Light response type hydrogel composite material and application thereof in pulpitis treatment

Abstract

The invention discloses a light response type hydrogel composite material and application thereof in treatment of pulpitis. The material is formed by compounding metal organic framework MOF (at) Cr-Al nanoparticles and GelMA hydrogel, is named as GelMA-MOF (at) Cr-Al, and has the following functions: (1) rapid cross-linking molding is performed through ultraviolet irradiation, so that precise clinical operation is realized; 2) active oxygen is removed, and an inflammation signal channel is regulated; and 3) promoting dentin differentiation. Experiments show that the GelMA-MOF (at) Cr-Al can significantly inhibit pulpitis and enhance dentin regeneration, and has excellent antibacterial performance and biocompatibility. The material overcomes the limitation of the traditional pulp capping material inorganic trioxide polymer (MTA), and provides a dual anti-inflammatory and regeneration strategy for dental pulp activity therapy.

Description

Technical Field

[0001] The present invention relates to the technical field of oral biomedical materials, and particularly relates to a light-responsive hydrogel composite material that can be used for the treatment of pulpitis. Background Art

[0002] The dental pulp is a complex biological tissue composed of multiple cell types and extracellular matrix, and plays a crucial role in maintaining the physiological functions of teeth, including the transportation of nutrients, the clearance of metabolic wastes, and tissue repair mechanisms. In young permanent teeth, dental pulp vitality is essential for tooth development and long-term health maintenance. The success of vital pulp therapy (VPT) fundamentally depends on activating the regenerative potential of stem cells in the inflamed dental pulp to promote tissue repair and maintain tooth vitality. However, the clinical efficacy of VPT is still limited by various factors, including the accurate assessment of the inflammatory state, the level of bacterial contamination, the tooth development stage, and the selection of key dental pulp capping materials.

[0003] Calcium hydroxide-based materials are considered the historical gold standard for dental pulp capping, demonstrating excellent antibacterial properties and the capacity to promote mineralization. However, their clinical limitations are well-known: rapid dissolution leads to impaired long-term sealing performance, cytotoxicity caused by extreme alkalinity (pH 12 - 13), and microleakage prone to occur in the formed porous dentin bridge. Although mineral trioxide aggregate (MTA) and calcium silicate-based materials exhibit better biocompatibility and sealing ability compared to calcium hydroxide, they still face challenges, including excessive setting time, tooth discoloration, and incomplete resolution of the inflammatory response. Notably, neither of these two materials can reliably induce odontoblast-like cell differentiation, which raises concerns about the true regenerative nature of the formed hard tissue barrier. These limitations highlight the urgent need to develop innovative dental pulp capping materials that can simultaneously achieve the dual functions of inflammation regulation and tissue regeneration.

[0004] The inflammatory microenvironment in infected dental pulp presents a paradoxical scenario. Moderate inflammation contributes to the clearance of bacteria through neutrophil recruitment and cytokine signaling, while excessive inflammation triggered by overactivation of reactive oxygen species (ROS) initiates a pathological cascade through the NF-κB / MAPK pathway. This oxidative stress disrupts cellular homeostasis by impairing adhesion molecule expression (such as integrins), cell cycle progression, and the differentiation ability of dental pulp stem cells (DPSCs). In addition, ROS and proteases produced by neutrophils cause collateral damage to the surrounding tissues during the fight against pathogens, thus forming a vicious cycle that hinders reparative dentin formation.

[0005] Emerging nanotechnology methods offer promising solutions to this therapeutic dilemma. Metal-organic frameworks (MOFs), which are crystalline porous materials constructed from metal nodes and organic ligands, have emerged as multifunctional platforms in biomedical applications. Their unique advantages include: 1) having intrinsic enzyme-mimicking activity (catalase) for scavenging reactive oxygen species; 2) enabling controlled release of metal ions to achieve continuous antibacterial effects; 3) being able to be internalized by cells, bypassing the limitations of transmembrane transport. These properties make MOFs ideal candidates for developing multifunctional dental pulp capping materials that can simultaneously address infection control, inflammation resolution, and tissue regeneration issues. Summary of the Invention

[0006] Aiming at the above problems of the prior art, the object of the present invention is to provide a photo-responsive hydrogel composite material for the treatment of pulpitis, which can effectively scavenge ROS, eliminate inflammation, promote dentin formation, and facilitate clinical operation.

[0007] To achieve the above object, the present invention provides a photo-responsive hydrogel composite material (GelMA-MOF@Cr-Al), which takes the metal-organic framework material MOF@Cr-Al self-assembled from metal ions Cr 3 + and Al3+ and an organic ligand as the functional core, and the methacrylated gelatin (GelMA) hydrogel as the bioactive matrix. The two are combined and can be used as a drug for treating pulpitis. Among them, MOF@Cr-Al is nanoparticles and is uniformly distributed in the GelMA hydrogel. The addition amount of MOF@Cr-Al is 2.5% - 5% of the mass of the GelMA hydrogel; the GelMA hydrogel also contains a photoinitiator, which initiates the cross-linking and curing of the GelMA hydrogel under light irradiation.

[0008] Furthermore, the organic ligand in the MOF@Cr-Al is preferably 2-methylimidazole, benzimidazole, 5-aminotetrazole, etc. In some embodiments of the present invention, 2-methylimidazole, aluminum nitrate, and chromium(III) chloride hexahydrate are synthesized into MOF@Cr-Al nanoparticles through a hydrothermal reaction. The particle size of the MOF@Cr-Al nanoparticles is 50 - 100 nm, with a cuboid morphology, and Cr 3 + and Al3+ are uniformly distributed in the material, and the molar ratio of Cr 3 + to Al3+ is preferably 1:1 - 3:1.

[0009] Furthermore, the photoinitiator is LAP (Lithium Phenyl-2,4,6-trimethylbenzoylphosphinate).

[0010] The present invention also provides a method for preparing the above-mentioned light-responsive hydrogel composite material GelMA-MOF@Cr-Al, which includes the following steps:

[0011] 1) Synthesize MOF@Cr-Al nanoparticles and disperse them in a buffer solution;

[0012] 2) Prepare an aqueous GelMA solution and add a photoinitiator;

[0013] 3) Add the MOF@Cr-Al nanoparticles to the GelMA solution in proportion, mix evenly, and then crosslink by light irradiation to cure and form a shape.

[0014] In the above step 1), preferably, MOF@Cr-Al nanoparticles are synthesized by a solvothermal reaction using 2-methylimidazole, aluminum nitrate, and chromium(III) chloride hexahydrate, the precipitate is collected by centrifugation, washed, and then dispersed in phosphate buffer solution (PBS).

[0015] If the photoinitiator used in the above step 2) is LAP, then 405 nm light irradiation is used for crosslinking in step 3).

[0016] In some embodiments of the present invention, in step 2), GelMA with a mass concentration of 5% - 10% and a photoinitiator LAP with a mass concentration of 0.25% are added to water, and heated to 60 - 70 °C to form a homogeneous solution.

[0017] The light-responsive hydrogel composite material GelMA-MOF@Cr-Al of the present invention can be used to prepare drugs for treating pulpitis, including acute and chronic pulpitis caused by bacterial infection, trauma, or chemical irritation. GelMA-MOF@Cr-Al achieves the treatment of pulpitis in the following ways:

[0018] 1. Rapid photocuring: Crosslinking can be achieved by irradiating with 405 nm light for 15 seconds, meeting the requirements of clinical operations;

[0019] 2. ROS scavenging: MOF@Cr-Al has catalase-like activity and can down-regulate inflammatory factors such as IL-1β, IL-6, and TNF-α;

[0020] 3. Antibacterial property: Release Cr 3 + and Al3+ ions to disrupt the bacterial cell membrane structure and inhibit the proliferation of Escherichia coli and Porphyromonas gingivalis;

[0021] 4. Promoting regeneration function: By regulating the TGF-β signaling pathway, up-regulate the expression of ALP, OCN, RUNX2, and DSPP, and promote odontoblastic differentiation.

[0022] The present invention integrates metal-organic framework MOF@Cr-Al nanoparticles with GelMA hydrogel. The obtained light-responsive hydrogel composite GelMA-MOF@Cr-Al can rapidly crosslink and form a shape under light irradiation to achieve precise clinical operations; effectively scavenge reactive oxygen species (ROS), regulate the NF-κB / MAPK inflammatory signaling pathway; and promote the odontoblastic differentiation of dental pulp stem cells (DPSCs). Experiments have shown that GelMA-MOF@Cr-Al significantly reduces inflammatory infiltration in a rat pulpitis model, restores the structure of the odontoblast layer, and has no significant cytotoxicity, with excellent antibacterial properties and biocompatibility. This treatment strategy with multiple functions overcomes the limitations of traditional calcium hydroxide and MTA materials, provides anti-inflammatory and regenerative strategies for pulp vitality treatment, marks a paradigm shift from traditional passive debridement methods to active tissue reprogramming, and is expected to redefine the clinical standards for pulp vitality treatment. Brief Description of the Drawings

[0023] Figure 1 . Schematic diagram for the preparation of the light-responsive hydrogel composite GelMA-MOF@Cr-Al in Example 1 of the present invention.

[0024] Figure 2 . Bright-field pictures of the solution state of the light-responsive hydrogel composite GelMA-MOF@Cr-Al prepared in Example 1 and the solid state formed after ultraviolet light crosslinking.

[0025] Figure 3 . Transmission electron microscope pictures of MOF@Al, MOF@Cr, and MOF@Cr-Al prepared in Example 1.

[0026] Figure 4 . Scanning electron microscope pictures of MOF@Al, MOF@Cr, and MOF@Cr-Al prepared in Example 1.

[0027] Figure 5 . Results of the morphological analysis using a scanning electron microscope and the elemental composition analysis of the light-responsive hydrogel composites GelMA-MOF@Cr-Al, GelMA-MOF@Cr, and GelMA-MOF@Al using energy-dispersive X-ray spectroscopy in Example 1.

[0028] Figure 6 . Results of the elemental analysis of MOF@Cr-Al using X-ray photoelectron spectroscopy (XPS) in Example 1.

[0029] Figure 7 . Experimental results of the release of metal ion Cr 3 + from GelMA-MOF@Cr, GelMA-MOF@Al, and GelMA-MOF@Cr-Al in Example 1.

[0030] Figure 8 . Experimental results of the release of metal ion Al3+ by GelMA-MOF@Cr, GelMA-MOF@Al, and GelMA-MOF@Cr-Al in Example 1.

[0031] Figure 9 . Cytotoxicity test results of different concentrations of MOF@Cr-Al in Example 2 after incubation with dental pulp stem cells for different times (1 day, 3 days, 5 days, and 7 days).

[0032] Figure 10 . RT-qPCR analysis was performed on iDPSCs treated with MOF@Al, MOF@Cr, and MOF@Cr-Al for 3 hours respectively in Example 3 to detect the mRNA expression levels of inflammatory factors interleukin 6 (IL-6) and tumor necrosis factor a. Among them, the positive control group was iDPSCs, and the negative control group (Control) was normal dental pulp stem cells.

[0033] Figure 11 . In vitro hydrogen peroxide scavenging rate test results of MOF@Cr-Al in Example 4, with MOF@Cr-Al concentrations of 200 μM and 8 mM.

[0034] Figure 12 . Results of the detection of reactive oxygen species levels in iDPSCs before and after treatment with MOF@Cr-Al by flow cytometry in Example 4, as well as the statistical analysis of the average fluorescence intensity of flow cytometry data. The P value was derived from the significance analysis of the difference between the experimental group and the iDPSCs group. **P<0.01, indicating a statistically significant difference.

[0035] Figure 13 . Detection results of the growth of Escherichia coli and colony counting statistics after treatment with MOF@Al, MOF@Cr, and MOF@Cr-Al by the plate coating method in Example 5.

[0036] Figure 14 . Scanning electron microscope detection results of Porphyromonas gingivalis and Escherichia coli before and after treatment with MOF@Al, MOF@Cr, and MOF@Cr-Al in Example 5.

[0037] Figure 15 . Results of alizarin red staining of cells after osteogenic induction of inflammatory dental pulp stem cells by different treatment groups of MOF@Al, MOF@Cr, and MOF@Cr-Al for 14 days in Example 6. The negative control was normal human dental pulp stem cells (hDPSC), and the positive control was hDPCS containing osteogenic induction medium (hDPSC+OM).

[0038] Figure 16. In Example 6, RT-qPCR was used to measure the changes in the mRNA expression levels of multiple markers related to osteogenic and odontogenic differentiation in iDPSCs treated with MOF@Cr, MOF@Al, and MOF@Cr-Al for 7 days.

[0039] Figure 17 . In Example 6, RT-qPCR was used to measure the changes in the mRNA expression levels of multiple markers related to osteogenic and odontogenic differentiation in iDPSCs treated with MOF@Cr, MOF@Al, and MOF@Cr-Al for 14 days.

[0040] Figure 18 . In Example 7, after 7-day root canal pulp capping treatment with different treatment groups of MOF@Al, MOF@Cr, and MOF@Cr-Al, the results of hematoxylin-eosin staining of sagittal sections of the maxillary first molar in the rat diffuse pulpitis model were obtained. Among them, dentin-forming layer cells were present on the inner wall of the root canal.

[0041] Figure 19 . In Example 8, after 7-day root canal pulp capping treatment with different treatment groups of MOF@Al, MOF@Cr, and MOF@Cr-Al, the results of immunohistochemical staining of osteopontin in sagittal sections of the maxillary first molar in the rat diffuse pulpitis model were obtained. Detailed implementation manners

[0042] The present invention will be further described below by way of examples, but the present invention is not limited to the scope of the described examples.

[0043] Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art; unless otherwise specified, the reagents used in the examples are all commercially available.

[0044] Example 1: Preparation and characterization of GelMA-MOF@Cr-Al

[0045] 1) Dissolve 2-methylimidazole (5 mM), aluminum nitrate (2 mM), and chromium(III) chloride hexahydrate (2 mM) in deionized water and react at 37 °C for 30 minutes;

[0046] 2) After centrifugation (12000 rpm, 5 minutes), take the precipitate, wash it 3 times with PBS, and disperse it for standby;

[0047] 3) Mix GelMA (10% w / v) with 0.25% LAP aqueous solution and heat it to complete dissolution at 60 °C;

[0048] 4) Add MOF@Cr-Al (mass content 2.5%), vortex and mix well, and then inject it into the mold;

[0049] 5) Curing was carried out by irradiating with a 405 nm light source for 15 seconds to obtain a porous hydrogel.

[0050] The experimental results are as Figure 2 shown. The hydrogel composite in solution state was photocured with ultraviolet light at a wavelength of 405 nm for 15 seconds. After ultraviolet light irradiation, the hydrogel composite formed a stable solid form, and the chromium-aluminum metal-organic framework hydrogel (GelMA-MOF@Cr-Al) could be obtained.

[0051] The morphologies of MOF@Al, MOF@Cr, and MOF@Cr-Al were characterized by transmission electron microscopy and scanning electron microscopy, as Figure 3 and Figure 4 shown. The synthesized MOF@Al, MOF@Cr, and MOF@Cr-Al exhibited uniform and stable particle sizes, showing a cuboid structure with a particle size of 50 - 100 nm.

[0052] In addition, after freeze-drying GelMA, GelMA-MOF@Cr, GelMA-MOF@Al, and GelMA-MOF@Cr-Al, the morphology was analyzed by scanning electron microscopy, and the elemental composition was analyzed by energy-dispersive X-ray spectroscopy (EDS). As Figure 5 the scanning electron microscopy results in Figure 6 showed that GelMA-MOF@Cr, GelMA-MOF@Al, and GelMA-MOF@Cr-Al exhibited a porous surface morphology, and the Cr and Al elements were uniformly distributed in the material. In addition, as

[0053] the results of X-ray photoelectron spectroscopy (XPS) elemental analysis in 3 also showed that the Cr and Al elements were present in the hydrogel.

[0053] To evaluate the ion release ability of GelMA-MOF@Cr-Al, the material was immersed in phosphate buffer solution (PBS, pH = 7.4), and the concentrations of Cr 3 + and Al3+ in the leaching solution were measured at 0, 6, 12, 24, and 48 hours. As Figure 7 and Figure 8 shown, compared with GelMA-MOF@Cr or GelMA-MOF@Al alone, the ion concentrations of GelMA-MOF@Cr-Al in the solution under physiological conditions and at the same time points (24 hours and 48 hours) were at a lower level, indicating that GelMA-MOF@Cr-Al could achieve the effect of slow release of metal ions Cr 3 + and Al3+, which was beneficial for the long-term treatment of pulpitis.

[0054] Example 2: In vitro cytocompatibility evaluation of GelMA-MOF@Cr-Al

[0055] To further explore its potential application in the treatment of human dental pulp stem cells (hDPSCs), we investigated the cytotoxicity of MOF@Cr-Al on hDPSCs. The results are as Figure 9 shown. The effect of MOF@Cr-Al on the proliferation of hDPSCs was evaluated using the CCK-8 assay. hDPSCs were treated with MOF@Al, MOF@Cr, and MOF@Cr-Al for 1 day, 3 days, 5 days, and 7 days, respectively. The results of the CCK-8 assay showed that different concentrations of MOF@Cr-Al did not inhibit the proliferation of hDPSCs compared with the blank control group, indicating that MOF@Cr-Al has good biosafety.

[0056] Example 3: Anti-inflammatory properties of MOF@Cr-Al

[0057] To study the effect of MOF@Cr-Al on the expression of inflammatory factors in inflamed dental pulp stem cells (iDPSCs), the levels of inflammatory cytokines under different treatment conditions were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). As Figure 10 shown, after iDPSCs were stimulated with lipopolysaccharide (LPS) for 3 hours, the expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly upregulated. However, after treatment with MOF@Al, MOF@Cr, and MOF@Cr-Al, the mRNA expression levels of these inflammatory factors (IL-6 and TNF-α) were significantly downregulated in iDPSCs. These results indicate that MOF@Cr-Al has good anti-inflammatory ability.

[0058] Example 4: Determination of the reactive oxygen species scavenging ability of MOF@Cr-Al

[0059] To evaluate the reactive oxygen species scavenging ability of MOF@Cr-Al, a hydrogen peroxide (H2O2) detection kit (Beyotime, catalog number: S0038) was used for detection. As Figure 11 shown, as the concentration of MOF@Cr-Al increased, the scavenging rate of H2O2 increased from 9.4% at 200 μmol / L to 38.0% at 8 mmol / L. These results indicate that MOF@Cr-Al has catalase-like activity and the ability to scavenge reactive oxygen species.

[0060] In addition, the intracellular reactive oxygen species levels in iDPSCs treated with MOF@Cr-Al were also evaluated. The results of flow cytometry ( Figure 12 ) showed that compared with untreated hDPSCs, LPS-treated iDPSCs produced a large amount of reactive oxygen species. After treatment with MOF@Cr-Al, the reactive oxygen species levels in iDPSCs were significantly reduced.

[0061] Example 5: Antibacterial Performance Evaluation of MOF@Cr-Al

[0062] The antibacterial activity of MOF@Cr-Al against Escherichia coli (E. coli) was evaluated by the colony counting method, and the morphological changes of bacteria treated with MOF@Cr-Al were observed using scanning electron microscopy (SEM). MOF@Al, MOF@Cr, and MOF@Cr-Al were co-cultured with E. coli and Porphyromonas gingivalis (P. gingivalis) for 16 hours and 24 hours respectively, with phosphate buffered saline (PBS) as the blank control. Colony counting was performed on the culture dishes, as Figure 13 shown, there were significant differences between the experimental group and the control group. The antibacterial effect of MOF@Cr-Al increased with the increase in concentration, and no visible colonies were formed on the culture dishes treated with 50 μmol / L MOF@Cr-Al.

[0063] Scanning electron microscopy ( Figure 14 ) results showed that E. coli treated with MOF@Cr-Al exhibited flagella breakage and cell surface shrinkage. The surface of P. gingivalis shrank, and MOF@Cr-Al affected the normal morphology of P. gingivalis.

[0064] Example 6: Biological Effects of MOF@Cr-Al on Odontoblastic Differentiation of iDPSCs

[0065] To investigate the effects of MOF@Cr-Al on osteogenic and odontoblastic differentiation of iDPSCs, the expression levels of markers related to osteogenic and odontoblastic differentiation in cells treated with MOF@Cr-Al were evaluated by alizarin red S (ARS) staining and RT-qPCR experiments.

[0066] Alizarin red S staining results ( Figure 15 ) showed that compared with normal dental pulp stem cells (hDPSCs) and inflamed dental pulp stem cells (iDPSCs), the staining of hDPSCs induced osteogenically was significantly enhanced. However, the staining of iDPSCs treated with MOF@Al and MOF@Cr-Al increased significantly, indicating a promoting effect on osteogenic / odontoblastic differentiation. In contrast, the staining of iDPSCs treated with MOF@Cr was lighter and there was no significant difference compared with iDPSCs only induced osteogenically.

[0067] The mRNA expression levels of multiple markers related to osteogenic and odontogenic differentiation in iDPSCs treated with MOF@Cr, MOF@Al, and MOF@Cr-Al were measured by RT-qPCR. Untreated hDPSCs expressed low levels of alkaline phosphatase (ALP), osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), and dentin sialophosphoprotein (DSPP). Osteogenic-induced hDPSCs significantly upregulated the expression of ALP, OCN, and RUNX2, while osteogenic-induced iDPSCs downregulated the expression of ALP, OCN, RUNX2, and DSPP. As Figure 16 shown, at 7 days, treatment with MOF@Cr-Al and MOF@Al significantly increased the expression levels of ALP, RUNX2, and DSPP (p < 0.05), while treatment with MOF@Cr alone upregulated the expression of RUNX2 (p < 0.01), and no significant changes were observed in other markers.

[0068] As Figure 17 shown, after 14 days of osteogenic induction, MOF@Al and MOF@Cr-Al significantly upregulated the mRNA expression levels of ALP, OCN, RUNX2, and DSPP (p < 0.05). MOF@Cr also moderately upregulated the expression of ALP, OCN, and RUNX2, although the upregulation of ALP and OCN was relatively weak (p < 0.05). The above experiments showed that MOF@Cr-Al significantly promoted the mRNA expression of markers related to osteogenic and odontogenic differentiation in inflamed dental pulp stem cells, so MOF@Cr-Al has the effect of promoting osteogenic and odontogenic differentiation.

[0069] Example 7: In vivo anti-inflammatory properties of GelMA-MOF@Cr-Al

[0070] A rat pulpitis model was established to evaluate the anti-inflammatory and repair effects of GelMA-MOF@Cr-Al in vivo. Histological evaluation was performed using hematoxylin-eosin staining and immunohistochemical staining to evaluate inflammatory cell infiltration, dental pulp tissue status, reparative dentin formation, and secondary infection, so as to evaluate the efficacy of dental pulp capping materials. The dental pulp of rat molars was stimulated with 1 μmol / L Escherichia coli LPS for 10 minutes and then directly filled without dental pulp capping. One week after treatment, the dental pulp of rat molars was taken for decalcified sectioning and hematoxylin-eosin staining and immunohistochemical staining.

[0071] Results of hematoxylin-eosin staining ( Figure 18)It was shown that after 7 days of LPS treatment, diffuse inflammatory reactions occurred in the dental pulp tissue, and the dental pulp tissue from the exposed pulp cavity to the middle and upper root canals underwent degradation and degeneration. In addition, no clear cell nuclei or matrix tissues were observed, and the odontoblast layer in the root canals disappeared. Extensive lymphocyte infiltration appeared in the lower root canals and apical regions, with small, round, and darkly stained cell nuclei, indicating the successful establishment of a rat pulpitis model. In the GelMA dental pulp coverage group, significant lymphocyte infiltration could be observed in the rat pulp cavity and root canals, indicating the presence of diffuse inflammatory reactions and the disappearance of the odontoblast layer. It was shown that GelMA alone had no significant effect on rat pulpitis.

[0072] In the samples of the GelMA-MOF@Cr-Al and the conventional pulp capping material mineral trioxide aggregate (MTA) groups, local lymphocyte infiltration and fibrotic dental pulp tissues could be observed under the capping materials, and the dental pulp tissues in the root canals maintained relatively normal structures. However, in the MTA group, the arrangement of the odontoblast layer in the root canals was disordered and unclear. In contrast, the GelMA-MOF@Cr-Al group presented a clear odontoblast layer, with tall and palisade-like cell arrangements. It was shown that GelMA-MOF@Cr-Al had good anti-inflammatory effects and the ability to restore the structure of the odontoblast layer.

[0073] Example 8: In vivo pro-regenerative properties of GelMA-MOF@Cr-Al

[0074] To further evaluate the differentiation ability of odontoblasts after dental pulp capping, immunohistochemical staining of osteocalcin (OCN) was performed. The staining results were as Figure 19 shown. In the GelMA-MOF@Cr-Al dental pulp coverage group, a tightly arranged odontoblast layer lining the inner wall of the root canal was observed, with strong brownish-yellow positive staining in the cytoplasm, indicating a high OCN expression level. GelMA-MOF@Cr-Al promoted the differentiation of odontoblasts and enhanced the expression of OCN, highlighting its potential as an effective dental pulp capping material.

Claims

1. A light-responsive hydrogel composite material, characterized in that, Including metal ions Cr 3 + and Al3+ self-assembled with organic ligands to form a metal-organic framework material MOF@Cr-Al, and a methacrylated gelatin GelMA hydrogel. Among them, MOF@Cr-Al is nanoparticles uniformly distributed in the GelMA hydrogel, and the addition amount of MOF@Cr-Al is 2.5% - 5% of the mass of the GelMA hydrogel; the GelMA hydrogel also contains a photoinitiator, which initiates the crosslinking and curing of the GelMA hydrogel under light illumination.

2. The photo-responsive hydrogel composite material according to claim 1, wherein The MOF@Cr-Al is nanoparticles synthesized by 2-methylimidazole, aluminum nitrate, and chromium(III) chloride hexahydrate through a hydrothermal reaction, with a cuboid morphology and a particle size of 50 - 100 nm.

3. The photo-responsive hydrogel composite material according to claim 2, wherein Cr 3 + and Al3+ are evenly distributed in the MOF@Cr-Al nanoparticles, and the molar ratio of the two is Cr 3 +:Al3+ = 1:1 to 3:

1.

4. The photo-responsive hydrogel composite material according to claim 1, wherein The photoinitiator is LAP.

5. The method for preparing the photo-responsive hydrogel composite material according to any one of claims 1 - 4, comprising the following steps: 1) Synthesize MOF@Cr-Al nanoparticles and disperse them in a buffer solution; 2) Prepare an aqueous solution of GelMA and add a photoinitiator; 3) Add the MOF@Cr-Al nanoparticles to the aqueous solution of GelMA in proportion, mix evenly, and then crosslink by light irradiation to cure and form a shape.

6. The preparation method according to claim 5, characterized in that, In step 1), MOF@Cr-Al nanoparticles are synthesized by 2-methylimidazole, aluminum nitrate, and chromium(III) chloride hexahydrate through a solvothermal reaction, the precipitate is collected by centrifugation, washed, and then dispersed in a phosphate buffer solution.

7. The preparation method according to claim 5, characterized in that, In step 2), the photoinitiator is LAP, and in step 3), crosslinking is carried out by 405 nm light irradiation.

8. The preparation method according to claim 7, characterized in that, In step 2), add GelMA with a mass concentration of 5% - 10% and a photoinitiator LAP with a mass concentration of 0.25% to water, and heat to 60 - 70 °C to form a homogeneous solution.

9. The application of the photo-responsive hydrogel composite material according to any one of claims 1 - 4 in the preparation of drugs for treating pulpitis.

10. The application according to claim 9, wherein The pulpitis includes acute and chronic pulpitis caused by bacterial infection, trauma, or chemical irritation.

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