CN112773931B

CN112773931B - Absorbable reinforced bone implant material and preparation method thereof

Info

Publication number: CN112773931B
Application number: CN202110002588.4A
Authority: CN
Inventors: 姜培齐; 石培国; 宋总安
Original assignee: Beijing Huatan Biotechnology Development Co ltd
Current assignee: Beijing Huatan Biotechnology Development Co ltd
Priority date: 2021-01-04
Filing date: 2021-01-04
Publication date: 2022-06-21
Anticipated expiration: 2041-01-04
Also published as: CN112773931A

Abstract

The invention provides an absorbable reinforced bone implant material and a preparation method thereof. The reinforced bone implant material can achieve the effect of preventing the surface of the metal fiber from being oxidized by using the polylactic acid and the metal fiber in a synergistic way, promotes the absorbability of the implant material, promotes the growth of bones by doping strontium, silver and selenium salt, reduces the corrosivity in vivo, ensures that the postoperative function of a patient is well recovered, can achieve the effect of being replaced by new bones after 12 months, and does not generate related complications.

Description

Absorbable reinforced bone implant material and preparation method thereof

Technical Field

The invention relates to the technical field of bone implants, in particular to an absorbable reinforced bone implant material and a preparation method thereof.

Background

The bio-absorbable material is a material which can be degraded and absorbed in the in vivo biological environment, and with the continuous and deep research on the bio-absorbable material and the cross fusion development of multiple disciplines such as materials science, biology, medicine and the like, the bio-absorbable material is widely applied to the medical field for manufacturing the human body implantable device. The development of orthopedics and the development of materials science are inseparable, and in recent years, the application research of absorbable materials in the orthopedics field is mainly focused on fracture internal fixation, and the absorbable materials are also used for bone and cartilage tissue engineering scaffolds, drug slow-release carriers and the like. The bio-absorbable material mainly comprises absorbable metal materials, high polymer materials, inorganic materials and composite materials 4. The bioabsorbable bone fracture plate, the screw, the intramedullary needle and the like are developed and applied to treating the fracture, and the implant can be degraded and absorbed after the fracture is healed, so that the secondary operation caused by taking out and fixing the implant internally is avoided; in addition, the absorbable implant can be added with medicines or growth factors to promote fracture healing and prevent infection, so the absorbable implant has wide application prospect.

At present, the degradable high polymer bone implantation medical instrument has insufficient support strength, and the degradable metal material is widely applied, but the pure metal material has poor corrosion resistance, and the recovery effect of a patient after being implanted into the body is poor, so that other complications are easily caused.

In view of the above, the present invention is particularly proposed.

Disclosure of Invention

The first purpose of the invention is to provide an absorbable reinforced bone implant material, which is characterized in that metal fibers are modified, the metal fibers and polylactic acid are cooperatively used, and strontium, silver and selenium salt are doped in the polylactic acid, so that the effect of preventing the surface of the metal fibers from being oxidized can be achieved, the absorbability of the implant material is promoted, the growth of bone is promoted by doping the strontium, the silver and the selenium salt, the in-vivo corrosivity is reduced, the postoperative function of a patient is well recovered, the effect of being replaced by new bone can be achieved after 12 months, and related complications do not occur.

The second purpose of the invention is to provide the preparation method of the reinforced bone implant material, which prevents the surface of the metal fiber from being oxidized by spraying polylactic acid on the surface of the metal fiber, enables the metal fiber to have good functionality in serving as the bone implant material, has no three wastes in the whole preparation method, and is safe and environment-friendly.

In order to achieve the above purpose of the present invention, the following technical solutions are adopted:

the invention provides an absorbable reinforced bone implant material which is mainly formed by mixing metal fibers and polylactic acid, wherein the polylactic acid is doped with strontium, silver and selenium salt.

The reinforced bone implant material improves the oxidation resistance and absorbability of the metal fiber by compounding the metal fiber and the polylactic acid, obviously enhances the bone growth speed by doping a plurality of elements in the polylactic acid, promotes the bone growth and enables a patient to quickly recover.

Among them, the addition of selenium is helpful to promote bone regeneration because it is found through research that fluoride is likely to cause bone cell apoptosis, and the addition of a proper amount of selenium has a good protective effect on bone cell apoptosis caused by fluorine of oxygen radical mediators, so that it is also advantageous to prevent fluoride poisoning by adding selenium, but the addition amount of selenium cannot be too large because if it is too large, not only the protective effect thereof is further improved, but also an inhibitory effect is caused, and thus the addition amount of selenium salt is 0.01 wt% -5 wt% of the polylactic acid in terms of selenium.

In addition, strontium regulates differentiation of MSCs (mesenchymal stem cells) into osteoblasts and promotes synthesis and precipitation of bone matrix proteins. Therefore, strontium has an osteoblast differentiation and osteogenesis promoting effect. Strontium can increase proliferation of preosteoblasts and pluripotent stem cells using at least two mechanisms. In addition, in animal models of osteoporosis, strontium can improve bone metabolism, prevent bone loss, and improve bone quality in osteoporotic animals. In the skeleton, strontium can replace a small amount of calcium in calcified tissue skeleton and tooth hydroxyapatite crystal, and the proper amount of strontium element is doped to improve the mechanical performance of bone and the strength of bone. Therefore, in order to ensure the proper amount of strontium, the amount of strontium salt added is preferably controlled to be between 0.5 wt% and 5 wt% of the polylactic acid in terms of strontium.

In order to resist infection, silver salt is doped in the polylactic acid, the addition amount of the silver salt is 0.01-3 wt% of the polylactic acid in terms of silver, and the silver salt is added in a proper amount to resist infection and has the effect of promoting bone growth by cooperating with strontium element and selenium element.

The amount of strontium salt added is 0.7 wt%, 1 wt%, 2 wt%, 3 wt%, etc. in terms of strontium, the amount of silver salt added is 0.05 wt%, 0.1 wt%, 0.5 wt%, 1 wt%, 2 wt%, 2.5 wt%, etc. in terms of silver, and the amount of selenium salt added is 0.05 wt%, 0.1 wt%, 0.5 wt%, 1 wt%, 2 wt%, 2.5 wt%, 3 wt%, 4 wt%, 4.5 wt%, etc. in terms of selenium.

Preferably, the metal element of the metal fiber is any one or combination of magnesium, aluminum, iron and zinc.

Preferably, the mass of the metal fiber is 0.1 wt% to 10 wt% of the mass of the polylactic acid. The addition amount of the polylactic acid needs to be appropriate to ensure that the effects of resisting oxidation and promoting absorbability can be achieved, and if the addition amount is too large, the absorbability of the bone material can be reduced. In addition to this, the mass of the metal fiber may be 0.5 wt%, 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 7 wt%, 8 wt%, 9 wt%, or the like of the mass of the polylactic acid.

The invention also provides a preparation method of the reinforced bone implant material, which comprises the following steps:

mixing and stirring solid powder or salt solution of strontium, silver and selenium salt and polylactic acid, and melting to obtain modified polylactic acid;

mixing metal powder, drawing wire to form metal fiber, spraying the metal modified polylactic acid on the surface of the metal fiber, and cutting into 1-2mm length.

In the preparation method, the polylactic acid is modified by strontium, silver and selenium salt, and then the surface of the drawn metal fiber is coated, although the coating thickness is preferably required to a certain extent, and is generally between 2 and 3 mu m, so that the polylactic acid can just play a role in oxidation resistance.

Preferably, the spraying of the modified polylactic acid further comprises a baking step, wherein the baking temperature is 140-150 ℃. Baking is also for robustness of the spray.

Preferably, the modified polylactic acid is crushed into micron-sized powder in advance and then is sprayed.

Preferably, the particle size of the crushed powder of the modified polylactic acid is 100-500 μm.

In order to fully improve the flatness and the uniformity after spraying, the adopted modified polylactic acid is pre-crushed into microparticles and then sprayed.

The bone implant material prepared by the preparation method can be a bone plate, a bone nail, a bone needle or a bone fragment and the like, and can be selected according to specific practical application scenes.

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

(1) the reinforced bone implant material provided by the invention has the advantages that the metal fiber is modified, the metal fiber and the polylactic acid are cooperatively used, and the polylactic acid is doped with strontium, silver and selenium salt, so that the effect of preventing the surface of the metal fiber from being oxidized can be achieved, the absorbability of the implant material is promoted, the growth of bone is promoted by doping the strontium, the silver and the selenium salt, the in-vivo corrosivity is reduced, the postoperative function of a patient is well recovered, the effect of being replaced by new bone can be achieved after 12 months, and related complications do not occur;

(2) according to the preparation method of the reinforced bone implant material, polylactic acid is sprayed on the surface of the metal fiber to prevent the surface of the metal fiber from being oxidized, so that the metal fiber has good functionality in serving as the bone implant material, and the whole preparation method is safe and environment-friendly without three wastes.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below.

Fig. 1 is a 60-day X-ray photograph of a bone implant material according to example 1 of the present invention after being implanted into a free leg bone;

fig. 2 is a 120-day X-ray film of the bone implant material according to example 1 of the present invention after being implanted into a free leg bone;

fig. 3 is a 240-day X-ray photograph of the bone implant material according to example 1 of the present invention after being implanted into a free leg bone;

fig. 4 is a 60-day X-ray photograph of the bone implant material of comparative example 1 after being implanted into a femur of a home;

fig. 5 is a 120-day X-ray film after the bone implant material of comparative example 1 is implanted into a femur of a home;

fig. 6 is a 240-day X-ray photograph after the bone implant material of comparative example 1 was implanted into a free leg bone.

Detailed Description

Embodiments of the present invention will be described in detail below with reference to examples, but it will be understood by those skilled in the art that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.

Example 1

The bone implant material is prepared as follows:

1) preparing strontium salt, silver salt and selenium salt solution in advance, controlling the temperature to be 30 ℃, uniformly stirring and mixing the strontium salt, silver salt and selenium salt solution and polylactic acid, heating to 300 ℃ for melting to obtain modified polylactic acid, and cooling;

2) uniformly mixing magnesium powder, aluminum powder, iron powder and zinc powder, extruding and drawing to form metal fibers, spraying the modified polylactic acid obtained in the step on the surfaces of the metal fibers by using a spray gun, drying at the temperature of 150 ℃ in a baking oven after spraying is finished, cutting into fibers with uniform length of 1mm, and then preparing and using the fibers.

Example 2

The bone implant material is prepared as follows:

1) preparing strontium salt, silver salt and selenium salt solution in advance, wherein the mass percentage concentration of all the salt solution is 30 wt%, controlling the temperature at 30 ℃, stirring and mixing the strontium salt, the silver salt and the selenium salt solution with polylactic acid uniformly, wherein the addition amount of strontium is 0.5 wt% of the polylactic acid, the addition amount of silver is 3 wt% of the polylactic acid, the addition amount of selenium is 0.01 wt% of the polylactic acid, heating to 350 ℃, melting to obtain modified polylactic acid, cooling, and crushing into polylactic acid powder with the granularity of 100 mu m;

2) uniformly mixing magnesium powder, aluminum powder, iron powder and zinc powder, extruding and drawing to form metal fibers, spraying the polylactic acid powder obtained in the above steps on the surfaces of the metal fibers by using a spray gun, wherein the spraying thickness is 3mm, the mass of the metal fibers is ensured to be 0.1 wt% of the mass of the polylactic acid, controlling the temperature in a baking oven at 140 ℃ after the spraying is finished, drying, cutting into uniform fibers with the length of 1.5mm, and then, preparing and using the uniform fibers.

Example 3

The bone implant material is prepared as follows:

1) preparing strontium salt, silver salt and selenium salt solution in advance, wherein the mass percentage concentration of all the salt solution is 30 wt%, controlling the temperature at 30 ℃, stirring and mixing the strontium salt, silver salt and selenium salt solution and polylactic acid uniformly, wherein the addition amount of strontium is 5 wt% of polylactic acid, the addition amount of silver is 0.01 wt% of polylactic acid, and the addition amount of selenium is 5 wt% of polylactic acid, heating to 350 ℃, melting to obtain modified polylactic acid, cooling, and crushing into polylactic acid powder with the granularity of 500 mu m;

2) uniformly mixing magnesium powder, aluminum powder, iron powder and zinc powder, extruding and drawing to form metal fibers, spraying the polylactic acid obtained in the step on the surface of the metal fibers by using a spray gun, wherein the spraying thickness is 3 mu m, and the mass of the metal fibers is 10 wt% of that of the polylactic acid, controlling the temperature of 140 ℃ in a baking oven after the spraying is finished, drying, cutting into uniform fibers with the length of 2mm, and then preparing and using the uniform fibers.

Example 4

The bone implant material is prepared as follows:

1) preparing strontium salt, silver salt and selenium salt solution in advance, wherein the mass percentage concentration of all the salt solution is 30 wt%, controlling the temperature at 30 ℃, stirring and mixing the strontium salt, silver salt and selenium salt solution and polylactic acid uniformly, wherein the addition amount of strontium is 2 wt% of polylactic acid, the addition amount of silver is 1 wt% of polylactic acid, and the addition amount of selenium is 2 wt% of polylactic acid, heating to 350 ℃, melting to obtain modified polylactic acid, cooling, and crushing into polylactic acid powder with the granularity of 300 mu m;

2) uniformly mixing magnesium powder, aluminum powder, iron powder and zinc powder, extruding and drawing to form metal fibers, spraying the polylactic acid powder obtained in the step on the surfaces of the metal fibers by using a spray gun, wherein the spraying thickness is 2.5mm, the mass of the metal fibers is ensured to be 2 wt% of the mass of the polylactic acid, controlling the temperature in a baking oven at 145 ℃ after the spraying is finished, drying, cutting into fibers with uniform length of 2mm, and then preparing and using the fibers.

Example 5

The procedure was as in example 4 except that strontium was added in an amount of 0.1 wt% based on the weight of the polylactic acid.

Example 6

The specific procedure was the same as in example 4 except that silver was added in an amount of 5 wt% based on the weight of polylactic acid.

Example 7

The procedure was as in example 4 except that selenium was added in an amount of 0.001 wt% based on the weight of the polylactic acid.

Example 8

The specific procedure was identical to example 4 except that the metal fibers were 12 wt% of the polylactic acid.

Comparative example 1

The specific procedure is identical to example 4, except that no polylactic acid is added.

Experimental example 1

The reinforced bone implant materials obtained in examples 1 to 8 and comparative example 1 of the present invention were mixed with an equal volume of glyceryl monostearate powder, heated and melted, and the biomechanical properties were measured using a constant-wing instrument biomechanical tester, wherein the following test samples were measured after the prepared samples were immersed in warm water for 12 hours and 3 days, and then taken out and dried for 3 hours:

TABLE 1 biomechanical test results of 12h immersion

Group of	Best force (N)	Maximum deformation (mm)	Appearance of the product
				Example 1	10.0	6.0	No crack and high hardness
Example 2	11.2	6.0	No crack and high hardness
				Example 3	11.3	6.0	No crack and high hardness
Example 4	11.4	6.0	No crack and high hardness
				Example 5	9.8	5.0	No crack and high hardness
Example 6	9.7	5.0	No crack and high hardness
				Example 7	9.5	5.0	No crack and high hardness
Example 8	9.2	5.0	No crack and high hardness
				Comparative example 1	8.7	4.0	Has cracks and good hardness retention

TABLE 2 biomechanical test results of immersion 3d

Group of	Maximum force (N)	Maximum deformation (mm)	Appearance of the product
				Example 1	10.0	6.0	No crack and high hardness
Example 2	11.2	6.0	No crack and high hardness
				Example 3	11.3	6.0	No crack and high hardness
Example 4	11.4	6.0	No crack and high hardness
				Example 5	9.7	5.0	No crack and high hardness
Example 6	9.6	5.0	No crack and high hardness
				Example 7	9.4	5.0	No crack and high hardness
Example 8	9.1	5.0	No crack and high hardness
				Comparative example 1	7.2	4.0	Cracked and crisp

As can be seen from the results in tables 1-2, the bone implant material according to the embodiments of the present invention has good mechanical stability, especially superior biomechanical strength, so it can be seen that the bone implant material according to the present invention can significantly improve the biomechanical properties by using polylactic acid and metal fiber in a synergistic manner, and it is certainly more advantageous for the stability of the bone material to control the added strontium, silver and selenium elements within a proper amount.

Because the proper amount of the strontium, the silver and the selenium has certain influence on the biomechanical strength such as the toughness of the bone implant material, if the addition amount is too large or too low, the bone implant material can not be ensured to be in the most excellent biomechanical strength range, the optimal mechanical strength of the bone implant material is ensured to be good in toughness, strength and deformation, and the bone implant material can still maintain excellent stability under the condition of strong impact of body fluid.

Experimental example 2

The bone implant material of example 1 of the present invention was prepared into a circular rod with a diameter of 2mmx6mm, and was implanted into a femur of a human body, X-ray films were taken at 60 days, 120 days, and 240 days, respectively, and the material absorption and bone growth conditions were as shown in fig. 1 to 3, and it can be seen from the figures that the implant material was substantially absorbed and the bone pores were substantially healed at 240 days, indicating that the bone implant material of the present invention has good absorption, fast postoperative recovery, and few side effects in vivo. Corresponding results were also obtained by subjecting the bone implant materials of examples 2-4 of the present invention to the above-described experiments.

In addition, the bone implant materials of examples 5 to 8 according to the present invention and comparative example 1 were subjected to the above-mentioned experiment, and it was found that when the X-ray film taken for 240 days did not reach the complete absorption of example 1, the bone pores were not healed, and thus when the amounts of strontium, silver and selenium were not appropriate, the bone absorption was affected, and particularly when the metal fiber content was large and the polylactic acid content was low in example 8, the side reaction was more and the functionality of polylactic acid was reduced, so that the recovery absorption rate was relatively slow.

Finally, comparative example 1 has the slowest absorption rate and the slowest bone hole healing rate because polylactic acid is not added at all, and particularly, referring to the X-ray films of FIGS. 4 to 6, the implant material is not absorbed at 240 days, and the bone hole healing rate is also very slow.

While particular embodiments of the present invention have been illustrated and described, it would be obvious that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention.

Claims

1. An absorbable reinforced bone implant material is characterized by being mainly formed by mixing metal fibers and polylactic acid, wherein the polylactic acid is doped with strontium salt, silver salt and selenium salt;

the addition amount of the strontium salt is 0.5-5 wt% of the polylactic acid calculated by strontium, the addition amount of the silver salt is 0.01-3 wt% of the polylactic acid calculated by silver, and the addition amount of the selenium salt is 0.01-5 wt% of the polylactic acid calculated by selenium;

the mass of the metal fiber is 0.1-10 wt% of that of the polylactic acid;

the metal element of the metal fiber is any one or combination of magnesium, aluminum, iron and zinc.

2. The method of preparing an absorbable reinforced bone implant material of claim 1, comprising the steps of:

mixing and stirring strontium salt, silver salt and selenium salt solid powder or salt solution with polylactic acid, melting to obtain modified polylactic acid, and cooling;

crushing the modified polylactic acid into micron-sized powder;

mixing metal powder, drawing wire to form metal fiber, spraying the modified polylactic acid on the surface of the metal fiber, and cutting into 1-2 mm.

3. The method according to claim 2, wherein the thickness of the spray coating on the surface of the metal fiber is 2 to 3 μm.

4. The method as claimed in claim 2, wherein the spraying step comprises a baking step, and the baking temperature is 140-150 ℃.

5. The method according to claim 2, wherein the particle size of the crushed powder of the modified polylactic acid is 100-500. mu.m.