CN102895706B - Biomedical anti-corrosion porous compound material and preparation method thereof - Google Patents

Abstract

The invention relates to a biomedical corrosion-resistant porous composite material and a preparation method thereof. The porous composite material is composed of a porous magnesium alloy substrate, a pretreatment layer and a polymer coating; the porous magnesium alloy substrate is magnesium zinc with a magnesium content > 90%. alloy, magnesium-calcium alloy, magnesium-lithium alloy, magnesium-strontium alloy, or ternary alloys composed of the alloy components of the above systems; the pore diameter of the porous magnesium alloy substrate is 100-1200 μm, the pore depth of the closed cells is 100-500 μm, and the porosity The pretreatment layer is an oxidation/phosphating layer with a thickness of 1-10 μm; the polymer coating is a degradable and aliphatic polymer material layer with a thickness of 5-30 μm. The preparation method includes preparing a porous magnesium alloy base material, obtaining an oxide film on the surface of the porous magnesium alloy base material and in the pores as an intermediate layer of a subsequent polymer coating, and coating a high molecular polymer layer. The invention reduces the corrosion rate of the porous magnesium alloy substrate and improves its strength and toughness.

Description

A biomedical corrosion-resistant porous composite material and preparation method thereof

technical field

The invention relates to orthopedic internal fixation materials in medical devices, belonging to the field of biomedical devices, in particular to a biomedical corrosion-resistant porous composite material that can be used for bone repair and a preparation method thereof.

Background technique

The repair of bone tissue injury has always been a major problem in clinical medicine. Bone injuries caused by natural disasters, traffic accidents, industrial injuries, sports trauma, bone tumor resection, metabolic osteoporosis (OP), and congenital bone diseases have become one of the major diseases that threaten people's health. At present, metal materials still play an important role in bone repair. Compared with ceramic materials and polymer materials, metals have high mechanical strength and fracture toughness, and are suitable for use in load-bearing areas. Applied metal biomaterials include stainless steel, cobalt-based alloys, titanium and titanium alloys, Ni-Ti alloys, and magnesium alloys, among which magnesium alloys are more widely used. A drawback of currently used metallic materials is the potential release of toxins or particles through corrosion or friction, thus causing inflammation, thereby reducing biocompatibility and causing tissue wear. More importantly, the elastic modulus of such metal materials does not match that of natural bone, which is prone to stress shielding. The use of magnesium alloy as a bone repair material has many advantages: 1) Mechanical compatibility: the elastic modulus is about 41-45GPa, and its density is 1.7-1.9g/ ^cm3 , which is equivalent to natural bone; 2) Biological characteristics: Magnesium It has good biocompatibility, it is also a common factor of many enzymes, it is also a key element of energy transport, storage and utilization, it can regulate and stabilize the structure of RNA and DNA, and it plays an important role in regulating cell growth and maintaining cell membrane structure ;3) Safety, magnesium is harmless to the human body, has good biocompatibility, excess magnesium can be excreted through urine; 4) biodegradability, absorbability; 5) local alkaline environment promotes osteoinduction function to promote new bone formation.

However, magnesium alloys still have many deficiencies as bone repair materials:

(1) Magnesium alloy has poor corrosion resistance, lively performance, and is easy to corrode to form oxide film: the research of Nanjing Medical University shows that due to the nature of magnesium alloy, it is loose and porous after being implanted as a dental bone repair material, which cannot be used in the experiment. Protects the gingival base. In order to solve the key problem of poor corrosion resistance of magnesium alloys in the human body, the laboratory adopted the micro-arc oxidation method to treat the surface of magnesium alloys and achieved relatively ideal results.

(2) The degradation speed of magnesium alloy is fast. The biodegradation speed of magnesium alloy in the human body is too fast, and it often corrodes seriously before the fracture fixation and healing are not completely stable, and the excessive corrosion degradation speed will cause a significant decrease in mechanical strength and reduce the risk of fracture. At the same time, the excessive release of magnesium ions and the high pH value trigger the excessive secretion of BMP-2, thereby activating osteoclasts and resulting in osteolysis.

(3) The absorption of magnesium ions has an important interaction with the absorption of VD, calcium and phosphorus: excessive magnesium ions will inhibit the precipitation and absorption of calcium and phosphorus when magnesium metabolism is disordered, resulting in imbalance of calcium absorption and delay of new bone formation .

The deficiencies in the above aspects of magnesium alloy limit its application. In order to improve the application value of magnesium alloy and reduce the side effects caused by its use, it is an important process to protect magnesium alloy from corrosion through various modification methods.

In order to solve the above-mentioned problems, the prior art begins to use porous magnesium and its alloys as bone repair materials, which is mainly based on the light weight and excellent mechanical properties of porous magnesium and its alloys, and the use of porous magnesium and its alloys for bone repair Like polymer porous scaffolds and ceramic porous scaffolds, it can provide three-dimensional growth space for cells, which is conducive to the exchange and transportation of nutrients and metabolites. The biological activity induced by itself can induce cell differentiation and growth and blood vessel growth.

At present, there are more and more explorations on the prospect of porous magnesium alloys in bone repair. At present, they mainly focus on: exploring the relationship between porosity, pore size and mechanical properties, and degradation properties. The degradation properties of porous magnesium/magnesium alloys and calcium phosphate composite porous materials research, biocompatibility studies. The invention uses porous magnesium alloy as the base to prepare composite bone repair material, and the composite material used is a polymer that can be used for bone repair. The composite bone repair material has the advantages of magnesium alloy, porous structure and polymer material, but at the same time They can overcome their respective shortcomings and have great application prospects in bone repair, but so far there are few research reports at home and abroad.

Contents of the invention

Aiming at the above deficiencies in the prior art, the present invention solves the corrosion and mechanical problems of porous magnesium alloys in the body, and provides a porous magnesium alloy medical composite material to improve the corrosion resistance and toughness of the composite material, and avoid magnesium After the alloy is implanted in the body, excessive hydrogen and magnesium ions are generated.

The invention also provides a preparation method of the biomedical corrosion-resistant porous composite material with simple operation and strong practicability.

In order to solve the above technical problems, the present invention adopts the following technical solution, a biomedical corrosion-resistant porous composite material, characterized in that it consists of a porous magnesium alloy substrate, a pretreatment layer and a polymer coating;

Among them, the porous magnesium alloy substrate is a magnesium-zinc alloy, magnesium-calcium alloy, magnesium-lithium alloy, magnesium-strontium alloy or a ternary alloy composed of the above-mentioned alloy components with a magnesium content greater than 90%; the pore diameter of the porous magnesium alloy substrate 100-1200μm, the pore depth of closed cells is 100-500μm, and the porosity is 30%-70%;

The pretreatment layer is an oxidation/phosphating layer with a thickness of 1-10 μm;

The polymer coating is a degradable, aliphatic polymer material layer with a thickness of 5-30 μm.

Further, the porous magnesium alloy substrate is AZ31 or Mg-Ca series magnesium alloy. The degradable and aliphatic polymer material is polylactic acid, poly-L-lactic acid, polycaprolactone, polyamide or polyurethane.

The present invention also provides a method for preparing a biomedical corrosion-resistant porous composite material, comprising the following sequential steps:

1) Preparation of porous magnesium alloy substrate:

a. Prepare any two alloys of as-cast magnesium-calcium, magnesium-lithium, magnesium-zinc and magnesium-strontium or a ternary alloy composed of said elements. In the alloy, except magnesium, the weight of other elements accounts for the total weight percentage of the ternary magnesium alloy <10%;

b. punching the porous magnesium alloy substrate;

2) For the pretreatment of porous magnesium alloys, the oxidation method is used to obtain a uniformly distributed oxide film on the surface and inside the pores of the porous magnesium alloy substrate as the intermediate layer of the subsequent polymer coating, or the phosphating method is used to obtain a uniformly distributed phosphating layer As the intermediate layer of the subsequent polymer coating, the oxidation method is micro _- arc oxidation method, _hydrogen peroxide oxidation method or alkalization oxidation method, and the oxidizing agent is H2O2 or HF;

3) Finally, the polymer is coated on the surface of the porous magnesium alloy substrate, and the combination of the porous magnesium alloy substrate and the polymer coating is controlled by changing the molecular weight of the polymer, the concentration of the polymer solution, and the thickness of the polymer coating .

Further, in the step 1), laser drilling or melt foaming method is used to adjust the pore size and porosity of the porous magnesium alloy; the melt foaming method melts the magnesium ingot and the intermediate alloy ingot, and adds thickener, The foaming agent is melted and foamed, and the content and size of the foaming agent are adjusted to adjust the pore diameter and porosity of the porous magnesium alloy; the thickener is SiC or Ca; the foaming agent is MgCO ₃ , TiH ₂ or ZrH ₂ .

The step 2) the pretreatment of the porous magnesium alloy is alkali washing/acid, and oxidation/phosphating treatment; the corresponding reagents are: NaOH, H ₃ PO ₄ :HNO ₃ , H ₂ O ₂ /HF, H _{3 PO4} /ZnO/ _NaF /NaNO3/NaNO2/Citric _acid /MEA and SDS.

In the step 3), the polymer is coated on the surface of the porous magnesium alloy substrate by the soaking method or the dripping method, or the polymer treatment layer is treated by the vacuum infiltration method.

The process of performing phosphating in step 2) is as follows:

a) Porous magnesium alloy substrate cleaning: alcohol or acetone cleaning;

b) Alkaline washing and degreasing: soak in 5% sodium hydroxide solution at 50°C for 15 minutes, wash with water, and set aside;

c) Phosphating treatment: Soak in phosphating solution for 15 minutes at room temperature; formula of phosphating solution is as follows: phosphoric acid: 25-35mL/L, zinc oxide: 1-2g/L, sodium fluoride: 1-3g/L L, sodium nitrite: 1~2g/L, sodium nitrate: 2~4g/L, sodium pyrophosphate: 2~4g/L, ethanolamine: 0.1~2g/L.

Furthermore, a method for preparing a biomedical corrosion-resistant porous composite material specifically includes the following steps:

1) Preparation of porous magnesium alloy substrate;

a1: Take any two of magnesium-calcium alloy, magnesium-lithium alloy, magnesium-zinc alloy and magnesium-strontium alloy to prepare as-cast ternary magnesium alloy. In the as-cast ternary magnesium alloy, except for magnesium, the weight of other elements accounts for three The total weight percentage of elemental magnesium alloy is <10%; it is made into extruded ternary magnesium alloy under the condition of 300-350°C;

a2: Use a laser drilling machine to drill holes in the extruded ternary magnesium alloy, with a pore diameter of 100-1200 μm, a closed hole depth of 100-500 μm, and a porosity of 30-70%;

2) Prepare the pretreatment layer as an oxide layer or a phosphating layer;

b1: Preparation of oxide layer:

Clean the porous magnesium alloy substrate prepared in step 1) with pure alcohol or pure acetone until there are no impurities;

Prepare H ₂ O ₂ oxidation solution with a concentration of 10% to 30% or HF oxidation solution with a concentration of 10% to 30%, soak the cleaned porous magnesium alloy substrate in the oxidation solution for oxidation treatment, the oxidation The treatment is carried out at room temperature, and the treatment time is 60s-600s;

b2: Preparation of phosphating layer:

Clean the porous magnesium alloy substrate prepared in step 1) with pure alcohol or pure acetone until there are no impurities;

Soak the porous magnesium alloy base material cleaned above at a temperature of 50°C in a 5% sodium hydroxide solution for 15 minutes, and then wash it with water; then soak the porous magnesium alloy base material in a phosphating solution for phosphorus Phosphating treatment, the phosphating treatment is carried out at room temperature, and the treatment time is 15 minutes; wherein, the formula of the phosphating solution is that 1 liter of the phosphating solution contains 25-35 mL of phosphoric acid, 1-2 g of zinc oxide, and 1 g of sodium fluoride. ～3g, sodium nitrite 1～2g, sodium nitrate 2～4g, sodium pyrophosphate 2～4g, ethanolamine 0.1～2g;

3) Preparation of degradable and aliphatic polymer material layer:

c1. Take a degradable and aliphatic polymer material with an average molecular weight of 50,000 to 300,000 and dissolve it in a volatile organic solvent, so that the concentration of the degradable and aliphatic polymer material is 1% to 10%; the volatile The organic solvent is dichloromethane, chloroform, acetone or tetrahydrofuran;

soaking the porous magnesium alloy substrate treated in step 2) in the solution of c1, extracting it, and then completely volatilizing the solvent at room temperature to 60°C;

Or titrate the solution prepared in step c1 on each surface of the porous magnesium alloy substrate treated in step 2), and then completely volatilize the solvent at room temperature to 60°C. The porous magnesium alloy base material in step 1) described in the scheme uses a melt foaming method to adjust the pore diameter and porosity of the porous magnesium alloy, melts the cast ternary magnesium alloy in step 1), and adds a tackifier, The foaming agent is melted and foamed, and the pore diameter, pore depth and porosity of the porous magnesium alloy are adjusted by adjusting the content and size of the foaming agent to prepare a porous magnesium alloy substrate.

The tackifier used in the present invention is SiC or Ca. As a tackifier, SiC can form a composite with the metal, thereby keeping the metal at a lower stirring temperature; as a tackifier, Ca particles can also prevent the combustion of magnesium alloys, and at the same time introduce less impurity elements, reducing Corrosion points of magnesium alloy substrates. The blowing agent used is MgCO ₃ , TiH ₂ or ZrH ₂ . Among them, MgCO ₃ is cheap and easy to obtain; TiH ₂ and ZrH ₂ have the best effect among many hydrides because the fastest temperature for releasing foaming gas H ₂ is 600 ° C and the melting point of magnesium (640 ° C) is relatively close foaming agent.

The degradable and aliphatic polymer materials used are polylactic acid, polylactic acid-glycolic acid copolymer, polycaprolactone, polyamide or polyurethane, mainly from the application of polymer materials in biomedicine, in which polylactic acid has obtained FDA approval, making polylactic acid bone nails, bone plates and polylactic acid fixation materials, even used to prepare polylactic acid hemostatic glue; polyamide has a similar structure to collagen in natural bone, so it is often combined with hydroxyapatite to prepare bone Repair materials; In addition, several other polymer materials are also widely used in bone repair because of their excellent mechanical properties and degradation properties.

The present invention selects four kinds of volatile solvents, mainly considering the effect of the polymer material layer and the ease of operation. The volatile solvents can be slowly volatilized at a lower temperature to obtain a smooth surface and no pores. Molecular membrane. Among them, dichloromethane and trichloromethane solvents can be basically volatilized in 24 hours under the condition of 25°C; tetrahydrofuran and acetone can be basically volatilized in 24 hours under the condition of 37°C. If the temperature is increased, the solvent volatilization can be further accelerated, so it can be The polymer material film is prepared simply and quickly.

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

1. The present invention adopts the composite of porous magnesium alloy base material and the polymer that can be used for bone repair, and combines the elastic modulus and density of the magnesium alloy with the matching property of natural bone and the toughness and corrosion resistance of the polymer, further The corrosion rate of the porous magnesium alloy substrate in the body is reduced, and the strength and toughness of the composite material are also significantly improved.

2. By adjusting the ratio of the porous magnesium alloy base material to the pretreatment layer and the polymer material layer, the present invention can conveniently control the mechanical properties of the material, so that the mechanical properties of the composite material can better match those of natural bone.

3. The present invention controls the bonding force between the polymer material layer and the porous magnesium alloy substrate by adjusting the composition of the pretreatment layer, thereby more controllably adjusting the degradability of the composite material. Realize the controllable degradation and absorption speed of composite materials in vivo, and solve the contradiction that the corrosion and degradation speed of magnesium alloy is relatively fast in the human environment, while the degradation speed of degradable and aliphatic polymer materials is relatively slow in vivo. By adjusting the porous magnesium alloy matrix The content of the polymer material and the polymer material and the thickness of the polymer material layer can effectively control the degradation rate of the composite material in the body.

4. The present invention considers the isotropic mechanical properties, corrosion degradation performance, and biocompatibility of composite materials, and also considers that after the porous structure is implanted, blood vessels and muscles of the human body can grow into the body, which is convenient for human tissues to transport blood supply and nutrition ; By adjusting the ratio of the porous magnesium alloy base material to the pretreatment layer and the polymer material layer, the macropore-micro-nanopore ratio of the composite scaffold is adjusted, thereby regulating the blood supply and muscle growth rate in the bone repair process.

5. The preparation method of the biomedical corrosion-resistant porous composite material of the present invention has simple steps and is easy to control. The degradability of the porous composite material is controlled by controlling the parameters to control the porosity, pore diameter and pore connectivity.

Description of drawings

Figure 1 shows the porous AZ31 substrate prepared by laser drilling method.

Fig. 2 shows porous magnesium, calcium, zinc ternary magnesium alloy substrates with different pore diameters and pore depths prepared by foaming method. The average pore diameter of Figure 2a is 3000 μm, and the average pore depth is 3000 μm; the average pore diameter of Figure 2b is 2000 μm, and the average pore depth is 2000 μm; the average pore diameter of Figure 2c is 1000 μm, and the average pore depth is 1000 μm; The average pore depth is 500 μm; wherein, the average pore diameter and average pore depth are the average values of 15 pores randomly selected on the porous magnesium, calcium, zinc ternary magnesium alloy substrate.

Figure 3 Magnesium alloy substrate, pretreatment layer, and polymer layer. Figure 3a is the AZ31 substrate; Figure 3b is the oxidation pretreatment layer; Figure 3c is the phosphating pretreatment layer; Figure 3d is the polymer coating.

Figure 4 Porous AZ31 substrate and porous AZ31 composite. Figure 4a is porous AZ31 substrate; Figure 4b is outside the pores of porous AZ31 substrate (×50); Figure 4c is inside the pores of porous AZ31 substrate (×50); Figure 4d is porous AZ31 composite material; Figure 4e is porous AZ31 composite material Outside the pores (×50); Fig. 4f Inside the pores of the porous AZ31 composite (×50). Among them, (×50) in Figure 4b, Figure 4c, Figure 4e, and Figure 4f indicates the magnification.

Figure 5 Corrosion control diagram of AZ31 material after SBF immersion for three months. Figure 5a is the corrosion diagram of porous AZ31 material; Figure 5b is the corrosion diagram of non-porous AZ31 composite material; Figure 5c is the corrosion diagram of closed-pore AZ31 composite material; Figure 5d is the corrosion diagram of through-hole AZ31 composite material.

Figure 6 SEM and EDS images of AZ31 composite material. Figure 6a is the SEM image of the non-porous AZ31 composite; Figure 6b is the SEM image of the closed-pore AZ31 composite; Figure 6c is the SEM image of the through-hole AZ31 composite; Figure 6d is the SEM image of the through-hole AZ31 composite; The SEM image of the hole outside the hole of the AZ31 composite material. Among them, I and O in Figures 6b and 6c represent the inside and outside of the pores of the porous material, respectively, and 10, 50 and 2000 in Figures 6a, 6b and 6c represent magnifications, respectively.

Fig. 7 is a comparison diagram of the porous AZ31 substrate and the Tafel curve of the porous AZ31 composite material in Examples 1-4.

Fig. 8 is a comparison diagram of the impedance of the porous AZ31 substrate and the porous AZ31 composite material of Examples 1-4.

Fig. 9 Mg ²⁺ release diagram of the porous AZ31 substrate and the porous AZ31 composite material of Examples 1-6.

Fig. 10 Schematic diagram of corrosion of magnesium alloy composites.

detailed description

The present invention will be described in further detail below in conjunction with the accompanying drawings and specific embodiments.

A biomedical corrosion-resistant porous composite material is composed of a porous magnesium alloy substrate, a pretreatment layer and a polymer coating;

Among them, the porous magnesium alloy substrate is a magnesium-zinc alloy, a magnesium-calcium alloy, a magnesium-lithium alloy, a magnesium-strontium alloy, or a ternary alloy composed of the above-mentioned alloy components (such as AZ31, Mg-Ca alloy, etc.) with a magnesium content greater than 90%. ); the pore diameter of the porous magnesium alloy substrate is 100-1200 μm, the pore depth of the closed cells is 100-500 μm, and the porosity is 30%-70%; the pretreatment layer is an oxidation/phosphating layer with a thickness of 1-10 μm; The material coating is a degradable, aliphatic polymer material layer with a thickness of 5-30 μm.

Examples 1-6 are corrosion-resistant porous composite materials for biomedical use. The parameters of the composite materials are shown in Table 1 (attached). A ternary magnesium alloy of magnesium, calcium and lithium for biomedical use was selected as a comparison. The corrosion resistance of the materials was tested by an electrochemical workstation; the surface morphology of all materials was tested by a tungsten filament scanning electron microscope.

Embodiment 1: Referring to Fig. 4-5 and Fig. 7-9, a method for preparing a porous magnesium alloy medical composite material comprises the following steps:

a. Preparation of porous magnesium alloy substrate by laser method

The substrate is AZ31 magnesium alloy (purchased commodity AZ31), the magnesium alloy is cut into AZ31 sheets of Φ12×3, and then the porous AZ31 substrate is prepared by laser drilling method. The pores are closed pores with a diameter of 100 μm and a depth of 100μm, porosity 30%, finally made into porous magnesium alloy substrate;

b, the method of porous magnesium alloy pretreatment layer:

Preparation of porous magnesium alloy oxide layer: prepare hydrogen peroxide with a concentration of 15%, soak the porous AZ31 substrate in hydrogen peroxide at room temperature for 2 seconds, and obtain an oxide layer on the surface and inside the pores of the porous magnesium alloy;

c. The method of porous AZ31 polymer layer:

Prepare the polylactic acid coating, prepare 3wt.% polylactic acid dichloromethane solution, soak the porous AZ31 substrate obtained with the pretreatment layer in the polylactic acid dichloromethane solution to obtain the polylactic acid coating, and the polylactic acid coating The thickness is 5 μm.

The untreated porous AZ31 was selected in the corrosion resistance test of the porous AZ31 composite, and the treated non-porous AZ31 was used as a control test.

Fig. 4 Porous magnesium alloy substrate and porous magnesium alloy composite material. Figure 4a is the porous magnesium alloy substrate; Figure 4b is outside the pores of the porous magnesium alloy substrate (×50); Figure 4c is inside the pores of the porous magnesium alloy substrate (×50); Figure 4a is the porous magnesium alloy composite material; Figure 4b is Outside the pores of the porous magnesium alloy composite (×50); Figure 4c inside the pores of the porous magnesium alloy composite (×50). Comparing the porous AZ31 composite material and the porous AZ31 substrate, it can be seen that the outer surface of the pores of the porous AZ31 material after coating the polymer layer is smooth and dense, but the inside of the closed cells is relatively rough, which is mainly due to the interface effect of the polymer material coating. , this effect has a certain impact on the binding force between the polymer material and the substrate, and this effect is affected by the pore size and pore depth. The smaller the pore size, the stronger the interface effect. Therefore, in the comparison between Example 1 and subsequent examples Corrosion performance is slightly weak.

Figure 5 Corrosion control diagram of magnesium alloy material after SBF immersion for three months. Figure 5a is the corrosion diagram of porous AZ31 material; Figure 5b is the corrosion diagram of non-porous AZ31 composite material; Figure 5c is the corrosion diagram of closed-pore AZ31 composite material; Figure 5d is the corrosion diagram of through-hole AZ31 composite material. Compared with the untreated porous AZ31 material and the AZ31 material treated with polylactic acid, it can be seen that the untreated AZ31 material, as shown in Figure 5a, has no complete structure after three months of corrosion, while the porous AZ31 material treated with polylactic acid AZ31 composite material, as shown in Figure 5a-5d, the AZ31 composite material still has a complete structure, this result shows that the coating of polymer materials plays an important role in improving the corrosion resistance of AZ31 material, the results are consistent with the electrochemical results match.

Fig. 7 is a comparison diagram of the porous AZ31 substrate and the Tafel curve of the porous AZ31 composite material in Examples 1-4. From the Ecorr and Icorr of the Tafel curve, it can be seen that the AZ31 Ecorr after polylactic acid treatment increased by 200mV, and Icorr decreased by nearly 4-5 orders of magnitude;

Fig. 8 is a comparison diagram of the impedance of the porous AZ31 substrate and the porous AZ31 composite material of Examples 1-4. The impedance of AZ31 after treatment with polylactic acid increased by 5-6 orders of magnitude compared with that without treatment;

Fig. 9 Mg ²⁺ release diagram of the porous AZ31 substrate and the porous AZ31 composite material of Examples 1-6. The release concentration of Mg ²⁺ is an index reflecting the corrosion rate of the material during immersion in SBF. The lower the release concentration of Mg ²⁺ means the slower the corrosion rate of the material during immersion. From the results in Figure 9, it can be seen that the comparison of closed-cell composite materials, with As the pore size increases, the corrosion rate of the material decreases, which is consistent with the results in Figure 4, indicating that the large pores are more conducive to the introduction of the polymer layer and further improve the corrosion resistance of the material; It has better corrosion resistance, which is mainly due to the small interface effect when the polymer material is coated in the hole of the through-hole composite material, which is more conducive to the combination of the polymer layer and the base layer, and enhances the corrosion resistance of the composite material.

Example 2:

The difference between this embodiment and embodiment 1 is as follows:

The difference in step 1) is:

a1 get magnesium-calcium alloy and magnesium-zinc alloy to prepare as-cast ternary magnesium alloy, in this as-cast ternary magnesium alloy, except magnesium element, the weight of calcium element and zinc element accounts for ternary magnesium alloy gross weight percentage and is 4%; The cast ternary magnesium alloy prepared in step a1 is made into an extruded ternary magnesium alloy at a temperature of 300-350°C;

a2 uses a laser drilling machine to drill holes in the extruded ternary magnesium alloy prepared in a1, with a pore diameter of 500 μm, a hole depth of 300 μm, and a porosity of 50%;

The difference in step 2) is that the prepared pretreatment layer is a phosphating layer, as follows:

Cleaning the porous magnesium alloy substrate prepared in step 1) with pure acetone until there are no impurities;

Then, soak the cleaned porous magnesium alloy substrate in a 5% sodium hydroxide solution for 15 minutes at a temperature of 50° C., then wash with water, and set aside;

Then soak the porous magnesium alloy base material treated above in a phosphating solution for phosphating treatment. The phosphating treatment is carried out at room temperature, and the treatment time is 15 minutes. Wherein, the formula of the phosphating solution is: The solution contains 25 mL of phosphoric acid, 1 g of zinc oxide, 1 g of sodium fluoride, 1 g of sodium nitrite, 2 g of sodium nitrate, 2 g of sodium pyrophosphate, and 0.1 g of ethanolamine; the thickness of the finally obtained phosphating layer is 3 μm.

The difference in step 3) is:

Prepare the chloroform solution of 3wt.% polycaprolactone;

Then soak the porous magnesium alloy substrate treated in step 2) in the chloroform solution of 3wt.% polycaprolactone, extract it, and then completely volatilize the solvent at room temperature to 60°C to obtain polycaprolactone Ester coating, the thickness of the polycaprolactone coating is 10 μm.

Example 3:

The difference between this embodiment and embodiment 1 is as follows:

The difference in step 1) is:

a1, get magnesium-calcium alloy and magnesium-strontium alloy to prepare as-cast ternary magnesium alloy, in this as-cast ternary magnesium alloy, except magnesium element, the weight of calcium element and strontium element accounts for ternary magnesium alloy gross weight percentage and is 4%, Extruded ternary magnesium alloy is made under the condition of 300-350℃;

a2, using a laser drilling machine to punch holes in the extruded ternary magnesium alloy prepared by a1, the hole diameter is 700 μm, the hole depth is 400 μm, and the porosity is 55%;

The difference in step 2) is that the prepared pretreatment layer is a phosphating layer, as follows:

First, clean the porous magnesium alloy substrate prepared in step 1) with pure alcohol or pure acetone until there are no impurities; soak in 5% sodium hydroxide solution for 15 minutes at a temperature of 50°C, and then washed, ready to use;

Then, soak the porous magnesium alloy base material treated above in a phosphating solution for phosphating treatment, the phosphating treatment is carried out at room temperature, and the treatment time is 15 minutes, wherein, the formula of the phosphating solution is: 1 liter of phosphorus The chemical solution contains 30 mL of phosphoric acid, 1.5 g of zinc oxide, 2 g of sodium fluoride, 1.5 g of sodium nitrite, 3 g of sodium nitrate, 3 g of sodium pyrophosphate, and 1 g of ethanolamine; the thickness of the finally obtained phosphating layer is 7 μm.

The difference in step 3) is:

Prepare a THF solution of 5wt.% polyamide;

Titrate 5wt.% polyamide tetrahydrofuran solution on each surface of the porous magnesium alloy substrate treated in step 2), and then completely evaporate the solvent at room temperature -60°C to obtain polyamide coating, polyamide coating The thickness of the layer was 20 μm.

Example 4:

The difference between this embodiment and embodiment 1 is as follows:

The difference in step 1) is:

a1, get magnesium-calcium alloy and magnesium-strontium alloy to prepare as-cast ternary magnesium alloy, in this as-cast ternary magnesium alloy, except magnesium element, the weight of calcium element and strontium element accounts for 3% of the total weight percentage of ternary magnesium alloy, Extruded ternary magnesium alloy is made under the condition of 300-350℃;

a2. The extruded ternary magnesium alloy is drilled with a laser drilling machine, the hole diameter is 1000 μm, the hole depth is 500 μm, and the porosity is 70%;

The difference in step 2) is that the prepared pretreatment layer is a phosphating layer, as follows:

Use pure alcohol or pure acetone to clean the porous magnesium alloy substrate prepared in step 1) until there are no impurities; soak in 5% sodium hydroxide solution for 15 minutes at a temperature of 50°C, and then wash with water. stand-by;

Soak the porous magnesium alloy base material treated above in a phosphating solution for phosphating treatment, the phosphating treatment is carried out at room temperature, and the treatment time is 15 minutes, wherein the formula of the phosphating solution is: 35mL of phosphoric acid, 2g of zinc oxide, 3g of sodium fluoride, 2g of sodium nitrite, 4g of sodium nitrate, 4g of sodium pyrophosphate, and 2g of ethanolamine were respectively contained in it; the thickness of the finally obtained phosphating layer was 10 μm.

The difference in step 3) is:

Prepare the THF solution of 6wt.% polyurethane;

Titrate 3wt.% polyurethane tetrahydrofuran solution on each surface of the porous magnesium alloy substrate treated in step 2), and then completely evaporate the solvent at room temperature -60°C to obtain a polyurethane coating. The thickness of the polyurethane coating is is 25 μm.

Example 5:

The difference between this embodiment and embodiment 1 is as follows:

The difference in step 1) is:

a1, get magnesium-calcium alloy and magnesium-lithium alloy to prepare as-cast ternary magnesium alloy, in this as-cast ternary magnesium alloy, except magnesium element, the weight of calcium element and lithium element accounts for ternary magnesium alloy gross weight percentage and is 3%, Extruded ternary magnesium alloy is made under the condition of 300-350℃;

a2. Use a laser drilling machine to drill holes in the extruded ternary magnesium alloy prepared in a1. The hole diameter is 1000mm, the hole depth is 3000mm (through hole), and the porosity is 70%;

The difference in step 2) is that the prepared pretreatment layer is a phosphating layer, as follows:

Clean the porous magnesium alloy substrate prepared in step 1) with pure alcohol or pure acetone until there is no impurity; oxidize the cleaned porous magnesium alloy substrate at a temperature of 50°C with a concentration of 5% hydrogen Soak in sodium solution for 15 minutes, then wash with water and set aside;

Then soak the treated porous magnesium alloy base material in the phosphating solution for phosphating treatment, the phosphating treatment is carried out at room temperature, and the treatment time is 15min, wherein, the formula of the phosphating solution is, 35mL of phosphoric acid, 2g of zinc oxide, 3g of sodium fluoride, 2g of sodium nitrite, 4g of sodium nitrate, 4g of sodium pyrophosphate, and 2g of ethanolamine were respectively contained in it; the thickness of the finally obtained phosphating layer was 10 μm.

The difference in step 3) is:

Prepare a THF solution of 6wt.% polylactic acid;

Titrate 6wt.% polylactic acid tetrahydrofuran solution on each surface of the porous magnesium alloy substrate treated in step 2), and then completely evaporate the solvent at room temperature -60°C to obtain polylactic acid coating, polylactic acid coating The thickness of the layer was 30 μm.

Embodiment 6:

The difference between this embodiment and embodiment 1 is:

The difference in step 1) is that the method for preparing the porous magnesium alloy is a melt foaming processing method, specifically as follows:

a1. Prepare porous magnesium alloy substrate by melt foaming processing method:

Get magnesium-calcium alloy and magnesium-lithium alloy to prepare as-cast ternary magnesium alloy, in this as-cast ternary magnesium alloy, except magnesium element, the weight of calcium element and lithium element accounts for 3% of the total weight percentage of ternary magnesium alloy; After the as-cast ternary magnesium alloy is melted, Ca is added as a tackifier, whose content is 10% of the ternary magnesium alloy; _MgCO3 is added as a foaming agent, whose content is 20% of the ternary magnesium alloy, and the obtained porous magnesium In the alloy substrate; the average pore diameter is 500 μm, the average pore depth is 500 μm, and the porosity is 60%;

The difference in step 2) is:

Prepare an HF oxidation solution with a concentration of 10%-30%, soak the cleaned porous magnesium alloy substrate in the oxidation solution for 60s at room temperature, so as to obtain an oxide layer on the surface and inside the pores of the porous magnesium alloy substrate, The thickness of the oxide layer is 10 μm;

The difference in step 3) is:

Prepare a chloroform solution of 3wt.% polylactic acid;

Soak the porous magnesium alloy substrate treated in step 2) in a 3wt.% polylactic acid solution in chloroform, extract it, and then completely evaporate the solvent at room temperature to 60°C to obtain a polylactic acid layer. The thickness of the polylactic acid layer is is 10 μm.

In addition, the step 3) prepares the polymer layer coating by leaching method or solution titration method; for the porous magnesium alloy substrate containing through holes, in order to make the polymer treatment layer in the pores uniform, vacuum infiltration method can also be used Carry out the treatment of the polymer treatment layer.

The resting time involved in Table 1 refers to the resting time selected during the Tafel curve and impedance test. The purpose of standing is to improve the stability of the surface of the material to be tested. In the table, the smaller the Icorr and the larger the Impedence, the stronger the corrosion resistance of the composite material. Mg ²⁺ in the table refers to the parameters measured when the SBF immersion method is used to test the corrosion resistance of composite materials. The Mg ²⁺ release concentration is an index reflecting the corrosion rate of the material during immersion in SBF. The higher the Mg ²⁺ release concentration Low means that the corrosion rate of the material is slower during the soaking process. The test method for Mg ²⁺ is to take the SBF liquid after the composite material is soaked in SBF for 21 days, and use the atomic absorption spectrometry to test the content of Mg ²⁺ . The content of Mg ²⁺ in the blank SBF The content is 57 mg/L.

The comparative examples in Table 1 refer to the porous AZ31 material with the AZ31 material as the matrix. The release concentrations of Icorr, Impedence and Mg ²⁺ of the comparative example and Examples 1-6 were tested under the same conditions.

According to the data in table 1, the Icorr among the examples 1-6 is all less than the Icorr of the comparative examples, and the Impedence is all greater than that of the comparative examples, which shows that the corrosion resistance of the composite magnesium alloy material in the examples 1-6 is lower than that of the comparative examples. The comparative example is strong, wherein the corrosion resistance of the composite magnesium alloy material in Example 6 is the strongest; in the comparative example in table 1, after the porous AZ31 material was soaked in SBF for 21 days, the SBF solution was taken, and the atomic absorption spectrometry was used to test the ^Mg2+ content is 328 mg/L, and the content of Mg ²⁺ of composite magnesium alloy material in embodiment 1-6 is all less than this value, thus shows that the corrosion rate of composite magnesium alloy material in embodiment 1-6 is slower, wherein embodiment 6 The corrosion rate of the composite magnesium alloy material is the slowest.

Referring to Figure 1 and Figure 2, Figure 1 is a porous AZ31 substrate prepared by laser drilling; the laser-drilled material in this figure has a pore diameter of 1000 μm, a hole depth of 500 μm, and a hole spacing of 1000 μm. Fig. 2 is a porous magnesium, calcium, zinc ternary magnesium alloy substrate prepared by foaming method; in this figure, the average pore diameter and pore depth of the melt foamed material are about 500 μm. From the comparison of Figure 1 and Figure 2, it can be found that the hole structure made by the laser drilling method is uniform and smooth, which is more conducive to the introduction of the pretreatment layer and the polymer layer.

See Figure 3 for the magnesium alloy substrate, pretreatment layer, and polymer layer. Figure 3a is the AZ31 substrate; Figure 3b is the oxidation pretreatment layer; Figure 3c is the phosphating pretreatment layer; Figure 3d is the polymer coating. From the point of view of the surface structure, the oxide layer has a network structure, and the results of EDS show that the composition of the oxide layer is MgO; the surface of the polylactic acid coating is smooth and has a dense structure, and this dense structure can enhance the corrosion resistance of the composite material. . In addition to examining the thickness of the polymer coating when the polymer layer improves the corrosion resistance of the composite material, the bonding force between the polymer coating and the base layer is also a very important factor. Considering the practical application, the preparation of the polymer layer should not be too high. Larger, it is more appropriate to control it at 10-20μm.

See Figure 6 for the SEM and EDS images of the AZ31 composite material. Figure 6a is the SEM image of the non-porous AZ31 composite; Figure 6b is the SEM image of the closed-pore AZ31 composite; Figure 6c is the SEM image of the through-hole AZ31 composite; Figure 6d is the SEM image of the through-hole AZ31 composite; The SEM image of the hole outside the hole of the AZ31 composite material. It can be seen from Figure 6 that during the immersion process in SBF, with the gradual degradation of the surface polymer layer, the substrate AZ31 is also gradually corroded, and crystal corrosion products are produced, which should be Mg(OH) ₂ and MgO in analysis.

See Figure 10 for a schematic diagram of the corrosion of magnesium alloy composite materials; the corrosion schematic diagram shows the pitting corrosion of magnesium alloys and the interaction between corrosion products of polylactic acid and corrosion products of magnesium alloys and the interaction relationship between corrosion of magnesium alloys. Studies have shown that the corrosion modes of magnesium alloys are mainly pitting corrosion and uniform corrosion, which is related to the grain size of magnesium alloys. When the grains are small, pitting corrosion gradually develops into uniform corrosion. However, for the convenience of description, the schematic diagram in the present invention, Pitting corrosion at the beginning of corrosion is selected as the model.

The present invention adopts the composite of degradable magnesium alloy and degradable polylactic acid to combine the elastic modulus and density matching adjustability of magnesium alloy with the toughness and corrosion resistance of polymer; at the same time, by adjusting the magnesium alloy substrate and The ratio of the coating polymer material can facilitate the control of the mechanical properties of the material. The invention can adjust the bonding force between the polymer coating and the magnesium alloy base material by adjusting the composition of the pretreatment layer, thereby more controllably adjusting the degradability of the composite material. The invention can obtain a composite material with good bone matching by adjusting the porosity of the magnesium alloy and the ratio relationship with the polymer, and at the same time, the problem of poor corrosion resistance of the magnesium alloy can be effectively solved by combining the pretreatment layer and the polymer treatment layer. In order to obtain a bone repair material that matches the mechanical properties of natural bone and has excellent corrosion resistance, it is expected to have important applications in the field of biomedicine.

Finally, it is noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described with reference to the preferred embodiments of the present invention, those skilled in the art should understand that it can be described in the form Various changes may be made in matter and details thereof without departing from the spirit and scope of the invention as defined in the appended claims.

Table 1:

Claims (6)

1. A method for preparing a biomedical corrosion-resistant porous composite material, characterized in that, the biomedical corrosion-resistant porous composite material is composed of a porous magnesium alloy substrate, a pretreatment layer and a polymer coating; Among them, the porous magnesium alloy substrate is AZ31, or a magnesium-calcium alloy with a magnesium content greater than 90%, or a magnesium-calcium alloy with a magnesium content greater than 90%, and a magnesium-zinc alloy, a magnesium-lithium alloy, and a magnesium-strontium alloy with a magnesium content greater than 90%. The formed ternary alloy; the pore diameter of the porous magnesium alloy substrate is 100-1200 μm, the pore depth of the closed cells is 100-500 μm, and the porosity is 30%-70%; The pretreatment layer is a phosphating layer with a thickness of 1-10 μm; The polymer coating is a degradable, aliphatic polymer material layer with a thickness of 5-30 μm; The preparation method specifically comprises the following steps: 1) Preparation of porous magnesium alloy substrate: a. Prepare as-cast AZ31, or magnesium-calcium alloy with magnesium content greater than 90%, or magnesium-calcium alloy with magnesium content greater than 90%, and magnesium-zinc alloy, magnesium-lithium alloy, and magnesium-strontium alloy with magnesium content greater than 90%. Ternary alloys, such as AZ31, or magnesium-calcium alloys with a magnesium content of more than 90%, or magnesium-calcium alloys with a magnesium content of more than 90% and magnesium-zinc alloys, magnesium-lithium alloys, and magnesium-strontium alloys with a magnesium content of more than 90%. Except magnesium element in ternary alloy, the weight percentage of other elements accounted for the total weight percentage of the above magnesium alloy is <10%; b. punching the porous magnesium alloy substrate; 2) Pretreatment of the porous magnesium alloy, using the phosphating method on the surface and inside the pores of the porous magnesium alloy substrate to obtain a uniformly distributed phosphating layer as the intermediate layer of the subsequent polymer coating; The process of phosphating is as follows: a) Porous magnesium alloy substrate cleaning: alcohol or acetone cleaning; b) Alkaline washing and degreasing: soak in 5% sodium hydroxide solution at 50°C for 15 minutes, wash with water, and set aside; c) Phosphating treatment: Soak in phosphating solution for 15 minutes at room temperature; formula of phosphating solution is as follows: phosphoric acid: 25-35mL/L, zinc oxide: 1-2g/L, sodium fluoride: 1-3g/L L, sodium nitrite: 1~2g/L, sodium nitrate: 2~4g/L, sodium pyrophosphate: 2~4g/L, ethanolamine: 0.1~2g/L; 3) Finally, the polymer is coated on the surface of the porous magnesium alloy substrate, and the combination of the porous magnesium alloy substrate and the polymer coating is controlled by changing the molecular weight of the polymer, the concentration of the polymer solution, and the thickness of the polymer coating . 2. The preparation method of the biomedical corrosion-resistant porous composite material according to claim 1, characterized in that: the degradable and aliphatic polymer material is polylactic acid, polycaprolactone, polyamide or polyurethane. 3. The preparation method of the biomedical corrosion-resistant porous composite material according to claim 1, characterized in that: the drilling in the step 1) adopts laser drilling or melt foaming method to adjust the pore diameter and porosity of the porous magnesium alloy ; The melt foaming method is used for as-cast AZ31 or magnesium-calcium alloys with a magnesium content greater than 90%, or magnesium-calcium alloys with a magnesium content greater than 90% and magnesium-zinc alloys, magnesium-lithium alloys, and magnesium-strontium alloys with a magnesium content greater than 90%. The formed ternary alloy is melted, adding a thickener and a foaming agent for melting and foaming, and adjusting the content and size of the foaming agent to adjust the pore diameter and porosity of the porous magnesium alloy; the thickener is SiC or Ca; The blowing agent is MgCO ₃ , TiH ₂ or ZrH ₂ . 4. The preparation method of the biomedical corrosion-resistant porous composite material according to claim 1, characterized in that: in the step 3), the polymer is coated on the surface of the porous magnesium alloy substrate by the soaking method or the dripping method, or The vacuum infiltration method is used for the treatment of the polymer material layer. 5. the preparation method of biomedical corrosion-resistant porous composite material according to claim 1, is characterized in that, specifically comprises the following steps: 1) Preparation of porous magnesium alloy substrate; a1: As-cast ternary magnesium alloy prepared from any one of magnesium-calcium alloy with magnesium content greater than 90%, magnesium-zinc alloy, magnesium-lithium alloy, and magnesium-strontium alloy with magnesium content greater than 90%. In addition to the magnesium element in the alloy, the weight percentage of other elements in the total weight of the ternary magnesium alloy is less than 10%, and the extruded ternary magnesium alloy is made under the condition of 300-350°C; a2: Use a laser drilling machine to drill holes in the extruded ternary magnesium alloy, with a pore diameter of 100-1200 μm, a closed hole depth of 100-500 μm, and a porosity of 30-70%; 2) Preparation of phosphating layer: Clean the porous magnesium alloy substrate prepared in step 1) with pure alcohol or pure acetone until there are no impurities; Soak the porous magnesium alloy base material cleaned above at a temperature of 50°C in a 5% sodium hydroxide solution for 15 minutes, and then wash it with water; then soak the porous magnesium alloy base material in a phosphating solution for phosphorus Phosphating treatment, the phosphating treatment is carried out at room temperature, and the treatment time is 15 minutes; wherein, the formula of the phosphating solution is that 1 liter of the phosphating solution contains 25-35 mL of phosphoric acid, 1-2 g of zinc oxide, and 1 g of sodium fluoride. ～3g, sodium nitrite 1～2g, sodium nitrate 2～4g, sodium pyrophosphate 2～4g, ethanolamine 0.1～2g; 3) Preparation of degradable and aliphatic polymer material layer: c1. Take a degradable and aliphatic polymer material with an average molecular weight of 50,000 to 300,000 and dissolve it in a volatile organic solvent, so that the concentration of the degradable and aliphatic polymer material is 1% to 10%; the volatile The organic solvent is dichloromethane, chloroform, acetone or tetrahydrofuran; soaking the porous magnesium alloy substrate treated in step 2) in the solution of c1, extracting it, and then completely volatilizing the solvent at room temperature to 60°C; Or add the solution prepared in step c1 dropwise onto each surface of the porous magnesium alloy substrate treated in step 2), and then completely volatilize the solvent at room temperature to 60°C. 6. The preparation method of the biomedical corrosion-resistant porous composite material according to claim 5, characterized in that, the porous magnesium alloy base material in the step 1) adopts a melt foaming method to adjust the pore diameter and porosity of the porous magnesium alloy, The as-cast ternary magnesium alloy prepared by any one of the magnesium-calcium alloy with a magnesium content greater than 90% and the magnesium-zinc alloy, magnesium-lithium alloy, and magnesium-strontium alloy with a magnesium content greater than 90% in step 1) is added to it. The adhesive and foaming agent are melted and foamed, and the pore diameter, pore depth and porosity of the porous magnesium alloy are adjusted by adjusting the content and size of the foaming agent to prepare the porous magnesium alloy substrate.