CN113149689A

CN113149689A - Method for modifying calcium silicate biological ceramic through magnesium

Info

Publication number: CN113149689A
Application number: CN202110364635.XA
Authority: CN
Inventors: 林立宁; 俞梦飞; 娄依婷; 应彬彬; 孙苗; 钱周旸
Original assignee: Zhejiang University ZJU
Current assignee: Zhejiang University ZJU
Priority date: 2021-04-06
Filing date: 2021-04-06
Publication date: 2021-07-23

Abstract

The invention discloses a method for modifying calcium silicate biological ceramic by magnesium, which is characterized by comprising the following steps: preparing biological ceramic powder; preparing 3D ceramic biological ink; preparing a porous support by adopting a 3D ceramic ink writing device; sintering the obtained bracket; and expanding the sintered biological ceramic stent. Compared with the background art, the invention has the beneficial effects that: the method of the invention uses Mg to partially replace Ca in calcium silicate, realizes the improvement of key performances such as mechanical performance, biodegradability and the like of the 3D printing biological ceramic scaffold, and has the advantages of bone regeneration potential and mechanical evolution in the aspect of repairing thin-walled bone defects.

Description

Method for modifying calcium silicate biological ceramic through magnesium

Technical Field

The invention relates to a method for modifying calcium silicate bioceramic by magnesium.

Background

The bioceramic material is a common ceramic material with specific biological or physiological functions, is commonly used in the fields of medicine or medicine-related fields, and mainly comprises a calcium phosphate bioceramic material, a calcium silicate bioceramic material, a composite bioceramic material and the like. Among them, the calcium phosphate bioceramic is not well satisfactory for clinical needs due to its poor degradability and lack of osteogenic induction ability. However, although the calcium silicate has faster degradation speed and osteogenesis rate, the pore structure of the pure CSi scaffold can not provide enough support for repairing bone defects due to over-plastic degradation and poor strength stability.

Disclosure of Invention

The present invention overcomes at least one of the deficiencies of the prior art described above,

the invention aims to provide a method for modifying calcium silicate bioceramic by magnesium, which comprises the following steps:

s1, preparing biological ceramic powder;

S2.3D preparing ceramic bio-ink;

s3, preparing a porous support by adopting a 3D ceramic ink writing device;

and S4, sintering the obtained support.

Further, in the step S1 of preparing the bioceramic powder, the Mg-containing CSi-Mgx powder is synthesized by a conventional chemical precipitation method to obtain the bioceramic powder with the particle size less than 5 μm.

Further, in the CSi-Mgx powder, x is 6%/10%/14%; the bioceramic powder was ground with a 400RPM grinder.

Further, step S23D ceramic bio-ink preparation was performed by mixing 5.0g of CSi-Mgx powder with 4.5g of 6% polyvinyl alcohol (PVA) solution to prepare a 3D ceramic ink.

Further, step S3, preparing the porous scaffold using the 3D ceramic ink writing device, is to add the CSi-Mgx ink into a 5ml syringe and extrude it from the conical nozzle by the movement of the plunger rod.

Further, step S3 is to prepare a porous scaffold using a 3D ceramic ink writing apparatus, and design a cylindrical porous CSi-Mgx scaffold model having a three-dimensional rectangular periodic porous structure using software.

Further, step S3 was to prepare a porous scaffold using a 3D ceramic ink writing device with an initial distance between fibers of 450 μm.

Further, step S3 is to prepare a porous support using a 3D ceramic ink writing device, set the moving speed of the glue dispensing device to 6mm/S, and the nozzle diameter to 450 μm.

Further, the stent obtained in step S4 is subjected to a sintering process in which a sample of the stent having a pore size of 1000 μm is dried at 80 ℃ overnight and sintered at a target temperature of 1150 ℃ in an air atmosphere at a heating rate of 2 ℃/min in a temperature-controlled oven by a microcontroller, and is maintained at the target temperature for 3 hours, and then naturally cooled.

Compared with the background art, the invention has the beneficial effects that:

the method of the invention uses Mg to partially replace Ca in calcium silicate, realizes the improvement of key performances such as mechanical performance, biodegradability and the like of the 3D printing biological ceramic scaffold, and has the advantages of bone regeneration potential and mechanical evolution in the aspect of repairing thin-walled bone defects.

Drawings

FIG. 1 is a flow chart of a method for modifying a calcium silicate bioceramic by magnesium according to the present invention.

Detailed Description

The invention is described in further detail below with reference to the figures and specific examples. The drawings are for illustrative purposes only and are not to be construed as limiting the patent; it will be understood by those skilled in the art that certain well-known structures and descriptions thereof may be omitted. Except for special indication, the medicines used in the invention are all commercial products.

According to the invention, the improvement of key performances such as mechanical property, biodegradability and the like of the 3D printing biological ceramic bracket is realized by partially replacing Ca in calcium silicate with Mg, and the effect of repairing bone defects is optimized.

The technical scheme adopted by the invention is as follows: a process for partially substituting Mg for Ca in calcium silicate comprising the steps of:

(1) preparation of bioceramic powder

CSi-Mgx powders doped with different amounts of Mg (x ═ 6, 10, 14%) were synthesized by conventional chemical precipitation methods and the powders were milled with a 400RPM mill to give bioceramic powders less than 5 μm. (too large a powder particle may cause clogging of a printing head due to agglomeration of powder)

(2)3D ceramic bio-ink preparation

CSi-Mgx powder and polyvinyl alcohol (PVA) solution are mixed to prepare the 3D ceramic ink. (5.0g of CSi-Mgx powder mixed with 4.5g of 6% polyvinyl alcohol (PVA) solution)

(3) Preparation of porous support by using 3D ceramic ink writing device

The CSi-Mgx ink was added to a 5ml syringe and extruded from a conical nozzle by movement of the plunger rod. A cylindrical porous CSi-Mgx bracket model with a three-dimensional rectangular periodic porous structure is designed by using software. The initial distance between the fibres was 450 μm. The moving speed of the dispensing device was 6mm/s and the nozzle diameter was 450. mu.m.

(4) Sintering the obtained stent

Drying a bracket sample with the pore diameter of 1000 mu m at 80 ℃ overnight, sintering the bracket sample in a furnace with the temperature controlled by a microcontroller at the target temperature of 1150 ℃ in an air atmosphere at the heating rate of 2 ℃/min, keeping the temperature for 3 hours after the target temperature is reached, naturally cooling the bracket sample to be below 100 ℃, and taking out the sample.

As a modification of the specific example, the powder obtained in step (1) was ground by a grinder at 400RPM to obtain a powder having a particle size of less than 5 μm.

As a modification of the specific example, the 3D ceramic ink in step (2) was obtained by mixing 5.0g of CSi-Mgx powder with 4.5g of 6% polyvinyl alcohol (PVA) solution.

The method for partially replacing Ca in calcium silicate by Mg realizes the improvement of key performances such as mechanical property, biodegradability and the like of the 3D printing biological ceramic scaffold, and has the advantages of bone regeneration potential and mechanical evolution in the aspect of repairing thin-walled bone defects.

The CSi-Mgx bioceramics showed significantly higher compressive strength than the CSi bioceramics as shown by compression tests. Before implantation, the CSi-Mg10 scaffold showed the highest compressive strength in all four groups of scaffolds (CSi, CSi-Mg6, CSi-Mg10, CSi-Mg14) (where the CSi-Mg10 group was > 65MPa, the CSi group was 20MPa, the CSi-Mg6 group was 45MPa, and the CSi-Mg14 group was 40 MPa). In the study of repairing skull bone defects in rabbits, the samples of the CSi-Mg10 group had significantly higher compressive strength at week 6 of implantation than the CSi group, and were still the highest (20.6-27.4 MPa) of all groups at the end of week 12 of implantation.

Compared with the pure calcium silicate bioceramic scaffold, the Mg-doped calcium silicate bioceramic scaffold is superior to the pure CSi scaffold in terms of osteoblast viability, ALP activity and expression of osteogenesis-related genes (including COL1, OCN, Osterix and Runx2) on the surface thereof, and the osteogenic gene expression is gradually enhanced as the doped Mg content is increased from 6% to 14%.

Mg in the bioceramic with mechanical strength can also enhance bone regeneration in a rabbit skull critical size bone defect repair model. In animal experiments it was demonstrated that at the same time point after stent implantation, the amount of new bone formation gradually increased as the Mg content doped in CSi increased from 6% to 14%. Therefore, for repairing certain bone defects, particularly thin-wall craniomaxillofacial bone defects, the CSi-Mg scaffold with proper Mg doping and high mechanical strength can achieve better clinical effect.

A method for modifying calcium silicate bioceramic (CSi) by magnesium (Mg) is used for partially replacing calcium component (CSi-Mgx) in calcium silicate, so that the improvement of key performances such as mechanical property, biodegradability and the like of a 3D printing bioceramic scaffold can be realized, and the effect of the scaffold on bone defect repair is optimized. A powder of CSi-Mgx (x ═ 6, 10, 14%) doped with Mg (6, 10, 14% refer to the proportion of the molecular weight of Mg in the Mg, Ca mixture) was synthesized by a conventional chemical precipitation method, the powder was ground in a grinder at 400RPM to obtain a powder with a particle size of less than 5 μm; ceramic ink was prepared by mixing 5.0g of CSi-Mgx powder with 4.5g of 6% polyvinyl alcohol solution, and a porous scaffold was prepared by using a 3D ceramic ink writing apparatus. The invention improves the mechanical strength (>40MPa) of the 3D printing porous biological ceramic scaffold without damaging the porosity (the change has no statistical difference, wherein the porosity of a control group CSi is 60 percent, and the porosity of a magnesium-containing group is 63 percent).

Magnesium (Mg) is another important biologically indispensable mineral microelement in bone remodeling, having the ability to enhance bone regeneration by bone substitutes. Various calcium magnesium silicate bioactive glasses and ceramics have been extensively studied for the regeneration and repair of bone. Furthermore, the mechanical properties of the calcium silicate ceramic can be significantly improved by doping a certain amount of Mg. Such CSi-Mgx ceramics exhibit significantly improved compactness, excellent toughness (>3.2MPa m1/2) and good bioactivity in simulated body fluids. Thus, it is reasonable to assume that this expected improvement in physicochemical and mechanical properties would allow a 3D porous CSi-Mgx bioceramic to better repair bone defects.

The formation of fully interconnected macroporous three-dimensional structures is a major goal in the fabrication of bone scaffolds. And 3D printing technology shows advantages in designing large pore size, connectivity and porosity among pores, and even high-strength structures according to mechanical principles.

Example 1

Firstly, a rabbit skull defect model (defect diameter is 8mm) is manufactured by a dental drill needle through an operation, then a Micro-CT is used for scanning a rabbit skull bone defect area, a bone defect model is built by utilizing 3D modeling software, and a corresponding support three-dimensional structure is designed according to a patient bone defect three-dimensional structure. CSi powder was synthesized by conventional chemical precipitation method, and the powder was ground in a grinder at 400RPM to obtain powder having a particle size of less than 5 μm; ceramic ink was prepared by mixing 5.0g of CSi-Mgx powder with 4.5g of 6% polyvinyl alcohol solution, and a stent having a square hole structure was prepared from bottom to top according to a standard Stereolithography (STL) file of a 3D model by using a 3D ceramic ink writing apparatus. The nozzle diameter was 450 μm, the moving speed of the nozzle was 6mm/s, and the layer thickness between adjacent layers was 400 μm. Subsequently, the stent sample having a pore size of 1000 μm was dried at 80 ℃ overnight, and sintered at a target temperature of 1150 ℃ in an air atmosphere at a heating rate of 2 ℃/min in a micro-controller temperature-controlled furnace and maintained at the target temperature for 3 hours, and then naturally cooled. The obtained scaffold has the external compressive strength of 20 MPa.

Example 2

Firstly, a rabbit skull defect model (defect diameter is 8mm) is manufactured by a dental drill needle through an operation, then a Micro-CT is used for scanning a rabbit skull bone defect area, a bone defect model is built by utilizing 3D modeling software, and a corresponding support three-dimensional structure is designed according to a patient bone defect three-dimensional structure. A CSi-Mg6 powder with diluted Mg doping was synthesized by conventional chemical precipitation method, the powder was milled in a mill at 400RPM to obtain a powder with a particle size of less than 5 μm; ceramic ink was prepared by mixing 5.0g of CSi-Mgx powder with 4.5g of 6% polyvinyl alcohol solution, and a stent having a square hole structure was prepared from below to above according to a standard Stereolithography (STL) file of a 3D model by using a 3D ceramic ink writing apparatus. The nozzle diameter was 450 μm, the moving speed of the nozzle was 6mm/s, and the layer thickness between adjacent layers was 400 μm. Subsequently, the stent sample having a pore size of 1000 μm was dried at 80 ℃ overnight, and sintered at a target temperature of 1150 ℃ in an air atmosphere at a heating rate of 2 ℃/min in a micro-controller temperature-controlled furnace and maintained at the target temperature for 3 hours, and then naturally cooled. The obtained scaffold had an in vitro compressive strength of 45 MPa.

Example 3

Firstly, a rabbit skull defect model (defect diameter is 8mm) is manufactured by a dental drill needle through an operation, then a Micro-CT is used for scanning a rabbit skull bone defect area, a bone defect model is built by utilizing 3D modeling software, and a corresponding support three-dimensional structure is designed according to a patient bone defect three-dimensional structure. A CSi-Mg10 powder with diluted Mg doping was synthesized by conventional chemical precipitation method, the powder was milled in a mill at 400RPM to obtain a powder with a particle size of less than 5 μm; ceramic ink was prepared by mixing 5.0g of CSi-Mgx powder with 4.5g of 6% polyvinyl alcohol solution, and a stent having a square hole structure was prepared from below to above according to a standard Stereolithography (STL) file of a 3D model by using a 3D ceramic ink writing apparatus. The nozzle diameter was 450 μm, the moving speed of the nozzle was 6mm/s, and the layer thickness between adjacent layers was 400 μm. Subsequently, the stent sample having a pore size of 1000 μm was dried at 80 ℃ overnight, and sintered at a target temperature of 1150 ℃ in an air atmosphere at a heating rate of 2 ℃/min in a micro-controller temperature-controlled furnace and maintained at the target temperature for 3 hours, and then naturally cooled. The obtained scaffold had an in vitro compressive strength of 65 MPa.

Example 4

Firstly, a rabbit skull defect model (defect diameter is 8mm) is manufactured by a dental drill needle through an operation, then a Micro-CT is used for scanning a rabbit skull bone defect area, a bone defect model is built by utilizing 3D modeling software, and a corresponding support three-dimensional structure is designed according to a patient bone defect three-dimensional structure. A CSi-Mg14 powder with diluted Mg doping was synthesized by conventional chemical precipitation method, the powder was milled in a mill at 400RPM to obtain a powder with a particle size of less than 5 μm; ceramic ink was prepared by mixing 5.0g of CSi-Mgx powder with 4.5g of 6% polyvinyl alcohol solution, and a stent having a square hole structure was prepared from below to above according to a standard Stereolithography (STL) file of a 3D model by using a 3D ceramic ink writing apparatus. The nozzle diameter was 450 μm, the moving speed of the nozzle was 6mm/s, and the layer thickness between adjacent layers was 400 μm. Subsequently, the stent sample having a pore size of 1000 μm was dried at 80 ℃ overnight, and sintered at a target temperature of 1150 ℃ in an air atmosphere at a heating rate of 2 ℃/min in a micro-controller temperature-controlled furnace and maintained at the target temperature for 3 hours, and then naturally cooled. The obtained stent has the in vitro compressive strength of 40 MPa.

Claims

1. A method for modifying a calcium silicate bioceramic by magnesium, comprising the steps of:

s1, preparing biological ceramic powder;

S2.3D preparing ceramic bio-ink;

s3, preparing a porous support by adopting a 3D ceramic ink writing device;

and S4, sintering the obtained support.

2. The method of claim 1, wherein the step S1 of preparing the bioceramic powder comprises synthesizing Mg-containing CSi-Mgx powder by conventional chemical precipitation method to obtain bioceramic powder with particle size less than 5 μm.

3. The method of claim 2, wherein x in the CSi-Mgx powder is 6%/10%/14%.

4. The method of claim 1, wherein the step S23D of preparing the ceramic bio-ink is to prepare the 3D ceramic ink by mixing CSi-Mgx powder with a polyvinyl alcohol solution.

5. The method of claim 1, wherein the step S3 of preparing the porous scaffold using the 3D ceramic ink writing device is to add the CSi-Mgx ink into a 5ml syringe and extrude the ink from a conical nozzle by the movement of a plunger rod.

6. The method of claim 1, wherein the step S3 is to prepare a porous scaffold by using a 3D ceramic ink writing device, and a cylindrical porous CSi-Mgx scaffold model with a three-dimensional rectangular periodic porous structure is designed by using software.

7. The method of claim 1, wherein the step S3 is performed by using a 3D ceramic ink writing device to prepare a porous scaffold, and the initial distance between fibers is 450 μm.

8. The method of claim 1, wherein the step S3 is to prepare the porous support using a 3D ceramic ink writing device, the moving speed of the dispensing device is 6mm/S, and the nozzle diameter is 450 μm.

9. The method of claim 1, wherein the step S4 is to sinter the scaffold sample with a pore size of 1000 μm at 80 deg.C overnight, and sinter the scaffold sample at 1150 deg.C in a micro-controller controlled temperature furnace at a heating rate of 2 deg.C/min in air atmosphere at a target temperature of 1150 deg.C, and keep the temperature at the target temperature for 3 hours, and then naturally cool.