TWI566920B - A Method of Making Biodegradable Calcium Silicate Medical Ceramics by Three - dimensional Printing Technology - Google Patents

Description

Method for manufacturing degradable calcium citrate biomedical ceramic by three-dimensional printing technology

The invention relates to a method for manufacturing calcium citrate biomedical ceramics, in particular to a method for manufacturing a degradable calcium citrate biomedical ceramic by three-dimensional printing technology.

With the rapid development of science and technology, the continuous improvement of medical technology has led to an increase in the average life expectancy of human beings, so the demand for medical resources is increasing. The skeleton is the hardest organ in the vertebrate. It is a dense connective tissue. Its main function is to support, exercise and protect the body as well as hematopoiesis and storage of minerals. As the population ages, there are more and more orthopaedic and dental-related patients, and millions of people rely on surgery to repair damaged or broken bones, teeth and joints every year.

In the past decade, the biomedical bone implant (Implant) has been widely used in clinical practice. Traditional autologous bone grafts can treat their bone defects, although there are no problems with infection and rejection, but the source of bone is limited. Allogeneic bone grafts may transmit the donor's own disease to the recipient, and also increase the chances of rejection and bacterial or viral infection, which may cause secondary morbidity, which in turn leads to the shortcomings of the treatment. In order to avoid the above disadvantages, Tissue Engineering (TE) was developed for the manufacture of artificial bones. Tissue engineering technology combines cells, engineering materials, scaffolds, and chemical factors to create artificial organs or repair damaged tissues.

Since cells cannot grow into the shape of a defected tissue or organ, it is necessary to guide the cell proliferation and differentiation with a specific shape of the 3D scaffold, thereby forming an extracellular matrix (ECM) to replace the damaged tissue, and good. The stent must meet the following conditions: Biocompatibility, Degradability, Porosity, Pore Size, Interconnected Pore, Mechanical Strength, Plasticity (Plasticity) ), Surface microstructure.

At present, the materials used for the preparation of the stent are mainly Bio-materials, and can be classified into metal, polymer, and ceramic. Biomedical metal (for example: 316L stainless Steel and titanium alloy stents do not metabolize over time after implantation in the human body, and there are problems such as stress shielding, abrasion or ion precipitation. Biomedical polymers (eg, PCL, PLA) stents, although having excellent plasticity, porosity, and degradability, are not mechanically strong and are not suitable for use in artificial bone implants.

Biomedical ceramics is the most noticeable bone scaffold material in the industry and academia in recent years. The reason is that the bone composition of the human body is similar to that of ceramic materials, and the biomedical ceramic materials do not cause material variation due to the implantation time of the implant (Implant). Natural bone tissue is mainly composed of Cortical bone and Sponge bone. The dense bone is a structure with low porosity and is mainly responsible for supporting the load. The sponge bone is a connected pore structure with a high porosity, and the pores are connected to each other, so as to provide more space for cell attachment, and the cells can easily take up oxygen and signal transmission between cells. However, ceramic materials are hard and brittle, and are easily brittle by conventional machining. Therefore, it is more difficult to manufacture a ceramic interconnected internal pore structure by a general processing method.

The use of biomedical ceramic materials to make bone scaffolds or artificial bones is the current development trend of tissue engineering. In addition to biomedical compatibility, biological activity and appropriate mechanical strength, biomedical ceramic materials also need to have appropriate porosity and internal interconnected pore structure. Therefore, many methods for producing ceramics having different porosities have been developed, such as particle precipitation method, freeze drying method, fiber bonding method, phase separation method, and sponge dipping method. Although the above method can produce a ceramic structure having a high porosity, the pore distribution is not uniform, and the pores and the pores cannot be ensured to communicate with each other, that is, these methods cannot produce a uniform inner communicating pore structure.

Another feature required for bone scaffolds is the rate of degradation. The stent needs to be metabolized over time to completely disappear, but the speed must be slightly slower than the rate of bone tissue regeneration, and eventually replaced by the regenerative tissue. The production of biomedical ceramic materials with degradable properties has been previously produced by conventional methods. In recent years, 3D printing technology has also been used to manufacture biomedical ceramic materials, which are described as follows:

There have been three main methods for producing calcium carbonate using cerium oxide and calcium oxide: Casting, hot pressure, and hot pressure and spark plasma sintering.

In addition to the conventional patent of calcium citrate, the Republic of China patent number I388348, the name "calcium silicate-based bone cement containing polymer and oligomer" and the preparation method thereof, is a mixture of calcium salt and strontium compound and gelatin. The calcium citrate material is prepared by a high temperature heat treatment method. This patent is only for material preparation methods and does not have the relevant technology for processing complex shapes.

In addition, the Republic of China Patent No.: I421062 describes the "forming method and molding equipment for porous biomedical ceramic skeleton brackets". The biomedical ceramic powder (such as: tricalcium phosphate, hydroxyapatite, etc.) and ceramic sol are used to make a porous biomedical ceramic skeleton scaffold by using the stacking principle. There is no mention of related methods for making calcium silicate ceramic materials.

Therefore, it is necessary to design a new method for manufacturing calcium silicate ceramics with degradable properties by laser three-dimensional printing technology to overcome the above drawbacks.

An object of the present invention is to provide a method for manufacturing a calcium citrate biomedical ceramic having degradable characteristics by using a laser three-dimensional printing technique, which can not only manufacture a conventional cutting method without the use of additive manufacturing technology. The finished ceramics of complex shape, and the ability to make ceramics with interconnected pore structures, can also increase the mechanical properties of porous ceramic structures.

An object of the present invention is to provide a method for producing calcium citrate biomedical ceramics having degradable characteristics by laser three-dimensional printing technology, and the calcium citrate biomedical ceramic manufactured by the invention is proved to be non-toxic and biological by cell culture. Capacitive, and calcium citrate has degradation properties that help bone regeneration.

Another object of the present invention is to provide a method for preparing a calcium citrate biomedical ceramic bone scaffold, which has a biomedical ceramic skeleton scaffold having both a dense bone and a sponge bone structure for bionic natural bone structure.

In order to achieve the above object, the present invention provides a method for producing a degradable calcium citrate biomedical ceramic by a three-dimensional printing technique, which comprises the following steps: a: using a drawing software to obtain a three-dimensional ceramic having an inner communicating pore structure. Model; b: the three-dimensional ceramic model is divided into several two-dimensional cross-section patterns by all layers of software, each of which contains a plurality of holes; c: the cerium oxide and the calcium carbonate are mixed in proportion with the zirconia balls Put into a container, place it in a ball mill to make it a semi-liquid material; d: use a roller, scraper or nozzle to evenly spread the semi-liquid material on the surface of a working platform; e: through a light source Scanning according to the two-dimensional cross-sectional pattern, the region scanned by the light source is solidified into a single layer two-dimensional thin layer, the unscanned region maintains a semi-liquid material; f: the lifting platform is lowered by a fixed height; g: Repeat steps (d)-(f) until the construction of a three-dimensional ceramic model; h: place the three-dimensional ceramic model in an ultrasonic oscillator, add deionized water to clean excess material on the surface of the model, and obtain a three-dimensional ceramic The green body; and i: the three-dimensional ceramic green body is placed in a high temperature furnace for heat treatment, heated to a suitable temperature and maintained for a period of time, so that the ceria and calcium carbonate are combined to form a calcium silicate ceramic.

In order to achieve the above object, the method for preparing a calcium citrate biomedical ceramic bone scaffold of the present invention comprises the following steps: a: preparing a ceramic-polymer composite slurry to prepare a bone scaffold; b: using a three-dimensional drawing software, Drawing a ceramic skeleton scaffold having an inner communicating hole structure; c: dividing the three-dimensional scaffold model into a plurality of two-dimensional cross-sectional patterns by a sliced soft body, the two-dimensional cross-sectional view containing a plurality of holes; d: using a roller, a scraper or a nozzle The liquid ceramic-polymer composite slurry is evenly laid on the surface of a working platform; e: the composite slurry is heated by a laser scanning system to heat the composite slurry to form a ceramic-polymer composite thin layer; f: lowering the lifting platform by a fixed height; g: repeating steps (d)-(f) until construction of a ceramic-polymer composite component; h: removing uncured composite slurry with deionized water , a three-dimensional ceramic-polymer composite green body can be obtained; and i: the three-dimensional ceramic-polymer composite green body is placed in a high temperature furnace for heat treatment to make the three-dimensional ceramic-polymer base Green laminate is converted into a biomedical ceramic bone scaffold.

The detailed description of the drawings and the preferred embodiments are set forth in the accompanying drawings.

10‧‧‧Laser Scanning System

11‧‧‧Ray beam

12‧‧‧ Beam expander

13‧‧‧Laser scanner

14‧‧‧F-θ lens

15‧‧‧Laser Power Meter

16‧‧‧ computer

1 is a schematic view showing a flow chart of a method for manufacturing a degradable calcium citrate biomedical ceramic by a three-dimensional printing technique according to a preferred embodiment of the present invention.

2 is a schematic view showing the degradation rate of calcium citrate and hydroxyapatite (HA) prepared by the method of the present invention after being immersed in an artificial body fluid (SBF) for four weeks.

Figure 3 is a schematic view showing the method of the present invention using different ratios of tannic acid After the high temperature treatment of calcium (Wollastonite) and hydroxyapatite (HA) to 1300 ° C, the volume shrinkage is 2 to 5%.

4 is a schematic view showing a flow chart of making a calcium silicate biomedical ceramic bone support by using a ceramic-polymer composite material according to another preferred embodiment of the present invention.

FIG. 5 is a schematic diagram showing a block diagram of a laser scanning system according to another preferred embodiment of the present invention.

FIG. 6 is a schematic view showing the XRD component analysis of the biomedical ceramic material prepared according to another preferred embodiment of the present invention after heat treatment at different temperatures.

Fig. 7 (a) is a schematic view showing the SEM crystal morphology observation of a biomedical ceramic material prepared by heat treatment at a temperature of 900 ° C according to another preferred embodiment of the present invention.

Fig. 7(b) is a schematic view showing the SEM crystal morphology observation of the biomedical ceramic material prepared by heat treatment at a temperature of 1100 °C according to another preferred embodiment of the present invention.

Fig. 7 (c) is a schematic view showing the SEM crystal morphology observation of the biomedical ceramic material prepared by heat treatment at a temperature of 1300 ° C according to another preferred embodiment of the present invention.

Fig. 7(d) is a schematic view showing the SEM crystal morphology observation of the biomedical ceramic material prepared by heat treatment at a temperature of 1500 °C according to another preferred embodiment of the present invention.

Fig. 8 is a schematic view showing the relationship between the number of cells and the number of culture days of the ceria and calcium citrate test pieces according to another preferred embodiment of the present invention.

Figure 9 is a schematic view showing an SEM image of the surface of a biomedical ceramic material to which an osteoblast (MG63) is attached to another preferred embodiment of the present invention.

Please refer to FIG. 1 to FIG. 2 , wherein FIG. 1 is a schematic flow chart of a method for manufacturing a degradable calcium citrate biomedical ceramic by a three-dimensional printing technique according to a preferred embodiment of the present invention; A schematic diagram of the degradation rate of calcium citrate and hydroxyapatite (HA) prepared by the method of the present invention after being immersed in an artificial body fluid (SBF) for four weeks.

As shown in the figure, the method for manufacturing a degradable calcium citrate biomedical ceramic by the three-dimensional printing technique of the present invention comprises the following steps: Step a: using a drawing software to obtain a three-dimensional structure having an internal communicating pore structure. Ceramic model; step b: the three-dimensional ceramic model is divided into several two-dimensional cross-section patterns by all layers of software, each of which contains a plurality of holes; step c: mixing the cerium oxide and the calcium carbonate in proportion The zirconia balls are placed in a container and placed in a ball mill to be ground in a semi-liquid state; step d: the semi-liquid material is evenly spread on the surface of a working platform by rollers, scrapers or nozzles; step e : scanning through a light source according to the two-dimensional cross-sectional pattern, the region scanned by the light source is solidified into a single layer two-dimensional thin layer, and the unscanned region maintains a semi-liquid material; step f: lowering the lifting platform Fixed height; step g: repeating steps (d)-(f) until construction completes a three-dimensional ceramic model; step h: placing the three-dimensional ceramic model in an ultrasonic oscillator, adding and removing Water can clean the surface of the model to obtain a three-dimensional ceramic green body; and step i: the three-dimensional ceramic green body is placed in a high temperature furnace for heat treatment, heated to a suitable temperature and held for a period of time to make cerium oxide and Calcium carbonate is compounded into a calcium citrate biomedical ceramic.

In the step a, the drawing software is used to obtain a three-dimensional ceramic model having an internal communicating pore structure; wherein the drawing model is, for example but not limited to, a three-dimensional drawing software, or a bone is obtained by computed tomography or nuclear magnetic resonance imaging. The two-dimensional cross-sectional view of the structure is constructed by using the three-dimensional curved soft weight to construct a high-resolution three-dimensional image of the bone structure.

In the step b, the three-dimensional ceramic model is divided into a plurality of two-dimensional cross-section patterns by all layers of software, and each two-dimensional cross-sectional view contains a plurality of holes.

In the step c, the cerium oxide and the calcium carbonate are mixed in proportion, and then placed in a container with a zirconia ball, and placed in a ball mill to be a semi-liquid material by ball milling; wherein the cerium oxide and calcium carbonate The mixing ratio is, for example but not limited to, 80 to 95:20 to 5 wt%, and the rotation speed of the ball mill is, for example but not limited to, 15 to 60 RPM, and the ball milling time is, for example but not limited to, 1 to 3 hours.

In the step d, the semi-liquid material is evenly spread on the surface of a working platform by using a roller, a scraper or a nozzle.

In the step e, the light source is scanned according to the two-dimensional cross-sectional pattern, and the region scanned by the light source is solidified into a single layer two-dimensional thin layer, and the unscanned region maintains a semi-liquid material; wherein the light source For example, but not limited to, carbon dioxide laser light, NdYAG laser light, UV light or UV heating lamp, wherein the power of the carbon dioxide laser light is, for example but not limited to, 5 to 20 W, and the scanning speed is, for example but not limited to, 50 to 300 mm/second and The scanning pitch is, for example but not limited to, 0.05 to 0.2 mm.

In the step f, the lifting platform is lowered by a fixed height; wherein the lifting height of the lifting platform is, for example but not limited to, 25 to 100 μm.

In this step g, the steps (d)-(f) are repeated until the construction of a three-dimensional ceramic model is completed.

In the step h, the three-dimensional ceramic model is placed in an ultrasonic oscillator, and deionized water is added to wash excess material on the surface of the model to obtain a three-dimensional ceramic green body; wherein the descending height of the lifting platform is, for example but not limited to, It is 25~100μm.

In the step i, the three-dimensional ceramic green body is placed in a high temperature furnace for heat treatment, heated to a suitable temperature and held for a period of time, so that the ceria and calcium carbonate are combined to form a calcium silicate ceramics; The heating rate of the high temperature furnace is, for example but not limited to, 2 to 10 ° C / min, and is heated to a suitable temperature such as, but not limited to, 1300 ° C and holding temperature, for example, but not limited to, 1 to 3 hours.

The invention adopts liquid cerium oxide (SiO ₂ ) and calcium carbonate (CaCO ₃ ) powder as raw materials, and uniformly mixes into a semi-liquid state with fluidity and viscous property, and solidifies (Solidify) reaction of the material by laser light heating. The ceramic green body is formed, and the cerium oxide and calcium carbonate are materialized into wollastonite by high temperature heat treatment, and the reaction formula is as shown in formula (1).

CaCO _{3 (solid)} + SiO _{2 (liquid)} = CaSiO _{3 (solid)} + CO _{2 (gas)} . . . . . (1)

Wollastonite, also known as calcium silicate (CaSiO3), is degradable to help bone regeneration. Commonly used biomedical ceramic materials such as Hydroxyapatite (HA) and Tricalcium phosphate (TCP), although biocompatibility, are not degradable. In addition, commonly used bone filling materials such as calcium sulfate and calcium carbonate have biocompatibility and degradability characteristics, however, because the degradation rate is too fast, the new bone has not formed and the degradation is completed.

As shown in Fig. 2, it is a degradation rate experiment of calcium citrate and HA immersed in artificial body fluid (SBF) around the method according to the method of the present invention. It can be seen from the figure that HA hardly degrades, calcium citrate and HA. Each 50% has a degradation rate of 1.5%, and the calcium citrate degradation rate is 4%. When the calcium ruthenate material is implanted in the human body, it will synthesize apatite with HPO4 in human body fluid, which not only has biocompatibility but also has a good osseointegration effect, which can enhance the implantation of the implant in the human body. Combines strength and has an appropriate rate of degradation to aid in the formation of new bone.

Please refer to FIG. 3 , which illustrates the method of the present invention, which uses a different particle size of cerium oxide and calcium carbonate as a raw material to be synthesized by high temperature treatment to 1300 ° C, and the volume shrinkage is 2 to 5%. Schematic, however, the shrinkage of hydroxyapatite is as high as 38%. As shown in Figure 3. Although cerium oxide will swell, calcium carbonate will shrink, causing the volumetric shrinkage of calcium citrate to drop drastically, reducing dimensional error and shape deformation. Significantly reducing the shrinkage and deformation of biomedical ceramics is a major feature of the biomedical ceramic manufacturing method of the present invention: calcium citrate can be made into a variety of artificial bone implants with small dimensional errors and in line with clinical use.

Referring to FIG. 4 to FIG. 7d, FIG. 4 is a schematic flow chart of a method for fabricating a calcium silicate biomedical ceramic bone support according to another preferred embodiment of the present invention; FIG. 5 is another preferred embodiment of the present invention. A schematic block diagram of a laser scanning system of an embodiment; FIG. 6 is a schematic view showing XRD component analysis of a biomedical ceramic material prepared according to another preferred embodiment of the present invention after heat treatment at different temperatures; FIG. 7(a) A schematic diagram of SEM crystal morphology observation after heat treatment of a biomedical ceramic material prepared according to another preferred embodiment of the present invention at a temperature of 900 ° C; FIG. 7(b) illustrates the present invention according to another preferred embodiment. The prepared biomedical ceramic material is subjected to heat treatment at a temperature of 1100 ° C, and a schematic view of SEM crystal morphology observation is carried out; FIG. 7 (c) shows a heat treatment of a biomedical ceramic material prepared at a temperature of 1300 ° C according to another preferred embodiment of the present invention. After that, a schematic view of the SEM crystal morphology observation is performed; and FIG. 7(d) is a schematic view showing the SEM crystal morphology observation of the biomedical ceramic material prepared by heat treatment at a temperature of 1500 ° C according to another preferred embodiment of the present invention.

As shown in the figure, the method for preparing a calcium citrate biomedical ceramic bone scaffold of the present invention comprises the following steps: Step a: preparing a ceramic-polymer composite slurry to prepare a bone scaffold; and step b: using a three-dimensional drawing The soft body is drawn with a ceramic skeleton support having an inner communicating hole structure; step c: dividing the three-dimensional support model into a plurality of two-dimensional cross-sectional patterns by the sliced soft body, the two-dimensional cross-sectional view containing a plurality of holes; step d: using a roller and a scraper Or the nozzle evenly spreads the semi-liquid ceramic-polymer composite slurry on a working level Step e: heating the composite slurry by laser light from a laser scanning system 10 to form a ceramic-polymer composite thin layer; step f: lowering the lifting platform by a fixed height; step g : Repeat steps (d)-(f) until the completion of a ceramic-polymer composite component; step h: remove the uncured composite slurry with deionized water to obtain a three-dimensional ceramic-polymer base The composite material green body; and the step i: the three-dimensional ceramic-polymer matrix composite material green body is placed in a high temperature furnace for heat treatment, and the three-dimensional ceramic-polymer matrix composite material green body is converted into a biomedical ceramic bone support.

In the step a, a ceramic-polymer-based composite slurry is prepared to prepare a bone scaffold; wherein the ceramic-polymer-based composite slurry is, for example but not limited to, a biomedical ceramic powder, a polymer powder, and a It is composed of ionized water or ball-milled by adding zirconium balls by a ceria powder, a calcium carbonate powder or an aqueous polyvinyl alcohol solution, wherein the ceria powder is, for example but not limited to, 20 to 80% by weight, and the calcium carbonate powder is, for example, However, it is not limited to 20 to 60% by weight, and the aqueous polyvinyl alcohol solution is, for example but not limited to, 20 to 50% by weight.

In the step b, using a three-dimensional drawing software, a ceramic skeleton scaffold having an inner communicating pore structure is drawn; wherein the drawing model is, for example but not limited to, a three-dimensional drawing software, or a bone structure is obtained by computer tomography or magnetic resonance imaging. Dimensional section view, using the three-dimensional surface of the captured three-dimensional section to create a high-resolution three-dimensional image of the bone structure.

In the step c, the three-dimensional scaffold model is divided into a plurality of two-dimensional cross-sectional patterns by the sliced soft body, and the two-dimensional cross-sectional view contains a plurality of holes.

In the step d, the semi-liquid ceramic-polymer composite slurry is evenly spread on the surface of a working platform by using a roller, a doctor blade or a nozzle.

In the step e, the composite slurry is heated by a laser scanning system to heat the composite slurry to form a ceramic-polymer composite thin layer; wherein the laser light is, for example but not limited to, carbon dioxide laser light.

In addition, as shown in FIG. 5, the laser scanning system 10 includes a laser beam 11, a beam expander 12, a laser scanner 13, an F-theta lens 14, a laser power meter 15, and a computer. 16. In order to stabilize the laser processing parameters, the laser beam 11 is first irradiated onto the laser power meter 15 for processing, the laser power density 15 is read, and the obtained value is analyzed by the computer 16 to perform voltage adjustment. Adjust this The output power of the laser beam 11 is such that the laser power density absorbed by the material is uniform, and a thin ceramic layer of uniform quality is produced.

In the step f, the lifting platform is lowered by a fixed height; wherein the lifting height of the lifting platform is, for example but not limited to, 10 to 100 μm. Among them, the height selection will be adjusted according to the complexity of the original structure and the porosity of the original. When the original structure is more complicated, the thicker the slurry layer thickness, and vice versa, the thicker, so as to reduce the molding time. In the porosity part, when the original porosity requirement is low, the thickness of the layer thickness is selected to be thin. When the original porosity requirement is high, the layer thickness with a larger height is selected.

In this step g, steps (d)-(f) are repeated until a ceramic-polymer matrix composite component is constructed. Through this process, any external shape and components of the internal structure can be formed, such as a ceramic-polymer composite bionic bone support.

In this step h, a three-dimensional ceramic-polymer composite green body is obtained by removing the uncured composite slurry with deionized water. After the processing is completed, the portion that has not been irradiated by the laser beam 11 remains in the form of a slurry. In order to remove the solidified slurry, it is removed by using deionized water to obtain a three-dimensional ceramic-polymer base. Green part.

In the step i, the three-dimensional ceramic-polymer composite green body is placed in a high temperature furnace for heat treatment, and the three-dimensional ceramic-polymer composite green body is converted into a biomedical ceramic bone support. The three-dimensional composite material green body comprises a polyvinyl alcohol polymer material, and the function thereof is to fix the three-dimensional ceramic green embryo structure, and the mechanical strength thereof is insufficient. Therefore, it is necessary to cause a chemical reaction between cerium oxide and calcium carbonate by a high-temperature heat treatment method to form calcium citrate. The heating rate is 2 to 10 degrees per minute and the holding time is 30 to 240 minutes. In the high-temperature heat treatment process, the temperature is first maintained to 300 degrees. This part is used to burn polyvinyl alcohol through high temperature disintegration, and the ceramic-polymer-based composite bionic bone scaffold is converted into biomedical ceramics. Bone support. At the same time, the internal moisture is removed to prevent the water from being volatilized when the temperature rises, and the biomedical ceramic bone support is cracked and destroyed.

As shown in FIG. 6 , after the heat treatment of the biomedical ceramic material prepared by the above examples at different temperatures, XRD component analysis and SEM crystal morphology observation, after the heat treatment temperature of 900 ° C, the composition is mostly cerium oxide element. And a small amount of calcium. When the heat treatment temperature was raised to 1100 ° C, most of the cerium oxide had been converted into cristobalite and began to precipitate calcium silicate (Wollastonite). Show carbonic acid Calcium can not only synthesize calcium citrate with cerium oxide, but also accelerate the conversion of cerium oxide to cristobalite. When heat treated to 1300 ° C and 1500 ° C, calcium silicate (Wollastonite) was also precipitated.

As the heat treatment temperature increases, the surface will begin to precipitate calcium silicate with different size structures. As shown in Fig. 7 (a), after heating to 900 ° C, CaSiO _{3 was} formed on the surface of the material. As the temperature increases, the surface begins to produce strip-like crystals, as shown in Figure 7(b), which produces a Needle-like crystal at 1100 °C. When the temperature is raised to 1300 °C. As shown in Fig. 7(c), the Needle-like crystal grows into a long needle-like structure, which is a typical crystal morphology of β-Wollastonite, which means that 1300 °C can indeed synthesize cerium oxide and calcium carbonate into calcium citrate. As shown in Fig. 7(d), when the temperature is heated to 1500 ° C, the needle-like structure disappears and turns to form a small-sized oval α-Wollastonite.

Please refer to FIG. 8 , which is a schematic diagram showing the relationship between the number of cells and the number of culture days of the ceria and calcium citrate test pieces according to another preferred embodiment of the present invention. In order to confirm the biocompatibility of the calcium carbonate biomedical ceramic bone scaffold synthesized by the present invention through cerium oxide and calcium carbonate, it is observed through in vitro cell culture whether the cells can be attached to the biomedical ceramic bone scaffold for subsequent bone growth and osseointegration. . As shown in Fig. 8, in order to compare the in vitro cell culture status of cerium oxide and calcium citrate biomedical ceramic bone scaffold. As can be seen from the figure, the number of cells made by the two materials will increase with the increase of the culture time. However, when the calcium citrate was cultured until the seventh day, the number of cells was three times that of cerium oxide. Therefore, calcium citrate is indeed helpful for cell attachment and growth.

Please refer to FIG. 9 , which is a schematic diagram showing the SEM image of the osteophyte-like cell (MG63) attached to the surface of the biomedical ceramic material of another preferred embodiment of the present invention. As shown, after a period of time, the osteoblasts (MG63) can be attached to the surface of the biomedical ceramic material after the biomedical ceramic bone scaffold made according to the method of the present invention.

Therefore, the calcium citrate biomedical ceramic produced by the method for manufacturing the degradable calcium citrate biomedical ceramic by the three-dimensional printing technique according to the present invention has the following advantages: 1. It uses the additive manufacturing technique. It can manufacture finished ceramics of complex shape that cannot be made by traditional cutting methods, and can make ceramics with internal interconnected pore structure, and can also increase the mechanical properties of porous ceramic structures; 2. Calcium citrate biomedical ceramics produced by the same Cell culture to verify its non-toxicity and biocompatibility, and calcium citrate has degradation characteristics to help bone regeneration; 3, the biomedical ceramic skeleton made by it The scaffold has both a dense bone and a sponge bone structure for bionic natural bone structure; 4, biomedical degradability; and 5, which can reduce the shrinkage rate and the deformation amount, and therefore, is indeed more advanced than the conventional technology.

The disclosure of the present invention is a preferred embodiment of the present invention. Any part of the present invention can be easily inferred from those skilled in the art without departing from the technical spirit of the present invention. .

In summary, the present invention, regardless of its purpose, means and efficacy, is showing its technical characteristics different from the prior art, and its first invention is practical and practical, and is also in compliance with the patent requirements of the invention, and is requested to be examined by the reviewing committee. Pray for the patents at an early date.

Claims (10)

A method for manufacturing a degradable calcium silicate ceramic by a three-dimensional printing technique, comprising the steps of: a: using a drawing software to obtain a three-dimensional ceramic model having an inner communicating pore structure; b: by using everything The layer software divides the three-dimensional ceramic model into a plurality of two-dimensional cross-section patterns, each of which contains a plurality of holes; c: the cerium oxide and the calcium carbonate are mixed in proportion and then placed in a container with the zirconia balls. Ball milling in a ball mill to make it a semi-liquid material; d: uniformly flattening the semi-liquid material on a working platform surface by using a roller, a scraper or a nozzle; e: scanning through a two-dimensional cross-sectional pattern through a light source The area scanned by the light source is solidified into a single layer of two-dimensional thin layer, the unscanned area maintains a semi-liquid material; f: the lifting platform is lowered by a fixed height; g: repeated (d)-(f The steps are completed until a three-dimensional ceramic model is constructed; h: the three-dimensional ceramic model is placed in an ultrasonic oscillator, and deionized water is added to wash excess material on the surface of the model to obtain a three-dimensional ceramic ; And i: the three-dimensional ceramic green body is placed in a high-temperature heat treatment furnace, heated to an appropriate temperature and holding temperature for some time, so that calcium carbonate and silicon dioxide into a calcium silicate compound reaction biomedical ceramic. The method of claim 1, wherein in the step a, the drawing model can use a three-dimensional drawing software, or obtain a two-dimensional cross-sectional view of the bone structure by a computed tomography or a nuclear magnetic resonance image. The two-dimensional sectional view uses a three-dimensional surface soft weight to create a high-resolution three-dimensional image of the bone structure. The method of claim 1, wherein in the step c, the mixing ratio of the ceria and the calcium carbonate is 80 to 95:20 to 5 wt%, and the rotation speed of the ball mill is 15 to 60 RPM, and the milling time is It is 1~3 hours. The method of claim 1, wherein in the step e, the light source is carbon dioxide laser light, NdYAG laser light, UV light or UV heating lamp, wherein the power of the carbon dioxide laser light is 5-20 W, sweeping The aiming speed is 50~300mm/sec and the scanning pitch is 0.05~0.2mm. The method of claim 1, wherein in the step f, the lifting platform has a descending height of 25 to 100 μm. The method of claim 1, wherein in the step i, the heating rate of the high temperature furnace is 2 to 10 ° C / min, and the heating is performed to a suitable temperature of 1300 ° C and the temperature is maintained for 1 to 3 hours. A method for preparing a calcium citrate biomedical ceramic bone scaffold comprises the following steps: a: preparing a ceramic-polymer composite slurry to prepare a bone scaffold; b: using a three-dimensional drawing software to draw an inner communicating pore structure Ceramic skeleton scaffold; c: the three-dimensional scaffold model is divided into several two-dimensional cross-section patterns by a sliced soft body, the two-dimensional cross-sectional view contains a plurality of holes; d: a semi-liquid ceramic-polymer base is used by a roller, a scraper or a nozzle The composite slurry is evenly laid on the surface of a working platform; e: the laser is irradiated by a laser scanning system to heat the composite slurry to form a ceramic-polymer composite thin layer; f: the lifting platform is lowered a fixed height; g: repeating steps (d)-(f) until construction of a ceramic-polymer composite component; h: removing the uncured composite slurry with deionized water to obtain a three-dimensional ceramic - a polymer matrix composite green body; and i: the three-dimensional ceramic-polymer matrix composite material green body is placed in a high temperature furnace for heat treatment, so that the three-dimensional ceramic-polymer matrix composite material green body is converted into a lifetime Ceramic bone scaffold. The method of claim 7, wherein in the step a, the ceramic-polymer composite slurry is composed of a biomedical ceramic powder, a polymer powder, and deionized water. The method of claim 7, wherein in the step b, the drawing model can use a three-dimensional drawing software, or obtain a two-dimensional cross-sectional view of the bone structure by a computed tomography or a nuclear magnetic resonance image, The two-dimensional sectional view uses a three-dimensional surface soft weight to create a high-resolution three-dimensional image of the bone structure. The method of claim 7, wherein in the step e, the laser light is carbon dioxide laser light, the laser scanning system comprises a laser beam, a beam expander, a laser scanner, An F-θ lens, a laser power meter, and a computer; in the step f, the lifting platform has a descending height of 10 to 100 μm.