CN114767937B - Tooth bone material for external demineralization of collagen - Google Patents
Tooth bone material for external demineralization of collagen Download PDFInfo
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- CN114767937B CN114767937B CN202210404652.6A CN202210404652A CN114767937B CN 114767937 B CN114767937 B CN 114767937B CN 202210404652 A CN202210404652 A CN 202210404652A CN 114767937 B CN114767937 B CN 114767937B
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Classifications
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
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- A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
- A61L27/3687—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
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- A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
- A61L27/3691—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by physical conditions of the treatment, e.g. applying a compressive force to the composition, pressure cycles, ultrasonic/sonication or microwave treatment, lyophilisation
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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- A—HUMAN NECESSITIES
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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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- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/12—Materials or treatment for tissue regeneration for dental implants or prostheses
Abstract
The application discloses a tooth bone material demineralized outside collagen. The tooth bone material is based on the size exclusion effect of collagen fibers, and the external mineral crystals outside the collagen fibers are removed by combining a macromolecular chelating agent with calcium outside the dentin collagen fibers, so that the external demineralized tooth bone material with unique nano structure and high mechanical strength is obtained. The external fiber demineralized dental bone material shows a unique nano structure formed by the internal mineralized collagen fibers, has excellent mechanical strength and biocompatibility, can effectively promote the adhesion and proliferation of cells, support the growth of cells, promote the osteogenic differentiation of stem cells, and the pores left after the external fiber minerals are removed are beneficial to tissue vascularization and nutrient transport. Therefore, the collagen external demineralized dental bone material can be used as a tissue engineering scaffold material to be applied to bone tissue regeneration, and has good biomedical application prospect.
Description
Technical Field
The application relates to the technical field of biomedical engineering, in particular to a tooth bone grafting material for external demineralization of collagen.
Background
The choice of bone graft material is varied, wherein autologous bone grafting is immune-free, has a shorter healing time and a faster rate of osseointegration, and is a gold standard for bone grafting surgery (piatetelli, a.; degidi, m.; di Stefano, d.a.; rubini, c.; fioroni, m.; strochi, r.; microvessel density in alveolar ridge regeneration with autologous and alloplastic bone. Implant de 2002,11 (4), 370-5). However, autogenous bone grafting has problems of more complications, high pain rate of patient self-reporting, high cost, etc. due to the need to open up the second operative field (Chavda, S.; levin, L.; human Studies of Vertical and Horizontal Alveolar Ridge Augmentation Comparing Different Types of Bone Graft Materials: A Systematic review.J Oral implatol 2018,44 (1), 74-84). Dentin matrix is prepared from isolated teeth. Previous studies have found that both dentin and maxillofacial bones originate embryologically from the neural crest and have the same origin (Yoshida, t.; vivatbutswiri, p.; morriss-Kay, g.; saga, y.; iseki, s.; cell lineage in mammalian craniofacial mesenchyme.mech Dev 2008,125 (9-10), 797-808). Dentin is assembled layer by inorganic mineral substances mainly comprising calcium phosphate and organic substances mainly comprising collagen, and has similar composition and structure with bone tissue [1]. Compared with other bone grafting materials, the dentin matrix is easier to obtain, has good biocompatibility and good osteoinductive property and bone conduction property, and is a bone grafting material with great potential (average, S.J.; sadaghiani, L.; sloan, A.J.; waddington, R.J.; analysing the bioactive makeup of demineralised dentine matrix on bone marrow mesenchymal stem cells for enhanced bone repair.Eur Cell Mater 2017,34,1-14).
In the related art, the mineral removal treatment of dentin matrixes adopts small molecular mineral removal agents such as EDTA and hydrochloric acid to carry out non-selective mineral removal treatment, and simultaneously removes minerals inside and outside collagen fibers, so that the technical defect of low mechanical strength exists.
Disclosure of Invention
In view of this, the present application provides a collagen-externally demineralized dental bone material capable of improving mechanical strength.
It is generally recognized that in the related art, the demineralization treatment of dentin substrate is performed by using small molecule demineralizers such as EDTA and hydrochloric acid.
Since bone tissue regeneration is a dynamic process, with the absorption of osteoclasts and the formation of new bone by osteoblasts, the rate of absorption of dentin matrix in the body becomes faster as minerals are removed, and if faster than the rate of new bone formation, the bone regeneration effect is not favored. In addition, the stem cells have "mechanical memory", the mechanical strength of the extracellular matrix influences the direction of stem cell differentiation, and a substrate similar to the mechanical strength of bone tissue induces osteoblast differentiation of stem cells, and insufficient mechanical strength of the scaffold substrate may influence osteoblast differentiation of cells.
The inventors have unexpectedly found that based on the collagen size exclusion effect, calcium ion chelators having a molecular weight greater than 40kDa selectively demineralize the collagen extracellular fibers, retain the intra-fiber minerals, and achieve collagen extracellular demineralization due to inability to enter the intra-dentin collagen fiber interstices. The collagen external demineralized dental bone material constructed by the inventor shows a unique nano structure formed by internal mineralized collagen fibers, has excellent mechanical strength and biocompatibility, can effectively promote cell adhesion and proliferation, support cell growth, and promote stem cell osteogenic differentiation. Based on this, the present invention has been created.
<Dental bone material>
The collagen external demineralized dental bone material is obtained by demineralizing dentin material by adopting a metal ion chelating agent with molecular weight of more than 40 kDa.
Here, the term "dental bone material" may be in various shapes such as powder, granule, tablet or block depending on the form of mechanical crushing.
<Metal ion chelating agent>
As used herein, "metal ion chelating agent" refers to a ligand capable of forming a coordination with a common coordination metal ion such as calcium. These coordinating metal ions may be exemplified by cations having an inert gas structure, or metal ions whose sublayer d orbitals have been filled, or transition metal ions having incomplete sublayers, or the like.
Suitable but non-limiting metal ion chelating agents are selected from one or more of polyacrylates, carboxymethyl cellulose salts, carboxymethyl chitosan, polyaspartate.
Suitable, but non-limiting, metal ion chelating agents are neutral or basic in pH.
<Ore removal treatment>
The ore removal treatment process comprises the following steps:
ultrasonic cleaning is carried out on dentin material to obtain material C;
carrying out impregnation treatment on the material C in an impregnation liquid containing the metal ion chelating agent to obtain a material D;
and freeze-drying the material D to obtain the dental bone material.
Suitably, but not by way of limitation, the time of the impregnation treatment is from 0.1 to 48 hours.
Suitably, but not by way of limitation, the freeze-drying temperature is-80 ℃ and the freezing time is 1 to 10 hours.
Suitably, but not by way of limitation, the ultrasonic cleaning is performed in sterile phosphate buffer.
The dental bone material is qualified but not limited to powder, granules, flakes or blocks and the like.
The application has the following beneficial effects:
(1) the preparation process of the collagen external demineralized dental bone material is simple and convenient, the preparation condition is loose, and the treatment time is short.
(2) The collagen external demineralized tooth bone material has unique physicochemical properties of collagen internal mineralization and external demineralization, reserves mineralized collagen fiber network, has good mechanical strength and nanotopography, is favorable for supporting cell growth, and promotes cell adhesion and proliferation.
(3) The collagen external demineralized dental bone material reserves dentin bioactive substances, removes collagen external mineral substances, has a large number of pores, is favorable for transporting nutrient substances and metabolic products and generating tissue vascularization, and is an excellent tissue engineering scaffold.
Drawings
Technical solutions and other advantageous effects of the present application will be made apparent from the following detailed description of specific embodiments of the present application with reference to the accompanying drawings.
Fig. 1 is a scanning electron microscope image of a related material according to example 1, comparative example 1, and comparative example 2 of the present application.
Fig. 2 is a view showing a microtome transmission electron microscope image of a related material according to example 1, comparative example 1, and comparative example 2 of the present application.
Fig. 3 is an atomic force microscope image of the related materials according to example 1, comparative example 1, and comparative example 2 of the present application.
Fig. 4 shows the results of measuring the elastic modulus of the related materials according to example 1, comparative example 1, and comparative example 2 of the present application.
FIG. 5 is a cytoskeletal staining image of the related materials according to example 1, comparative example 1 and comparative example 2 of the present application.
FIG. 6 shows the results of PCR detection of the related materials according to example 1, comparative example 1 and comparative example 2 of the present application.
Fig. 7 is a three-dimensional reconstruction map of Micro CT of the related materials according to example 1, comparative example 1, and comparative example 2 of the present application.
Detailed Description
The present invention will be described in further detail with reference to the following examples in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
<Procedure of the examples>
Example 1
S1, taking fresh human isolated teeth, ultrasonically cleaning with deionized water for 3 times, filtering to remove water, adding disinfectant (75% ethanol), soaking for 15 minutes at normal temperature, filtering to remove the solution, soaking with sterile deionized water for 1 hour, ultrasonically cleaning for 5 minutes, and repeating the soaking ultrasonic cleaning for 3 times;
s2, removing enamel of teeth by using a mechanical method, opening pulp, and removing pulp tissues to obtain a dentin matrix-based material A;
s3, crushing the material A by using an electric grinder, and collecting dentin powder with the particle size of 0.2-0.8mm to obtain a material B;
s4, soaking the material B in sterile Phosphate Buffer (PBS) for ultrasonic cleaning, replacing liquid every 10 minutes, cleaning for 30 minutes, and removing the cleaning liquid to obtain a material C;
s5, adding the material C into 15%wt PAAN (Mw=225 kDa) sodium polyacrylate aqueous solution, stirring for 12 hours, removing the solution, then injecting sterile PBS for ultrasonic cleaning, replacing liquid every 10 minutes, cleaning for 30 minutes, and centrifuging to obtain a precipitate to obtain a material D;
s6, freeze-drying the material D prepared in the step S5, and continuing at the temperature of-80 ℃ for 10 hours to obtain freeze-dried collagen external demineralized dental powder;
s7, carrying out vacuum sealing packaging on the freeze-dried external demineralized collagen bone powder, and carrying out irradiation sterilization to obtain the external demineralized collagen bone powder material.
Example 2
S1, taking fresh human isolated teeth, ultrasonically cleaning with deionized water for 3 times, filtering to remove water, adding disinfectant (75% ethanol), soaking for 15 minutes at normal temperature, filtering to remove the solution, soaking with sterile deionized water for 1 hour, ultrasonically cleaning for 5 minutes, and repeating the soaking ultrasonic cleaning for 3 times;
s2, removing enamel of teeth by using a mechanical method, opening pulp, and removing pulp tissues to obtain a dentin matrix-based material A;
s3, cutting the material A by using a slow saw to obtain a 2 multiplied by 1mm cubic dentin sheet material B;
s4, soaking the material B in sterile Phosphate Buffer (PBS) for ultrasonic cleaning, replacing liquid every 10 minutes, cleaning for 30 minutes, and removing the cleaning liquid to obtain a material C;
s5, adding the material C into 15%wt PAAN (Mw=225 kDa) sodium polyacrylate aqueous solution, stirring for 24 hours, removing the solution, then injecting sterile PBS for ultrasonic cleaning, replacing liquid every 10 minutes, cleaning for 30 minutes, and centrifuging to obtain a precipitate to obtain a material D;
s6, freeze-drying the material D prepared in the step S5, and continuing at the temperature of-80 ℃ for 10 hours to obtain freeze-dried collagen external demineralized dental bone slices;
and S7, carrying out vacuum sealing packaging on the freeze-dried collagen external demineralized dental bone slice, and carrying out irradiation sterilization to obtain the collagen external demineralized dental bone slice material.
Example 3
The procedure of example 1 was repeated except that sodium polyacrylate in S5 of example 1 was replaced with carboxymethyl chitosan.
Example 4
The procedure of example 1 was repeated except that the sodium polyacrylate of example 1, S5, was replaced with polyaspartate.
Example 5
The procedure of example 1 was repeated except that sodium polyacrylate in S5 of example 1 was replaced with carboxymethyl cellulose.
Comparative example 1
Untreated dental bone material.
Comparative example 2
The only difference from the examples is that the sodium polyacrylate aqueous solution treatment process referred to in S5 is replaced by EDTA gradient treatment process: material C was demineralized by immersing it in 17% (5 minutes), 10% (5 minutes), 5% (10 minutes) EDTA solution, respectively, in the same manner as in example 1.
<Evaluation>
1. Evaluation procedure
A. SEM images of the dental bone materials obtained in example 1, comparative example 1 and comparative example 2 were carried out, and the specific test procedures were as follows:
the dental bone material was immersed in 2.5% glutaraldehyde and fixed at room temperature for 1 hour, at 4℃for 24 hours, dehydrated at room temperature by sequentially using 50%, 70%,80%, 90%, 100% alcohol gradient treatments each for 5 minutes, immersed in HDMS for 30 minutes, vacuum-dried at room temperature for 1 hour, and after 30mA current spraying for 120 seconds, observed by using a field emission scanning electron microscope (Zeiss SIGMA).
B. Ultra-thin slice transmission electron microscopy images of the dental bone material obtained in example 1, comparative example 1, and comparative example 2 were performed as follows:
(1) Sequentially dehydrating the dental bone material at room temperature by using ethanol solutions with gradient concentration (70%, 80%,95% and 100% x 3), wherein each gradient treatment lasts for 1 hour, and standing overnight in 100% ethanol solution;
(2) Placing the dental bone material in 100% propylene oxide for 3 hours at room temperature, and changing liquid every hour;
(3) Uniformly mixing propylene oxide and embedding resin according to the volume ratio of 1:1, soaking a dental bone material in the mixture, and replacing the new mixed solution after 4 hours for overnight;
(4) Uniformly mixing propylene oxide and embedding resin according to the volume ratio of 1:3, soaking the dental bone material therein, and vacuum drying for 8 hours;
(5) Placing the sample in an epoxy resin embedding mould, embedding with pure resin, and then placing the mould in a 60 ℃ oven for drying and curing for 48 hours;
(6) The resin block thus embedded was cut into 50nm thick ultra-thin slices using a microtome (UC 7, leica), salvaged with a single-groove carbon film transmission electron microscope copper mesh, dried, and observed with a transmission microscope (HT 7700, hitachi).
C. Atomic force microscope images were performed on the dental bone materials obtained in example 1, comparative example 1, and comparative example 2, and specific test procedures were as follows:
the dental bone material was embedded in epoxy resin, sequentially polished with 600, 1200, 2000 grit sandpaper, then sequentially polished with 9, 3, 1, 0.25, 0.05 micron polishing solutions in an automated polisher (MetaDi, buehler). Detection was performed using the Peakforce QNM mode of atomic force microscopy (MultiMode 8, bruker). Each scanning area has a size of 20×20 μm 2 。
D. The elastic modulus of the dental bone material obtained in example 1, comparative example 1 and comparative example 2 was measured as follows:
the dental bone material was embedded in epoxy resin, sequentially polished with 600, 1200, 2000 grit sandpaper, then sequentially polished with 9, 3, 1, 0.25, 0.05 micron polishing solutions in an automated polisher (MetaDi, buehler). Detection was performed using the Peakforce QNM mode of atomic force microscopy (MultiMode 8, bruker). Each scanning area has a size of 20×20 μm 2 6 regions of interest of size 2 x 2 were randomly selected for each sample to count their elastic modulus.
E. Cytoskeletal staining images were performed on the dental bone materials obtained in example 1, comparative example 1, and comparative example 2, and specific test procedures were as follows:
immersing the dental bone material into a cell culture mediumIn (2X 10) 4 Individual/cm 2 Is inoculated with mesenchymal stem cells of rat bone marrow (third generation) at 37 ℃ and 5% CO 2 After 1 day of incubation in the environment, 3 times with PBS, fixation with 4% paraformaldehyde for 15 minutes, permeation with 0.1% Triton-100 for 15 minutes, blocking with 4% Bovine Serum Albumin (BSA) for 30 minutes, incubation with FITC-labeled phalloidin staining for 30 minutes, final incubation with Dapi dye for 5 minutes, blocking with anti-fluorescence quenching blocking solution, and rinsing with PBS for 5 minutes X3 times between each of the above steps. The prepared samples were observed under a confocal microscope (sp 8, leica).
F. The dental bone materials obtained in example 1, comparative example 1 and comparative example 2 were subjected to PCR detection as follows:
immersing the dental bone material in a cell culture medium at a ratio of 1×10 5 Individual/cm 2 Is inoculated with mesenchymal stem cells of rat bone marrow (third generation) at 37 ℃ and 5% CO 2 After 1 day of environmental culture, the culture medium is changed into an osteogenesis culture medium, the osteogenesis culture is carried out for 7 days respectively, RNA is extracted by using an RNA extraction kit (CWBIO), cDNA is synthesized by reversing the extracted RNA by using a reverse transcription kit (TAKARA), and the expression level of osteogenesis differentiation specific genes ALP, col1a1 and BSP is detected by using a real-time fluorescence quantitative PCR technology SYBR Green method.
G. The dental bone materials obtained in example 1, comparative example 1 and comparative example 2 were implanted into the skull defect of the rat and repaired for 8 weeks, and then were subjected to micro CT detection, and the specific test procedures are as follows:
after 8-week-old rats were inhaled and anesthetized with isoflurane, a rat skull defect model was prepared by using a hand-held electric grinder equipped with a circular cutting drill having a diameter of 5mm, and the dental bone materials obtained in example 1, comparative example 2 were implanted into the rat skull defect area and sutured, after 8 weeks, the rats were sacrificed, skull tissues were taken, immersed in 4% paraformaldehyde for 24 hours, and then rinsed with running water for 24 hours, and Micro CT (Bruker) scanning reconstruction was performed.
2. Evaluation results
As shown in FIG. 1, a and b represent untreated dental bone material (comparative example 1), c and d represent EDTA demineralized dental bone material (comparative example 2), and e-g represent collagenous extracollagen demineralized dental bone material (example 1).
As can be seen from fig. 1, the EDTA-treated dental bone material consisted of a loose collagen mesh, and minerals outside the collagen fibers of the external demineralized dental bone material were selectively demineralized, and mineralized collagen fibers containing only intra-fiber minerals (indicated by arrows) were clearly seen.
As shown in fig. 2, a represents untreated dental bone material (comparative example 1), b represents EDTA demineralized dental bone material (comparative example 2), and c represents collagen external demineralized dental bone material (example 1).
As can be seen from fig. 2, the surface of EDTA demineralized dental bone material is composed of a fully demineralized collagen mesh, while the surface of collagen outer demineralized dental bone material is kept with the minerals in collagen, and single mineralized collagen fibers (yellow arrows) are seen, and the minerals outside collagen are selectively removed.
As shown in fig. 3, a, b, and c are topography of untreated dental bone material (comparative example 1), EDTA-treated demineralized dental bone material (comparative example 2), and collagen-coated demineralized dental bone material (example 1), respectively.
As can be seen from fig. 3, the small plugs on the surface of the external demineralized dental bone material are removed, and the external demineralized dental bone material is in a unique nanoscale morphology after the external fiber demineralization, while the surface of the dentin matrix subjected to EDTA demineralization is in a micron-scale undulating morphology due to collagen collapse.
As shown in fig. 4, UDM, PDM, EDM in this figure is untreated dental bone material (comparative example 1), EDTA-treated demineralized dental bone material (comparative example 2), and collagen-external demineralized dental bone material (example 1), respectively.
From the results of fig. 4, it is shown that the mechanical strength of the external demineralized dental bone material is similar to that of the untreated dental bone material, and is significantly higher than that of the EDTA-treated demineralized dental bone material.
As shown in fig. 5, a, b, and c in this figure are untreated dental bone material (comparative example 1), EDTA-treated demineralized dental bone material (comparative example 2), and collagen-external demineralized dental bone material (example 1), respectively.
The results in fig. 5 show that the collagen extracollagenous demineralized dental bone material significantly promotes cell adhesion and proliferation.
As shown in fig. 6, UDM, PDM, EDM in this figure is untreated dental bone material (comparative example 1), EDTA-treated demineralized dental bone material (comparative example 2), and collagen-external demineralized dental bone material (example 1), respectively.
The results of FIG. 6 show that the collagen exo-demineralized bone material induced BMSC osteogenic differentiation is optimal after 7 days of co-culture.
As shown in fig. 7, UDM, PDM, EDM in this figure is untreated dental bone material (comparative example 1), EDTA-treated demineralized dental bone material (comparative example 2), and collagen-external demineralized dental bone material (example 1), respectively.
The results of FIG. 7 show a three-dimensional reconstruction of bone defect repair effect Micro CT 8 weeks after implantation of different dental bone materials into a rat skull defect model. The result shows that the bone defect repairing effect of the external collagen demineralized dental bone material is optimal.
The present invention is not limited to the above-mentioned embodiments, and any changes or substitutions that can be easily understood by those skilled in the art within the technical scope of the present invention are intended to be included in the scope of the present invention.
Claims (3)
1. The application of the external demineralized dental bone material of collagen is characterized in that the external demineralized dental bone material of collagen is obtained by demineralizing dentin material by adopting a metal ion chelating agent with the molecular weight of more than 40 kDa;
the tooth bone material of the external demineralization of collagen is nano-scale, and is applied to the material for inducing the bone formation and differentiation of BMSC;
the metal ion chelating agent is one or more than two of polyacrylate, carboxymethyl cellulose salt, carboxymethyl chitosan, chitosan and polyaspartate;
the pH of the metal ion chelating agent is neutral or alkaline;
the process of the ore removal treatment comprises the following steps:
ultrasonic cleaning is carried out on dentin material to obtain material C;
carrying out impregnation treatment on the material C in an impregnation liquid containing the metal ion chelating agent to obtain a material D;
freeze-drying the material D to obtain the dental bone material;
the time of the dipping treatment is 0.1 to 48 hours.
2. The use of a dental bone material according to claim 1, wherein the freeze-drying temperature is-80 ℃ and the freezing time is 1-10 hours.
3. The use of a dental bone material according to claim 1, wherein the ultrasonic cleaning is performed in a sterile phosphate buffer.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102068318A (en) * | 2010-12-21 | 2011-05-25 | 四川大学 | Manufacturing method of biological tooth root bracket material |
| CN109010917A (en) * | 2018-08-20 | 2018-12-18 | 杭州恒睿生物科技有限公司 | A method of preparing the three-dimensional mineralized collagen timbering material with multilevel structure |
| CN109620740A (en) * | 2019-01-14 | 2019-04-16 | 中国人民解放军第四军医大学 | Carboxymethyl chitosan is used to prepare the application of dentin collagen fiber demineralization material |
| KR20190055302A (en) * | 2017-11-14 | 2019-05-23 | 한국치아은행 주식회사 | Method of manufacturing Bone-grafting complex and Bone-grafting complex manufactured thereby |
| CN110327221A (en) * | 2019-04-16 | 2019-10-15 | 中国人民解放军第四军医大学 | A kind of dentin collagen fiber demineralization material and the preparation method and application thereof |
-
2022
- 2022-04-18 CN CN202210404652.6A patent/CN114767937B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102068318A (en) * | 2010-12-21 | 2011-05-25 | 四川大学 | Manufacturing method of biological tooth root bracket material |
| KR20190055302A (en) * | 2017-11-14 | 2019-05-23 | 한국치아은행 주식회사 | Method of manufacturing Bone-grafting complex and Bone-grafting complex manufactured thereby |
| CN109010917A (en) * | 2018-08-20 | 2018-12-18 | 杭州恒睿生物科技有限公司 | A method of preparing the three-dimensional mineralized collagen timbering material with multilevel structure |
| CN109620740A (en) * | 2019-01-14 | 2019-04-16 | 中国人民解放军第四军医大学 | Carboxymethyl chitosan is used to prepare the application of dentin collagen fiber demineralization material |
| CN110327221A (en) * | 2019-04-16 | 2019-10-15 | 中国人民解放军第四军医大学 | A kind of dentin collagen fiber demineralization material and the preparation method and application thereof |
Non-Patent Citations (4)
| Title |
|---|
| Bone induction of human tooth and bone crushed by newlydeveloped automatic mill;Masaru MURATA，et al.;《Journal of the Ceramic Society of Japan》;20100601;第118卷(第6期);第435页右栏第2段 * |
| Extrafibrillar collagen demineralization-based chelate-and-rinse technique bridges the gap between wet and dry dentin bonding;Sui Mai，et al.;《Acta Biomaterialia》;20170715;第57卷;第436页右栏第2段、第437页左栏第1-3段 * |
| Sui Mai，et al..Extrafibrillar collagen demineralization-based chelate-and-rinse technique bridges the gap between wet and dry dentin bonding.《Acta Biomaterialia》.2017,第57卷 * |
| 张富强.口腔修复基础与临床.上海科学技术出版社,2004,133-134. * |
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