Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions of the embodiments of the present invention will be clearly and completely described below. 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.
The embodiment of the invention provides a preparation method of a periodontal local delivery preparation, please refer to fig. 1, which comprises the following steps:
s1 Synthesis of PD Polymer
Carrying out esterification reaction on polyvinyl alcohol and 3, 4-dihydroxyphenylalanine, and grafting the 3, 4-dihydroxyphenylalanine on a polyvinyl alcohol long chain to obtain the PD polymer.
Specifically, the rich reducing functional groups (catechol group and amino group) in 3, 4-Dihydroxyphenylalanine (DOPA) enable the compound to show excellent performance in the aspect of scavenging ROS, and can also show synergistic antioxidant activity and photo-thermal responsiveness after undergoing a chelation reaction with metal ions.
In some embodiments, the molar ratio of polyvinyl alcohol to 3, 4-dihydroxyphenylalanine is 4-8: 1; preferably 5-7:1, and can effectively eliminate excessive ROS caused by periodontitis by further improving the continuous antibacterial capacity of the product by controlling the molar ratio of the polyvinyl alcohol to the 3, 4-dihydroxyphenylalanine. Specifically, the molar ratio of polyvinyl alcohol to 3, 4-dihydroxyphenylalanine may be 4:1, 5:1, 6:1, 7:1, 8:1, or the like, or may be any value between the above adjacent ratio values.
In some embodiments, the molecular weight of the polyvinyl alcohol is 85-124kDa, the molecular weight of the polyvinyl alcohol is preferably controlled within the above range, and the molecular weight is too large and too small, which is not favorable for improving the antibacterial ability of the product.
Further, the preparation process of the PD polymer comprises the following steps: dissolving polyvinyl alcohol, and reacting with 3, 4-dihydroxyphenylalanine in the presence of a catalyst, wherein the reaction temperature is controlled to be 75-85 ℃, and the reaction time is 12-15 h. The reaction temperature and time are further controlled to ensure that the polyvinyl alcohol and the 3, 4-dihydroxyphenylalanine fully react, and the grafting rate of the 3, 4-dihydroxyphenylalanine is improved. Specifically, the reaction temperature may be 75 ℃, 76 ℃, 77 ℃, 78 ℃, 79 ℃, 80 ℃, 81 ℃, 82 ℃, 83 ℃, 84 ℃, 85 ℃ or the like, or may be any value between the above adjacent temperature values; the reaction time may be 12h, 13h, 14h, 15h, or the like, or may be any value between the above adjacent time values.
In some embodiments, an inert gas, such as nitrogen, is introduced during the reaction process, and may protect the catalyst from oxidation during the reaction process.
Specifically, the solvent used for dissolving the polyvinyl alcohol may be dimethyl sulfoxide (DMSO), or may be other organic solvents, and is not limited herein.
In some embodiments, the catalyst is NaHSO4·H2O; the mass ratio of the catalyst to the polyvinyl alcohol is 2-4: 1. Specifically, the mass ratio of the catalyst to the polyvinyl alcohol may be 2:1, 3:1, 4:1, or the like.
In some embodiments, after the reaction of the polyvinyl alcohol and the 3, 4-dihydroxyphenylalanine is completed, the product is prepared in a gel state to remove unreacted raw materials while facilitating the preparation of the product in a gel state.
The preparation process of the gel is not limited, and a common method in the prior art can be adopted. In some embodiments, the solution obtained after the reaction of polyvinyl alcohol and 3, 4-dihydroxyphenylalanine is dialyzed for 2 to 4 days, and then rotary-evaporated and lyophilized to obtain a product in a gel state.
S2、MnO2Synthesis of nanoplatelets
MnO2The nano sheet can be prepared from a commercially available material or by adopting the synthesis method provided by the embodiment of the invention, so that MnO is generated2The nano-sheet is preferably in the form of solution, which is beneficial to the subsequent reaction with phenolic hydroxyl.
In some embodiments, the process for preparing the manganese dioxide solution comprises: mixing the aqueous solution of manganese salt with the solution of tetramethyl ammonium pentahydrateCentrifuging for 10-15h after reaction, washing the obtained solid intermediate product, drying, dissolving in water, and centrifuging to remove precipitate to obtain MnO2A solution; wherein the tetramethylammonium pentahydrate solution is prepared by dissolving tetramethylammonium pentahydrate in hydrogen peroxide.
The manganese ions are oxidized to manganese dioxide by the double oxidation of the tetramethylammonium pentahydrate solution and hydrogen peroxide.
In some embodiments, the reaction process is to add the tetramethylammonium pentahydrate solution into the manganese salt aqueous solution, and after stirring for 0.5-3min at the rotation speed of 1200-1500rpm, continue stirring at 800rpm for 10-14h at 600-800 rpm.
In some embodiments, the process for preparing the aqueous solution of manganese salt comprises: dissolving 0.755 to 0.805g of manganese salt in 20 to 30mL of water; preferably, the manganese salt is MnCl2. In other embodiments, the manganese salt may also be a nitrate salt.
In some embodiments, the process for preparing the tetramethylammonium pentahydrate solution comprises: 4.3-4.5g of tetramethyl ammonium pentahydrate is dissolved in 40-50mL of hydrogen peroxide with the mass fraction of 2-4%.
S3 synthesis of PDMO hydrogel
And then the PD polymer is reacted with the manganese dioxide nanosheet, and phenolic hydroxyl groups on the PD polymer are utilized to chelate metal manganese ions, so that the manganese dioxide nanosheet has enzyme-like activity and endows the material with good ROS scavenging activity.
It is necessary to supplement that the manganese dioxide nanosheets have good photothermal effect, but the manganese dioxide nanosheets are not uniformly distributed and are difficult to stay at the action part for a long time to play the function, which greatly limits the application of the manganese dioxide nanosheets. In the application, the hydrogel can protect substances encapsulated in the hydrogel, prolong the retention time of the encapsulated substances and continuously release the encapsulated substances at the action site. Thus, incorporation of manganese dioxide nanoplates into a suitable injectable hydrogel may achieve better antioxidant activity and antimicrobial effect.
In some embodiments, the process of chelating a manganese metal ion with a phenolic hydroxyl group on a PD polymer comprises: and (3) reacting the formed solution of the PD polymer with a manganese dioxide solution for 0.5-1h to crosslink the PD polymer with manganese ions into gel.
In the practical operation process, the freeze-dried PD polymer in the gel state is heated and dissolved in deionized water, so that the concentration of the formed solution of the PD polymer is 150-250mg/mL (such as 150mg/mL, 160mg/mL, 170mg/mL, 180mg/mL, 190mg/mL, 200mg/mL, 210mg/mL, 220mg/mL, 230mg/mL, 240mg/mL and 250mg/mL) of aqueous solution; the mass ratio of PD polymer to manganese dioxide is controlled to be 100:2-6 (such as 100:2, 100:3, 100:4, 100:5 and 100:6), and the quality control of manganese dioxide requires testing MnO2The content of manganese dioxide in the solution is calculated to obtain the required MnO2Volume of solution. Specifically, MnO2The content of manganese dioxide in the solution is determined by adding MnO2The solution was evaporated to dryness and weighed.
The embodiment of the invention also provides a periodontal local delivery preparation, which is prepared by the preparation method and has metal manganese ions chelated on the PD polymer.
It is noted that the periodontal topical delivery formulations provided in the examples of the present invention are comparable to existing common commercial forms of topical treatment for periodontitis, such as minocycline hydrochloride ointmentThe periodontal local delivery preparation constructed by the research can be firmly adhered to periodontal tissues for a long time under the actions of continuous secretion, flushing, swallowing and the like of saliva in the unique environment of the oral cavity, so that the multiple effects of ROS resistance, inflammation resistance, bacteria resistance and the like are further exerted, the biological safety is good, and the clinical application prospect is very good.
In some embodiments, the periodontal local delivery formulation is in the form of a hydrogel that protects the substance encapsulated therein, prolongs the retention time of the encapsulated substance, and provides sustained release at the site of action.
The embodiment of the invention also provides application of the periodontal local delivery preparation in preparation of a medicament for treating periodontitis, and the periodontal local delivery preparation can be compounded with other raw materials to form a medicament, which is not limited herein.
The features and properties of the present invention are described in further detail below with reference to examples.
Example 1
The present embodiment provides a method for preparing a periodontal local delivery formulation, comprising the steps of:
(1) synthesis of PD polymer: dissolving 50mmol of PVA with molecular weight of 85-124kDa in 110mL DMSO solution at 100 deg.C, adding 12g NaHSO4·H2Catalyzing by O, when the temperature is reduced to 80 ℃, adding 8mmol of 3, 4-Dihydroxyphenylalanine (DOPA) in N2Reacting for 13 hours under the protection of (1), dialyzing in a dialysis bag for 3 days after the temperature is reduced to room temperature after the reaction is finished, removing excessive water by a rotary evaporator, and freeze-drying in a freeze-drying machine for 3 days.
(2)MnO2Synthesis of nanosheets: 0.755g of MnCl2Dissolved in 20mL of deionized water, 4.3g of tetramethylammonium pentahydrate (TMAOH) was dissolved in 40mL of 3% H2O2Adding TMAOH solution into MnCl2The solution is rapidly stirred for 1min at the rotating speed of 1300rpm, then is continuously stirred for 12h at 700rpm, and is washed three times by ethanol and deionized water after centrifugation. Freeze-drying the black precipitate material, dissolving the freeze-dried material in deionized water with the concentration of 10mg/mL, performing ultrasonic treatment for 10h, centrifuging the solution at 10000g for 10min, and removing the precipitate to obtain MnO2The solution was taken out of 1mL of MnO2The solution is weighed and quantified after being fully dried to obtain MnO2The concentration of (3) is 16 mg/ml.
(3) Synthesis of PDMO hydrogel: dissolving lyophilized PD polymer in deionized water under heating to give a solution with a concentration of 200mg/mL, adding MnO to 0.25mL of PD solution2Solution, control of MnO2The amount of nanosheet added was 1mg (PD polymer and MnO)2The mass ratio of the nanosheets is 100:2), and the two are fully stirred and reacted for 1h at normal temperature to obtain PDMO hydrogel recorded as PDMO 1.
Example 2
The only difference from example 1 is: controlling MnO2The addition amount of the nano sheet is 2mg, and the PD polymer and MnO are2The mass ratio of the nanosheets is 100:4, and the obtained hydrogel is marked as PDMO 2.
Example 3
The only difference from example 1 is: controlling MnO2The addition amount of the nano-sheet is 3mg, and the PD polymer and MnO are2The mass ratio of the nanosheets is 100:6, and the obtained hydrogel is marked as PDMO 3.
Example 4
The present embodiment provides a method for preparing a periodontal local delivery formulation, comprising the steps of:
(1) synthesis of PD polymer: 45mmol of PVA with molecular weight of 146-186kDa is dissolved in 100mL of DMSO solution at 100 ℃ and after complete dissolution, 5g of NaHSO is added4·H2Catalyzing by O, when the temperature is reduced to 75 ℃, adding 6mmol of 3, 4-Dihydroxyphenylalanine (DOPA) in N2Reacting for 12h under the protection of (1), after the reaction is finished, dialyzing in a dialysis bag for 2 days after the temperature is reduced to room temperature, removing excessive water by a rotary evaporator, and freeze-drying in a freeze-drying machine for 2 days.
(2)MnO2Synthesis of nanosheets: 0.755g of MnCl2Dissolved in 20mL of deionized water, 4.3g of tetramethylammonium pentahydrate (TMAOH) was dissolved in 50mL of 3% H2O2Adding TMAOH solution into MnCl2The solution is rapidly stirred for 1min at the rotating speed of 1200rpm, then is continuously stirred for 12h at the rotating speed of 600rpm, and is washed by ethanol and deionized water for three times after centrifugation. Freeze-drying the black precipitate material, dissolving the freeze-dried material in deionized water with the concentration of 10mg/mL, performing ultrasonic treatment for 10h, finally centrifuging the solution for 10min at 8800g, and removing the precipitate to obtain MnO2And (3) solution.
(3) Synthesis of PDMO hydrogel: specific procedure with reference to example 1, the reaction time was changed to 0.5h only.
Example 5
The present embodiment provides a method for preparing a periodontal local delivery formulation, comprising the steps of:
(1) synthesis of PD polymer: dissolving 55mmol of PVA with molecular weight of 89-98kDa in 120mL of DMSO solution at 100 ℃, and adding 8g of NaHSO after complete dissolution4·H2Catalyzing with O, cooling to 85 deg.C, adding 11mmol of 3, 4-Dihydroxyphenylalanine (DOPA) in N2Under the protection of (1), reacting for 15 hours, after the reaction is finished,after the temperature is reduced to room temperature, dialyzing in a dialysis bag for 4 days, removing excessive water by a rotary evaporator, and freeze-drying in a freeze dryer for 3 days.
(2)MnO2Synthesis of nanosheets: 0.805g of MnCl2Dissolved in 30mL of deionized water, 4.5g of tetramethylammonium pentahydrate (TMAOH) was dissolved in 45mL of 3% H2O2Adding TMAOH solution into MnCl2In the solution, after rapidly stirring at 1500rpm for 1min, continuously stirring at 800rpm for 12h, centrifuging, and washing with ethanol and deionized water for three times respectively. Freeze-drying the black precipitate material, dissolving the freeze-dried material in deionized water with the concentration of 10mg/mL, performing ultrasonic treatment for 10h, centrifuging the solution at 10000g for 10min, and removing the precipitate to obtain MnO2And (3) solution.
(3) Synthesis of PDMO hydrogel: the specific procedure was as in example 1, except that the reaction time was changed to 1.0 h.
Comparative example 1
The only difference from example 1 is: MnO of2The nano-sheets are replaced by equal amount of CeO2And (3) nanoparticles.
Comparative example 2
PDMO hydrogel with different proportions and minocycline hydrochloride ointment which is a currently common and commercially available local treatment dosage form for periodontitisComparing them with each other to compare their anti-inflammatory, antibacterial and periodontal treatment effects.
Test example 1
The PD and PDMO prepared in the examples were subjected to material characterization.
(1) MnO prepared in test example2Scanning electron microscopy of the nanoplate, as shown in FIG. 2, shows MnO2The nano-sheet presents a uniform nano-scale sheet structure, and the diameter is about 200-300 nm.
(2) Scanning electron micrographs of the PD and PDMO1 hydrogels prepared in example 1 were tested as shown in fig. 3.
From FIG. 3, it can be seen that both PD and PDMO1 hydrogels are loose porous structures, and MnO can be seen2The nano-sheets are uniformAttached to the PD.
(3) The Mapping profile of the PDMO1 hydrogel prepared in example 1 was tested as shown in fig. 4.
As can be seen from FIG. 4, Mn is uniformly dispersed in the PDMO hydrogel, demonstrating MnO2The nano-sheets are uniformly dispersed in the PDMO hydrogel.
(4) The energy spectrum of the PD prepared in example 1 and the PDMO1, PDMO2, and PDMO3 hydrogels prepared in examples 1-3 were tested and the weight percentages of the different elements are shown in fig. 5. In fig. 5, a represents the test results for PD, B represents the test results for PDMO1 hydrogel, C represents the test results for PDMO2 hydrogel, and D represents the test results for PDMO3 hydrogel.
As can be seen from FIG. 5, all three PDMO hydrogels contained Mn, demonstrating MnO2The nano sheets are all present in the PDMO hydrogel, and the content of the nano sheets is gradually increased.
(5) The PDMO1 hydrogel prepared in example 1 was tested for XPS diffraction pattern and the results are shown in fig. 6.
As can be seen from FIG. 6, MnO2Mn ions in the nano-sheets are represented by the coexistence of three-valence and four-valence, and the proportion of Mn ions is Mn3+：Mn4+84%: 16 percent, and the results prove that the Mn ions have good electron transfer capability and good oxidation resistance.
Test example 2
The materials prepared in the examples were tested for their antioxidant properties.
(1) Placing 1, 1-diphenyl-2-trinitrophenylhydrazine (DPPH), absolute ethanol and diluted material into an EP tube, observing the color change, and mixing with the commonly used commercial periodontal preparation PileoAnd (6) carrying out comparison. The results are shown in FIG. 7, in which A represents the color change of the DPPH solution after adding different materials, and B represents the OD value (. multidot.P) of the color of the DPPH solution after adding different materials, which was analyzed by a microplate reader<0.0001)。
As can be seen from A in FIG. 7, the colors of the PD and PDMO groups change, and the color of the PDMO group changes more than that of the PD groupIs obvious. In FIG. 7, B is a quantitative analysis of each group demonstrating that PDMO hydrogel has a significantly increased ability to scavenge ROS and is superior to the commercial periodontal formulation, piolol
(2) Hydroxyl radical (OH) scavenging of materials was verified using 3,3',5,5' -Tetramethylbenzidine (TMB)-) Ability of (c): 0.02g of TMB was weighed out and dissolved in 10ml of absolute ethanol, and 0.002g of FeSO was weighed out4Dissolving in 10ml deionized water, diluting 3% hydrogen peroxide 1Mm, diluting the material to 20mg/ml, and adding H into EP tube2O2、FeSO4And (4) observing the color change of the solution and TMB, and acquiring an OD value by using a microplate reader. As a result, as shown in FIG. 8, A in FIG. 8 shows the color change of the TMB solution after the addition of the different materials, and B in FIG. 8 shows the OD value of the color of the TMB solution after the addition of the different materials was analyzed by a microplate reader.
As can be seen from a in fig. 8, the PDMO group changed more significantly than the PD group, and the DPPH solutions of PDMO1, PDMO2, and PDMO3 became lighter in color in sequence. In FIG. 8, B is a quantitative analysis of each group, demonstrating that PDMO hydrogel scavenges OH-Has an ability significantly increased compared with PD, and MnO is added2The amount is increased and is superior to the commercial periodontal preparation
(3) Scavenging superoxide anions (O) using Nitrotetrazolium Blue (NBT) validation materials2-) The results are shown in FIG. 9. In FIG. 9, A shows the color change of the NBT solution after adding different materials, and B shows the OD value (. about.P.) of the color of the NBT solution after adding different materials, which was analyzed by a microplate reader<0.01，****P<0.0001)。
As can be seen from FIG. 9, the PD solution has a certain scavenging O2-Ability of adding MnO2O of post-PDMO hydrogel2-The scavenging capacity is gradually increased.
(4) To verify the antioxidant stress effect of the material on cells, Raw264.7 cells were treated at 1X 105After plating, the material was stimulated with LPS to stimulate cellsAfter 6h of co-incubation, ROS scavenging effect was observed with DCFH-DA fluorescent probe, and the results are shown in FIG. 10.
As shown in FIG. 10, the addition of LirioboAnd the oxidation state of the cell can be improved to a certain extent after the PD hydrogel is added, and the oxidative stress state of the cell can be further improved after the PDMO hydrogel is added, so that the PDMO hydrogel has good oxidation resistance.
(5) Verifying the anti-oxidative stress effect of the material on cells: cells Raw264.7 at 1X 105After plating, the material was co-cultured with LPS-stimulated cells, and then further treated with Ru (dpp)3Cl2The fluorescent probe was used to observe the ROS scavenging effect, and the results are shown in FIG. 11.
As can be seen from FIG. 11, the addition of the derivative IvoraxAnd the oxidation state of the cell can be improved to a certain extent after the PD hydrogel is added, the oxidative stress state of the cell can be further improved after the PDMO hydrogel is added, and the PDMO hydrogel is further proved to have good oxidation resistance.
Test example 3
The near-infrared thermal responsiveness of the PDMO hydrogel prepared by the embodiment of the invention is tested.
The test method comprises the following steps: detecting with near infrared exciter (wavelength is 808nm), placing the materials into 24-well plate, grouping, respectively irradiating under near infrared light for 10min, taking a picture with near infrared camera every minute, and recording, wherein FIG. 12 shows that hydrogel of different groups is at 1.4W/cm2The thermal map change per minute within 10min of 808nm near infrared light irradiation. Fig. 13 is a quantitative analysis of the temperature change at each time point, and fig. 14 is a graph of the temperature change of different groups of hydrogels repeated for 5 cycles, which shows that the PDMO hydrogel has good near infrared thermal response performance.
Test example 4
The antibacterial effect of the PDMO hydrogel prepared by the embodiment of the invention is tested.
(1) After incubating the hydrogels of different groups with Staphylococcus Aureus (SA) and Escherichia Coli (EC), respectively, for 8 hours, the mixed solution of the material and bacteria was then plated and Colony Forming Units (CFU) were observed, with the results shown in fig. 15 and 16.
As can be seen from fig. 15 and 16, the CFU of the PDMO hydrogels in the three groups were significantly less than the control, PVA, PD and commercial peizo groups, while the PD group CFU was less than the control, PVA and peizo groups. The experimental results prove that the PD has certain antibacterial capacity, and the PDMO hydrogel has more excellent antibacterial performance.
(2) After co-culturing the different groups of hydrogels and Porphyromonas gingivalis (P.g) for 24 hours, the Amar blue assay was performed on the material and bacteria mixed solution, and the results are shown in FIG. 17.
As can be seen from FIG. 17, the proliferation amount of P.g in the three groups of PDMO hydrogel and the Pirex is obviously less than that in the control, PVA and PD groups, and the PDMO hydrogel is also proved to have excellent antibacterial performance.
Test example 5
The in vitro biocompatibility of the PDMO hydrogel prepared in the examples of the present invention was tested.
The biological safety performance of the hydrogels of different groups is evaluated, after the material and Raw264.7 cells are co-cultured for 1 day and 3 days, the cell proliferation condition is observed by using CCK8, as shown in figure 18, the results of 1 day and 3 days show no obvious cytotoxicity, and the PDMO hydrogel is proved to have good biocompatibility.
Test example 6
The PDMO hydrogel prepared according to the present invention was tested for in vivo biosafety and periodontitis treatment effect.
Male SD rats of 4-6 weeks were selected and after one week of acclimation feeding, a periodontitis model was established after the first molars of the left upper jaw were wound around the neck of the teeth with 0.2mm orthodontic wires and fixed, as shown in fig. 19. After 10 days of modeling, dosing was performed, once every three days, and near infrared irradiation was performed after dosing. Four weeks after administration, the material was taken, and blood from each rat was subjected to blood-based routine, blood biochemical detection and analysis to evaluate the in vivo biosafety of the PDMO hydrogel. As shown in fig. 20 and 21, the PDMO hydrogel has no significant blood toxicity, and no significant toxicity to major organs such as heart, liver, kidney, and the like, and the PDMO hydrogel is proved to have good biocompatibility.
Then, the materials are taken for alveolar bone CT scanning, three-dimensional reconstruction is carried out, the distance from the enamel cementum boundary to the crest of the alveolar ridge is compared, and the experimental result is shown in figure 22, so that the PDMO2 hydrogel has the best alveolar bone reconstruction capability.
Test example 7
The hydrogel materials prepared in example 1 and comparative example 1 were tested for their antioxidant properties. The color change was observed using DPPH, absolute ethanol and diluted material placed in an EP tube. The results are shown in FIG. 23, where the color change ratio of the PDMO1 hydrogel group is PD-CeO2The color change of the group is more obvious, and the DPPH clearance rate of the PDMO1 hydrogel group is higher than that of the PD-CeO hydrogel group2The higher group proves that the capability of PDMO hydrogel for scavenging ROS is better than that of PD-CeO2。
Test example 8
Test examples 1-3 and commercial periodontal topical formulationThe anti-inflammatory, antibacterial and periodontitis treatment effects were compared. As shown in FIG. 7, FIG. 8, FIG. 10 and FIG. 11, the oxidation resistance of all 3 PDMO hydrogels was superior to that of Mylar. As shown in FIG. 15 and FIG. 16, the 3 PDMO hydrogels showed superior antibacterial activity against Staphylococcus Aureus (SA) and Escherichia Coli (EC) than P. As shown in fig. 22, PDMO2 hydrogel has better alveolar bone reconstruction ability than mylar. The results prove that the PDMO hydrogel constructed by the invention has better anti-inflammatory, antibacterial and periodontitis treatment effects than common commercial periodontal preparations.
In summary, the invention provides a periodontal local delivery preparation, a preparation method and an application thereof, wherein polyvinyl alcohol (PVA) is used as a carrier, mussel adhesive protein 3, 4-Dihydroxyphenylalanine (DOPA) is grafted on the PVA, phenolic hydroxyl on the DOPA is used for chelating metal manganese ions, and the excellent wet adhesion performance of the DOPA and manganese dioxide are used for preparing the preparationThe pseudoenzyme activity of the nano-sheet constructs MnO with ROS (reactive oxygen species) integration responsiveness and NIR (near infrared) photothermal responsiveness2The nano-sheet mussel bionic composite material serving as a periodontal local delivery preparation has the following advantages:
(1) the injection has good injectability and molding capacity, is convenient to operate, and is suitable for periodontal defects of different shapes;
(2) the adhesive has good adhesion and can be firmly adhered to periodontal tissues to continuously and slowly release Mn ions;
(3) has high ROS scavenging activity and anti-inflammatory effect;
(4) has good near infrared thermal responsiveness and antibacterial effect;
(5) has good biological safety;
(6) has good periodontal treatment effect and alveolar bone reconstruction ability.
The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and various modifications and changes will occur to those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.