Thermoplastic biomedical material for 3D printing and preparation method thereof

Abstract

The invention provides a thermoplastic biomedical material for 3D printing and a preparation method thereof. The printing material is endowed with intelligent characteristics of self-repairing, stimulation response, biological activity release and the like through precise regulation and control of material components (a dynamic cross-linked network and a nano reinforced phase). By combining the flexibility of thermoplastic poly (urethane-urea) and the rigidity of polyether ketone, the elastomer material with impact resistance and bearing capacity is successfully developed, the contradiction that a traditional material cannot meet dynamic and static mechanical requirements at the same time is solved, the operation process is simple, the repeatability is high, the toughness and the impact strength are ultrahigh, and the cost is low. The technical blank of high-performance biomedical materials is filled, and a new path is opened up for personalized medical treatment, minimally invasive surgery and long-term implantation treatment through three-in-one innovation of'material-process-function '.

Description

Technical Field

[0001] The present invention relates to a thermoplastic biomedical material for 3D printing and a preparation method thereof, which belongs to the technical field of polymer materials. In particular, it relates to a 3D-printable thermoplastic biomedical material and a preparation method thereof. Background Art

[0002] With the help of technological innovation, 3D printing of biomedical materials has strongly promoted the realization of personalized precision medicine, and at the same time broken through the limitations of traditional biomaterials in terms of performance and function. Integrating materials science, bioengineering and artificial intelligence technologies (such as using machine learning to optimize printing parameters) has promoted the coordinated development of bionic material design and intelligent manufacturing technologies, provided interdisciplinary solutions for frontier fields such as tissue engineering and drug controlled release, and accelerated the transformation process of regenerative medicine from the laboratory to the clinic.

[0003] Due to the mechanical response mechanism dominated by a single phase state, traditional biomedical materials are difficult to simultaneously meet the dynamic (such as high toughness under impact and cyclic loading) and static (such as high modulus and tensile strength) mechanical requirements. Taking bone repair materials as an example, they need to have both high rigidity (modulus > 1 GPa) to support bones and flexibility (elongation at break > 200%) to buffer stress. However, traditional metal or polymer materials (such as titanium alloy with a modulus of 110 GPa and PLA with an elongation at break < 10%) have contradictions such as the conflict between strength and toughness, and between fatigue resistance and hardness. Existing improvement strategies (such as using rigid fillers for reinforcement and constructing gradient pore structures) often come at the cost of sacrificing dynamic performance (increased brittleness of composites and decreased impact resistance of gradient structures) or biological activity. In addition, traditional implant materials (such as metals, ceramics or general polymers) rely on standardized production, are difficult to adapt to complex anatomical structures, have problems such as poor mechanical properties (such as mismatched elastic modulus and easy brittle fracture) and insufficient morphological adaptability, and are prone to adverse consequences such as stress shielding and the need for secondary surgery.

[0004] Therefore, there is an urgent need for a new type of biomedical material that can simultaneously meet dynamic and static mechanical requirements. Summary of the Invention

[0005] Aiming at the many problems existing in traditional biomedical materials, especially the problem of being unable to simultaneously meet dynamic and static mechanical requirements, the present invention provides a thermoplastic biomedical material for 3D printing and a preparation method thereof.

[0006] The thermoplastic biomedical material of the present invention has ultra-high toughness and impact strength, filling the technical gap of high-performance biomedical materials. Through the trinity innovation of "material - process - function", it has opened up a new path for personalized medicine, minimally invasive surgery and long-term implant treatment. The preparation method has simple operating procedures and high repeatability.

[0007] Term Explanation

[0008] Interpenetrating network: A blend composed of two or more mutually penetrating cross-linked polymers. It is formed by the continuous interpenetration of the networks obtained by cross-linking cross-linked polymer A and cross-linked polymer B respectively.

[0009] Dynamic cross-linked network: A cross-linked network structure is formed through reversible chemical bonds or physical interactions. This cross-linked structure can dissociate and re-assemble under specific conditions, thereby endowing the material with excellent reparability, remodelling ability and self-healing ability. For example, temperature-controlled cross-linking, light-controlled cross-linking, pH-sensitive cross-linking, etc. These dynamic cross-linking reactions have extensive applications in the fields of intelligent materials, drug release systems, 3D printing, etc.

[0010] Fused deposition modelling: A process developed by American scholar Dr. Scott Crump in 1988. It is a method that does not use a laser for processing. Its principle: The nozzle moves in the x-y direction and the z direction under computer control. The filament is heated to a temperature slightly higher than its melting point in the nozzle and extruded through a nozzle with a fine nozzle.

[0011] The present invention is realized through the following technical solutions:

[0012] In the first aspect of the present invention, a thermoplastic biomedical material for 3D printing is provided.

[0013] A thermoplastic biomedical material that can be used for 3D printing is composed of the following raw materials in parts by weight: 60 - 80 wt% of thermoplastic poly(urethane-urea), 20 - 40 wt% of polyether ketone PEK, and 1 - 5 wt% of surface-modified nanocellulose.

[0014] The thermoplastic biomedical material of the present invention uses thermoplastic poly(urethane-urea) as the flexible matrix and polyether ketone as the rigid reinforcing phase. Through melt blending, an interpenetrating network structure is formed, and polyether ketone is dispersed in the continuous phase of thermoplastic polyurethane TPU to achieve the synergistic load-bearing of rigidity and toughness.

[0015] Surface-modified nanocellulose is used as an interfacial compatibilizer. Its hydroxyl groups form hydrogen bonds with the polar groups of polyether ketone / thermoplastic polyurethane, greatly improving the interlayer bonding strength (interlayer shear strength > 15 MPa).

[0016] Preferably according to the present invention, the substitution rate of polycaprolactone groups introduced into the molecular chain of the thermoplastic poly(urethane-urea) is 5-20 mol%.

[0017] Preferably according to the present invention, the thermoplastic biomedical material for 3D printing is composed of the following raw materials in parts by weight: 70-80 wt% of thermoplastic poly(urethane-urea), 20-35 wt% of polyether ketone, and 2-5 wt% of surface-modified nanocellulose.

[0018] The second object of the present invention is to provide a preparation method of the above-mentioned thermoplastic biomedical material for 3D printing.

[0019] The preparation method of the above-mentioned thermoplastic biomedical material for 3D printing includes the following steps:

[0020] a) Mix the chain extender with the polyurethane prepolymer system and react to prepare thermoplastic poly(urethane-urea) particles through a granulation device;

[0021] b) According to the ratio, blend the thermoplastic polyurethane-urea particles, polyether ketone particles and surface-modified nanocellulose in a screw extruder to obtain a composite wire;

[0022] c) Layer-by-layer print the composite wire through a fused deposition modeling 3D printer to obtain the thermoplastic biomedical material.

[0023] Preferably according to the present invention, in step a), the polyurethane prepolymer is prepared by reacting poly(1,4-butylene adipate) with isophorone diisocyanate at 80-100 °C for 2-6 hours.

[0024] The polyurethane prepolymer and the thermoplastic poly(urethane-urea) particles can be prepared according to the existing technology.

[0025] Preferably according to the present invention, the surface-modified nanocellulose is prepared by the following method:

[0026] 1) Add 1 g of nanocellulose to 50 mL of dimethylformamide (DMF), stir at room temperature for 1-2 hours to fully disperse the nanocellulose in DMF to obtain a dispersion;

[0027] 2) Then add 0.1 g of 4-dimethylaminopyridine (DMAP) and 0.5 mL of triethylamine (TEA) to the above dispersion, and continue to stir for 30 minutes to make them evenly distributed in the system;

[0028] 3) Then slowly add 5 g of stearic acid. After adding stearic acid, slowly raise the temperature of the reaction system to 80 °C, and continuously stir and react at this temperature for 12-24 hours. At this temperature, the carboxyl group of stearic acid reacts with the hydroxyl group of nanocellulose to form an ester bond, realizing the grafting of long-chain fatty acid groups;

[0029] 4) After the reaction is completed, cool the reaction solution to room temperature, then slowly pour it into a large amount of absolute ethanol. Collect the precipitate by centrifugation or filtration, wash the collected precipitate with absolute ethanol 3 - 5 times, and centrifuge or filter after each washing to remove unreacted stearic acid, DMAP, TEA, and DMF impurities. Place the washed product in a vacuum drying oven and dry it at 40 - 50 °C for 12 - 24 hours to obtain surface - modified nanocellulose.

[0030] In the present invention, by grafting long - chain fatty acid groups onto the hydroxyl groups of cellulose to form ester or ether bonds, surface - modified nanocellulose is obtained, which greatly increases the hydrophobicity of the material, improves the dispersion performance of cellulose in the oily matrix, and maintains its original mechanical strength.

[0031] Preferably according to the present invention, in step b), the blending temperature is 160 - 200 °C and the rotation speed is 50 - 80 rpm.

[0032] Preferably according to the present invention, in step c), the nozzle temperature of the 3D printer is 120 - 140 °C.

[0033] Preferably according to the present invention, in step c), during the 3D printing process, the printing path is a bionic fiber orientation mode, so that the polyether ketone fibers are arranged along the main stress direction, and the inter - layer misalignment angle is 10 - 30°, optimizing the anti - delamination performance.

[0034] The preparation method of the present invention uses a low - temperature composite printing technology, fused deposition modeling (printing temperature 120 - 140 °C), controls the polyether ketone fibers to be oriented along the printing path (orientation degree > 70%), and realizes anisotropic mechanical properties (longitudinal tensile strength > 80 MPa, transverse > 50 MPa).

[0035] The above - mentioned thermoplastic biomedical materials applicable to 3D printing are used in the fields of tissue engineering, orthopedic surgery, dentistry, cardiovascular or maxillofacial surgery.

[0036] Advantages of the present invention

[0037] 1. By precisely regulating the material components (such as dynamic cross - linked network, nano - reinforcing phase) in the present invention, intelligent properties such as self - repair, stimulus response, and bioactive release are imparted to the printed materials. Combining the flexibility of thermoplastic poly(urethane - urea) with the rigidity of polyether ketone, an elastomer material with both impact resistance and load - bearing capacity is successfully developed, solving the contradiction that traditional materials cannot simultaneously meet the dynamic and static mechanical requirements.

[0038] 2. Through the design of a multi - scale rigid - flexible phase structure (polyether ketone / poly(urethane - urea) interpenetrating network) and 3D printing directional regulation in the present invention, the synergistic optimization of dynamic / static mechanical properties is realized, breaking through the limitations of a single material system.

[0039] 3. Through the trinity innovation of "material - process - function", the present invention has opened up a new path for personalized medicine, minimally invasive surgery and long - term implant treatment, and has significant scientific research value and social and economic benefits. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] The accompanying drawings forming a part of this application are used to provide a further understanding of this application. The schematic embodiments and descriptions thereof of this application are used to explain this application and do not constitute an improper limitation to this application.

[0041] Figure 1 It is a physical diagram of the composite wire made by blending thermoplastic poly(urethane - urea), polyether ketone and surface - modified nanocellulose in Example 1, with a diameter of 1.8 mm.

[0042] Figure 2 It is the three - time repeated tensile strain - stress curve of the composite wire made in Example 1.

[0043] Figure 3 It is the product diagram obtained by 3D printing in Example 1. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0044] It should be noted that the following detailed description is exemplary and is intended to provide further explanation of this application. Unless otherwise specified, all technical and scientific terms used in the present invention have the same meaning as commonly understood by those of ordinary skill in the technical field to which this application belongs.

[0045] The following will further elaborate on the present invention in conjunction with specific embodiments. It should be noted that the said specific embodiments are interpretations rather than limitations of the present invention.

[0046] Preparation of surface - modified nanocellulose in the embodiment:

[0047] 1) Add 1 g of nanocellulose into 50 mL of DMF, and stir at room temperature for 2 hours to fully disperse the nanocellulose in DMF to obtain a dispersion.

[0048] 2) Then add 0.1 g of 4 - dimethylaminopyridine (DMAP) and 0.5 mL of triethylamine (TEA) to the above - mentioned dispersion, and continue to stir for 30 minutes to make them evenly distributed in the system.

[0049] 3) Then slowly add 5 g of stearic acid. After adding stearic acid, slowly raise the temperature of the reaction system to 80 °C, and continuously stir and react at this temperature for 20 hours. At this temperature, the carboxyl group of stearic acid reacts with the hydroxyl group of nanocellulose to form an ester bond, realizing the grafting of long - chain fatty acid groups.

[0050] 4) After the reaction is completed, cool the reaction solution to room temperature, and then slowly pour it into a large amount of absolute ethanol. Collect the precipitate by centrifugation or filtration, wash the collected precipitate with absolute ethanol 3-5 times, and centrifuge or filter after each washing to remove unreacted stearic acid, DMAP, TEA, and DMF impurities. Place the washed product in a vacuum drying oven and dry it at 45 °C for 20 hours to obtain surface-modified nanocellulose.

[0051] Example 1:

[0052] A preparation method of a thermoplastic biomedical material for 3D printing is as follows:

[0053] a) Vacuum dehydrate 100 g of poly(butylene adipate) (molecular weight 1000) PBA 1000 at 120 °C for 2 h. After the temperature drops to room temperature, sequentially add 66.6 g of isophorone diisocyanate IPDI, 400 mL of DMF, and 0.7 mL of dibutyltin dilaurate DBTDL. Under a nitrogen atmosphere, heat in an 85 °C oil bath and carry out a prepolymerization reaction for 2 h with magnetic stirring. After the reaction is completed, cool the temperature to room temperature to obtain a polyurethane prepolymer. Add a solution of 34 g of isophorone diamine IPDA dissolved in 500 mL of DMF to the polyurethane prepolymer, and react at room temperature with magnetic stirring under a nitrogen atmosphere for 3 h. After the reaction is completed, granulate through a granulation device to obtain poly(urethane-urea) elastomer particles;

[0054] b) Blend 140 g of poly(urethane-urea) elastomer particles, 52 g of polyether ketone particles, and 8 g of surface-modified nanocellulose in a screw extruder at a temperature of 180 °C and a rotation speed of 60 rpm to obtain a composite wire;

[0055] c) Pass the composite wire through a fused deposition modeling 3D printer, plan the printing path as a bionic fiber orientation mode, with an interlayer misalignment angle of 30°, a nozzle temperature of 120 °C, and print layer by layer.

[0056] The composite wire obtained by blending in step b) is shown in Figure 1 , with a diameter of 1.8 mm. The three repeated tensile strain-stress curves of the composite wire are shown in Figure 2 , indicating that the composite wire is an elastomeric material with both impact resistance and load-bearing capacity.

[0057] Example 2:

[0058] A preparation method of a thermoplastic biomedical material for 3D printing is as follows:

[0059] a) 100 g of poly(1,4-butylene adipate) (molecular weight 1000) PBA 1000 was dehydrated under vacuum at 120 °C for 2 h. After the temperature was lowered to room temperature, 66.6 g of isophorone diisocyanate IPDI, 400 mL of DMF, and 0.7 mL of dibutyltin dilaurate DBTDL were added in sequence. Under a nitrogen atmosphere, it was heated in an oil bath at 85 °C and pre-polymerized with magnetic stirring for 2 h. After the reaction ended, the temperature was lowered to room temperature to obtain a polyurethane prepolymer. A solution of 34 g of isophorone diamine IPDA dissolved in 500 mL of DMF was added to the polyurethane prepolymer, and the reaction was carried out with magnetic stirring at room temperature under a nitrogen atmosphere for 3 h. After the reaction ended, it was granulated through a granulating device to obtain poly(urethane-urea) elastomer particles;

[0060] b) 140 g of poly(urethane-urea) elastomer particles, 74 g of polyether ketone particles, and 6 g of surface-modified nanocellulose were melt-blended in a screw extruder at a temperature of 180 °C and a rotation speed of 60 rpm to obtain a composite wire;

[0061] c) The composite wire was printed layer by layer through a fused deposition modeling 3D printer with the printing path planned in a biomimetic fiber orientation pattern, an interlayer misalignment angle of 20°, and a nozzle temperature of 130 °C.

[0062] Example 3:

[0063] A method for preparing a thermoplastic biomedical material for 3D printing is as follows:

[0064] a) 100 g of poly(1,4-butylene adipate) (molecular weight 1000) PBA 1000 was dehydrated under vacuum at 120 °C for 2 h. After the temperature was lowered to room temperature, 66.6 g of isophorone diisocyanate IPDI, 400 mL of DMF, and 0.7 mL of dibutyltin dilaurate DBTDL were added in sequence. Under a nitrogen atmosphere, it was heated in an oil bath at 85 °C and pre-polymerized with magnetic stirring for 2 h. After the reaction ended, the temperature was lowered to room temperature to obtain a polyurethane prepolymer. A solution of 34 g of isophorone diamine IPDA dissolved in 500 mL of DMF was added to the polyurethane prepolymer, and the reaction was carried out with magnetic stirring at room temperature under a nitrogen atmosphere for 3 h. After the reaction ended, it was granulated through a granulating device to obtain poly(urethane-urea) elastomer particles;

[0065] b) 160 g of poly(urethane-urea) elastomer particles, 44 g of polyether ketone particles, and 6 g of surface-modified nanocellulose were melt-blended in a screw extruder at a temperature of 180 °C and a rotation speed of 60 rpm to obtain a composite wire;

[0066] c) The composite wire was printed layer by layer through a fused deposition modeling 3D printer with the printing path planned in a biomimetic fiber orientation pattern, an interlayer misalignment angle of 20°, and a nozzle temperature of 130 °C.

[0067] Example 4:

[0068] Preparation method of thermoplastic biomedical material for 3D printing, the steps are as follows:

[0069] a) Vacuum dehydrate 100 g of poly(butylene adipate) (molecular weight 1000) PBA 1000 at 120 °C for 2 h. After the temperature drops to room temperature, sequentially add 66.6 g of isophorone diisocyanate IPDI, 400 mL of DMF, and 0.7 mL of dibutyltin dilaurate DBTDL. Under a nitrogen atmosphere, heat in an 85 °C oil bath and carry out a prepolymerization reaction for 2 h with magnetic stirring. After the reaction ends, cool the temperature to room temperature to obtain a polyurethane prepolymer. Add a solution of 34 g of isophorone diamine IPDA dissolved in 500 mL of DMF to the polyurethane prepolymer, and react for 3 h with magnetic stirring at room temperature under a nitrogen atmosphere. After the reaction ends, granulate through a granulating device to obtain poly(urethane-urea) elastomer particles;

[0070] b) Blend 140 g of poly(urethane-urea) elastomer particles, 58 g of polyether ketone particles, and 2 g of surface-modified nanocellulose in a screw extruder at a temperature of 180 °C and a rotation speed of 60 rpm to obtain a composite wire;

[0071] c) Pass the composite wire through a fused deposition modeling 3D printer, plan the printing path as a bionic fiber orientation pattern, with an interlayer misalignment angle of 10°, a nozzle temperature of 140 °C, and print layer by layer.

[0072] Comparative Example 1:

[0073] Same as the preparation method described in Example 1, the difference is that:

[0074] In step b), blend 100 g of poly(urethane-urea) elastomer particles and 100 g of polyether ketone particles in a screw extruder at a temperature of 180 °C and a rotation speed of 60 rpm to obtain a composite wire, and the others are carried out according to Example 1.

[0075] Comparative Example 2:

[0076] Same as the preparation method described in Example 1, the difference is that:

[0077] In step b), blend 170 g of poly(urethane-urea) elastomer particles, 29 g of polyether ketone particles, and 1 g of surface-modified nanocellulose in a screw extruder at a temperature of 180 °C and a rotation speed of 60 rpm to obtain a composite wire, and the others are carried out according to Example 1.

[0078] Comparative Example 3:

[0079] Same as the preparation method described in Example 1, the difference is that:

[0080] In step c), the composite wire is passed through a molten 3D printer, and the printing path is planned in a bionic fiber orientation mode, with an interlayer misalignment angle of 40°, a nozzle temperature of 140 °C, and printed layer by layer.

[0081] Performance testing

[0082] The thermoplastic composites prepared in Examples 1-4 and Comparative Examples 1-3 of this application were subjected to tensile testing and impact resistance testing. Three test specimens were prepared for each sample, and the test data were averaged.

[0083] The specific test results are shown in Table 1 below.

[0084]

[0085] From the results in Table 1, it can be seen that the thermoplastic composite prepared in Example 1 has the best mechanical properties.

[0086] Since polyether ketone is a rigid reinforcing phase dispersed in the thermoplastic polyurethane continuous phase, the mechanical properties of the material are improved; surface-modified nanocellulose, as an interfacial compatibilizer, forms hydrogen bonds between its hydroxyl groups and the polar groups of polyether ketone / thermoplastic polyurethane, greatly enhancing the interlayer bonding strength, improving the mechanical properties of the composite material, improving the processing performance, improving the dimensional stability, enhancing the biocompatibility, and promoting the dispersion of fillers, etc. If there are too many rigid reinforcing phases, the ability to absorb and disperse impact energy becomes weaker when subjected to impact, and the impact resistance performance deteriorates.

[0087] The above are only the preferred embodiments of this application and are not used to limit this application. For those skilled in the art, various changes and modifications can be made to this application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of this application shall be included within the protection scope of this application.

Claims

1. A thermoplastic biomedical material that can be used for 3D printing, which is composed of the following raw materials in parts by weight: 60 - 80 wt% of thermoplastic poly(urethane - urea), 20 - 40 wt% of polyether ketone (PEK), 1 - 5 wt% of surface - modified nano - cellulose.

2. The thermoplastic biomedical material usable for 3D printing according to claim 1, characterized in that, The substitution rate of polycaprolactone groups introduced into the molecular chain of the thermoplastic poly(urethane - urea) is 5 - 20 mol%.

3. The thermoplastic biomedical material usable for 3D printing according to claim 1, wherein It is composed of the following raw materials in parts by weight: 70 - 80 wt% of thermoplastic poly(urethane - urea), 20 - 35 wt% of polyether ketone, 2 - 5 wt% of surface - modified nano - cellulose.

4. The preparation method of the thermoplastic biomedical material for 3D printing according to claim 1, comprising the following steps: a) Mix and react the chain extender with the polyurethane prepolymer system, and prepare thermoplastic poly(urethane - urea) particles through a granulation device; b) According to the ratio, blend the thermoplastic polyurethane - urea particles, polyether ketone particles and surface - modified nano - cellulose in a screw extruder to obtain a composite wire; c) Layer - by - layer print the composite wire through a fused deposition modeling 3D printer to obtain a thermoplastic biomedical material.

5. The preparation method according to claim 4, characterized in that, In step a), the polyurethane prepolymer is prepared by reacting poly(1,4 - butanediol adipate) with isophorone diisocyanate at 80 - 100 °C for 2 - 6 hours.

6. The preparation method according to claim 4, characterized in that, The surface - modified nano - cellulose is prepared by the following method: 1) Add 1 g of nano - cellulose to 50 mL of dimethylformamide (DMF), stir at room temperature for 1 - 2 hours to fully disperse the nano - cellulose in DMF to obtain a dispersion; 2) Then add 0.1 g of 4 - dimethylaminopyridine (DMAP) and 0.5 mL of triethylamine (TEA) to the above - mentioned dispersion, and continue to stir for 30 minutes to make them evenly distributed in the system; 3) Then slowly add 5 g of stearic acid. After adding stearic acid, slowly raise the temperature of the reaction system to 80 °C, and continuously stir and react at this temperature for 12 - 24 hours. At this temperature, the carboxyl group of stearic acid reacts with the hydroxyl group of nano - cellulose to form an ester bond, realizing the grafting of long - chain fatty acid groups; 4) After the reaction, cool the reaction solution to room temperature, then slowly pour it into a large amount of absolute ethanol, collect the precipitate by centrifugation or filtration, wash the collected precipitate with absolute ethanol 3 - 5 times, and centrifuge or filter after each washing to remove unreacted stearic acid, DMAP, TEA and DMF impurities. The washed product is placed in a vacuum drying oven and dried at 40 - 50 °C for 12 - 24 hours to obtain surface - modified nano - cellulose.

7. The preparation method according to claim 4, characterized in that, In step b), the blending temperature is 160 - 200 °C and the rotation speed is 50 - 80 rpm.

8. The preparation method according to claim 4, wherein In step c), the nozzle temperature of the 3D printer is 120 - 140 °C.

9. The preparation method according to claim 4, characterized in that, In step c), during the 3D printing process, the printing path is in a biomimetic fiber orientation mode, making the polyether ketone fibers arranged along the main stress direction, and the inter - layer misalignment angle is 10 - 30°, optimizing the anti - delamination performance.

10. The application of the thermoplastic biomedical material for 3D printing according to claim 1 in the fields of tissue engineering, orthopedic surgery, dentistry, cardiovascular or maxillofacial surgery medicine.

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