CN115920124B - Functional biological ceramic composite scaffold material for repairing bone cartilage and preparation method thereof - Google Patents
Functional biological ceramic composite scaffold material for repairing bone cartilage and preparation method thereof Download PDFInfo
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- CN115920124B CN115920124B CN202211485696.2A CN202211485696A CN115920124B CN 115920124 B CN115920124 B CN 115920124B CN 202211485696 A CN202211485696 A CN 202211485696A CN 115920124 B CN115920124 B CN 115920124B
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Classifications
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P10/00—Technologies related to metal processing
- Y02P10/25—Process efficiency
Abstract
The invention relates to a functional biological ceramic composite scaffold material for repairing bone cartilage and a preparation method thereof, in particular to a zinc-cobalt bimetal organic framework functional biological ceramic composite scaffold material and preparation and application thereof. The zinc-cobalt bimetal organic framework functionalized biological ceramic composite support material comprises the following components: a three-dimensional porous biological ceramic bracket and a zinc-cobalt bimetal organic frame coating growing on the surface of the three-dimensional porous biological ceramic bracket in situ.
Description
Technical Field
The invention relates to an osteochondral tissue engineering scaffold material, in particular to a functional biological ceramic composite scaffold material for repairing osteochondral and a preparation method thereof, and particularly relates to a zinc-cobalt bimetal organic framework functional biological ceramic composite scaffold material and preparation and application thereof, belonging to the field of biological materials and tissue engineering.
Background
Repair treatment of osteoarthritis involving subchondral bone injury due to high levels of reactive oxygen species is a significant clinical challenge. High levels of reactive oxygen species destroy cellular redox regulated signaling pathways, inhibit superoxide dismutase and peroxidase secretion, thereby reducing antioxidant capacity, exacerbating oxidative stress, inducing chondrocyte DNA and mitochondrial damage and, accelerating chondrocyte functional failure and apoptosis, and eventually inducing or exacerbating osteoarthritis formation and causing osteochondral defects to be difficult to heal. At present, the repair and treatment of osteochondral defects using osteochondral tissue engineering scaffold materials is considered as one of the effective methods for solving the related problems. However, it is difficult for conventional osteochondral tissue engineering scaffolds to scavenge active oxygen and maintain the stability of redox reactions of the bone microenvironment. Therefore, designing an osteochondral tissue engineering scaffold material with an antioxidant stress function is a key place for repairing and treating osteoarthritis involving subchondral bone injury.
Disclosure of Invention
Aiming at the problems that the bone cartilage tissue engineering scaffold material is difficult to remove active oxygen and resist oxidative stress, the invention provides a Zn/Co-MOF functionalized biological ceramic composite scaffold material and a preparation method thereof, and the preparation method of the composite scaffold material solves the problems that the bone tissue engineering scaffold material prepared by the prior art cannot accurately regulate and control the internal structure of the scaffold material, remove free radicals, resist oxidative stress and the like.
In one aspect, the invention provides a bio-ceramic composite scaffold material functionalized by a zinc-cobalt bimetallic organic framework, comprising: a three-dimensional porous biological ceramic bracket and a zinc-cobalt bimetal organic frame coating growing on the surface of the three-dimensional porous biological ceramic bracket in situ.
Preferably, the three-dimensional porous biological ceramic bracket is made of biological active ceramic or/and biological active glass, and is selected from at least one of beta-phase tricalcium phosphate, hydroxyapatite and melilite; the bioactive glass comprises SiO 2 -CaO-P 2 O 5 Glass system in which SiO 2 、CaO、P 2 O 5 Mass ratio= (45-90): (5-30): (1-10).
The invention is found by research: (1) The bioactive ceramic (glass) has the characteristics of good bone conduction, osseointegration, bone induction and the like, and also has the characteristic of cartilage tissue growth. Research shows that the biological ceramic (glass) bracket can provide good physical properties and biological activity for bone regeneration. In addition, ion-doped bioceramic (glass) scaffolds can release bioactive ions to promote cartilage and subchondral bone regeneration. Nevertheless, bioceramics (glasses) are still not effective in scavenging active oxygen and have the function of treating inflammation. (2) Among the numerous catalysts, metal-organic frameworks (MOFs) present great advantages in terms of catalysis and scavenging of active oxygen. The MOF material is a porous crystal material formed by self-assembly of metal ions or clusters and organic ligands through coordination, and has excellent catalytic activity due to the characteristics of porosity and high specific surface area. Research shows that partial zinc-based and cobalt-based MOF materials have biocompatibility, biodegradability and capability of catalyzing and scavenging active oxygen. In addition, zinc and cobalt metal ions in degradation products of zinc-based and cobalt-based MOF materials can promote osteogenic differentiation and chondrocyte maturation within a certain range. Therefore, the inventor creatively combines a zinc-cobalt bimetal organic framework (Zn/Co-MOF) and a beta-TCP biological ceramic bracket to prepare the multifunctional composite bracket material which has both the anti-oxidative stress performance and biomechanics, and is expected to be applied to the repair and treatment of the osteoarthritis involving the subchondral bone defect.
Preferably, the zinc-cobalt bimetal organic frame coating material is a zinc-cobalt bimetal organic frame material, and the ratio of cobalt to zinc is between 0.1: 10-10: between 0.1.
Preferably, the thickness of the zinc-cobalt bimetal organic framework coating is 500 nm-10 mu m; the mass of the zinc-cobalt bimetal organic framework coating is 0.5-5 wt% of the mass of the three-dimensional porous biological ceramic bracket.
Preferably, the three-dimensional porous biological ceramic bracket has a macroporous structure, and the porosity is 20-80%; the size of the macroporous structure is 100 mu m-1 mm.
On the other hand, the invention provides a preparation method of the zinc-cobalt bimetal organic framework functionalized biological ceramic composite bracket material, which comprises the following steps: immersing the three-dimensional porous biological ceramic stent into an organic ligand solution, adding a zinc-cobalt bimetallic solution, reacting, washing and drying to obtain the biological ceramic composite stent material with the zinc-cobalt bimetallic organic framework functionalization.
Preferably, the concentration of the organic ligand solution is 0.05-0.5 mol/L, and the solvent is at least one selected from deionized water, absolute ethyl alcohol and acetone; the organic ligand comprises at least one of 2-methylimidazole, porphyrin, terephthalic acid and the like;
the solute in the zinc-cobalt bimetallic solution is zinc salt and cobalt salt, and the solvent is at least one of deionized water, absolute ethyl alcohol and acetone;
the zinc salt is Zn (NO) 3 ) 2 ·6H 2 O、ZnCl 2 And Zn 3 SO 4 At least one of (a) and (b);
the cobalt salt is selected from Co (NO) 3 ) 2 ·6H 2 O、CoCl 2 ·6H 2 O and CoSO 4 ·7H 2 At least one of O;
the molar ratio of the zinc salt to the cobalt salt is 0.1: 10-10: 0.1, preferably 4 to 7:1, a step of;
the total concentration of the zinc salt and the cobalt salt is in the range of 0.05 to 0.5mol/L, preferably 0.10 to 0.25mol/L.
Preferably, the ratio of the three-dimensional porous bioceramic scaffold to the organic ligand solution is (0.01 g-0.1 g): 1mL; the three-dimensional porous bioceramic (glass) scaffold: zinc cobalt bimetallic organic framework precursor solution consisting of organic ligand solution and zinc cobalt bimetallic solution= (0.01 g-0.1 g): 1mL;
the reaction temperature is 20-60 ℃, the reaction time is 1-16h, and preferably 2-4 h;
preferably, the volume ratio of the organic ligand solution to the zinc cobalt bimetallic solution is (5-10): 1.
preferably, the preparation method of the three-dimensional porous biological ceramic bracket comprises the following steps:
(1) Uniformly mixing the bioactive ceramic powder and the binder solution to obtain printing ink; the binder comprises at least one of sodium alginate, F-127 and polyvinyl alcohol; the concentration of the binder solution is 0.5-20wt%.
(2) The printing ink is subjected to 3D printing technology to prepare a wet bracket blank, and then the bracket blank is dried and sintered to obtain the three-dimensional porous biological ceramic bracket;
preferably, the drying comprises drying at 37 ℃ for 24-48 hours;
preferably, the temperature of the debonding is 400-650 ℃;
preferably, the sintering temperature is 900-1400 ℃.
In the invention, the Zn/Co-MOF functionalized bioceramic composite stent material is prepared by combining a 3D printing technology and a hydrothermal method, and is hopeful to provide a new strategy for repairing and treating osteoarthritis related to subchondral bone defects clinically. The 3D printing technology is used as an emerging rapid prototyping technology means, and the external shape, the internal structure and the connectivity of the holes of the material can be accurately controlled, so that the personalized porous support material can be obtained by using the 3D printing technology. In addition, compared with other coating synthesis technologies, the hydrothermal method has the characteristics of convenience in operation, low synthesis temperature and small damage to materials, and can effectively construct the MOF coating on the surface of the stent material.
In still another aspect, the invention provides an application of the zinc-cobalt bimetal organic framework functionalized bioceramic composite scaffold material in preparing an osteochondral repair material, which is characterized in that the osteochondral repair material is preferably a osteochondral defect knee joint material.
The beneficial effects are that:
in the invention, the application field of the Zn/Co-MOF catalyst is wide, and compared with inorganic zinc and cobalt ions, the Zn/Co-MOF catalyst has various enzyme activities and better catalytic activity, so as to efficiently catalyze and remove various active oxygen. The Zn/Co-MOF functionalized bioceramic composite scaffold material can provide good biomechanical properties, and simultaneously can effectively remove various active oxygen (such as superoxide anions and hydrogen peroxide are converted into oxygen and water), improve cell activity and promote regeneration of osteochondral defects. The successful application of the bimetal MOF functionalized 3D printing bracket material greatly promotes the successful solution of the great clinical challenge of repairing and treating the osteoarthritis involving the subchondral bone injury, and has great potential in the treatment aspect of the related fields of the osteoarthritis.
The Zn/Co-MOF functionalized bioceramic composite stent material is prepared by adopting a 3D printing technology to prepare a bioceramic (glass) stent, and combining the Zn/Co-MOF and the bioceramic (glass) stent by a hydrothermal method to prepare the Zn/Co-MOF functionalized bioceramic composite stent material. The detection of the physical and chemical properties and the biological properties of the scaffold material shows that the scaffold material has a three-dimensional communicated and controllable macroporous structure, has good biocompatibility and promotes proliferation, adhesion and differentiation of mesenchymal stem cells and chondrocytes in an inflammatory microenvironment.
Drawings
FIG. 1 is an optical photograph of a Zn/Co-MOF functionalized bioceramic composite scaffold material prepared in example 1;
FIG. 2 is a Scanning Electron Microscope (SEM) image of the Zn/Co-MOF functionalized bioceramic composite stent material prepared in example 1;
FIG. 3 is a Scanning Electron Microscope (SEM) image of the Zn/Co-MOF functionalized bioceramic composite scaffold material prepared in example 3, which shows that the Zn/Co-MOF functionalized bioceramic composite scaffold material is preferable at 2-4h (scale of 50.0 μm);
FIG. 4 is an optical photograph (ABTS and 17 MOF-TCP) and an absorption spectrum (the abscissa is Wavelength Wavelength/nm, and the ordinate is Absorbance Absorbance/a.u.);
FIG. 5 shows a Zn/Co-MOF functionalized bioceramic composite stent material prepared in example 1 and 100mmol/L H 2 O 2 Oxygen production after the reaction (Time Time/min on the abscissa and oxygen solubility Oxygen solubility (mg/L) on the ordinate);
FIG. 6 shows adhesion of rabbit bone marrow-derived mesenchymal stem cells on the Zn/Co-MOF functionalized bioceramic composite scaffold material prepared in example 1;
FIG. 7 shows adhesion of rabbit-derived chondrocytes to the Zn/Co-MOF functionalized bioceramic composite scaffold material prepared in example 1;
FIG. 8 is an optical photograph of a repair of osteochondral defects after 12 weeks in the Blank, beta-TCP and 17MOF-TCP group of example 9;
FIG. 9 is a graph showing the statistics of bone cartilage neogenesis in New Zealand rabbits implanted with the Zn/Co-MOF functionalized bioceramic composite scaffold material of example 9;
FIG. 10 is an analysis of the in vivo osteochondral tissue section of New Zealand rabbits implanted with the Zn/Co-MOF functionalized bioceramic composite scaffold material of example 9.
Detailed Description
The invention is further illustrated by the following embodiments, which are to be understood as merely illustrative of the invention and not limiting thereof.
In the present disclosure, a bio-ceramic composite scaffold material functionalized by a zinc-cobalt bimetallic organic framework comprises: a three-dimensional porous scaffold material is constructed by a zinc-cobalt bimetallic organic framework coating with various enzyme catalytic activities and a bioactive ceramic scaffold. Wherein the zinc-cobalt bimetal organic framework coating grows on the surface of the bioactive ceramic bracket in situ.
The zinc-cobalt bimetal organic framework functionalized biological ceramic composite scaffold material prepared by the invention has a three-dimensional communicated and controllable macroporous structure, good biocompatibility, and functions of removing various active oxygen and resisting oxidation stress, so that proliferation, adhesion and differentiation of bone marrow mesenchymal stem cells and chondrocytes in an inflammatory microenvironment and repair of experimental animal bone cartilage are promoted, and a new strategy is provided for repairing and treating clinical bone cartilage defects.
Preferably, the ratio of cobalt to zinc of the zinc cobalt bimetallic organic framework is between 0.1:10 to 10:0.1, the concentration is between 0.05 and 0.5mol/L.
In one embodiment of the invention, the preparation of the bio-ceramic composite scaffold material functionalized by the zinc-cobalt bimetallic organic framework comprises the following steps: 3D printing to prepare beta-phase tricalcium phosphate or biological glass bracket material; and carrying a zinc-cobalt bimetal organic frame on the bracket by a hydrothermal method.
And (3) preparing beta-tricalcium phosphate (beta-TCP) or a bioglass bracket material by a 3D printing technology, and sieving the beta-TCP or bioglass powder through a 200-mesh screen. And then uniformly mixing beta-TCP powder or bioglass, sodium alginate and F-127 (20 wt%) according to a certain mass ratio to obtain printing ink, preparing the support material by using 3D printing technology, drying at 37 ℃ for 24-48 h, degreasing at 400-650 ℃, and sintering at 900-1150 ℃ for later use. The 3D printing technology is used for preparing the support material, and the 3D printing technology is based on extrusion type, but is not limited to extrusion type, and also comprises photo-curing, laser sintering technology, ink-jet printing technology and the like.
The preparation method of the zinc-cobalt bimetal organic framework functionalized biological ceramic composite bracket material comprises the following steps: immersing the beta-TCP or the bioglass stent into a 2-methylimidazole solution, adding a zinc-cobalt bimetallic solution, and reacting (for example, the reaction time is 1-12 h) to obtain the 3D printing bioceramic stent with the surface being the zinc-cobalt bimetallic organic framework coating and the catalytic active oxygen removal function.
In an alternative embodiment, the zinc cobalt bimetallic organic framework precursor solution is a zinc salt (Zn (NO 3 ) 2 ·6H 2 O), cobalt salts (Co (NO) 3 ) 2 ·6H 2 A mixed solution of O) a solution and a 2-methylimidazole solution; the volume ratio of the 2-methylimidazole solution to the zinc salt and cobalt salt bimetallic solution is (5-10): 1. the total concentration range of the zinc salt and the cobalt salt is 0.05-0.5 mol/L. Zn (NO) adopted in zinc-cobalt bimetallic organic framework precursor solution 3 ) 2 ·6H 2 O and Co (NO) 3 ) 2 ·6H 2 The ratio of O is 0.1:10-10:0.1. The mass volume ratio of the biological ceramic composite bracket to the zinc-cobalt bimetallic organic frame precursor solution is 0.01 g/mL-0.1 g/mL.
The present invention will be further illustrated by the following examples. It is also to be understood that the following examples are given solely for the purpose of illustration and are not to be construed as limitations upon the scope of the invention, since numerous insubstantial modifications and variations will now occur to those skilled in the art in light of the foregoing disclosure. The specific process parameters and the like described below are also merely examples of suitable ranges, i.e., one skilled in the art can make a suitable selection from the description herein and are not intended to be limited to the specific values described below.
Example 1
A preparation method of a Zn/Co-MOF functionalized bioceramic composite stent material comprises the following steps:
(1) And preparing the beta-TCP ceramic support printing ink. The beta-TCP powder is sieved by a 200-mesh screen. Then 10.00g of beta-TCP powder, 0.06g of sodium alginate and 8.00g g F-127 (20 wt%) are mixed and stirred uniformly, and then sealed for preservation;
(2) Designing the appearance and the internal structure of a beta-TCP ceramic support material by using computer-aided software, wherein a support material model is a cylinder (phi=10mm), and the trend included angle of two adjacent layers of ink is 45 degrees;
(3) And preparing the beta-TCP ceramic support material by a 3D printing technology. Filling the prepared printing ink into a charging barrel of a 3D printer, then running a 3D printing program, and adjusting the air pressure of the printer to 2.0-6.0 bar and the printing speed to 6-13 mm/s; printing ink lines on glass sheets of a carrying platform, precisely forming the ink lines according to a layer-by-layer stacking mode to obtain a required beta-TCP ceramic support material, drying the material at 37 ℃ for 24 hours, degreasing the material at 600 ℃ for 2 hours, and sintering the material at 1150 ℃ for 3 hours for later use;
(4) The preparation method of the Zn/Co-MOF functionalized bioceramic composite stent material comprises the following steps: 5g of the β -TCP ceramic stent was immersed in 50mL of 2-methylimidazole aqueous solution (0.119 mol/L), and 5mL of (Zn (NO) 3 ) 2 ·6H 2 O+Co(NO 3 ) 2 ·6H 2 O)(0.17mol/L)，Zn(NO 3 ) 2 ·6H 2 O:Co(NO 3 ) 2 ·6H 2 O=5: 5, reacting for 3h, washing and drying for later use.
Example 2
A preparation method of a Zn/Co-MOF functionalized bioceramic composite stent material comprises the following steps:
(1) And preparing the beta-TCP ceramic support printing ink. The beta-TCP powder is sieved by a 200-mesh screen. Then 10.00g of beta-TCP powder, 0.06g of sodium alginate and 8.00g g F-127 (20 wt%) are mixed and stirred uniformly, and then sealed for preservation;
(2) Designing the appearance and the internal structure of a beta-TCP ceramic support material by using computer-aided software, wherein a support material model is a cylinder (phi=10mm), and the trend included angle of two adjacent layers of ink is 45 degrees;
(3) And preparing the beta-TCP ceramic support material by a 3D printing technology. Filling the prepared printing ink into a charging barrel of a 3D printer, then running a 3D printing program, and adjusting the air pressure of the printer to 2.0-6.0 bar and the printing speed to 6-13 mm/s; printing ink lines on glass sheets of a carrying platform, precisely forming the ink lines according to a layer-by-layer stacking mode to obtain a required beta-TCP ceramic support material, drying the material at 37 ℃ for 24 hours, degreasing the material at 600 ℃ for 2 hours, and sintering the material at 1150 ℃ for 3 hours for later use;
(5) The preparation method of the Zn/Co-MOF functionalized bioceramic composite stent material comprises the following steps: 5g of the β -TCP ceramic stent was immersed in 50mL of 2-methylimidazole aqueous solution (0.119 mol/L), and 5mL of (Zn (NO) 3 ) 2 ·6H 2 O+Co(NO 3 ) 2 ·6H 2 O)(0.12mol/L)，Zn(NO 3 ) 2 ·6H 2 O:Co(NO 3 ) 2 ·6H 2 O=5: 5, reacting for 3h, washing and drying for later use.
Example 3
A preparation method of a Zn/Co-MOF functionalized bioceramic composite stent material comprises the following steps:
(1) And preparing the beta-TCP ceramic support printing ink. The beta-TCP powder is sieved by a 200-mesh screen. Then 10.00g of beta-TCP powder, 0.06g of sodium alginate and 8.00g g F-127 (20 wt%) are mixed and stirred uniformly, and then sealed for preservation;
(2) Designing the appearance and the internal structure of a beta-TCP ceramic support material by using computer-aided software, wherein a support material model is a cylinder (phi=10mm), and the trend included angle of two adjacent layers of ink is 45 degrees;
(3) And preparing the beta-TCP ceramic support material by a 3D printing technology. Filling the prepared printing ink into a charging barrel of a 3D printer, then running a 3D printing program, and adjusting the air pressure of the printer to 2.0-6.0 bar and the printing speed to 6-13 mm/s; printing ink lines on glass sheets of a carrying platform, precisely forming the ink lines according to a layer-by-layer stacking mode to obtain a required beta-TCP ceramic support material, drying the material at 37 ℃ for 24 hours, degreasing the material at 600 ℃ for 2 hours, and sintering the material at 1150 ℃ for 3 hours for later use;
(6) The preparation method of the Zn/Co-MOF functionalized bioceramic composite stent material comprises the following steps: 5g of the β -TCP ceramic stent was immersed in 50mL of 2-methylimidazole aqueous solution (0.119 mol/L), and 5mL of (Zn (NO) 3 ) 2 ·6H 2 O+Co(NO 3 ) 2 ·6H 2 O)(0.50mol/L)，Zn(NO 3 ) 2 ·6H 2 O:Co(NO 3 ) 2 ·6H 2 O=5: 5, reacting for 3h, washing and drying for later use.
Example 4
A preparation method of a Zn/Co-MOF functionalized bioceramic composite stent material comprises the following steps:
(1) Preparing the biological glass bracket printing ink. The bioglass powder is screened through a 200-mesh screen. Then 10.00g of bioglass powder, 0.06g of sodium alginate and 8.00g g F-127 (20 wt%) are mixed and stirred uniformly, and then sealed for preservation;
(2) Designing the appearance and the internal structure of a biological glass bracket material by using computer-aided software, wherein a bracket material model is a cylinder (phi=10mm), and the trend included angle of two adjacent layers of ink is 45 degrees;
(3) And 3D printing technology to prepare the biological glass bracket material. Filling the prepared printing ink into a charging barrel of a 3D printer, then running a 3D printing program, and adjusting the air pressure of the printer to 2.0-6.0 bar and the printing speed to 6-13 mm/s; printing ink lines on glass sheets of a carrying platform, precisely forming the glass sheets in a layer-by-layer stacking mode to obtain a required biological glass bracket material, drying at 37 ℃ for 24 hours, degreasing at 600 ℃ for 2 hours, and sintering at 1150 ℃ for 3 hours for later use;
(7) The preparation method of the Zn/Co-MOF functionalized bioceramic composite stent material comprises the following steps: 5g of the bioglass stent was immersed in 50mL of 2-methylimidazole aqueous solution (0.119 mol/L), and 5mL of (Zn (NO) 3 ) 2 ·6H 2 O+Co(NO 3 ) 2 ·6H 2 O)(0.25mol/L)，Zn(NO 3 ) 2 ·6H 2 O:Co(NO 3 ) 2 ·6H 2 O=5: 5, reacting for 1-16h, washing and drying for later use.
Example 5
The Zn/Co-MOF functionalized bioceramic composite stent material prepared in example 1 is tested for antioxidant activity, and comprises the following steps:
(1) Adding the Zn/Co-MOF functionalized bioceramic composite stent material prepared in the embodiment 1 into an ABTS working solution, and carrying out light-shielding reaction for 3 hours;
(2) The color change of the solution was observed and the absorbance value of the final solution at about 730nm was measured with a microplate reader. Using ABTS working solution as a blank control group;
(3) As shown in FIG. 3, the color of the ABTS working solution in the Zn/Co-MOF functionalized bioceramic composite stent material group becomes light, and the absorbance at about 730nm is reduced, which indicates that the Zn/Co-MOF functionalized bioceramic composite stent material can effectively remove ABTS free radicals and has good antioxidant activity.
Example 6
The Zn/Co-MOF functionalized bioceramic composite stent material prepared in example 1 is subjected to catalase activity test, and comprises the following steps:
(1) Adding the Zn/Co-MOF functionalized bioceramic composite stent material prepared in embodiment 1 into H 2 O 2 (100 mmol/L) of the working solution, and reacting for 10min;
(2) Observing oxygen production amount of 0-10min, and recording dissolved oxygen amount every 30 s;
(3) As shown in FIG. 4, the Zn/Co-MOF functionalized bioceramic composite stent material continuously generates oxygen within 10min, and the dissolved oxygen in the solution is continuously increased, which indicates that the Zn/Co-MOF functionalized bioceramic composite stent material can catalyze H 2 O 2 Conversion to O 2 And H 2 O, withGood catalase-like activity.
Example 7
The adhesion condition of rabbit bone marrow mesenchymal stem cells on the Zn/Co-MOF functionalized bioceramic composite scaffold material prepared in the example 1 is studied, and the method comprises the following steps:
(1) Sterilizing the Zn/Co-MOF functionalized bioceramic composite stent material prepared in the example 1 at high temperature and high pressure, cleaning the material with sterile PBS for 3 times, and placing the material into a 24-hole culture plate;
(2) Will contain 5X 10 5 The bone marrow stem cells of rabbit origin were inoculated onto each scaffold material and cultured in MEM-alpha medium containing 10% fetal bovine serum and 1% penicillin streptomycin mixture at 37℃and 5% CO 2 Incubating in an incubator in atmosphere;
(3) With a composition of 200. Mu. Mol/L H 2 O 2 After 24h of stimulation, washing with PBS buffer for three times at 37 ℃ for fixation, and staining the nuclei and cytoskeleton with benzindole and rhodamine-phalloidin;
(4) The adhesion of cells on the scaffolds was observed with a Leica confocal laser scanning microscope (TCS SP8, leica, germany).
As shown in figure 5, rabbit bone marrow mesenchymal stem cells are well adhered to and fully spread on the Zn/Co-MOF functionalized bioceramic composite scaffold material, which shows that the Zn/Co-MOF functionalized bioceramic composite scaffold material is favorable for adhesion of bone marrow mesenchymal stem cells, has good biocompatibility and can also clear H 2 O 2 Protecting the cell activity.
Example 8
The adhesion condition of rabbit-derived chondrocytes on the Zn/Co-MOF functionalized bioceramic composite scaffold material prepared in example 1 is studied, and the method comprises the following steps:
(1) Sterilizing the Zn/Co-MOF functionalized bioceramic composite stent material prepared in the example 1 at high temperature and high pressure, cleaning the material with sterile PBS for 3 times, and placing the material into a 24-hole culture plate;
(2) Will contain 2.5X10 6 Inoculation of individual rabbit bone marrow mesenchymal stem cellsOnto each scaffold material, culturing with DMEM medium containing 10% fetal bovine serum and 1% penicillin streptomycin mixed solution, and culturing at 37deg.C and 5% CO 2 Incubating in an incubator in atmosphere;
(3) With a composition of 200. Mu. Mol/L H 2 O 2 After 24h of stimulation, washing with PBS buffer for three times at 37 ℃ for fixation, and staining the nuclei and cytoskeleton with benzindole and rhodamine-phalloidin;
(4) The adhesion of cells on the scaffolds was observed with a Leica confocal laser scanning microscope (TCS SP8, leica, germany).
The results are shown in figure 6, rabbit-derived chondrocytes are well adhered to and fully spread on the Zn/Co-MOF functionalized bioceramic composite scaffold material, and the result shows that the Zn/Co-MOF functionalized bioceramic composite scaffold material is favorable for chondrocyte adhesion, has good biocompatibility and can also remove H 2 O 2 Protecting the cell activity.
Example 9
The Zn/Co-MOF functionalized bioceramic composite scaffold material prepared in example 1 is used for researching the repair condition of bone cartilage defects in vivo, and comprises the following steps:
(1) Constructing a New Zealand white rabbit (2.5 kg) osteochondral defect model, then implanting the Zn/Co-MOF functionalized bioceramic composite stent material prepared in the example 1 into the osteochondral defect, taking the non-implanted stent material as a blank control, and taking the implanted beta-TCP stent as a positive control;
(2) After 12 weeks, rabbit osteochondral tissue samples were collected (see FIG. 7), micro-CT scan was performed, bone defect portion of the bone cartilage was quantitatively analyzed for new bone condition by CT-An software, and tissue sections were obtained and repair of cartilage and subchondral bone were detected by Van Gieson staining.
As shown in FIG. 7, the cartilage repair result without the implanted stent is poor, the implanted beta-TCP stent group is improved somewhat, and the cartilage repair effect of the implanted beta-TCP stent group is optimal. This fully demonstrates that the Zn/Co-MOF functionalized bioceramic composite scaffold material accelerates repair of osteochondral defects.
As shown in FIG. 8, the number of new bones of the non-implanted stent and the implanted beta-TCP stent groups is relatively small, and the BV/TV value of the Zn/Co-MOF functionalized bioceramic composite stent group is obviously larger, which indicates that the Zn/Co-MOF functionalized bioceramic composite stent material promotes the repair of osteochondral defects.
As shown in fig. 9, analysis of bone and cartilage growth in new zealand rabbit with support implant revealed that the load-implanted Zn/Co-MOF functionalized bioceramic composite support group had good neogenesis compared with the other two groups, both subchondral bone and cartilage. The MOF functionalized scaffold not only has the function of promoting the regeneration of bone cartilage, but also has the treatment capability of osteoarthritis, and fully proves the repair and treatment potential of the material system in relation to the injury osteoarthritis.
The preparation process can prepare the beta-TCP ceramic stent material with different internal structures by adjusting printing parameters and designing different stent material models; by controlling the concentration of the Zn/Co-MOF precursor solution, zn (NO 3 ) 2 ·6H 2 O and Co (NO) 3 ) 2 ·6H 2 The mixture ratio of O, the reaction time of the beta-TCP ceramic bracket and the Zn/Co-MOF precursor solution, and the Zn/Co-MOF functionalized bioceramic composite bracket materials with different component contents and different internal structures are prepared.
The analysis of physicochemical property and biological property of the composite scaffold material shows that the Zn/Co-MOF functionalized bioceramic composite scaffold material prepared by the invention has a three-dimensional communicated and controllable macroporous structure, good biomechanics and biocompatibility, and can remove various active oxygen, resist oxidative stress, and further promote osteogenic differentiation of rabbit bone marrow-derived mesenchymal stem cells and proliferation and maturation of chondrocytes in an inflammatory microenvironment. Therefore, the Zn/Co-MOF functionalized bioceramic composite scaffold material prepared by the invention is expected to provide a new strategy for repairing and treating the cartilage defect clinically.
The above description of the invention in connection with specific embodiments is not intended to limit the invention to those embodiments. Accordingly, modifications and substitutions without departing from the general inventive concept should be made thereto.
Claims (14)
1. A bio-ceramic composite scaffold material functionalized by a zinc-cobalt bimetal organic framework, which is characterized by comprising the following components: a three-dimensional porous biological ceramic bracket and a zinc-cobalt bimetal organic frame coating growing on the surface of the three-dimensional porous biological ceramic bracket in situ.
2. The zinc-cobalt bimetal organic frame functionalized biological ceramic composite bracket material according to claim 1, wherein the zinc-cobalt bimetal organic frame coating material is a zinc-cobalt bimetal organic frame material, and the ratio of cobalt to zinc is between 0.1: 10-10: between 0.1.
3. The zinc-cobalt bimetal organic frame functionalized biological ceramic composite bracket material according to claim 1, wherein the thickness of the zinc-cobalt bimetal organic frame coating is 500-nm-10 μm; the mass of the zinc-cobalt bimetal organic framework coating is 0.5-5 wt% of the mass of the three-dimensional porous biological ceramic bracket.
4. The zinc-cobalt bimetal organic framework functionalized bioceramic composite bracket material according to claim 1, wherein the three-dimensional porous bioceramic bracket is made of bioactive ceramics or/and bioactive glass, and is at least one of beta-phase tricalcium phosphate, hydroxyapatite and melilite; the bioactive glass comprises SiO 2 -CaO-P 2 O 5 Glass system in which SiO 2 、CaO、P 2 O 5 Mass ratio = (45-90): (5-30): (1-10).
5. The zinc-cobalt bimetal organic framework functionalized bioceramic composite stent material according to any one of claims 1 to 4, wherein the three-dimensional porous bioceramic stent has a macroporous structure with a porosity of 20 to 80%; the size of the macroporous structure is 100 mu m-1 mm.
6. A method for preparing the zinc-cobalt bimetallic organic framework functionalized bioceramic composite stent material according to any one of claims 1 to 5, comprising: immersing the three-dimensional porous biological ceramic bracket into an organic ligand solution, adding the organic ligand solution into a zinc-cobalt bimetallic solution for reaction, and washing and drying to obtain the biological ceramic composite bracket material with the zinc-cobalt bimetallic organic framework functionalization.
7. The method according to claim 6, wherein the concentration of the organic ligand solution is 0.05 to 0.5mol/L, and the solvent is at least one selected from deionized water, absolute ethyl alcohol and acetone; the organic ligand comprises at least one of 2-methylimidazole, porphyrin and terephthalic acid;
the solute in the zinc-cobalt bimetallic solution is zinc salt and cobalt salt, and the solvent is at least one of deionized water, absolute ethyl alcohol and acetone;
the zinc salt is Zn (NO) 3 ) 2 ·6H 2 O、ZnCl 2 And ZnSO 4 At least one of (a) and (b);
the cobalt salt is selected from Co (NO) 3 ) 2 ·6H 2 O、CoCl 2 ·6H 2 O and CoSO 4 ·7H 2 At least one of O;
the total concentration range of the zinc salt and the cobalt salt is 0.05-0.5 mol/L;
the molar ratio of the zinc salt to the cobalt salt is 0.1: 10-10: 0.1.
8. the preparation method according to claim 7, wherein the total concentration of the zinc salt and the cobalt salt is in the range of 0.10 to 0.25 mol/L;
the molar ratio of the zinc salt to the cobalt salt is 4-7: 1.
9. the method of any one of claims 6-8, wherein the ratio of the three-dimensional porous bioceramic scaffold to organic ligand solution is (0.01 g-0.2 g): 1mL;
the three-dimensional porous bioceramic scaffold: zinc cobalt bimetallic organic framework precursor solution consisting of organic ligand solution and zinc cobalt bimetallic solution= (0.01 g-0.1 g): 1mL; the reaction temperature is 20-60 ℃ and the reaction time is 1-16 h.
10. The method of claim 9, wherein the reaction time is 2 to 4h; the volume ratio of the organic ligand solution to the zinc-cobalt bimetallic solution is (5-10): 1.
11. the method of any one of claims 6-8, wherein the method of preparing the three-dimensional porous bioceramic scaffold comprises:
(1) Uniformly mixing the bioactive ceramic powder and the binder solution to obtain printing ink; the binder comprises at least one of sodium alginate, F-127 and polyvinyl alcohol; the concentration of the binder is 0.5-20%;
(2) And (3) preparing a wet bracket blank from the printing ink by a 3D printing technology, and drying, debonding and sintering to obtain the three-dimensional porous biological ceramic bracket.
12. The method of claim 11, wherein the drying comprises drying 24-48 h at 37 ℃;
the temperature of the de-bonding is 400-650 ℃;
the sintering temperature is 900-1400 ℃.
13. Use of a zinc-cobalt bimetallic organic framework functionalized bioceramic composite scaffold material according to any one of claims 1-5 for the preparation of osteochondral repair materials.
14. The use of a zinc-cobalt bimetal organic framework functionalized bioceramic composite scaffold material according to claim 13 for preparing a osteochondral repair material, wherein the osteochondral repair material is a osteochondral defect knee joint material.
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| Metal-Organic Framework Functionalized Bioceramic Scaffolds with Antioxidative Activity for Enhanced Osteochondral Regeneration;Yufang Zhu et al;Advanced Science;20230224;1-14 * |
| 卟啉基金属有机框架负载高铁酸钾:光–化学动力学联合治疗肿瘤性能研究;朱钰方;无机材料学报;20210617;1305-1315 * |
| 柔性可弯曲高容量复合织物电极的制备及性能;杨超;复合材料学报;20211009;3804-3814 * |
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