CN113233887A

CN113233887A - Controllable porous calcium phosphate scaffold and preparation method thereof

Info

Publication number: CN113233887A
Application number: CN202110587564.XA
Authority: CN
Inventors: 郭立坤; 贾恒星; 朱向东; 樊渝江; 张兴栋
Original assignee: Sichuan University
Current assignee: Sichuan University
Priority date: 2021-05-27
Filing date: 2021-05-27
Publication date: 2021-08-10

Abstract

The invention relates to a controllable porous calcium phosphate support and a preparation method thereof, wherein the calcium phosphate support comprises calcium phosphate ceramic and calcium phosphate bone cement, a porous structure is arranged on the calcium phosphate support, the porous structure comprises a macro-porous structure, a micro-porous structure and a through hole structure, the calcium phosphate support comprises a crystal structure, the through hole structure is arranged between the crystal structures, and the shape of the calcium phosphate support is designed according to the defect part of a patient in a matching way. The invention improves the preparation method of the sacrificial material, and adopts the 3D printing technology with higher precision, so as to prepare more complicated and various pore structures; the scaffold prepared by the invention has controllable micropores and through holes between the crystals of the scaffold, the degradation rate of the scaffold is changed by controlling the pore structure, and meanwhile, the pore structure influences the growth rate and growth volume of new bones and blood vessels, so that the bioactivity and osteogenesis of the bone implantation scaffold are further improved; the method has the advantages of simple process flow, easy operation, stable structural performance of the prepared bracket, high compressive strength and good cell compatibility.

Description

Controllable porous calcium phosphate scaffold and preparation method thereof

Technical Field

The invention relates to the field of medical materials for bone repair, in particular to a controllable porous calcium phosphate scaffold and a preparation method thereof.

Background

The repair of large segmental bone defects caused by trauma, tumors, infection and congenital deformities remains a challenge for orthopedic surgeons, and such irregular bone defects require a filling material with good form adaptability to fill the defect. With the continuous development of 3D printing technology in recent years, it is not difficult to prepare the scaffold requiring a complex shape structure, but it is still difficult to prepare the scaffold satisfying bone repair conditions in all aspects of performance.

Most of current 3D prints and mostly directly prints, print structure and equal to final model promptly, printing material and printing method need suitable adaptation, this means that various 3D printing methods all have self restrictive condition, especially need to print the preceding processing and adjust printing material in order to satisfy printing apparatus requirement, and adjust printer printing parameter well, and the most crucial point lies in that present a large amount of 3D prints the support and does not have controllable micropore in addition, and this has also directly influenced its osteogenesis nature. And the indirect printing perfectly avoids the difficulties, and also keeps the advantage of preparing a complex structure by a 3D printing technology.

Indirect 3D printing is a printing process that prints a sacrificial material with well-established 3D printing techniques, refills with ceramic paste, and then forms by thermally or chemically removing the sacrificial mold. This method has been used, Steffen Esslinger et al (Steffen Esslinger, Rainer Garow. additive manufacturing of biological screens by combining of FDM and slip casting [ J ]. Journal of the European Ceramic Society,2020,40 (11.) by printing a sacrificial mold with FDM, pouring a Ceramic slurry, and sintering to form the Ceramic.

Chinese patent CN201810276029.0 also discloses a method for preparing calcium phosphate scaffold by indirect 3D printing, in which a sacrificial mold is prepared by FDM technique, and then the sacrificial material is removed by organic solvent to leave the calcium phosphate scaffold. However, the FDM preparation sacrificial mold also has a disadvantage that the FDM has a very limited printing structure because the nozzle extrudes the molten material, the precision depends on the diameter of the nozzle, the nozzle diameter used in the patent is 0.3mm, a fine structure cannot be prepared, and the through hole structure left by the sacrificial mold is very single, so that a hole structure support which is beneficial to the growth of cells and tissues cannot be prepared, and the bioactivity and the bone conductivity of the support are further influenced.

Therefore, a mode of combining a casting technology with a 3D printing technology is designed, so that the support is provided with a micropore structure and through holes among micropores under the conditions of complex appearance and through macro holes; the defects of low controllability of pore structure modeling and small adjustable pore diameter range in the bone implantation scaffold are improved, the degradation rate of the scaffold is changed by controlling the pore structure, and the growth rate and growth volume of new bones and blood vessels are influenced by the pore structure, so that the bioactivity and osteogenesis of the bone implantation scaffold are further improved, and the bone implantation scaffold is necessary for technicians in the field.

Disclosure of Invention

In view of the above, the present application provides a controllable porous calcium phosphate scaffold and a preparation method thereof, which improve the defects of a bone implantation scaffold that the controllable degree of the pore structure shape is low and the adjustable pore size range is small, further improve the bioactivity and osteogenesis of the bone implantation scaffold, and improve the comprehensive performance of the scaffold.

In order to achieve the above object, the present application provides the following technical solutions.

A controlled porous calcium phosphate scaffold, wherein the composition of the calcium phosphate scaffold comprises at least one of a calcium phosphate ceramic and a calcium phosphate cement; the calcium phosphate bracket is provided with a plurality of hole structures;

the preparation method of the calcium phosphate scaffold comprises the following steps:

s1, prefabricating a sacrificial mold with through holes;

s2, preparing slurry;

s3, filling the prepared slurry into a sacrificial mold;

and S4, removing the sacrificial mold and sintering or self-hardening forming.

The pore structure comprises a macro-pore structure, a micro-pore structure and a through-pore structure, the calcium phosphate support comprises a crystal structure, and the through-pore structure is arranged between the crystal structures.

The shape of the calcium phosphate bracket is designed according to the matching of the defect part of the patient.

Preferably, the calcium phosphate ceramic comprises one or more of hydroxyapatite, beta tricalcium phosphate and the like.

Preferably, the calcium phosphate cement comprises one or more of tetracalcium phosphate, octacalcium phosphate, monocalcium phosphate monohydrate, monocalcium phosphate, dicalcium phosphate dihydrate, amorphous calcium phosphate, alpha-tricalcium phosphate.

Preferably, the shape of the crystal structure comprises one or more combinations of needle-like, sheet-like, and net-like shapes.

Preferably, the porosity of the calcium phosphate scaffold is 20-90%; the pore diameter of the macro-pore structure is 200-800 μm; the pore diameter of the microporous structure is 1-200 μm; the through hole structure is a through channel for connecting the macro hole and the micro hole, and the diameter of the through hole structure is less than 800 mu m.

Preferably, the shape of the microporous structure comprises one or more combinations of spheres, rods, and irregular geometries.

Preferably, the preparation method of the calcium phosphate scaffold comprises the following steps:

s1, prefabricating a sacrificial mold with through holes;

s2, preparing slurry;

s3, filling the prepared slurry into a sacrificial mold;

s4, removing the sacrificial mold and sintering or self-hardening molding;

preferably, the method for preparing the mold in step S1 includes creating a sacrificial mold model with a complex shape and an appropriate internal pore structure by using modeling software, and printing out the sacrificial mold entity by using a 3D printer.

Preferably, the slurry in step S2 includes an inorganic material, an in-situ pore former; the inorganic material comprises calcium and phosphorus elements; the calcium and phosphorus-containing elements comprise calcium and phosphorus ceramics and calcium phosphate bone cement. The inorganic material is prepared into slurry to be used according to the designed proportion.

In one embodiment, the method for preparing the calcium phosphate scaffold further comprises the following steps: s5, immersing the stent prepared in the step S4 in a drug to prepare a drug composite stent.

The pore diameter of the macro-pore structure can be adjusted by adjusting the model precision and/or the 3D printer precision and/or the slurry foaming degree;

the method for adjusting the pore diameter of the microporous structure comprises the steps of adjusting the size and the shape of the pore-forming agent and/or the foaming degree of slurry;

furthermore, the calcium phosphate scaffold has certain mechanical property, and the compressive strength is more than 3 Mpa; preferably greater than 5 Mpa.

The beneficial technical effects obtained by the invention are as follows:

(1) the traditional bone repair material is combined with the 3D printing technology, so that a compound pore structure with various pore diameters of a macro-pore structure, a micro-pore structure and a through-pore structure can be stably prepared, the instability of pore forming in the traditional process is overcome, and a foundation is laid for preparing a support with a complex pore structure;

(2) the invention improves the preparation method of the sacrificial material, selects the 3D printing technology with higher precision, and can quickly and simply prepare the bracket which conforms to the shape of the bone defect, thereby realizing the personalized customization scheme of the bracket;

(3) the stent prepared by the invention has various pore structures required in vivo, wherein through pore structures are arranged among crystals, thus being beneficial to the exchange of nutrient substances and the growth of blood vessels and bone tissues after implantation;

(5) according to the invention, the degradation rate is matched with the human bone growth rate by adjusting the porosity and the slurry components, the degradation is complete within 3 months to 3 years, and the bone repair requirement is better met;

(6) the process flow of the invention is easy to operate, the prepared scaffold has stable structural performance and higher mechanical property, the compressive strength is more than 3Mpa, and the cell compatibility is good.

The foregoing description is only an overview of the technical solutions of the present application, so that the technical means of the present application can be more clearly understood and the present application can be implemented according to the content of the description, and in order to make the above and other objects, features and advantages of the present application more clearly understood, the following detailed description is made with reference to the preferred embodiments of the present application and the accompanying drawings.

The above and other objects, advantages and features of the present application will become more apparent to those skilled in the art from the following detailed description of specific embodiments thereof, taken in conjunction with the accompanying drawings.

Drawings

In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings needed to be used in the description of the embodiments or the prior art will be briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present application, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts. Throughout the drawings, like elements or portions are generally identified by like reference numerals. In the drawings, elements or portions are not necessarily drawn to scale.

Figure 1 is a software modeling of a calcium phosphate scaffold;

FIG. 2 is a porous scaffold formed after sintering

FIG. 3 is a scanning electron micrograph of a calcium phosphate scaffold;

FIG. 4 is a scanning electron micrograph of the microstructure of a calcium phosphate scaffold;

FIG. 5 is a confocal microscope of cell survival on calcium phosphate scaffolds.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application, and it is obvious that the described embodiments are some embodiments of the present application, but not all embodiments. In the following description, specific details such as specific configurations and components are provided only to help the embodiments of the present application be fully understood. Accordingly, it will be apparent to those skilled in the art that various changes and modifications may be made to the embodiments described herein without departing from the scope and spirit of the present application. In addition, descriptions of well-known functions and constructions are omitted in the embodiments for clarity and conciseness.

It should be appreciated that reference throughout this specification to "one embodiment" or "the embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present application. Thus, the appearances of the phrase "one embodiment" or "the present embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

Further, the present application may repeat reference numerals and/or letters in the various examples. This repetition is for the purpose of simplicity and clarity and does not in itself dictate a relationship between the various embodiments and/or configurations discussed.

The term "and/or" herein is merely an association describing an associated object, meaning that three relationships may exist, e.g., a and/or B, may mean: a exists alone, B exists alone, and A and B exist at the same time, and the term "/and" is used herein to describe another association object relationship, which means that two relationships may exist, for example, A/and B, may mean: a alone, and both a and B alone, and further, the character "/" in this document generally means that the former and latter associated objects are in an "or" relationship.

The term "at least one" herein is merely an association relationship describing an associated object, and means that there may be three relationships, for example, at least one of a and B, may mean: a exists alone, A and B exist simultaneously, and B exists alone.

It is further noted that, herein, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion.

Example 1

Figure 1 is a software modeling of a calcium phosphate stent whose profile is designed to match the patient's defect site.

As shown in fig. 2, a controllable porous calcium phosphate scaffold, the components of which comprise calcium phosphate ceramic and calcium phosphate cement, wherein a porous structure is arranged on the calcium phosphate scaffold, the porous structure comprises a macro-porous structure, a micro-porous structure and a through-porous structure, the calcium phosphate scaffold has a crystal structure, and the through-porous structure is arranged between the crystal structures.

Further, the calcium-phosphorus ceramic comprises one or more of hydroxyapatite and tricalcium phosphate.

Further, the calcium phosphate cement comprises one or more of tetracalcium phosphate, octacalcium phosphate, monocalcium phosphate monohydrate, monocalcium phosphate, calcium hydrogen phosphate dihydrate, amorphous calcium phosphate, and tricalcium phosphate.

As shown in fig. 3, the size of the crystal structure is in the range of 10nm-10 μm; the shape of the crystal structure comprises one or more combination of needle shape, sheet shape and net shape.

Further, the porosity of the calcium phosphate scaffold is 20-90%; the pore diameter of the macro-pore structure is 200-800 μm; the pore diameter of the microporous structure is 1-200 μm; the through hole structure is a through channel for connecting the macro hole and the micro hole, and the diameter of the through hole structure is less than 800 mu m.

Further, the shape of the microporous structure of the calcium phosphate scaffold comprises one or more of a combination of a sphere, a rod and an irregular geometry.

As shown in fig. 4, the calcium phosphate scaffold has a fine crystal structure, such as a needle-like, sheet-like, or net-like crystal structure, and there are a large number of gaps, i.e., tiny through holes, between the fine crystal structures, which together form a porous microstructure of the scaffold, which is also a structure of a bionic natural bone.

Further, the preparation method of the calcium phosphate scaffold comprises the following steps:

s1, prefabricating a sacrificial mold with through holes;

s2, preparing slurry;

s3, filling the prepared slurry into a sacrificial mold;

s4, removing the sacrificial mold and self-hardening or sintering for molding;

further, the preparation method of the calcium phosphate scaffold also comprises the following steps: s5, immersing the stent prepared in the step S4 in a drug to prepare a drug composite stent.

Further, in step S1, as shown in fig. 1, the method for preparing the mold in step S1 includes creating a sacrificial mold model with a complex shape and an appropriate internal pore structure by using modeling software, and printing out the sacrificial mold entity by using a 3D printer.

Further, the slurry obtained in step S2 includes an inorganic material and an in-situ pore-forming agent; the inorganic material comprises calcium and phosphorus elements; the calcium and phosphorus containing elements comprise calcium and phosphorus ceramics and/or calcium phosphate bone cement; the inorganic material is prepared into slurry to be used according to the designed proportion.

As shown in figure 5, the survival of cells on the calcium phosphate scaffold prepared by the invention is good, and the scaffold has good cell compatibility.

Example 2

This embodiment is performed based on embodiment 1, and the same points as embodiment 1 are not repeated.

This example mainly describes the method of controlling the pore structure in the scaffold.

The method for adjusting the aperture of the macro-pore structure comprises the steps of adjusting model precision and 3D printer precision; the source of the macro-pore structure is obtained by demoulding a sacrificial mould prepared by a printer, so that the size and the shape of the macro-pore structure depend on the size and the shape of the printed sacrificial mould, the minimum size of the sacrificial mould depends on the precision of the printer, and the size and the shape of the macro-pore structure are obtained by constructing a model through software and demoulding after 3D printing.

The method for adjusting the pore diameter of the microporous structure comprises the steps of adjusting the size and the shape of a pore-forming agent; the microporous structure is obtained by adding a pore-forming agent into the perfusion slurry and then eliminating the pore-forming agent after the support is formed. Therefore, the regulation and control of the microporous structure are realized by adding pore-forming agents with different sizes and shapes. The currently commonly used spherical pore-forming agent is PMMA, the diameter of the PMMA is within the range of 0.1-300 mu m, and the preparation of micropores with spherical shapes and sizes of 1-200 mu m can be carried out. The shape of the rod is also prepared by the same method. Preparing micropores with irregular geometric shapes, adopting sodium chloride as a pore-forming agent, and soaking the formed stent in water for dissolution.

The method for adjusting the aperture of the through hole structure comprises the step of controlling the liquid content in the slurry. After the scaffold is formed, the liquid components in the slurry are dried, leaving more minute through-holes, and more liquid is present in such holes.

The microstructure regulating method comprises the steps of selecting different base materials and curing liquid, and regulating the crystal structure of the bone cement growing in the solution, or realizing the regulation through the sintering process of a Biphase Calcium Phosphate (BCP) material.

The scaffold prepared by the embodiment has controllable micropores and through holes among crystals of the scaffold, and the pore structures have larger specific surface area, so that the protein adsorption and cell adhesion proliferation after implantation are facilitated; in the embodiment, the degradation rate is matched with the human bone growth rate by adjusting the porosity and the slurry components, the degradation is complete within 3 months to 3 years, and the bone repair requirement is better met.

Example 3

This example mainly describes a method for preparing a scaffold having a porosity of 60%, 400 μm through macro pores, 60 μm spherical micropores, and a suitable amount of through pores between crystals.

The support adopts photosensitive resin as a sacrificial mold material, the pore-forming agent adopts 60-micron PMMA microspheres, and the perfusion slurry is a mixture of hydroxyapatite and alpha-tricalcium phosphate.

The implementation steps comprise:

s301, prefabricating a photosensitive resin sacrificial model by using an SLA 3D printer: firstly, a cylinder model with the diameter of 10mm and the height of 3mm is constructed by using solidworks software, interconnected cylinder structures with the diameter of 400 mu m are constructed in the model, 400 mu m through macro pores are formed after demoulding, and a distance of 1.5mm is kept between the cylinder structures to control the porosity of the stent. After the model construction is finished, converting the model into an STL format file, importing the STL format file into a printer, and setting printing parameters, wherein the wavelength is 300-500nm, the thickness is 25-100 mu m, and the single-layer scanning time is 2-10 seconds. And finishing the preparation of the sacrificial mold after printing.

S302, slurry pouring and bracket forming: according to the hydroxyapatite ratio of alpha-tricalcium phosphate 1: 9, preparing 1 g of powder material, adding 0.1 g of PMMA microsphere pore-forming agent with the spherical diameter of 60 mu m, and vibrating for 5-10 minutes by using a vortex oscillator to uniformly mix. 550ul of curing liquid (prepared by mixing 8% by weight of citric acid and 10% by weight of sodium hydrogen phosphate in a ratio of 1: 1) is added according to the liquid-solid ratio of 0.5. Stirring to make the components uniform, and blending to obtain mixed slurry. The slurry was then poured into molds using a pouring tool, and then cured in a constant temperature and humidity cabinet at 60 ℃ and 100% relative humidity for 72 hours, and then taken out to an oven to dry for 24 hours.

S303, removing the sacrificial mold: and (3) placing the prepared bracket mold compound in a sintering furnace for degreasing treatment, setting the heating rate to be 5 ℃/min, heating to 700 ℃, demolding, keeping the temperature for 2 hours, and then cooling along with the furnace.

The preparation method of the embodiment has simple operation steps and easily controlled preparation conditions.

Example 4

This example mainly introduces a method for preparing a scaffold having a porosity of 75%, 600 μm through macro pores, and 30 μm spherical micropores, which comprises the following steps:

s401, prefabricating a photosensitive resin sacrificial model by using an SLA 3D printer: a 10mm diameter, 3mm high cylinder model was first constructed using solidworks software, in which interconnected cylinder structures were constructed with a diameter of 600 μm and a 1mm spacing between them to increase the porosity of the scaffold. The subsequent steps are similar to example 1. .

S402, slurry pouring and bracket forming: weighing 1 g of pure alpha-tricalcium phosphate powder material, adding 0.1 g of PMMA microsphere pore-forming agent with the spherical diameter of 30 mu m, and vibrating for 5-10 minutes by using a vortex oscillator to uniformly mix the materials. 550ul of curing liquid (which is formed by mixing 10 wt% of citric acid and 10 wt% of disodium hydrogen phosphate according to a ratio of 1: 1) is added according to a liquid-solid ratio of 0.5. Stirring to make the components uniform, and blending to obtain mixed slurry. The slurry was then poured into molds using a pouring tool, and then cured in a constant temperature and humidity cabinet at 60 ℃ and 100% relative humidity for 72 hours, and then taken out to an oven to dry for 24 hours.

S403, removing the sacrificial mold: and (3) placing the prepared bracket mold compound in a sintering furnace for degreasing treatment, setting the heating rate to be 5 ℃/min, heating to 700 ℃, demolding, keeping the temperature for 2 hours, and then cooling along with the furnace.

Example 5

This embodiment mainly introduces a method for preparing a scaffold having a plate-like crystal structure, a crystal size of less than 2 μm, a porosity of 70%, 500 μm through macro pores, and 30 μm micro pores. The method comprises the following specific steps:

s501, prefabricating a photosensitive resin sacrificial model by using an SLA 3D printer: a cylinder model of 10mm diameter and 3mm height was first constructed using solidworks software, in which interconnected cylinder structures of 500 μm diameter were constructed with a 0.9mm spacing between them to achieve the target porosity. Converted to STL format and printed out of the sacrificial mold.

S502, slurry pouring and bracket forming: weighing 1 g of pure alpha-tricalcium phosphate powder material, adding 0.2 g of PMMA microsphere pore-forming agent with the spherical diameter of 30 mu m, and vibrating for 5-10 minutes by using a vortex oscillator to uniformly mix the materials. 550ul of curing liquid (up water) was added. Stirring to make the components uniform, and blending to obtain mixed slurry. The slurry was then poured into molds using a pouring tool, and then cured in a constant temperature and humidity cabinet at 60 ℃ and 100% relative humidity for 72 hours, and then taken out to an oven to dry for 24 hours.

S503, removing the sacrificial mold: and (3) placing the prepared bracket mold compound in a sintering furnace for degreasing treatment, setting the heating rate to be 5 ℃/min, heating to 700 ℃, demolding, keeping the temperature for 2 hours, and then cooling along with the furnace.

Example 6

This example mainly introduces a method for preparing a scaffold having a needle-like and block-like crystal structure, a crystal size of less than 1 μm, a porosity of 70%, 500 μm through macro pores, and 30 μm micro pores, which comprises the following steps:

s601, prefabricating a photosensitive resin sacrificial model by using an SLA 3D printer: a cylinder model of 10mm diameter and 3mm height was first constructed using solidworks software, in which interconnected cylinder structures of 500 μm diameter were constructed with a 0.9mm spacing between them to achieve the target porosity. Converted to STL format and printed out of the sacrificial mold.

S602, slurry pouring and support forming: weighing pure alpha-tricalcium phosphate powder material, adding the powder material into a ball milling tank, and adding pure ethanol. Putting the mixture into a ball mill, setting the rotating speed to be 300r/min and the time length to be 4 hours. And taking out the powder and drying to obtain the alpha-tricalcium phosphate powder with the particle size of less than 5 mu m. 1 g of alpha-tricalcium phosphate is weighed, 0.2 g of PMMA microsphere pore-forming agent with the spherical diameter of 30 mu m is added, and the mixture is vibrated for 5 to 10 minutes by a vortex oscillator to be uniformly mixed. 550ul of a setting solution (made by mixing 8% by weight citric acid and 8% disodium hydrogen phosphate in a ratio of 1: 1) was added. Stirring to make the components uniform, and blending to obtain mixed slurry. The slurry was then poured into molds using a pouring tool, and then cured in a constant temperature and humidity cabinet at 60 ℃ and 100% relative humidity for 72 hours, and then taken out to an oven to dry for 24 hours.

S603, removing the sacrificial mold: and (3) placing the prepared bracket mold compound in a sintering furnace for degreasing treatment, setting the heating rate to be 5 ℃/min, heating to 700 ℃, demolding, keeping the temperature for 2 hours, and then cooling along with the furnace.

Example 7

This example mainly introduces a Biphasic Calcium Phosphate (BCP) scaffold with 60% porosity, and the scaffold has 500 μm through macro-pores, 80 μm irregular micro-pores, and a large number of inter-crystalline through-holes, and the specific preparation process is as follows:

s701, prefabricating a photosensitive resin sacrificial model by using an SLA 3D printer: a cylinder model of 10mm diameter and 3mm height was first constructed using solidworks software, in which interconnected cylinder structures of 500 μm diameter were constructed with a 0.9mm spacing between them to achieve the target porosity. Converted to STL format and printed out of the sacrificial mold.

S702, slurry pouring and support forming: 1 g of BCP powder is weighed, 0.2 g of irregular sodium chloride pore-forming agent with the spherical diameter of 80 mu m is added, and the mixture is vibrated for 5 to 10 minutes by a vortex oscillator to be uniformly mixed. 550ul of binding fluid (5% wt. polyvinyl alcohol solution) was added. Stirring to make the components uniform, and blending to obtain mixed slurry. The slurry was then poured into the mold using a pouring tool, after which the mixture of mold and slurry was removed to an oven and dried for 24 hours.

S703, removing the sacrificial mold: placing the prepared bracket mold compound in a sintering furnace for degreasing treatment, setting the heating rate to be 5 ℃/min, heating to 550 ℃, demolding, keeping the temperature for 1 hour, heating to 1100 ℃ at the heating rate of 3 ℃/min, keeping the temperature for 2 hours, cooling along with the furnace, taking out after cooling to room temperature, placing in RO water for more than 24 hours, and completely removing sodium chloride particles.

The above description is only a preferred embodiment of the present invention, and it is not intended to limit the scope of the present invention, and various modifications and changes may be made by those skilled in the art. Variations, modifications, substitutions, integrations and parameter changes of the embodiments may be made without departing from the principle and spirit of the invention, which may be within the spirit and principle of the invention, by conventional substitution or may realize the same function.

Claims

1. A controlled porous calcium phosphate scaffold, wherein the composition of the calcium phosphate scaffold comprises at least one of a calcium phosphate ceramic and a calcium phosphate cement; the calcium phosphate bracket is provided with a plurality of hole structures;

s1, prefabricating a sacrificial mold with through holes;

s2, preparing slurry;

s3, filling the prepared slurry into a sacrificial mold;

and S4, removing the sacrificial mold and sintering or self-hardening forming.

2. A controlled porous calcium phosphate scaffold according to claim 1, wherein said calcium phosphate ceramic comprises one or more of hydroxyapatite, β tricalcium phosphate.

3. A controlled porous calcium phosphate scaffold according to claim 1, wherein said calcium phosphate cement comprises one or more of tetracalcium phosphate, octacalcium phosphate, monocalcium phosphate monohydrate, monocalcium phosphate, dicalcium phosphate dihydrate, amorphous calcium phosphate, alpha tricalcium phosphate.

4. The controllable porous calcium phosphate scaffold according to claim 1, wherein the pore structure comprises a macro-pore structure, a micro-pore structure and a through-pore structure; the calcium phosphate support is provided with a pore structure, the pore structure comprises a macro pore structure, a micropore structure and a through hole structure, the calcium phosphate support is provided with a crystal structure, and the through hole structure is arranged between the crystal structures.

5. A controlled porous calcium phosphate scaffold according to claim 4, wherein the porosity of said calcium phosphate scaffold is 20-90%; the pore diameter of the macro-pore structure is 200-800 μm; the pore diameter of the microporous structure is 1-200 μm; the through hole structure is a through channel for connecting the macro holes and the micro holes, the diameter is less than 800 mu m, and the compressive strength of the calcium phosphate scaffold is more than 3 Mpa.

6. The controllable porous calcium phosphate scaffold according to claim 5, wherein the shape of the microporous structure comprises one or more of a combination of spherical shape, rod shape, and irregular geometric shape.

7. The controlled porous calcium phosphate scaffold according to claim 5, wherein the shape of the crystal structure comprises one or more of needle-like, sheet-like, and net-like combinations.

8. The controllable porous calcium phosphate scaffold according to any one of claims 1-6, wherein the preparation method of the mold in step S1 comprises creating a sacrificial mold model with a complex shape and an appropriate internal pore structure by using modeling software, and printing out the sacrificial mold entity by using a 3D printer.

9. The controllable porous calcium phosphate scaffold according to any one of claims 1 to 6, wherein the slurry in step S2 of the preparation method comprises an inorganic material, an in-situ pore-forming agent; the inorganic material comprises calcium and phosphorus elements; the calcium and phosphorus-containing elements comprise calcium and phosphorus ceramics and calcium phosphate bone cement.

10. The controllable porous calcium phosphate scaffold according to any one of claims 1 to 6,

the preparation method of the calcium phosphate scaffold also comprises the following steps: s5, immersing the stent prepared in the step S4 in a drug to prepare a drug composite stent.