KR-102964039-B1 - MICRO CARRIER, CELL COMPOSITE, AND MEDICAL COMPOSITION, COSMETIC COMPOSITION, MEDICAL ARTICLES AND COSMETIC ARTICLES USING THE SAME

Abstract

According to the present invention, the invention relates to a polymer microparticle having a core-shell structure comprising: a core comprising a first biocompatible polymer, a metal ion, and an organic crosslinking agent comprising one or more reactive functional groups; and a shell surrounding all or part of the core and comprising a second biocompatible polymer, a metal ion, and an organic crosslinking agent comprising one or more reactive functional groups; and a cell adhesion-inducing layer formed on the surface of the polymer microparticle, the invention relates to a microcarrier comprising the same, a cell complex comprising the same, a medical composition, a cosmetic composition, a medical supply, and a cosmetic supply.

Inventors

• 김윤섭
• 김지선

Assignees

• 주식회사 엘지화학

Dates

Publication Date

20260512

Application Date

20210930

Claims (20)

1. A polymer microparticle having a core-shell structure, comprising: a core comprising a first biocompatible polymer, a metal ion, and an organic crosslinking agent comprising one or more reactive functional groups; and a shell surrounding all or part of the core and comprising a second biocompatible polymer, a metal ion, and an organic crosslinking agent comprising one or more reactive functional groups; and A cell adhesion-inducing layer formed on the surface of the above polymer microparticles; comprising The above core comprises a polymer matrix in which a first biocompatible polymer is crosslinked via an organic crosslinking agent comprising one or more metal ions and reactive functional groups, and The above shell comprises a polymer matrix in which a second biocompatible polymer is crosslinked via an organic crosslinking agent comprising one or more metal ions and reactive functional groups, and The above core, with respect to the total volume of the polymer matrix contained in the core, A polymer matrix in which hyaluronic acid is crosslinked via an organic crosslinking agent containing one or more metal ions and reactive functional groups, comprising more than 50 volume%, and The above shell, with respect to the total volume of the polymer matrix contained in the shell, A microcarrier comprising more than 50 volume% of a polymer matrix crosslinked via an organic crosslinking agent containing one or more metal ions and reactive functional groups, wherein gelatin.
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3. In paragraph 1, The first biocompatible polymer above comprises hyaluronic acid, and The second biocompatible polymer is a microcarrier comprising gelatin.
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6. In paragraph 1, The above polymer microparticles are microcarriers having an average diameter of 1 μm or more in distilled water.
7. In paragraph 1, Based on the cross-section having the longest diameter of the above polymer microparticle, A microcarrier in which the thickness of the shell is 95% or less of the longest diameter of the polymer microparticle.
8. In paragraph 1, An organic crosslinking agent comprising one or more of the above-mentioned reactive functional groups, A microcarrier comprising a crosslinking agent having 1 to 30 carbon atoms and containing one or more reactive functional groups.
9. In paragraph 1, The above polymer microparticles are Microcarriers having an average compressive strength of 0.1 mN or more when deformed to 25% of the average particle diameter.
10. In paragraph 1, The above polymer microparticles are A microcarrier having a sphericity of 0.9 or greater and 1.0 or less, which is the ratio of the longest diameter to the shortest diameter (major axis ratio) of any particle in an optical photograph.
11. In paragraph 1, A microcarrier comprising one or more cell-adhesive materials selected from the group consisting of gelatin, collagen, fibronectin chitosan, polydopamine, poly L-lysine, vitronectin, peptides including RGD, acrylic polymers including RGD, lignin, cationic dextran, and derivatives thereof, wherein the cell adhesion-inducing layer comprises gelatin, collagen, fibronectin chitosan, polydopamine, poly L-lysine, vitronectin, peptides including RGD, acrylic polymers including RGD, lignin, cationic dextran, and derivatives thereof.
12. In paragraph 1, The cell adhesion-inducing layer is a microcarrier having a layer thickness of 1 nm to 10,000 nm.
13. In paragraph 1, The microcarrier is a microcarrier having an average diameter of 1 μm to 1000 μm.
14. In paragraph 1, The above microcarrier is a microcarrier having a cell adhesion of 2000% or more calculated by the following mathematical formula: [Mathematical Formula] Cell adhesion = (Number of cells after adding microcarrier to cell culture medium and culturing at 37°C for 7 days / Number of cells initially included in cell culture medium) X 100.
15. In paragraph 1, The above microcarrier is a microcarrier that is a microcarrier for cell culture.
16. The microcarrier of claim 1; and A cell complex comprising a cell attached to the surface of the microcarrier above.
17. A medical composition comprising either the microcarrier of claim 1 or the cell complex of claim 16.
18. A cosmetic composition comprising either the microcarrier of claim 1 or the cell complex of claim 16.
19. A medical product comprising the medical composition of claim 17.
20. A beauty product comprising the beauty composition of claim 18.

Description

Microcarrier, cell complex, and medical composition, cosmetic composition, medical articles and cosmetic articles containing the same The present invention relates to a microcarrier capable of realizing excellent mechanical strength and stability, enabling immediate injection into the body after 3D culture without a cell detachment process, and providing a stable environment for adherent cells to increase cell viability and contribute to a high in vivo implantation rate, as well as cell complexes, medical compositions, cosmetic compositions, medical supplies, and cosmetic supplies containing the same. As the fields of biopharmaceuticals and regenerative medicine expand, there is a growing demand for mass cell culture technology capable of efficiently producing cells, tissues, microorganisms, and more. Adherent cells are cultured using microcarriers within a 3D bioreactor. Cells, culture medium, and microcarriers are placed inside the bioreactor, and the medium is stirred to bring the cells and microcarriers into contact, thereby allowing the cells to attach to the surface of the microcarriers for culture. The microcarriers used in this process are suitable for large-scale cell culture because they provide a high surface area to volume ratio, which allows cells to attach and proliferate. However, when expanding the culture of adherent cells using microcarriers, a process of recovering the cells through a cell detachment process is essential after the culture is completed. This cell detachment process is induced by using proteolytic enzymes or changing the temperature; however, the addition of such a detachment process has the problem of increasing manufacturing costs, reducing economic feasibility, and potentially causing cell damage. The development of new materials and processes to address this is continuously underway. In particular, for cell therapies involving the injection of cells into the body, efforts are being made to eliminate separation and purification processes by ensuring the biocompatibility of microcarriers used for cell culture. In this case, particles are required that possess the strength to withstand the stress exerted by the fluid surrounding the carrier during the culture process and after in vivo injection. Furthermore, in the case of transdermal drug delivery technology, which involves loading microcarriers containing drugs or physiologically active substances onto microneedles for delivery, the microcarriers must utilize polymers suitable for biocompatibility and possess sufficient strength to prevent particle deformation during passage through the stratum corneum layer of the skin. Microcarriers that have stably penetrated the dermis can then deliver the loaded drug locally or systemically to act on the necessary lesions. Hyaluronic acid, primarily used as a biocompatible material, is a biopolymer composed of N-acetyl-D-glucosamine and D-glucuronic acid, with these repeating units linearly linked. It is abundant in the vitreous humor of the eye, synovial fluid of joints, and rooster combs. Due to its excellent biocompatibility and viscoelasticity, hyaluronic acid is commonly used as an injectable material; however, its use is limited because it degrades easily in vivo or under acidic or alkaline conditions. Furthermore, when applied to microcarriers, hyaluronic acid exhibits a negative charge within the biological pH range, which has led to a problem of significantly reduced cell adhesion. Furthermore, gelatin is a polymer obtained by hydrolyzing collagen, a biological connective tissue, and is utilized as a scaffold for cell culture. Although it can capture or culture cells, its strength is weak and it is sensitive to temperature, so efforts are being made to improve its strength by introducing functional groups through chemical methods. Accordingly, there is a need to develop microcarriers or polymer microparticles that are biocompatible and possess excellent physical properties, such as physical strength and stability against heat and enzymes. In addition, spherical microcarriers capable of increasing surface efficiency have been developed to overcome the limitations of conventional two-dimensional culture in the mass expansion process of adherent cells using microcarriers and are being used in three-dimensional expansion culture. However, in conventional technology where cells are recovered through a cell detachment process after the end of culture, there were problems such as increased manufacturing costs due to the addition of a detachment process and cell damage. In addition, in the case of injectable cell therapies, since the cells are mainly injected into the affected area while suspended in a liquid, there was a limitation in that the in vivo transplantation rate and cell viability were low due to an environment that was not stable for the survival of adherent cells and immune responses within the body. Accordingly, there is a need to develop microcarriers that can be inj