CN110917398A - Method for oxidation resistance of biomaterial and biomaterial - Google Patents
Method for oxidation resistance of biomaterial and biomaterial Download PDFInfo
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Abstract
The application discloses an anti-oxidation method of a biological material and the biological material, wherein the anti-oxidation method comprises the following steps: under the preset condition, carrying out anti-oxidation treatment on the biological material by using a reducing agent, and storing the biological material subjected to the anti-oxidation treatment in a dry state. Through adopting the reductant to carry out anti-oxidant treatment to biomaterial, can be so that biomaterial self has certain antioxidant capacity, under uncontrollable external environment, unpredictable's change does not take place for protection material itself that can be fine. Meanwhile, the biological material subjected to anti-calcification treatment is stored in a dry form, the biological material is stored in the dry form, the requirement on the storage condition is lower, the storage time is longer, and the biological material has the capability of tolerating adverse environment. Meanwhile, the biological material stored in a dry form can be directly used after being unsealed and completely packaged without rinsing and assembling, so that the application is more convenient, and the rescue time is saved.
Description
Technical Field
The application belongs to the technical field of biological material treatment, and particularly relates to an anti-oxidation method of a biological material and the biological material.
Background
The biological material is a natural or artificial special functional material which is used for contacting and interacting with a living system and can carry out diagnosis, treatment, replacement, repair or induced regeneration on cells, tissues and organs of the biological material, and is also called as a biomedical material. The biological material comprises artificial synthetic material and natural material; there are single materials, composite materials, and hybrid materials that are a combination of living cells or natural tissues and inanimate materials. Biomaterials are not drugs per se, and their therapeutic approaches are essentially characterized by direct binding and interaction with the living organism.
At present, the dry preservation method is generally adopted for the biological material, but the biological material is easily influenced by the external environment to change unpredictably or even lose the original function in the dry preservation process.
Disclosure of Invention
The application provides an anti-oxidation method of a biological material and the biological material, which aim to solve the technical problem that the biological material is easily influenced by external environment and changed in the process of being preserved by a dry-state preservation method.
In order to solve the technical problem, the application adopts a technical scheme that: a method of anti-oxidation of a biomaterial comprising: under the preset condition, carrying out anti-oxidation treatment on the biological material by using a reducing agent, and storing the biological material subjected to the anti-oxidation treatment in a dry state.
According to an embodiment of the present application, the reducing agent comprises one or more of sodium borohydride, sodium cyanoborohydride and/or sodium triacetoxyborohydride.
According to an embodiment of the present application, the anti-oxidation treatment of the biological material with a reducing agent comprises: the reducing agent is diluted with a buffer to obtain a reducing solution, and the biological material is soaked with the reducing solution.
According to an embodiment of the present application, the anti-oxidation treatment of the biological material with a reducing agent further comprises: and (3) oscillating, ultrasonically or stirring the reduction solution soaked with the biological material.
According to an embodiment of the present application, the concentration of the reducing agent in the reducing solution is 0.01% to 10%.
According to an embodiment of the present application, the preset conditions include a soaking time and a treatment temperature for soaking the biological material in the reducing solution; wherein the soaking time is 0.5-48 hours, and the treatment temperature is 4-58 ℃.
According to an embodiment of the present application, the buffer comprises phosphate buffered saline, 2 morpholinoethanesulfonic acid, 4-hydroxyethylpiperazine ethanesulfonic acid, carbonate buffered saline, absolute ethanol, physiological saline or ethanol/physiological saline mixed solution.
According to an embodiment of the present application, the preserving the biological material in a dry state after the anti-oxidation treatment comprises: freeze-drying, glycerating and dehydrating the biological material subjected to the antioxidant treatment and/or performing gradient dehydration on ethanol, and then storing the biological material in a dry state.
According to an embodiment of the application, the biomaterial comprises porcine aortic valve, porcine/bovine pericardium, bovine muscle/achilles tendon, porcine bladder, porcine/bovine dermal matrix, porcine small intestine submucosa matrix, porcine/bovine peritoneum, blood vessels, xenogenic or xenogenic bone, porcine eye cornea or tympanic membrane.
In order to solve the technical problem, the application adopts a technical scheme that: a biomaterial which has been subjected to an anti-calcification treatment by any of the methods described above.
The beneficial effect of this application is: through adopting the reductant to carry out anti-oxidant treatment to biomaterial, can be so that biomaterial self has certain antioxidant capacity, under uncontrollable external environment, unpredictable's change does not take place for protection material itself that can be fine. The adopted reducing agent has a continuous reduction effect, so that oxidation caused by the external environment can be effectively resisted in the subsequent storage, treatment and use processes of the biological material. Meanwhile, the biological material subjected to anti-calcification treatment is stored in a dry form, the biological material is stored in the dry form, the requirement on the storage condition is lower, the storage time is longer, and the biological material has the capability of tolerating adverse environment. Meanwhile, the biological material stored in a dry form can be directly used after being unsealed and completely packaged without rinsing and assembling, so that the application is more convenient, and the rescue time is saved.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings needed to be used in the description of the embodiments are briefly introduced below, it is obvious that the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without inventive efforts, wherein:
FIG. 1 is a schematic flow diagram of an embodiment of a method of antioxidant of a biomaterial of the present application;
FIG. 2 is a graph showing the results of measuring the change in aldehyde group content of the antioxidant-treated and non-antioxidant-treated biomaterials of the present application;
fig. 3 is a schematic flow diagram of another embodiment of a method of antioxidant of a biomaterial of the present application.
Detailed Description
The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application, and it is obvious that the described embodiments are only a part of the embodiments of the present application, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.
Referring to fig. 1, fig. 1 is a schematic flow chart of an embodiment of a method for oxidation resistance of a biomaterial according to the present application.
An embodiment of the present application provides an anti-oxidation method for a biomaterial, the method including:
s101: under the preset condition, the biological material is subjected to anti-oxidation treatment by using a reducing agent, and the biological material subjected to the anti-oxidation treatment is stored in a dry state.
In one embodiment, the biomaterial comprises a porcine aortic valve, porcine/bovine pericardium, bovine muscle/achilles tendon, porcine bladder, porcine/bovine dermal matrix, porcine small intestine submucosa matrix, porcine/bovine peritoneum, blood vessels, xenogenic or xenogenic bone, porcine eye cornea, or tympanic membrane.
In one embodiment, the reducing agent comprises one or more of sodium borohydride, sodium cyanoborohydride, and/or sodium triacetoxyborohydride. Through adopting the reductant to carry out anti-oxidant treatment to biomaterial, can be so that biomaterial self has certain antioxidant capacity, under uncontrollable external environment, unpredictable's change does not take place for protection material itself that can be fine. The reducing agents have a continuous reducing effect, so that oxidation caused by the external environment can be effectively resisted in the subsequent storage, treatment and use processes of the biological material; in addition, the reducing agents have small residues on the biological materials, are harmless to human bodies, and are suitable for oxidation resistance of the biological materials.
In one embodiment, the predetermined conditions include a soaking time and a treatment temperature for the reducing solution to soak the biological material. The soaking time is 0.5-48 hours, specifically, the soaking time can be 0.5 hour, 12 hours, 24 hours, 36 hours or 48 hours, and the soaking time is not limited herein; the treatment temperature is 4 ℃ to 58 ℃, specifically, the treatment temperature is 4 ℃, 18 ℃, 31 ℃, 42 ℃ or 58 ℃, and the treatment temperature is not limited herein.
In one embodiment, the anti-oxidant treatment of the biological material with a reducing agent comprises: the reducing agent is diluted with a buffer to obtain a reducing solution, and the biological material is soaked with the reducing solution.
The concentration of the reducing agent in the reducing solution is 0.01% to 10%, and specifically, the concentration of the amine compound may be 0.01%, 3%, 5%, 8%, and 10%, which is not limited herein.
Wherein the buffer system comprises PBS (phosphate buffered saline solution) and the acid-base condition is pH 7.4; MES (2 morpholinoethanesulfonic acid) at pH 5.5 under acid-base conditions; HEPES (4-hydroxyethyl piperazine ethanesulfonic acid) at pH 7.5 under acid-base conditions; CBS (carbonate buffer solution) with an acid-base condition of pH 10.3; absolute ethyl alcohol; normal saline and ethanol/normal saline mixed solution.
The anti-oxidative treatment of the biological material with a reducing agent further comprises: the reducing solution soaked with the biological material is oscillated, ultrasonically or stirred, so that the flow speed of the reducing solution can be increased, and the anti-oxidation treatment of the biological material can be accelerated.
In one embodiment, preserving the biological material in a dry form after the anti-oxidant treatment comprises: freeze drying the biological material after the antioxidation treatment, glycerizing dehydration and/or ethanol gradient dehydration, and storing the biological material in a dry state. The biological material is stored in a dry state, has lower requirement on the storage condition, has longer storage time and has the capability of tolerating adverse environment. Meanwhile, the biological material stored in a dry form can be directly used after being unsealed and completely packaged without rinsing and assembling, so that the application is more convenient, and the rescue time is saved.
Wherein the glycerolysis dehydration comprises soaking the biological material in a mixed solution of high-concentration glycerol (80% -95%) and a small amount of absolute ethyl alcohol to absorb water in the biological material; the ethanol gradient dehydration comprises soaking the biological material in 75%/80% ethanol solution (ethanol mixed with normal saline) for 3-30 min, soaking in 95% ethanol solution (ethanol mixed with normal saline) for 3-30 min, and soaking in anhydrous ethanol for 3-30 min to achieve dehydration effect on the biological material; freeze-drying includes prefreezing, annealing, and resolution drying.
The following will be further explained in connection with two embodiments:
example 1
1. And (3) antioxidant treatment:
sodium borohydride is used as a reducing agent, and PBS solution is used as a buffer solution. 0.5g of sodium borohydride was weighed and dissolved in 100ml of absolute ethanol, and then the porcine aortic valve was placed and shaken at room temperature for 24 hours at a rotation speed of 50 rpm. It should be noted that the porcine aortic valve may be subjected to an anti-calcification treatment before the anti-oxidation treatment, and the porcine aortic valve used herein is subjected to the anti-calcification treatment.
2. Drying:
and (3) shaking and cleaning the pig origin aortic valve which is subjected to the oxidation resistance treatment for 3 times by using a PBS solution, wherein each time is 10 minutes, then carrying out freeze drying treatment by using a freeze dryer, and boxing and storing the freeze-dried pig origin aortic valve.
Example 2
1. And (3) antioxidant treatment:
sodium triacetoxyborohydride is used as a reducing agent, and a PBS solution is used as a buffer solution. 100ml of PBS solution containing 0.5% sodium triacetoxyborohydride is measured, the pH value is adjusted to 7.40 by using sodium hydroxide solution, the solution is poured into a container, 3 bovine pericardium sheets with the diameter of 50mm are added, and the container is placed in a refrigerator at the temperature of 4 ℃ and refrigerated for 48 hours. It should be noted that the bovine pericardium may be cross-linked before the antioxidant treatment, and the bovine pericardium used herein may be cross-linked with glutaraldehyde.
2. Drying:
the bovine pericardium was removed and washed 3 times with 80%/20% ethanol/normal saline solution at room temperature for 15 minutes each time.
Soaking the cleaned bovine pericardium in 95% ethanol solution for 2 hours, taking out, soaking in absolute ethanol for 2 hours, replacing with new absolute ethanol solution, continuing to soak for 2 hours, repeating for three times, and exposing in air to completely volatilize ethanol to obtain dehydrated bovine pericardium.
The method of the two embodiments is adopted to respectively process three samples, and the aldehyde content and the performance of the samples are respectively detected before and after the samples are processed, and the specific detection results are as follows:
1. variation of aldehyde group content (nmol/g) of the antioxidant treated and non-antioxidant treated biomaterials:
referring to fig. 2, fig. 2 is a schematic diagram of the detection results of the aldehyde group content change of the biological materials of the present application after oxidation resistance treatment and before oxidation resistance treatment,
specifically, fig. 2 shows the change of aldehyde group content in 60 days of the sample 1 subjected to the anti-oxidation treatment by the method of example 1, and the change of aldehyde group content in 60 days of the biological material which is not subjected to the anti-oxidation treatment and is from the same source as the sample 1, respectively, and it can be seen from fig. 2 that the aldehyde group content in 60 days of the sample 1 subjected to the anti-oxidation treatment slightly increases and is gradually decreased, and the sample has a higher capability of resisting adverse environments because the increase of the total aldehyde group content is small compared with the sample not subjected to the anti-oxidation treatment.
2. Temperature change (deg.C) before and after oxidation resistance, see in particular Table 1 below:
table 1: temperature change of thermal denaturation before and after oxidation resistance
As can be seen from table 1, the samples of example 1 and example 2 have no statistical difference in heat distortion temperature before and after oxidation resistance, so the oxidation resistance method in the present application is mild and has no substantial damage to biological materials.
3. Calcium detection (in μ g/mg) 8 weeks after subcutaneous implantation in mice is described in detail in table 2 below:
table 2: calcium assay (unit. mu.g/mg) 8 weeks after subcutaneous implantation in mice
| Examples 1 to 1 | 1-2 | 1-3 | Example 2-1 | 2-2 | 2-3 | |
| Time/ |
0 | 3 | 7 | 14 | 28 | 56 |
| Before oxidation resistance | 0.037 | 0.496 | 8.974 | 15.986 | 38.941 | 54.333 |
| After oxidation resistance | 0.04 | 0.071 | 2.601 | 4.671 | 10.586 | 17.213 |
As can be seen from table 2, in the samples of example 1 and example 2, calcium detection was performed after the mice were subcutaneously implanted for 8 weeks before and after oxidation resistance, respectively, and the calcium content after oxidation resistance was significantly reduced.
In summary, different from the situation of the prior art, the oxidation resistance method of the biomaterial provided by the application can enable the biomaterial to have certain oxidation resistance by performing oxidation resistance treatment on the biomaterial by using the reducing agent, and can well protect the biomaterial from unpredictable changes under an uncontrollable external environment. The adopted reducing agent has a continuous reduction effect, so that oxidation caused by the external environment can be effectively resisted in the subsequent storage, treatment and use processes of the biological material. Meanwhile, the biological material subjected to anti-calcification treatment is stored in a dry form, the biological material is stored in the dry form, the requirement on the storage condition is lower, the storage time is longer, and the biological material has the capability of tolerating adverse environment. Meanwhile, the biological material stored in a dry form can be directly used after being unsealed and completely packaged without rinsing and assembling, so that the application is more convenient, and the rescue time is saved.
Referring to fig. 3, fig. 3 is a schematic flow chart of another embodiment of the oxidation resistance method for biological material of the present application.
Another embodiment of the present application provides a method for oxidation resistance of a biomaterial, the method comprising:
in another embodiment, before the biological material is resistant to oxidation, the method further comprises the step of anti-calcification of the biological material, which comprises the following specific steps:
s201: under predetermined conditions, the biological material is subjected to an anti-calcification treatment with an amine compound.
In another embodiment, the biomaterial comprises a porcine aortic valve, porcine/bovine pericardium, bovine muscle/achilles tendon, porcine bladder, porcine/bovine dermal matrix, porcine small intestine submucosa matrix, porcine/bovine peritoneum, blood vessels, xenogenic or xenogenic bone, porcine eye cornea, or tympanic membrane.
In another embodiment, the biomaterial is cross-linked with an aldehyde compound before being subjected to the anti-calcification treatment. The aldehyde compounds include dialdehyde compounds such as glyoxal, and monoaldehyde compounds such as formaldehyde and acetaldehyde. The biological material after the aldehyde compound crosslinking treatment is easy to have residual aldehyde functional groups and initiate calcification. The amino group of the amine compound can react with the aldehyde group which can initiate the calcification of the biological material, so that the aldehyde group is sealed, the fact that the residual aldehyde group can initiate the calcification of the biological material is avoided, the amine compound is used for carrying out anti-calcification treatment on the biological material, the negative influence brought by the aldehyde compound is reduced to the minimum, and therefore the amine compound has strong anti-calcification performance.
In another embodiment, the amine compound is a diamine compound, and the diamine compound has two amino groups, so that the diamine compound can not only react with residual aldehyde groups, but also react with one aldehyde group by using two amino groups, so as to enhance the crosslinking effect.
Further, the amine compound includes one or more of ethylenediamine, hexamethylenediamine, octamethylenediamine, lysine, arginine, asparagine, or glutamine.
In another embodiment, the predetermined conditions include a soaking time and a treatment temperature for soaking the biological material with the amine compound solution. The soaking time is 2-72 hours, specifically, the soaking time can be 2 hours, 20 hours, 37 hours, 50 hours or 72 hours, and is not limited herein; the treatment temperature is 4 ℃ to 58 ℃, the treatment temperature is 4 ℃, 15 ℃, 31 ℃, 45 ℃ or 58 ℃, and the treatment temperature is not limited herein.
In another embodiment, the anti-calcification treatment of biological material with an amine compound comprises: diluting the amine compound with a buffer solution to obtain an amine compound solution, and soaking the biological material with the amine compound solution.
The concentration of the amine compound in the amine compound solution is 0.01% to 10%, and specifically, the concentration of the amine compound may be 0.01%, 3%, 5%, 8%, and 10%, which is not limited herein.
Wherein the buffer system comprises PBS (phosphate buffered saline solution) and the acid-base condition is pH 7.4; MES (2 morpholinoethanesulfonic acid) at pH 5.5 under acid-base conditions; HEPES (4-hydroxyethyl piperazine ethanesulfonic acid) at pH 7.5 under acid-base conditions; CBS (carbonate buffer solution) with an acid-base condition of pH 10.3; absolute ethyl alcohol; normal saline and ethanol/normal saline mixed solution.
The anti-calcification treatment of biological material with an amine compound further comprises: the inactivation solution is vibrated, ultrasonically treated or stirred, so that the flowing speed of the amine compound solution can be increased, and the anti-calcification treatment on the biological material can be accelerated.
S202: under the preset condition, the biological material is subjected to anti-oxidation treatment by using a reducing agent, and the biological material subjected to the anti-oxidation treatment is stored in a dry state.
The content of step S202 in this embodiment is substantially the same as the corresponding steps in the above embodiments, and is not described here again.
Generally, the processing steps of the biological material are aldehyde crosslinking, anti-calcification and anti-oxidation treatment in sequence. The biological material is subjected to anti-calcification treatment by the method, and the amine compound is used for carrying out anti-calcification treatment on the biological material, so that the negative influence brought by the aldehyde compound is minimized, and the biological material has stronger anti-calcification performance. The biological material is subjected to anti-oxidation treatment by the method, so that the biological material has certain anti-oxidation capacity, and the material can be well protected from unpredictable change in an uncontrollable external environment. The biological material which is subjected to anti-calcification and anti-oxidation treatment and stored in a dry state has stable performance and is convenient to store.
According to the biological material, the biological material is treated by the anti-oxidation method in any one of the embodiments, so that the biological material is subjected to anti-oxidation treatment by the reducing agent, the biological material can have certain anti-oxidation capacity, and the material can be well protected from unpredictable change in an uncontrollable external environment. Wherein the biomaterial comprises porcine aortic valve, porcine/bovine pericardium, bovine muscle/achilles tendon, porcine bladder, porcine/bovine dermal matrix, porcine small intestine submucosa matrix, porcine/bovine peritoneum, blood vessel, xenogenic or xenogenic bone, porcine eye cornea or tympanic membrane.
The above description is only an example of the present application and is not intended to limit the scope of the present application, and all modifications of equivalent structures and equivalent processes, which are made by the contents of the specification and the drawings, or which are directly or indirectly applied to other related technical fields, are intended to be included within the scope of the present application.
Claims (10)
1. A method of anti-oxidation of a biomaterial, comprising:
under the preset condition, carrying out anti-oxidation treatment on the biological material by using a reducing agent, and storing the biological material subjected to the anti-oxidation treatment in a dry state.
2. The method of claim 1, wherein the reducing agent comprises one or more of sodium borohydride, sodium cyanoborohydride, and/or sodium triacetoxyborohydride.
3. The method of claim 1, wherein the anti-oxidant treatment of the biological material with a reducing agent comprises:
the reducing agent is diluted with a buffer to obtain a reducing solution, and the biological material is soaked with the reducing solution.
4. The method of claim 3, wherein the anti-oxidant treatment of the biological material with a reducing agent further comprises:
and (3) oscillating, ultrasonically or stirring the reduction solution soaked with the biological material.
5. The method of claim 3, wherein the concentration of the reducing agent in the reducing solution is 0.01% to 10%.
6. The method according to claim 3, wherein the preset conditions include a soaking time and a treatment temperature for the reducing solution to soak the biological material; wherein the soaking time is 0.5-48 hours, and the treatment temperature is 4-58 ℃.
7. The method of claim 3, wherein the buffer comprises phosphate buffered saline, 2 morpholinoethanesulfonic acid, 4-hydroxyethylpiperazine ethanesulfonic acid, carbonate buffered saline, absolute ethanol, normal saline, or an ethanol/normal saline mixed solution.
8. The method of claim 1, wherein the preserving the biological material in a dry form after the antioxidant treatment comprises:
freeze-drying, glycerating and dehydrating the biological material subjected to the antioxidant treatment and/or performing gradient dehydration on ethanol, and then storing the biological material in a dry state.
9. The method of claim 1, wherein the biological material comprises porcine aortic valve, porcine/bovine pericardium, bovine muscle/achilles tendon, porcine bladder, porcine/bovine dermal matrix, porcine small intestine submucosa matrix, porcine/bovine peritoneum, blood vessels, xenogenic or xenogenic bone, porcine eye cornea, or tympanic membrane.
10. A biomaterial, characterized in that it has been subjected to an anti-oxidant treatment according to the method of any one of claims 1-9.
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