Patent Application
20220347351
The present disclosure relates to a biocompatible porous scaffold, a support composition for human body transplantation comprising the same, and a method for preparing the same.
Recently, as the fields of bionics, material engineering, and surgical operation have been greatly developed, tissue engineering for the purpose of replacing and regenerating lost body tissues is making remarkable progress. Tissue engineering aims to understand the correlation between the structure and function of biological tissues by combining life science, engineering, and medicine, and it aims to maintain, improve, or restore body functions through artificial tissues that can be transplanted in the body in order to replace with normal tissues or regenerate damaged tissues or organs based on this.
The loss of body tissues is due to various causes such as degenerative diseases, trauma, surgical removal of tumors, and certain congenital malformations, and the body tissues can be restored to the original state only through the regeneration of irreversibly lost tissues. In order to induce regeneration of lost tissues through tissue engineering, it is important to first prepare a biodegradable polymer support (scaffold) similar to biological tissues. The main requirement of the support material used for the regeneration of human body tissues is that the tissue cells should sufficiently play a role of a substrate or frame so that the tissue cells may adhere to the material surface to form a tissue with a three-dimensional structure, and they should also be able to play a role of an intermediate barrier located between the transplanted cells and the patient cells.
After the scaffold is transplanted into a subject, when engraftment of cells necessary for tissue regeneration is induced, and the formation of new tissues is initiated, the newly formed tissues should fill the space as they disappear over time. Therefore, it is preferable that the scaffold is a biodegradable one that does not require surgical removal, and the scaffold should not cause immunorejection, inflammatory response, or long-term fibrous encapsulation, should not undergo shrinkage of the graft volume, and should be free from serious complications such as prosthetic implants.
Therefore, after serving as a physical support for an appropriate period, the scaffold should have a certain level of mechanical strength and elastic force along with biodegradability in order to efficiently induce tissue reformation while disappearing naturally. Therefore, for this purpose, it is very important to select a structure that is the most suitable for the most suitable natural or synthetic polymer.
Numerous papers and patent documents are referenced throughout the present specification and their citations are indicated. The disclosure contents of the cited papers and patent documents are inserted into the present specification by reference in their entirety to more clearly describe the level of the technical field to which the present disclosure pertains and the content of the present disclosure.
The present inventors have made intensive research efforts in order to develop a scaffold for efficient tissue regeneration that can be prepared by a relatively simple process while having sufficient physical strength and excellent biocompatibility. As a result, the present inventors have discovered that, when a mesh-type support composed of strands each having a certain diameter while having pores each having a certain size is prepared with a first polymer, and then the surface of the mesh-type support is coated with a second polymer having biocompatibility as a polymer different from the first polymer, the mesh-type support coated with the second polymer can be used as scaffolds for human body transplantation for various uses, including artificial ligaments and supports for reinforcing the abdominal wall, by showing not only high tensile strength and biocompatibility, but also a remarkably excellent cell engraftment rate.
Further, the present inventors have completed the present disclosure by discovering the fact that, when two biocompatible polymers with different structures and functions are manufactured into a three-dimensional porous structure and a two-dimensional porous structure respectively, and then joined, remarkably improved physical properties are exhibited while maintaining the unique functions such as tissue regeneration, wound healing, provision of in vivo binding force, and the like.
Accordingly, an object of the present disclosure is to provide a porous scaffold and a method for preparing the same.
Another object of the present disclosure is to provide a support for human body transplantation including the porous scaffold.
Other objects and advantages of the present disclosure will become more apparent from the following detailed description of the invention, claims, and drawings.
According to an aspect of the present disclosure, the present disclosure provides a method for preparing a porous scaffold, comprising:
(a) producing a polymer mesh having pores with an area of 0.1 to 0.5 mm2 and strands each having a diameter of 0.1 to 0.3 mm from a solution of a first polymer; and
(b) coating the surface of the produced polymer mesh with a solution of a second polymer having biocompatibility.
The present inventors have made intensive research efforts in order to develop a scaffold for efficient tissue regeneration that can be prepared by a relatively simple process while having sufficient physical strength and excellent biocompatibility. As a result, the present inventors have discovered that, when a mesh composed of strands each having a diameter of 0.1 to 0.3 mm while having pores of 0.1 to 0.5 mm2 is prepared with a first polymer, and then the surface of the mesh is coated with a second polymer having biocompatibility as a polymer different from the first polymer, the mesh coated with the second polymer can be used as scaffolds for human body transplantation for various uses, including artificial ligaments and supports for reinforcing the abdominal wall, by showing not only high tensile strength and biocompatibility, but also a remarkably excellent cell engraftment rate.
The term “scaffold” in the present specification refers to a tissue engineering structure for promoting recovery and regeneration of damaged tissues by attaching living cells, specifically, cells derived from damaged tissues or cells involved in the recovery of the damaged tissues. The term “cell attachment” indicates that cells are directly or indirectly adsorbed to a matrix or other cells while maintaining their intrinsic biological activities. Specifically, the scaffold according to the present disclosure may have a planar structure consisting of a single mesh or a three-dimensional structure in which a plurality of meshes are stacked.
The term “polymer” in the present specification refers to a synthetic or natural high molecular compound in which the same or different types of monomers are continuously combined. Thus, examples of the polymer include homopolymers (polymers in which one type of monomer is polymerized) and interpolymers prepared by the polymerization of at least two different monomers, and examples of the interpolymers include both copolymers (polymers prepared from two different monomers) and polymers prepared from more than two different monomers.
According to a specific embodiment of the present disclosure, the first polymer used in the present disclosure is selected from the group consisting of polycaprolactone (PCL), poly(L-lactic acid) (PLLA), poly(glycolic acid) (PGA), poly(lactic-co-glycolic acid) (PLGA), poly(L-lactide-co-ε-caprolactone) (LCL), and combinations thereof
More specifically, the first polymer is polycaprolactone (PCL).
According to the present disclosure, the first polymer forms a mesh having pores each having a certain size while strands each having a certain thickness at regular intervals intersect. In order to efficiently achieve recovery and regeneration of damaged tissues which are the ultimate object of the present disclosure, the pores should have the most suitable size in terms of the mechanical strength and elastic force of the mesh itself as well as attachment, proliferation, and activity maintenance of cells, and induction of new blood vessels during the tissue regeneration. Accordingly, the suitable pore area is specifically 0.1 to 0.5 mm2, more specifically 0.1 to 0.4 mm2, still more specifically 0.2 to 0.3 mm2, and most specifically about 0.25 mm2.
The term “pore area” in the present specification refers to the average area of repeated pores appearing through the intersection of strands in the mesh structure according to the present disclosure prepared with the first polymer, and such an area refers to the area measured before performing coating using a second polymer solution to be described later.
Moreover, the diameter of the strand forming the mesh together with the above-described pore area is important in order to secure physical properties suitable as a support for human body transplantation by having appropriate elastic modulus and tensile modulus. Accordingly, the strand has a suitable diameter of specifically 0.1 to 0.3 mm, more specifically 0.15 to 0.25 mm, and most specifically about 0.2 mm.
The step of producing the polymer mesh from the first polymer solution according to the present disclosure may use various methods known in the art, and examples of the methods include a three-dimensional printing method, a solvent-casting particulate leaching method, a gas foaming method, a fiber mesh/fiber bonding method, a phase separation method, a melt molding method, a freeze drying method, and an electrospinning method, but are not limited thereto.
According to the present disclosure, the scaffold has biocompatibility, in addition to the mechanical strength described above, by coating a polymer mesh, prepared with a first polymer solution, with a second polymer solution having biocompatibility.
The term “biocompatibility” in the present specification refers to properties that do not cause short-term or long-term side effects when administered in vivo and in contact with cells, tissues or body fluids of organs, and specifically, refers to tissue compatibility and blood compatibility that do not cause tissue necrosis or coagulate blood in contact with biological tissues or blood, as well as biodegradability that disappears after a certain period of time after administration in vivo.
The term “biodegradability” in the present specification refers to properties of being naturally decomposed when exposed to a physiological solution of pH 6 to 8, and specifically, refers to properties capable of being decomposed according to the passage of time by body fluids in a living body, degrading enzymes, or microorganisms. A biodegradable polymer usable in the present disclosure may also be any synthetic or natural polymer as long as it is a polymer having the above-described biodegradability, and examples thereof include collagen, gelatin, chitosan, hyaluronic acid, poly(valerolactone), poly(hydroxy butylate), poly(hydroxyvalerate), and combinations thereof, but are not limited thereto.
According to a specific embodiment of the present disclosure, the second polymer having biocompatibility is a natural polymer, more specifically collagen, and most specifically type 1 collagen.
According to a more specific embodiment of the present disclosure, the collagen solution is used at a concentration of 0.2 to 0.8% (v/v), more specifically 0.3 to 0.7% (v/v), and most specifically 0.4 to 0.6% (v/v).
The term “coating” in the present specification refers to forming a new layer having a certain thickness by modifying a specific material on the target surface, and the target surface and the coating material may be modified through an ionic bond or noncovalent bond. The term “noncovalent bond” is a concept including bonds generated by acting interactions such as hydrogen bonds and van der Waals bonds alone or together with the physical bonds as well as physical bonds such as adsorption, cohesion, entanglement, and entrapment. In the present disclosure, when the polymer mesh is coated with the second polymer solution, a sealed layer may be formed while completely surrounding the surface of the mesh, or a partially sealed layer may be formed.
According to a specific embodiment of the present disclosure, the method according to the present disclosure further comprises performing plasma treatment on a surface of the polymer mesh between the step (a) and the step (b).
According to the present disclosure, when a polymer mesh is prepared using a hydrophobic polymer such as polycaprolactone (PCL) as the first polymer, the polymer mesh may be homogeneously coated with a hydrophilic second polymer having biocompatibility through a pretreatment process that imparts hydrophilicity to a hydrophobic mesh. When plasma discharge is applied to the surface of a polymer material, as gas-reactive species are formed, the hydrophilicity of the surface increases through reaction with the polymer surface layer and cleavage of elemental bonds through energy transfer.
Specifically, plasma treatment may be performed under medium vacuum conditions of 1.0 to 0.1 Torr at room temperature.
Specifically, the plasma surface treatment is performed for 45 to 90 seconds, more specifically 50 to 80 seconds, and most specifically 50 to 70 seconds.
As shown in Examples to be described later, when plasma treatment is performed for 45 seconds or more, the hydrophilicity of the surface is increased so that a uniform collagen film is formed with almost no air bubbles generated on the surface of the mesh. However, when plasma treatment is performed for more than 90 seconds, there is a disadvantage in that the molecular weight is reduced from the surface of the first polymer so that the mechanical strength is weakened.
According to another aspect of the present disclosure, the present disclosure provides a porous scaffold comprising:
(a) a first polymer mesh having pores with an area of 0.1 to 0.5 mm2 and strands each having a diameter of 0.1 to 0.3 mm; and
(b) a second polymer having biocompatibility with which the surface of the first polymer mesh is coated.
Since the first polymer and the second polymer used in the present disclosure have already been described above, their descriptions are omitted in order to avoid excessive overlapping.
According to still another aspect of the present disclosure, the present disclosure provides a support composition for human body transplantation comprising the porous scaffold.
The term “transplantation” in the present specification refers to a process of delivering biological tissues, cells, or an artificial support that accommodates the biological tissues and cells from a donor to a recipient for the purpose of maintaining the functional integrity of the tissues or cells transplanted into the recipient. Accordingly, the term “support for transplantation” refers to a physical support used in the process of delivering the biological tissues or cells to the recipient.
According to a specific embodiment of the present disclosure, the support composition according to the present disclosure is a support composition used for ligament reconstruction, craniofacial reconstruction, maxillofacial reconstruction, tissue reconstruction after removal of melanoma or head and neck cancer, chest wall reconstruction, delayed burn reconstruction, pelvic reinforcement, genital reinforcement, or abdominal wall reinforcement, and more specifically a support composition used for ligament reconstruction or abdominal wall reinforcement.
According to another aspect of the present disclosure, the present disclosure provides a method for tissue reconstruction comprising transplanting the above-described support composition according to the present disclosure in vivo.
According to another aspect of the present disclosure, the present disclosure provides a method for preparing a dual structure porous scaffold, comprising embossing a first polymer having biocompatibility into a mesh form on the surface of a support containing a second polymer having biocompatibility.
The present inventors have completed the present disclosure by discovering the fact that, when two biocompatible polymers with different structures and functions are manufactured into a three-dimensional porous structure and a two-dimensional porous structure respectively, and then joined, remarkably improved physical properties are exhibited while maintaining the unique functions of the respective polymers such as tissue regeneration, wound healing, provision of binding force, and the like.
Since the second polymer used in the present disclosure has already been described above, the description thereof is omitted in order to avoid excessive overlap. The second polymer having biocompatibility according to the present disclosure may be collagen, and in this case, the support containing the second polymer may be a collagen sponge.
The term “sponge” in the present specification refers to a spongy porous material which is composed of a three-dimensional network connected by an ionic or covalent bond of polymers and uses water as a dispersion medium. The collagen sponge according to the present disclosure may be used without limitation as long as it is a spongy structure having voids or pores in collagen, and for example, it may be prepared by freeze-drying a collagen solution or dispersion, or various commercially available ready-made collagen sponges may be purchased and used.
Since the first polymer used in the present disclosure has also been described above, the description thereof is omitted in order to avoid excessive overlap. Specifically, the first polymer according to the present disclosure may be polycaprolactone (PCL).
The dual structure porous scaffold according to the present disclosure may be fabricated as a conjugate of a collagen sponge-PCL mesh by embossing a first polymer, for example, PCL into a mesh form on a second polymer-containing support, for example, the surface of a collagen sponge. The term “embossing” in the present specification refers to a process of bonding PCL polymer to the sponge surface so that a mesh form is engraved on the surface of the collagen sponge in a protruding form.
According to a specific embodiment of the present disclosure, the embossing may be performed by outputting the first polymer in a mesh form using a three-dimensional printer on the surface of the second polymer-containing support.
According to a specific embodiment of the present disclosure, the mesh form includes strands each having a diameter of 0.3 to 0.5 mm and a spacing between the strands of 0.1 to 0.3 mm.
According to another aspect of the present disclosure, the present disclosure provides a dual structure porous scaffold including the following:
(a) a support containing a second polymer having biocompatibility; and
(b) a first polymer mesh which is bonded to the surface of the support and has biocompatibility.
Since the process of bonding the first polymer mesh to the second polymer-containing support using a first polymer, a second polymer, a support, and embossing which are used in the present disclosure has already been described above, the description thereof will be omitted in order to avoid excessive overlap.
The dual structure porous scaffold according to the present disclosure (for example, a collagen sponge-PCL mesh conjugate) is excellent in tensile strength and bonding strength compared to general collagen sponges used for regenerative treatment of bone tissues, skin tissues, etc. and has biodegradable properties, thereby providing a more stable bonding function and a remarkably improved fixation function within the human body for the period required for wound healing and tissue regeneration.
The features and advantages of the present disclosure are summarized as follows:
(a) the present disclosure provides a porous scaffold having excellent tissue engineering characteristics and a method for preparing the same; and
(b) the scaffold according to the present disclosure not only can be prepared by a simple process, but also can exhibit a remarkably excellent cell engraftment rate as well as high tensile strength and biocompatibility so that it can be usefully used as a support composition for human body transplantation of various uses, including artificial ligaments and supports for reinforcing the abdominal wall.
Hereinafter, the present disclosure will be described in more detail through examples. These examples are only for illustrating the present disclosure in more detail, and it will be obvious to those skilled in the art that the scope of the present disclosure is not limited by these examples according to the subject matter of the present disclosure.
A three-dimensional printer (Biobots, USA) was used in order to prepare a three-dimensional polymer structure, and the three-dimensional printing technique can easily adjust the size of a mesh depending on conditions such as nozzle diameter, temperature, discharge pressure, and nozzle movement speed. The present inventors selected a mesh form including strands each having a diameter of 0.2 mm and a spacing of 1.0 mm between the strands as the design that can most stably support the damaged ligament and abdominal wall (
In order to fabricate a polymer mesh, the diameter of the nozzle was set to 0.1 to 0.5 mm, the nozzle temperature was set to 80 to 90° C, the discharge pressure was set to 50 to 100 psi, and the nozzle movement speed was set to 2 to 5 mm/s. The polycaprolactone mesh prepared under these conditions was processed into a circular specimen having a diameter of 1.5 cm through a punching operation, washed with 70% ethanol for about 30 minutes in order to remove foreign substances, and then dried at room temperature for 2 hours.
The surface of the mesh was coated with collagen in order to impart biocompatibility to the polycaprolactone mesh prepared by three-dimensional printing. In order to homogeneously coat collagen, the present inventors introduced a pretreatment process that imparts hydrophilicity by subjecting polycaprolactone with strong hydrophobicity before coating to surface treatment using plasma. First of all, a collagen solution was prepared by dissolving atelocollagen (type 1, medical device grade, Dalim Tissen Co., Ltd., Korea) extracted from porcine dermis in 0.5 M acetic acid at a concentration of 0.5% at 4° C for 12 hours.
In order to select the optimal plasma treatment time for the most efficient collagen coating, the caprolactone mesh having been dried after washing was placed on a slide glass, and then treated using a plasma surface treatment machine (PDC-32G Plasma Cleaner, Harrick Plasma, USA) for 0, 15, 30, 45, and 60 seconds under medium vacuum conditions of 1.0 to 0.1 Torr. After the surface treatment process, 250 μl of a collagen solution per specimen was put therein to coat the mesh surface with collagen at 4° C for 30 minutes, and the collagen-coated mesh was observed with an optical microscope (EVOS® XL Core Cell Imaging System, Thermo Fisher scientific, USA) (
Thereafter, the present inventors tried to evaluate the optimal concentration of collagen with which the surface is coated by considering physical properties, biocompatibility, etc. that the polymer mesh should have as a human body insert. For this, collagen solutions were prepared by dissolving atelocollagen in 0.5 M acetic acid at various concentrations (0.1, 0.5, 0.75, and 1.0%) at 4° C for 12 hours, plasma surface treatment was performed for 60 seconds, and then 250 μl of the collagen solution was put into each of the mesh specimens to carry out a coating operation at 4° C for 30 minutes. Each sample that had been subjected to the coating operation was cooled to −70° C for 12 hours and then dried using a freeze dryer (FreeZone 12 plus, Labconco, USA) for 24 hours in order to create a porous surface structure of collagen with which the surface thereof is coated. Thereafter, a neutralization operation was performed in order to remove acetic acid present in the form of a salt inside freeze-dried collagen. For this, after the specimen that had been freeze-dried was washed 4 times for 15 minutes using anhydrous alcohol (ethanol absolute, Merck KGaA, Germany), 0.5 M NaOH (Duksan General Science, Korea) was dissolved in 70% ethanol, and then the neutralization operation of acetic acid was performed 4 times for 15 minutes. Thereafter, in order to remove the residual amount of NaOH present in the specimen, the collagen-coated mesh was sequentially washed 4 times for 15 minutes using 50% ethanol, 30% ethanol, and tertiary distilled water. After the collagen-coated mesh that had been washed was cooled to −70° C for 12 hours, and dried using a freeze dryer for 24 hours as mentioned above, images were obtained using a digital camera (EOS 500D, Canon, Japan) (
Next, the surface shapes of the collagen-coated meshes were observed using an electron microscope (FE-SEM, MERLIN, Zeiss, Germany) in order to observe the micro-shapes of the collagen-coated meshes (
The tensile strength values were measured in order to analyze the physical strength values of the biodegradable meshes for transplantation fabricated in the present disclosure. In order to secure analysis results with higher reliability, acellular allogeneic dermis (CG Derm, Korea) commercially available as a ready-made article for the purpose of reconstruction of soft tissues of the human body was set as a comparison group, and the strength thereof was compared with that of the mesh for transplantation developed by this research team. To this end, after each specimen was processed into a 1 cm×5 cm rectangle and soaked in physiological saline for 30 minutes, the tensile strength was measured while the specimen was pulled at a speed of 1 mm per second using an all-around test analyzer (Universal Testing Systems, Instron 3360, USA). As a result, acellular allogeneic dermis that was the ready-made article showed a lower elastic force than the mesh for transplantation according to the present disclosure until it showed a tensile modulus of 50%, but showed the highest tensile strength of 15.27 MPa at the point of showing a tensile modulus of 124% (
Elements present on the surface of the mesh for transplantation according to the present disclosure depending on whether or not the mesh is coated with collagen were analyzed using Energy Dispersive X-Ray Spectroscopy (EDS) (EDAX, USA). As a result, it could be confirmed that only carbon and oxygen components were detected in the polycaprolactone mesh that was not coated with collagen, whereas nitrogen in the peptide was detected in the specimen whose surface was coated with collagen so that 12.71% of the nitrogen element in the total element ratio was existed (
Human dermal-derived fibroblasts (LONZA, USA) were cultured on the mesh surface in order to evaluate the reactivity between the collagen-coated mesh for transplantation and cells in an in vitro environment. After the previously prepared circular specimens having a diameter of 1.5 cm were placed on a 24-well tissue culture plate (TCP, Corning, USA), 70% ethanol was put thereinto, and a sterilization operation was performed for 30 minutes under a UV lamp. Thereafter, 50,000 fibroblasts (passage number 4) were seeded in each specimen and cells were seeded even in TCP as a control group, and then each of the fibroblasts was cultured at 37° C under 5% carbon dioxide conditions using a medium in which 10 v/v % Fetal bovine serum (FBS) (Gibco, USA) and 1 v/v % antibiotic (Gibco, USA) were mixed with Dulbecco's Modified Eagle Medium (DMEM) (low glucose, Gibco, USA) for 7 days. At this time, in order to analyze behaviors of the cells, the survival/proliferation behaviors of the cells were comparatively analyzed by performing live and dead assays (Thermo Fisher Scientific, USA) on the 1st and 7th days after the start of culture. To this end, after each specimen was washed three times with a phosphate buffer solution (PBS, Gibco, USA) at the end of the culture, calcein AM and ethidium homodimer-1 (EthD-1) in the live and dead assay kit were diluted to concentrations of 2 μM and 4 μM respectively, the diluted solutions were put into each specimen, and the cells were stained at room temperature for 30 minutes, and then the stained cells were observed using a confocal fluorescence microscope (LSM700, Zeiss, Germany) (
In order to evaluate the inflammatory responses and biodegradation behaviors depending on whether or not the mesh for transplantation according to the present disclosure is coated with collagen, after transplanting meshes together with acellular allogeneic dermis (thickness: 1.5 mm, MegaDerm, L&C Bio, Korea) on the dorsal skin of Sprague Dawley (SD) rats (6 weeks old, male N=4, Orient Bio, Korea) and euthanizing the rats at week 6, week 12, and week 20 to collect tissues, the collected tissues were stained with Masson's Trichrome (Sigma Aldrich, USA) to observe the cross sections of the tissues with an optical microscope (CX43, Olympus, Tokyo, Japan) (
As shown in
In order to analyze the previously observed inflammatory responses, the thickness values of the films formed on the implant periphery were measured (
Next, in order to compare the biodegradation behaviors of the implants, changes in the thickness of each of the implants for 20 weeks were measured (
After performing immunostaining on the previously collected tissues in order to evaluate the ability to induce angiogenesis depending on whether or not the mesh for transplantation according to the present disclosure is coated with collagen, staining the cell nucleuses with 4′,6-diamidino-2-phenylindole (DAPI, Blue signal, Sigma Aldrich, USA), and staining vascular endothelial cells with CD31 (Red signal, Thermo Fisher Scientific, Waltham, Mass., USA), the stained cell nucleuses and vascular endothelial cells were observed using a confocal microscope (LSM700, Carl Zeiss, Oberkochen, Germany) (
As can be seen from the fluorescence micrographs of
Arterioles of the SD rats are known to have a diameter of 20 to 40 μm, and the numbers of blood vessels satisfying the diameter conditions of arterioles per unit area (mm2) was quantified through immunofluorescence staining (
As another aspect of the present disclosure, the present inventors dissolved atelocollagen (Type 1, medical device grade, Dalim Tissen Co., Ltd, Korea) extracted from porcine dermis in 0.5M acetic acid at a concentration of 3.0% by weight in order to fabricate a collagen-containing sponge bonded with a polymer mesh. Thereafter, after putting the dissolved atelocollagen in a brass mold, the brass mold was immersed in liquid nitrogen (−196° C) to freeze, and then freeze-dried for 24 hours according to the method described above in Example 1. Thereafter, the dried collagen sponge was subjected to dehydrothermal treatment (DHT) in an oven at 120° C for 24 hours to prepare a collagen sponge (
A PCL-collagen conjugate was fabricated by fixing the sponge to a three-dimensional printing stage in order to reinforce the physical properties of the prepared collagen sponge, and directly printing PCL on the sponge in a mesh form including strands each having a diameter of 0.4 mm and a spacing between the strands of 2.0 mm under the printing conditions applied for polymer mesh fabrication in Example 1 (
Next, the surface shapes and cross-sectional shapes of the mesh structure in which PCL was bonded onto the collagen sponge through three-dimensional printing were observed using an electron microscope (
In order to compare and analyze the physical strengths of the prepared collagen sponge-polymer mesh conjugate, tensile strengths, and bonding strengths with a stitching fiber used when fixing the human body were respectively measured. As can be seen from the tensile strength measurement result of
As the specific parts of the present disclosure have been described in detail above, these specific descriptions are only preferred embodiments for those of ordinary skill in the art, and it is clear that the scope of the present disclosure is not limited thereto. Accordingly, the substantial scope of the present disclosure will be defined by the appended claims and their equivalents.
| Number | Date | Country | Kind |
|---|---|---|---|
| 10-2020-0129849 | Oct 2019 | KR | national |
| 10-2019-0125136 | Oct 2019 | KR | national |
This application is a U.S. National Stage entry of International Patent Application no. PCT/KR2020/013786, filed Oct. 8, 2020, which claims the benefit of priority of Korean Patent Applications nos. 10-2020-0129849, filed Oct. 8, 2020, and 10-2019-00125136, filed Oct. 10, 2019.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/KR2020/013786 | 10/8/2020 | WO |
