A nitric oxide injectable hydrogel and its preparation method and application

Abstract

The present invention relates to the technical field of medical products, and specifically to a nitric oxide injectable hydrogel, its preparation method, and application. The hydrogel comprises a sodium alginate system, D-(+)-glucono-delta-lactone, and sodium dihydrogen phosphate, wherein the mass-to-volume ratio of the sodium alginate system, D-(+)-glucono-delta-lactone, and sodium dihydrogen phosphate is 10 mL:0.36 g:0.142 g; the sodium alginate system comprises sodium alginate, deionized water, a nitric oxide donor, and calcium carbonate. The preparation method comprises cross-linking D-(+)-glucono-delta-lactone, sodium alginate, and calcium carbonate, and then incorporating a nitric oxide donor. The application is for the preparation of a nitric oxide-releasing 3D-printed artificial bone composite scaffold. The hydrogel disclosed in the present invention has the advantages of uniform distribution of nitric oxide donors and strong nitric oxide loading capacity. The preparation method is mild and low-cost, and has important application value in medical product technology.

Description

Technical Field

[0001] The present invention relates to the technical field of medical products, and in particular to an injectable nitric oxide hydrogel and a preparation method and application thereof. Background Art

[0002] In our daily lives, we are surrounded by a large number of different types of pathogens, making us very susceptible to infection. Currently, the main way to combat bacterial infections is through antibiotic treatment. However, excessive use of antibiotics can easily lead to bacterial resistance, making the development of new antibacterial materials particularly important. Recent studies have found that nitric oxide (NO) can destroy bacterial cell membranes and genetic information and prevent bacteria from obtaining energy. It has the properties of high antibacterial efficiency and low resistance to drug resistance. Its application in the antibacterial field has received widespread attention, and the field of NO-based medical products has also developed rapidly.

[0003] Hydrogels, three-dimensional cross-linked networks with excellent biocompatibility and swelling properties, have been widely used in various fields, including bioengineering and biomedicine. Compared to conventional hydrogels, injectable hydrogels have attracted increasing attention due to their moisture retention and plasticity. Currently, injectable hydrogels are used as biomedical materials in various fields, including tissue engineering, drug delivery, wound healing, and contact lenses. The main advantage of injectable hydrogels in controlled drug release is their ability to adapt to the local microenvironment and, upon injection, gel and integrate into local tissues to reach the target site. Injectable hydrogels can achieve sustained release of nitric oxide (NO), potentially enabling synergistic tumor therapy at the target site without damaging other tissues. However, currently available injectable hydrogels for nitric oxide release suffer from low NO loading capacity, slow release rate, and short release duration. Therefore, the development of injectable hydrogels with high NO loading capacity, high release rate, long release duration, strong antibacterial properties, and the ability to achieve slow and controlled NO release is of great significance and has great potential for application. Summary of the Invention

[0004] In order to address the shortcomings and deficiencies of the prior art, the primary purpose of the present invention is to provide an injectable nitric oxide hydrogel that can achieve a high loading amount of nitric oxide and can automatically and slowly release nitric oxide.

[0005] The second object of the present invention is to provide a method for preparing the injectable hydrogel.

[0006] The third object of the present invention is to provide applications of the above-mentioned injectable hydrogel. The nitric oxide injectable hydrogel provided by the present invention is widely used in biomedical engineering, has good research and development prospects, and can be used in medical implants.

[0007] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0008] A nitric oxide injectable hydrogel comprises a sodium alginate system, D-(+)-glucono-delta-lactone, and sodium dihydrogen phosphate; the mass-to-volume ratio of the sodium alginate system, D-(+)-glucono-delta-lactone, and sodium dihydrogen phosphate is 10 mL:0.36 g:0.142 g; the nitric oxide injectable hydrogel has the advantages of a strong nitric oxide loading capacity, a high nitric oxide release rate, a long nitric oxide release duration, and is biodegradable, and exhibits important application value in medical product technology.

[0009] Furthermore, the sodium alginate system consists of sodium alginate, deionized water, a nitric oxide donor and calcium carbonate.

[0010] Furthermore, the mass volume ratio of the sodium alginate, deionized water, nitric oxide donor and calcium carbonate is 0.4g:10mL:0.01-0.03g:0.36g.

[0011] Furthermore, the nitric oxide donor is SNAP or GSNO.

[0012] A method for preparing an injectable nitric oxide hydrogel, comprising the following steps:

[0013] (1) Sodium alginate was dissolved in deionized water to prepare a sodium alginate solution, and magnetic stirring was performed for 30 minutes until the sodium alginate was completely dissolved. Then, a nitric oxide donor was dispersed in the sodium alginate solution under magnetic stirring to form a suspension;

[0014] (2) dispersing calcium carbonate into the suspension generated in step (1) under magnetic stirring to generate a sodium alginate system;

[0015] (3) adding D-(+)-glucono-δ-lactone and sodium dihydrogen phosphate to the sodium alginate system generated in step (2) in sequence, and reacting for 10 minutes to obtain the nitric oxide injectable hydrogel; the mass volume ratio of the sodium alginate system, D-(+)-glucono-δ-lactone and sodium dihydrogen phosphate is 10 mL:0.36 g:0.142 g;

[0016] The preparation method utilizes D-(+)-glucono delta-lactone to induce the in situ synthesis of an injectable hydrogel via crosslinking of sodium alginate and calcium ions. A nitric oxide donor is then successfully incorporated into the hydrogel to produce an injectable hydrogel capable of controlled nitric oxide release. The nitric oxide injectable hydrogel prepared using the method provided by the present invention has a strong nitric oxide loading capacity and strong antibacterial properties, enabling the slow and controlled release of nitric oxide.

[0017] Furthermore, in the above step (2), the mass volume ratio of sodium alginate, deionized water, nitric oxide donor and calcium carbonate in the sodium alginate system is 0.4g:10mL:0.01-0.03g:0.36g.

[0018] Furthermore, the nitric oxide donor is SNAP or GSNO.

[0019] The application of the above-mentioned nitric oxide injectable hydrogel is for the preparation of nitric oxide-releasing 3D-printed artificial bone composite scaffolds.

[0020] Furthermore, the preparation of the nitric oxide-releasing 3D printed artificial bone composite scaffold adopts the following steps:

[0021] (1) Using a 3D bioprinter to print a mixed 3D bioprinting material of polylactic acid, calcium carbonate, and hydroxyapatite, the material was optimized and directly and accurately printed into 3D printed porous cubic material scaffolds with different pore contents, and the scaffolds were solidified by hydrothermal reaction at the same time;

[0022] (2) The injectable hydrogel was embedded in the 3D printed artificial bone composite scaffolds with different pores prepared in step (1), and nitric oxide-releasing 3D printed artificial bone composite scaffolds with different nitric oxide concentrations were successfully obtained.

[0023] Furthermore, in step (1), the pore content of the 3D printed porous cubic material scaffold is 300-1000um.

[0024] Beneficial effects:

[0025] The nitric oxide injectable hydrogel provided by the present invention is added with D-(+)-glucono δ-lactone and sodium alginate, which can achieve a high loading amount of nitric oxide and can automatically and slowly release nitric oxide, thereby solving the problems of low nitric oxide loading amount and serious burst release phenomenon of existing carrier materials, and can achieve long-term sustained release of nitric oxide in the human body. The preparation method of the nitric oxide injectable hydrogel provided by the present invention has mild conditions, and has the advantages of simple process production flow, convenient operation and no use of toxic and harmful solvents. The nitric oxide injectable hydrogel provided by the present invention is widely used in biomedical engineering, has good research and development utilization prospects, and can be applied to medical implants. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0027] Figure 1 It is a comparison chart of FTIR spectra of pure SNAP, Alg-GDL, Alg-GDL-10, Alg-GDL-20 and Alg-GDL-30 prepared in Examples 1-3.

[0028] Figure 2 In the figure, A is the SEM image of Alg-GDL without SNAP, B is the SEM image of Alg-GDL-10 prepared in Example 1, C is the SEM image of Alg-GDL-20 prepared in Example 2, D is the SEM image of Alg-GDL-30 prepared in Example 3, E is the sulfur element distribution diagram of Alg-GDL-30 prepared in Example 3, and F is the nitrogen element distribution diagram of Alg-GDL-30 prepared in Example 3.

[0029] Figure 3 In FIG. 1 , A is a statistical graph of NO release data of Alg-GDL-10 prepared in Example 1, B is a statistical graph of NO release data of Alg-GDL-20 prepared in Example 2, and C is a statistical graph of NO release data of Alg-GDL-30 prepared in Example 3.

[0030] Figure 4 In the figure, A is the antibacterial results of Alg-GDL without SNAP, Alg-GDL-10, Alg-GDL-20, and Alg-GDL-30 prepared in Examples 1-3 against Gram-positive bacteria, and B is the antibacterial results of Alg-GDL without SNAP, Alg-GDL-10, Alg-GDL-20, and Alg-GDL-30 prepared in Examples 1-3 against Gram-negative bacteria.

[0031] Figure 5 1 is a comparison chart of the swelling properties of Alg-GDL without SNAP, Alg-GDL-10, Alg-GDL-20, and Alg-GDL-30 prepared in Examples 1-3.

[0032] Figure 6 1 is a graph comparing the degradation performance of Alg-GDL without SNAP, Alg-GDL-10, Alg-GDL-20 and Alg-GDL-30 prepared in Examples 1-3. DETAILED DESCRIPTION

[0033] The following will clearly and completely describe the technical solutions of the present invention in conjunction with the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0034] Example 1

[0035] A method for preparing an injectable nitric oxide hydrogel, comprising the following steps:

[0036] (1) 0.4 g of SA was dissolved in 10 mL of deionized water to prepare SA solution. The solution was magnetically stirred for 30 min until SA was completely dissolved. Then, 10.0 mg of SNAP was dispersed in 10 mL of SA solution under magnetic stirring to form a suspension.

[0037] (2) Under magnetic stirring, 0.36 g of CaCO3 was dispersed into 10 mL of the suspension generated in step (1) to generate a new suspension;

[0038] (3) 0.36 g of D-(+)-glucono delta-lactone and 0.142 g of NaH2PO4 were added to the suspension generated in step (2) and reacted for 10 minutes to obtain an injectable alginate hydrogel Alg-GDL-10.

[0039] Example 2

[0040] A method for preparing an injectable nitric oxide hydrogel, comprising the following steps:

[0041] (1) 0.4 g of SA was dissolved in 10 mL of deionized water to prepare SA solution. The solution was magnetically stirred for 30 min until SA was completely dissolved. Then, 20.0 mg of SNAP was dispersed in 10 mL of SA solution under magnetic stirring to form a suspension.

[0042] (2) Under magnetic stirring, 0.36 g of CaCO3 was dispersed into 10 mL of the suspension generated in step (1) to generate a new suspension;

[0043] (3) 0.36 g of D-(+)-glucono delta-lactone and 0.142 g of NaH2PO4 were added to the suspension generated in step (2) and reacted for 10 minutes to obtain an injectable alginate hydrogel Alg-GDL-20.

[0044] Example 3

[0045] A method for preparing an injectable nitric oxide hydrogel, comprising the following steps:

[0046] (1) 0.4 g of SA was dissolved in 10 mL of deionized water to prepare SA solution. The solution was magnetically stirred for 30 min until SA was completely dissolved. Then, 30.0 mg of SNAP was dispersed in 10 mL of SA solution under magnetic stirring to form a suspension.

[0047] (2) Under magnetic stirring, 0.36 g of CaCO3 was dispersed into 10 mL of the suspension generated in step (1) to generate a new suspension;

[0048] (3) 0.36 g of D-(+)-glucono delta-lactone and 0.142 g of NaH2PO4 were added to the suspension generated in step (2) and reacted for 10 minutes to obtain an injectable alginate hydrogel Alg-GDL-30.

[0049] Example 4

[0050] FTIR spectroscopy was performed on pure SNAP, D-(+)-gluconoδ-lactone injectable alginate hydrogel Alg-GDL without SNAP, and Alg-GDL-10, Alg-GDL-20, and Alg-GDL-30 prepared in Examples 1-3. The organic functional groups in the four groups of hydrogels were characterized by FT-IR spectroscopy. The results are as follows: Figure 1 As shown, Alg-GDL is at 3425 cm -1 and 1612cm -1 There are characteristic peaks at 1032cm, which can be assigned to the stretching vibration peaks of -OH and -COO- respectively. -1 The characteristic peak at 1415cm is the stretching vibration peak of COC. -1 The characteristic peak at 1327 cm-1 can be attributed to the ionic bond formed between sodium alginate and the carboxyl group of calcium ion. -1 and 1248cm -1 There are two characteristic peaks at , which can be attributed to the characteristic peaks of amide bands.

[0051] Example 5

[0052] The corresponding morphology of the hydrogel was observed by scanning electron microscopy. Figure 2 A shows that the surface of Alg-GDL is very rough with many protrusions, which may be due to the structure generated by the ionic cross-linking of the hydrogel. Figure 2 BD showed that Alg-GDL-10, Alg-GDL-20 and Alg-GDL-30 also had a rough surface with many protrusions, indicating that there was no significant morphological difference between Alg-GDL-10, Alg-GDL-20 and Alg-GDL-30 and Alg-GDL. Figure 2As shown in Figures BD, Alg-GDL-10, Alg-GDL-20, and Alg-GDL-30 locally exhibit very compact morphologies. This is likely due to the use of low-molecular-weight sodium alginate in hydrogel synthesis, which rapidly leads to dense crosslinking in the presence of excess calcium ions during the initial crosslinking phase. The results indicate that the presence of SNAP does not affect the morphology of the hydrogels, likely due to its incorporation into the hydrogels via a loading mechanism.

[0053] Example 6

[0054] The distribution of sulfur and nitrogen elements in the freeze-dried hydrogel of the Alg-GDL-30 sample prepared in Example 3 was detected. The results are as follows: Figure 2 As shown in Figures EF, compared with Alg-GDL, sulfur and nitrogen were detected in Alg-GDL-30, and the distribution of these two elements in the hydrogel was uniform. These results indicate that SNAP can be successfully loaded into the hydrogel and evenly distributed.

[0055] Example 7

[0056] The ability of Alg-GDL-10, Alg-GDL-20 and Alg-GDL-30 prepared in Examples 1-3 to release nitric oxide was tested. Figure 3 As shown. Figure 3 A shows that the total nitric oxide release time of Alg-GDL-10 reaches 34 hours, and the higher release rate occurs in the first 2 hours. This may be due to the rapid decomposition of SNAP on the surface after the injected hydrogel is soaked and dissolved in PBS. In the first 20 hours, the concentration is maintained above 0.01ppb / mg for slow release. Thereafter, the nitric oxide concentration is slowly released at a concentration below 0.001ppb / mg for 14 hours. Figure 3 As shown in Figure B, the total release time of Alg-GDL-20 reaches 47 hours. The concentration of nitric oxide is maintained at above 0.02 ppb / mg in the first 12 hours. The release rate slowly decreases after 12 hours. Compared with Alg-GDL-10, the concentration of nitric oxide released by Alg-GDL-20 is significantly increased. Figure 3As shown in Figure 3, the total nitric oxide release time of Alg-GDL-30 is 36 hours, with a slowly decreasing trend. During the first 20 hours, the nitric oxide release concentration is above 0.02 ppb / mg and decreases slowly, reaching a more pronounced peak at 21 hours. This is likely due to the transient and rapid decomposition of SNAP caused by the addition of PBS solution. Compared with Alg-GDL-10 and Alg-GDL-20, the overall trend of the nitric oxide release curve of Alg-GDL-30 is similar to that of the former two. Integrating the curves revealed that the total amount and concentration of nitric oxide released increased with increasing SNAP concentration. These results indicate that the nitric oxide release time of the three hydrogels, Alg-GDL-10, Alg-GDL-20, and Alg-GDL-30, is greater than 24 hours, and the amount of nitric oxide released and the instantaneous release rate are positively correlated with the SNAP concentration.

[0057] Example 8

[0058] The antibacterial activity of Alg-GDL, Alg-GDL-10, Alg-GDL-20, and Alg-GDL-30 prepared in Examples 1-3 above, against Gram-positive and Gram-negative bacteria was tested. Dried samples of Alg-GDL, Alg-GDL-10, Alg-GDL-20, and Alg-GDL-30 were tested for antibacterial activity for 24 hours. The samples were diluted and plated using the ten-fold dilution method, and the antibacterial performance was evaluated by counting the number of bacterial colonies. Figure 4 Figure A shows the antibacterial results of Alg-GDL, Alg-GDL-10, Alg-GDL-20, and Alg-GDL-30 against Gram-positive bacteria. Compared with Alg-GDL, the bacterial count of Alg-GDL-10 was reduced by 1.1 orders of magnitude, and the bacterial counts of Alg-GDL-20 and Alg-GDL-30 were reduced by 1.2 and 1.3 orders of magnitude, respectively. Alg-GDL-30 achieved the best antibacterial rate of 95%. Figure 4Figure B shows the antibacterial results of Alg-GDL, Alg-GDL-10, Alg-GDL-20, and Alg-GDL-30 against Gram-negative bacteria. Compared to Alg-GDL, the bacterial count in Alg-GDL-10 was reduced by 1.0 orders of magnitude, and the bacterial counts in Alg-GDL-20 and Alg-GDL-30 were reduced by 1.2 and 1.3 orders of magnitude, respectively. Alg-GDL-30 exhibited the highest antibacterial activity, reaching an antibacterial rate of 95%. The results indicate that Alg-GDL-10, Alg-GDL-20, and Alg-GDL-30 exhibited excellent antibacterial activity against both types of bacteria. Furthermore, the antibacterial activity of Alg-GDL-10, Alg-GDL-20, and Alg-GDL-30 demonstrates that the antibacterial activity of the nitric oxide injectable hydrogel provided herein gradually increases with increasing SNAP concentration.

[0059] Example 9

[0060] The swelling properties of Alg-GDL, Alg-GDL-10, Alg-GDL-20 and Alg-GDL-30 prepared in Examples 1-3 were tested by gravimetric method. Figure 5As shown, Alg-GDL, Alg-GDL-10, Alg-GDL-20, and Alg-GDL-30 gradually reached swelling equilibrium within three days. The swelling ratio of Alg-GDL was 41.3%. The mass of Alg-GDL increased rapidly within the first 12 hours and maintained a relatively stable growth rate over the next two days. After the third day, the mass of Alg-GDL slowly increased and tended to reach equilibrium. The swelling ratio of Alg-GDL-10 was 36.5%. Compared with Alg-GDL, the mass increase rate in the first 6 hours and the second day was smaller, but the swelling curve trends were similar. The swelling ratio of Alg-GDL-20 reached 34.9%, with the highest mass growth rate observed on the first day. Compared with Alg-GDL, the growth rate after one day was smaller. The swelling rate of Alg-GDL-30 was 34.0%. Compared with Alg-GDL, Alg-GDL-10, and Alg-GDL-20, Alg-GDL-30 always had the lowest mass growth rate and achieved the lowest swelling rate after reaching equilibrium. The results show that the swelling rate of the nitric oxide injectable hydrogel provided by the present invention decreases slightly with increasing SNAP concentration, among which Alg-GDL has the highest swelling rate of 41.3%. This may be due to the hydrophobicity of SNAP and the water absorption of sodium alginate, which leads to the reduction of the swelling performance of the SNAP-loaded hydrogel. In addition, since the SNAP concentration in Alg-GDL-10, Alg-GDL-20, and Alg-GDL-30 is very low, the swelling performance of the hydrogel is mainly determined by the hydrogel matrix. Therefore, the effect of SNAP loading on the swelling rate of the hydrogel is not significant.

[0061] Example 10

[0062] The degradation performance was evaluated by statistically analyzing the mass changes of Alg-GDL, Alg-GDL-10, Alg-GDL-20 and Alg-GDL-30 prepared in Examples 1-3 under physiological conditions within two weeks. Figure 6As shown, after two weeks, the remaining mass of Alg-GDL was 108.5%, and degradation began at a moderate rate on the fourth day. Alg-GDL-10, with a remaining mass of 91.1%, exhibited a similar overall degradation trend, but exhibited a faster degradation rate compared to the Alg-GDL hydrogel. The remaining masses of Alg-GDL-20 and Alg-GDL-30 hydrogels were 63.4% and 52.2%, respectively. Compared to the Alg-GDL hydrogel, degradation rates were faster starting on the fourth day, with the degradation rate showing a trend of initially rapid and then slowing. The mass of the Alg-GDL-30 hydrogel decreased sharply from the fourth to the fifth day. The mass of the Alg-GDL-20 hydrogel decreased sharply from the fifth to the tenth day. We speculate that the nitric oxide released by SNAP degradation may have led to the formation of pores within the hydrogel, allowing PBS to enter the hydrogel and accelerate degradation. Furthermore, as degradation progressed, the binding force weakened. The hydrogel weight remained above 100% on the fourth day, due to swelling behavior. By comparing the degradation properties of Alg-GDL, Alg-GDL-10, Alg-GDL-20 and Alg-GDL-30, the present invention believes that the presence of SNAP will accelerate the degradation of the hydrogel.

[0063] Example 11

[0064] The nitric oxide injectable hydrogels Alg-GDL-10, Alg-GDL-20, and Alg-GDL-30 prepared in Examples 1-3 were used to prepare nitric oxide-releasing 3D printed artificial bone composite scaffolds. The specific steps are as follows:

[0065] (1) Using a 3D bioprinter to print a mixed 3D bioprinting material of polylactic acid, calcium carbonate, and hydroxyapatite for optimization, directly and accurately print 3D printed porous cubic material scaffolds with different pore contents (pores of 300-1000 μm), and simultaneously perform hydrothermal reaction to solidify the scaffolds;

[0066] (2) The nitric oxide injectable hydrogels Alg-GDL-10, Alg-GDL-20, and Alg-GDL-30 prepared in Examples 1-3 were respectively embedded in 3D-printed artificial bone composite scaffolds with different porosities, and nitric oxide-releasing 3D-printed artificial bone composite scaffolds with different nitric oxide concentrations were successfully obtained.

Claims

1. A nitric oxide injectable hydrogel, characterized in that: The nitric oxide injectable hydrogel comprises a sodium alginate system, D-(+)-glucono-delta-lactone and sodium dihydrogen phosphate; the volume mass ratio of the sodium alginate system, D-(+)-glucono-delta-lactone and sodium dihydrogen phosphate is 10 mL: 0.36 g: 0.142 g; The sodium alginate system consists of sodium alginate, deionized water, a nitric oxide donor and calcium carbonate; The preparation method of the nitric oxide injectable hydrogel is as follows: (1) Sodium alginate is dissolved in deionized water to prepare a sodium alginate solution, and magnetic stirring is performed until the sodium alginate is completely dissolved. Under magnetic stirring, the nitric oxide donor is dispersed in the sodium alginate solution to form a suspension; (2) Dispersing calcium carbonate into the suspension generated in step (1) under magnetic stirring to generate a sodium alginate system; (3) D-(+)-glucono delta-lactone and sodium dihydrogen phosphate are added to the sodium alginate system generated in step (2) in sequence, and the nitric oxide injectable hydrogel is obtained after reacting for 8-12 minutes.

2. The hydrogel according to claim 1, wherein The mass volume ratio of the sodium alginate, deionized water, nitric oxide donor and calcium carbonate is 0.4 g:10 mL:0.01-0.03 g:0.36 g.

3. The hydrogel according to claim 2, characterized in that The nitric oxide donor is SNAP or GSNO.

4. A method for preparing the hydrogel according to any one of claims 1 to 3, characterized in that: The preparation method adopts the following steps: (1) Sodium alginate is dissolved in deionized water to prepare a sodium alginate solution, and magnetic stirring is performed until the sodium alginate is completely dissolved. Under magnetic stirring, the nitric oxide donor is dispersed in the sodium alginate solution to form a suspension; (2) Dispersing calcium carbonate into the suspension generated in step (1) under magnetic stirring to generate a sodium alginate system; (3) D-(+)-glucono delta-lactone and sodium dihydrogen phosphate are added to the sodium alginate system generated in step (2) in sequence, and the mixture is reacted for 8 to 12 minutes to obtain the nitric oxide injectable hydrogel.

5. Use of the injectable hydrogel according to any one of claims 1 to 3, characterized in that: The application is to use the hydrogel to prepare a nitric oxide-releasing artificial bone scaffold.

6. The use according to claim 5, characterized in that The nitric oxide-releasing artificial bone scaffold is 3D printed.

7. The use according to claim 6, characterized in that The preparation method of the nitric oxide-releasing artificial bone scaffold is as follows: (1) Polylactic acid, calcium carbonate, and hydroxyapatite are mixed to 3D print a porous cubic material scaffold, and the scaffold is solidified by hydrothermal reaction; (2) The injectable hydrogel is embedded in the porous cubic material scaffold prepared in step (1) to obtain a nitric oxide-releasing 3D printed artificial bone scaffold.

Images