A near-infrared response magnesium-releasing antioxidant double-layer microneedle and a preparation method and application thereof

Abstract

The application provides a near-infrared response magnesium-releasing and antioxidant double-layer microneedle and a preparation method and application thereof. The double-layer microneedle comprises a needle tip layer and a backing layer, the needle tip layer contains MoS2@PDA@Mg 2+ The application discloses a composite particle, which is composed of molybdenum disulfide nanosheets, surface-coated polydopamine and coordination-loaded magnesium ions. The preparation method comprises the following steps: one-step reaction of molybdenum disulfide, dopamine and magnesium salt to obtain the composite particle, and then preparation of the composite particle into a needle tip layer precursor solution together with GelMA, PVA and the like, and two-step light cross-linking molding with a backing layer precursor solution. The double-layer microneedle can rapidly release magnesium ions under near-infrared irradiation, the release amount is 4.6 times that of a non-irradiation group, can significantly scavenge DPPH, ABTS and other free radicals, can relieve cell oxidative stress induced by lipopolysaccharide, and can effectively promote new bone formation and trabecular reconstruction in a rat tooth socket model. The application realizes the synergistic effect of light-controlled magnesium release and antioxidant, and is suitable for the fields of neural microenvironment reconstruction and bone regeneration.

Description

Technical Field

[0001] This application relates to the field of oral biomaterials and tissue repair technology, specifically to a near-infrared responsive magnesium-releasing antioxidant bilayer microneedle, its preparation method, and its application. Background Technology

[0002] Early restoration of extraction sockets is a crucial step affecting postoperative alveolar bone preservation and the success of subsequent implant treatment. Current research indicates that extraction socket restoration is not simply a process of filling bone defects, but a dynamic process jointly regulated by oxidative stress, inflammatory response, neural support, cell recruitment, and the biomechanical microenvironment. In the early postoperative period, local reactive oxygen species levels are significantly elevated, easily leading to impaired function of repair-related cells, inhibiting the recruitment and differentiation of osteogenic precursor cells, and thus hindering the initiation of bone formation. Simultaneously, local nerve ending damage caused by tooth extraction weakens the repair phenotype of Schwann cells and other neural support cells, further reducing the efficiency of neuro-bone synergistic repair.

[0003] To address the aforementioned issues, existing research has attempted to promote wound repair using strategies such as antioxidant materials, magnesium-loaded sustained-release systems, hydrogels, or microneedles. However, current technologies still have the following shortcomings: most systems only possess a single antioxidant or ion delivery function, failing to simultaneously meet the complex microenvironmental regulation needs of the extraction socket in its early stages; existing magnesium release systems are mostly based on continuous release modes of material diffusion or degradation, making it difficult to match the dynamic needs of different repair stages, easily leading to insufficient release in the early stages or excessive release in the later stages; ordinary hydrogels or membrane materials are prone to dislocation or dissolution under saliva rinsing and chewing disturbances, failing to achieve effective retention; existing microneedle systems are mainly for skin drug delivery, lacking suitable structural designs for irregular, moist oral wounds such as extraction sockets accompanied by bleeding and exudation.

[0004] Therefore, there is an urgent need to develop a dual-layer microneedle product that combines wet adhesion fixation, continuous antioxidant capacity, and near-infrared triggered magnesium release capacity to achieve precise intervention in the early postoperative microenvironment of tooth extraction sockets. Summary of the Invention

[0005] To address the technical problems of existing materials in tooth extraction socket restoration, such as poor fixation in the moist oral environment, insufficient regulation of the high reactive oxygen microenvironment postoperatively, uncontrollable magnesium ion release, and difficulty in simultaneously achieving nerve-bone synergistic repair, this invention provides a near-infrared responsive magnesium-releasing antioxidant bilayer microneedle, its preparation method, and its application. This bilayer microneedle consists of a wet-adhesive backing layer and a functional tip layer disposed thereon: the backing layer uses a gelatin methacryloyl / polyvinyl alcohol / polyacrylic acid (GelMA / PVA / PAA) composite system, which can stably adhere to the tooth extraction socket wound in the moist dynamic environment of the oral cavity, resisting saliva erosion and chewing disturbance; the tip layer uses a GelMA / PVA matrix material, internally loaded with MoS2@PDA@Mg. 2+The composite functional particles contain molybdenum disulfide, which continuously scavenge reactive oxygen species and generates a mild photothermal effect under near-infrared irradiation. Polydopamine acts as an interface layer, providing magnesium ion coordination sites, thereby achieving basal release in the absence of light and on-demand accelerated magnesium release triggered by near-infrared irradiation. This invention achieves proactive and precise intervention in the early postoperative microenvironment of tooth extraction sockets through the synergistic effect of wet adhesion fixation and photothermal-responsive magnesium release / antioxidant action, promoting nerve-bone synergistic repair and improving the quality and efficiency of bone regeneration.

[0006] In a first aspect, a method for preparing near-infrared responsive magnesium-releasing antioxidant bilayer microneedles includes the following steps: S1: Molybdenum disulfide, dopamine hydrochloride, and magnesium chloride are mixed and reacted in a buffer solution to obtain MoS2@PDA@Mg 2+ Composite particles; S2: Mix the matrix polymer material, photocrosslinking initiator and the composite particles to obtain the needle tip layer precursor solution; S3: Mix the backing material with the photocrosslinking initiator to obtain the backing precursor liquid; S4: Fill the microneedle mold with the needle tip layer precursor liquid and perform the first photocrosslinking to preliminarily shape the needle tip layer; then cover the needle tip layer with the backing layer precursor liquid and perform the second photocrosslinking to crosslink the backing layer and combine it with the needle tip layer. After demolding, the double-layer microneedle is obtained.

[0007] This invention selects molybdenum disulfide (MoS2) as the functional core because it possesses both reactive oxygen species scavenging capabilities and near-infrared photothermal effects, simultaneously meeting the dual requirements of early oxidative stress regulation in extraction sockets and external magnesium release response. Polydopamine (PDA) is coated onto the surface of molybdenum disulfide as an interface modification layer, which on the one hand improves the stability of the composite particles, and on the other hand, utilizes its abundant functional groups to provide magnesium ion coordination sites, achieving effective magnesium ion loading. The resulting MoS2@PDA@Mg 2+ The composite functional particles are a three-layer composite structure with molybdenum disulfide as the base, modified with polydopamine, and further loaded with magnesium ions.

[0008] Preferably, the mass ratio of dopamine hydrochloride to molybdenum disulfide is 2:1, the mass ratio of magnesium chloride to molybdenum disulfide is 5:1, the reaction temperature is 40°C, and the reaction time is 24 hours.

[0009] Preferably, the matrix polymer material in S2 is a composite system of gelatin methacryloyl (GelMA) and polyvinyl alcohol (PVA), wherein the mass-volume concentration of gelatin methacryloyl is 15% and the mass-volume concentration of polyvinyl alcohol is 5%; the photocrosslinking initiator is lithium phenyl-2,4,6-trimethylbenzoylphosphonate with a mass-volume concentration of 0.25%; the MoS2@PDA@Mg 2+The final concentration of the composite particles was 1 mg / mL. GelMA provided photocrosslinking molding capability and biocompatibility, while PVA enhanced the integrity and mechanical stability of the needle body, thereby ensuring the molding quality and local delivery function of the microneedle array.

[0010] Preferably, the backing layer material in S3 is a composite system of gelatin methacryloyl (GelMA), polyvinyl alcohol (PVA), and polyacrylic acid (PAA), wherein the mass-volume concentration of gelatin methacryloyl is 15%, the mass-volume concentration of polyvinyl alcohol is 5%, and the mass-volume concentration of polyacrylic acid is 2%; the photocrosslinking initiator is lithium phenyl-2,4,6-trimethylbenzoylphosphonate with a mass-volume concentration of 0.25%. GelMA and PVA together construct a support network with good strength and toughness, while PAA endows the material with interfacial adhesion ability in a humid environment, significantly improving the adhesion stability of the double-layer microneedles on the tooth extraction socket wound and effectively resisting dislocation caused by saliva erosion and chewing disturbance.

[0011] Preferably, the first photocrosslinking is performed by irradiating with a 405 nm light source for 30 seconds, and the second photocrosslinking is performed by irradiating with a 405 nm light source for 90 seconds.

[0012] Secondly, the present invention provides a near-infrared responsive magnesium-releasing antioxidant bilayer microneedle, comprising a backing layer and a tip layer bonded to the backing layer; the tip layer comprises a matrix polymer material, a photocrosslinking initiator, and a functional nanocomponent, wherein the functional nanocomponent is MoS2@PDA@Mg. 2+ .

[0013] Preferably, the backing layer is a wet adhesion support layer for attaching to the extraction socket wound in a moist oral environment. The backing layer is used to improve the adhesion stability of the material on the surface of the extraction socket wound and to reduce dislocation caused by saliva erosion and mechanical disturbance; the needle tip layer is a functional release layer, forming a microneedle array that can penetrate into the superficial tissue of the wound to establish local diffusion channels and deliver antioxidant and magnesium-releasing functional components.

[0014] Thirdly, this invention provides the application of near-infrared responsive magnesium-releasing antioxidant bilayer microneedles in the preparation of products for tooth extraction socket repair. The bilayer microneedles can be used alone as a wound covering and repair material for tooth extraction sockets, or they can be used in combination with other oral medical materials or instruments to create a series of tooth extraction socket repair products, including but not limited to: tooth extraction socket wound repair patches, alveolar bone regeneration guiding membranes, postoperative local microenvironment regulation patches, and oral tissue engineering scaffolds.

[0015] In summary, the present invention has at least one of the following beneficial technical effects: 1. This invention employs a double-layer integrated microneedle structure consisting of a wet-adhesive backing layer and a functional needle tip layer. The polyacrylic acid in the backing layer gives the material strong adhesion in the moist environment of the oral cavity, effectively resisting saliva erosion and chewing disturbance, thus solving the technical problems of easy dislocation and difficulty in fixation of existing tooth extraction socket restoration materials.

[0016] 2. The bilayer microneedles provided by this invention have MoS2@PDA@Mg loaded in the tip layer. 2+ The composite particles integrate reactive oxygen species scavenging and magnesium ion delivery. Molybdenum disulfide continuously exerts its antioxidant effect, while polydopamine provides coordination loading for magnesium ions, overcoming the limitations of existing technologies that are single-function and difficult to synergistically regulate.

[0017] 3. This invention utilizes the near-infrared photothermal effect of molybdenum disulfide to achieve dual-mode delivery of magnesium ions: "basic release without light exposure + near-infrared triggered accelerated release". The release rate can be adjusted as needed according to the dynamic requirements of different stages of tooth extraction socket repair, overcoming the defects of insufficient early release and excessive late release of magnesium in traditional passive magnesium release systems, which is beneficial to nerve-bone synergistic repair. Attached Figure Description

[0018] To more clearly illustrate the technical solutions of the embodiments of this application, the drawings used in the description of the embodiments of this application will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0019] Figure 1 This application illustrates the MoS2@PDA@Mg provided in an embodiment. 2+ Scanning electron microscope (SEM) morphology of the composite particles; Figure 2 The present application provides photographs and morphological diagrams of the double-layer microneedles according to embodiments of this application. Figure 2 Image A shows a physical picture of a double-layer microneedle patch. Figure 2 B is a magnified morphology image of the microneedle array; Figure 3 The diagram shows the near-infrared response magnesium release performance and antioxidant capacity of the bilayer microneedles provided in this application embodiment. Figure 3 A represents the Mg levels in PBS over 12 hours for different treatment groups. 2+ Release curve chart, Figure 3 B is a bar chart showing the free radical scavenging rates of different treatment groups; Figure 4 This diagram illustrates the regulatory effect of the bilayer microbes provided in this application on lipopolysaccharide-induced oxidative stress in Schwann cells. Figure 4 A shows bright-field images of cells in each group (scale bar 50 μm). Figure 4B shows ROS fluorescence staining images of cells in each group (scale bar 50 μm). Figure 4 C is a bar chart of the quantitative analysis of the average fluorescence intensity of cells in each group (mean±SD, P<0.05, **P<0.001). Figure 5 This diagram illustrates the in vivo evaluation of the promoting effect of the bilayer microparticles provided in this application on bone regeneration in a rat tooth extraction socket model. Figure 5 A shows the micro-CT 3D reconstruction images of the extraction socket regions in each group. Figure 5 B is a graph showing the results of the quantitative analysis. Detailed Implementation

[0020] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. The following description of at least one exemplary embodiment is merely illustrative and is in no way intended to limit the present invention or its application or use. Based on the embodiments of the present invention, any product that is the same as or similar to the present invention, derived by any person under the guidance of the present invention or by combining the features of the present invention with other prior art, falls within the protection scope of the present invention. Furthermore, all other embodiments obtained by those skilled in the art without inventive effort are within the protection scope of the present invention.

[0021] Specific experimental steps or conditions are not specified in the embodiments; they can be performed according to the conventional experimental steps or conditions described in the prior art. Reagents and other instruments used, unless otherwise specified, are all commercially available conventional reagent products. Furthermore, the accompanying drawings are merely illustrative diagrams of the embodiments of the present invention and are not necessarily drawn to scale. The same reference numerals in the drawings denote the same or similar parts, and therefore, repeated descriptions of them will be omitted. Some block diagrams shown in the drawings are functional entities and do not necessarily correspond to physically or logically independent entities.

[0022] Techniques, methods, and devices known to those skilled in the art may not be discussed in detail, but where appropriate, such techniques, methods, and devices should be considered part of this specification.

[0023] In the description of this invention, it should be understood that the use of terms such as "first" and "second" to define components is merely for the purpose of distinguishing the corresponding components. Unless otherwise stated, the above terms have no special meaning and therefore should not be construed as limiting the scope of protection of this invention.

[0024] Furthermore, the technical features involved in the different embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0025] To enable those skilled in the art to better understand this application, the following embodiments are provided to illustrate in detail a near-infrared responsive magnesium-releasing antioxidant bilayer microneedle, its preparation method, and its application.

[0026] Example Example 1: Preparation of near-infrared responsive magnesium-releasing antioxidant bilayer microneedles S1: 100 mg of molybdenum disulfide nanosheets were dispersed in 100 mL of Tris-HCl buffer (pH 8.5) and sonicated to ensure uniform dispersion. Then, 200 mg of dopamine hydrochloride and 500 mg of magnesium chloride were added, and the mixture was stirred at 40 °C for 24 h to allow dopamine to polymerize in situ on the molybdenum disulfide surface, forming a polydopamine coating layer. Simultaneously, magnesium ions coordinated with the functional groups on the polydopamine surface. After the reaction, the mixture was centrifuged at 10000 r / min for 15 min and washed three times with deionized water to obtain MoS2@PDA@Mg. 2+ Composite particles. The calculated mass ratio of dopamine hydrochloride to molybdenum disulfide was 2:1. The microstructure of the obtained composite particles was observed using scanning electron microscopy (SEM), and the results are as follows. Figure 1 As shown.

[0027] S2: Dissolve GelMA in deionized water to prepare a 15% (w / v) solution; add PVA to bring the final concentration to 5% (w / v); add photoinitiator LAP to bring the final concentration to 0.25% (w / v); then add the above MoS2@PDA@Mg 2+ The composite particles were mixed to a final concentration of 1 mg / mL to obtain the needle tip precursor solution.

[0028] S3: Dissolve GelMA, PVA and PAA in deionized water to achieve mass-volume concentrations of 15%, 5% and 2%, respectively; add photoinitiator LAP to achieve a final concentration of 0.25% (w / v), and mix well to obtain the backing layer precursor solution.

[0029] S4: The tip layer precursor solution is added to the microneedle mold to fully fill the mold cavity, and then pre-crosslinked by irradiation with 405 nm wavelength light for 30 s. Subsequently, the backing layer precursor solution is added above the mold, and then irradiated with 405 nm light for 90 s to allow the backing layer to fully crosslink and bond with the tip layer. After demolding, a bilayer microneedle is obtained. By controlling the different crosslinking times of the two layers, the degree of crosslinking of the tip layer is lower than that of the backing layer, forming a gradient structure that facilitates the release of functional components while also ensuring wet adhesion and fixation. The resulting bilayer microneedles are then sequentially cleaned, sterilized, and sealed for storage.

[0030] The overall appearance and morphology of the prepared bilayer microneedles were observed, and the results are as follows: Figure 2 As shown. Figure 2 Image A shows the actual double-layer microneedle patch. It can be seen that the microneedle patch is fully formed, the substrate is flat, the array is evenly distributed, the edges are continuous, and there is no obvious damage, warping or collapse. Figure 2 B is a magnified morphological image of the microneedle array, showing that the outline of each microneedle is clear and the arrangement is regular. The needle tip is complete and relatively sharp, and no obvious breakage, bending or fusion is observed, indicating that the prepared bilayer microneedles have good formability and structural integrity.

[0031] Example 2: Near-infrared response release performance and antioxidant capacity test The bilayer microneedles prepared in Example 1 were placed in a phosphate buffer solution, and two groups were set up: an illuminated group and a non-illuminated group. The illuminated group was intermittently irradiated with an 808 nm near-infrared light source, and samples were taken at different time points. The Mg content in the solution was determined using inductively coupled plasma optical emission spectrometry (ICP-OES) or a corresponding method. 2+ Concentration was used to evaluate its near-infrared response release performance, and the results are as follows: Figure 3 As shown in Figure A.

[0032] Simultaneously, the antioxidant capacity of the material was evaluated using the DPPH free radical scavenging method, the ABTS cation free radical scavenging method, catalase (CAT) activity assay, superoxide dismutase (SOD) activity assay, and hydroxyl radical (·OH) scavenging method, respectively. The results are as follows: Figure 3 As shown in B.

[0033] like Figure 3 As shown in Figure A, the pure MoS2 microneedle group showed Mg within 12 hours. 2+ The release rate remained consistently close to 0 mmol / L, consistent with the expectation that it contains no magnesium ions, indicating that MoS2 itself does not participate in the release of magnesium ions. MoS2@PDA@Mg 2+ The microneedle group exhibited a slow and continuous release characteristic without near-infrared irradiation, with a release amount of only about 0.45 mmol / L over 12 hours, indicating that the PDA coating effectively inhibits the release of Mg. 2+ This effectively confines and stabilizes the magnesium ions, successfully avoiding the initial burst release problem and facilitating long-term sustained release. Upon application of 808 nm near-infrared irradiation, the composite microneedle group exhibited rapid burst release within 2 hours, reaching approximately 1.35 mmol / L, followed by a slow release phase, with a total release of approximately 2.08 mmol / L over 12 hours, 4.6 times that of the unirradiated group. Based on the excellent photothermal conversion effect of MoS2, near-infrared irradiation increases the local temperature, causing the PDA coating structure to loosen or degrade, while simultaneously accelerating ion diffusion, thereby precisely triggering the release of magnesium ions.2+ Controllable release.

[0034] like Figure 3 As shown in Figure B, the scavenging rates of antioxidant indicators reveal a clear gradient in the antioxidant capacity of different microneedle systems. The pure MoS2 microneedle group exhibits certain intrinsic antioxidant activity, but its overall scavenging rate is low, indicating limited performance. (MoS2@PDA@Mg) 2+ The microneedle group showed a significant improvement in antioxidant capacity under conditions without near-infrared irradiation. This is mainly attributed to the fact that PDA itself is rich in phenolic hydroxyl groups, which have a strong free radical scavenging ability, while Mg... 2+ The introduction of MoS2@PDA@Mg may stabilize the active structure of PDA through coordination or directly participate in the antioxidant reaction, resulting in a synergistic enhancement effect. Further near-infrared irradiation further enhances the effect. 2+ The microneedle group showed a significantly improved antioxidant capacity, outperforming the unirradiated group in all test indicators. This indicates that near-infrared irradiation activates the photothermal effect of MoS2, accelerating the oxidation of Mg. 2+ Release from the microneedles allows more Mg to be released. 2+ It participates in the antioxidant process; on the other hand, local heating enhances the mobility of PDA segments and the activity of phenolic hydroxyl groups, thereby synergistically amplifying the overall free radical scavenging efficiency.

[0035] In summary, this dual-layer microneedle system possesses basic antioxidant protection capabilities under light-free conditions, while achieving a dual synergistic antioxidant effect of "enhanced release + enhanced activity" under near-infrared irradiation, making it suitable for treatment scenarios requiring on-demand regulation of oxidative stress levels.

[0036] Example 3: In vitro efficacy evaluation The in vitro regulatory effect of the bilayer microneedles described in this invention was evaluated using a lipopolysaccharide (LPS)-induced cellular oxidative stress model. Cell morphology was observed using a bright-field microscope. Figure 4 A) ROS fluorescent staining ( Figure 4 B) and quantitative analysis of average fluorescence intensity ( Figure 4 (C) The effects of different treatment groups on the oxidative stress state of Schwann cells were systematically investigated.

[0037] Experimental groups: blank control group, LPS model group (in vitro oxidative stress / inflammation model group), blank microneedle group, MoS2 microneedle group, MoS2@PDA@Mg 2+ Microneedle assembly, MoS2@PDA@Mg 2+ Microneedle combined with near-infrared irradiation group.

[0038] like Figure 4As shown in Figure A, the cells in the blank control group had normal morphology and good adhesion; the cells in the LPS model group showed obvious morphological changes, with some cells shrinking and floating; the cell morphology of each microneedle treatment group was improved to varying degrees, especially MoS2@PDA@Mg 2+ The cell morphology of the microneedling combined with near-infrared irradiation group was closest to that of the blank control group.

[0039] ROS fluorescence staining and quantitative analysis results are as follows: Figure 4 As shown in B and 4C: The ROS fluorescence signal in the blank control group cells was extremely weak; the green fluorescence in the LPS model group cells was significantly enhanced, with the average fluorescence intensity greatly increased compared to the blank control group (P<0.001), indicating that LPS successfully induced an increase in intracellular reactive oxygen species levels. The blank microneedle group had limited effect on improving LPS-induced oxidative stress, and the ROS fluorescence intensity was not significantly different from that of the model group. The MoS2 microneedle group could reduce ROS levels to some extent, with the average fluorescence intensity decreasing compared to the model group (P<0.05). MoS2@PDA@Mg 2+ The microneedle group further reduced the fluorescence signal and its antioxidant effect was significantly better than that of the MoS2 microneedle group (P<0.05). Among them, MoS2@PDA@Mg 2+ The microneedle combined with near-infrared irradiation group showed the weakest ROS fluorescence, with an average fluorescence intensity close to that of the blank control group, which was significantly different from the model group (P<0.001).

[0040] The MoS2@PDA@Mg of this invention 2+ Microneedling combined with near-infrared irradiation can effectively remove LPS-induced excess reactive oxygen species, significantly alleviate the oxidative stress state of Schwann cells, improve cell function, and promote the recovery of repair-related phenotypes, thereby providing favorable conditions for the reconstruction of the neural microenvironment and subsequent bone regeneration.

[0041] Example 4: Evaluation of in vivo repair-promoting performance A rat tooth extraction socket model was used to evaluate the in vivo repair-promoting effect of the double-layer microneedles described in this invention. The in vivo regulatory effect was comprehensively assessed by detecting early oxidative stress levels, changes in the inflammatory microenvironment, and subsequent bone repair in the local tissue of the tooth extraction socket.

[0042] The rat tooth extraction socket model was randomly divided into a blank control group, a blank microneedle group, a MoS2 microneedle group, and a MoS2@PDA@Mg group. 2+ Microneedle assembly and MoS2@PDA@Mg 2+ Microneedling combined with near-infrared irradiation group. Tissue samples were taken at different time points after surgery, and the levels of local oxidative stress and inflammatory factors were detected by ELISA. New bone formation was assessed by micro-CT scanning and three-dimensional reconstruction 4 weeks after surgery.

[0043] like Figure 5As shown in Figure A, the blank control group showed significant bone defects in the extraction socket area, with little and uneven new bone formation; the blank microneedle group and the MoS2 microneedle group showed some improvement in new bone formation, but the trabeculae were sparse and the connectivity was poor; MoS2@PDA@Mg 2+ New bone formation was more significant in the microneedle group, with most of the bone defect area being filled by new bone tissue; MoS2@PDA@Mg 2+ The bone defect in the microneedle combined with near-infrared irradiation group was basically repaired. The newly formed bone tissue was dense and continuous, the trabecular structure was clear and regularly arranged, and it fused well with the surrounding host bone.

[0044] like Figure 5 As shown in Figure B, the new bone volume fraction (BV / TV), trabecular bone thickness (Tb.Th), and trabecular bone number (Tb.N) in each microneedle treatment group were significantly higher than those in the blank control group (P<0.05). Among them, MoS2@PDA@Mg 2+ The microneedle combined with near-infrared irradiation group had the highest values ​​for all indicators, which were 3.2 times, 2.5 times, and 2.8 times higher than those of the blank control group, respectively (P<0.001).

[0045] The MoS2@PDA@Mg of this invention 2+ The microneedle combined with near-infrared irradiation group can effectively alleviate the adverse microenvironment in the early stage of tooth extraction sockets, reduce local oxidative stress levels, improve tissue repair conditions, and significantly promote new bone formation and trabecular bone structure reconstruction, thereby accelerating the tissue repair process of tooth extraction sockets and demonstrating good in vivo repair-promoting performance.

[0046] In summary, the bilayer microneedles described in this invention achieve a synergistic effect of photocontrolled magnesium release and antioxidant activity, and have promising application prospects in the fields of neural microenvironment reconstruction and bone regeneration.

[0047] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.

[0048] Although preferred embodiments of the present application have been described, those skilled in the art, upon learning the basic inventive concept, can make other changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments as well as all changes and modifications falling within the scope of the embodiments of the present application.

[0049] Finally, it should be noted that in this document, relational terms such as "first" and "second" are used only to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or terminal device that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or terminal device. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or terminal device that includes said element.

[0050] The above provides a detailed description of the near-infrared responsive magnesium-releasing antioxidant bilayer microneedles, their preparation method, and applications. Specific examples have been used to illustrate the principles and implementation methods of this application. The descriptions of the above embodiments are only for the purpose of helping to understand the methods and core ideas of this application. At the same time, for those skilled in the art, there will be changes in the specific implementation methods and application scope based on the ideas of this application. Therefore, the content of this specification should not be construed as a limitation of this application.

Claims

1. A method for preparing near-infrared responsive magnesium-releasing antioxidant bilayer microneedles, characterized in that, Includes the following steps: S1: Molybdenum disulfide, dopamine hydrochloride, and magnesium chloride are mixed and reacted in a buffer solution to obtain MoS2@PDA@Mg 2+ Composite particles; S2: Mix the matrix polymer material, photocrosslinking initiator and the composite particles to obtain the needle tip layer precursor solution; S3: Mix the backing material with the photocrosslinking initiator to obtain the backing precursor liquid; S4: Fill the microneedle mold with the needle tip layer precursor liquid and perform the first photocrosslinking to preliminarily shape the needle tip layer; then cover the needle tip layer with the backing layer precursor liquid and perform the second photocrosslinking to crosslink the backing layer and combine it with the needle tip layer. After demolding, the double-layer microneedle is obtained.

2. The preparation method according to claim 1, characterized in that, The mass ratio of dopamine hydrochloride to molybdenum disulfide is 2:1, the mass ratio of magnesium chloride to molybdenum disulfide is 5:1, the reaction temperature is 40℃, and the reaction time is 24 hours.

3. The preparation method according to claim 1, characterized in that, The matrix polymer material in S2 is a composite system of gelatin methacryloyl and polyvinyl alcohol, wherein the mass-volume concentration of gelatin methacryloyl is 15% and the mass-volume concentration of polyvinyl alcohol is 5%; the photocrosslinking initiator is lithium phenyl-2,4,6-trimethylbenzoylphosphonate, with a mass-volume concentration of 0.25%; the MoS2@PDA@Mg 2+ The final concentration of the composite particles was 1 mg / mL.

4. The preparation method according to claim 1, characterized in that, The backing material in S3 is a composite system of gelatin methacryloyl, polyvinyl alcohol and polyacrylic acid, wherein the mass-volume concentration of gelatin methacryloyl is 15%, the mass-volume concentration of polyvinyl alcohol is 5%, and the mass-volume concentration of polyacrylic acid is 2%; the photocrosslinking initiator is lithium phenyl-2,4,6-trimethylbenzoylphosphonate with a mass-volume concentration of 0.25%.

5. The preparation method according to claim 1, characterized in that, The first photocrosslinking was performed by irradiating with a 405 nm light source for 30 seconds, and the second photocrosslinking was performed by irradiating with a 405 nm light source for 90 seconds.

6. A near-infrared responsive magnesium-releasing antioxidant bilayer microneedle prepared by the preparation method according to any one of claims 1 to 5, characterized in that, It includes a backing layer and a needle tip layer bonded to the backing layer; the needle tip layer comprises a matrix polymer material, a photocrosslinking initiator, and a functional nanocomponent, wherein the functional nanocomponent is MoS2@PDA@Mg 2+ .

7. The double-layer microneedle according to claim 6, characterized in that, The backing layer is a wet adhesive support layer used to adhere to the extraction socket wound in a moist oral environment.

8. The use of a bilayer microneedle as described in claim 6 or 7 in the preparation of a product for tooth extraction socket restoration.

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