CN113209376A - Normal-temperature neutral preparation method of functional HA/CMCS composite biological ceramic bone scaffold with toughness - Google Patents
Normal-temperature neutral preparation method of functional HA/CMCS composite biological ceramic bone scaffold with toughness Download PDFInfo
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Abstract
The invention provides a normal-temperature neutral preparation method of a functional HA/CMCS composite biological ceramic bone scaffold with toughness, which takes Hydroxyapatite (HA)/carboxymethyl chitosan (CMCS) composite powder and PVA high-molecular aqueous solution as matrix materials and combines the piezoelectric ink-jet printing technology (3DP) and calcium chloride (CaCl)2) The solution is crosslinked and post-treated to prepare the composite biological ceramic bone scaffold which is tough and HAs HA/CMCS. The invention provides a method for realizing normal-temperature neutral manufacturing of a functional HA/CMCS composite bioceramic artificial bone scaffold by taking HA and CMCS composite powder as matrix materials and combining a 3DP printing process for the first time. In addition, the normal-temperature neutral forming characteristic of the preparation method meets the process requirement of cooperative manufacturing of active substances (amino acid, growth factor and active protein), so that the biological ceramic scaffold has the biological functional characteristics endowed by the bioactive substances on the basis of having adjustable material components, mechanical characteristics and pore structures, which is difficult to realize by the conventional process.
Description
Technical Field
The invention relates to the field of biomedical engineering, in particular to a normal-temperature neutral preparation method of a functional HA/CMCS composite biological ceramic bone scaffold with toughness.
Background
The skeleton is one of the important organs of the human body, the excellent self-repairing capability is ensured by the internal complex structure and the dynamic remodeling process, but the self-repairing of the bone can not be realized frequently due to the large-section bone defect caused by external trauma, tumor and the like, and the auxiliary treatment is needed by the bone transplantation operation at the moment. The method is a common clinical treatment method through autologous bone, allogeneic bone or xenogeneic bone transplantation, however, the methods have the problems of limited supply sources, immunological rejection, gene pollution and the like, and the clinical application of the methods is always limited. In recent years, with the development of bone tissue engineering, a new solution is provided for the repair and reconstruction of bone defects by inoculating seed cells cultured in vitro into a porous scaffold, implanting the seed cells into a bone defect, and stimulating the proliferation and differentiation of the seed cells with growth factors to repair the bone tissue defect.
The implanted bone scaffold needs to bear the functions of cell climbing, load bearing, material transportation and the like in a human body, and higher requirements are provided for the biological, mechanical and structural characteristics of the scaffold. The biological characteristics of the scaffold require that the scaffold has good biocompatibility and degradability so as to provide a place for cell adhesion proliferation and growth of new bones; the mechanical properties of the stent require that the stent has enough strength and toughness matched with autologous bones so as to avoid the phenomenon of crushing or stress shielding caused by insufficient or overhigh strength and reduce the possibility of brittle fracture of the stent in a complex mechanical environment in a human body; the structural characteristics of the scaffold require the scaffold to have an open porous structure and interconnected network to ensure the transportation of nutrients and the discharge of metabolic wastes in the scaffold. In order to meet these requirements, researchers are trying to find solutions from material and process aspects.
Hydroxyapatite HA is the main inorganic salt component in bone tissues, HAs high biocompatibility and osteoinductive capacity, and is the most ideal bone repair material. However, fracture toughness of hydroxyapatite: (<1.0MPa·m1/2) And the bending strength (50-100 MPa) is low, and a single HA scaffold can not meet the mechanical requirements of a human bone scaffold, so that the research on the HA composite scaffold is started to improve the performance of the HA composite scaffold. The carboxymethyl chitosan CMCS is a natural alkaline polysaccharide, has excellent biocompatibility, degradability and nontoxicity, and is an excellent bone tissue repair material. Researches find that the CMCS is compounded with phosphate ceramic to improve the mechanical property and the pore structure of the ceramic scaffold to a certain extent, and the composite is beneficial to mineralized substance precipitation and the adhesion and proliferation of osteoblasts and has excellent bone repair potential.
In the existing preparation method of the biological ceramic bone scaffold, the main important difficulty is that in order to meet the strength requirement of the scaffold, high-energy post-treatment such as high-temperature sintering, chemical curing and the like is generally required to be carried out on the prepared bone scaffold, which undoubtedly increases the probability of contamination of the scaffold, and meanwhile, the bone scaffold after high-temperature sintering has no toughness, and cannot realize the cooperative manufacture of active substances.
Disclosure of Invention
The invention provides a normal-temperature neutral preparation method of a functional HA/CMCS composite bioceramic bone scaffold with high toughness, aiming at the contradiction between strength and toughness, bioactive substances and high-energy post-treatment in the existing preparation process of the bone tissue engineering scaffold. The method is based on a 3DP printing process, takes HA/CMCS mixed powder as printing powder and PVA solution as a binder, takes biological active substances as auxiliary materials in the printing process for cooperative manufacture, and finally obtains a forming bracket through calcium chloride solution crosslinking and solidification.
On one hand, the bone scaffold prepared by the process combines the high hardness and the high biocompatibility of the HA material and the high toughness and the biodegradation characteristics of the CMCS material, so that the formed scaffold can keep enough strength and toughness in the degradation process. On the other hand, CMCS endows the scaffold with large-size pores which are highly communicated, contributes to normal proliferation and differentiation of cells, and accelerates invasion and replacement of blood vessels and bone tissues. In addition, the whole process flow is carried out in a normal-temperature neutral environment, and high-energy post-treatment such as high-temperature sintering, chemical curing and the like is not needed, so that the cooperative printing of active substances is guaranteed, the biological characteristics of the bone scaffold are endowed, and the effect of accelerating the repair and reconstruction of bone defects is achieved.
The technical scheme of the invention is as follows:
the normal-temperature neutral preparation method of the functional HA/CMCS composite biological ceramic bone scaffold with toughness is characterized in that hydroxyapatite HA and carboxymethyl chitosan CMCS composite powder, PVA high-molecular aqueous solution and bioactive substances are used as matrix materials, and piezoelectric ink-jet printing technology and CaCl are adopted2The solution cross-linking post-treatment realizes the preparation of the functional HA/CMCS composite biological ceramic bone scaffold with toughness. Due to the use of the HA/CMCS composite powder, the forming support HAs the respective advantages of two materials, and the strength and the toughness are both considered. Meanwhile, the normal-temperature neutral bonding process meets the process requirement of cooperative printing of the bioactive substances, so that the scaffold has the biological functional characteristics endowed by the bioactive substances on the basis of adjustable material components, mechanical properties and structural characteristics, and provides process guidance for the preparation of an ideal bone scaffold.
Further, the normal-temperature neutral preparation method of the functional HA/CMCS composite biological ceramic bone scaffold with toughness specifically comprises the following steps:
step 1: preparing HA and CMCS composite powder, PVA glue and PBS buffer solution containing bioactive substances; wherein the CMCS powder accounts for 1-5% of the composite powder by mass, and the PVA concentration in the PVA glue is 1-3%;
step 2: adding the prepared composite powder into a powder storage cylinder of a three-dimensional printer, and respectively filling the prepared PVA glue and the PBS buffer solution containing the bioactive substances into different ink boxes of the three-dimensional printer;
and step 3: importing the established three-dimensional model of the bone scaffold into a three-dimensional printer, and starting a printing program after setting printing parameters; in the printing process, PVA glue and PBS buffer solution containing bioactive substances are selectively deposited at specific positions of a powder bed of the composite powder to construct a single-layer structure of the support, and then the single-layer structure is continuously printed layer by layer to obtain the whole structure;
and 4, step 4: standing for a period of time after printing is finished, taking out the molded bracket, blowing out excessive powder, drying, and placing the bracket on CaCl2Soaking in PBS buffer solution to make CMCS in the bracket fully cross-linked; and cleaning the bracket by using deionized water, and drying to finally obtain the functional HA/CMCS composite bioceramic artificial bone bracket with certain strength and toughness.
Further, in the step 1, CMCS powder is taken according to the mass fraction of 1-5% and doped in HA powder and mixed uniformly to obtain composite powder.
Further, in the step 1, the PVA high polymer material is weighed according to the mass fraction of 1-3%, dispersed in deionized water, heated in a water bath at the temperature of 90-98 ℃, and stirred until completely dissolved to obtain the PVA glue.
Further, in step 1, a trace amount (about 1. mu.g/ml) of the bioactive substance was dispersed in a PBS buffer solution to prepare a PBS buffer solution containing the bioactive substance.
Furthermore, in the step 1, the carboxylation degree of the CMCS is more than 80%, and the molecular weight range is 2-15 ten thousand.
Further, in the step 1, the HA powder HAs a spherical or needle-shaped powder particle size of 20-80 μm.
Further, in the step 1, the PVA has an average polymerization degree of 1720 to 1770 and an alcoholysis degree of 99.79%.
Further, in step 1, the bioactive substances include but are not limited to fibroblast growth factor, beta-transforming growth factor (TGF-beta), bone morphogenetic protein (BMP-9), and other cell growth factors, and antibiotics or anticancer drugs.
Further, in step 4, the scaffolds were incubated in a medium containing 2% w/v CaCl2In PBS buffer to fully crosslink the CMCS in the scaffold.
Advantageous effects
1. The normal-temperature neutral preparation method of the functional HA/CMCS composite biological ceramic bone scaffold capable of strengthening and reinforcing effectively solves the contradiction between the strength of the scaffold and the biological functional characteristics. The strength of the scaffold is ensured, high-energy post-treatment processes such as high-temperature sintering, chemical curing and the like are avoided, the cooperative manufacturing of bioactive substances in the scaffold is realized, and a novel process method is provided for the manufacturing of the HA/CMCS composite biological ceramic bone scaffold.
2. The bone scaffold prepared by the method HAs the advantages of HA and CMCS, HAs certain strength and toughness and good biocompatibility and degradability, and meets the requirements of clinical mechanical and biological properties. And the 3DP printing process and the incorporation of the CMCS phase realize the controllable manufacture of the pore structure with highly communicated scaffolds, and are beneficial to the invasion of bone tissues and blood vessels into the scaffolds.
3. The synchronous printing of the bioactive substances ensures the precise distribution of the bioactive substances in the specific parts of the bracket, so that the active substances can stably and effectively play a role in the bone repair process, and the bone repair process is accelerated.
Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.
Drawings
The above and/or additional aspects and advantages of the present invention will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which:
fig. 1 is a porous artificial bone scaffold prepared according to an embodiment of the present invention.
Detailed Description
The invention aims at the preparation of the prior bone tissue engineering scaffoldIn the process, the contradiction between the strength and the toughness, the biological active substances and the high-energy post-treatment exists, and the normal-temperature neutral preparation method of the functional HA/CMCS composite biological ceramic bone scaffold with toughness and toughness is provided. The method takes Hydroxyapatite (HA)/carboxymethyl chitosan (CMCS) composite powder and PVA high molecular water solution as matrix materials, and combines the piezoelectric ink-jet printing technology (3DP) and calcium chloride (CaCl)2) The solution is crosslinked and post-treated to prepare the composite biological ceramic bone scaffold which is tough and HAs HA/CMCS. The invention provides a method for realizing normal-temperature neutral manufacturing of a functional HA/CMCS composite bioceramic artificial bone scaffold by taking HA and CMCS composite powder as matrix materials and combining a 3DP printing process for the first time. In addition, the normal-temperature neutral forming characteristic of the preparation method meets the process requirement of cooperative manufacturing of active substances (amino acid, growth factor and active protein), so that the biological ceramic scaffold has the biological functional characteristics endowed by the bioactive substances on the basis of having adjustable material components, mechanical characteristics and pore structures, which is difficult to realize by the conventional process.
The following detailed description of embodiments of the invention is intended to be illustrative, and not to be construed as limiting the invention.
The tough and functional bioceramic artificial bone scaffold is compounded by hydroxyapatite, carboxymethyl chitosan, PVA high-molecular binder and functional active substances. The support specification is the cylinder structure, and diameter 15mm, height 15mm, and the size allowable deviation is 0.5mm, and support inside is full of the square hole structure that link up, and the hole side length is 1 mm.
The specific steps of this example are as follows:
example one (CMCS content 1%):
1. weighing CMCS powder in HA powder according to the proportion that the CMCS powder accounts for 1 percent of the mass fraction of the composite powder, and uniformly mixing the two kinds of powder through mechanical stirring to obtain HA/CMCS composite powder for later use;
2. weighing PVA high molecular material according to the mass fraction of 2 wt%, dispersing the PVA high molecular material in deionized water, heating the PVA high molecular material in a water bath by an electromagnetic stirrer, controlling the temperature to be 90 ℃, and stirring the PVA high molecular material for about 2 hours until the PVA high molecular material is completely dissolved to obtain PVA glue with the mass fraction of 2 wt% for later use;
3. diluting bone morphogenetic protein (BMP-9) solution to 1 μ g/ml by PBS buffer solution to obtain BMP-9 phosphate buffer solution with concentration of 1 μ g/ml for later use;
4. adding the prepared mixed powder into a powder storage cylinder of a three-dimensional printer, and respectively filling the prepared PVA glue and the bioactive substance buffer solution into different ink boxes of the three-dimensional printer;
5. and importing the support model established in the CAD software, and starting a printing program after setting printing parameters. In the printing process, PVA glue and BMP-9PBS buffer solution are selectively deposited at a specific position of the composite powder bed to construct a single-layer structure of the bracket, and then the whole structure is obtained by continuously printing layer by layer;
6. and standing for 3h after printing is finished, and taking out the molded bracket to ensure that the bracket is not damaged in the taking-out process. Blowing off the excess powder with compressed air, drying in a sterile vacuum oven at 37 deg.C for 2 hours, and then drying in a vacuum oven containing 2% w/v CaCl2Soaking in PBS buffer solution for 1h, washing with deionized water after CMCS in the scaffold is fully crosslinked, and fully drying in a sterilization vacuum drying oven at 37 ℃ to finally obtain the HA/CMCS composite bioceramic artificial bone scaffold containing BMP-9.
The porous bone tissue engineering scaffold prepared in the example is shown in fig. 1, and through experimental tests, the overall porosity of the porous bone scaffold prepared in the example is 75.2%; the compressive strength is 6.25MPa, and the impact strength is 3.98KJ/m2。
Example two (CMCS content 3%):
1. weighing CMCS powder in the HA powder according to the mass fraction of 3%, and uniformly mixing the two kinds of powder by mechanical stirring to obtain HA/CMCS composite powder for later use;
2. weighing PVA high molecular material according to the mass fraction of 2 wt%, dispersing the PVA high molecular material in deionized water, heating the PVA high molecular material in a water bath by an electromagnetic stirrer, controlling the temperature to be 94 ℃, and stirring the PVA high molecular material for about 2 hours until the PVA high molecular material is completely dissolved to obtain PVA glue with the mass fraction of 2 wt% for later use;
3. diluting bone morphogenetic protein (BMP-9) solution to 1 μ g/ml by PBS buffer solution to obtain BMP-9 phosphate buffer solution with concentration of 1 μ g/ml for later use;
4. adding the prepared mixed powder into a powder storage cylinder of a three-dimensional printer, and respectively filling the prepared PVA glue and the bioactive substance buffer solution into different ink boxes of the three-dimensional printer;
5. and importing the support model established in the CAD software, and starting a printing program after setting printing parameters. In the printing process, PVA glue and BMP-9PBS buffer solution are selectively deposited at a specific position of the composite powder bed to construct a single-layer structure of the bracket, and then the whole structure is obtained by continuously printing layer by layer;
6. and standing for 3h after printing is finished, and taking out the molded bracket to ensure that the bracket is not damaged in the taking-out process. Blowing off the excess powder with compressed air, drying in a sterile vacuum oven at 37 deg.C for 2 hours, and then drying in a vacuum oven containing 2% w/v CaCl2Soaking in PBS buffer solution for 1h, washing with deionized water after CMCS in the scaffold is fully crosslinked, and fully drying in a sterilization vacuum drying oven at 37 ℃ to finally obtain the HA/CMCS composite bioceramic artificial bone scaffold containing BMP-9.
Experimental tests prove that the overall porosity of the porous bone scaffold prepared in the embodiment is 78.3%; the compressive strength is 8.75MPa, and the impact strength is 6.48KJ/m2。
Example three (CMCS content 5%):
1. weighing CMCS powder in the HA powder according to the mass fraction of 5%, and uniformly mixing the two kinds of powder by mechanical stirring to obtain HA/CMCS composite powder for later use;
2. weighing PVA high molecular material according to the mass fraction of 2 wt%, dispersing the PVA high molecular material in deionized water, heating the PVA high molecular material in a water bath by an electromagnetic stirrer, controlling the temperature to be 98 ℃, and stirring the PVA high molecular material for about 2 hours until the PVA high molecular material is completely dissolved to obtain PVA glue with the mass fraction of 2 wt% for later use;
3. diluting bone morphogenetic protein (BMP-9) solution to 1 μ g/ml by PBS buffer solution to obtain BMP-9 phosphate buffer solution with concentration of 1 μ g/ml for later use;
4. adding the prepared mixed powder into a powder storage cylinder of a three-dimensional printer, and respectively filling the prepared PVA glue and the bioactive substance buffer solution into different ink boxes of the three-dimensional printer;
5. and importing a bracket model established by CAD software, and starting a printing program after setting printing parameters. In the printing process, the binder and the BMP-9PBS buffer solution are selectively deposited at a specific position of the powder bed to construct a single-layer structure of the stent, and then the single-layer structure is continuously printed layer by layer to obtain the whole structure;
6. and standing for 3h after printing is finished, and taking out the molded bracket to ensure that the bracket is not damaged in the taking-out process. Blowing off the excess powder with compressed air, drying in a sterile vacuum oven at 37 deg.C for 2 hours, and then drying in a vacuum oven containing 2% w/v CaCl2Soaking in PBS buffer solution for 1h, washing with deionized water after CMCS in the scaffold is fully crosslinked, and fully drying in a sterilization vacuum drying oven at 37 ℃ to finally obtain the HA/CMCS composite bioceramic artificial bone scaffold containing BMP-9.
Through experimental tests, the overall porosity of the porous bone scaffold prepared in the embodiment is 80.1%; the compressive strength is 9.86MPa, and the impact strength is 7.94KJ/m2。
Example four (pure HA, control):
1. weighing PVA high molecular material according to the mass fraction of 2 wt%, dispersing the PVA high molecular material in deionized water, heating the PVA high molecular material in a water bath by an electromagnetic stirrer, controlling the temperature to be 95 ℃, and stirring the PVA high molecular material for about 2 hours until the PVA high molecular material is completely dissolved to obtain PVA glue with the mass fraction of 2 wt% for later use;
2. diluting bone morphogenetic protein (BMP-9) solution to 1 μ g/ml by PBS buffer solution to obtain BMP-9 phosphate buffer solution with concentration of 1 μ g/ml for later use;
3. adding HA powder into a powder storage cylinder of a three-dimensional printer, and respectively filling the prepared PVA glue and bioactive substance buffer solution into different ink boxes of the three-dimensional printer;
4. and importing the support model established in the CAD software, and starting a printing program after setting printing parameters. In the printing process, the binder and the BMP-9PBS buffer solution are selectively deposited at a specific position of the powder bed to construct a single-layer structure of the stent, and then the single-layer structure is continuously printed layer by layer to obtain the whole structure;
5. and standing for 3h after printing is finished, and taking out the molded bracket to ensure that the bracket is not damaged in the taking-out process. Blowing out redundant powder by using compressed air, and then drying for 2 hours in a sterilization vacuum drying oven at 37 ℃ to obtain the pure HA bioceramic artificial bone scaffold containing BMP-9.
Through experimental tests, the overall porosity of the porous bone scaffold prepared in the embodiment is 68.6%; the compressive strength is 2.37MPa, and the impact strength is 1.06KJ/m2。
Example five (CMCS content 6%, control):
1. weighing CMCS powder in the HA powder according to the mass fraction of 6%, and uniformly mixing the two kinds of powder by mechanical stirring to obtain HA/CMCS composite powder for later use;
2. weighing PVA high molecular material according to the mass fraction of 2 wt%, dispersing the PVA high molecular material in deionized water, heating the PVA high molecular material in a water bath by an electromagnetic stirrer, controlling the temperature to be 90 ℃, and stirring the PVA high molecular material for about 2 hours until the PVA high molecular material is completely dissolved to obtain PVA glue with the mass fraction of 2 wt% for later use;
3. diluting bone morphogenetic protein (BMP-9) solution to 1 μ g/ml by PBS buffer solution to obtain BMP-9 phosphate buffer solution with concentration of 1 μ g/ml for later use;
4. adding the prepared mixed powder into a powder storage cylinder of a three-dimensional printer, and respectively filling the prepared PVA glue and the bioactive substance buffer solution into different ink boxes of the three-dimensional printer;
5. and importing the support model established in the CAD software, and starting a printing program after setting printing parameters. In the printing process, the binder and the BMP-9PBS buffer solution are selectively deposited at a specific position of the powder bed to construct a single-layer structure of the stent, and then the single-layer structure is continuously printed layer by layer to obtain the whole structure;
6. and standing for 3h after printing is finished, and taking out the molded bracket to ensure that the bracket is not damaged in the taking-out process. Blowing off the excess powder with compressed air, drying in a sterile vacuum oven at 37 deg.C for 2 hours, and then drying in a vacuum oven containing 2% w/v CaCl2Soaking in PBS buffer solution for 1h, and washing with deionized water after the CMCS in the stent is fully crosslinkedAnd fully drying in a sterilizing vacuum drying oven at 37 ℃ to finally obtain the HA/CMCS composite bioceramic artificial bone scaffold containing BMP-9.
Through experimental tests, the overall porosity of the porous bone scaffold prepared in the embodiment is 81.5%; the compressive strength is 7.43MPa, and the impact strength is 6.35KJ/m2。
The high-strength bioceramic bionic bone scaffold prepared by the method has a large number of highly-communicated microporous structures, and the porosity, compressive strength and impact strength of the scaffolds with different CMCS contents can be respectively measured by a liquid displacement method, a universal mechanical testing machine and a drop hammer impact method, and are shown in Table 1. The increase of the CMCS content of the bracket can be seen, the porosity, the compressive strength and the impact strength of the bracket are all increased, which shows that the method meets the requirements of the bracket on large porosity and simultaneously satisfies the balance of the bracket strength and toughness, so that the bracket has good structure and mechanical properties. The result of determining the promotion effect of the scaffold on the osteogenic differentiation of the rat bone marrow mesenchymal stem cells shows that the activity of the BMP-9 is represented, and the result shows that the bioactivity of the BMP-9 is good, thereby meeting the biological function requirement of the scaffold.
TABLE 1 porosity and mechanical Properties of scaffolds with different composite powder component ratios
Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention, and that variations, modifications, substitutions and alterations can be made in the above embodiments by those of ordinary skill in the art without departing from the principle and spirit of the present invention.
Claims (10)
1. A normal-temperature neutral preparation method of a functional HA/CMCS composite biological ceramic bone scaffold with toughness is characterized by comprising the following steps: hydroxyapatite HA and carboxymethyl chitosan CMCS composite powder, PVA high molecular water solution and bioactive substances are taken as matrix materialsMaterial, by piezo ink-jet printing technique and CaCl2The solution cross-linking post-treatment realizes the preparation of the functional HA/CMCS composite biological ceramic bone scaffold with toughness.
2. A normal-temperature neutral preparation method of a functional HA/CMCS composite biological ceramic bone scaffold with toughness is characterized by comprising the following steps: the method comprises the following steps:
step 1: preparing HA and CMCS composite powder, PVA glue and PBS buffer solution containing bioactive substances; wherein the CMCS powder accounts for 1-5% of the composite powder by mass, and the PVA concentration in the PVA glue is 1-3%;
step 2: adding the prepared composite powder into a powder storage cylinder of a three-dimensional printer, and respectively filling the prepared PVA glue and the PBS buffer solution containing the bioactive substances into different ink boxes of the three-dimensional printer;
and step 3: importing the established three-dimensional model of the bone scaffold into a three-dimensional printer, and starting a printing program after setting printing parameters; in the printing process, PVA glue and PBS buffer solution containing bioactive substances are selectively deposited at specific positions of a powder bed of the composite powder to construct a single-layer structure of the support, and then the single-layer structure is continuously printed layer by layer to obtain the whole structure;
and 4, step 4: standing for a period of time after printing is finished, taking out the molded bracket, blowing out excessive powder, drying, and placing the bracket on CaCl2Soaking in PBS buffer solution to make CMCS in the bracket fully cross-linked; and cleaning the bracket by using deionized water, and drying to finally obtain the functional HA/CMCS composite bioceramic artificial bone bracket with certain strength and toughness.
3. The normal-temperature neutral preparation method of the functional HA/CMCS composite biological ceramic bone scaffold with toughness as claimed in claim 2, is characterized in that: in the step 1, CMCS powder is taken according to the mass fraction of 1-5% and is doped into HA powder and is uniformly mixed, and composite powder is obtained.
4. The normal-temperature neutral preparation method of the functional HA/CMCS composite biological ceramic bone scaffold with toughness as claimed in claim 2, is characterized in that: in the step 1, a PVA high polymer material is weighed according to the mass fraction of 1-3%, dispersed in deionized water, heated in a water bath at the temperature of 90-98 ℃, and stirred until completely dissolved to obtain the PVA glue.
5. The normal-temperature neutral preparation method of the functional HA/CMCS composite biological ceramic bone scaffold with toughness as claimed in claim 2, is characterized in that: in step 1, a trace amount of bioactive substances are dispersed in a PBS buffer solution to prepare the PBS buffer solution containing the bioactive substances.
6. The normal-temperature neutral preparation method of the functional HA/CMCS composite biological ceramic bone scaffold with toughness as claimed in claim 2, is characterized in that: in the step 1, the carboxylation degree of CMCS is more than 80%, and the molecular weight range is 2-15 ten thousand.
7. The normal-temperature neutral preparation method of the functional HA/CMCS composite biological ceramic bone scaffold with toughness as claimed in claim 2, is characterized in that: in the step 1, the HA powder HAs a particle size of spherical or acicular powder of 20-80 μm.
8. The normal-temperature neutral preparation method of the functional HA/CMCS composite biological ceramic bone scaffold with toughness as claimed in claim 2, is characterized in that: in the step 1, the average polymerization degree of PVA is 1720-1770, and the alcoholysis degree is 99.79%.
9. The normal-temperature neutral preparation method of the functional HA/CMCS composite biological ceramic bone scaffold with toughness as claimed in claim 2, is characterized in that: in step 1, the bioactive substances include, but are not limited to, fibroblast growth factor, beta-transforming growth factor, bone morphogenetic protein, and antibiotics or anticancer drugs.
10. The normal-temperature neutral preparation method of the functional HA/CMCS composite biological ceramic bone scaffold with toughness as claimed in claim 2, which is characterized in thatIn the following steps: in step 4, the scaffolds were incubated in a medium containing 2% w/v CaCl2In PBS buffer to fully crosslink the CMCS in the scaffold.
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