阅读说明：本技术 复合材料及其制备方法和用途 (Composite material, preparation method and application thereof ) 是由 杨佼佼 李继遥 侯嫒琳 何利邦 梁坤能 于 2020-07-07 设计创作，主要内容包括：本发明提供了一种复合材料及其制备方法和用途,复合材料包括：内核,包含玉米蛋白和单宁酸的复合物；和外壳,包含分别接枝到玉米蛋白和单宁酸的复合物上的亲水聚氨基酸和疏水聚氨基酸,亲水聚氨基酸含有亲水链段,疏水聚氨基酸含有疏水链段。本发明能够与脱矿牙本质和脱矿牙釉质有很好的结合,并促进牙体硬组织再矿化。(The invention provides a composite material and a preparation method and application thereof, wherein the composite material comprises the following components in parts by weight: an inner core comprising a complex of zein and tannic acid; and a shell comprising a hydrophilic polyamino acid and a hydrophobic polyamino acid grafted to a complex of zein and tannic acid, respectively, the hydrophilic polyamino acid comprising a hydrophilic segment and the hydrophobic polyamino acid comprising a hydrophobic segment. The invention can be well combined with demineralized dentin and demineralized enamel and promote the remineralization of hard tissues of teeth.)

1. A composite material, comprising:

an inner core comprising a complex of zein and tannic acid; and

a shell comprising a hydrophilic polyamino acid and a hydrophobic polyamino acid grafted to said complex of zein and tannic acid, respectively, said hydrophilic polyamino acid comprising a hydrophilic segment and said hydrophobic polyamino acid comprising a hydrophobic segment.

2. The composite material according to claim 1, characterized in that the hydrophilic segment and the hydrophobic segment contain a carboxyl group and/or a phosphate group.

3. The composite material of claim 2, wherein the hydrophilic segment is polyglutamic acid, polyaspartic acid, polyacrylic acid, and the hydrophobic segment is polyalanine, polylactic acid.

4. The composite material of claim 2, wherein the complex of zein and tannic acid is a nanoparticle.

5. The composite material as claimed in claim 1, wherein the complex of zein and tannic acid is loaded with a drug, and the hydrophilic segment of the hydrophilic polyamino acid is introduced with a functional group, wherein the functional group is galactose or glucose.

6. Use of a composite material according to any one of claims 1 to 5 as a dental hard tissue repair material.

7. A method of making a composite material, the method comprising:

obtaining a polyamino acid solution comprising a hydrophilic polyamino acid comprising a hydrophilic segment and a hydrophobic polyamino acid comprising a hydrophobic segment;

obtaining a compound of zein and tannic acid;

grafting the hydrophilic polyamino acid and the hydrophobic polyamino acid to the complex of zein and tannic acid to form a composite material.

8. The method of claim 7, wherein the step of obtaining the complex of zein and tannin comprises:

dissolving zein in a first mixed solvent to obtain a first solution, wherein the first mixed solvent comprises water and liquid alcohol;

adding tannic acid into the first solution, adjusting the pH to 3-10, and stirring to obtain a second solution;

quickly adding the second solution into stirred water, and stirring to obtain a ZP solution;

the step of obtaining the solution of the polyamino acid comprises:

dissolving polyaspartic acid and polyalanine in a second mixed solvent, and fully stirring to obtain the polyamino acid solution, wherein the second mixed solvent comprises water and liquid alcohol;

the grafting step comprises:

and adding the ZP solution into the polyamino acid solution, fully stirring, and freeze-drying to obtain the composite material.

9. The method of preparing a composite material according to claim 7, further comprising:

loading a drug into the complex of zein and tannic acid;

introducing different functional groups into the hydrophilic chain segment of the polyamino acid of the composite material, wherein the functional groups are galactose or glucose.

10. Use of a composite material according to any one of claims 1 to 5 for the manufacture of a dental restoration for restoring a tooth, comprising:

placing the composite material in an oral cavity;

the composite material adheres to the hard dental tissue and induces the deposition of calcium and phosphorus ions in saliva to form a dental restoration.

Technical Field

The invention belongs to the technical field of materials, and particularly relates to a composite material for repairing hard tissues of a tooth body, a preparation method of the composite material and application of the composite material.

Background

Oral health is one of the important indicators for measuring the physical and mental health of residents, and the hard dental tissue in the oral tissue is the hardest part of the human body and is characterized by high mineralization, low organic matrix content and lack/few content of differentiable active cells, so that the damaged mature hard dental tissue is difficult to self-repair. However, it is very common that hard dental tissue is damaged due to mechanical wear, bacteria or acidic drinks. Taking children's caries as an example, the fourth national oral epidemiological survey published in 2018 shows that: the caries rate of 5-year-old children and the permanent caries rate of 12-year-old children are respectively 70.9% and 34.5%, which are respectively 5.8% and 7.8% higher than that before ten years, while only 4.1% and 16.5% of caries are effectively treated in the 5-year-old group and the 12-year-old group. Therefore, the method has important social significance and wide application prospect by exploring a convenient and efficient dental hard tissue repair material.

The design of the dental hard tissue restoration material requires consideration of the physical environment, chemical environment and microbial environment in the oral cavity at the same time. The physical environment mainly refers to that the hard tissues of the teeth are rubbed and pressed by chewing for a long time, and the hard tissues of the teeth are washed and soaked by saliva and are impacted by external force occasionally; the chemical environment mainly refers to the pH change of the oral environment, the internal current influence after the material is implanted and the like caused by eating, oral diseases and other factors; the microbial environment mainly means that when certain factors (such as long-term use of antibiotics) in the environment interfere balance between organisms and normal bacterial colonies, inherent ecological community imbalance can be caused, and then the bacterial colonies are provided with opportunities for harming the organisms, and meanwhile, the oral cavity is used as a semi-open environment, and the risk of invasion of external pathogenic bacteria cannot be ignored. These all place special requirements on the oral biomaterial such as high mechanical properties, chemical inertness, biological stability, etc. Meanwhile, although different types of artificial repair materials including resins, metals, ceramics and composite materials have been widely used in clinical applications, these materials are easily eroded by oral bacteria and are difficult to match the properties of the surrounding native hard dental tissue, so that the existing treatment methods have problems of low patient adaptability, poor treatment persistence, secondary caries and the like to some extent.

Disclosure of Invention

The exemplary embodiments provide a composite material that can be well combined with demineralized dentin and demineralized enamel and promote remineralization of dental hard tissues.

One aspect of the present invention provides a composite material comprising: an inner core comprising a complex of zein and tannic acid; and a shell comprising a hydrophilic polyamino acid and a hydrophobic polyamino acid grafted to a complex of zein and tannic acid, respectively, the hydrophilic polyamino acid comprising a hydrophilic segment and the hydrophobic polyamino acid comprising a hydrophobic segment.

Alternatively, the hydrophilic and hydrophobic segments may contain carboxyl groups and/or phosphate groups.

Alternatively, the hydrophilic segment may be polyglutamic acid, polyaspartic acid, polyacrylic acid, and the hydrophobic segment may be polyalanine, polylactic acid.

Alternatively, the complex of zein and tannic acid may be a nanoparticle.

Alternatively, a complex of zein and tannic acid can be loaded with a drug, and a functional group can be introduced on a hydrophilic segment of the hydrophilic polyamino acid, wherein the functional group can be galactose or glucose.

Another aspect of the present invention provides the use of a composite material as described above as a dental hard tissue repair material.

In another aspect, the present invention provides a method for preparing a composite material, the method comprising: obtaining a polyamino acid solution, wherein the polyamino acid solution comprises a hydrophilic polyamino acid and a hydrophobic polyamino acid, the hydrophilic polyamino acid comprises a hydrophilic chain segment, and the hydrophobic polyamino acid comprises a hydrophobic chain segment; obtaining a compound of zein and tannic acid; grafting a hydrophilic polyamino acid and a hydrophobic polyamino acid to a complex of zein and tannic acid to form a composite material.

Alternatively, the step of obtaining a complex of zein and tannic acid may comprise: dissolving zein in a first mixed solvent to obtain a first solution, wherein the first mixed solvent comprises water and liquid alcohol; adding tannic acid into the first solution, adjusting the pH to 3-10, and stirring to obtain a second solution; and quickly adding the second solution into the stirred water, and stirring to obtain the ZP solution.

Alternatively, the step of obtaining the solution of the polyamino acid may comprise: dissolving polyaspartic acid and polyalanine in a second mixed solvent, and stirring to obtain polyamino acid solution, wherein the second mixed solvent comprises water and liquid alcohol.

Alternatively, the grafting step may comprise: and adding the ZP solution into a polyamino acid solution, fully stirring, and freeze-drying to obtain the composite material.

Optionally, the method may further comprise: loading a drug into a complex of zein and tannic acid; different functional groups are introduced into the hydrophilic chain segment of the polyamino acid of the composite material, and the functional groups can be galactose or glucose.

A further aspect of the invention provides the use of a composite material as described above for the manufacture of a dental restoration for restoring a tooth, comprising: placing the composite material in the oral cavity; the composite material adheres to the hard dental tissue and induces the deposition of calcium and phosphorus ions in the saliva to form a dental restoration.

Compared with the prior art, the composite material prepared by the invention can perform electrostatic adsorption, hydrophobic aggregation and self-adaptive adhesion on the hard tooth tissue, and realizes strong interface interaction, antibiosis and high-efficiency induction of damaged hard tooth tissue regeneration on the hard tooth tissue.

Drawings

The accompanying drawings, which are included to provide a further understanding of the inventive concepts, are incorporated in and constitute a part of this specification, illustrate exemplary embodiments of the inventive concepts and together with the description serve to explain the principles of the inventive concepts.

FIG. 1 is a schematic representation of light weight streptococci adsorbing to the hard tissue surface of the tooth and inducing calculus formation.

FIG. 2 is a schematic representation of the Streptococcus mitis of FIG. 1.

Fig. 3 is a schematic diagram illustrating a composite material according to an exemplary embodiment of the invention.

Reference numerals:

1-inner core, 2-hydrophilic long pilus, 3-hydrophobic short pilus, 4-toxin, 100-compound of zein and tannin, 200-hydrophilic polyamino acid and 300-hydrophobic polyamino acid.

Detailed Description

The ideal dental hard tissue repair material faces a key scientific problem: how to realize the effective interface interaction between the material and the original hard tooth tissue in the complex environment of the oral cavity, especially the bacterial environment, and finally reconstruct and maintain the hard tooth tissue structure for a long time.

The formation of hard tooth tissue is a biomineralization process, which is regulated by organic components in the body. These organic components mainly include two parts of hydrophobic macromolecules and acidic macromolecules. Hydrophobic macromolecules such as collagen molecules form a hydrophobic matrix through self-assembly and the like so as to serve as a mineralized basic structure frame, acidic macromolecules immobilized on the hydrophobic matrix attract mineral ions in a solution to gather to an organic matrix, and finally mineral crystal nucleation and growth are induced by means of structure, charge, stereochemical matching and the like of the organic matrix. For example, dentin matrix phosphoprotein 1 attracts calcium ions through protein acidic residues, the beta sheet configuration induces directional growth of hydroxyapatite; the micron-sized band-shaped body assembled by the tooth amelogenin can control the nucleation and growth of hydroxyapatite crystals through space limitation. Biomineralization forms biominerals which are always in dynamic equilibrium of dissolution and recrystallization in normal environment, namely dynamic equilibrium of demineralization and remineralization. This new tissue formed by remineralization is identical in composition, structure and properties to the native mineral tissue. Therefore, promoting remineralization of dental hard tissues becomes a viable approach to repair damaged dental hard tissues.

The traditional means for promoting remineralization of tooth hard tissues is to add calcium, phosphorus and fluorine sources to the surface of damaged tooth hard tissues, and then high concentrations of calcium, phosphorus and fluorine can form fluorapatite to be deposited on the surface of the hard tissues so as to repair the damaged parts. However, the interface between the new tooth hard tissue and the original tooth hard tissue obtained by the method cannot be completely matched, the crystal structure is different, and the long-acting property cannot be maintained in the subsequent oral bacterial environment.

According to the invention, a new material is designed, strong interface binding force is provided by a bionic means, the lasting antibacterial capability is realized, and the effect of rapidly promoting the remineralization of the damaged part of the hard tissue of the tooth is achieved.

Dental calculus is a mineralized dental plaque biofilm which is characterized by fast formation, firm adhesion and long retention time, and the main component of the dental calculus is hydroxyapatite. The research on the formation process of dental calculus finds that: unlike the inability to self-repair after damage to the hard tissues of the tooth, dental calculus can be generated within 12 to 15 hours; the dental calculus has high adhesion with the hard tissues of the tooth body and cannot be even removed by washing or a toothbrush; without the use of special means such as tooth cleaning, calculus can persist on the hard tissue surface of the tooth for a long period of time. Although the mechanism of calculus formation is not clear, bacteria have been recognized to play an important role therein. There are research surfaces, bacteria (including streptococcus mitis, streptococcus mutans, streptococcus sanguis, streptococcus salivarius, etc.) first adhere to saliva-acquired membranes naturally generated on the surface of the tooth body through the actions of electric charge, polarity, stereo effect, etc., or directly adhere to the surface of the tooth body to form dental plaque; subsequently, the dental plaque guides the hydroxyapatite to rapidly form and grow to form a mineralized biological film, namely dental calculus; during this process, the bacteria release toxins that further disrupt the tooth structure.

In the research on bacteria related to dental calculus, the combination of the bacteria and the dental surface is the key for forming dental calculus, and Streptococcus mitis (Streptococcus mitis) has high interface combination force with hard tissues of the dental body. As shown in FIG. 2, the structure of light-weight streptococci was dissected, with dimensions of 600 to 800 nm, consisting of a spherical or ellipsoidal core 1 and pili of varying length. The hydrophilic long pilus 2 is generally longer than 150 nanometers and is rich in functional groups such as rhamnose, glucose, galactose, N-acetylglucosamine, N-acetylgalactosamine and the like; the length of the hydrophobic short pilus 3 is generally 50-80 nanometers, and the hydrophobic short pilus is rich in a large amount of hydrophobic connexin proteins; and the inner core 1 is a support structure by a cell wall, a cell membrane, etc. Exploring the adsorption of Streptococcus mitis to the hard tissues of the tooth, although the process is not fully understood, can be simplified to three steps. The research considers that: initially, calcium (Ca) in saliva²⁺) The sugar functional group on the long fungus hair and the carboxyl (-COO-) or the sulfonic (-SO) on the saliva acquired membrane are connected through the calcium bridge function₃ ^2-) Or the sugar functional group of the long pilus is directly combined with calcium of the hard tissue of the tooth body, thereby attracting bacteria to be close to the hard tissue of the tooth bodyThen, the short pili strongly bind to the hard tissue of the tooth body by virtue of their hydrophobic nature, excluding moisture between the tooth body and the bacteria, fig. 1(a) and (b) show that the pili bind to the tooth body; finally, the bacteria, by virtue of their own softness, adhere adaptively to the hard tissues of the tooth, and fig. 1(c) shows that the pili adhere to the tooth. Then, the streptococcus mitis forms dental plaque together with other related bacteria, and the dental plaque achieves biomineralization by utilizing self chemical groups and structural characteristics, and calcium and phosphorus ions in saliva are induced to deposit to form dental calculus, and fig. 1(d) shows that dental plaque biomineralization forms dental calculus. During this process the bacteria continuously release toxins, eventually forming a hard bacteria-hydroxyapatite complex (as shown in figure 1).

In order to solve the problems that the strong interface bonding force of the existing repair material and the original hard tooth tissue is difficult to maintain in a complex oral environment, the remineralization capacity of the hard tooth tissue is poor, the long-acting stability is poor and the like, an applicant carefully analyzes the molecular mechanism of strong adsorption of the light streptococcus to the surface of the hard tooth tissue, takes the light streptococcus as a blue book and designs a material with a similar structure to the light streptococcus.

In molecular design, the structure of the bacteria is simplified into a bacterial surface layer formed by stretching hydrophilic long pili, a bacterial middle layer formed by gathering hydrophobic short pili and a bacterial core formed by supporting cell walls and cell membranes.

Finally, based on the compound of zein and tannic acid with good biocompatibility and polyamino acid, a series of 'artificial bacteria' capable of being specifically adsorbed to the surface of the hard dental tissue are synthesized, wherein the compound of zein and tannic acid with different sizes is used as a core, polyaspartic acid and polypropylenic acid with different chain lengths and different chain numbers are used as shells, and the artificial bacteria are finally applied to in-situ repair of the hard dental tissue.

Fig. 3 is a schematic diagram illustrating the synthesis of a composite material with similar light streptococcus functional groups and structures according to an exemplary embodiment of the invention. Referring to fig. 3, a composite material according to an exemplary embodiment of the present invention includes: an inner core comprising a complex of zein and tannic acid 100; a shell comprising a hydrophilic polyamino acid 200 and a hydrophobic polyamino acid 300 grafted onto a complex 1 of zein and tannic acid, respectively, the hydrophobic polyamino acid comprising a hydrophobic segment and the hydrophilic polyamino acid comprising a hydrophilic segment.

The polyamino acid (Poly (alpha-amino acid), P alpha AA) is an ordered chain polypeptide formed by directly polymerizing alpha-amino acid. Besides the advantages of polypeptide (the polypeptide is a short chain formed by amino acids and amido bonds, and has the same skeleton structure and side chain groups as natural protein, in addition, the polypeptide has wide provenance, good biocompatibility and biodegradability, so the polypeptide is an excellent natural protein simulant), the polyamino acid is simple to synthesize, controllable in structure, low in cost and wide in application prospect. The hydrophilicity and the hydrophobicity of the polyamino acid can be adjusted by selecting amino acid monomers with different hydrophilicity/hydrophobicity; the polyamino acid with different side chain groups can be obtained by selecting amino acid monomers with different side chain chemical structures or modifying the side chain of the polyamino acid by a chemical method. Meanwhile, the chain length of the polyamino acid can also be adjusted by methods such as a feeding ratio, temperature, a solvent and the like. Therefore, specific polyamino acid structures (such as polyaspartic acid and polyalanine) can be used as a simulant of a natural organic matrix to attract mineral ions to be enriched, and biomimetic mineralization is realized. From this, it is known that polyamino acids can act as a mimic of bacterial pili.

The compound of zein and tannic acid is zein/tannic acid nano particles, can guide biomimetic mineralization or serve as a carrier of a medicament, serve as nucleation sites and templates of biomimetic mineralization and serve as a source of medicament release. Thus, the complex of zein and tannic acid is a suitable mimic of the bacterial core.

Based on the structural and functional characteristics of the streptococcus mitis, the applicant firstly proposes a new design concept of the dental hard tissue repair material: the generation process of dental calculus is reproduced by simulating the structure of 'inner core-hydrophobic short pilus-hydrophilic long pilus' of light streptococcus through materials, so that the rapid and efficient dental hard tissue repair is realized.

According to an exemplary embodiment of the present invention, the polyamino acid includes a hydrophilic polyamino acid and a hydrophobic polyamino acid. The hydrophilic polyamino acid contains a hydrophilic segment and the hydrophobic polyamino acid contains a hydrophobic segment. The hydrophilic segment contains a carboxyl group and/or a phosphate group. The carboxyl and phosphate radicals are used for guiding the calcium and phosphorus ions to deposit and remineralize, and simultaneously form electrostatic interaction with calcium so as to enhance adsorption. The hydrophilic chain segment can be polyglutamic acid, polyaspartic acid and polyacrylic acid. The hydrophobic segment contains carboxyl or/and phosphate, and the hydrophobic segment can be poly-alanine or polylactic acid.

As an alternative embodiment, in order to adapt to the bacterial environment of the oral cavity, by taking the idea that the bacteria release toxin and the zein/tannin nanoparticles can be used as drug carriers, the zein/tannin nanoparticles can be loaded with drugs (such as triclosan antibacterial drugs and the like) to realize the long-acting release of the drugs, so that the in-situ adsorption/repair/antibacterial effect of the materials on the hard tissues of the tooth body is continuously optimized.

As an alternative embodiment, various functional groups, such as galactose, glucose, etc., are introduced into the hydrophilic segment of the hydrophilic polyamino acid for different application requirements.

According to another aspect of the present invention, there is provided a method for preparing the above composite material, comprising:

(1) obtaining a complex of zein and tannic acid.

Dissolving zein in the first mixed solvent, stirring for 10 min-10 h to fully dissolve the zein in the first mixed solvent, and then standing at 0-25 ℃ for 6-20 h to obtain a first solution. The compound is placed at 0-25 ℃ for a period of time so as to preserve and fully stretch the structure of the compound, preferably, the compound is placed at 2-10 ℃ for 10-15 hours, and further preferably, the compound is placed at 3-6 ℃ for 11-13 hours. The first mixed solvent comprises 10: 90-90: 10 water and ethanol. The present invention is not limited thereto, and the first mixed solvent may also be a mixed solvent of water and a liquid alcohol such as methanol, propanol, butanol, pentanol, hexanol, etc. The ratio of water to ethanol is within the above range so that water and ethanol are sufficiently dissolved. Preferably, the second mixed solvent includes a solvent having a volume ratio of 30: 10-70: 50 parts of water and ethanol. Further preferably, the second mixed solvent includes a solvent having a volume ratio of 70: 10-70: 40 of water and ethanol.

Adding tannic acid into the first solution, adjusting the pH value to 3-10, and stirring at 20-70 ℃ for 5 min-5 h to obtain a second solution. Adjusting the pH to the above range can facilitate dissolution of tannic acid and subsequent material preparation, preferably adjusting the pH to 5-8, further preferably adjusting the pH to 6-7. Stirring for 5 min-5 h at 20-70 ℃ to realize full dissolution and uniformity of the first solution and the tannic acid. Preferably, the mixture is stirred for 30min to 2h at the temperature of 40 to 55 ℃.

And then, quickly adding the second solution into the stirred water, and stirring for 20 s-2 h to obtain a ZP (Zein particles) solution. Wherein the stirring speed (rotating speed) of the stirred water can be 100-5000 rpm, the stirring time is controlled to be 20 s-2 h, and uniform nano particles can be obtained. Preferably, the stirring speed of the stirred water can be 500-3000 rpm, and the stirring time is controlled to be 5 min-1 h. More preferably, the stirring speed of the stirred water can be 800-1500 rpm, and the stirring time is controlled to be 10-30 min.

(2) Obtaining a polyamino acid solution, the polyamino acid solution comprising a hydrophilic polyamino acid and a hydrophobic polyamino acid, the hydrophilic polyamino acid comprising a hydrophilic segment and the hydrophobic polyamino acid comprising a hydrophobic segment. The method specifically comprises the following steps:

and (3) dissolving the polyaspartic acid and the polyalanine in the second mixed solvent, and fully stirring to obtain the polyamino acid solution. Wherein the second mixed solvent comprises 10: 90-90: 10 water and ethanol. However, the present invention is not limited thereto, and the second mixed solvent may be a mixed solvent of water and a liquid alcohol such as methanol, propanol, butanol, pentanol, hexanol, and the like, similar to the first mixed solvent. The ratio of water and liquid alcohol in the above range allows water and liquid alcohol to be sufficiently dissolved. Preferably, the second mixed solvent includes a solvent having a volume ratio of 30: 10-70: 50 parts of water and ethanol. Further preferably, the second mixed solvent includes a solvent having a volume ratio of 70: 10-70: 40 of water and ethanol.

(3) Hydrophilic polyamino acid and hydrophobic polyamino acid are grafted to a complex of zein and tannic acid to form a composite material with a core-shell structure. Specifically, the method comprises the following steps:

and adding the ZP solution into the polyamino acid solution, fully stirring and freeze-drying to obtain a bacterial structure simulant, namely the polyaspartic acid long chain and polyalanine short chain grafted corn protein/tannin nano particle composite material.

As an alternative embodiment, an antibacterial drug can be loaded in the zein/tannin nano particles to realize long-acting release of the drug, so as to continuously optimize the in-situ adsorption/repair/antibacterial effect of the material on the hard tissues of the tooth body. Preferably, after the hydrophilic polyamino acid and the hydrophobic polyamino acid are grafted to the zein/tannin nanoparticles, the antibacterial drug is loaded in the zein/tannin nanoparticles. If the graft step is preceded by loading and then bonding to the composite, there is leakage of the drug during the bonding process.

The procedure for loading "artificial bacteria" with drugs (triclosan for example) is as follows: the method comprises the steps of dissolving accurately weighed triclosan in water, dropwise adding the solution into the water dispersed with 'artificial bacteria' to vibrate for 24 hours, centrifuging, taking the lower-layer solid, performing vacuum drying to obtain the 'artificial bacteria' carrying the medicine, taking the upper-layer liquid, measuring the concentration of the triclosan by using ultraviolet rays, calculating the amount of the loaded medicine, and further calculating the medicine carrying amount. The drug loading calculation method comprises the following steps:

as an alternative embodiment, to further simulate the high adsorption capacity of the hydrophilic long pili of bacteria to the hard tissues of the tooth body, different bacterial functional groups, such as galactose, glucose, etc., can be introduced into the obtained polyamino acid hydrophilic segment of the material. Taking galactose as an example, under an ice salt bath, 1 equivalent of carboxyl (from the composite material obtained in the step (3)) is firstly dispersed in THF, then 1.2 times of equivalent of EDCl, HOBt and a certain equivalent of amino (galactose) are sequentially added, and after the reaction at normal temperature overnight, the product is obtained through water washing, centrifugation and drying.

In a preferred exemplary embodiment, the method of making the composite material of the present invention comprises the steps of:

1) preparing zein/tannin nano particles with a bacterial nucleus structure.

(1) Zein is dissolved in a solvent with a volume ratio of 70:30 of ethanol/water mixed solvent, stirring for 2 hours, and standing overnight at 4 ℃; (2) adding a certain amount of tannic acid into the solution, adjusting the pH to 7, and stirring at 55 ℃ for 1 h; (3) and (3) quickly adding the solution obtained in the step (2) into water which is stirred (the stirring speed is 1000rpm), and stirring for 20min to obtain the ZP solution.

2) Preparing a bacterial structure simulator-a composite material of polyaspartic acid long chain and polyalanine short chain grafted zein/tannin.

(1) Dissolving polyaspartic acid and polyalanine in an ethanol/water mixed solvent with a volume ratio of 70:30, and fully stirring a polyamino acid solution to obtain the polyaspartic acid-polyalanine compound; (2) adding the polyamino acid solution into the ZP solution obtained in the step (3) of the step 1), fully stirring, and freeze-drying to obtain the bacterial structure simulant.

According to a further aspect of the invention, the use of the above-mentioned composite material for the manufacture of a dental restoration for restoring a tooth comprises: placing the composite material in the oral cavity; the composite material adheres to the hard dental tissue and induces the deposition of calcium and phosphorus ions in the saliva to form a dental restoration. The composite material can be well combined with demineralized dentin and demineralized enamel, and can promote the remineralization of hard tissues of teeth by utilizing the biomimetic mineralization capability of the composite material.

According to the invention, inspired by the function of a dental plaque biomembrane in the dental calculus generation process, by analyzing the structural characteristics of oral bacteria with strong binding force with the tooth surface, the artificial bacteria, namely the composite material of zein/tannin nano particles grafted short-chain polyalanine/polyaspartic acid, is designed, and the structure of nano inner core/hydrophobic short pilus/hydrophilic long pilus of the bacteria is simulated, so that the strong adsorption and biomineralization of the tooth surface/saliva acquired membrane under water are realized. The composite material can perform electrostatic adsorption, hydrophobic aggregation and self-adaptive adhesion on the hard tooth tissue, and realizes strong interface interaction, antibiosis and high-efficiency induction of damaged hard tooth tissue regeneration on the hard tooth tissue. Meanwhile, harmful substances are released into medicines, so that the antibacterial effect is achieved, and the long-acting stability of the new tissues of the tooth body is realized.

Although certain exemplary embodiments and implementations have been described herein, other embodiments and modifications will be apparent from the description. The inventive concept is therefore not limited to the exemplary embodiments, but is to be defined by the appended claims along with their full scope of equivalents.