CN108310456B - Preparation method of graphene oxide/nano-hydroxyapatite composite silica gel modified porous scaffold material - Google Patents
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Abstract
The invention discloses a preparation method of a graphene oxide/nano-hydroxyapatite composite silica gel modified porous scaffold material, belonging to the technical field of biological materials, and the method comprises the following steps of firstly preparing a graphene oxide/nano-hydroxyapatite composite powder material by an ion co-titration method by taking graphene oxide, a calcium source and a phosphorus source as raw materials; adding silica gel and a pore-forming agent, carrying out extrusion molding through a mold to obtain a support material, and then placing the support in alcohol for soaking and sintering in an inert atmosphere furnace to finally obtain a porous support material; the prepared porous support material has components close to human bones and a porous structure, the pore size is distributed at 300-800 mu m, the porosity is 30-70%, the compressive strength reaches 0.9-4.2 Mpa, the biodegradability and the osteogenesis property in simulated body fluid are good, and the porous support material is free of cytotoxicity.
Description
Technical Field
The invention relates to a preparation method of a graphene oxide/nano-hydroxyapatite composite silica gel modified porous scaffold material, belonging to the technical application field of biomedical materials.
Background
Bones are the main components of the human skeletal system and are responsible for the important functions of support, weight bearing, movement and the like. However, bone defects caused by diseases, trauma, aging, sports trauma and the like are one of the problems to be solved urgently in clinic. The tissue engineering material is widely applied as a good biological implant material, the scaffold material is implanted into a defect part, and bone cells implanted in a porous scaffold are continuously proliferated while the material is gradually degraded, so that the aim of repairing bone tissue defect is fulfilled. The ideal bone tissue scaffold material meets the following points: (1) the biodegradable polymer has good biocompatibility, and degradation products are non-toxic and do not cause inflammatory reaction; (2) the size of the pore size is suitable for the growth of new bones, and the average pore size of the bone scaffold is about 200-800 mu m; (3) the material has certain mechanical strength and can provide support for the new tissue; (4) has osteoconductive or osteoinductive properties, and can promote bone deposition and bone growth; (5) has good biodegradability.
Graphene Oxide (GO) isSP 2The hybridized two-dimensional structure material has the structure and performance similar to graphene, and the surface of the material contains rich oxygen-containing functional groups which are used for connecting various organic small molecules and have high molecular weightThe seed, the biological macromolecule and other functional groups provide a large number of active sites. Meanwhile, due to the good biological performance of the graphene oxide, the graphene oxide can be widely applied to the field of biomedicine. Hydroxyapatite (HAP) is a main inorganic component in natural bone, is a main component of an inorganic phase of a dental tissue, can be strongly chemically bonded with bone formation on an interface after being implanted into the bone tissue, has a certain induction effect on the growth of new bone, and is mainly used for repairing, replacing or enhancing the functions of human tissues or organs.
Due to the fact that the graphene oxide is added to toughen the hydroxyapatite, the brittleness of the graphene oxide is overcome. Researchers can obtain a scaffold material with better biological performance by adopting gelatin crosslinking modification to prepare a porous scaffold material, but the bonding property of the gelatin and the graphene oxide is poor, so that the mechanical property of the scaffold is poor, the scaffold is poor in degradability in simulated human body fluid, the preparation process is complex, and the practicability is low.
Disclosure of Invention
Aiming at the defects of the prior art, the porous scaffold material is prepared by modifying the silica gel, the silica gel has better biological property, the sintering mechanical property after modification is greatly improved, the binding property with the graphene oxide is better, the degradability in the simulated human body fluid is better, the apatite Ca/P formed by in vitro biological deposition and mineralization is close to the bone component of the human body, and no toxic cells exist, meanwhile, the artificial stearic acid globule is used as the pore-forming agent, and the pores of the scaffold have certain controllability.
The invention provides a preparation method of a graphene oxide/nano-hydroxyapatite composite silica gel modified porous scaffold material, which specifically comprises the following steps:
(1) uniformly dispersing graphene oxide in a calcium source solution, and continuously stirring in a water bath at 30-60 ℃ to obtain a solution A, wherein the mass ratio of the graphene oxide to the calcium source is 1 (2.0-6.3), the stirring speed is 250-350 r/min, and the temperature is increased to 30-60 ℃ at the heating rate of 3-5 ℃/min in the water bath;
(2) adjusting the pH value of the solution A to 9.5-11.5, and then dropwise adding a phosphorus source solution at 30-60 ℃, wherein the molar ratio of calcium to phosphorus in the step (1) is 1.67;
(3) continuously stirring for 16-24 h at 30-60 ℃ after titration, then sealing and aging for 12-24 h at normal temperature, cleaning and drying to obtain a composite powder material;
(4) adding silica gel into the composite powder material obtained in the step (3), stirring to uniformly mix the silica gel and the composite powder material, and adding a pore-forming agent to obtain a sample B, wherein the mass ratio of the silica gel to the composite powder material is 1 (5-8), and the mass ratio of the pore-forming agent to the composite powder material is 1 (1.5-5.0);
(5) extruding and forming the sample B to obtain a bracket material, soaking the bracket material in analytically pure alcohol, and drying to obtain a sample C;
(6) and (3) heating the sample C to 200 ℃ at the heating rate of 1-3 ℃/min in an inert atmosphere, preserving the heat at 200 ℃ for 1-3 h, and cooling to room temperature along with the furnace to obtain the porous support material.
The calcium source in the step (1) is calcium nitrate, calcium sulfate, calcium hydroxide or calcium chloride, and the concentration of calcium ions in the calcium source solution is 0.038-0.075 mol/L.
And (2) adjusting the pH value of the solution A by adopting an ammonia water solution with the concentration of 0.023-0.030 mol/L.
And (3) dropwise adding the phosphorus source solution in the step (2) at a speed of 5-15 mL/min.
And (3) the phosphorus source in the step (2) is diammonium hydrogen phosphate, potassium dihydrogen phosphate or phosphoric acid, and the concentration of phosphate ions in the phosphorus source solution is 0.045-0.090 mol/L.
And (4) the mass percent of the silicon dioxide in the silica gel is 30%.
And (4) the pore-forming agent is stearic acid, sodium chloride, polymethyl methacrylate, sodium bicarbonate or sodium carbonate.
And (5) soaking the analytically pure alcohol in the analytically pure alcohol at the temperature of 30-37 ℃ for 4-6 hours.
And (6) the inert atmosphere is nitrogen or argon atmosphere.
The invention has the beneficial effects that:
(1) the graphene oxide/nano-hydroxyapatite composite material prepared by the solution ion co-titration method has good biological performance, and the graphene oxide and the hydroxyapatite are combined in a chemical bond form, so that the mechanical performance of the composite material is further improved; the biological performance of the composite material can be further improved under the modification of silica gel, and the pores of the bracket can have certain controllability by using a pore-forming agent; the porous scaffold material has good biological performance and is expected to have good application prospect in the future.
(2) The silicon-modified graphene oxide/nano-hydroxyapatite composite bone tissue porous scaffold material prepared by the invention comprises the specific components of graphene oxide, nano-hydroxyapatite and silicon dioxide, the mass ratio of the graphene oxide to the nano-hydroxyapatite to the silicon dioxide is 1 (0.84-2.64) to 0.07-0.16), the porous scaffold material has the components close to human bone and a porous structure, the pore size distribution is 300-800 mu m, the porosity is 30-70%, the compressive strength reaches 0.9-4.2 MPa, the in vitro biological mineralization performance is good, and the cytotoxicity is non-toxic.
Drawings
FIG. 1 is an SEM image of the porous support material prepared in example 1;
FIG. 2 is a SEM + EDS spectrum of the porous scaffold material prepared in example 3 mineralized for 14 days;
FIG. 3 is a graph showing cytotoxicity analysis of the porous scaffold materials obtained in example 4 and comparative example 1;
fig. 4 is a graph comparing the compressive strength of the porous scaffold prepared in example 5 with that of the porous scaffold prepared in comparative example 2.
Detailed Description
The invention will be described in more detail with reference to the following figures and examples, but the scope of the invention is not limited thereto.
Example 1
A preparation method of a graphene oxide/nano-hydroxyapatite composite silica gel modified porous scaffold material specifically comprises the following steps:
(1) adding 1.25g of calcium nitrate into a beaker filled with 200mL of distilled water, preparing into 0.038mol/L calcium nitrate solution, and placing the calcium nitrate solution on a magnetic stirrer to be continuously stirred, wherein the rotating speed of the magnetic stirrer is 250 revolutions per minute, so that the raw materials are completely dissolved; then heating in a water bath at a heating rate of 3 ℃/min, controlling the temperature of the solution to be 37 ℃, then adding 0.282g of graphene oxide powder, and continuously stirring to uniformly disperse the graphene oxide powder to obtain a solution A;
(2) measuring ammonia water by using a measuring cylinder, adding the ammonia water into deionized water to prepare an ammonia water solution with the concentration of 0.025mol/L, and adjusting the pH value of the solution A to 10 by using the ammonia water solution; adding diammonium phosphate into 100mL of distilled water to prepare 0.0455mol/L diammonium phosphate solution, stirring to dissolve the diammonium phosphate solution to obtain diammonium phosphate solution, then adding diammonium phosphate solution at a dropping speed of 15mL/min according to the molar ratio of calcium to phosphorus of 1.67, and keeping the temperature at 37 ℃ in the titration process;
(3) after titration, continuously stirring for 16 hours at the stirring temperature of 35 ℃, then placing at normal temperature for sealed aging for 16 hours, and cleaning and drying to obtain the graphene oxide/nano-hydroxyapatite composite powder material;
(4) adding silica gel into the composite powder material obtained in the step (3), wherein the mass percentage of silica in the silica gel is 30%, stirring to uniformly mix the silica gel and the silica gel, and adding a stearic acid pore-forming agent to obtain a sample B, wherein the mass ratio of the silica gel to the composite powder material is 1:8, and the mass ratio of the pore-forming agent to the composite powder material is 1: 1.5;
(5) extruding and molding the sample B through a die to obtain a bracket material, soaking the bracket material in analytical pure alcohol at the soaking temperature of 30 ℃ for 4 hours, and drying to obtain a sample C;
(6) and (3) placing the sample C in an atmosphere furnace, heating to 200 ℃ at the heating rate of 1 ℃/min under the nitrogen atmosphere, keeping the temperature at 200 ℃ for 2h, and cooling to room temperature along with the furnace to obtain the porous scaffold material, wherein the porosity of the scaffold is 30%, and the compressive strength of the scaffold is 4.2 MPa.
Fig. 1 is a scanning electron microscope image of the porous scaffold material prepared in the embodiment, and fig. 1 (b) is a partial enlarged view of fig. 1 (a), and it can be seen from the image that the porous scaffold has more pore distribution and has a good interconnected pore structure, the pores are left when the pores are formed by stearic acid pellets, the pore size is controlled by preparing stearic acid pellets with a certain particle size, the pore size of the scaffold is about 300-800 μm, the pore size range of human bone is basically compounded, and the scaffold material is used as a basis for preparing a better bone tissue scaffold material.
Example 2
A preparation method of a graphene oxide/nano-hydroxyapatite composite silica gel modified porous scaffold material specifically comprises the following operations:
(1) adding 1.47g of calcium nitrate into a beaker filled with 200mL of distilled water, preparing into 0.045mol/L calcium nitrate solution, placing the calcium nitrate solution on a magnetic stirrer for continuous stirring, wherein the rotating speed of the magnetic stirrer is 250 revolutions per minute, and completely dissolving the raw materials; then heating in a water bath at a heating rate of 4 ℃/min, controlling the temperature of the solution to be 37 ℃, then adding 0.282g of graphene oxide powder, and continuously stirring to uniformly disperse the graphene oxide powder to obtain a solution A;
(2) ammonia water is measured by a using cylinder and added into deionized water to prepare an ammonia water solution with the concentration of 0.025mol/L, and the pH value of the solution A is adjusted to 9.5 by using the ammonia water solution; adding diammonium phosphate into 100mL of distilled water to prepare 0.054mol/L diammonium phosphate solution, stirring to dissolve the diammonium phosphate solution to obtain diammonium phosphate solution, then adding diammonium phosphate solution at a dropping speed of 10mL/min according to the molar ratio of calcium to phosphorus of 1.67, and keeping the temperature at 37 ℃ in the titration process;
(3) after titration, continuously stirring for 20 hours at the stirring temperature of 40 ℃, then placing at normal temperature for sealed aging for 12 hours, and cleaning and drying to obtain the graphene oxide/nano-hydroxyapatite composite powder material;
(4) adding silica gel into the composite powder material obtained in the step (3), wherein the mass percentage of silica in the silica gel is 30%, stirring to uniformly mix the silica gel and the silica gel, and adding a sodium chloride pore-forming agent to obtain a sample B, wherein the mass ratio of the silica gel to the composite powder material is 1:6, and the mass ratio of the pore-forming agent to the composite powder material is 1: 2;
(5) extruding and molding the sample B through a die to obtain a bracket material, soaking the bracket material in analytical pure alcohol at the soaking temperature of 30 ℃ for 4 hours, and drying to obtain a sample C;
(6) and (3) placing the sample C in an atmosphere furnace, heating to 200 ℃ at the heating rate of 2 ℃/min under the nitrogen atmosphere, preserving the heat for 2h at 200 ℃, and cooling to room temperature along with the furnace to obtain the porous scaffold material, wherein the porosity of the scaffold is 45%, and the compressive strength of the scaffold is 3.2 MPa.
Example 3
A preparation method of a graphene oxide/nano-hydroxyapatite composite silica gel modified porous scaffold material specifically comprises the following operations:
(1) 2.448g of calcium sulfate is added into a beaker filled with 200mL of distilled water, the solution is prepared into 0.045mol/L calcium sulfate solution, the solution is placed on a magnetic stirrer to be continuously stirred, and the rotating speed of the magnetic stirrer is 300 r/min, so that the raw materials are completely dissolved; then heating in water bath at a heating rate of 5 ℃/min, controlling the temperature of the solution to be 30 ℃, then adding 0.897g of graphene oxide powder, and continuously stirring to uniformly disperse the graphene oxide powder to obtain a solution A;
(2) measuring ammonia water by using a measuring cylinder, adding the ammonia water into deionized water to prepare an ammonia water solution with the concentration of 0.030mol/L, and adjusting the pH value of the solution A to 10.5 by using the ammonia water solution; adding diammonium phosphate into 100mL of distilled water to prepare 0.054mol/L diammonium phosphate solution, stirring to dissolve the diammonium phosphate solution to obtain diammonium phosphate solution, then adding diammonium phosphate solution at a dropping speed of 10mL/min according to the molar ratio of calcium to phosphorus of 1.67, and keeping the temperature at 30 ℃ in the titration process;
(3) after titration, continuously stirring for 24 hours at the stirring temperature of 30 ℃, then placing at normal temperature for sealed aging for 15 hours, and cleaning and drying to obtain the graphene oxide/nano-hydroxyapatite composite powder material;
(4) adding silica gel into the composite powder material obtained in the step (3), wherein the mass percentage of silica in the silica gel is 30%, stirring to uniformly mix the silica gel and the silica gel, and adding a sodium carbonate pore-forming agent to obtain a sample B, wherein the mass ratio of the silica gel to the composite powder material is 1:5, and the mass ratio of the pore-forming agent to the composite powder material is 1: 2.5;
(5) extruding and molding the sample B through a die to obtain a bracket material, soaking the bracket material in analytical pure alcohol at the soaking temperature of 35 ℃ for 5 hours, and drying to obtain a sample C;
(6) and (3) placing the sample C in an atmosphere furnace, heating to 200 ℃ at the heating rate of 2 ℃/min under the nitrogen atmosphere, preserving the heat for 3h at 200 ℃, and cooling to room temperature along with the furnace to obtain the porous scaffold material, wherein the porosity of the scaffold is 50%, and the compressive strength of the scaffold is 2.1 MPa.
FIG. 2 is SEM and EDS of the porous scaffold obtained in this example after mineralization in simulated human body fluid (SBF) for 14 days, from which it can be seen that the porous scaffold surface is formed with more spherical-like round particles, which are deposited calcium phosphate salts due to the presence of more negatively charged oxygen-containing functional groups such as-COOH, -OH, PO, etc. on the material itself4 3-Etc., whereas more Ca is present in the simulated body fluid, the electronegativity of the stent surface makes more Ca2+Can be deposited on, and PO4 3-Binding to form a calcium phosphate salt. Through EDS energy spectrum analysis, the Ca/P in the deposited calcium phosphate is 1.62, which is close to human bone calcium phosphate, and simultaneously, the stent has better osteogenesis.
Example 4
A preparation method of a graphene oxide/nano-hydroxyapatite composite silica gel modified porous scaffold material specifically comprises the following operations:
(1) adding 1.33g of calcium chloride into a beaker filled with 200mL of distilled water, preparing into 0.06mol/L calcium chloride solution, placing the calcium chloride solution on a magnetic stirrer for continuous stirring, wherein the rotating speed of the magnetic stirrer is 300 revolutions per minute, and completely dissolving the raw materials; then heating in a water bath at a heating rate of 5 ℃/min, controlling the temperature of the solution to be 45 ℃, then adding 0.21g of graphene oxide powder, and continuously stirring to uniformly disperse the graphene oxide powder to obtain a solution A;
(2) measuring ammonia water by using a measuring cylinder, adding the ammonia water into deionized water to prepare an ammonia water solution with the concentration of 0.030mol/L, and adjusting the pH value of the solution A to 10.5 by using the ammonia water solution; adding monopotassium phosphate into 100mL of distilled water to prepare 0.072mol/L potassium dihydrogen phosphate solution, stirring to dissolve the solution to obtain potassium dihydrogen phosphate solution, then adding the potassium dihydrogen phosphate solution at a dropping speed of 8mL/min according to the molar ratio of calcium to phosphorus of 1.67, and keeping the temperature at 37 ℃ in the titration process;
(3) after titration, continuously stirring for 16 hours at the stirring temperature of 40 ℃, then placing at normal temperature for sealed aging for 13 hours, and cleaning and drying to obtain the graphene oxide/nano-hydroxyapatite composite powder material;
(4) adding silica gel into the composite powder material obtained in the step (3), wherein the mass percentage of silica in the silica gel is 30%, stirring to uniformly mix the silica gel and the silica gel, and adding a sodium bicarbonate pore-forming agent to obtain a sample B, wherein the mass ratio of the silica gel to the composite powder material is 1:6, and the mass ratio of the pore-forming agent to the composite powder material is 1: 5;
(5) extruding and molding the sample B through a die to obtain a bracket material, soaking the bracket material in analytical pure alcohol at the soaking temperature of 37 ℃ for 5 hours, and drying to obtain a sample C;
(6) placing the sample C in an atmosphere furnace, heating to 200 ℃ at the heating rate of 3 ℃/min, keeping the temperature at 200 ℃ for 3h under the argon atmosphere, cooling to room temperature along with the furnace to obtain the porous scaffold material, wherein the porosity of the scaffold is 70%, and the compressive strength of the scaffold is 0.7MPa
Comparative example 1
A preparation method of a nano hydroxyapatite silica gel modified porous scaffold material comprises the following specific operations:
(1) adding 1.33g of calcium chloride into a beaker filled with 200mL of distilled water, preparing into 0.06mol/L calcium chloride solution, placing the calcium chloride solution on a magnetic stirrer for continuous stirring, wherein the rotating speed of the magnetic stirrer is 300 r/min, completely dissolving the raw materials to obtain solution A, heating in a water bath at the heating rate of 5 ℃/min, and controlling the temperature of the solution to be 45 ℃;
(2) measuring ammonia water by using a measuring cylinder, adding the ammonia water into deionized water to prepare an ammonia water solution with the concentration of 0.030mol/L, adjusting the pH value of the solution A to be 10.5 by using the ammonia water solution, adding monopotassium phosphate into 100mL of distilled water to prepare a 0.072mol/L potassium dihydrogen phosphate solution, stirring to dissolve the solution to obtain a potassium dihydrogen phosphate solution, then adding the potassium dihydrogen phosphate solution at the dropping speed of 8mL/min according to the molar ratio of calcium to phosphorus of 1.67, and keeping the temperature at 37 ℃ in the titration process;
(3) after titration, continuously stirring for 16 hours at the stirring temperature of 40 ℃, then placing at normal temperature for sealed aging for 13 hours, and cleaning and drying to obtain the graphene oxide/nano-hydroxyapatite composite powder material;
(4) adding silica gel into the composite powder material obtained in the step (3), wherein the mass percentage of silica in the silica gel is 30%, stirring to uniformly mix the silica gel and the silica gel, and adding a sodium bicarbonate pore-forming agent to obtain a sample B, wherein the mass ratio of the silica gel to the powder material is 1:6, and the mass ratio of the pore-forming agent to the powder material is 1: 5;
(5) extruding and molding the sample B through a die to obtain a bracket material, soaking the bracket material in analytical pure alcohol at the soaking temperature of 37 ℃ for 5 hours, and drying to obtain a sample C;
(6) and (3) placing the sample C in an atmosphere furnace, heating to 200 ℃ at the heating rate of 3 ℃/min, keeping the temperature of 200 ℃ for 3 hours in the nitrogen atmosphere, and cooling to room temperature along with the furnace to obtain the porous support material.
FIG. 3 is a cytotoxicity analysis chart of the porous scaffold materials obtained in example 4 and comparative example 1, from which it can be seen that the cell proliferation degree of the porous scaffold materials obtained in example 4 and comparative example 1 is more than 80%, and the porous scaffold materials are all cell-non-toxic; the cell proliferation degrees of the graphene oxide/nano-hydroxyapatite porous scaffold and the leaching solution are reduced along with the increase of the concentration of the leaching solution, and under the same concentration of the leaching solution, the corresponding cell proliferation degrees of the graphene oxide/nano-hydroxyapatite porous scaffold prepared in the example 4 are greater than those of the porous scaffold obtained in the comparative example, and meanwhile, the biological activity of the porous scaffold is improved by adding the graphene oxide.
Example 5
A preparation method of a graphene oxide/nano-hydroxyapatite composite silica gel modified porous scaffold material specifically comprises the following operations:
(1) adding 1.11g of calcium hydroxide into a beaker filled with 200mL of distilled water, preparing into 0.075mol/L calcium hydroxide solution, placing the solution on a magnetic stirrer for continuous stirring, wherein the rotating speed of the magnetic stirrer is 350 revolutions per minute, and completely dissolving the raw materials; then heating in water bath at a heating rate of 5 ℃/min, controlling the temperature of the solution to be 60 ℃, adding 0.538g of graphene oxide powder, and continuously stirring to uniformly disperse the graphene oxide powder to obtain a solution A;
(2) measuring ammonia water by using a measuring cylinder, adding the ammonia water into deionized water to prepare an ammonia water solution with the concentration of 0.023mol/L, and adjusting the pH value of the solution A to 11.5 by using the ammonia water solution; adding diammonium phosphate into 100mL of distilled water to prepare 0.09mol/L diammonium phosphate solution, stirring to dissolve the diammonium phosphate solution to obtain diammonium phosphate solution, then adding diammonium phosphate solution at a dropping speed of 5mL/min according to the molar ratio of calcium to phosphorus of 1.67, and keeping the temperature at 60 ℃ in the titration process;
(3) after titration, continuously stirring for 24 hours at the stirring temperature of 60 ℃, then placing at normal temperature for sealed aging for 24 hours, and cleaning and drying to obtain the graphene oxide/nano hydroxyapatite composite powder material;
(4) adding silica gel into the composite powder material obtained in the step (3), wherein the mass percentage of silica in the silica gel is 30%, stirring to uniformly mix the silica gel and the silica gel, and adding a polymethyl methacrylate pore-forming agent to obtain a sample B, wherein the mass ratio of the silica gel to the composite powder material is 1:7, and the mass ratio of the pore-forming agent to the composite powder material is 1: 4.5;
(5) extruding and molding the sample B through a die to obtain a bracket material, soaking the bracket material in analytical pure alcohol at the soaking temperature of 37 ℃ for 6 hours, and drying to obtain a sample C;
(6) and (3) placing the sample C in an atmosphere furnace, heating to 200 ℃ at the heating rate of 2 ℃/min, preserving the heat for 1h at 200 ℃ in the nitrogen atmosphere, and cooling to room temperature along with the furnace to obtain the porous support material, wherein the porosity of the porous support material is 40%.
The mass ratios of the pore-forming agent and the composite powder material in example 5 were respectively 1:3 and 1:2, and other process conditions were unchanged, and the porosities of the porous scaffold materials obtained by preparation were 50% and 60%, indicating that the amount of the pore-forming agent increased and the porosity of the porous scaffold materials obtained by preparation thereof increased.
Comparative example 2
A preparation method of a nano hydroxyapatite silica gel modified porous scaffold material specifically comprises the following operations:
(1) adding 1.11g of calcium hydroxide into a beaker filled with 200mL of distilled water, preparing a 0.075mol/L calcium hydroxide solution, placing the solution on a magnetic stirrer for continuous stirring, wherein the rotating speed of the magnetic stirrer is 350 r/min, completely dissolving the raw materials to obtain a solution A, heating in a water bath at a heating rate of 5 ℃/min, and controlling the temperature of the solution to be 60 ℃;
(2) measuring ammonia water by using a measuring cylinder, adding the ammonia water into deionized water to prepare an ammonia water solution with the concentration of 0.023mol/L, and adjusting the pH value of the solution A to 11.5 by using the ammonia water solution; adding diammonium phosphate into 100mL of distilled water to prepare 0.09mol/L diammonium phosphate solution, stirring to dissolve the diammonium phosphate solution to obtain diammonium phosphate solution, then adding diammonium phosphate solution at a dropping speed of 5mL/min according to the molar ratio of calcium to phosphorus of 1.67, and keeping the temperature at 60 ℃ in the titration process;
(3) after titration, continuously stirring for 24 hours at the stirring temperature of 60 ℃, then placing at normal temperature for sealed aging for 24 hours, and cleaning and drying the nano hydroxyapatite powder material;
(4) adding silica gel into the powder material obtained in the step (3), wherein the mass percentage of silica in the silica gel is 30%, stirring to uniformly mix the silica gel and the silica gel, and then respectively adding polymethyl methacrylate pore-forming agents to obtain a sample B, wherein the mass ratio of the silica gel to the composite powder material is 1:7, and the mass ratio of the pore-forming agents to the powder material is 1: 4.5;
(5) respectively carrying out extrusion forming on the sample B through a die to obtain a bracket material, soaking the bracket material in analytical pure alcohol at the soaking temperature of 37 ℃ for 6 hours, and drying to obtain a sample C;
(6) and respectively placing the sample C in an atmosphere furnace, heating to 200 ℃ at the heating rate of 2 ℃/min, preserving the heat for 1h at 200 ℃ in the nitrogen atmosphere, and cooling to room temperature along with the furnace to obtain three porous support materials with different porosities, wherein the porosities are respectively 40%.
The mass ratios of the pore-forming agent and the composite powder material in comparative example 2 were 1:3 and 1:2, respectively, and other process conditions were unchanged, and the porosities of the porous scaffold materials obtained by the preparation were 50% and 60%, indicating that the amount of the pore-forming agent increased and the porosity of the porous scaffold materials obtained by the preparation increased correspondingly.
FIG. 4 is a graph comparing the compressive strength of porous scaffolds with different porosities, prepared according to example 5, with that of the porous scaffolds with different porosities, prepared according to comparative example 2, and it can be seen from the graph that the compressive strength of the two porous scaffolds is continuously reduced along with the increase of the porosities, and is greater than 4MPa at a porosity of 40%, wherein the compressive strength of the porous scaffolds prepared according to the present example is higher than that of the porous scaffolds prepared according to the comparative example; when the porosity is 50%, the compressive strength of the two porous scaffolds is greater than 2MPa, and the compressive strength of the porous scaffold prepared in the example is higher than that of the porous scaffold prepared in the comparative example; in addition, when the porosity is 60%, the compressive strength of the two porous scaffolds is about 1MPa, and the compressive strength of the porous scaffold prepared in the example is higher than that of the porous scaffold prepared in the comparative example, which shows that the compressive strength of the porous scaffold can be enhanced and the mechanical properties of the porous scaffold can be improved by adding the graphene oxide.
Claims (8)
1. A preparation method of a graphene oxide/nano-hydroxyapatite composite silica gel modified porous scaffold material is characterized by comprising the following steps:
(1) uniformly dispersing graphene oxide in a calcium source solution, and continuously stirring in a water bath at 30-60 ℃ to obtain a solution A, wherein the mass ratio of the graphene oxide to the calcium source is 1 (2.0-6.3), the stirring speed is 250-350 r/min, and the temperature is increased to 30-60 ℃ at the heating rate of 3-5 ℃/min in the water bath;
(2) adjusting the pH value of the solution A to 9.5-11.5, and then dropwise adding a phosphorus source solution at 30-60 ℃, wherein the molar ratio of calcium to phosphorus in the step (1) is 1.67;
(3) continuously stirring for 16-24 h at 30-60 ℃ after titration, then sealing and aging for 12-24 h at normal temperature, cleaning and drying to obtain a composite powder material;
(4) adding silica gel into the composite powder material obtained in the step (3), stirring to uniformly mix the silica gel and the composite powder material, and adding a pore-forming agent to obtain a sample B, wherein the mass ratio of the silica gel to the composite powder material is 1 (5-8), and the mass ratio of the pore-forming agent to the composite powder material is 1 (1.5-5.0); the mass percent of silicon dioxide in the silica gel is 30%;
(5) extruding and forming the sample B to obtain a bracket material, soaking the bracket material in analytically pure alcohol, and drying to obtain a sample C;
(6) and (3) heating the sample C to 200 ℃ at the heating rate of 1-3 ℃/min in an inert atmosphere, preserving the heat at 200 ℃ for 1-3 h, and cooling to room temperature along with the furnace to obtain the porous support material.
2. The preparation method of the graphene oxide/nano-hydroxyapatite composite silica gel modified porous scaffold material according to claim 1, wherein the calcium source in the step (1) is calcium nitrate, calcium sulfate, calcium hydroxide or calcium chloride, and the concentration of calcium ions in a calcium source solution is 0.038-0.075 mol/L.
3. The preparation method of the graphene oxide/nano-hydroxyapatite composite silica gel modified porous scaffold material according to claim 1, wherein in the step (2), the pH value of the solution A is adjusted by using an ammonia water solution with a concentration of 0.023-0.030 mol/L.
4. The preparation method of the graphene oxide/nano-hydroxyapatite composite silica gel modified porous scaffold material according to claim 1, wherein the dropping speed of the phosphorus source solution in the step (2) is 5-15 mL/min.
5. The preparation method of the graphene oxide/nano-hydroxyapatite composite silica gel modified porous support material according to claim 1, wherein the phosphorus source in the step (2) is diammonium hydrogen phosphate, potassium dihydrogen phosphate or phosphoric acid, and the concentration of phosphate ions in a phosphorus source solution is 0.045-0.090 mol/L.
6. The preparation method of the graphene oxide/nano-hydroxyapatite composite silica gel modified porous scaffold material according to claim 1, wherein the pore-forming agent in the step (4) is stearic acid, sodium chloride, polymethyl methacrylate, sodium bicarbonate or sodium carbonate.
7. The preparation method of the graphene oxide/nano-hydroxyapatite composite silica gel modified porous scaffold material according to claim 1, wherein the soaking temperature in the analytically pure alcohol in the step (5) is 30-37 ℃ and the soaking time is 4-6 hours.
8. The preparation method of the graphene oxide/nano-hydroxyapatite composite silica gel modified porous scaffold material according to claim 1, wherein the inert atmosphere in the step (6) is nitrogen or argon.
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