CN108079379B

CN108079379B - Porous tantalum

Info

Publication number: CN108079379B
Application number: CN201611026777.0A
Authority: CN
Inventors: 叶雷
Original assignee: Chongqing Runze Pharmaceutical Co Ltd
Current assignee: Chongqing Runze Pharmaceutical Co Ltd
Priority date: 2016-11-22
Filing date: 2016-11-22
Publication date: 2020-05-15
Anticipated expiration: 2036-11-22
Also published as: CN108079379A

Abstract

The invention discloses a porous tantalum, which comprises a material body, a porous cavity and a multi-level porous material, wherein the porous cavity is formed by grading pore sizes of materials and a cavity wall surrounding each level of the porous cavity; the cavity wall of the superior large pore cavity is made of inferior cavity wall structure materials which are composed of inferior small pore cavity structures with smaller pore diameters than the pore cavities, the pore cavities of each level of porous materials are communicated with each other, the pore cavities of each level of porous materials are also communicated with each other, and the water contact angle of the pore cavity wall surface of the primary porous material with the largest porous tantalum is not more than 48.5 degrees, so that the hydrophilicity of the cavity wall surface of the primary pore cavity with the largest size is obviously improved, the biocompatibility is improved, the combination of the cavity wall surface with blood and tissue fluid is facilitated, the adsorption of protein is facilitated, the adhesion, the growth and the spreading of osteoblasts are facilitated, and the regeneration of bone tissues is facilitated.

Description

Porous tantalum

Technical Field

The invention relates to a porous material, in particular to porous tantalum for a medical implant material.

Background

Tantalum metal has been widely used in the fields of chemical industry, metallurgy, aerospace, and the like. Because tantalum has no reaction with body fluid and no irritation to body tissues, and is very well compatible with body tissues, tantalum also becomes an ideal material for manufacturing surgical implants. Such as cardiac pacemakers, skull defect repairs, vascular clamps, femoral stem prostheses, wires, sheets or meshes for nerve repair, and the like. However, dense tantalum metal has a large specific gravity and a high elastic modulus, and has a poor effect of being directly implanted into a human body, and thus, porous tantalum has been developed. The basic structure of the porous tantalum metal has the characteristics of high integral volume porosity, high surface friction coefficient, low elastic modulus and the like, so that the porous tantalum metal is expected to become a new material with good development prospect in the field of clinical application of orthopedics.

Many studies have been conducted on porous tantalum, such as Zardiacas et al, which have conducted research on the flexural strength and fatigue properties of porous tantalum (Structure, metals, and mechanical properties of a porous foam [ J ]. Journal of biological materials research, 2001, 58(2): 180-; zhang Y et al conducted a porous tantalum tribological behavior study (Interfacial frictionbhavior; cancellous bone, scientific bone, and a novel porous tantalum tribological material. J musculosokines Res. 1999); cohen R. investigated the biocompatibility of porous tantalum implants in vivo (Cohen R. A porous tantalum trabecular metal: Basic science Am JOrthop.2002; 31(4): 216-; research on the preparation of porous tantalum by chemical vapor deposition (CN 105177523A a medical porous tantalum metal material and its preparation method) was conducted by zhao german wei et al. However, the medical implant material prepared by the series of research results still has poor practical application effect. At present, no matter the porous tantalum medical implant material reported in documents or seen in the market, after the porous tantalum medical implant material is implanted into a human body, the effect of the bone tissue of the human body growing into the implant material is not good, namely, the implant material can not realize the regeneration of the bone tissue, and can not become a bone repair material in the true sense.

The invention content is as follows:

the invention aims to provide a medical implant regeneration material, namely a porous tantalum material, which is beneficial to the growth of bone tissues and has good bone repair effect.

The inventor thinks that as a bone implantation regeneration material, after being implanted into a human body, the bone implantation regeneration material is firstly contacted with blood and tissue liquid and then contacted with organism tissue cells, if a good material-cell interface relation is obtained, the surface of the bone implantation regeneration material is required to have excellent wettability, the wettability is better, the hydrophilicity is higher, the molecular contact opportunities are more, the adhesion of the blood, the tissue liquid and the cells on the surface of the material is more and more uniform, the interface combination performance is better, and the bone tissue is more and more beneficial to the growth of the bone tissue to meet the real regeneration function of the bone repair material.

The purpose of the invention is realized by the following technical scheme:

the porous tantalum comprises a material body, wherein the material body is a multi-level porous material formed by pore cavities and cavity walls, wherein the pore cavities are graded according to the pore size of the material; wherein the cavity wall of the upper large pore cavity is made of a lower cavity wall structure material composed of a lower small pore cavity structure with a smaller pore diameter than the pore diameter of the upper large pore cavity, the pore cavities of each porous material are communicated with each other, the pore cavities of each porous material are also communicated with each other, and the water contact angle of the cavity wall surface of the pore cavity of the largest porous tantalum material is not more than 48.5 degrees. The porous tantalum with the structure not only can obviously improve the hydrophilicity of the wall surface of the primary pore cavity, but also is particularly beneficial to the combination of the wall surface with blood and tissue fluid, is beneficial to the adsorption of protein, the adhesion, the growth and the spreading of osteoblasts and the regeneration of bone tissues, and has good regeneration function after being implanted into a human body.

Furthermore, the water contact angle of the maximum primary pore cavity wall surface of the porous tantalum is not more than 34.8 degrees, so that the wall surface has better hydrophilicity, and the porous tantalum bone regeneration effect is better.

Furthermore, the water contact angle of the maximum primary pore cavity wall surface of the porous tantalum is not more than 21 degrees, so that the hydrophilicity of the cavity wall surface is further improved, and the regeneration capacity of porous tantalum bone is stronger.

Furthermore, the water contact angle of the maximum primary pore cavity wall surface of the porous tantalum is not more than 5.2 degrees, so that the hydrophilicity of the cavity wall surface is further remarkably improved, and the regeneration capacity of porous tantalum bone is further remarkably improved.

Furthermore, if the porous tantalum is classified into at least three stages, the porous tantalum can effectively realize the effect of remarkably improving the hydrophilicity of the wall surface of the cavity, so that the regeneration effect of the porous tantalum bone is remarkably improved.

Furthermore, the pore diameter of the maximum primary pore cavity of the porous tantalum is 100-1500 μm, which is very helpful for bone tissue to grow into the porous tantalum implant material.

Furthermore, the same-grade porous material consisting of the same-grade pore cavities and the cavity walls in the material body of the porous tantalum is a continuous structure in the material body, so that each grade of porous material can be used as a grade of independent porous material to exist in the body to play the unique role of the grade of pore, and the porous tantalum body has the beneficial effects of multiple functions.

Furthermore, the maximum outer boundary of the continuous structure body formed by the same-grade porous material of the porous tantalum is equivalent to the maximum space boundary of the whole material body of the porous tantalum. The structure can lead the porous materials at all levels to have different physical and chemical properties in the whole material space, and lead the whole material body to meet the function requirements in various aspects.

Furthermore, the cavities of the same-stage porous material of each stage of the porous tantalum are uniformly distributed in the material body, so that the overall material body has uniform performance.

The invention has the beneficial effects that:

(1) the porous tantalum provided by the invention has the advantages that as the cavity wall of the upper large pore cavity is made of the lower cavity wall structure material which is made of the lower small pore cavity structure with the smaller pore diameter than the upper pore cavity, the cavity wall of the largest primary pore cavity is rougher, so that the hydrophilicity of the cavity wall of the largest primary pore cavity is improved, and the communicated lower pore cavity has the capillary action, so that the hydrophilicity of the cavity wall is further enhanced. The structural characteristics of the porous tantalum are particularly beneficial to the combination of the cavity wall surface with blood and tissue fluid, the adsorption of protein, the adhesion, growth and spreading of osteoblasts, the improvement of biocompatibility and the regeneration of bone tissues.

(2) The pore cavities of each grade of the porous tantalum are communicated with each other, and the pore cavities of each grade are also communicated with each other, so that blood and interstitial fluid can flow more smoothly in the porous tantalum, and the corresponding functions of the porous tantalum are completed.

(3) The porous tantalum provided by the invention can enable each stage of porous tantalum to respectively complete respective unique functions, and the whole porous tantalum material can meet the requirements of multiple functions.

(4) Because the pores of each level of the porous tantalum are uniformly distributed, the performance of the porous tantalum is uniform and stable.

Detailed Description

The detailed embodiments are given on the premise of the technical solution of the present invention, but the scope of the present invention is not limited to the following embodiments. It will be apparent that various substitutions and alterations can be made to the present invention without departing from the spirit and scope of the invention as defined by the appended claims, based on common technical knowledge and/or common usage in the art.

Examples of the invention are given in detail below:

example 1

The porous tantalum of the present embodiment has secondary pores, wherein the walls of the uniformly distributed and interconnected primary pores (large pores) have uniformly distributed and interconnected secondary pores (small pores), and the pores of each level are also interconnected. Each stage of porous tantalum is a continuous structural body, the maximum outer boundary of each stage of porous tantalum is equivalent to the space boundary of the whole material body, and the cavities of the same stage of porous material of each stage are uniformly distributed in the material body. The preparation method of the porous tantalum with the secondary pore structure comprises the following steps: preparing tantalum powder, a pore-forming agent for preparing a secondary pore cavity, a bonding agent and distilled water into slurry according to a proportion, ultrasonically dispersing, uniformly soaking the slurry in polyester foam to form a blank, drying, sintering the dried blank in vacuum, and carrying out conventional subsequent heat treatment on the sintered blank according to a tantalum material process to obtain the porous tantalum with the secondary pore. The pore sizes of the primary pore cavity and the secondary pore cavity are respectively controlled by the pore size of the polyester foam and the particle size of the pore-forming agent.

Specifically, in the porous tantalum with the secondary pores of the embodiment, the pore size of the smallest-level pore space (second-level pore space) is 5-20 mu m, and the pore size of the upper-level pore space (first-level pore space) which is one level larger than the pore size of the smallest-level pore space is 1200-1500 mu m. The detailed preparation method comprises the following steps:

(1) material preparation

Tantalum powder with the particle size of 20nm is used as a raw material, urea with the particle size of 10-30 μm is used as a pore forming agent of the smallest primary pore cavity of porous tantalum to be manufactured, polyvinyl alcohol with the particle size of below 50nm is used as a bonding agent, and the steps are as follows: urea: polyvinyl alcohol: distilled water is mixed according to the volume ratio of 20: 1: 1: 45, preparing slurry and carrying out ultrasonic dispersion for 40 min.

(2) And uniformly soaking the slurry by using the polyester foam with the aperture of 1300 mu m-1650 mu m to form a green body and drying.

(3) And (3) vacuum sintering the dried green body: vacuum degree of 7X 10^-4And Pa, heating the compact blank to 650 ℃ at the speed of 1.8 ℃/min, heating the blank to 1520 ℃ at the speed of 23 ℃/min, heating the blank to 1580 ℃ at the speed of 13 ℃/min, preserving the heat for 3 hours, and carrying out conventional subsequent heat treatment on the sintered blank according to a tantalum material process to obtain the porous tantalum with the secondary pores.

Taking the prepared porous tantalum sample, observing the appearance of the upper surface of the sample close to the surface of the wall of the first-stage cavity at one side by adopting a FEINova Nano SEM 400 field emission scanning electron microscope, finding out the horizontal plane 5 of the wall of the first-stage cavity close to the plane and with the size larger than 400 Mum x 400 Mum, testing the water contact angle of the horizontal plane of the wall of the first-stage cavity at the 5 position from the upper surface and the side by using a PT-705D contact angle measuring instrument, wherein the drop of the taken deionized water is 0.03 mu l, and the test result is shown in Table 1.

TABLE 1 measurement of Water contact Angle of the surface of the wall of the first stage lumen

Cavity wall number of cavity	Measurement of water contact angle on the surface of the lumen wall
		1	49.3°
2	47.8°
		3	48.1°
4	49.1°
		5	48.2°
Mean value of	48.5°

The water contact angle of the smooth surface of pure tantalum is 55.2 degrees, and therefore, the hydrophilicity of the wall surface of the first-stage porous cavity of the porous tantalum adopting the multi-stage porous cavity structure is obviously improved.

Example 2

The porous tantalum of the present embodiment has secondary pores, wherein the walls of the uniformly distributed and interconnected primary cavities have uniformly distributed and interconnected secondary cavities, and the cavities of the various levels are also interconnected. Each stage of porous tantalum is a continuous structural body, the maximum outer boundary of each stage of porous tantalum is equivalent to the space boundary of the whole material body, and the cavities of the same stage of porous material of each stage are uniformly distributed in the material body. The aperture of the minimum-level pore space (second-level pore space) is 20-40 mu m, and the aperture of the upper-level pore space (first-level pore space) which is one level larger than the aperture of the minimum-level pore space is 800-1200 mu m.

The preparation method is similar to that of the embodiment 1, wherein the pore size of the pore cavity is controlled by the particle size of the pore-forming agent and the pore size of the polyester foam, and in the step (1), the preparation of the material, the weight ratio of tantalum powder: urea: polyvinyl alcohol: the volume ratio of the distilled water is 20: 2: 1: 50, the aperture of the polyester foam is 920-1330 mu m.

The water contact angle of the porous tantalum primary cavity wall surface was 44.5 ° as tested in example 1.

Example 3

The porous tantalum of the present embodiment has secondary pores, wherein the walls of the uniformly distributed and interconnected primary cavities have uniformly distributed and interconnected secondary cavities, and the cavities of the various levels are also interconnected. Each stage of porous tantalum is a continuous structural body, the maximum outer boundary of each stage of porous tantalum is equivalent to the space boundary of the whole material body, and the cavities of the same stage of porous material of each stage are uniformly distributed in the material body. The aperture of the minimum-level pore space (second-level pore space) is 30-60 mu m, and the aperture of the upper-level pore space (first-level pore space) which is one level larger than the aperture of the minimum-level pore space is 600-800 mu m.

The preparation method is similar to that of the embodiment 1, wherein the pore size of the pore cavity is controlled by the particle size of the pore-forming agent and the pore size of the polyester foam, and in the step (1), the preparation of the material, the weight ratio of tantalum powder: urea: polyvinyl alcohol: the volume ratio of distilled water is 16: 4: 1: and 40, the aperture of the polyester foam is 710-920 mu m.

The water contact angle of the porous tantalum primary cavity wall surface was 34.8 ° as tested in example 1.

Example 4

A porous tantalum has three stages of cells, each stage of cell being interconnected, and each stage of cell also being interconnected. Each stage of porous tantalum is a continuous structural body, the maximum outer boundary of each stage of porous tantalum is equivalent to the space boundary of the whole material body, and the cavities of the same stage of porous material of each stage are uniformly distributed in the material body. The preparation method of the porous tantalum with the three-stage pore cavity structure comprises the following steps: preparing tantalum powder, a pore-forming agent for preparing a third-stage pore cavity, a pore-forming agent for preparing a second-stage pore cavity, a binder and distilled water into slurry according to a proportion, ultrasonically dispersing, uniformly soaking the slurry with polyester foam to form a blank, drying, sintering the dried blank in vacuum, and carrying out conventional subsequent heat treatment on the sintered blank according to a tantalum material process to obtain the porous tantalum with the third-stage pore. The aperture of the first stage pore cavity is controlled by the aperture of the polyester foam, and the aperture of the second stage pore cavity and the third stage pore cavity is controlled by the particle size of the pore-forming agent.

Specifically, in the porous tantalum having a three-dimensional through-hole structure of the present embodiment, the pore diameter of the pore of the largest pore (first-level pore) that is through in three dimensions is 400 μm to 600 μm, the wall of the largest pore is provided with a through-hole second-level pore, the pore diameter of the pore is 15 μm to 30 μm, the wall of the second-level pore is provided with a through-hole third-level pore (minimum-level pore), the pore diameter is 500nm to 700nm, and the detailed preparation method of the porous tantalum is as follows:

(1) material preparation

Adopting tantalum powder with the particle size of 20nm, urea with the particle size of 600nm-800nm, methylcellulose with the particle size of 22 μm-37 μm and polyvinyl alcohol with the particle size of less than 50nm, mixing the tantalum powder: urea: methyl cellulose: polyvinyl alcohol: distilled water in a volume ratio of 14: 5: 25: 2: 90 preparing into slurry, and ultrasonically dispersing for 40 min.

(2) And uniformly soaking the slurry by using polyester foam with the pore size of 510-720 mu m to form a blank body and drying.

(3) And (3) vacuum sintering the dried green body: vacuum degree of 7X 10^-4And Pa, heating the blank to 650 ℃ at the speed of 1.8 ℃/min, heating the blank to 1520 ℃ at the speed of 23 ℃/min, heating the blank to 1580 ℃ at the speed of 13 ℃/min, preserving the heat for 3 hours, and carrying out conventional subsequent heat treatment on the sintered blank according to a tantalum material process to obtain the porous tantalum with the three-level holes.

The water contact angle of the porous tantalum primary cavity wall surface was 21 deg. as tested in example 1.

Preparing 2 bars with the size of phi 5 multiplied by 8mm from the porous tantalum, taking another porous tantalum prepared by a chemical vapor deposition method with only a single pore cavity and the pore diameter of the pore cavity of 400 to 600 mu m, preparing 2 bars with the size of phi 5 multiplied by 8mm, sterilizing by gamma-rays, sealing and packaging for later use, wherein the wall surface of the cavity is a compact and smooth surface, and the water contact angle of the wall surface of the cavity is 55.2 degrees.

2 healthy male New Zealand big-ear white rabbits with the age of about 5 months and the weight range of 3.5-4kg are selected to carry out experimental animals, the rabbits are injected with the dose of 0.3m1/kg of fast-sleeping New No. two to complete induction anesthesia, and after 1 minute, the rabbits are injected with the dose of 1ml/kg of pentobarbital injection with the concentration of 3%. After anesthesia is finished, the femoral condyles on the two sides and the surrounding areas are preserved, the rabbit is fixed on an operating table, and the single is laid after the surrounding areas of the operating area on one side are disinfected. Cutting skin at the position of the condyle of the femur, separating muscle and fascia bluntly to see periosteum, exposing the cut periosteum to cortical bone, fully exposing the external condyle of the femur, selecting a relatively flat bone surface for positioning, drilling osteoclastic cortex at low speed by using an electric drill, then preparing a cylindrical defect with the diameter of about 5.1 mm and the depth of about 8.1mm, and cooling by using normal saline all the time when preparing the defect so as to prevent the injury of peripheral bone tissues caused by too much heat, implanting the porous tantalum rod prepared by the invention, and suturing the cut tissues layer by layer after flushing the wound with hydrogen peroxide and a large amount of normal saline; fixing the rabbit after turning over on the operating table, re-sterilizing the contralateral operation area and laying a sheet, wherein the operation method is the same as that described above, and implanting the other leg into a porous tantalum rod prepared by a chemical vapor deposition method. The other rabbit was subjected to the same operation, and after completion of the operation, 1.0g of cefazolin sodium was intramuscularly injected daily for three days to prevent infection.

After 8 and 12 weeks of implantation of the porous tantalum rods in the animals, one animal was sacrificed by intramuscular injection of an excess of 3% pentobarbital injection. Carefully taking out the condyle of the femur of the rabbit, and observing the growth condition of the defective bone of the condyle of the femur.

Rabbit femoral condyles taken after 8 and 12 weeks were soaked overnight in formalin solution for fixation, and bone blocks surrounding the specimens were carefully trimmed and embedded in acrylic resin. The embedded block is vertically and continuously sliced along the direction of a transverse axis by a hard tissue microtome (Leica-LA), each sample is sliced into 3 pieces with the thickness of about 150-200 mu m at different positions, the slices are ground to the thickness of 50 mu m by a grinding machine and are polished, the processed hard tissue slices are stained by Van Giesen, an Image is collected under an optical microscope (LEIICA MTLA), the condition that new bones grow into a porous tantalum rod is observed, and after the Image is collected, the area ratio of the new bones is quantitatively analyzed by using Image pro p1us6.0 professional Image analysis software.

After the porous tantalum rod is implanted in a rabbit body for 8 weeks, the area of the porous tantalum rod bone tissue grown into the pores of the porous tantalum rod prepared in the embodiment accounts for 72% of the total area of the pores of the porous tantalum rod, and the bone tissue grown into the porous tantalum rod prepared by the chemical vapor deposition method is only 18%.

After the porous tantalum rod is implanted into the rabbit body for 12 weeks, the area of the porous tantalum rod bone tissue grown into the pores of the porous tantalum rod prepared in the embodiment accounts for 93% of the total area of the pores of the porous tantalum rod, and the bone tissue grown into the porous tantalum rod prepared by the chemical vapor deposition method is only 25%.

Example 5

A porous tantalum has three-stage pore cavities, the pore diameter of the three-dimensionally through largest pore (first-stage pore) pore cavity is 100-400 μm, the wall of the largest pore cavity is provided with a through second-stage pore cavity, the pore diameter of the pore cavity is 1-10 μm, the wall of the second-stage pore cavity is provided with a through third-stage pore cavity (smallest-stage pore), the pore diameter is 6-8 nm, and all the pore cavities are mutually communicated. Each stage of porous tantalum is a continuous structural body, the maximum outer boundary of each stage of porous tantalum is equivalent to the space boundary of the whole material body, and the cavities of the same stage of porous material of each stage are uniformly distributed in the material body. The preparation method refers to example 4, wherein the pore size of the pore is controlled by the particle size of the pore-forming agent and the pore size of the polyurethane foam, and urea is changed into a block copolymer F127.

The water contact angle of the porous tantalum primary cavity wall surface was 5.2 ° as tested in example 1.

Claims

1. Porous tantalum comprising a body of material, characterized in that: the material body is a multi-level hole material which is formed by a hole cavity and a cavity wall, wherein the hole cavity is formed by grading the aperture of the material; wherein the cavity wall of the upper large pore is made of lower cavity wall structure material composed of lower small pore structure smaller than the pore diameter of the pore, the pores of each porous material are communicated with each other, the pores of each porous material are also communicated with each other, and the water contact angle of the surface of the cavity wall of the pore of the largest first porous material of the porous tantalum is not more than 48.5 degrees; the cavities of the same level of porous material of each stage in the porous tantalum are uniformly distributed within the material body.

2. The porous tantalum of claim 1, wherein: the water contact angle of the surface of the wall of the largest primary cavity of the porous tantalum is not more than 34.8 degrees.

3. The porous tantalum of claim 1, wherein: the water contact angle of the surface of the wall of the largest primary cavity of the porous tantalum is not more than 21 degrees.

4. The porous tantalum of claim 1, wherein: the water contact angle of the surface of the wall of the largest primary pore cavity of the porous tantalum is not more than 5.2 degrees.

5. The porous tantalum of claim 3 or 4, wherein: the porous tantalum has a grading number of at least three.

6. The porous tantalum of any one of claims 1 to 5, wherein: the pore diameter of the largest primary pore of the porous tantalum is 100-1500 mu m.

7. The porous tantalum of any one of claims 1 to 6, wherein: the same-grade porous material consisting of the same-grade pore cavity and the cavity wall in the porous tantalum body is a continuous structure in the material body.

8. The porous tantalum of claim 7, wherein: the maximum outer boundary of the continuous structure of the same level of porous material is equivalent to the maximum spatial boundary of the entire body of porous tantalum material.