Method for realizing accurate regeneration and functional reconstruction of gingival structure in combination with regeneration induction

Abstract

The invention provides a method for realizing accurate regeneration and functional reconstruction of a gingival structure in combination with regeneration induction, relates to the field of traction gingival structure regeneration and functional reconstruction, and relates to 4D bionic scaffold design, a cell activation and directional regeneration system, a microorganism-immune regulation and control network and real-time monitoring and self-adaptive repair. The 4D bionic stent is designed into a shape memory hydrogel matrix, a 4D response mechanism and a bionic micro-gradient structure. The shape memory hydrogel matrix is specifically composed of materials; according to the material, a shape memory hydrogel matrix is prepared from 60% of PVA, 30% of gelatin and 10% of an elastin system, temperature triggering is carried out, a response mechanism is started when the oral temperature is lower than 37 DEG C, the crystal glue matrix is attached to the curved surface of the gingiva, and the shape memory hydrogel matrix and the curved surface of the gingiva are in contact. The shrinkage rate of the hydrogel matrix is 15%. The method has the advantage that the regeneration and functional reconstruction of the gingival structure can be accurately realized.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of regenerating and reconstructing gingival structure, and particularly relates to a method for realizing precise regeneration and reconstruction of gingival structure by combining regeneration induction. BACKGROUND

[0002] Gingival tissue is an important supporting tissue in the oral cavity, and its damage or loss will cause a series of oral dysfunction and aesthetic problems.

[0003] At present, gingival regeneration technology faces many challenges. Traditional gingival regeneration scaffold materials mostly do not have dynamic response characteristics, are difficult to adapt to the complex changes of temperature, pH and other environments in the oral cavity, cannot closely fit the gingival curved surface, cause large interface stress, affect cell adhesion and tissue growth, and have fixed pore structure, which is not conducive to the release of antibacterial components and the drainage of exudate. In terms of cell regeneration, the homing efficiency and directional differentiation ability of stem cells need to be improved, and the delivery of exosomes lacks precise targeting, which affects the tissue repair effect. In addition, the complex microbial environment in the oral cavity is easy to cause biofilm formation and inflammatory reaction.

[0004] The traditional method has limited effect on microbial-immune regulation, and excessive inflammatory reaction will hinder the regeneration and reconstruction of gingival tissue. At the same time, the existing technology lacks real-time monitoring and self-adaptive repair ability of the gingival tissue regeneration process, and it is difficult to adjust the treatment strategy in time according to the tissue state. Therefore, there is an urgent need for a new technology that can solve the above problems and realize precise regeneration and reconstruction of gingival structure. SUMMARY

[0005] The purpose of the present application is to solve the problems existing in the prior art, and to provide a method for realizing precise regeneration and reconstruction of gingival structure by combining regeneration induction.

[0006] In order to achieve the above purpose, the technical scheme adopted by the present application is as follows: the method for realizing precise regeneration and reconstruction of gingival structure by combining regeneration induction comprises: 4D biomimetic scaffold design, cell activation and directional regeneration system, microbial-immune regulation network and real-time monitoring and self-adaptive repair, and the 4D biomimetic scaffold design is divided into shape memory hydrogel matrix, 4D response mechanism and biomimetic microgradient structure.

[0007] The shape memory hydrogel matrix is specifically composed of materials:

[0008] Material composition: the shape memory hydrogel matrix is made of PVA, gelatin and elastin system, and the proportion of each component of the PVA, gelatin and elastin system is 60%, 30% and 10%.

[0009] The 4D response mechanism is specifically composed of temperature trigger and use environment:

[0010] Temperature trigger: the response mechanism is activated when the oral temperature is lower than 37°, the hydrogel matrix is attached to the gingival surface, and the shrinkage rate of the hydrogel matrix is 15%;

[0011] Use environment: when the hydrogel matrix is in an inflammatory area (PH < 6.5), the pores of the hydrogel matrix expand, and the pore size of the hydrogel matrix expands from 50 μm to 120 μm.

[0012] The biomimetic micro- gradient structure specifically consists of a mechanical gradient and a blood vessel access channel:

[0013] Mechanical gradient: the hydrogel matrix is constructed by an electric field assisted 3D printing technology to form a Young's modulus gradient, the surface layer Young's modulus is 2 MPa, and the deep layer is 0.8 MPa;

[0014] Blood vessel access channel: the diameter of the spiral microchannel built in the stent is 80 μm, and the migration speed of the blood vessel guide channel is 3 times higher than that without the channel structure.

[0015] With this preferred scheme, PVA provides good mechanical properties and water solubility, gelatin has good biocompatibility and cell adhesion, elastin imparts elasticity to the material, four-armed polyethylene glycol acrylate as a crosslinking agent can form a dynamic crosslinking network, making the material have shape memory characteristics, and also provides a stable mechanical environment for gingival tissue regeneration, and is conducive to promoting the release of antibacterial ingredients and exudate drainage, and improving the microenvironment of the inflammatory area; the micro- gradient structure can simulate the mechanical transition of natural gingiva from free gingiva to attached gingiva, providing suitable mechanical signals for gingival cells in different parts to guide directional growth and differentiation; the blood vessel guide channel can promote angiogenesis and provide sufficient nutrient supply for gingival tissue regeneration.

[0016] Preferably, the cell activation and directional regeneration system includes in-situ activation of stem cell nests and intelligent delivery of exosomes.

[0017] The in-situ activation of stem cell nests specifically consists of chemical niches and nano-pulse electric fields:

[0018] Chemical niche design: the surface of the stent is fixed with SDF-1α chemotactic factors, the density of the chemotactic factors is ≥ 50 ng / cm 2 , the chemotactic factors attract host gingival mesenchymal stem cells (GMSCs) to home, the recruitment efficiency of the chemotactic factors within 24 hours reaches 90%, and the chemotactic factors provide seed cells for gingival tissue regeneration;

[0019] Nano-pulsed electric field: the nano-pulsed electric field integrates a microelectrode array, the microelectrode array applies a nano-pulsed electric field of 50 mV / cm, 1 Hz, activates Piezo1 ion channels to induce stem cell osteogenic differentiation, and increases alkaline phosphatase (ALP) activity by 400%.

[0020] The exosome smart delivery specifically comprises a gingival stem cell exosome (GMSC-Exo) and a targeted damage area, which are composed of:

[0021] Gingival stem cell exosome (GMSC-Exo): the gingival stem cell exosome (GMSC-Exo) is encapsulated in a thermosensitive liposome by liposome fusion technology, the phase transition temperature of the thermosensitive liposome is 38℃, and the gingival stem cell exosome can continuously release repairative miRNAs (such as miR-21, miR-1246);

[0022] Targeted damage area: the exosome surface is modified with a gingival-specific peptide (GSP, sequence: CKIPKPSSV), and the targeting efficiency is increased by 8 times compared with the unmodified group.

[0023] With this preferred scheme, the chemical niche is designed to provide sufficient seed cells for gingival tissue regeneration; the nano-pulsed electric field can promote the formation and stability of the periodontal ligament-alveolar bone interface; the gingival stem cell exosome (GMSC-Exo) can regulate cell gene expression, promote cell proliferation, differentiation, and apoptosis regulation; the targeted damage area: realizes lesion enrichment, the targeting efficiency is increased by 8 times compared with the unmodified group, increases the concentration of exosomes in the damaged part, and enhances the repair effect.

[0024] Preferably, the microbe-immune regulation network comprises an anti-biofilm nanotrap.

[0025] The anti-biofilm nanotrap specifically comprises a functionalized nanorod array, quorum sensing interference, and macrophage phenotype transformation regulation

[0026] Functionalized nanorod array: the functionalized nanorod array constructs zinc oxide nanorods with a diameter of 200 nm on the surface of the scaffold, and the zinc oxide nanorods with a spacing of 300 nm form a nanorod array;

[0027] Quorum sensing interference: the AI-2 analog (D-ribose analog) is loaded in the nanotrap, the AI-2 analog blocks the quorum sensing (QS) system of pathogenic bacteria, and the biofilm formation inhibition rate reaches 92%;

[0028] Macrophage phenotype transformation regulation: the macrophage phenotype transformation regulation uses PLGA microspheres as carriers to load IL-4 / IL-13 cytokines.

[0029] With the preferred scheme, the functionalized nanorod array can physically pierce the bacterial cell membrane, the killing rate of P.gingivalis is >99%, and the bacterial adhesion and biofilm formation are effectively inhibited; the quorum sensing interference can destroy the synergistic pathogenic mechanism of bacteria and reduce the risk of infection; when the microspheres respond to MMP-2 enzyme to release cytokines, the macrophage phenotype transformation can transform M1 type macrophages into M2 type, the transformation rate is >80%, the excessive inflammatory response is inhibited, and an immune microenvironment conducive to tissue regeneration is created.

[0030] Preferably, the real-time monitoring and adaptive repair include an embedded biosensor.

[0031] The embedded biosensor specifically includes a PH pressure dual-mode sensor, an inflammation warning system and a light-controlled tissue remodeling.

[0032] PH pressure dual-mode sensor: the integrated graphene / PDMS flexible sensor has a sensitivity of 0.1 kPa -1 .

[0033] Inflammation warning system: when the sensor detects that the concentration of TNF-α is >20 pg / mL, the in-stent pulsed release of dexamethasone is automatically triggered, and the dose of dexamethasone is 0.1 μg / cm 2 , and the inflammatory response is inhibited in time.

[0034] Light-controlled tissue remodeling: upconversion nanoparticles (NaYF4:Yb 3 +,Er 3+ ) are doped in the hydrogel matrix to form a near-infrared responsive hydrogel.

[0035] With the preferred scheme, the PH pressure dual-mode sensor can realize real-time sensing of the pH value and pressure change of the gingival tissue, and the mechanical state data of the gingival tissue is sent to the mobile phone APP every 6 hours through wireless transmission technology, so that the real-time monitoring of the gingival tissue regeneration process is realized; the inflammation warning system can inhibit the inflammatory response in time and prevent the damage of inflammation to the gingival tissue regeneration; under the irradiation of 808 nm laser, the upconversion nanoparticles convert the near-infrared light into heat energy, so that the local temperature is raised (ΔT=5℃), the shape-memory effect of the hydrogel is activated, the shape of the scaffold is finely adjusted and repaired to adapt to the morphological change in the gingival tissue regeneration process, and precise tissue remodeling is realized.

[0036] Compared with the prior art, the advantages and positive effects of the present application are that,

[0037] The application realizes dynamic deformation adaptation of the stent under temperature and pH response, closely fits the gingival curved surface and improves the microenvironment of the inflammation area through 4D biomimetic stent design; the cell activation and directional regeneration system improves the homing efficiency and directional differentiation ability of stem cells, realizes cell-level regeneration induction; the microbe-immune regulation network effectively inhibits biofilm formation and excessive inflammatory response; the real-time monitoring and adaptive repair module realizes real-time monitoring and dynamic adjustment of the gingival tissue regeneration process. The synergistic effect of the core technology modules can accurately realize the regeneration and functional reconstruction of the gingival structure, and provides an efficient and reliable solution for gingival tissue damage repair. DETAILED DESCRIPTION

[0038] In order to more clearly understand the above-mentioned purposes, features and advantages of the present application, the present application will be further described below in conjunction with the embodiments. It should be noted that the embodiments of the present application and the features in the embodiments can be combined with each other without conflict.

[0039] In the following description, a large number of specific details are set forth in order to provide a thorough understanding of the present application, however, the present application can also be implemented in other ways different from those described herein, therefore, the present application is not limited to the specific embodiments disclosed in the following description.

[0040] Embodiment 1, the present application provides a method for realizing precise regeneration and functional reconstruction of gingival structure by combining regeneration induction, including 4D biomimetic stent design, cell activation and directional regeneration system, microbe-immune regulation network and real-time monitoring and adaptive repair, the 4D biomimetic stent design is divided into shape memory hydrogel matrix, 4D response mechanism and biomimetic microgradient structure.

[0041] The shape memory hydrogel matrix is specifically composed of material composition:

[0042] Material composition: the shape memory hydrogel matrix is made of PVA, gelatin and elastin system, the proportion of each component of PVA, gelatin and elastin system is 60%, 30% and 10%.

[0043] The 4D response mechanism is specifically composed of temperature trigger and use environment:

[0044] Temperature trigger: the response mechanism is started when the oral temperature is lower than 37°, the water crystal glue matrix is fitted with the gingival curved surface, and the shrinkage rate of the hydrogel matrix is 15%;

[0045] Use environment: when the hydrogel matrix is in the inflammation area (PH<6.5), the pores of the hydrogel matrix expand, and the pore size of the hydrogel matrix expands from 50μm to 120μm.

[0046] The biomimetic microgradient structure is specifically composed of mechanical gradient and blood vessel access channel:

[0047] Mechanical gradient: The hydrogel matrix is constructed by electric field-assisted 3D printing technology to build a Young's modulus gradient, the surface layer Young's modulus is 2 MPa, and the deep layer is 0.8 MPa;

[0048] Vessel access channel: The diameter of the spiral microchannel in the stent is 80 μm, and the migration speed of the blood vessel guide channel is 3 times higher than that without the channel structure.

[0049] PVA provides good mechanical properties and water solubility, gelatin has good biocompatibility and cell adhesion, elastin gives the material elasticity, four-arm polyethylene glycol acrylate as a crosslinking agent can form a dynamic crosslinking network, making the material have shape memory characteristics, and providing a stable mechanical environment for gingival tissue regeneration, and is conducive to promoting the release of antibacterial ingredients and exudate drainage, and improving the microenvironment of the inflammatory area; the release of the micro-ladder structure can simulate the mechanical transition of the natural gingiva from the free gingiva to the attached gingiva, providing suitable mechanical signals for the gingival cells in different parts to guide the directional growth and differentiation of the cells; the blood vessel guide channel can promote angiogenesis and provide sufficient nutrient supply for gingival tissue regeneration.

[0050] Cell activation and directional regeneration system includes in-situ activation of stem cell nest and intelligent delivery of exosome.

[0051] The in-situ activation of stem cell nest is specifically chemical niche design and nano-pulse electric field composition:

[0052] Chemical niche design: SDF-1α chemotactic factor is fixed on the surface of the scaffold, and the density of the chemotactic factor is ≥50 ng / cm 2 , the chemotactic factor attracts host gingival mesenchymal stem cells (GMSCs) to home, the recruitment efficiency of the chemotactic factor within 24 hours reaches 90%, and the chemotactic factor provides seed cells for gingival tissue regeneration;

[0053] Nano-pulse electric field: The nano-pulse electric field integrates a micro electrode array, applies a nano-pulse electric field of 50 mV / cm, 1 Hz to the micro electrode array, activates Piezo1 ion channels to induce stem cell osteogenic differentiation, and the alkaline phosphatase (ALP) activity is increased by 400%.

[0054] Intelligent delivery of exosome is specifically composed of loading gingival stem cell exosome (GMSC-Exo) and targeting damaged area:

[0055] Loading gingival stem cell exosome (GMSC-Exo): The loading gingival stem cell exosome (GMSC-Exo) encapsulates the GMSC-Exo in a thermosensitive liposome by liposome fusion technology, the phase transition temperature of the thermosensitive liposome is 38℃, and the loading gingival stem cell exosome can continuously release repairative miRNA (such as miR-21, miR-1246);

[0056] Targeting the damaged area: the exosome surface is modified with a gingiva-specific peptide (GSP, sequence: CKIPKPSSV), which improves the targeting efficiency by 8 times compared to the unmodified group.

[0057] Chemical niche design provides sufficient seed cells for gingival tissue regeneration; nano-pulsed electric field can promote the formation and stability of periodontal ligament-alveolar bone interface; loading gingival stem cell exosomes (GMSC-Exo) can regulate cell gene expression, promote cell proliferation, differentiation and apoptosis regulation; targeting the damaged area: achieving lesion enrichment, the targeting efficiency is improved by 8 times compared to the unmodified group, increasing the concentration of exosomes at the injury site and enhancing the repair effect.

[0058] Microbial-immune regulation network includes anti-biofilm nanotrap.

[0059] The anti-biofilm nanotrap specifically consists of functionalized nanocolumn array, quorum sensing interference, and macrophage phenotype transformation regulation

[0060] Functionalized nanocolumn array: functionalized nanocolumn array constructs zinc oxide nanocolumns with a diameter of 200 nm on the surface of the scaffold, and zinc oxide nanocolumns with a spacing of 300 nm form a nanocolumn array;

[0061] Quorum sensing interference: AI-2 analog (D-ribose analog) is loaded between the nanocolumns, which blocks the quorum sensing (QS) system of pathogenic bacteria, and the biofilm formation inhibition rate reaches 92%;

[0062] Macrophage phenotype transformation regulation: PLGA microspheres are used as carriers to load IL-4 / IL-13 cytokines.

[0063] Functionalized nanocolumn array: This array can physically pierce the bacterial cell membrane, with a killing rate of >99% for P. gingivalis, effectively inhibiting bacterial adhesion and biofilm formation; Quorum sensing interference can disrupt the synergistic pathogenic mechanism of bacteria, reducing the risk of infection; When the microspheres respond to MMP-2 enzyme to release cytokines, macrophage phenotype transformation regulation can convert M1 macrophages to M2, with a conversion rate of >80%, inhibiting excessive inflammatory response and creating an immune microenvironment conducive to tissue regeneration.

[0064] Real-time monitoring and adaptive repair include embedded biosensors.

[0065] Embedded biosensors specifically consist of PH pressure dual-mode sensing, inflammation warning system, and light-controlled tissue remodeling

[0066] PH pressure dual-mode sensing: The integrated graphene / PDMS flexible sensor has a sensitivity of 0.1 kPa -1 ;

[0067] Inflammation warning system: automatically trigger intrastent dexamethasone pulse release when the sensor detects TNF-a concentration > 20 pg / mL, dexamethasone dose 0.1 pg / cm 2 and timely inhibit inflammatory response.

[0068] Light-controlled tissue remodeling: incorporation of upconversion nanoparticles (NaYF4:Yb 3 +,Er 3+ ) in hydrogel matrix, forming near-infrared responsive hydrogel.

[0069] PH pressure bimodal sensing can real-time sense the pH value and pressure changes of gingival tissue, and send the mechanical state data of gingival tissue to the mobile phone APP every 6 hours through wireless transmission technology, realizing real-time monitoring of gingival tissue regeneration process; inflammation warning system: timely inhibition of inflammatory response to prevent inflammation from damaging gingival tissue regeneration; light-controlled tissue remodeling under 808 nm laser irradiation, upconversion nanoparticles convert near-infrared light into heat energy, causing local warming (AT = 5℃), activating the shape-memory effect of hydrogel, fine-tuning the shape of the scaffold to adapt to the morphological changes during gingival tissue regeneration, and realizing precise tissue remodeling.

[0070] The overall working principle is the preparation of a 4D biomimetic scaffold

[0071] Preparation of shape memory hydrogel matrix: according to the ratio of PVA / gelatin / elastin 6:3:1, dissolve each component in deionized water, heat to 50℃ and stir until completely dissolved to obtain a mixed solution. Add an appropriate amount of four-arm polyethylene glycol acrylate (4-arm PEG-AC) as a dynamic crosslinking agent, stir uniformly, and then crosslink by ultraviolet light irradiation to form a shape memory hydrogel matrix.

[0072] Construction of biomimetic micro-graded structure: using electric field assisted 3D printing technology, the prepared hydrogel matrix is used as printing material. During the printing process, by adjusting the electric field parameters, the solidification degree of the material is controlled, and a mechanical gradient structure with a surface Young's modulus of 2 MPa and a deep layer of 0.8 MPa is constructed. At the same time, in the printing process, according to the designed spiral path, a blood vessel guiding channel with a diameter of 80 pm is printed.

[0073] Construction of cell activation and directional regeneration system

[0074] In situ activation of stem cell nest: SDF-1a chemotactic factor is fixed on the surface of 4D biomimetic scaffold by chemical coupling method, and the density of chemotactic factor is controlled to be greater than or equal to 50 ng / cm 2The microelectrode array was integrated on the surface of the scaffold with a distance of 500 μm between electrodes, and connected to an external power supply through wires to apply a nano-pulse electric field of 50 mV / cm at 1 Hz.

[0075] Exosome smart delivery part: gingival stem cells were extracted, cultured and their exosomes (GMSC-Exo) were collected. The GMSC-Exo were encapsulated in thermosensitive liposomes by liposome fusion technology, and the phase transition temperature of the thermosensitive liposomes was 38℃. The gingival-specific peptide (GSP, sequence: CKIPKPSSV) was modified on the surface of the liposomes by chemical coupling method to connect the peptide segment to the surface of the liposomes. The encapsulated exosomes were uniformly loaded into the pores of the 4D biomimetic scaffold.

[0076] Construction of microbial-immune regulation network

[0077] Anti-biofilm nanotrap part: zinc oxide nanorod arrays with a diameter of 200 nm and a spacing of 300 nm were prepared on the surface of the 4D biomimetic scaffold by chemical vapor deposition. AI-2 analogues (D-ribose analogues) were loaded into the scaffold material by physical adsorption, and the loading amount was 10 μg / cm 2 .

[0078] Macrophage phenotype regulation part: PLGA microspheres were prepared by emulsion polymerization, and IL-4 and IL-13 cytokines were encapsulated in the microspheres. The microspheres were uniformly dispersed in the matrix of the 4D biomimetic scaffold, and the diameter of the microspheres was 1-5 μm, and the loading amount of the cytokines was 5 ng / microsphere.

[0079] Integration of real-time monitoring and self-adaptive repair module

[0080] Embedded biosensor: graphene / PDMS flexible sensors were prepared into a thin film by microfabrication technology, and the size of the sensor matched the 4D biomimetic scaffold. The sensor was pasted on the inner surface of the scaffold, and connected to the wireless transmission module through wires. The wireless transmission module can send the pH and pressure data collected by the sensor to the mobile phone APP in real time. A drug release device was integrated inside the scaffold, loaded with dexamethasone, and when the sensor detected that the concentration of TNF-α was >20 pg / mL, the drug release device was triggered by wireless signal, and the release dose was 0.1 μg / cm 2 .

[0081] Light-controlled tissue remodeling part: when preparing the shape memory hydrogel matrix, upconversion nanoparticles (NaYF4:Yb 3 +,Er 3+ ) were doped at a concentration of 1 wt%. The scaffold was irradiated using an 808 nm laser irradiation device, and the laser power density was 1 W / cm 2The irradiation time is adjusted according to requirements, local temperature rising is realized, shape-memory effect is activated, and fine repair is realized.

[0082] After each part is prepared, the device is obtained by assembling in the order of the 4D bionic scaffold, the cell activation and directional regeneration system, the microorganism-immune regulation network and the real-time monitoring and self-adaptive repair module. In use, the device is implanted into the gum damage site, and the precise regeneration and functional reconstruction of the gum structure are realized by the synergistic effect of the modules.

[0083] The above is only a preferred embodiment of the present application, and is not intended to limit the present application in other forms. Any person skilled in the art can modify or change the above disclosed technical content to equivalent embodiments applied to other fields, but any simple modification, equivalent change and modification made to the above embodiments without departing from the technical solution content of the present application, according to the technical essence of the present application, still belongs to the protection scope of the technical solution of the present application.

Claims

1. A method for achieving precise regeneration of gingival structure and functional reconstruction by combining regenerative induction, characterized by: include: 4D biomimetic scaffold design, cell activation and directional regeneration system, microbial-immune regulatory network, and real-time monitoring and adaptive repair. The 4D biomimetic scaffold design includes a shape memory hydrogel matrix, a 4D response mechanism, and a biomimetic micro-gradient structure. The shape memory hydrogel matrix is ​​specifically composed of the following materials: Material composition: The shape memory hydrogel matrix is ​​made of PVA, gelatin and elastin system, and the proportions of the PVA, gelatin and elastin system are 60%, 30% and 10% respectively; The 4D response mechanism is specifically composed of temperature trigger and usage environment: Temperature trigger: The response mechanism is activated when the oral temperature is lower than 37°C, the crystal gel matrix is ​​bonded to the gum surface, and the shrinkage rate of the hydrogel matrix is ​​15%; Usage environment: When the hydrogel matrix is ​​in an inflammatory area and the pH is less than 6.5, the pores of the hydrogel matrix expand, and the pore size of the hydrogel matrix increases from 50 μm to 120 μm; The bionic micro-gradient structure is specifically composed of a mechanical gradient and a blood vessel access channel: Mechanical gradient: The hydrogel matrix is ​​constructed with a Young's modulus gradient through electric field-assisted 3D printing technology, with the Young's modulus of the surface layer being 2 MPa and the deep layer being 0.8 MPa; Blood vessel guiding channel: The spiral microchannel built into the stent has a diameter of 80μm, and the migration speed of the blood vessel guiding channel is increased by 3 times compared with the structure without channel.

2. The method of combining regeneration induction to achieve precise regeneration of gingival structure and functional reconstruction according to claim 1, characterized in that: The cell activation and directed regeneration system includes in situ activation of stem cell niches and intelligent delivery of exosomes; The in situ activation of the stem cell niche is specifically composed of chemical niche design and nano-pulsed electric field: Chemical niche design: The surface of the scaffold is fixed with SDF-1α chemokine, and the density of the chemokine is ≥50ng / cm 2 The chemokine attracts host gingival mesenchymal stem cells to home, and the recruitment efficiency of the chemokine reaches 90% within 24 hours. The chemokine provides seed cells for gingival tissue regeneration; Nano-pulsed electric field: The nano-pulsed electric field integrates a micro-electrode array. The nano-pulsed electric field of 50mV / cm and 1Hz applied to the micro-electrode array activates the Piezo1 ion channel to induce osteogenic differentiation of stem cells, and the alkaline phosphatase activity is increased by 400%; The exosome intelligent delivery is specifically composed of loaded gingival stem cell exosomes and targeted damaged areas: Loaded gingival stem cell exosomes: the loaded gingival stem cell exosomes are encapsulated in thermosensitive liposomes by liposome fusion technology. The phase transition temperature of the thermosensitive liposomes is 38°C. The loaded gingival stem cell exosomes can continuously release restorative miRNA; Targeting damaged areas: The exosome surface is modified with gum-specific peptides, and the targeting efficiency is increased 8 times compared to the unmodified group.

3. The method of combining regeneration induction to achieve precise gingival structure regeneration and functional reconstruction according to claim 1, characterized in that: The microbial-immune regulatory network includes anti-biofilm nanotraps; The anti-biofilm nanotrap is specifically composed of a functionalized nanopillar array, quorum sensing interference, and macrophage phenotypic deformation regulation; Functionalized nanopillar array: The functionalized nanopillar array is constructed on the surface of the stent with zinc oxide nanopillars with a diameter of 200 nm, and the zinc oxide nanopillars are spaced 300 nm apart to form a nanopillar array; Quorum sensing interference: The medium is loaded with AI-2 analogs, which block the quorum sensing system of pathogenic bacteria, and the biofilm formation inhibition rate reaches 92%; Macrophage phenotype deformation regulation: The macrophage phenotype deformation regulation uses PLGA microspheres as carriers to load IL-4 / IL-13 cytokines.

4. The method of claim 1 for achieving precise regeneration and functional reconstruction of gingival structure by combining regeneration induction, characterized in that: The real-time monitoring and adaptive repair include embedded biosensors; The embedded biosensor specifically comprises pH and pressure dual-mode sensing, inflammation early warning system and light-controlled tissue remodeling; pH pressure dual-mode sensing: The integrated graphene / PDMS flexible sensor has a sensitivity of 0.1 kPa -1 ; Inflammation early warning system: When the sensor detects TNF-α concentration greater than 20 pg / mL, it automatically triggers the release of dexamethasone pulses within the stent. The dexamethasone dose is 0.1 μg / cm 2 Inhibit inflammatory response in a timely manner; Light-controlled tissue remodeling: Upconversion nanoparticles are incorporated into the hydrogel matrix to form a near-infrared responsive hydrogel.