CN110117348B

CN110117348B - Polyurethane material, preparation method and application thereof, polymer material and 3D (three-dimensional) stent

Info

Publication number: CN110117348B
Application number: CN201910343734.2A
Authority: CN
Inventors: 阮长顺; 胡成深; 刘娟
Original assignee: Shenzhen Institute of Advanced Technology of CAS
Current assignee: Shenzhen Institute of Advanced Technology of CAS
Priority date: 2019-04-26
Filing date: 2019-04-26
Publication date: 2021-02-19
Anticipated expiration: 2039-04-26
Also published as: CN110117348A; WO2020215800A1

Abstract

The invention discloses a polyurethane material, a preparation method and application thereof, a polymer material and a 3D bracket, and relates to the technical field of new materials. The polyurethane material is mainly obtained by chain extension of a prepolymer A through a chain extender, wherein the chain extender comprises a carbon material with hydroxyl on the surface or an analogue thereof; the structural general formula of the prepolymer A is shown in formula 1, wherein X is- (CH)₂CH₂) -or

Y is optionally substituted C1-C12 alkyl, optionally substituted C1-C12 cycloalkyl, optionally substituted C6-C12 aromatic, optionally substituted C6-C12 heterocyclic, or optionally substituted C6-C12 heteroaryl; m, n represent respective degrees of polymerization; the number average molecular weight of prepolymer A was 250-. According to the invention, the carbon material is prepared into the amphiphilic polyurethane, so that the material modification and enhancement can be carried out on various organic/inorganic material processing systems, and the mechanical property and biocompatibility of the material can be remarkably improved.

Description

Polyurethane material, preparation method and application thereof, polymer material and 3D (three-dimensional) stent

Technical Field

The invention relates to the technical field of new materials, and particularly relates to a polyurethane material, a preparation method and application thereof, a polymer material and a 3D (three-dimensional) bracket.

Background

With the introduction of the concept of additive manufacturing, the three-dimensional printing technology has been rapidly developed in recent years, and has shown a good application prospect in the biomedical field, and can customize and customize complicated tissues and organs individually and produce in batch in a programmed and controllable manner. At present, the precision of three-dimensional printing equipment on the market generally reaches 100 microns, and even the tissue engineering material can be accurately and programmatically prepared in the field of artificial blood vessels. However, finding a bio-ink suitable for clinical applications is relatively difficult because of the need to maintain biocompatibility while maintaining good and suitable mechanical properties and the need to be able to introduce the relevant bioactive substances, whereas traditional materials of chemical synthesis have difficulty in fully satisfying the above characteristics.

At present, aiming at the development of biological ink in the field of tissue engineering, the original materials are usually chemically modified or doped with inorganic-organic active materials, but the existing materials can only improve certain performances such as mechanics, biological or cell adhesion and proliferation in a targeted manner, and the application of the materials in a wider range is limited.

Some bio-ink and biomedical materials containing graphene have appeared, and graphene is added to biological materials as a doping material, but due to the aggregation property of graphene nanoparticles, graphene nanoparticles are not easily dispersed in most solvents and exhibit the characteristic of easy aggregation, so the introduction of graphene of biomedical materials generally relies on chemical modification to improve the dispersibility and biocompatibility of graphene. However, the simple surface modification can only help the graphene to disperse into the matrix material, and the performance improvement of the matrix material is very limited. In addition, for each processing system of a base material, only the surface modification of graphene can be performed in a targeted manner, so that the graphene can be dispersed in the processing system, and the reports on the dispersible graphene oxide applicable to various processing systems are rare. And the chemical modification process cannot avoid complicated reaction steps and various surface modification processes, and cannot avoid the use of toxic reagents, so that the time, the procedure and the safety cost are increased while introducing the graphene.

At present, no modified graphene additive which can be suitable for various processing systems exists, the special performance is endowed to the material while the graphene reinforced material can be uniformly introduced, and the material is convenient to process and form with a base material.

It would therefore be desirable to provide a material enhancer that addresses at least one of the above problems.

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

Disclosure of Invention

One of the purposes of the invention is to provide a polyurethane material which has amphipathy, can be stably dispersed in various common organic/inorganic polymer material processing systems, and can remarkably increase the mechanical property and biocompatibility of the material.

The second purpose of the invention is to provide a preparation method of polyurethane material, which is prepared by pre-polymerizing polyethylene glycol or polypropylene glycol and diisocyanate and then performing chain extension on carbon material with hydroxyl on the surface or the like, and the reaction process is short.

The invention also aims to provide application of the polyurethane material or the polyurethane material prepared by the preparation method of the polyurethane material as a material reinforcing agent in processing and molding of organic and/or inorganic polymer materials.

The fourth purpose of the invention is to provide a polymer material, which comprises a base material and the polyurethane material or the polyurethane material prepared by the preparation method of the polyurethane material.

The fifth purpose of the invention is to provide a 3D scaffold which is mainly prepared from the polymer material.

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

in a first aspect, a polyurethane material is provided, wherein the polyurethane material is mainly obtained by chain extension of a prepolymer A through a chain extender, and the chain extender comprises a carbon material with hydroxyl on the surface or the like;

the structural general formula of the prepolymer A is as follows:

wherein X is- (CH)₂CH₂) -or

Y is optionally substituted C1-C12 alkyl, optionally substituted C1-C12 cycloalkyl, optionally substituted C6-C12 aromatic, optionally substituted C6-C12 heterocyclic, or optionally substituted C6-C12 heteroaryl;

m represents the polymerization degree of polyurethane, m is more than or equal to 1, and n is more than 1;

the number average molecular weight of the prepolymer A is 250-.

In a second aspect, a preparation method of the polyurethane material is provided, which comprises the following steps:

(a) providing prepolymer A: pre-polymerizing a reactant A and diisocyanate to obtain a prepolymer A, wherein the reactant A comprises polyethylene glycol or polypropylene glycol; the molar ratio of the reactant A to the diisocyanate is 1:1-1: 2;

(b) and adding a chain extender into the prepolymer A for chain extension, wherein the chain extender comprises a carbon material with hydroxyl on the surface or the like, so as to obtain the polyurethane material.

Preferably, on the basis of the technical scheme of the present invention, the diisocyanate includes one or more of aliphatic diisocyanate, aromatic diisocyanate and alicyclic diisocyanate, and preferably includes one or more of 1, 6-hexamethylene diisocyanate, lysine diisocyanate, isophorone diisocyanate, 4-dicyclohexylmethane diisocyanate, 4-diphenylmethane diisocyanate, toluene diisocyanate or xylylene diisocyanate.

Preferably, on the basis of the technical scheme of the present invention, the carbon material with hydroxyl on the surface or the analogue thereof includes a two-dimensional carbon material, a three-dimensional carbon material or black scales, preferably includes one or more of graphene, graphene oxide, reduced graphene oxide, carbon nanotubes, fullerene or black phosphorus, and further preferably is graphene oxide.

In a third aspect, the application of the polyurethane material or the polyurethane material prepared by the preparation method of the polyurethane material as a material reinforcing agent in processing and molding of organic and/or inorganic polymer materials is provided.

In a fourth aspect, a polymer material is provided, which comprises a base material and the polyurethane material or the polyurethane material prepared by the preparation method of the polyurethane material;

preferably, the matrix material is an organic and/or inorganic polymer material, preferably polylactic acid-glycolic acid copolymer or polyethylene glycol diacrylate;

preferably, the mass percentage of the polyurethane material in the matrix material is 2.5-7.5%.

In a fifth aspect, a 3D scaffold is provided, made primarily from the above-described polymeric material.

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

(1) the polyurethane material is mainly obtained by chain extension of a prepolymer A through a carbon material or an analogue thereof with hydroxyl on the surface, the prepolymer A has hydrophilic and hydrophobic chain segments and therefore has amphiphilicity, and the carbon material or the analogue thereof is used as a chain extender to connect a plurality of chain segments of the prepolymer A to prepare a high-molecular dispersible polyurethane system, so that the carbon material or the analogue thereof has the amphiphilicity of being stably dispersed in an organic/inorganic solvent and can be uniformly dispersed in a sol state. The polyurethane material can be uniformly dispersed in various polar and nonpolar solvents for at least 24 hours without coagulation, which shows that the polyurethane material can be applied to most polymer processing systems and has wide and universal application prospect.

(2) The polyurethane material can be directly used as an additive to be added into other polymer matrix materials for molding, does not relate to chemical reaction, and has the advantages of safety, energy conservation and convenient use. Without affecting the inherent, characteristic properties of the polymer matrix, as well as processability and formability. The material can be added into a base material to carry out industrial large-scale printing production, and has potential industrial application capability.

(3) After the matrix material added with the polyurethane material is molded, the mechanical property and biocompatibility of the material are obviously enhanced, and the material can have the specific properties of carbon material such as conductivity, adsorptivity, photo-thermal property, drug loading and releasing, shape memory and the like.

Drawings

FIG. 1 is a schematic diagram of a process for synthesizing a polyurethane material according to an embodiment of the present invention;

FIG. 2 is an infrared spectrum of the polyurethane obtained in examples 1 to 3 of the present invention and comparative example 1 (the left side is a full-wavelength infrared spectrum, and the right side is an enlarged spectrum of the wavelength of the section A in the left side);

FIG. 3 shows the preparation of polyurethanes obtained in example 1 according to the invention and in comparative example 1¹H NMR chart;

FIG. 4 is a graph showing the mechanical properties after molding of PEGDA and PLGA materials without and with different amounts of the polyurethane of example 1 (wherein (a) is a graph showing the change of compressive stress with strain after molding of PEGDA materials without and with different amounts of the polyurethane of example 1), (b) is a graph showing the change of compressive stress with strain after molding of PEGDA materials without and with different amounts of the polyurethane of example 1, (c) is a graph showing the change of elongation at break after molding of PEGDA materials without and with different amounts of the polyurethane of example 1, (d) is a graph showing the change of compressive stress with strain after molding of PLGA materials without and with different amounts of the polyurethane of example 1, (e) is a graph showing the change of tensile stress after molding of PLGA materials without and with different amounts of the polyurethane of example 1, (f) is a graph showing the change of elongation at break after molding of PLGA materials without and with different amounts of the polyurethane of example 1);

FIG. 5 is a plot of viscosity versus shear rate for PEGDA and PLGA materials without and with the polyurethane of example 1 (where (a) is a plot of viscosity versus shear rate for PEGDA and without and with the polyurethane of example 1, (b) is a plot of viscosity versus shear rate for PLGA material without and with the polyurethane of example 1);

fig. 6 is a graph showing results of biocompatibility tests of PLGA material and PEGDA material scaffolds without and with the addition of the polyurethane of example 1 (wherein (a) is a live-dead staining pattern after 7 days of osteoblast culture in the PLGA material scaffold without the addition of the polyurethane, (b) is a live-dead staining pattern after 7 days of osteoblast culture in the PLGA material scaffold with the addition of the polyurethane of example 1, (c) is a live-dead staining pattern after 7 days of osteoblast culture in the PEGDA material scaffold without the addition of the polyurethane, (d) is a live-dead staining pattern after 7 days of osteoblast culture in the PEGDA material scaffold with the addition of the polyurethane of example 1, (e) is a cell count result after 7 days of osteoblast culture in the PLGA material without the addition of the polyurethane of example 1 and in the PEGDA material scaffold);

FIG. 7 is a graph showing the temperature measurements of the PLGA material and PEGDA material stents after infrared irradiation without and with the polyurethane of example 1;

fig. 8 is a graph showing drug loading release performance of PLGA material and PEGDA material stents without and with the polyurethane of example 1 (wherein (a) is a graph showing drug loading release performance of PEGDA material stents without and with the polyurethane of example 1, and (b) is a graph showing drug loading release performance of PLGA material stents without and with the polyurethane of example 1).

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.

According to a first aspect of the present invention, there is provided a polyurethane material obtained by chain-extending a prepolymer a with a chain extender comprising a carbon material having hydroxyl groups on the surface or the like;

the structural general formula of the prepolymer A is as follows:

wherein X is- (CH)₂CH₂) -or

Y is optionally takenSubstituted C1-C12 alkyl, optionally substituted C1-C12 cycloalkyl, optionally substituted C6-C12 aromatic, optionally substituted C6-C12 heterocyclic, or optionally substituted C6-C12 heteroaryl; m represents the polymerization degree of polyurethane, m is more than or equal to 1, n>1; the number average molecular weight of prepolymer A was 250-.

Polyurethane (PU) is a multi-block polymer rich in urethane bonds (-NHCOO-) and composed of a soft segment with a lower softening temperature and a hard segment with a higher softening temperature. The molecular structure of the polyurethane material has good designability, and polyurethane materials with different properties can be designed and synthesized by selecting different soft segments and hard segments and different proportions of the soft segments and the hard segments, so that the polyurethane material has good processability.

The carbon material has good mechanical properties and other special properties, and is widely applied to polymer materials, for example, graphene is a two-dimensional sheet nano carbon material consisting of single-layer carbon atoms, and has great potential in the aspects of improving the mechanical, electrical and thermal properties of polymers. The uniformity and quality of graphene dispersed into a polymer body as a nano-additive is directly related to its effectiveness in improving performance. However, due to intermolecular interaction forces of graphene, the strong tendency of graphene stacking makes graphene very poorly dispersible in most organic/inorganic media. To ameliorate this problem, it is common practice to surface-modify graphene to reduce surface interactions so that it can be dispersed in a solvent. However, the simple surface modification can only help the graphene to disperse into the matrix material, the performance improvement of the matrix material is very limited, the method can only be used for enhancing a certain specific material or a processing system, complicated reaction steps and various surface modification processes cannot be avoided in the chemical modification process, the processing process is complicated, and the method is not suitable for wide application. At present, no modified graphene additive which can be suitable for various processing systems exists, the mechanical properties, the optical properties, the electrical properties and the biocompatibility of various base materials can be improved while graphene can be uniformly introduced, and the characteristics of the base materials are hardly influenced.

Therefore, it is necessary to design a carbon material-based reinforcing agent suitable for various organic/inorganic systems, which will greatly reduce the cost of personalized modification, and has potential application prospects in the fields of coating materials, building materials, industrial damping materials, photoelectric materials and biomedical materials due to the universality of application, and on the other hand, will enable many materials which originally have application limitations due to self-performance defects to find further application possibility after being modified by the addition of the reinforcing agent.

The polyurethane material of the present invention is obtained by chain-extending prepolymer a with a carbon material having hydroxyl groups on the surface or the like, and a plurality of segments of prepolymer a are connected with each other with a carbon material having hydroxyl groups on the surface or the like as a chain extender.

Prepolymer A

The structural general formula of the prepolymer A is as follows:

wherein X represents- (CH)₂CH₂) -or

Y represents an optionally substituted C1-C12 alkyl group, an optionally substituted C1-C12 cycloalkyl group, an optionally substituted C6-C12 aromatic group, an optionally substituted C6-C12 heterocyclic group or an optionally substituted C6-C12 heteroaryl group; m represents the polymerization degree of polyurethane, m is more than or equal to 1, n>1。

The source of the polymer A is not limited, and a typical source is obtained by polymerizing a polymeric diol (polyethylene glycol or polypropylene glycol) with a diisocyanate.

A typical reaction sequence is as follows:

wherein m represents the polymerization degree of polyurethane, and is more than or equal to 1, the minimum is 1 time, and the maximum is limited time; n >1, maximum finite number.

X is- (CH)₂CH₂) -or

I.e. polymeric glycols

Is polyethylene glycol

Or polypropylene glycol

Preferably, the polymeric glycol has a number average molecular weight of 200-.

Preferably, n ranges from 4 to 460, and n can be 4, 5, 6, 7, 8, 10, 12, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 110, 120, 130, 150, 160, 180, 200, 250, 300, 350, 400, 450, or 460.

Y is optionally substituted C1-C12 alkyl, optionally substituted C1-C12 cycloalkyl, optionally substituted C6-C12 aromatic, optionally substituted C6-C12 heterocyclic, or optionally substituted C6-C12 heteroaryl.

"optionally substituted" means substituted or unsubstituted, optionally substituted C1-C12 alkyl, i.e., C1-C12 alkyl or substituted C1-C12 alkyl, the substituents are not limited and may include halogen, amino, aminoalkyl, ester or acyl, and the like, as well as others.

In some embodiments, Y may be methylene, ethylene, propylene, isopropylene, butylene, pentylene, hexylene, heptylene, octylene, nonylene, naphthylene, decylene, 1, 2-cyclohexylene, 1, 3-cyclohexylene, 1, 4-cyclohexylene, phenyl, 1, 2-phenylene, 1, 3-phenylene, 1, 4-phenylene, tolyl, or xylyl, in some preferred embodiments, Y is C1-C12 alkyl or C6-C12 aromatic, for example Y may preferably be hexylene, phenyl, tolyl, or xylyl.

It is understood that the diisocyanate may include an aliphatic diisocyanate, an aromatic diisocyanate, or an ester ring diisocyanate. Exemplary aliphatic diisocyanates include, but are not limited to, 1, 6-hexamethylene diisocyanate, lysine diisocyanate, isophorone diisocyanate, or 4, 4-dicyclohexylmethane diisocyanate, and the like; exemplary aromatic diisocyanates include, but are not limited to, 4-diphenylmethane diisocyanate, toluene diisocyanate, or xylylene diisocyanate, and the like.

In some embodiments, exemplary prepolymer a structures are as follows:

that is, X is- (CH)₂CH₂) -Y is hexylene and m is 1; or the like, or, alternatively,

that is, X is- (CH)₂CH₂) Y is hexylene and m is 2.

Chain extender

The polyurethane material is a product obtained by chain extending prepolymer A with a chain extender.

The chain extender includes a carbon material having hydroxyl groups on the surface or the like. "carbon material having hydroxyl group on the surface or the like" means a carbon material having hydroxyl active group on the surface or the like, the hydroxyl active group being derived from a hydroxyl group or a carboxyl group; the carbon material having hydroxyl groups on the surface thereof includes two-dimensional or three-dimensional carbon materials, the two-dimensional carbon material is typically graphene (graphene also has hydroxyl groups on the surface thereof, but in a small amount), graphene oxide or reduced graphene oxide, the three-dimensional carbon material is typically carbon nanotube or fullerene, and the carbon material having hydroxyl groups on the surface thereof is typically black phosphorus. Preferably, an exemplary chain extender is graphene oxide, i.e., an exemplary polyurethane material is prepolymer a after graphene oxide chain extension.

In some embodiments, the polyurethane material has the general structural formula:

wherein the content of the first and second substances,

and the end-capping group is:

R₃either of (i) H, or,

x>1，n>1。

in some embodiments, exemplary polyurethane materials are structured as follows:

wherein the content of the first and second substances,

and the end-capping group is:

R₃either of (i) H, or,

x>1，n>1. that is, X is- (CH)₂CH₂) Y is hexylene.

At R₂In the long molecular chain of (A), there are several R₂-1 is an ordered repeating structure, R ₂2 is terminal (i.e. with R)₂-2 end-capping), wherein R₂-1 is:

R₂-2 is

The polyurethane material is mainly obtained by chain extension of a prepolymer A through a carbon material or an analogue thereof with hydroxyl on the surface, the prepolymer A has hydrophilic and hydrophobic chain segments and therefore has amphiphilicity, and the carbon material or the analogue thereof is used as a chain extender to connect a plurality of chain segments of the prepolymer A to prepare a high-molecular dispersible polyurethane system, so that the carbon material or the analogue thereof has the amphiphilicity of being stably dispersed in an organic/inorganic solvent and can be uniformly dispersed in a sol state. The polyurethane material can be uniformly dispersed in various polar and nonpolar solvents for at least 24 hours without coagulation, which shows that the polyurethane material can be applied to most polymer processing systems and has wide and universal application prospect.

The polyurethane material can be directly used as an additive to be added into other polymer matrix materials for molding, does not relate to chemical reaction, and has the advantages of safety, energy conservation and convenient use. Without affecting the inherent, characteristic properties of the polymer matrix, as well as processability and formability. The material can be added into a base material to carry out industrial large-scale printing production, and has potential industrial application capability.

After the matrix material added with the polyurethane material is molded, the mechanical property and the biocompatibility of the matrix material can be improved, the adhesion and proliferation of cells can be promoted to a certain extent, the polyurethane material has wide application prospect in the aspect of biomedical materials, and the material can be endowed with the special properties of carbon materials such as photo-thermal property, drug loading and release, conductivity, adsorptivity, shape memory and the like.

According to a second aspect of the present invention, there is provided a method for preparing the polyurethane material, comprising the steps of:

The descriptions of the diisocyanate and the carbon material having hydroxyl groups on the surface or the like can be referred to the corresponding descriptions in the first aspect of the present invention, and will not be described herein again.

The molar ratio of reactant a to diisocyanate is illustratively, for example, 1:1, 2:3, or 1: 2.

When the ratio is 1:1, m is large, when the ratio is 2:3, m is 2, and when the ratio is 1:2, m is 1.

The molar ratio is less than 1:1, the hydroxyl groups can not be further reacted, the molar ratio is more than 1:2, and part of diisocyanate does not participate in the reaction.

The invention firstly uses polyethylene glycol or polypropylene glycol as a soft segment and diisocyanate as a hard segment for prepolymerization to obtain a prepolymer A, then uses a carbon material with hydroxyl on the surface or the like as a chain extender for chain extension, and connects a plurality of prepolymerized chain segments through the carbon material or the like. The preparation method is simple, short in reaction flow, not harsh in conditions, low in cost, energy-saving and environment-friendly. The polyurethane material prepared by the method has the same advantages as the polyurethane material of the first aspect.

In some embodiments, in step (a), the prepolymerization temperature is in the range of 50 to 80 ℃, e.g., 50 ℃, 55 ℃, 60 ℃, 65 ℃, 70 ℃, 75 ℃ or 80 ℃, and the prepolymerization time is in the range of 1 to 4h, e.g., 1h, 2h, 3h or 4 h.

Preferably, a catalyst is added in the prepolymerization, the catalyst is stannous octoate, and the molar ratio of the stannous octoate to the reactant A is 0.001:1-0.01:1, such as 0.001:1, 0.002:1, 0.005:1, 0.008:1 or 0.01: 1.

By optimizing the prepolymerization reaction conditions and the polymerization degree, the polymer A obtains better amphipathy.

In some embodiments, in step (b), the chain extension reaction temperature is 35-55 ℃, e.g., 35 ℃, 40 ℃, 45 ℃, 50 ℃ or 55 ℃, and the chain extension reaction time is 8-24h, e.g., 8h, 9h, 10h, 11h, 12h, 14h, 16h, 18h, 20h, 22h or 24 h.

Preferably, the mass ratio of the carbon material having hydroxyl groups on the surface or the like to the reactant a is 0.1:100 to 1:100, for example, 0.1:100, 0.2:100, 0.5:100, 0.8:100, or 1: 100.

In some embodiments, a typical polyurethane material is prepared by selecting polyethylene glycol (PEG) (with a number average molecular weight of 200-. The synthesis process is shown in figure 1 and comprises the following steps:

(1) according to the PEG: carrying out prepolymerization on HDI (hexamethylene diisocyanate) at a molar ratio of 1:1-1:2, wherein the prepolymerization temperature is 50-80 ℃, stannous octoate is used as a catalyst, the molar ratio of the stannous octoate to PEG is 0.001:1-0.01:1, and the prepolymerization time is 1-4 h;

(2) after the prepolymerization is finished, adding graphene oxide, wherein the mass ratio of the graphene oxide to polyethylene glycol is 0.1:100-1:100, reacting for 8-24h at 35-55 ℃, and washing off unreacted graphene oxide by using absolute ethyl alcohol to obtain the amphiphilic polyurethane containing the graphene block.

The polyurethane can be dispersed in various organic and inorganic systems, is added for enhancement and modification before other organic materials are molded, can uniformly introduce graphene into a matrix material, simultaneously improve the mechanical property and biocompatibility of the material, and endow the matrix material with the unique properties of graphene, such as photo-thermal property, drug loading and releasing property and the like, which are not possessed originally.

According to a third aspect of the present invention, there is provided a use of the polyurethane material or the polyurethane material prepared by the preparation method of the polyurethane material as a material reinforcing agent in processing and molding of organic and/or inorganic polymer materials.

According to the invention, the carbon material such as graphene or the like is prepared into the amphiphilic polyurethane, the polyurethane can be dispersed in various organic and inorganic systems, can be used as a material reinforcing agent for reinforcing a polymer material, does not need to further perform modification reaction aiming at a specific polymer matrix needing to be modified, only needs to be directly added before other materials are processed and molded, is simple and convenient, has application universality, and improves the production efficiency. The amphiphilic polyurethane has potential application prospect in the field of processing and forming of coating materials, building materials, industrial damping materials, photoelectric materials, biomedical materials and other materials.

According to a fourth aspect of the present invention, there is provided a polymer material comprising a base material and the polyurethane material described above or a polyurethane material obtained by the method for producing the polyurethane material described above.

The polymer material may be a variety of functional materials including, but not limited to, coating materials, building materials, industrial damping materials, photovoltaic materials, or biomedical materials, among others.

The matrix material is not limited and includes various organic and/or inorganic polymer materials such as polylactic acid-glycolic acid copolymer or polyethylene glycol diacrylate, etc.

The polymer material added with the polyurethane material has better mechanical property and biocompatibility, and has photo-thermal property, electrical property and drug-loading and drug-releasing property which may not be possessed originally, and the original characteristics of the matrix material are not influenced.

In some embodiments, the polyurethane material is added in an amount of 2.5-7.5%, i.e., the mass percentage of polyurethane material to matrix material may be 2.5%, 3%, 4%, 5%, 6%, or 7.5%.

The polymer is well enhanced by only adding a small amount of polyurethane material before molding, and the mechanical property, biocompatibility and the like are improved to different degrees after molding.

According to a fifth aspect of the present invention, there is provided a 3D scaffold, prepared from the above-mentioned polymeric material.

The rheological property of the polymer material is not affected after the base material is added with the polyurethane material, the enhanced base material can still be used for preparing and processing a complete biomedical bracket by three-dimensional printing, has positive effects on the proliferation and adhesion of cells, and simultaneously ensures that the bracket has photothermal property and drug loading and releasing property.

The invention is further illustrated by the following specific examples and comparative examples, but it should be understood that these examples are for purposes of illustration only and are not to be construed as limiting the invention in any way. All the raw materials related to the invention can be obtained commercially.

Example 1 preparation of amphiphilic polyurethane containing graphene oxide blocks

An amphiphilic polyurethane containing a graphene oxide block is prepared by synthesizing a polyurethane material by using polyethylene glycol (PEG)10000 as a soft segment, 1, 6-Hexamethylene Diisocyanate (HDI) as a hard segment and Graphene Oxide (GO) as a chain extender.

The preparation method of the amphiphilic polyurethane containing the graphene oxide block comprises the following steps:

(1) toluene and PEG were added to the reaction kettle, stirred to dissolve the PEG in toluene, and then the molar ratio PEG: HDI is added in a ratio of 1:1, and the molar ratio of stannous octoate is as follows: adding stannous octoate into PEG (0.001: 1), and carrying out prepolymerization for 4 hours at 60 ℃ under the condition of nitrogen to obtain prepolymer A;

(2) adding GO which accounts for 0.1 wt% of PEG into the prepolymer A, reacting for 16 hours at 55 ℃, and washing away unreacted GO by using absolute ethyl alcohol to obtain the amphiphilic polyurethane containing the graphene block.

Example 2

This example differs from example 1 in that step (2) adds 0.2 wt% of GO, based on PEG, with the remainder unchanged.

Example 3

This example differs from example 1 in that step (2) adds 1 wt% of GO, based on PEG, and the rest is unchanged.

Example 4

This example differs from example 1 in that PEG 10000 was replaced with polypropylene glycol 2000.

Example 5

This example differs from example 1 in that HDI is replaced by TDI (toluene diisocyanate).

Example 6

This example differs from example 1 in that, in step (1), PEG: the HDI molar ratio was 1: 2.

Example 7

This example differs from example 1 in that, in step (1), PEG: the HDI molar ratio was 2: 3.

The more HDI, the harder the material, the higher the molecular weight, and the higher the molecular weight and the yield in example 1 than in example 6.

Example 8 preparation of amphiphilic polyurethane containing Fullerene blocks

An amphiphilic polyurethane containing fullerene blocks is prepared by taking polyethylene glycol (PEG)10000 as a soft segment, 1, 6-Hexamethylene Diisocyanate (HDI) as a hard segment and fullerene as a chain extender.

The preparation method of the amphiphilic polyurethane containing the fullerene block comprises the following steps:

(1) toluene and PEG were added to the reaction kettle, stirred to dissolve the PEG in toluene, and then the molar ratio PEG: HDI is added in a ratio of 1:1, and the molar ratio of stannous octoate is as follows: adding stannous octoate into PEG (0.002: 1), and carrying out prepolymerization for 3 hours at 75 ℃ under the nitrogen condition to obtain prepolymer A;

(2) adding fullerene accounting for 0.1 wt% of PEG into the prepolymer A, reacting for 24 hours at 45 ℃, and washing out unreacted fullerene by using absolute ethyl alcohol to obtain the amphiphilic polyurethane containing fullerene blocks.

Comparative example 1

This comparative example differs from example 1 in that the GO in step (2) was replaced with ethylene glycol, the remainder being unchanged, yielding a polyurethane.

Test example 1 structural characterization of amphiphilic polyurethane containing graphene oxide block

By passing¹The polyurethane materials were characterized by H NMR and ATR-IR (attenuated Total reflectance Infrared Spectroscopy), and the results are shown in FIGS. 2 and 3.

As shown in fig. 2, graphene oxide is a two-dimensional material of carbon, and the carbon has a bond of C ═ C double bonds, and 1645cm is contained in the amphiphilic polyurethane containing a graphene oxide block (examples 1 to 3)^-1The characteristic absorption peak of a graphene C ═ C double bond appears, the characteristic peak is not seen in the PPU material (comparative example 1) which is not added with the graphene for chain extension, and the graphene control group is at 1645cm^-1The characteristic peak appears.

As shown in fig. 3, graphene oxide brings a large amount of active hydrogen after entering the polyurethane segment, and shows a sharp single peak (arrow), while PPU without graphene oxide (comparative example 1) has significantly less active hydrogen at the same 1.5ppm and no distinct peak. The active hydrogen of the graphene oxide-doped PPU (comparative example 1 physically mixed GO) at 1.7ppm chemical shift shows a blunt peak. This illustrates the successful intercalation of graphene oxide into the polyurethane molecular segments in example 1.

By passing¹H NMR and ATR-IR detection prove that the amphiphilic polyurethane material containing the graphene oxide block is successfully synthesized.

Test example 2 mechanical Properties of base Material to which the Material of the present invention was added

The material reinforcing performance of the invention is proved by selecting polylactic acid-glycolic acid copolymer (PLGA) as a matrix material of an organic processing system and selecting polyethylene glycol diacrylate (PEGDA) as a matrix material of an inorganic processing system.

2.5 wt%, 5 wt% and 7.5 wt% of the polyurethane material of example 1 were added before the PLGA material was molded, and the mechanical properties of the material were tested after molding. 2.5 wt%, 5 wt% and 7.5 wt% of the polyurethane material of example 1 were added before the PEGDA material was molded, and the mechanical properties of the material were tested after molding, according to the following test methods: PLGA material: after a tetrafluoroethylene plate is used for film paving, a dynamic mechanical analyzer is used for measuring the tensile strength and the elongation at break;

PEGDA material: the resulting material was molded into a columnar shape using a tetrafluoroethylene mold, and the fracture stress and the compression ratio at the time of fracture were measured.

The results are shown in FIG. 4. As can be seen from FIG. 4, the PLGA material and PEGDA material added with 2.5%, 5% and 7.5% of the polyurethane material of the present invention have different improvements in mechanical properties after molding. Wherein, a, b and c show that the compression modulus of the amphiphilic polyurethane and the PEGDA material is improved after the amphiphilic polyurethane and the PEGDA material are jointly molded. d, e and f show that after the amphiphilic polyurethane and the PLGA material are formed together, the breaking stress and the breaking elongation of the amphiphilic polyurethane and the PLGA material are obviously improved.

Test example 3 three-dimensional printing was performed on a base material to which the material of the present invention was added

The three-dimensional printing stent processing is carried out on the PLGA material and the PEGDA material added with 5 wt% of the polyurethane material of the embodiment 1 under the condition of the same parameters, the viscosity and the shear rate of the PLGA material and the PEGDA material before and after the addition are tested, and the test method comprises the following steps: preparing equal-concentration PLGA ink, adding 5% PGUC into one group, and not adding the other group, and performing ink rheology test by using a rheometer, wherein the PEGDA is the same as the method. The results are shown in FIG. 5.

As can be seen from FIG. 5, the rheological properties of the polymer matrix materials PEGDA and PLGA added with the polyurethane material of the present invention are not affected, that is, the processability of the matrix material is not affected, the reinforced matrix material can be printed in three dimensions to prepare a complete biomedical stent, the shear thinning performance is improved, and thus a finer stent can be prepared.

SEM images of the printed scaffolds were analyzed using Adobe Acrobat pro software and pore size calculations were performed, the results are shown in table 1.

TABLE 1

PEGDA	PEGDA (5% of example 1)	PLGA	PLGA (5% example 1)
				0.136±0.006	0.189±0.014	0.086±0.014	0.105±0.034

As can be seen from Table 1, the PEGDA and PLGA materials with the addition of the polyurethanes of the present invention enable the printing of larger, more uniform pore size products.

Experimental example 4 biocompatibility test of Stent

The scaffolds printed by the PLGA material and the PEGDA material without the polyurethane material of example 1 and the PLGA material and the PEGDA material with the polyurethane material of example 1 added in an amount of 5 wt% were tested for biocompatibility by respectively planting 10000 osteoblasts on the scaffold, culturing for 7 days, dying and counting the cells on the scaffold with CCK-8. The results are shown in FIG. 6.

Biocompatibility tests show that the PLGA material and the PEGDA material which are added by 5 percent have positive effects on osteoblast proliferation and adhesion.

Test example 5 other Performance test of stent

After the stents printed by the PLGA material and the PEGDA material without the polyurethane material of the example 1 and the PLGA material and the PEGDA material with the polyurethane material of the example 1 of 5 weight percent are irradiated for 1min by near infrared with 808nm, the temperature is measured, and the test method is as follows: and carrying out real-time infrared temperature measurement on the support by using an infrared thermometer. The results are shown in FIG. 7.

The result shows that the temperature of the material containing the polyurethane is obviously increased after 808nm infrared irradiation for one minute, and the support processed and molded by the material added with the polyurethane has the photo-thermal property.

The drug loading and releasing performance of the processed and molded stent is explored by taking minocycline as a prototype drug:

the stents printed with the PLGA material and PEGDA material without the polyurethane material of example 1 and with the PLGA material and PEGDA material with the polyurethane material of example 1 added at 5 wt% were immersed in a 0.25 wt% minocycline hydrochloride (NIR) solution for 1 hour for drug loading, and then rinsed three times with PBS and immersed in an equal amount of PBS, and the amount of minocycline released was measured at 1,2, 3, and 4 hours, as shown in fig. 8.

As a result, the PLGA stent containing no polyurethane can hardly carry the medicine, and the PEGDA is water-absorbent gel and can carry a certain medicine. However, after 808nm infrared irradiation at 2 hours, the stent containing the polyurethane of the present invention generates a burst release of the drug, indicating that the stent has good drug loading and drug controlled release effects after the polyurethane material of the present invention is added.

Therefore, the polymer material using the polyurethane has better mechanical property, can further have the drug loading and releasing performance, photo-thermal performance and the like, and the performances of the rheological property, the formability, the biocompatibility and the like of the raw materials are not negatively influenced or even slightly improved. In addition, the invention is convenient to use, only small amount of direct addition is carried out before matrix molding, the complex modification steps and modification steps are further reduced, no complex chemical reaction is involved, and the complex design and modification processes in the traditional material modification process are improved. This means that the material has wide potential application prospect in the processing and forming of various materials such as coating materials, building materials, industrial damping materials and biomedical materials.

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. The polyurethane material is characterized by being mainly obtained by chain extending a prepolymer A by graphene oxide;

the structural general formula of the prepolymer A is as follows:

wherein X is- (CH)₂CH₂) -or

the number average molecular weight of the prepolymer A is 250-;

the prepolymer A is obtained by pre-polymerizing a reactant A and diisocyanate, wherein the molar ratio of the reactant A to the diisocyanate is 1:1-1: 1.5; reactant A comprises polyethylene glycol or polypropylene glycol;

the structural general formula of the polyurethane material is as follows:

wherein the content of the first and second substances,

or R₃；

R₃H, or

R₄H, or

x>1，n>1。

2. Polyurethane material according to claim 1, characterized in that X is- (CH-) - (CH)₂CH₂) A; n ranges from 4 to 460.

3. A polyurethane material according to claim 1, wherein Y is methylene, ethylene, propylene, isopropylene, butylene, pentylene, hexylene, heptylene, octylene, nonylene, naphthylene, decylene, 1, 2-cyclohexylene, 1, 3-cyclohexylene, 1, 4-cyclohexylene, 1, 2-phenylene, 1, 3-phenylene, 1, 4-phenylene, methylenephenyl or dimethylenephenyl; m is 1 or 2.

4. A method for preparing a polyurethane material according to any one of claims 1 to 3, comprising the steps of:

(a) providing prepolymer A: pre-polymerizing a reactant A and diisocyanate to obtain a prepolymer A, wherein the reactant A comprises polyethylene glycol or polypropylene glycol; the molar ratio of the reactant A to the diisocyanate is 1:1-1: 1.5;

(b) adding graphene oxide into the prepolymer A for chain extension to obtain a polyurethane material;

the diisocyanate comprises one or more of aliphatic diisocyanate, aromatic diisocyanate and alicyclic diisocyanate.

5. The method for preparing a polyurethane material according to claim 4, wherein in the step (a), the temperature of the prepolymerization is 50 to 80 ℃ and the time of the prepolymerization is 1 to 4 hours;

the prepolymerized catalyst is stannous octoate, and the molar ratio of the stannous octoate to the reactant A is 0.001:1-0.01: 1;

in the step (b), the chain extension reaction temperature is 35-55 ℃, and the chain extension reaction time is 8-24 h;

the mass ratio of the graphene oxide to the reactant A is 0.1:100-1: 100.

6. Use of a polyurethane material according to any one of claims 1 to 3 or of a polyurethane material obtained by a process for the preparation of a polyurethane material according to claim 4 or 5 as a material reinforcing agent in the processing and shaping of organic and/or inorganic polymer materials.

7. A polymer material comprising a base material and a polyurethane material produced by the method of producing a polyurethane material according to any one of claims 1 to 3 or a polyurethane material according to any one of claims 4 or 5;

the matrix material is an organic and/or inorganic polymer material;

the polyurethane material accounts for 2.5-7.5% of the mass of the matrix material.

8. A 3D scaffold prepared from the polymeric material of claim 7.