KR102045986B1 - Mobile bio-scaffold controlled by magnetic field and manufacturing method thereof - Google Patents

Abstract

Provided is a magnetic field controllable mobile biocarrier.
The present invention includes a first ring, a second ring connected to intersect with respect to the first ring, and a third ring connected to intersect with respect to the first ring and the second ring. A sphere having a plurality of gaps formed between the rings; And a magnetic layer formed on an outer surface of the sphere, wherein the sphere is cloud-moved in one direction by rotating by an interaction between a magnetic field and a rotating magnetic field applied from the outside.

Description

Mobile bio-carrier with magnetic field control and manufacturing method therefor {Mobile bio-scaffold controlled by magnetic field and manufacturing method}

The present invention relates to a magnetic field controllable mobile biotransformer and a method of manufacturing the same, and more particularly, to a magnetic support provided in the biological supporter, the magnetic field controllable mobile biotransformer capable of controlling the movement of the biotransformer by an externally applied magnetic field. And to a method for producing the same.

Recently, in the field of biotechnology, tissue engineering for the treatment and regeneration of tissues has been developed.

Tissue engineering integrates the basic concepts and techniques of life sciences and engineering to understand the correlation between structure and function of biological tissues, and to maintain and improve the functioning of our bodies by creating and replacing the tissues. Applied research aimed at restoring.

However, despite the rapid growth of high levels of medical technology, organ damage or tissue damage frequently occurs, and organ transplants to treat them are technical difficulties, high costs, lack of donors, and the use of immunosuppressants. There are many problems such as side effects.

Accordingly, the necessity for the development of artificial organs and tissue regeneration using tissue engineering is emerging as a new approach of organ transplantation.

The basic principle of tissue engineering is to collect the necessary tissue from the patient's body, separate the cells from the tissue, and then culture the separated cells in a support to prepare a cell-support complex, and then transplant the cell-support complex back into the human body. will be.

Such cell-supports must meet various conditions as well as in vivo safety. First, it should be made of a material that helps the activity of cell attachment, proliferation, and differentiation, and should be made of a porous structure that facilitates cell proliferation and tissue regeneration throughout the support, and interconnection between pores of such porous structure This should be good.

In addition, the biosupport should be biocompatible, have pores to provide a large surface area for easy integration of the cells and tissues to be implanted, and biodegradable materials may need to be used depending on the location of application.

Currently used biocarriers are mainly used for the regeneration of bones, skin, organs, etc., the shape of the structure and the size of the pores suitable for the cells and tissues to be implanted in the biocarriers are determined. The formation of new tissue on the structure is very important because it is strongly influenced by the porosity, the size of the structure, and the three-dimensional intercellular interconnect structure. Proper pore structure is required to carry a sufficient number of cells, and interconnected pore structures are required for nutrient diffusion.

In recent years, research and development to manufacture a bio-carrier that can be used more effectively and stably in the treatment and regeneration of such tissues continues.

Accordingly, Korean Patent Laid-Open Publication No. 10-2013-0120572 (Nov. 5, 2013) discloses a porous three-dimensional structure including cells and a method of manufacturing the same.

However, in the related art, in order to insert such a support in vivo and to position the implantation site, there is a difficulty in inserting the support directly and fixing it in a desired position with the help of surgical methods and machines. In addition, such a method has a problem that there is a risk of infection and trauma in the insertion process, and there is a limit to application to a dangerous part when exposed to external areas such as inaccessible local areas or blood vessels and brain tissue.

The present invention is to solve the above problems, the object of the present invention is to provide a magnetic field controllable mobile biotransformer having excellent biocompatibility, which can be precisely and quickly moved to a target point by an externally applied magnetic field. There is a purpose.

In addition, an object of the present invention is to provide a magnetically controllable mobile biocarrier capable of improving the propulsion efficiency during cloud movement by an external magnetic field by providing a spherical support.

As a specific means for achieving the above object, the present invention, a first ring, a second ring connected to intersect with respect to the first ring and a third ring connected to intersect with the first ring and the second ring. Spheres provided with an asymmetric ring and having a plurality of gaps formed between the first ring and the third ring; And a magnetic layer formed on the sphere, wherein the sphere is cloud-movable in one direction by rotating by an interaction between a rotating magnetic field applied from the outside and a magnetic axis formed by the magnetic layer. Provided is a mobile biocarrier.

Preferably the sphere may be made of a resin material or may be provided with a biodegradable material that is naturally degraded in the human body.

Preferably the magnetic layer may be covered in whole or in part on the sphere.

Preferably the spheres may have a protective layer made of a biocompatible material.

Preferably, the sphere having a plurality of gaps may include cells cultured in the inner space.

In another aspect, the present invention is asymmetrically provided with a first ring, a second ring connected to intersect with respect to the first ring and a third ring connected to intersect with respect to the first ring and the second ring. Forming a sphere having a plurality of gaps between the third and third rings; And forming the magnetic layer on the outer surface of the sphere so that the sphere contacts the inside of the living body and is clouded in one direction by the interaction between the rotating magnetic field applied from the outside and the magnetic axis formed by the magnetic layer. Provided is a method of manufacturing a magnetic field controllable mobile biocarrier.

Preferably, after the magnetic layer forming step, the method may further include forming a protective layer made of a biocompatible material to cover the magnetic layer.

More preferably, after the magnetic layer forming step, it may include the step of culturing the cells in the sphere having the plurality of gaps.

According to the present invention as described above, the following effects are obtained.

(1) Because of its excellent biocompatibility, it is possible to prevent the occurrence of side effects in the process of inserting into the human body.

(2) Since the movement of the living body support can be controlled by a rotating magnetic field applied from the outside, cells can be directly delivered to local areas, blood vessels, and brain tissues without the help of surgical methods and machines.

1 is an overall perspective view of a magnetic field controllable mobile biocarrier according to an embodiment of the present invention.
2 is a cross-sectional perspective view showing the XZ-axis plane of the magnetic field controllable mobile biocarrier according to an embodiment of the present invention.
3 is a cross-sectional perspective view illustrating a YZ axis plane of a magnetic field controllable mobile biocarrier according to an exemplary embodiment of the present invention.
Figure 4 is an enlarged cross-sectional view of a movable magnetic field controllable mobile carrier according to an embodiment of the present invention.
Figure 5 is a state diagram showing the state of cell culture in the magnetic field controllable mobile carrier according to an embodiment of the present invention.
6 is an operational state diagram of a magnetic field controllable mobile biocarrier according to an embodiment of the present invention.

DETAILED DESCRIPTION Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, in describing in detail the structural principle of the preferred embodiment of the present invention, when it is determined that the detailed description of the related known functions or configurations may unnecessarily obscure the subject matter of the present invention, the detailed description thereof will be omitted.

In addition, the same reference numerals are used for parts having similar functions and functions throughout the drawings.

In addition, throughout the specification, when a part is 'connected' to another part, it is not only 'directly connected' but also 'indirectly connected' with another element in between. Include. In addition, the term 'comprising' a certain component means that the component may be further included, without excluding the other component unless specifically stated otherwise.

On the other hand, throughout the specification, the X-axis, Y-axis and Z-axis refers to three axes orthogonal to each other, the X-axis is a direction perpendicular to the imaginary plane formed by the first ring with respect to Figure 1, the Y-axis is the first ring It is a direction parallel to the imaginary plane formed by, Z-axis refers to a direction parallel to the height direction of the plane formed with respect to the first ring.

Magnetic field controllable mobile biocarrier according to a preferred embodiment of the present invention and a method for manufacturing the same by controlling the movement of the biocarrier by a rotating magnetic field applied from the outside so as to deliver cells to local parts such as internal tissues or microvascular vessels of the human body There are technical features.

The magnetic field controllable biosupport 10 according to the preferred embodiment of the present invention includes the sphere 100 and the magnetic layer 200.

1 is an overall perspective view of a magnetic field controllable mobile biocarrier according to an embodiment of the present invention.

Referring to FIG. 1, the sphere 100 forms a space in which the cells 20 can be cultured, and the first ring 110 and the second ring in order to increase the transfer efficiency of transporting the cells 20 to a target point. The ring 120 and the third ring 130 are connected to each other so as to have a substantially spherical shape.

2 and 3 are cross-sectional perspective views showing the XZ-axis plane and the YZ-axis plane of the magnetic field controllable mobile biocarrier according to an embodiment of the present invention.

Referring to FIG. 2, on the XZ plane, the first ring 110 is provided to have a circular cross section, and the second ring 120 is connected to perpendicularly cross the first ring 110. In addition, the third ring 130 is disposed horizontally with respect to the first ring 110 is connected to cross the first ring 110 and the second ring 120.

Referring to FIG. 3, on the YZ plane, the second ring 120 is disposed to have a circular cross section, and the first ring 110 is connected to perpendicularly cross the second ring 120. In addition, the third ring 130 is disposed horizontally with respect to the second ring 120 is connected to cross the first ring 110 and the second ring 120.

Accordingly, the magnetic field controllable biosupport 10 may have one of the cross sections cut by the XY, YZ, and XZ planes on a XYZ coordinate as a circular cross section.

Here, the first ring to the third ring is shown and described as being provided in a circular ring shape, but is not limited to this, provided in an oval ring shape to be formed as an ellipsoid or a circular ring and an elliptic ring are combined with each other. It can be provided in different shapes.

Figure 4 is an enlarged cross-sectional view of a movable magnetic field controllable mobile carrier according to an embodiment of the present invention.

Referring to FIG. 4, a magnetic layer 200 and a protective layer 300 may be provided on an outer surface of the sphere 100 including the first to third rings.

The sphere 100 is not particularly limited as long as it is a material and a form that can be used as a conventional biotransformer, a biodegradable material which is made of a resin material such as polymer, ceramic, nanofiber, or can be naturally decomposed in the human body, It may be made of a biodegradable magnetic material or the like.

Preferably, the sphere 100 may be manufactured by lithography using a photocurable polymer to form a micro size that is easily moved in vivo.

Here, the photocurable polymer is a polymer that is cured when irradiated with light, and there is no particular limitation as long as it can form a three-dimensional biocarrier through a lithography method. More preferably, SU-8 polymer, KMPR, IP-L or It may be a single or mixed form, such as IP-G. Most preferably SU-8 polymer.

Since the sphere 100 may control the movement of the biocarrier 10 by an external magnetic field by forming the magnetic layer 200 on the outer surface, the sphere 100 may not be operated by a surgical method and a machine, and the biocarrier may be applied to the implanted site ( 10) can be located.

The magnetic layer 200 may be formed of a metal having a certain strength of magnetism and having no high corrosiveness (reactivity), and more preferably nickel (Ni), iron (Fe), cobalt (Co), or neodymium (Nd). It may be a single or mixed form, such as), most preferably may include nickel (Ni).

Accordingly, the sphere 100 is rotated by the interaction between the rotating magnetic field and the magnetic layer 200 applied from the outside, thereby moving the clouds in one direction to transport the cells 20 to the target point.

Here, the magnetic layer 200 is shown and described as being formed on the entire outer surface of the sphere 100, but is not limited to this, the inner and outer surfaces of the sphere, the first ring 110 to the third ring 130 ) May be selectively provided in, or partially provided on the outer surface of the sphere 100, such as formed at the intersection between the ring and the ring.

Figure 5 is a state diagram showing the state of cell culture in the magnetic field controllable mobile delivery vehicle according to an embodiment of the present invention.

As the sphere 100 is shown in Figure 5, since the first ring 110 to the third ring 130 are connected to cross each other at a predetermined interval a plurality of gaps on the outer peripheral surface of the sphere 100 Is formed. Through such a gap, the biological support 10 is formed as a cell-support complex by culturing cells 20 for special use for regeneration of bone, skin, organs, etc. in the internal space of the sphere 100.

However, the present invention is not limited thereto, and the drug may be stored in the internal space of the sphere 100 to deliver the drug to a target point.

Here, the size of the gap may be adjusted by connecting the first ring 110 to the third ring 130 to cross each other depending on the cells and tissues that are implanted in the biotransformer 10, and there is no particular limitation thereto.

6 is an operational state diagram of a magnetic field controllable mobile biocarrier according to an embodiment of the present invention.

As shown in FIG. 6, the biocarrier 10 may be obtained by using a tool such as an endoscope, which is not shown in the form of a cell-support complex, by culturing cells 20 of tissue to be implanted into a gap or an inner space of the biocarrier. As it is implanted in the human body, it is important not to cause side effects.

Accordingly, the sphere 100 includes a protective layer 300 covering the entire outer surface so that there are no side effects in vivo. However, the present invention is not limited thereto, and the protective layer 300 may be formed to cover the entire outer surface of the magnetic layer 200.

Here, the protective layer 300 is preferably made of a material having excellent biocompatibility, and may be a single or mixed form of titanium (Ti), medical stainless steel, alumina (Al ₂ O ₃ ) or gold (Au). Preferably, it may include titanium (Ti).

Referring to the magnetic field controllable mobile biotransformer and its manufacturing method are as follows.

Magnetic field controllable biosupport of the present invention comprises the steps of forming a sphere; And forming a magnetic layer on an outer surface of the sphere.

Forming the sphere is to form a sphere 100 capable of carrying the cell 20 at the same time the body 20 is cultured, the first ring 110 and the first ring 110 A first ring 110 to a second ring 120 connected to cross with respect to the first ring 110 and a third ring 130 connected to cross with respect to the second ring 120. A sphere 100 having a plurality of gaps is formed between the third rings 130.

The method for preparing such spheres includes particle leaching, emulsion freeze-drying, high pressure gas expansion, and phase separation, which are methods for preparing conventional biosupports. ), Fused Deposition Modeling (FDM), or lithography.

Preferably, the magnetic field controllable biosupport may prepare a three-dimensional bio-scaffold by lithography using a photocurable polymer.

Forming the magnetic layer is to form a magnetic layer 200 on the outer surface of the sphere 100, the sphere 100 by controlling the movement of the sphere 100 by interacting with a rotating magnetic field applied from the outside To do this.

The method of forming the magnetic layer is not particularly limited as long as it is a general coating method, but more preferably, it can be coated by a method such as electron beam deposition, immersion, electroplating, sputtering or chemical vapor deposition. have.

Accordingly, the magnetic field controllable biosupport according to the present invention does not have the help of surgical methods and machines as in the prior art, and rotates the magnetic field control provided externally to a dangerous part when exposed to the outside such as a local site or blood vessel and brain tissue. Through the cell 20 may be delivered to the target point.

Preferably, after the magnetic layer forming step, in order to improve stability and biocompatibility in vivo, a biocompatible metal may be coated on the outer circumferential surface of the magnetic layer 200.

The biocompatible metal is not particularly limited as long as it is stable in vivo and has excellent biocompatibility, and more preferably, such as titanium (Ti), medical stainless steel, alumina (Al ₂ O ₃ ), or gold (Au) alone. Or it may be in a mixed form, and most preferably may include titanium (Ti).

As with the coating of the magnetic material, if there is no particular limitation as long as it is a conventional coating method, it may be more preferably coated by a method such as electron beam deposition, immersion, electroplating, sputtering or chemical vapor deposition.

Preferably, after the magnetic layer forming step, the cells to be delivered to the target point in the interior space of the plurality of gaps and spheres may be stored or the drug.

Accordingly, since the magnetic support capable of controlling the magnetic field of the present invention and its manufacturing method have excellent biocompatibility, it is possible to prevent the occurrence of side effects in the process of inserting into the human body and using the rotating magnetic field applied from the outside. Because the movement can be controlled, there is an effect that can directly deliver cells to local areas, blood vessels and brain tissue without the help of surgical methods and machinery.

The present invention described above is not limited to the above-described embodiments and the accompanying drawings, and various substitutions, modifications, and alterations are possible within the scope without departing from the technical spirit of the present invention. It will be evident to those who have knowledge of.

10: magnetic field controllable carrier 20: cell
100; Sphere 110: First Ring
120: second ring 130: third ring
200: magnetic layer 300: protective layer

Claims (8)

A first ring, a second ring connected to intersect with respect to the first ring and a third ring connected to intersect with respect to the first ring and the second ring are provided asymmetrically and the first to third ring Spheres having a plurality of gaps formed therebetween; And
It includes; a magnetic layer formed on the sphere,
The sphere is a magnetic field controllable mobile carrier, characterized in that the rolling movement in one direction by rotating by the interaction between the magnetic field formed by the magnetic layer and the magnetic layer applied from the outside. The method of claim 1,
The sphere is a magnetic field controllable mobile biocarrier characterized in that it is provided with any one of a resin material, a biodegradable material or a biodegradable magnetic material that is naturally decomposed in the human body. The method according to claim 1 or 2,
And the magnetic layer is entirely or partially covered by the sphere. The method according to claim 1 or 2,
And the sphere comprises a protective layer made of a biocompatible material. The method of claim 1,
The sphere having a plurality of gaps is a magnetic field controllable mobile carrier, characterized in that it comprises cells cultured in the inner space or to store the drug. A first ring, a second ring connected to intersect with respect to the first ring and a third ring connected to intersect with respect to the first ring and the second ring are provided asymmetrically and the first to third ring Forming a sphere having a plurality of gaps therebetween; And
And forming the magnetic layer on the outer surface of the sphere so that the sphere contacts the inside of the living body and moves in one direction by the interaction between the rotating magnetic field applied from the outside and the magnetic axis formed by the magnetic layer. Method of manufacturing a magnetic field controllable mobile biocarrier. The method of claim 6,
After the magnetic layer forming step,
And forming a protective layer made of a biocompatible material so as to cover the magnetic layer. The method of claim 6,
After the magnetic layer forming step,
The method of manufacturing a magnetic field controllable mobile biocarrier comprising the step of culturing cells or storing drugs in a sphere having a plurality of gaps.

Images