阅读说明：本技术 自润滑高强互穿网络水凝胶仿生关节软骨及其制备方法 (Self-lubricating high-strength interpenetrating network hydrogel bionic articular cartilage and preparation method thereof ) 是由 熊党生 陈俊玥 崔玲玲 于 2020-12-04 设计创作，主要内容包括：本发明公开了一种自润滑高强互穿网络水凝胶仿生关节软骨及其制备方法。所述方法将聚乙烯醇、两性离子甜菜碱、光引发剂α-酮戊二酸和交联剂N,N’-亚甲基双丙烯酰胺均匀分散在水中配置成混合溶液,然后将混合溶液放置在紫外光下通过辐照进行自由基聚合反应,最后经过物理交联制得自润滑高强互穿网络水凝胶仿生关节软骨。本发明利用共混的方法,将两性离子均匀地分散在基体成分中,所制备的互穿水凝胶成分均匀,结构与性能均表现稳定；利用辐照交联和物理交联相结合的方式,在保持高含水量的同时,进一步提高了产物的力学性能和摩擦学性能,适用于关节软骨替换修复及含水溶液环境减摩耐磨等领域。(The invention discloses a self-lubricating high-strength interpenetrating network hydrogel bionic articular cartilage and a preparation method thereof. Uniformly dispersing polyvinyl alcohol, zwitterionic betaine, a photoinitiator alpha-ketoglutaric acid and a crosslinking agent N, N' -methylene bisacrylamide in water to prepare a mixed solution, then placing the mixed solution under ultraviolet light to perform free radical polymerization reaction through irradiation, and finally performing physical crosslinking to prepare the self-lubricating high-strength interpenetrating network hydrogel bionic articular cartilage. The invention utilizes the blending method to uniformly disperse zwitterions in matrix components, and the prepared interpenetrating hydrogel has uniform components and stable structure and performance; by using the mode of combining irradiation crosslinking and physical crosslinking, the mechanical property and the tribological property of the product are further improved while the high water content is maintained, and the method is suitable for the fields of articular cartilage replacement and repair, aqueous solution environment friction reduction and wear resistance and the like.)

1. The preparation method of the self-lubricating high-strength interpenetrating network hydrogel bionic articular cartilage is characterized by comprising the following steps of:

uniformly dispersing PVA, MPDSAH, a photoinitiator alpha-ketoglutaric acid and a cross-linking agent N, N' -methylene bisacrylamide in water to prepare a mixed solution, then placing the mixed solution under ultraviolet light to perform free radical polymerization reaction through irradiation, and finally performing physical cross-linking to prepare the self-lubricating high-strength interpenetrating network hydrogel bionic articular cartilage.

2. The method according to claim 1, wherein the mixed solution contains 5 to 20 wt% of PVA and 5 to 15 wt% of MPDSAH.

3. The method according to claim 1, wherein the mixed solution has a PVA concentration of 15 wt% and an MPDSAH concentration of 10 wt%.

4. The method according to claim 1, wherein the photoinitiator α -ketoglutaric acid and the crosslinking agent N, N' -methylenebisacrylamide are added in an amount of 0.1 wt% based on the PVA.

5. The preparation method according to claim 1, wherein the ultraviolet light irradiation time is 2-8 h.

6. The method according to claim 1, wherein the UV irradiation time is 5 hours.

7. The method according to claim 1, wherein the physical crosslinking is performed by repeated freeze thawing.

8. The preparation method according to claim 7, wherein in the repeated freezing and thawing process, the freezing time is 12-24 hours, the thawing time is 2-4 hours, and the process is repeated for 5 times.

9. The self-lubricating high-strength interpenetrating network hydrogel bionic articular cartilage prepared by the preparation method according to any one of claims 1 to 8.

Technical Field

The invention belongs to the field of high polymer materials, and relates to a self-lubricating high-strength interpenetrating network hydrogel bionic articular cartilage and a preparation method thereof.

Background

Articular cartilage is a tough, resilient, load-bearing connective tissue with specific biological and biomechanical properties. The cartilage can play a role in buffering and absorbing shock, so that the bones can slide mutually in an extremely low friction mode. Mature chondrocytes do not contain blood vessels and nutrients and are difficult to self-repair. Current research in cartilage repair has focused primarily on the synthesis of articular cartilage substitutes or biomaterials that can stimulate the regeneration of new tissue. The hydrogel has excellent biocompatibility, high water-containing property and swelling property, and has a structure and performance similar to those of natural articular cartilage, so that the hydrogel becomes a research hotspot of bionic articular cartilage.

Polyvinyl alcohol is a commonly used synthetic hydrogel material, has stable chemical properties, high elasticity, easy molding, wear resistance, shock absorption and good biocompatibility.

Zwitterions are believed to play an important role in boundary lubrication. Under the action of shearing, a hydration layer formed by zwitterions can be rapidly exchanged with surrounding water molecules, so that a fluid-like effect is generated, and the friction coefficient and macroscopic wear are effectively reduced.

Upon swelling the zwitterionic substance PMPC (poly (2-methacryloyloxyethyl phosphorylcholine)) into a PAMPS (poly (2-acrylamido-2-methylpropanesulfonic acid)) single-network Hydrogel, Milner et al performed irradiation crosslinking to form a double-network Hydrogel, which demonstrated that zwitterions can improve the frictional properties of the Hydrogel, but the swelling manner did not guarantee the uniformity and isotropy of the internal structure, and the mechanical properties were much different from those of natural Cartilage (Milner P E, Parkes M, Puetzer J L, et al.A Low Friction Reinforcement, Bipharic and Boundary biomedical materials, 2017: S1742706106773.).

Disclosure of Invention

The invention provides a self-lubricating high-strength interpenetrating network hydrogel bionic articular cartilage and a preparation method thereof, aiming at the problem that the friction performance and the mechanical performance of the artificial articular cartilage in the prior art are poor.

The technical solution of the invention is as follows:

the preparation method of the self-lubricating high-strength interpenetrating network hydrogel bionic articular cartilage comprises the following steps:

uniformly dispersing polyvinyl alcohol (PVA), zwitterionic betaine (MPDSAH), photoinitiator alpha-Ketoglutaric acid (alpha-Ketoglutaric acid) and cross-linking agent N, N' -methylene bisacrylamide in water to prepare a mixed solution, then placing the mixed solution under ultraviolet light to perform free radical polymerization through irradiation, and finally performing physical cross-linking to prepare the self-lubricating high-strength interpenetrating network hydrogel bionic articular cartilage.

Further, in the mixed solution, the concentration of PVA is 5-20 wt%, preferably 15 wt%; the concentration of MPDSAH is 5-15 wt%, preferably 10 wt%.

In a specific embodiment of the invention, the photoinitiator alpha-ketoglutaric acid and the cross-linking agent N, N' -methylenebisacrylamide are added in an amount of 0.1 wt% of PVA.

Furthermore, the ultraviolet irradiation time is 2-8 h, preferably 5 h.

Furthermore, the physical crosslinking mode adopts a mode of repeated freezing and thawing.

Furthermore, in the repeated freezing and thawing process, the freezing time is 12-24 hours, the thawing time is 2-4 hours, and the process is repeated for 5 times.

Under the action of ultraviolet irradiation, free radical polymerization is carried out on a betaine monomer MPDSAH, and C-C double bonds in the structure are opened to form a polymer pMPDSAH; in the repeated cold thawing process, the polymer pMPDSAH and PVA are crosslinked to form the hydrogel with the double-network structure in a hydrogen bond mode.

Compared with the prior art, the invention has the following advantages:

(1) the invention utilizes the blending method to uniformly disperse zwitterions in matrix components, and the prepared interpenetrating hydrogel has uniform components and stable structure and performance.

(2) The invention utilizes the mode of combining irradiation crosslinking and physical crosslinking, maintains high water content, further improves the tribological property and mechanical property of the product, reduces the friction coefficient by 50 percent, and improves the tensile strength by more than 40 times to the maximum.

(3) The reagent used in the invention does not need special treatment, the preparation process is simple, the reaction condition is mild, and the method is suitable for large-scale production.

Drawings

FIG. 1 is a schematic diagram of a preparation process of the self-lubricating high-strength interpenetrating network hydrogel bionic articular cartilage.

FIG. 2 is a graph of the molecular formulae of polyvinyl alcohol and zwitterionic betaine.

FIG. 3 is an infrared spectrum of the interpenetrating network hydrogel prepared.

FIG. 4 is an SEM image of the prepared sample of interpenetrating network hydrogel PVA-5% MPDSAH-5 h.

FIG. 5 is a graph of water content test results for different interpenetrating network hydrogels.

FIG. 6 is a graph of tensile strain versus stress for different interpenetrating network hydrogels.

FIG. 7 is a graph of the results of friction performance testing of different interpenetrating network hydrogels.

FIG. 8 is a graph showing the comparison of friction coefficients of different interpenetrating network hydrogels at different friction times.

Detailed Description

The present invention will be described in more detail with reference to the following examples and the accompanying drawings.

In the following examples, the polyvinyl alcohol (PVA) used was 1799 type, the degree of polymerization was 1700, and the degree of alcoholysis was 99% or more, and was purchased from Nanjing lattice chemical technology Co.

In the following examples, samples of interpenetrating network hydrogels prepared in each example were designated as PVA-x% MPDSAH-yh, where x% represents the mass fraction of MPDSAH and yh represents the time of polymerization of the mixed solution under UV light.

Example 1

(1) Preparing a mixed aqueous solution of PVA accounting for 15 percent of the mass fraction of the mixed solution and MPDSAH accounting for 5 percent of the mass fraction of the mixed solution.

(2) Adding a cross-linking agent N, N' -methylene bisacrylamide accounting for 0.1 percent of the mass fraction of PVA and a photoinitiator alpha-ketoglutaric acid into the mixed solution in the step 1.

(3) The mixed solution was heated and stirred at 95 ℃ to assume a colorless transparent state.

(4) Pouring the uniformly mixed solution into a culture dish, placing under an ultraviolet lamp, and irradiating for different time: 2h, 5h and 8 h.

(5) And (4) putting the sample obtained in the step 4 into a refrigerator for freezing for 21h and unfreezing for 3 h.

(6) Repeat step 5 times.

(7) And (4) putting the hydrogel obtained in the step (6) into deionized water to remove impurities such as monomers, cross-linking agents and the like remained on the surface, so as to obtain the interpenetrating network hydrogel.

FIG. 3 is an infrared spectrum of the interpenetrating network hydrogel prepared in example 1. PVA-5% MPDSAH-5h IR spectrum at 3298cm^-1A characteristic peak of a large number of-OH appears at 1091cm^-1The characteristic peak of S ═ O appears, indicating that PVA is blended with MPDSAH to successfully prepare interpenetrating network hydrogel.

FIG. 4 is an SEM image of the sample of interpenetrating network hydrogel prepared in example 1, PVA-5% MPDSAH-5h, and the hydrogel sample is observed to have a three-dimensional network-like porous tissue structure.

Example 2

(1) Preparing a mixed solution of PVA accounting for 15 percent of the mass fraction of the mixed solution and MPDSAH accounting for 10 percent of the mass fraction of the mixed solution.

(2) Adding a cross-linking agent N, N' -methylene bisacrylamide accounting for 0.1 percent of the mass fraction of PVA and a photoinitiator alpha-ketoglutaric acid into the mixed solution in the step 1.

(3) The mixed solution was heated and stirred at 95 ℃ to assume a colorless transparent state.

(4) And pouring the uniformly mixed solution into a culture dish, placing under an ultraviolet lamp, and irradiating for 5 hours.

(5) And (4) putting the sample obtained in the step 4 into a refrigerator for freezing for 21h and unfreezing for 3 h.

(6) Repeat step 5 times.

(7) And (4) putting the hydrogel obtained in the step (6) into deionized water to remove impurities such as monomers, cross-linking agents and the like remained on the surface, so as to obtain the interpenetrating network hydrogel.

Example 3

(1) Preparing a mixed solution of PVA accounting for 15 percent of the mass fraction of the mixed solution and MPDSAH accounting for 15 percent of the mass fraction of the mixed solution.

(2) Adding a cross-linking agent N, N' -methylene bisacrylamide accounting for 0.1 percent of the mass fraction of PVA and a photoinitiator alpha-ketoglutaric acid into the mixed solution in the step 1.

(3) The mixed solution was heated and stirred at 95 ℃ to assume a colorless transparent state.

(4) And pouring the uniformly mixed solution into a culture dish, placing under an ultraviolet lamp, and irradiating for 5 hours.

(5) And (4) putting the sample obtained in the step 4 into a refrigerator for freezing for 21h and unfreezing for 3 h.

(6) Repeat step 5 times.

(7) And (4) putting the hydrogel obtained in the step (6) into deionized water to remove impurities such as monomers, cross-linking agents and the like remained on the surface, so as to obtain the interpenetrating network hydrogel.

Comparative example 1

(1) Preparing a PVA solution accounting for 15 percent of the mass fraction of the mixed solution.

(2) Adding a cross-linking agent N, N' -methylene bisacrylamide accounting for 0.1 percent of the mass fraction of the PVA and a photoinitiator alpha-ketoglutaric acid into a PVA solution.

(3) The PVA solution was heated and stirred at 95 ℃ to assume a colorless transparent state.

(4) Pouring the dissolved, uniform and transparent solution into a culture dish, placing under an ultraviolet lamp, and irradiating for different 5 h.

(5) And (4) putting the sample obtained in the step 4 into a refrigerator for freezing for 21h and unfreezing for 3 h.

(6) Repeat step 5 times.

(7) And (4) putting the hydrogel obtained in the step (6) into deionized water to remove impurities such as monomers, cross-linking agents and the like remained on the surface, and preparing the PVA hydrogel PVA-0% MPDSAH-5 h.

Comparative example 2

(1) Preparing a mixed solution of PVA accounting for 15 percent of the mass fraction of the mixed solution and MPDSAH accounting for 5 percent of the mass fraction of the mixed solution.

(2) Adding a cross-linking agent N, N' -methylene bisacrylamide accounting for 0.1 percent of the mass fraction of PVA and a photoinitiator alpha-ketoglutaric acid into the mixed solution in the step 1.

(3) The mixed solution was heated and stirred at 95 ℃ to be colorless and transparent, and poured into a petri dish.

(4) Putting into refrigerator, freezing for 21h, and thawing for 3 h.

(5) Repeat step 4 5 times.

(6) And (4) putting the hydrogel obtained in the step (5) into deionized water to remove impurities such as monomers, cross-linking agents and the like remained on the surface, and preparing the hydrogel PVA-5% MPDSAH-0 h.

FIG. 5 shows the water content of the IPN hydrogels of different examples and comparative examples, and it can be seen that the samples of the hydrogels prepared by the experiments are kept at a high level. The water content of the sample is not greatly influenced by ultraviolet irradiation and MPDSAH addition, and the water content is still kept above 78%.

FIG. 6 is a graph of tensile strain versus stress for interpenetrating network hydrogels of various examples and comparative examples. It can be seen that the addition of MPDSAH increased the tensile modulus of the hydrogel, the tensile strength of the sample PVA-15% MPDSAH-5h was 5.543MPa, which is more than two times higher than that of the sample PVA-0% MPDSAH-5h (2.47MPa) without betaine; the mechanical property of the hydrogel sample can be effectively improved by increasing the ultraviolet irradiation time, the tensile strength of the sample PVA-5% MPDSAH-8h is 9.872MPa, and the tensile strength is improved by more than 40 times compared with that of the sample PVA-5% MPDSAH-0h (0.241MPa) which is not irradiated.

FIG. 7 shows the results of the tribological performance testing of interpenetrating network hydrogels of different examples and comparative examples. The addition of the MPDSAH can be seen to obviously reduce the tribological performance of the hydrogel sample, and the friction coefficient of the sample PVA-15% MPDSAH-5h is reduced from 0.2819 +/-0.0547 to 0.1354 +/-0.00903 compared with the sample PVA-0% MPDSAH-5h without betaine, so that the addition of the MPDSAH can play a self-lubricating effect. And in the experiment, the friction coefficient can be further reduced by controlling the irradiation time, and compared with the sample PVA-5% MPDSAH-8h which is not irradiated, the friction coefficient is reduced from 0.4033 +/-0.04261 to 0.1592 +/-0.01172, which shows that the tribological performance of the hydrogel is effectively improved by irradiation crosslinking.

Fig. 8 is a comparison result of friction coefficients of the interpenetrating network hydrogels of different examples and comparative examples at different friction times, and it can be seen from the figure that, in the long-time friction experiment process, the addition of MPDSAH and the ultraviolet irradiation time have positive effects on the stability of the hydrogel, the change range of the friction coefficients of the sample with longer irradiation time and the sample with high added MPDSAH content is not large along with the increase of the friction time, the abrasion of the hydrogel sample can be reduced in the long-time abrasion experiment, and the lower friction coefficient can be maintained.