CN115591010A - High-activity stem cell biological injectable carrier material and preparation method thereof - Google Patents
High-activity stem cell biological injectable carrier material and preparation method thereof Download PDFInfo
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- CN115591010A CN115591010A CN202211399526.2A CN202211399526A CN115591010A CN 115591010 A CN115591010 A CN 115591010A CN 202211399526 A CN202211399526 A CN 202211399526A CN 115591010 A CN115591010 A CN 115591010A
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- A—HUMAN NECESSITIES
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
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- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
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Abstract
The invention discloses a high-activity stem cell biological injectable carrier material and a preparation method thereof, wherein the preparation method comprises the following steps: the composite material comprises the following components of laponite, a high polymer material and a chemical cross-linking agent, wherein the mass ratio of the high polymer material to the laponite is 0.01-100; the polymer material is one or a combination of silk fibroin, gelatin, quaternary ammonium salt chitosan, chitin, collagen and laminin. The invention has the characteristics of simple synthesis, uniform and stable structure, high biological activity and capability of being prepared clinically.
Description
Technical Field
The invention relates to the technical field of biomedical materials, in particular to a high-activity stem cell biological injectable carrier material and a preparation method thereof.
Background
In recent years, irregular orthopedic diseases caused by environmental pollution, natural disasters, traffic accidents and population aging seriously threaten human health. Although autologous bone grafting and allogeneic bone grafting have high activity as a treatment means for the conventional bone injury, there are problems of limited bone source, injury and immunogenicity, and the like. The current clinical artificial bone repair material has a single structure, lacks bionic bone components, and has low biological activity so as to limit the clinical application. Mesenchymal Stem Cells (MSC) are currently expected to treat bone defect diseases caused by deformity, trauma and other diseases, and effectively enhance bone regeneration at bone defect sites. Also, direct use of MSCs often leads to limited bone regeneration due to problems of cell aging, poor osteogenic differentiation, and impaired angiogenic response processes. Thus, the healing efficacy of stem cells is highly dependent on a biologically active carrier that effectively immobilizes MSCs to fix the cells at the site of defect.
Compared with the traditional bone repair materials (autologous bone grafting and allogeneic bone grafting), the injectable material has the advantages of small wound, high bionic functionality, simplicity and convenience in operation, safety, effectiveness, wide sources, high osteogenic activity and the like, can be filled into any part in a minimally invasive mode in an injection mode, is convenient for carrying stem cells to transplant to treat related diseases, can be used for immobilizing active factors and managing drug release, and obtains wide attention in the fields of tissue engineering and regeneration. However, the current injectable cell carrier composite biomaterial generally has the problems of poor biological activity, insufficient stem cell induction capability and the like.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide a high-activity stem cell biological injectable carrier material and a preparation method thereof, and the high-activity stem cell biological injectable carrier material has the characteristics of simple synthesis, uniform and stable structure, high biological activity and capability of being prepared clinically. To achieve the above objects and other advantages in accordance with the present invention, there is provided a highly active stem cell bio-injectable carrier material, comprising:
the mass ratio of the high molecular material to the laponite is 0.01-100, the laponite is a completely artificially synthesized product, is insoluble in water, can be completely and uniformly dispersed in water under the stirring condition, is in a nano-sheet structure, is dispersed in water to form a sheet crystal, and has 50-55mmol/100g of negative charge on the surface and 4-5mmol/100g of positive charge on the edge of the crystal due to partial absorption of particles, so that the laponite can generate a self-assembly effect in water to form a stable structure due to the charge attraction effect. So that the material is selected as a physical cross-linking agent to become a main body part of the injectable material;
the polymer material is one or the combination of silk fibroin, gelatin, quaternary ammonium salt chitosan, chitin, collagen and laminin, has the advantages of wide source, low price, good biocompatibility and the like, and is widely applied to various biological materials.
Preferably, the mass content of the laponite is 5 to 95wt%, the mass content of the polymer material is 0 to 30wt%, and the laponite is commercially available from Rockwood corporation.
Preferably, the total mass of the laponite and the polymeric material is 80-100wt% of the solid phase component of the support material.
Preferably, the laponite is a nanodisk with a diameter of 25nm and a thickness of 0.92 nm.
Preferably, the chemical cross-linking agent is one of genipin, 1-ethyl-3- [ 3-dimethylaminopropyl ] carbodiimide hydrochloride, N-hydroxysuccinimide, 6- [3'- (2-pyridyldithio) propionamido ] hexanoic acid sulfonyl succinimide ester, and 2-hydroxy-4' - (2-hydroxyethoxy) -2-methyl propiophenone.
Preferably, the laponite is lithium magnesium silicate sodium salt.
A preparation method of a high-activity stem cell bio-injectable carrier material comprises the following steps:
s1, mixing a high polymer material with water, and heating to completely dissolve the high polymer material to obtain an aqueous solution of the high polymer material;
s2, adding a chemical cross-linking agent into water or the aqueous solution of the high polymer material, and fully mixing to obtain a first mixed solution;
and S3, adding the first mixed solution into the laponite, and fully mixing until the obtained mixture loses fluidity to prepare the injectable composite material.
The injectable carrier material is applied to the treatment and repair of bone defects by a novel high-bioactivity stem cell carrier in vivo.
Example 1
A preparation method of a high-activity stem cell bio-injectable carrier material comprises the following steps:
1) Providing laponite, an optional polymeric material, and a specific chemical cross-linking agent;
2) Providing water or optionally mixing the high polymer material with water, and heating to completely dissolve to obtain an aqueous solution of the high polymer material;
3) Adding the chemical cross-linking agent into water or the aqueous solution of the high polymer material, fully mixing to obtain a first mixed solution, and filtering and disinfecting the first mixed solution through a 0.22-micron filter;
4) And adding the first mixed solution into the laponite, namely the autoclaved sterile laponite, and fully mixing until the obtained mixture loses fluidity to prepare the injectable stem cell carrier composite material.
Compared with the prior art, the invention has the beneficial effects that: through the self-assembly characteristic of the laponite, the cross-linking characteristic of the low-toxicity chemical cross-linking agent containing bioactive ions and the biological activity of the laponite, a high polymer material is introduced, and an injectable stem cell carrier material with good biocompatibility is quickly formed through physical/chemical action, so that the defects of poor activity immobilization and low differentiation capacity of stem cells are overcome.
Drawings
Fig. 1 is a physical and chemical performance diagram and an injectable performance diagram of a laponite/gelatin/genipin injectable composite material according to the high-activity stem cell biological injectable carrier material and the preparation method of the invention;
fig. 2 is a scanning electron microscope result diagram of the laponite/gelatin/genipin injectable material 1 according to the high activity stem cell biological injectable carrier material and the preparation method of the invention;
fig. 3 is a graph of rheological results of the laponite/gelatin/genipin injectable material 1 according to the high activity stem cell bio-injectable carrier material and the preparation method of the present invention;
fig. 4 is a cell live-dead staining result diagram of the high activity stem cell biological injectable carrier material and the preparation method thereof and the laponite/gelatin/genipin injectable material 1 according to the present invention;
fig. 5 is a graph showing the results of alkaline phosphatase staining and alizarin red staining for 7 days of laponite/gelatin/genipin injectable material 1 according to the highly active stem cell biological injectable carrier material and the preparation method of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be obtained by a person skilled in the art without making any creative effort based on the embodiments in the present invention, belong to the protection scope of the present invention.
Referring to fig. 1-5, a high activity stem cell bio-injectable carrier material comprises: the coating comprises the following components of spodumene, a high polymer material and a chemical cross-linking agent, wherein the mass ratio of the high polymer material to the spodumene is 0.01-100;
the polymer material is one or the combination of silk fibroin, gelatin, quaternary ammonium salt chitosan, chitin, collagen and laminin, and the concentration of the laponite in the high-activity injectable stem cell carrier material is 20-100mg/ml, the concentration of the polymer material is 1-100mg/ml, and the concentration of the cross-linking agent is 0.1-20mg/ml according to the concentration of the prepared solution. The materials are blended and compounded to obtain the injectable stem cell carrier composite material with stable structure, high performance and high activity.
Furthermore, the mass content of the laponite is 5-95wt%, and the mass content of the high polymer material is 0-30wt%.
Furthermore, the total mass of the laponite and the high polymer material is 80-100wt% of the solid phase component of the carrier material.
Further, the diameter of the laponite was 25nm, and the thickness was 0.92 nm.
Further, the chemical cross-linking agent is genipin, 1-ethyl-3- [ 3-dimethylaminopropyl ] carbodiimide hydrochloride, N-hydroxysuccinimide, 6- [3'- (2-pyridyldithio) propionamido ] hexanoic acid sulfonyl succinimide ester, and 2-hydroxy-4' - (2-hydroxyethoxy) -2-methyl propiophenone.
Further, the laponite is lithium magnesium silicate sodium salt.
A preparation method of a high-activity stem cell bio-injectable carrier material comprises the following steps:
s1, mixing a high polymer material with water, and heating to completely dissolve the high polymer material to obtain an aqueous solution of the high polymer material;
s2, adding a chemical cross-linking agent into water or the aqueous solution of the high polymer material, and fully mixing to obtain a first mixed solution;
and S3, adding the first mixed solution into the laponite, and fully mixing until the obtained mixture loses fluidity to prepare the injectable composite material.
The injectable carrier material is applied to the treatment and repair of bone defects by a novel high-bioactivity stem cell carrier in vivo.
Example 1 preparation of laponite/gelatin/genipin injectable Stem cell Carrier composite 1
(1) 1g of gelatin was added to 25mL of ultrapure water, and the mixture was heated at 37 ℃ to completely dissolve the gelatin.
(2) 25mg of genipin powder was added to the solution of step 1 and mixed well.
(3) And (3) adding 1g of laponite powder into the solution obtained in the step (2), and fully mixing until the solution loses fluidity, thus obtaining the laponite/gelatin/genipin injectable stem cell carrier composite material 1.
Example 2 preparation of laponite/silk fibroin/genipin stem cell vector composite 2
(1) Adding 4L ultrapure water into 20g silk fibroin, and heating at 37 deg.C to dissolve silk fibroin completely.
(2) 4g of genipin powder was added to the solution of step 1 and mixed well.
(3) And (3) adding 160g of laponite powder into the solution obtained in the step (2), and quickly dispersing and uniformly mixing until the solution loses fluidity to obtain the laponite/silk fibroin/genipin stem cell carrier composite material 2.
Example 3 preparation of laponite/collagen/genipin injectable Stem cell Carrier composite 3
(1) To 20g of collagen, 4L of ultrapure water was added, and the mixture was heated at 37 ℃ to completely dissolve hyaluronic acid.
(2) 4g of genipin powder was added to the solution of step 1 and mixed well.
(3) And (3) adding 160g of laponite powder into the solution obtained in the step (2), and quickly dispersing and uniformly mixing until the solution loses fluidity to obtain the laponite/collagen/genipin stem cell carrier composite material 3.
Example 4 preparation of a laponite/gelatin/2959 injectable Stem cell Carrier composite 4
(1) 1g of modified gelatin (Gelma) was added to 25mL of ultrapure water, and heated at 37 ℃ to completely dissolve the gelatin.
(2) 50mg of 2959 powder was added to the solution of step 1 and mixed well.
(3) And (3) adding 1g of laponite powder into the solution obtained in the step (2), fully mixing until the solution loses fluidity, and then carrying out chemical crosslinking through ultraviolet irradiation to obtain the laponite/gelatin/2959 injectable stem cell carrier composite material 4.
The number of devices and the scale of the processes described herein are intended to simplify the description of the invention, and applications, modifications and variations of the invention will be apparent to those skilled in the art.
While embodiments of the invention have been described above, it is not intended to be limited to the details shown, described and illustrated herein, but is to be accorded the widest scope consistent with the principles and novel features herein disclosed, and to such extent that such modifications are readily available to those skilled in the art, and it is not intended to be limited to the details shown and described herein without departing from the general concept as defined by the appended claims and their equivalents.
Claims (8)
1. A high activity stem cell bio-injectable carrier material comprising:
the composite material comprises the following components of laponite, a high polymer material and a chemical cross-linking agent, wherein the mass ratio of the high polymer material to the laponite is 0.01-100;
the polymer material is one or a combination of silk fibroin, gelatin, quaternary ammonium salt chitosan, chitin, collagen and laminin.
2. The highly active stem cell bio-injectable carrier material according to claim 1, wherein the mass content of laponite is 5-95wt%, and the mass content of the polymer material is 0-30wt%.
3. The highly active stem cell bio-injectable carrier material of claim 1, wherein the total mass of the laponite and the polymeric material is 80-100wt% of the solid phase component of the carrier material.
4. The highly active stem cell bio-injectable carrier material of claim 1, wherein the laponite is a nanodisk with a diameter of 25nm and a thickness of 0.92 nm.
5. The highly active stem cell bioinjectable carrier material of claim 1, wherein the chemical cross-linking agent is one of genipin, 1-ethyl-3- [ 3-dimethylaminopropyl ] carbodiimide hydrochloride, N-hydroxysuccinimide, 6- [3'- (2-pyridyldithio) propionamido ] hexanoic acid sulfonyl succinimide ester, and 2-hydroxy-4' - (2-hydroxyethoxy) -2-methylpropiophenone.
6. The highly active stem cell bio-injectable carrier material of claim 1, wherein said laponite is lithium magnesium silicate sodium salt.
7. The method for preparing a high activity stem cell bio-injectable carrier material according to claim 1, comprising the steps of:
s1, mixing a high polymer material with water, and heating to completely dissolve the high polymer material to obtain an aqueous solution of the high polymer material;
s2, adding a chemical cross-linking agent into water or the aqueous solution of the high polymer material, and fully mixing to obtain a first mixed solution;
and S3, adding the first mixed solution into the laponite, and fully mixing until the obtained mixture loses fluidity to prepare the injectable composite material.
8. Use of the injectable carrier material of claim 1 in vivo, a novel highly bioactive stem cell carrier for the therapeutic repair of bone defects.
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