (17), avec mouvement de retrait-occultation
des électrodes (14) ;
c) séparation de la table collectrice centrale (17) du tube capillaire d'électrofilage
(3), par action de déplacement (33) de l'actionneur (12) ;
d) répétition de cycles séquentiels d'exposition de paires d'électrodes (7) au tube
capillaire d'électrofilage (3) de (a), application d'une dépression à la couche de
fibres alignées (b) et séparation de la table collectrice centrale (17) du tube capillaire
d'électrofilage (3) de (c), autant de fois que nécessaire pour former une matrice
en couche fibreuse bidimensionnelle (2), avec l'alignement requis ;
e) répétition des cycles, tels que décrits aux étapes (a), (b) et (c), autant de fois
que nécessaire, dans lesquels au moins un des facteurs d'électrofilage est modifié
par rapport à ceux définis à l'étape (a), (b) ou (c) pour former une matrice de couches
fibreuses bidimensionnelles (2), avec l'alignement requis, cet alignement étant différent
de celui obtenu aux étapes (a), (b), (c) et (d) ;
f) répétition des cycles d'exposition de (e) autant de fois que nécessaire, dans lesquels
au moins un des facteurs d'électrofilage est modifié par rapport à ceux définis au
cycle précédent pour former une matrice de couches fibreuses bidimensionnelles (2),
avec l'alignement requis, cet alignement étant différent de celui obtenu au cycle
précédent
dans lequel :
le mouvement contrôlé d'éloignement du tube d'électrofilage par rapport à la table
collectrice centrale après chaque couche de fibres déposées permet l'accumulation
de couches successives et la formation d'une matrice tridimensionnelle dont l'épaisseur
dépend du nombre de couches de fibres déposées, de l'épaisseur des fibres et du degré
de compactage entre les couches est contrôlé par la dépression et la dépression fixe
les fibres à la table.
4. Procédé de production de matrices tridimensionnelles de fibres polymères alignées en continu selon la revendication
précédente, qui se manifeste dans le système selon l'une quelconque des revendications
1 ou 2 caractérisé en ce que le support périphérique présente un réseau multi-électrodes et en ce que chaque électrode présente un déplacement individuel contrôlé en direction de l'axe
du tube capillaire d'électrofilage, comportant deux positions, l'une d'exposition
et l'autre de retrait-occultation par rapport au tube capillaire d'électrofilage.
5. Procédé de fabrication de matrices tridimensionnelles de fibres polymères alignées en continu selon l'une
quelconque des revendications précédentes 3 ou 4, qui se manifeste dans le système
selon l'une quelconque des revendications 1 ou 2 caractérisé en ce que la table collectrice centrale est délimitée par le support périphérique des multi-électrodes
consistant en la zone d'accumulation de fibres électrofilées intégrant ces trous qui
s'étend de sa surface jusqu'à une cavité à l'intérieur d'elle qui est ladite cavité
reliée à une pompe à vide avec régulation de pression, dans lequel la table collectrice
centrale a un mouvement contrôlé en direction de l'axe du tube capillaire permettant
sa séparation ou son approche du tube capillaire d'électrofilage.
6. Procédé de fabrication de matrices tridimensionnelles de fibres polymères alignées en continu selon l'une
quelconque des revendications précédentes 3 à 5, qui aboutit dans le système selon
l'une quelconque des revendications 1 ou 2 caractérisé par le mouvement d'exposition et de retrait-occultation des électrodes insérées dans
des trous du support périphérique vers le tube capillaire d'électrofilage résultant
d'une force électromagnétique contrôlée qui se développe à l'extrémité de l'électrode
opposée à la surface supérieure du support périphérique par l'action du flux magnétique
entre un aimant permanent fixé sur l'électrode et une bobine d'induction positionnée
dans la zone inférieure du support périphérique.
7. Procédé de production de matrices tridimensionnelles de fibres polymères alignées en continu selon l'une
quelconque des revendications précédentes 3 à 6, qui se manifeste dans le système
selon l'une quelconque des revendications 1 ou 2 caractérisé en ce que le dépôt et l'alignement du flux de fibres est effectué lorsqu'une ou plus paires
d'électrodes sont maintenues en position exposée par rapport au tube capillaire d'électrofilage,
et leurs polarités négatives respectives sont activées, selon l'orientation visée
du dépôt de fibres formant ainsi une couche de fibres bidimensionnelles alignées.
8. Procédé de fabrication de matrices tridimensionnelles de fibres polymères alignées en continu selon l'une
quelconque des revendications précédentes 3 à 7, qui se manifeste dans le système
selon l'une quelconque des revendications 1 ou 2 caractérisé par le mouvement de retrait-occultation des électrodes, par rapport au tube capillaire
d'électrofilage, vers l'intérieur de son trou dans le support périphérique pour supporter
et le dépôt des fibres sur la table collectrice centrale suivi de la séparation des
fibres des extrémités des électrodes.
9. Procédé de production de matrices tridimensionnelles de fibres polymères alignées en continu selon l'une
quelconque des revendications précédentes 3 à 8, qui se manifeste dans le système
selon l'une quelconque des revendications 1 ou 2 caractérisé par le mouvement d'éloignement contrôlé du tube capillaire d'électrofilage par rapport
à la surface de la table collectrice centrale, après chaque couche bidimensionnelle
de fibres alignées, pour accumuler des couches successives de fibres sur la table
collectrice centrale pour la formation d'une structure matricielle de fibres tridimensionnelle
dans laquelle son épaisseur dépend du nombre de couches de fibres bidimensionnelles
déposées, de l'épaisseur des fibres et du degré de compactage entre les couches requis
par l'action du système et la dépression.
10. Procédé de fabrication de matrices tridimensionnelles de fibres polymères alignées en continu selon l'une
quelconque des revendications précédentes 3 à 9, qui se manifeste dans le système
selon l'une quelconque des revendications 1 ou 2 caractérisé par les couches successives de fibres déposées dans le module collecteur, maintenues
en position dans la table collectrice centrale, par action de la force de succion
générée dans les trous de la surface de la table collectrice centrale par action de
la dépression générée dans la chambre intérieure de la table collectrice centrale
qui communique avec la pompe à vide.
11. Procédé de production de matrices tridimensionnelles de fibres polymères alignées en continu selon l'une
quelconque des revendications précédentes 3 à 10, qui se manifeste dans le système
selon l'une quelconque des revendications 1 ou 2 caractérisé par le contrôle de pression dans la pompe à vide contrôlant le degré de compactage entre
les couches de fibres bidimensionnelles formées et la porosité dans la direction perpendiculaire
du plan de couche de fibres déposées.
12. Procédé de production de réseaux tridimensionnels de fibres polymères alignées en continu selon l'une quelconque
des revendications précédentes 3 à 11, qui se manifeste dans le système selon l'une
quelconque des revendications 1 ou 2 caractérisé en ce que les paramètres sont contrôlés par une unité de contrôle informatique (9) et les mouvements
des électrodes étant contrôlés par un programme informatique.
13. Matrices tridimensionnelles de fibres polymères alignées caractérisées par 27 couches de fibres polymères bidimensionnelles, avec 9 motifs d'alignement (301),
(302), (303), (304), (305), (306), (307), (308) et (309), d'une épaisseur totale de
3,24 mm.
14. Matrices tridimensionnelles de fibres polymères alignées, selon la revendication précédente,
caractérisées par un alignement préférentiel des fibres, (i) parallèlement dans la surface qu'elles
occupent, (ii) sans aucun alignement préférentiel dans la zone intermédiaire, et (iii)
les fibres sont alignées d'une manière verticale vers la surface dans la zone la plus
profonde.
15. Matrices tridimensionnelles de fibres polymères alignées, telles que décrites dans
l'une quelconque des revendications 13 ou 14, caractérisées en ce qu'elles sont appliquées en médecine, en médecine régénératrice et/ou en ingénierie du
cartilage.