CN111070376A

CN111070376A - 3D printing bionic porous bioceramic artificial bone and preparation method thereof

Info

Publication number: CN111070376A
Application number: CN201911358387.7A
Authority: CN
Inventors: 曾庆丰; 李建宾; 魏静; 杨彦召; 杨智宇; 益明星
Original assignee: Xi'an Particle Cloud Biotechnology Co ltd
Current assignee: Xi'an Particle Cloud Biotechnology Co ltd
Priority date: 2019-12-25
Filing date: 2019-12-25
Publication date: 2020-04-28
Anticipated expiration: 2039-12-25
Also published as: CN111070376B

Abstract

The invention discloses a 3D printing bionic porous bioceramic artificial bone and a preparation method thereof, wherein a porous bioceramic artificial bone model is designed by adopting a TPMS combined CSG method, printable slurry is prepared by adopting bioceramic powder and a binder, and a 3D silk-free printing process is combined, macro pores and micro pores are distributed in the prepared porous bioceramic artificial bone, the pore diameter of the micro pores is less than 100 mu m, and the pore diameter of the macro pores is 200-800 mu m; the total porosity is 20-80%, the communication rate among macro pores is not lower than 99%, the precise design of the porosity, the communication and the uniformity in the artificial bone is realized, and meanwhile, the good pore communication is ensured; the adopted raw materials have good biocompatibility, the macro pores provide channels for cells and interstitial fluid to enter, the micropores better adsorb nearby interstitial fluid for cell growth, and the combination of the micropores and the macro pores can improve the speed of cell growth and new bone generation, thereby being beneficial to the application of the porous bioceramic artificial bone in the clinical treatment of repair of large-section bone defects of human bodies.

Description

3D printing bionic porous bioceramic artificial bone and preparation method thereof

Technical Field

The invention belongs to the field of bone repair materials, and particularly relates to a 3D printing bionic porous bioceramic artificial bone and a preparation method thereof.

Background

In the treatment of orthopedic disorders, the problem of bone defect repair caused by trauma, infection, tumor resection, osteomyelitis and the like has been one of the problems in the field. At present, artificial bones or bone grain materials are generally used for filling and treating small-size defect parts clinically, and for repairing large-scale bone defects, particularly large-section bones of limbs, autologous bones, allogeneic bones or xenogeneic bones are transplanted to defect parts in patients. However, the source of autogenous bone is very limited, and the practice of repairing the west wall for the east wall will cause more trauma to the patient. The transplantation of the allogeneic bone or the xenogeneic bone has the serious problems of high infection rate, rejection reaction and the like, and the two conditions greatly limit the clinical popularization and application of the allogeneic bone or the xenogeneic bone. The artificial bone is less used for repairing large-size or large-section bone defects of limbs clinically at present, mainly because the artificial bone is difficult to meet the regulation and control requirements of various aspects such as process preparation, biomechanics and the like in the aspects of forming characteristics, mechanical properties, pore structures and the like, and the existing artificial bone has unsatisfactory effects in promoting osteoblast differentiation and bone ingrowth. Therefore, the defect repair of large-size bones with large limbs is an international problem which troubles the field of orthopedic clinical repair.

In order to solve the problem, Bonfield et al proposed a bionic artificial bone concept in 1980, namely an inorganic bioceramic reinforced organic polymer composite material. Since then, biomimetic artificial bones have become one of the hot research directions in the field of biomaterials. A variety of artificial bone products having different compositions and characteristics are also emerging on the medical market. However, because of the conventional preparation methods, such as a gas foaming method, a pore-forming agent adding method, a particle sintering method and an organic foam impregnation method, although artificial bones with different pore sizes and porosities can be manufactured, the regulation and control of parameters such as pore size, pore interconnectivity and pore space trend are lacked, that is, only rough and macroscopic control of parameters such as porosity and pore size can be realized, key parameters such as form, size and distribution of pores are difficult to quantitatively and accurately regulate, the bionic requirement of mutual connectivity among micropores is difficult to realize, the optimization and improvement design of a microscopic three-dimensional space geometric configuration is difficult to realize, and meanwhile, the bionic porous artificial bones with integrated macro-microstructure are difficult to manufacture.

The analysis shows that the existing bionic artificial bone composite material is similar to natural bone in composition, but has larger difference in microstructure. Therefore, in order to make the performance of the artificial bone approach or reach the level of natural bone, in addition to the biomimetic composition, the microstructure biomimetic is also required, and the core of the latter is the biomimetic grain geometry, the biomimetic gradient pore and the biomimetic macroscopic appearance.

Disclosure of Invention

In order to solve the problems in the prior art, the invention provides a 3D printing bionic porous bioceramic artificial bone and a preparation method thereof, wherein a bioceramic artificial bone model with a porous structure is designed by combining TPMS (thermoplastic Periodic minimum surface) and CSG (structural solid geometry), printable slurry is prepared by adopting bioceramic powder and a binder, and a 3D filament-free printing process is combined to prepare the porous bioceramic artificial bone with excellent mechanical properties, and meanwhile, the bionic porous bioceramic artificial bone with bionic calcium-phosphorus ceramic components, bionic grain geometric structures and bionic gradient pores is realized, so that the clinical application of the artificial bone in repairing large bones of four limbs is facilitated.

In order to achieve the purpose, the invention adopts the technical scheme that the method for designing the bionic porous artificial bone model by combining TPMS and CSG comprises the following steps:

s11, obtaining a bone defect solid model: (1) directly modeling by adopting CAD software to obtain a standard component entity model, and storing the standard component entity model as an STL format file; (2) acquiring fault DICOM data of a bone defect part of a patient by using a medical image technology, performing three-dimensional reconstruction on the fault DICOM data, acquiring a bone defect solid model with a matched form by design, and storing the bone defect solid model as an STL format file;

s12, designing a curved surface unit configuration by using a TPMS or CAD method, defining the porosity as 20-80%, and exporting a curved surface unit configuration file in an OBJ format, wherein the unit configuration comprises a G curved surface unit configuration, a P curved surface unit configuration and an R curved surface unit configuration;

s13, adjusting the surface normal direction and the boundary of a closed isosurface of the OBJ-format curved surface unit configuration file obtained in the S12, and scaling the curved surface unit configuration model in the S12 to a design size in an equal proportion according to the size parameters of the S11 bone defect entity model to obtain a curved surface unit configuration with a target size;

s14, arraying and combining the curved surface unit configurations obtained in the S13 to obtain a combined body, enabling the size of the combined body to be larger than that of the bone defect solid model, and completely wrapping the bone defect solid model;

and S15, registering the bone defect solid model obtained in the S11 and the combined body obtained in the S14 by using a CSG design method, adjusting the positions of the bone defect solid model obtained in the S11 and the combined body obtained in the S14, performing intersection operation on the bone defect solid model and the combined body to obtain the porous artificial bone model taking the curved surface unit configuration as the basic unit, and exporting the porous artificial bone model in an STL format file.

In S12, the porous artificial bone model adopts a gradient porous structure of uniform porosity or bionic bone.

A bionic porous bioceramic artificial bone is characterized in that a porous artificial bone model with a curved surface unit configuration as a basic unit is obtained by adopting TPMS combined CSG design and is prepared by adopting a 3D filament-free printing process; macro pores and micro pores are distributed in the porous bioceramic artificial bone, the pore diameter of each micro pore is less than 100 micrometers, and the pore diameter of each macro pore is 200-800 micrometers; the total porosity is 20-80%, and the communication rate among macro pores is not less than 95%.

The porous bioceramic artificial bone has a uniform porous or bionic bone gradient porous structure.

A preparation method of a bionic porous bioceramic artificial bone, which comprises the following steps,

s21, preparing a binder;

s22, uniformly mixing the biological ceramic powder and the binder obtained in the step S21 according to mass fraction to obtain slurry, putting the slurry into a dispensing syringe, and defoaming to obtain uniform printable slurry, wherein the biological ceramic powder comprises one or a mixture of more of hydroxyapatite, β -tricalcium phosphate, calcium silicate and bioglass;

s23, loading the porous bioceramic artificial bone model file into the bioceramic 3D printer, and loading the uniform printable slurry into a feed inlet of the bioceramic 3D printer; setting printing parameters, and starting a biological ceramic 3D printer for printing; stacking and forming layer by layer to obtain a porous bioceramic artificial bone primary blank with the aperture larger than 200 mu m;

s24, freeze-drying the porous bioceramic artificial bone blank obtained in the step S23 to remove water, and obtaining the porous bioceramic artificial bone with the porosity of 20% -80%, the micropore diameter of which is less than 100 microns, and the macropore diameter of which is 200 microns-800 microns;

s25, packaging and sterilizing to obtain the bionic porous bioceramic artificial bone product.

In S21, the binder is one or more of polyvinyl alcohol, polyvinyl pyrrolidone, chitosan and collagen.

In S21, the PVA used in the binder and purified by recrystallization of PVA has a purity and alcoholysis degree of not less than 99.5%.

S22, the printable slurry obtained by the method comprises the following components in percentage by mass: 30-90% of biological ceramic powder, 2-8% of binder and the balance of water.

The outer surface of the freeze-dried porous bioceramic artificial bone is deposited with a degradable membrane in a vapor phase mode, the thickness of the degradable membrane is gradually thickened from the edge to the center, the thickness is uniformly thickened from 50 micrometers to 300 micrometers, and chitosan is used as a raw material of the degradable membrane.

And (3) performing cross-linking treatment on the porous bioceramic artificial bone blank or the freeze-dried porous bioceramic artificial bone.

Compared with the prior art, the invention has at least the following beneficial effects:

according to the invention, through a design method of TPMS combined with CSG, the precise design of the porosity, the connectivity and the uniformity of a macro-pore structure in an artificial bone is realized, so that not only can a standard type porous bioceramic artificial bone model be obtained, but also a personalized porous bioceramic artificial bone model can be realized through a digital design technology according to medical images; according to the invention, the biological ceramic powder and the binder are reasonably proportioned, and the porous biological ceramic artificial bone is prepared by adopting a 3D printing process, so that good forming characteristics, mechanical properties and pore structure can be ensured, pores which are accurately controlled in the manufacturing process can be realized, the pore distribution, pore size and shape can be controlled, and the porous structure can provide a proper microenvironment, i.e. a physical and biochemical stimulation and nutrition conveying channel is provided for the growth and the function exertion of cells.

Furthermore, the invention designs the porous bioceramic artificial bone model with the gradient structure, the interior of the porous bioceramic artificial bone model is similar to cancellous bone of human bone, the position close to the surface of the porous bioceramic artificial bone model is similar to cortical bone of human bone, and the porous bioceramic artificial bone model has better bionic performance.

The porous bioceramic artificial bone model is designed based on a TPMS combined CSG method, printable bioceramic slurry is prepared by adopting bioceramic powder and a binder, and finally the porous bioceramic artificial bone is prepared by a bioceramic 3D printer and has 20-80% of pores, and the adopted raw materials have good biocompatibility and biodegradability; the surface porous structure can also promote the composition between the bracket and the surrounding tissues so as to improve the mechanical stability of the implant, and the network structure of pores is beneficial to guiding and promoting the formation of new tissues and improving the efficacy of the artificial bone in bone defect repair; the invention provides an implementation scheme for repairing the defect of the artificial bone in the large bone segments of the four limbs, and is beneficial to clinically applying the porous bioceramic artificial bone to repair the defect of the large bone segments of the human body.

Furthermore, the invention adopts purified PVA as the binder; the generation of bubbles can be reduced in the material mixing process, and after the 3D printing of the artificial bone is completed, the strength of the artificial bone is 20-30% higher than that of the artificial bone printed by PVA which is not subjected to recrystallization purification processing.

Furthermore, a small amount of polyvinyl pyrrolidone (PVP) is added into the polyvinyl alcohol binder, so that the binding property can be improved, a flow increasing agent effect can be achieved, the spray head is prevented from being blocked in the printing process, a polyvinyl pyrrolidone (PVP) solution is used as an auxiliary binder, and a mixed solution of PVA and PVP is used as a binder to better meet the printing binding property, so that the printing slurry cannot be agglomerated and has good printing forming property.

Furthermore, after the printing of the artificial bone is finished, a layer of degradable membrane with gradually changed thickness is deposited on the surface of the artificial bone, so that the strength in the artificial bone implant can be optimized, and the release speed after carrying the medicine is reduced; the membrane layer is thin or an uncovered area firstly degrades to release the medicine, the area with the thicker thickness releases the medicine, the time of medicine release can be accurately controlled by controlling the thickness of the membrane layer, the problem that the medicine release speed of a common artificial bone is too fast or the release time can not be controlled is solved, the membrane layer can isolate moisture to a certain extent, the strength of the artificial bone after meeting water can be maintained, and the service performance of the artificial bone is obviously enhanced.

Furthermore, the strength of the porous bioceramic artificial bone can be effectively improved by performing cross-linking treatment on the porous bioceramic artificial bone.

Drawings

FIG. 1 is a flow chart of the process for preparing the artificial bone of the present invention.

Fig. 2a is a bone defect solid model, fig. 2b is a schematic diagram of array combination of the R-surface unit configuration, and fig. 2c is a schematic diagram of an individualized bone defect model with the R-surface unit configuration as a basic unit.

Figure 3a is a schematic illustration of a P surface element configuration,

figure 3b is a schematic diagram of the configuration of the G-shaped surface unit,

FIG. 3c is a schematic view of the configuration of the R-shaped surface unit

FIG. 4a is a schematic representation of the porosity of 40% in the R-surface unit configuration,

FIG. 4b is a schematic representation of the porosity of 50% for the R-surface unit configuration,

figure 4c is a schematic representation of a porosity of 60% for the R-surface unit configuration,

FIG. 5 is a macroscopic picture of the porous bioceramic artificial bone prepared in example 1 of the present invention,

FIG. 6 shows the microstructure of the artificial bone made of porous bioceramic obtained in example 1 of the present invention,

FIG. 7 is a scanning electron microscope image of the artificial bone made of porous bioceramic obtained in example 1 of the present invention,

FIG. 8 is a hard tissue slice of a porous bioceramic artificial bone prepared in example 1 of the present invention implanted in a beagle dog for 12 weeks,

FIG. 9 is a schematic view of a porous bioceramic artificial bone model with a gradient structure and R-shaped surface units as basic units,

FIG. 10 is a diagram of a porous bioceramic artificial bone object prepared in example 3 of the present invention.

Detailed Description

The present invention will be described in detail below with reference to the following detailed description and the accompanying drawings.

The bionic porous bioceramic artificial bone has a multi-scale internal pore structure, internal pores are communicated in a three-dimensional mode, and a biological microenvironment with a good growth channel and space can be provided for osteoblasts; the three-dimensional continuous pores, proper pore size and high porosity are beneficial to the absorption of nutrient substances and the discharge of metabolic waste, and the osteogenic activity of the artificial bone in vivo is enhanced.

The bionic artificial bone with a porous structure can be prepared by combining a design method of TPMS (Triply Periodic Minimal surface) and CSG (structured solid geometry) and a silkless 3D printing process; the TPMS curved surface has periodicity in 3 independent directions in a three-dimensional space, and is a minimized curved surface. By changing mathematical function parameters describing the TPMS curved surface, the porosity and the pore size can be accurately adjusted, the gradient structure design can be realized, and meanwhile, good pore connectivity is ensured; by combining with a CSG design method, the invention preferably adopts a CAD to realize the CSG design method, can obtain an artificial bone model with accurately controllable external form and internal structure, realizes the regulation and control of the mechanical property of a pore unit structure, ensures that the artificial bone structure has similar biomechanical property with surrounding tissues, and can design an artificial bone model with gradient according to the characteristics of human bones, namely an internal spongy bone model, which is a structure close to a surface cortical bone layer, and figures 9a, 9b and 9c are respectively schematic diagrams of porous bioceramic artificial bone models which are designed by the invention and have different gradient structures by taking R curved surface unit configuration as a basic unit.

Referring to fig. 2a, 2b and 2c, the method for designing artificial bone structure by using TPMS and CSG includes the following steps:

s12, designing a unit configuration by using a TPMS or CAD method, defining the porosity as 20-80%, and exporting a curved surface unit configuration file in an OBJ format, wherein the curved surface unit configuration comprises a G curved surface unit configuration, a P curved surface unit configuration and an R curved surface unit configuration; different types of surface unit configurations are shown in fig. 3a, 3b and 3c, respectively, and R surface unit configurations with different porosities are shown in fig. 4a, 4b and 4 c;

s13, adjusting the boundary of the normal direction and the closed isosurface of the surface of the curved surface unit configuration file in the OBJ format obtained in the S12, and scaling the curved surface unit configuration model in the S12 to a design size in an equal proportion according to the size parameters of the S11 bone defect solid model to obtain a unit configuration with a target size;

The invention designs a porous artificial bone model with accurately controllable external form and internal structure based on TPMS combined CSG, and prepares the porous bioceramic artificial bone capable of being used for repairing the defects of the large bones of the limbs by adopting a bioceramic 3D printer by combining the structure of the porous artificial bone model, the proportion of hydroxyapatite, β -tricalcium phosphate, calcium silicate, bioglass and a binder.

Preferably, the purified PVA is used, the PVA with the purity and alcoholysis degree of more than 99.5% is adopted, the generation of bubbles can be reduced in the material mixing process, the strength of the artificial bone is 20% -30% higher than that of the artificial bone printed by the PVA which is not processed by recrystallization purification after the 3D printing of the artificial bone is finished, and the prepared porous bioceramic artificial bone has excellent mechanical property.

The porous bioceramic artificial bone is prepared by a 3D printing process, and after preparation and forming, the surface of the porous bioceramic artificial bone is further treated by a post-treatment process;

the method comprises the steps of carrying out vapor deposition on a layer of degradable film with gradually changed thickness on the porous bioceramic artificial bone after printing is finished, carrying out physical vapor deposition on a degradable multilayer film with gradually changed thickness consisting of chitosan, degrading and releasing the medicine in an area with thin film thickness or uncovered area, releasing the medicine in an area with thicker thickness, controlling the film thickness to accurately control the time of medicine release, and obviously enhancing the service performance of the artificial bone.

The biological ceramic 3D printing process can process the artificial bone with a complex shape and the internal pore structure thereof, and the macroscopic and microscopic structures of the processed porous biological ceramic artificial bone are similar to the design model, so that the uniform molding can be realized, and the gradient structure designed by the model can be realized.

The invention takes Hydroxyapatite (HA), β -tricalcium phosphate (β -TCP), calcium silicate and Bioglass (BG) biomaterial powder as a base material for 3D biological printing and forming, prepares a binder which is matched with the base material, meets the requirement of binding performance and is harmless to human bodies, adopts one or more of polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP), Chitosan (CS) and collagen as the binder, and the binder is safe and nontoxic and HAs no pollution to the inorganic biomaterial.

According to the invention, a silk-free 3D printing process is selected to realize the porous biological ceramic artificial bone with a porous and gradient structure; the porous bioceramic artificial bone prepared by the silk-free printing technology shows a honeycomb structure inside, the section of a bone trabecula has a plurality of fine pore structures with the diameter less than 100 mu m, and the appearance of the bone trabecula is similar to that of human cancellous bone; through detection, the porosity of the porous material is close to the porosity parameter set by theory, and the pores are well communicated, so that the creeping growth of cells and the diffusion of nutrient substances, metabolic wastes and oxygen are facilitated.

The following examples are based on the technical solution of the present invention:

example 1:

s1, preparation of aqueous PVA (polyvinyl alcohol): dissolving 4g of polyvinyl alcohol powder in 46g of water for injection, and stirring for 1.5h at the constant temperature of 95 ℃ by using a magnetic stirrer to prepare a polyvinyl alcohol aqueous solution with the mass fraction of 8%; centrifuging the solution twice by a centrifuge at a rotation speed of 3000rad/min for 5 min/time, and removing impurities to obtain a uniform and transparent solution;

s2, preparing the biological ceramic powder, namely weighing 33.57g of hydroxyapatite powder and 22.38g of β tricalcium phosphate powder, and uniformly mixing the weighed materials to obtain uniform biological ceramic powder, wherein the mass ratio of the hydroxyapatite to the β tricalcium phosphate is 3: 2;

s3, putting 52.8% of the biological ceramic powder obtained in the S2 and 47.2% of the polyvinyl alcohol solution obtained in the S1 into a homogenizer by mass fraction, firstly premixing for 1min at 800rad/min, then uniformly mixing for 4 times at a rotating speed of 2000rad/min, stirring for 1min each time, putting the uniformly mixed slurry into a dispensing syringe, and defoaming for 6 times by using a defoaming machine to obtain uniform printable slurry;

s4, designing the artificial bone structure by combining TPMS and CSG, which comprises the following steps:

s41, acquiring fault DICOM data of a patient bone defect part by using a medical image technology, importing the data into 3D digital radiography (3D digital radiography) software for three-dimensional reconstruction, acquiring a bone defect entity model with a form matching through design, and storing a file format as STL;

s42, designing an R curved surface unit configuration by using a TPMS method or CAD software, setting the porosity to be 80%, and exporting the configuration in an OBJ format;

s43, importing the OBJ file into FreeCAD software for further processing, adjusting the boundary of a normal and closed isosurface, and scaling the unit model to a target size in an equal proportion according to the size parameters of the S41 bone defect solid model;

s44, in FreeCAP software, array combination is carried out on the unit configuration obtained in the S43, so that the size of the combined body after array is larger than that of the bone defect solid model, and the bone defect solid model can be completely surrounded;

s45, importing the STL file obtained in S41 into FreeCAD software by a CSG design method, adjusting the position of the combination body obtained in S44, and performing intersection operation on the STL file and the combination body to obtain a porous bioceramic artificial bone model taking an R curved surface configuration as a basic unit, wherein the model is exported in an STL format;

s5, installing the slurry pipe at the feed inlet of the biological ceramic 3D printer, leading the model into PCPrinter MF150 software for slicing and layering, setting printing parameters, and printing and forming through the printer;

and S6, freeze-drying the printed matter by using a freeze dryer, and removing water to form micropores. Pre-freezing for 6 hours at minus 50 ℃, slowly heating up to minus 30 ℃ to minus 10 ℃ at intervals of 5 ℃, carrying out first-stage freeze drying for 6 hours, carrying out heat preservation drying for 3 hours at 0 ℃ to 10 ℃, carrying out resolution drying at 30 ℃ and keeping the temperature constant for more than 3 hours, carrying out double-layer packaging after freeze drying is finished, and carrying out irradiation sterilization to obtain the porous bioceramic artificial bone finished product.

The porous bioceramic artificial bone obtained in the embodiment has the advantages that the macroscopic morphology can be matched in a personalized manner, the pore size and the porosity are controllable, the pore passages are communicated, and the structure strength and the biological performance are good, as shown in fig. 5 and 6, the surface of the porous bioceramic artificial bone is provided with a porous structure which is communicated with each other, the structure is realized in a 3D printing mode, the size of the macroscopic porous structure is larger than 100 micrometers, as shown in fig. 6, a large number of capillary micropores are distributed on the wall of the macroscopic pore, the micropores are mainly formed by leaving vacancies through freeze-drying moisture as shown in fig. 7, and the multi-scale pore structure not only conforms to the growth and migration of bone cells, is favorable for the adhesion of the bone cells, but also provides favorable conditions for the transportation of nutrient substances and metabolites.

After the prepared porous bioceramic artificial bone is implanted into a beagle dog for 12 weeks, hard tissue slicing is performed, Van Gieson staining is performed, and the result is shown in FIG. 8, wherein FIG. 8 shows that a plurality of newly formed bones grow into macro pores of the porous bioceramic artificial bone prepared by the invention, more callus (red) is formed in the implanted porous bioceramic artificial bone, a large amount of newly formed bone tissues (red) are observed in macro pores and pores of the porous bioceramic artificial bone printed by 3D, and the formation of new bones is obvious; more matrix cells and fibrous tissues are distributed in the central area and micropores of the porous bioceramic artificial bone. Inflammatory cell infiltration is not found at the interface of the implanted porous bioceramic artificial bone, foreign body reaction does not exist in the surface implant, the porous bioceramic artificial bone prepared by the method is proved to have good biocompatibility, and animal test results prove that the artificial bone prepared by the method can promote the healing of critical-size bone defects and has good in-vivo bone formation promoting effect.

Example 2:

s1, dissolving 4g of polyvinyl alcohol powder in 46g of water for injection, stirring for 1.5h at a constant temperature of 95 ℃ by using a magnetic stirrer to prepare a polyvinyl alcohol aqueous solution with the mass fraction of 8%, centrifuging the solution twice by using a centrifugal machine at a rotating speed of 3000rad/min for 5 min/time, and removing impurities to obtain a uniform and transparent solution;

s2, weighing 30g of calcium silicate powder and 30g of β tricalcium phosphate powder, and uniformly mixing the calcium silicate powder and the β tricalcium phosphate powder to obtain uniform bioceramic powder, wherein the mass ratio of calcium silicate to β -tricalcium phosphate is 1: 1;

s3, putting 52.8% of the bioceramic powder obtained in the S2 and 47.2% of polyvinyl alcohol solution obtained in the S1 into a homogenizer by mass fraction, firstly premixing for 1min at 800rad/min, then uniformly mixing for 4 times at a speed of 2000rad/min, stirring for 1min each time, putting the uniformly mixed slurry into a dispensing syringe, and defoaming for 6 times by using a defoaming machine to obtain uniform printable slurry;

s4, designing the artificial bone structure by adopting the TPMS and CSG combined method, which comprises the following steps:

s41, directly modeling by adopting CAD software to obtain a porous artificial bone model, and storing the porous artificial bone model as an STL format file;

s42, designing a P curved surface unit configuration by utilizing a TPMS method in OCTAVE software, setting the porosity to be 60%, and exporting the configuration in an OBJ format;

and S43, importing the OBJ file into FreeCAD software for further processing, and adjusting the boundary of the isosurface normal and closed. Scaling the unit structural model to a target size in an equal proportion according to the size parameters of the S41 bone defect solid model;

s45, introducing the STL file obtained in S41 into FreeCAD by a CSG design method, adjusting the position of the combination obtained in S44, and performing intersection operation on the STL file and the combination to obtain a porous artificial bone model taking a P curved surface configuration as a basic unit, wherein the model file is exported in an STL format;

s5, installing the slurry pipe at the feed inlet of the biological ceramic 3D printer, importing the model file into PCPrinterMF150 software for slicing and layering, setting printing parameters, and printing an artificial bone primary blank by the printer;

s6, freeze-drying the artificial bone blank obtained in the step S5 by a freeze-drying machine, removing water to form micropores, specifically, pre-freezing for 6 hours at-50 ℃, slowly raising the temperature at 5 ℃ intervals, carrying out first-stage freeze-drying for 6 hours at-30 ℃ to-10 ℃, carrying out heat preservation and drying for 3 hours at 0-10 ℃, carrying out resolution drying at 30 ℃ and keeping the temperature for more than 3 hours, and after freeze-drying, carrying out double-layer packaging and irradiation sterilization to obtain the finished product of the porous bioceramic artificial bone.

The porous bioceramic artificial bone obtained by the embodiment has controllable pore diameter and porosity, and has communicated pore channels, good structural strength and biological performance.

Example 3

S1, preparing a polyvinyl alcohol aqueous solution: dissolving polyvinyl alcohol powder in water for injection to obtain a polyvinyl alcohol aqueous solution with the mass fraction of 8%, stirring the polyvinyl alcohol aqueous solution on a magnetic stirrer at the constant temperature of 95 ℃ for 1.5h, and centrifuging the polyvinyl alcohol aqueous solution twice by using a centrifuge at the rotating speed of 3000rad/min for 5min each time to remove impurities to obtain a uniform and transparent solution;

s2, putting 52.8% of bioceramic powder and 47.2% of polyvinyl alcohol solution obtained in the step S1 into a homogenizer, premixing for 1min at the rotating speed of 800rad/min, stirring for 4 times and uniformly mixing for 1min each time at the rotating speed of 2000rad/min, putting the uniformly mixed slurry into a dispensing syringe, defoaming for 6 times by using a defoaming machine to obtain uniform printable slurry, wherein the mass ratio of calcium silicate to β -tricalcium phosphate in the bioceramic powder is 1: 1;

s3, designing a porous bioceramic artificial bone model with an R curved surface configuration as a basic unit by using a TPMS combined CSG method, and exporting a bone model file to be printed in an STL format;

s31, acquiring fault DICOM data of a bone defect part of a patient by using the medical image, importing the data into 3D Scriber software for three-dimensional reconstruction to obtain a bone defect solid model with a form matching, and storing the file format as STL;

s32, designing an R curved surface unit configuration by using a TPMS method or CAD software, setting the porosity to be 65%, and exporting the configuration in an OBJ format;

s33, importing the OBJ file into FreeCAD software to adjust the surface normal direction and close the boundary of the isosurface, and scaling the unit structural model to the target size in an equal proportion according to the size parameters of the S31 bone defect solid model;

s34, in FreeCAP software, array combination is carried out on the unit configuration obtained in the S33, so that the size of the assembly after array is larger than that of the bone defect solid model, and the assembly completely surrounds the bone defect solid model;

s35, importing the STL file obtained in the S31 into FreeCAD software, adjusting the position of the combination body obtained in the S31 and the combination body obtained in the S34, performing intersection operation on the combination body and the combination body to obtain a porous artificial bone model taking an R curved surface configuration as a basic unit, and exporting the model in an STL format;

and S4, mounting the uniform slurry printable material pipe obtained in the S2 at the feed inlet of the biological ceramic 3D printer, loading the bone model file to be printed obtained in the S3 into the biological ceramic 3D printer, adjusting printing parameters, and stacking and forming layer by layer to obtain the designed porous biological ceramic artificial bone primary blank with regular macro pores.

S5, placing the porous bioceramic artificial bone blank formed in the S4 into a freeze dryer for freeze drying to remove water, forming micropores, pre-freezing for 6 hours at-50 ℃, slowly heating at-30 ℃ to-20 ℃ at intervals of 5 ℃, carrying out first-stage freeze drying for 6 hours, carrying out heat preservation drying for 3 hours at 0-10 ℃, carrying out resolution drying at 30 ℃ and keeping the temperature for more than 3 hours; and then carrying out double-layer packaging and irradiation sterilization to obtain a porous bioceramic artificial bone finished product, wherein the porosity of the artificial bone finished product is 65%, as shown in figure 10.

Example 4

s2, print powder preparation: weighing 20g of hydroxyapatite powder and 30g of biological glass powder, and uniformly mixing the hydroxyapatite powder and the biological glass powder to obtain uniform printing powder; namely, the mass ratio of the hydroxyapatite to the bioglass is 2: 3;

s3, putting 52.8% of printing powder obtained in the S2 and 47.2% of polyvinyl alcohol solution obtained in the S1 into a homogenizer by mass fraction, firstly premixing for 1min at 800rad/min, then uniformly mixing for 4 times at a rotating speed of 2000rad/min, stirring for 1min each time, putting the uniformly mixed slurry into a dispensing syringe, and defoaming for 6 times by using a defoaming machine to obtain uniform printable slurry;

s41, designing a standard bone defect solid model by using CAD software, and storing a file format as STL;

s42, designing R surface unit configurations with the porosity of 50%, 60% and 70% by using a TPMS method or CAD software, and exporting the R surface unit configurations in an OBJ format;

s43, further processing the three OBJ files, adjusting the normal direction of the surface and the boundary of the closed surface, and scaling the unit structural model to a target size in an equal proportion according to the size parameters of the S41 bone defect solid model;

and S44, carrying out array combination on the unit configurations obtained in the S43 according to the requirements of a gradient structure to form a combined body. The size of the combined body is larger than that of the bone defect solid model, so that the combined body can completely wrap the bone defect solid model;

s45, reasonably adjusting the positions of the bone defect solid model obtained in the S41 and the combination obtained in the S44, and performing intersection operation on the bone defect solid model and the combination to obtain a gradient porous bioceramic artificial bone model taking an R curved surface configuration as a basic unit, wherein the model is derived in an STL format;

s5, installing the slurry pipe at the feed inlet of the biological ceramic 3D printer, guiding the model into the biological ceramic 3D printer for slicing and layering, setting printing parameters, and printing and forming through the biological ceramic 3D printer;

and S6, freeze-drying the printed matter by using a freeze dryer, and removing water to form micropores. Pre-freezing for 6 hours at minus 50 ℃, slowly heating up to minus 30 ℃ to minus 10 ℃ at intervals of 5 ℃, carrying out first-stage freeze drying for 6 hours, carrying out heat preservation drying for 3 hours at 0 ℃ to 10 ℃, carrying out resolution drying at 30 ℃ and keeping the temperature constant for more than 3 hours, and carrying out irradiation sterilization by adopting double-layer packaging after freeze drying is finished to obtain the porous bioceramic artificial bone finished product.

The biological ceramic artificial bone obtained by the method has controllable pore diameter and porosity, intercommunicated pore channels, good structural strength and biological performance, and the porosity of the product is respectively 50%, 60% and 70% after porous biological ceramic artificial bone models with the porosity of 50%, 60% and 70% are respectively printed.

Example 5:

s1, dissolving polyvinyl alcohol powder in water for injection to prepare a polyvinyl alcohol aqueous solution with the mass fraction of 8%, stirring the polyvinyl alcohol aqueous solution on a magnetic stirrer at the constant temperature of 95 ℃ for 1.5h, and centrifuging the polyvinyl alcohol aqueous solution twice by using a centrifuge at the rotating speed of 3000rad/min for 5min each time to remove impurities to obtain a uniform and transparent solution;

s2, putting 52.8% by mass of biological ceramic powder and 47.2% by mass of the polyvinyl alcohol solution obtained in the step S1 into a homogenizer, premixing for 1min at the rotating speed of 800rad/min, stirring for 4 times and uniformly mixing for 1min each time, putting the uniformly mixed slurry into a dispensing syringe, and defoaming for 6 times by using a defoaming machine to obtain uniform printable slurry, wherein the mass ratio of calcium silicate to biological glass in the biological ceramic powder is 1: 1;

s3, designing a porous bioceramic artificial bone model with an R curved surface configuration as a basic unit by using a TPMS combined CSG method, and exporting a bone model file to be printed in an STL format; wherein the porosity is 45%;

S5, placing the porous bioceramic artificial bone blank formed in the S4 into a freeze dryer for freeze drying to remove water, forming micropores, pre-freezing for 6 hours at-50 ℃, slowly heating at-30 ℃ to-10 ℃ at intervals of 5 ℃, carrying out first-stage freeze drying for 6 hours, carrying out heat preservation drying for 3 hours at 0-10 ℃, carrying out resolution drying at 30 ℃ and keeping the temperature for more than 3 hours; obtaining a porous biological ceramic artificial bone finished product, wherein the porosity is 45%;

s6, double-layer packaging and sterilizing by irradiation.

Through the operations, the porous bioceramic artificial bone can be finally obtained, wherein the average pore diameter of macro pores is 380 mu m, and the macro pores are formed by 3D printing and leaving vacancies after water is removed in the freeze-drying process.

Example 6:

s1, preparing a polyvinyl alcohol-collagen-chitosan composite solution:

dissolving polyvinyl alcohol powder in water for injection, preparing 1% polyvinyl alcohol aqueous solution, stirring for 1h at a constant temperature of 95 ℃ on a magnetic stirrer, centrifuging for 5min at a rotating speed of 3000rad/min by using a centrifuge to remove impurities, standing at normal temperature, adding collagen and chitosan to enable the mass ratio of the collagen and the chitosan to be 20%, and stirring on a table at 4 ℃ overnight to obtain uniform white paste; the mass fraction of polyvinyl alcohol and collagen is 7%;

s2, placing β -tricalcium phosphate accounting for 56% of the mass and white paste accounting for 44% of the mass into a material cup, uniformly mixing in a homogenizer at a rotating speed of 500rad/min, premixing for 1min, stirring for 4 times at a rotating speed of 1000rad/min, uniformly mixing for 1min each time, filling the uniformly mixed slurry into a dispensing syringe, and defoaming for 4 times by using a defoaming machine to obtain uniform printing slurry.

S3, designing a porous bioceramic artificial bone model with a P curved surface configuration as a basic unit by using a TPMS combined CSG method, and exporting a bone model file to be printed in an STL format; its porosity was 70%;

s4, the material pipe of the uniform slurry is installed at the feed inlet of the bioceramic 3D printer, the uniform slurry is uniformly extruded through a 400-micron spray head, printing parameters are adjusted, and the porous bioceramic artificial bone blank with the pore diameter larger than 200 microns is obtained by stacking and forming layer by layer, the physical and chemical structure of the material is basically reserved in the printing process, and cytotoxicity is avoided.

S5, placing the composite artificial bone blank obtained in the S4 into a freeze dryer for freeze drying to form micropores, pre-freezing for 6 hours at minus 50 ℃, slowly raising the temperature at intervals of 5 ℃, carrying out first-stage freeze drying for 10 hours at minus 20 ℃ to minus 15 ℃, preserving the heat for 3 hours at 0 ℃, carrying out resolution drying at 30 ℃ and keeping the constant temperature for more than 3 hours to obtain a porous bioceramic artificial bone finished product, wherein the porosity is 70%;

s6, placing the composite artificial bone obtained in the S5 in a vacuum furnace, vacuumizing the vacuum furnace to 10Pa, heating to 110 ℃, carrying out vacuum thermal dehydration and crosslinking treatment for 5 days, and releasing vacuum after the temperature of the furnace is reduced to normal temperature to take out the artificial bone.

And S7, performing double-layer packaging, and performing irradiation sterilization to obtain the porous bioceramic artificial bone product.

The porous bioceramic artificial bone finally obtained by the method has controllable and uniform macro-pore diameter, the pore passages are mutually communicated, and the cross section of the bone contains irregular cellular-like structure micropores.

The porous bioceramic artificial bone with the three-dimensional pore structure is beneficial to adhesion, growth and differentiation of osteoblasts, promotes new bone growth, strengthens connection between the implanted porous bioceramic artificial bone and a raw bone, can provide a growth space and a channel for growth of osteoblasts, blood vessels and the like, increases the contact surface area of tissue fluid and the artificial bone, transmits active substances and nutrient substances into an implant body, promotes bone regeneration, and accelerates the healing process.

A small amount of polyvinyl pyrrolidone (PVP) is added into the polyvinyl alcohol adhesive, so that the adhesive property can be improved, the effect of a flow increasing agent can be achieved, the spray head is prevented from being blocked in the printing process, a polyvinyl pyrrolidone (PVP) solution is used as an auxiliary adhesive, and a mixed solution of PVA and PVP is used as the adhesive to better meet the printing adhesive property, so that the printing slurry cannot be agglomerated, the printing is smooth, and the printing forming performance is good.

Example 7:

s1, firstly, adding 5g of polyvinyl alcohol powder into 45g of water for injection, heating in a water bath, slowly heating to 95 ℃ to prepare a PVA solution with the mass fraction of 10%, then adding 3g of PVP into the prepared PVA solution, and finally, stirring the mixed solution on a magnetic stirrer at the speed of 150r/min to obtain a uniform solution, thus obtaining the binder;

s2, placing the hydroxyapatite, the β -tricalcium phosphate, the binder obtained from the S1 and the water for injection into a homogenizer, premixing for 1min at a rotating speed of 800rad/min, stirring for 4 times at a rotating speed of 2000rad/min, uniformly mixing for 1min each time, placing the uniformly mixed slurry into a dispensing syringe, defoaming for 6 times by using a defoaming machine, and obtaining uniform printable slurry, wherein the printable slurry comprises 23% of the hydroxyapatite, 36% of the β -tricalcium phosphate, 8% of the binder and the balance of the water for injection;

s3, designing a personalized bone defect model with a P curved surface configuration as a basic unit by using a TPMS combined CSG method, and exporting a bone model file to be printed in an STL format;

and S4, printing the artificial bone by using a biological ceramic 3D printer, loading printable slurry obtained in S2 into a charging barrel, performing high-speed centrifugal defoaming, loading the bone model file to be printed obtained in S3 into PCPrinter MF150 software of the biological ceramic 3D printer, adjusting printing parameters, uniformly extruding the slurry through a screw valve at a constant speed, moving a printing head along X, Y, Z three directions, and sequentially printing layer by layer to obtain an artificial bone blank.

S5, placing the artificial bone primary blank obtained in the S4 in a freeze dryer for freeze drying for 28 hours; and then carrying out double-layer packaging on the freeze-dried artificial bone and carrying out irradiation sterilization treatment to obtain a porous bioceramic artificial bone finished product.

The type I collagen is a natural high molecular adhesive, is non-toxic, harmless and degradable, has excellent biological properties such as low antigenicity, biodegradability, biocompatibility, cell adaptability and the like, but is often compounded with other materials to avoid the defects existing in single application due to the defects of high degradation rate and poor physical properties when being used alone, and the Chitosan (CS) is a natural high molecular polymer and has the effects of stopping bleeding, inhibiting bacteria, resisting bacteria, biocompatibility and promoting wound healing; the artificial bone prepared by mixing the type I collagen and the Chitosan (CS) solution as the adhesive has stronger water absorption performance than the artificial bone prepared by mixing the type I collagen and the Chitosan (CS) solution as the adhesive, and the artificial bone is quickly absorbed and maintained after the cell suspension is dripped, so that the nutrition can be quickly obtained after the cells are inoculated, and the strength and the biological performance of the artificial bone are improved.

Example 8:

s1, weighing 550mg of type I collagen (Sigma) and 210mg of chitosan respectively, dissolving in 0.05mol/L acetic acid solution, stirring for 90min at the constant temperature of 4 ℃ at the rotating speed of 18000r/min, vacuumizing, standing overnight in a refrigerator at 4 ℃, and fully mixing to obtain gel suspension to obtain a binder;

s2, placing the hydroxyapatite, the β -tricalcium phosphate, the calcium silicate, the binder obtained from the S1 and the water for injection into a homogenizer, premixing for 1min at a rotating speed of 800rad/min, stirring for 4 times at a rotating speed of 2000rad/min, uniformly mixing for 1min each time, placing the uniformly mixed slurry into a dispensing syringe, defoaming for 6 times by using a defoaming machine, and obtaining uniform printable slurry, wherein the hydroxyapatite is 20%, the β -tricalcium phosphate is 20%, the calcium silicate is 20%, the binder is 4%, and the balance is the water for injection;

s3, designing a bone defect model taking a G curved surface configuration as a basic unit by using a TPMS combined CSG method, and exporting a bone model file to be printed in an STL format;

and S4, printing the artificial bone by using a biological ceramic 3D printer, loading the bone model file to be printed obtained in the step S3 into PCPrinter MF150 software, adjusting printing parameters, uniformly extruding slurry through a screw valve at a constant speed, moving a printing head along X, Y, Z three directions, and sequentially printing layer by layer to obtain an artificial bone primary blank.

S5, placing the porous bioceramic artificial bone blank obtained in the S4 in 1% genipin solution, crosslinking for 1h at the temperature of 37 ℃, and then cleaning for 3 times by using 0.01mol/LPBS solution;

s6, freeze-drying the porous bioceramic artificial bone processed in the S5 for 28 hours in a freeze-drying oven; and then carrying out double-layer packaging on the freeze-dried porous bioceramic artificial bone and carrying out irradiation sterilization treatment to obtain a porous bioceramic artificial bone finished product, wherein the porosity of the porous bioceramic artificial bone finished product is 40%.

The strength of the porous bioceramic artificial bone can be effectively improved through crosslinking treatment.

Example 9

S1, dissolving polyvinyl alcohol powder in water for injection to prepare polyvinyl alcohol aqueous solution with mass fraction of 8%, stirring for 1.5h at constant temperature of 95 ℃ on a magnetic stirrer, and centrifuging twice by using a centrifuge with the speed of 3000rad/min for 5min to remove impurities to obtain uniform and transparent solution.

S2, putting hydroxyapatite, β -tricalcium phosphate and polyvinyl alcohol solution into a homogenizer, premixing for 1min at 800rad/min, stirring for 6 times at 1 rad/min, uniformly mixing, putting the uniformly mixed slurry into a dispensing syringe, and defoaming for 2 times by using a defoaming machine to obtain uniform printable slurry, wherein the content of the hydroxyapatite in the printable slurry is 25.5%, the content of the β -tricalcium phosphate is 34.8%, and the content of the polyvinyl alcohol solution is 39.7%;

s3, designing a personalized bone defect model with a P curved surface configuration as a basic unit by using a TPMS combined CSG method, and exporting the model in an STL format;

s4, mounting the uniform material pipe capable of printing the slurry on a feed inlet of a bioceramic 3D printer, adjusting printing parameters, inputting a prepared model file, and stacking and molding layer by layer to obtain a designed porous bioceramic artificial bone blank with regular macro pores;

and S5, freeze-drying the formed primary blank in a freeze dryer to remove water, and forming micropores. Pre-freezing for 6 hours at minus 50 ℃, slowly heating up to minus 30 ℃ to minus 10 ℃ at intervals of 5 ℃, carrying out first-stage freeze drying for 6 hours, carrying out heat preservation drying for 3 hours at 0 ℃ to 10 ℃, carrying out resolution drying at 30 ℃ and keeping the temperature constant for more than 3 hours, and then carrying out irradiation sterilization to obtain the porous bioceramic artificial bone; the porosity thereof is 40%;

s6, dissolving chitosan in 2.0% acetic acid to prepare a solution with the mass fraction of chitosan being 2%, filtering to remove insoluble substances, adding PVA which is soaked for 24 hours and fully swelled with the mass fraction being 8% in a corresponding proportion, and uniformly mixing the solution to obtain mixed gel; placing the artificial bone and the mixed gel in a vacuum chamber, heating the mixed gel to evaporate the mixed gel into a gas state, depositing the gas state on the surface of the porous bioceramic artificial bone to form a film, and taking out the film; the mass ratio of chitosan to PVA is 1: 2; the maximum thickness of the degradable gradient film is 300 mu m, and the minimum thickness of the degradable gradient film is 50 mu m; the gradual change mode of the degradable gradual change film is as follows: uniformly reducing the vertex angles from 300 mu m to 50 mu m by taking the perpendicular bisector of the two vertex angles as a starting point and the four vertex angles as an end point; a layer of degradable membrane with gradually changed thickness is deposited on the surface of the porous bioceramic artificial bone to play a role in slowly releasing the medicine.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included therein.

Claims

1. A method for designing a bionic porous bioceramic artificial bone model by adopting TPMS and CSG is characterized by comprising the following steps:

s12, designing a unit configuration by utilizing a TPMS method or CAD software modeling, defining the porosity as 20% -80%, and exporting a curved surface unit configuration file in an OBJ format, wherein the curved surface unit configuration comprises a G curved surface unit configuration, a P curved surface unit configuration and an R curved surface unit configuration;

s13, adjusting the boundary of the normal direction of the surface and the closed isosurface of the curved surface unit configuration file in the OBJ format obtained in the S12, and scaling the curved surface unit configuration model in the S12 to a design size in an equal proportion according to the size parameters of the S11 bone defect solid model to obtain the curved surface unit configuration with a target size;

and S15, registering the bone defect solid model obtained in the S11 and the combined body obtained in the S14, adjusting the positions of the bone defect solid model obtained in the S11 and the combined body obtained in the S14, performing intersection operation on the bone defect solid model and the combined body to obtain the porous bioceramic artificial bone model taking the curved surface unit configuration as the basic unit, and exporting the porous bioceramic artificial bone model in an STL format file.

2. The method for designing the biomimetic porous bioceramic artificial bone model according to claim 1, wherein in S12, the porous bioceramic artificial bone model adopts a gradient porous structure of uniform porous or biomimetic bone.

3. A bionic porous bioceramic artificial bone is characterized in that a porous bioceramic artificial bone model with a curved surface unit configuration as a basic unit is obtained by adopting TPMS combined CSG design and is prepared by adopting a 3D silkless printing process; macro pores and micro pores are distributed in the porous bioceramic artificial bone, the pore diameter of each micro pore is less than 100 micrometers, and the pore diameter of each macro pore is 200-800 micrometers; the total porosity is 20-80%, and the communication rate among macro pores is not less than 95%.

4. The biomimetic porous bioceramic artificial bone according to claim 3, wherein the porous bioceramic artificial bone is a uniformly porous or gradient porous structure of a biomimetic bone.

5. A preparation method of a bionic porous bioceramic artificial bone is characterized by comprising the following steps,

s21, preparing a binder;

s23, loading the porous bioceramic artificial bone model file into the bioceramic 3D printer, and loading the uniform printable slurry into a feed inlet of the bioceramic printer; setting printing parameters; starting a biological ceramic 3D printer for printing, and stacking and forming layer by layer to obtain a porous biological ceramic artificial bone primary blank with the aperture larger than 200 mu m;

6. The method for preparing a bionic porous bioceramic artificial bone according to claim 5, wherein the binder is one or more of polyvinyl alcohol, polyvinyl pyrrolidone, chitosan and collagen.

7. The method for preparing the artificial bone of the bionic porous bioceramic as claimed in claim 6, wherein the PVA adopted by the binder in the S21 is purified by recrystallization, and the purity and alcoholysis degree of the PVA are not lower than 99.5%.

8. The method for preparing the artificial bone of the bionic porous bioceramic according to claim 5, wherein the printable slurry obtained in S22 comprises, by mass: 30-90% of biological ceramic powder, 2-8% of binder and the balance of water.

9. The method for preparing a bionic porous bioceramic artificial bone according to claim 5, wherein a degradable membrane is vapor-deposited on the outer surface of the freeze-dried porous bioceramic artificial bone, the thickness of the degradable membrane is gradually increased from the edge to the center, the thickness of the degradable membrane is uniformly increased from 50 μm to 300 μm, and chitosan is used as a raw material of the degradable membrane.

10. The method for preparing the bionic porous bioceramic artificial bone according to claim 5, wherein the porous bioceramic artificial bone is prepared by cross-linking a porous bioceramic artificial bone blank or a freeze-dried porous bioceramic artificial bone.