CN103845757B - A kind of artificial articular cartilage material and preparation method thereof - Google Patents

Abstract

The invention discloses an artificial articular cartilage material, which relates to the field of chemical modification of hydrogel soft materials, and is prepared by modifying polyacrylamide-sodium alginate hydrogel with graphene oxide and hydroxyapatite, and adopting free radical polymerization The obtained PAM-ALG-GO-HA composite hydrogel. Its preparation is: gradually add needle-shaped nano-HA particles to the pre-uniformly dispersed GO solution to form a mixed aqueous solution, and add acrylamide monomer, ALG monomer and related reagents for synthesizing PAM-ALG hydrogel, and use free radical polymerization The reaction prepared PAM-ALG-GO-HA composite hydrogel. The present invention makes full use of the two-dimensional structure of the GO nanosheet itself, the functional groups on the surface and the excellent biological activity of HA to chemically modify the PAM-ALG hydrogel, effectively improving the mechanical properties and biological activity of the PAM-ALG hydrogel , which expands the application range of PAM-ALG hydrogels, has clear scientific significance and great application value.

Description

A kind of artificial articular cartilage material and preparation method thereof

technical field

The invention relates to a chemical modification method of a hydrogel soft material, in particular to a preparation method of a novel artificial articular cartilage material PAM-ALG-GO-HA.

Background technique

With the intersecting development of bionics and new materials, the research on new materials with excellent performance prepared by bionic human body structure has been paid more and more attention. A layer of 2-7mm thick smooth and elastic tissue-articular cartilage covering the surface of the human knee joint can withstand various high-load pressures and impacts in a person's life cycle, and the natural life span can be as high as 70-80 years. And it can make the joints move freely, and at the same time, it can absorb the energy generated by the vibration during human activities, and play the role of cushioning and protecting the joints. At present, the "gold standard" of artificial knee replacement materials is cobalt-based alloy and ultra-high molecular weight polyethylene. This standard only uses hard ultra-high molecular weight polyethylene as the material between the contact surfaces of the prosthetic joint. On the one hand, it cannot effectively Dispersing the stress generated by the joint during movement will cause loosening and dislocation of the implanted prosthesis; on the other hand, long-term clinical observations have shown that the ultra-high molecular weight polyethylene material will rub against the surrounding metal alloy during long-term service to generate wear debris. Eventually the late wear of the artificial joint can be very severe. These failure phenomena have a lot to do with the fact that the current design of artificial joints does not have the natural structure of bionic human joints, and there is no design of articular cartilage and other defects. Therefore, it is particularly necessary and urgent to prepare new artificial articular cartilage materials.

PAM-ALG new hydrogel material is expected to be used in artificial cartilage and artificial muscle due to its microporous structure similar to natural cartilage, high water absorption and elasticity, good biocompatibility and certain self-repair function. And flexible robot manufacturing and other fields have been applied. However, it is estimated that during daily walking, the stress carried by the cartilage at the knee joint is 1.2 to 7.2 times the body weight, and the stress carried by the cartilage at the hip joint is 2.5 to 5.8 times the body weight. Under such a high stress, the mechanical properties of this soft material as an artificial articular cartilage replacement material cannot meet the high stress requirements for articular cartilage in normal human sports activities. Secondly, this kind of soft material is used as artificial muscle and other artificial soft tissue replacement materials. Although it has strong biocompatibility, it cannot be integrated with surrounding tissues due to its poor bioactivity. Therefore, it is necessary to further improve the PAM-ALG hydrogel according to its specific application environment.

Contents of the invention

Aiming at the above-mentioned prior art, the present invention provides an artificial articular cartilage material and a preparation method thereof. The polyacrylamide-sodium alginate hydrogel is chemically modified by using graphene oxide and hydroxyapatite, and the hydrogel is fully utilized. Based on the characteristics of natural articular cartilage, the chemical modification of PAM-ALG hydrogel with GO nanosheets with excellent mechanical properties and HA with good biological activity effectively improved the mechanical properties and biological activity of PAM-ALG hydrogel.

In order to solve the above-mentioned technical problems, an artificial articular cartilage material of the present invention is characterized in that polyacrylamide-sodium alginate hydrogel is modified with graphene oxide and hydroxyapatite, and the polyacrylamide-sodium alginate hydrogel is prepared by free radical polymerization. Acrylamide-sodium alginate-graphene oxide-hydroxyapatite composite hydrogel.

A kind of preparation method of artificial articular cartilage material of the present invention, comprises the following steps:

Prepare an aqueous solution of graphene oxide nanosheets, and perform ultrasonic treatment to keep the temperature of the graphene oxide nanosheets solution in the range of 10-50°C;

The needle-shaped nano-hydroxyapatite particles with a particle size of 10-1000nm are uniformly dispersed in the aqueous solution of graphene oxide nanosheets. During the mixing process, the temperature range of the aqueous solution is controlled at 10-80°C. After uniform mixing, hydroxyapatite is obtained Stable mixed aqueous solution with graphene oxide;

In an oxygen-free environment, add the raw materials for free radical polymerization to synthesize polyacrylamide and sodium alginate hydrogel in the above mixed aqueous solution in sequence, and after 20-90min, undergo free radical polymerization at a temperature of 30-70°C. Thus, polyacrylamide-sodium alginate-graphene oxide-hydroxyapatite composite hydrogel was obtained.

Further, in the present invention, the mass ratio of acrylamide monomer in polyacrylamide-sodium alginate-graphene oxide-hydroxyapatite composite hydrogel: sodium alginate monomer: graphene oxide: hydroxyapatite For 500: (40-70): (1-5): (5-35).

Compared with prior art, the beneficial effect of the present invention is:

The present invention makes full use of the two-dimensional structure of graphene oxide (GO) nanosheet itself and the functional groups on the surface and the excellent biological activity of hydroxyapatite (HA) to treat polyacrylamide-sodium alginate (PAM-ALG) hydrogel The chemical modification can effectively improve the mechanical properties and biological activity of PAM-ALG hydrogel, and expand the application range of PAM-ALG hydrogel, which has clear scientific significance and great application value.

Description of drawings

Figure 1 is the microscopic morphology of PAM-ALG hydrogel and PAM-ALG-GO-HA composite hydrogel (c and d) in Example 1 of the present invention; where a and b are PAM-ALG hydrogel The microscopic topography of the figure, c and d are the microscopic topography of the PAM-ALG-GO-HA composite hydrogel;

Fig. 2 is the infrared spectrogram of GO, HA, PAM-ALG hydrogel, PAM-ALG-HA and PAM-ALG-GO-HA composite hydrogel in Example 1 of the present invention;

Fig. 3 is the stress-strain diagram of the compression test of the PAM-ALG hydrogel and the PAM-ALG-GO-HA composite hydrogel in Example 1 of the present invention.

detailed description

The invention is an artificial articular cartilage material, which is polyacrylamide-sodium alginate hydrogel modified with graphene oxide and hydroxyapatite, and prepared by free radical polymerization. Alkene-hydroxyapatite composite hydrogel, wherein the mass ratio of acrylamide monomer: sodium alginate monomer: graphene oxide: hydroxyapatite is 500: (40-70): (1-5): (5-35). According to the fact that the two-dimensional structure of GO has a large specific surface area and provides many grafting points for the synthesis of hydrogels, the dehydration and condensation reaction between the carboxyl functional groups on GO and the amino functional groups in the hydrogel is used to realize the synthesis of GO and hydrogels. The cross-linking reaction improves its mechanical properties. And the introduction of HA complex modification into the hydrogel further improves the biological activity of the hydrogel.

A kind of preparation method of artificial articular cartilage material of the present invention, comprises the following steps:

Prepare an aqueous solution of graphene oxide nanosheets,

uniformly dispersing needle-shaped nano-hydroxyapatite particles with a particle size of 10-1000nm in an aqueous solution of graphene oxide nanosheets to obtain a stable mixed aqueous solution of hydroxyapatite and graphene oxide;

In an oxygen-free environment, add the raw materials for free radical polymerization to synthesize polyacrylamide and sodium alginate hydrogel in the above mixed aqueous solution in sequence, and after 20-90min, undergo free radical polymerization at a temperature of 30-70°C. Thus, polyacrylamide-sodium alginate-graphene oxide-hydroxyapatite composite hydrogel was obtained.

The anaerobic protective gas used in the anaerobic protective environment is subject to no reaction with the colloidal solution, and commonly used protective gases such as nitrogen and argon can be selected; the raw materials for synthesizing PAM and ALG hydrogel are sequentially added, including: monomer 1: acrylamide; initiator: ammonium persulfate; covalent bond crosslinker: methylene bisacrylamide; catalyst: N,N,N',N',-tetramethyldiacetamide; ionic bond crosslinker : Anhydrous calcium chloride; Monomer 2: Sodium alginate; Dehydrating agent: Carbodiimide and N-hydroxysuccinimide. Wherein, the acrylamide is in an oxygen-free environment, and the initiator ammonium persulfate generates primary free radicals to initiate a crosslinking reaction between the acrylamide and the covalent crosslinking agent. At the same time, sodium alginate ALG and divalent cation Ca ²⁺ will form an ionic cross-linking reaction. When the two monomers exist at the same time, the grid formed by the PAM chain will also undergo a dehydration condensation reaction with the grid formed by the ALG chain to form a covalent bond cross-link and tightly bond together. At the same time, on the one hand, because GO itself has a two-dimensional structure, that is, the longitudinal thickness is between a few to tens of nanometers and the lateral length is between nanometers and micrometers, this huge specific surface area provides a great opportunity for the synthesis of hydrogels. many grafting points. On the other hand, the carboxyl functional groups on GO and the amino functional groups on PAM undergo a dehydration condensation reaction, which increases the network crosslinking degree of PAM-ALG hydrogel and further enhances the mechanical properties of the composite hydrogel.

The specific preparation process of the present invention is described below through specific examples. The embodiments of the present invention are provided for accurate understanding, and by no means limit the present invention. Under the inspiration of the present invention, various replacements, changes and modifications made by those skilled in the art without departing from the gist of the present invention all belong to the protection scope of the present invention.

Example 1:

1) The aqueous solution of graphene oxide GO nanosheets prepared by the Hummers method was fully ultrasonicated for 1 hour.

2) Mechanically blend 5% HA in the 15ml GO nanosheet aqueous solution with a concentration of 2mg/ml above, and ultrasonically oscillate for 30min to ensure that HA is uniformly dispersed in the GO nanosheet aqueous solution.

3) In the above mixed solution of GO and HA, under the protective environment of high-purity nitrogen, the raw materials for the synthesis of PAM-ALG hydrogel by free radical polymerization, namely, monomer 1: 5 g of acrylamide; initiator: over Ammonium sulfate 0.015g; covalent bond crosslinking agent: methylenebisacrylamide 0.0031g; catalyst: N,N,N',N',-tetramethyldiacetamide 16μL; ionic bond crosslinking agent: anhydrous chlorine Calcium 0.0661g; monomer 2: sodium alginate 0.5g; dehydrating agent: carbodiimide 0.04g and N-hydroxysuccinimide 0.02g. After 60 min, the PAM-ALG-GO-HA composite hydrogel was prepared by free radical polymerization at a temperature of 50 °C.

Microscopic topography of hydrogel and PAM-ALG-GO-HA composite hydrogel as shown in Figure 1. From Figure 1(a) and (b), it can be found that the microscopic morphology of the hydrogel presents a blood vessel-like three-dimensional porous network structure with a pore size of several microns. This structure is similar to the microscopic morphology of natural human articular cartilage. The porous grid allows the interstitial fluid to flow freely between the interconnected pores, which will disperse the pressure on the joints caused by external movements. Structure is critical to the lubricating, shock absorbing and swelling functions of articular cartilage. The microscopic morphology of the PAM-ALG-GO-HA composite hydrogel (Fig. 1c and Fig. 1d) shows that by introducing the inorganic reinforcement phases GO and HA into the PAM-ALG hydrogel, the hydrogel is hardened, and the PAM - During the freeze-drying process of the ALG-GO-HA composite hydrogel, the hard hydrogel grid prevented the growth of HA crystals, so it can be clearly seen in Figure 1c that there is a flocculent thin layer tightly Attached to the grid edge of the polymer hydrogel matrix. In summary, the microscopic morphology of the hydrogel and PAM-ALG-GO-HA composite hydrogel showed a microporous grid shape, and the grid distribution was relatively uniform.

Figure 2 is the infrared spectrum of GO, HA, hydrogel, PAM-ALG-HA and PAM-ALG-GO-HA composite hydrogel. It can be found from the figure that GO and HA respectively mark the corresponding characteristic peak positions as shown in the figure, in which the peak position of 1263.10 cm ^-1 in the infrared spectrum of the hydrogel corresponds to the stretching vibration peak of the CN bond in the secondary amine bond, which is It shows that the two kinds of monomer mesh PAM and ALG in the hydrogel are combined in the form of chemical bonds. In the infrared spectrum of the PAM-ALG-GO-HA composite hydrogel, the peak position at 1418.59 cm ^-1 corresponds to the stretching vibration peak of the CN bond in the amide bond, which indicates that the monomeric PAM in GO and the hydrogel network produced chemical crosslinking reaction.

Fig. 3 is the compressive test stress-strain diagram of the hydrogel before and after PAM-ALG composited with GO and HA. It can be seen from the figure that after adding GO and HA, the slope of the curve, that is, the compressive elastic modulus, is greatly increased, so the composite hydrogel has stronger mechanical properties.

Example 2:

1) The aqueous solution of graphene oxide GO nanosheets prepared by Brodie method was fully ultrasonicated for 1.5 hours.

2) Mechanically blend 3% HA in the 20ml GO nanosheet aqueous solution with a concentration of 0.5mg/ml above, and ultrasonically oscillate for 40min to ensure that HA is uniformly dispersed in the GO nanosheet aqueous solution.

3) In the above mixed solution of GO and HA, in the protective environment of high-purity argon, the raw materials for the synthesis of PAM-ALG hydrogel by free radical polymerization, namely, monomer 1: acrylamide; initiator: over Ammonium sulfate 0.015g; covalent bond crosslinking agent: methylenebisacrylamide 0.0031g; catalyst: N,N,N',N',-tetramethyldiacetamide 16μL; ionic bond crosslinking agent: anhydrous chlorine Calcium 0.0661g; monomer 2: sodium alginate 0.6g; dehydrating agent: carbodiimide 0.04g and N-hydroxysuccinimide 0.02g. After 40 min, the PAM-ALG-GO-HA composite hydrogel was prepared by free radical polymerization at a temperature of 60 °C.

Example 3:

1) The aqueous solution of graphene oxide GO nanosheets prepared by the Staudenmaier method was fully ultrasonicated for 2 hours.

2) Mechanically blend 5% HA in the 25ml GO nanosheet aqueous solution with a concentration of 2mg/ml above, and ultrasonically oscillate for 30min to ensure that HA is uniformly dispersed in the GO nanosheet aqueous solution.

3) In the above mixed solution of GO and HA, under the protective environment of high-purity nitrogen, add the raw materials for the synthesis of PAM-ALG hydrogel by free radical polymerization, that is, monomer 1: acrylamide; initiator: persulfuric acid Ammonium 0.015g; covalent bond cross-linking agent: methylenebisacrylamide 0.0031g; catalyst: N,N,N',N',-tetramethyldiacetamide 16μL; ionic bond cross-linking agent: anhydrous chloride Calcium 0.0661g; monomer 2: sodium alginate 0.5g; dehydrating agent: carbodiimide 0.04g and N-hydroxysuccinimide 0.02g. After 80 min, the PAM-ALG-GO-HA composite hydrogel was prepared by free radical polymerization at a temperature of 40 °C.

Example 4:

1) The aqueous solution of graphene oxide GO nanosheets prepared by the Hummers method was fully ultrasonicated for 1 hour.

2) Mechanically blend 7% HA in the 15ml GO nanosheet aqueous solution with a concentration of 2mg/ml above, and ultrasonically oscillate for 40min to ensure that HA is uniformly dispersed in the GO nanosheet aqueous solution.

3) In the above mixed solution of GO and HA, in the protective environment of high-purity argon, the raw materials for the synthesis of PAM-ALG hydrogel by free radical polymerization, namely, monomer 1: acrylamide; initiator: over Ammonium sulfate 0.015g; covalent bond crosslinking agent: methylenebisacrylamide 0.0031g; catalyst: N,N,N',N',-tetramethyldiacetamide 16μL; ionic bond crosslinking agent: anhydrous chlorine Calcium 0.0661g; monomer 2: sodium alginate 0.6g; dehydrating agent: carbodiimide 0.04g and N-hydroxysuccinimide 0.02g. After 60 min, the PAM-ALG-GO-HA composite hydrogel was prepared by free radical polymerization at a temperature of 50 °C.

Although the present invention has been described above in conjunction with the drawings, the present invention is not limited to the above-mentioned specific embodiments, and the above-mentioned specific embodiments are only illustrative, rather than restrictive. Under the inspiration, many modifications can be made without departing from the gist of the present invention, and these all belong to the protection of the present invention.

Claims (2)

1. an artificial articular cartilage material, it is characterized in that, polyacrylamide-Sodium Alginate Hydrogel Films is modified with graphene oxide and hydroxyapatite, and the polyacrylamide-sodium alginate-graphene oxide-hydroxyapatite composite aquogel adopting Raolical polymerizable to prepare; Acrylamide monomer in polyacrylamide-sodium alginate-graphene oxide-hydroxyapatite composite aquogel: sodium alginate monomer: graphene oxide: the mass ratio of hydroxyapatite is 500:(40-70): (1-5): (5-35).

2. the preparation method of a kind of artificial articular cartilage material as claimed in claim 1, is characterized in that: comprise the following steps:

Preparation stannic oxide/graphene nano sheet aqueous solution, supersound process, makes stannic oxide/graphene nano sheet solution temperature remain on 10-50 DEG C of scope;

Be that the needle nano-hydroxy apatite even particulate dispersion of 10-1000nm is in stannic oxide/graphene nano sheet aqueous solution by granularity, in mixed process, aqueous temperature scope control, at 10-80 DEG C, after Homogeneous phase mixing, obtains hydroxyapatite and the stable mixed aqueous solution of graphene oxide;

Under anaerobic protection of the environment, the raw material of Raolical polymerizable synthesis polyacrylamide and Sodium Alginate Hydrogel Films is added successively in above-mentioned mixed aqueous solution, wherein, the raw material of Raolical polymerizable synthesis polyacrylamide and Sodium Alginate Hydrogel Films comprises: monomer 1: acrylamide; Initiator: Ammonium persulfate.; Covalently cross-linked dose: methylene diacrylamide; Catalyst: N, N, N ', N ' ,-tetramethyl diacetayl amide; Ionic crosslinking agent: anhydrous calcium chloride; Monomer 2: sodium alginate; Dehydrant: carbodiimides and N-hydroxy-succinamide; Through 20-90min, by Raolical polymerizable at 30 ~ 70 DEG C of temperature, thus obtain polyacrylamide-sodium alginate-graphene oxide-hydroxyapatite composite aquogel; Acrylamide monomer in described polyacrylamide-sodium alginate-graphene oxide-hydroxyapatite composite aquogel: sodium alginate monomer: graphene oxide: the mass ratio of hydroxyapatite is 500:(40-70): (1-5): (5-35).