Dental pulp regeneration structure based on piezoelectric intelligent material and preparation method thereof

Abstract

The invention provides a dental pulp regeneration structure based on a piezoelectric intelligent material and a preparation method of the dental pulp regeneration structure, and relates to the technical field of dental pulp regeneration, the preparation method of the dental pulp regeneration structure based on the piezoelectric intelligent material comprises the following steps: mixing a biodegradable polymer and piezoelectric ceramic in chloroform to form uniform slurry, the method comprises the following steps: constructing a three-dimensional porous scaffold with periodically arranged pores by adopting a 4D printing method, wherein the Poisson ratio of the three-dimensional porous scaffold is-0.3 to-0.8; and a piezoelectric material film is attached to the surface of the three-dimensional porous bracket. The tissue scaffold forming the three-dimensional space complex has a negative Poisson's ratio superstructure design, the energy absorption effect can be remarkably improved, the piezoelectric property can be enhanced, the differentiation efficiency of tissue cell nerves can be improved through stronger electrical stimulation, and dental pulp regeneration is promoted.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of dental pulp regeneration, in particular to a dental pulp regeneration structure based on piezoelectric intelligent material and a preparation method thereof. BACKGROUND

[0002] The morphology and structure of young permanent teeth have not yet developed maturely, and are prone to cause pulp infection, necrosis and apical tissue inflammation due to factors such as trauma, caries and developmental deformities. If not timely intervention, it will lead to the development of the root to stop, the root apex hole cannot be closed, and even cause complications such as chronic apical periodontitis. Although the traditional root canal treatment method can control infection, it cannot promote the continuous development of the tooth root, and may affect the mechanical properties and service life of the tooth in the long term. In recent years, dental pulp regeneration technology has been widely concerned in the treatment of young permanent teeth. This method can ensure the continuous development of the tooth root of young permanent teeth, preserve the vital pulp during treatment and guide the regeneration of dental pulp. For non-pulp teeth, a three-dimensional space complex of tissue cells-intelligent material is constructed and implanted into the pulp cavity of the affected tooth to promote blood revascularization and the proliferation and differentiation of tissue cells, induce nerve differentiation, and ultimately form a reparative dental pulp-dentin complex. Dental pulp regeneration technology is replacing root canal treatment and becoming the mainstream method for repairing damaged dental pulp.

[0003] However, the related technology still has the following problems: the nerve differentiation efficiency of the traditional chemical induction method is low, which affects the recovery of the dental pulp sensory function and restricts the development of the dental pulp regeneration technology; the regeneration speed of the tissue cells is slow, which is difficult to meet the demand of rapid repair of young permanent teeth; and the vascularization ability is insufficient, which leads to limited blood supply of the regenerated dental pulp and affects the long-term survival rate. SUMMARY

[0004] The problem solved by the present application is how to solve the problems of low nerve differentiation efficiency, slow tissue cell regeneration speed and insufficient vascularization ability after the three-dimensional space complex of tissue cells-intelligent material is implanted into the pulp cavity of the affected tooth.

[0005] To solve the above problems, the present application provides a dental pulp regeneration structure based on piezoelectric intelligent material and a preparation method thereof.

[0006] In a first aspect, the present application provides a preparation method of a dental pulp regeneration structure based on piezoelectric intelligent material, comprising the following steps: S1: taking a biodegradable polymer and a piezoelectric ceramic and mixing them in chloroform to form a uniform slurry, and using a 4D printing method to construct a three-dimensional porous scaffold with periodically arranged pores, the Poisson's ratio of the three-dimensional porous scaffold being -0.3 to -0.8; S2: attaching a piezoelectric material film to the surface of the three-dimensional porous scaffold.

[0007] Optionally, the biodegradable polymer is polycaprolactone, poly(lactic-co-glycolic acid) or polylactic acid.

[0008] Optionally, the piezoelectric ceramic is BaTiO3 or ZnO.

[0009] Optionally, the porosity of the three-dimensional porous scaffold is ≥ 70%.

[0010] Optionally, the three-dimensional porous scaffold is a concave hexagonal lattice, the unit cell size of the concave hexagonal lattice is 1-3 mm, and the wall thickness is 100-300 μm.

[0011] Optionally, the nozzle temperature of the 4D printing method is 150-200 °C, and the printing speed is 2-8 mm / s.

[0012] Optionally, between step S1 and step S2, there is also a step: S11: heat treating the three-dimensional porous scaffold at 50-70 °C for 0.5-1.5 h to trigger the shape memory effect of the three-dimensional porous scaffold, so that the three-dimensional porous scaffold spontaneously shrinks by 10%-30% to adapt to the dental pulp cavity; S12: applying a direct current electric field of 1-3 kV / mm to the three-dimensional porous scaffold at 70-90 °C for 20-40 min to make the piezoelectric ceramic particles directionally arrange to improve the piezoelectric coefficient.

[0013] Optionally, the thickness of the piezoelectric material film is 20-100 μm.

[0014] Optionally, the piezoelectric material film attached to the surface of the three-dimensional porous scaffold comprises: In-situ electrospinning: in-situ electrospinning of PVDF-TrFE composite material on the surface of the three-dimensional porous scaffold, the fiber diameter is 500 nm-2 μm, the thickness of the piezoelectric material film is 20-50 μm, and annealing at 80-100 °C and polarization at 90-110 MV / m are performed to obtain a β phase content of more than 80%; or Solution casting + hot pressing: casting a BaTiO3-PVDF composite solution to the surface of the three-dimensional porous scaffold, volatilizing the solvent at 50-70 °C, and hot pressing at 90-110 °C for 5-15 min to obtain a piezoelectric material film with a thickness of 50-100 μm; or Using multi-nozzle 4D printing, uniformly extruding the slurry and PVDF-graphene composite ink synchronously, and integrally constructing the three-dimensional porous scaffold and the piezoelectric material film.

[0015] In a second aspect, the present application provides a dental pulp regeneration structure based on piezoelectric smart material, which is prepared by using the preparation method of the dental pulp regeneration structure based on piezoelectric smart material according to any one of the above.

[0016] The tooth pulp regeneration structure based on the piezoelectric intelligent material and the preparation method thereof have the following beneficial effects: the three-dimensional porous support has pores, which facilitates filling of different tissue cells; for a non-pulp tooth, tissue cells and bioactive factors are filled in the geometric pores of the three-dimensional porous support to form a three-dimensional space complex; and the three-dimensional space complex is transplanted into the pulp cavity of the non-pulp tooth, so that the purpose of tooth pulp regeneration is achieved. When the tooth is subjected to mechanical movement such as occlusion, the three-dimensional porous support is deformed under the action of mechanical load, and the deformation of the three-dimensional porous support drives the deformation of the outer piezoelectric material film, thereby causing polarization, causing the upper and lower surfaces of the three-dimensional space complex to have different electric charges, so that the conversion of mechanical energy into electrical energy is realized, and a certain electrical signal is generated to stimulate the nerve differentiation of tissue cells and the directional induction of odontoblast cells. The electrical stimulation can effectively improve the nerve differentiation efficiency and multiplication efficiency of tissue cells, realize the functional regeneration of the tooth pulp-odontoblast complex, and obtain a functional recovery effect closer to the natural tooth pulp by optimizing stem cell regulation, enhancing synchronous regeneration of blood vessels and nerves, and improving mechanical stability. Since the tissue support constituting the three-dimensional space complex has a negative Poisson's ratio superstructure design, the energy absorption effect can be significantly improved, the piezoelectric performance is enhanced, and stronger electrical stimulation can improve the efficiency of nerve differentiation of tissue cells and promote tooth pulp regeneration. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 A flowchart of the preparation method of the tooth pulp regeneration structure based on the piezoelectric intelligent material according to the embodiment of the present application; Figure 2 A structure schematic diagram of the tooth pulp regeneration structure based on the piezoelectric intelligent material according to the embodiment of the present application; Figure 3 A structure schematic diagram of the three-dimensional porous support according to the embodiment of the present application; Figure 4 A structure schematic diagram of the three-dimensional porous support not subjected to mechanical load to produce deformation according to the embodiment of the present application; Figure 5 A structure schematic diagram of the three-dimensional porous support subjected to mechanical load to produce deformation according to the embodiment of the present application; Explanation of reference signs: 1, three-dimensional porous support; 2, piezoelectric material film. DETAILED DESCRIPTION

[0018] To make the above-mentioned objects, features, and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings. Although some embodiments of the present invention are shown in the drawings, it should be understood that the present invention can be implemented in various forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided to provide a more thorough and complete understanding of the present invention. It should be understood that the accompanying drawings and embodiments of the present invention are for illustrative purposes only and are not intended to limit the scope of protection of the present invention.

[0019] Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used in this invention's description is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "comprising" and its variations as used herein are open-ended inclusion, meaning "including but not limited to"; the term "based on" means "at least partially based on"; the term "one embodiment" means "at least one embodiment"; the term "another embodiment" means "at least one additional embodiment"; the term "some embodiments" means "at least some embodiments"; and the term "optionally" means "optional embodiments". Definitions of other terms will be given in the description below.

[0020] Among related technologies, pulp regeneration has become a hot topic in oral medicine research in recent years, aiming to restore the biological function of the pulp-dentin complex and achieve long-term stable tooth preservation. In the field of pulp regeneration, pulp regeneration of young permanent teeth is currently the most commonly used approach. Young permanent teeth have strong tissue regeneration potential due to their unclosed apex (apical foramen diameter is usually >1mm) and the presence of viable pulp stem cells and rich blood supply in the periapical region. Although this approach has achieved some success in clinical applications, some problems remain, such as low cell migration efficiency, insufficient angiogenesis, incomplete nerve recovery, and hindered root development.

[0021] To address the problems existing in the aforementioned related technologies, embodiments of the present invention provide a dental pulp regeneration structure based on piezoelectric smart materials and its preparation method.

[0022] like Figure 1 As shown, an embodiment of the present invention provides a method for preparing a dental pulp regeneration structure based on piezoelectric smart materials, comprising the following steps: S1: Biodegradable polymers and piezoelectric ceramics are mixed in chloroform to form a uniform slurry. A three-dimensional porous scaffold 1 with periodically arranged pores is constructed using a 4D printing method. The Poisson's ratio of the three-dimensional porous scaffold 1 is -0.3 to -0.8. S2: A piezoelectric material film 2 is attached to the surface of the three-dimensional porous support 1.

[0023] In this embodiment, as shown in Figure 2 , a three-dimensional porous scaffold 1-piezoelectric material film 2 composite structure with multiple biomimetic characteristics is constructed, as shown in Figure 3 , the three-dimensional porous scaffold 1 with negative Poisson's ratio characteristics, the unique hyperbolic topological structure is realized by the precisely designed fillable voids, which is extracellular matrix biomimetic, providing an optimized three-dimensional physical microenvironment for cell migration and tissue growth; the surface integrated piezoelectric material film 2 can be dynamically electrically regulated, and can generate electricity autonomously through physiological mechanical stimulation, match the electrophysiological parameters of dental pulp development, avoid the invasiveness of external power supply, and realize self-powered tissue regeneration.

[0024] By utilizing the electromechanical transduction characteristics of piezoelectric ceramics, precise regulation of stem cells is realized. When the three-dimensional porous scaffold 1 structure is subjected to physiological mechanical load such as chewing, the built-in piezoelectric functional layer can convert mechanical stimulation into dynamic electrical signals, forming a spatiotemporal specific electrical physiological microenvironment. This biomimetic electrical stimulation can significantly promote the differentiation of neural crest-derived stem cells into dental pulp neurons and the directional induction of odontoblasts, achieving functional regeneration of dental pulp-dentin complex. By optimizing stem cell regulation, enhancing synchronous vascular and nerve regeneration, and improving mechanical stability, a functional recovery effect closer to natural dental pulp can be achieved.

[0025] As shown in Figure 3 , the three-dimensional porous scaffold 1 is made of piezoelectric ceramics with piezoelectric effect combined with 4D printing technology, and has negative Poisson's ratio characteristics. As shown in Figure 4 , the three-dimensional porous scaffold 1 has pores, which are convenient for filling different tissue cells. For non-pulp teeth, tissue cells and bioactive factors are filled in the geometric pores of the three-dimensional porous scaffold 1 to form a three-dimensional spatial complex. Transplanting the above-mentioned three-dimensional spatial complex into the pulp cavity of non-pulp teeth can achieve the purpose of dental pulp regeneration. As shown in Figure 5 , when the tooth undergoes mechanical movement such as occlusion, the three-dimensional porous scaffold 1 is subjected to mechanical load and deforms, and the deformation of the three-dimensional porous scaffold 1 drives the deformation of the external piezoelectric material film 2, thereby causing polarization phenomenon, causing the upper and lower surfaces of the three-dimensional spatial complex to produce different charges, thereby realizing the conversion of mechanical energy to electrical energy, generating a certain electrical signal to stimulate tissue cell neural differentiation. This electrical stimulation will effectively improve the neural differentiation efficiency and proliferation efficiency of tissue cells, which is beneficial to dental pulp tissue regeneration. Because the tissue scaffold that constitutes the three-dimensional spatial complex has a negative Poisson's ratio superstructure design, the energy absorption effect can be significantly improved, and the piezoelectric performance is enhanced. Stronger electrical stimulation can improve the efficiency of neural differentiation of tissue cells and promote dental pulp regeneration.

[0026] 4D printing can form complex microstructures and can be customized according to the shape of the tooth to adapt to different pulp cavity structures, so as to maximize the retention of the patient's own teeth. The three-dimensional porous scaffold 1 prepared by 4D printing can deform with external excitation and time, thereby collecting mechanical energy and converting the collected mechanical energy into electrical energy to generate an electrical signal to stimulate cell differentiation and promote dental pulp tissue regeneration. The three-dimensional porous scaffold 1 prepared by 4D printing technology can precisely control the spatial positioning of multiple cells, and different tissue cells are suspended and positioned at different positions of the three-dimensional porous scaffold 1, which is beneficial to realize the interaction between different cells and realize the regeneration of the overall morphology of the tissue.

[0027] The present application proposes a strategy of electric stimulation combined with chemical induction for dental pulp regeneration, which breaks through the limitation of low efficiency of traditional single growth factor induction, and simultaneously utilizes the natural occlusal force to drive the deformation of the piezoelectric ceramic material to generate electricity, so that the upper and lower surfaces of the material generate different electric charges to generate electricity without external power supply, thereby realizing continuous and dynamic electrical signal regulation. The microstructure of the piezoelectric material (such as porosity and surface charge) is optimized to precisely match the cell microenvironment and improve the quality of tissue regeneration. In combination with the vascularization strategy, the piezoelectric potential is utilized to promote the migration of endothelial cells and angiogenesis, thereby improving the survival rate of the regenerated tissue. The three-dimensional scaffold (porosity ≥ 70%) is constructed by using 4D printing technology, and the volume shrinks when subjected to pressure, thereby reserving space for tissue regeneration. The present application solves some problems existing in traditional dental pulp regeneration technology through the innovative application of piezoelectric materials, and has scientific advancement and clinical feasibility, thereby having a broad market application prospect.

[0028] Specifically, the three-dimensional porous scaffold 1 can adopt a superstructure design, such as an inner concave hexagon or a chiral honeycomb structure, has a tensile expansion effect (Poisson's ratio -0.3 to -0.8), can significantly enhance the energy absorption capacity, and the energy absorption rate is increased by 30% to 50%, thereby significantly enhancing the piezoelectric conversion efficiency. Gradient pore structure design can be used, a lower density microstructure design is selected near the dental pulp, more space can be filled with more tissue cells and growth factors and other substances conducive to cell differentiation and proliferation, and the microstructure density is increased near the dental crown, thereby increasing the load bearing capacity, the pore size is 50 to 500 μm, the porosity is 70% to 90%, the spatial precise positioning of cells and growth factors is realized, and the vascularization and nerve regeneration are promoted.

[0029] The three-dimensional porous scaffold 1 is deformed due to extrusion or occlusion and other mechanical movements, and due to the negative Poisson's ratio characteristic, the three-dimensional porous scaffold 1 becomes thin and small, thereby leaving space for the growth of the dental pulp and facilitating the regeneration of the dental pulp.

[0030] Specifically, the three-dimensional porous scaffold 1 with negative Poisson's ratio is formed by 4D printing and personalized molding, which is adapted to the complex pulp cavity morphology, and the matching degree is ≥ 95%, and the deformation is completed under the body temperature trigger (such as 37 to 42℃), thereby improving the operability of the operation.

[0031] Optionally, the biodegradable polymer is polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or polylactic acid (PLA).

[0032] In this optional embodiment, by selecting PCL, PLGA and PLA, three types of controllable degradation materials, not only the gradient matching of degradation kinetics is achieved, but also multi-level mechanical stimulation is formed through the difference in material stiffness. The high elastic modulus of PCL can transmit the mastication stress, the rigid structure of PLA can maintain the scaffold morphology, and the flexible characteristics of PLGA are conducive to the remodeling of extracellular matrix, solving the technical problem of mismatch between the degradation rate of the biological scaffold and the speed of tissue regeneration.

[0033] Specifically, polycaprolactone (PCL) refers to an aliphatic polyester material with a long degradation period, which can be implemented by using a linear polymer with a molecular weight of 50,000 to 100,000. It has a high crystallinity and can degrade in vivo for more than 12 months, providing sustained mechanical support for the three-dimensional porous scaffold 1. Poly(lactic-co-glycolic acid) (PLGA) refers to a degradable material formed by copolymerization of lactic acid and glycolic acid. By adjusting the molar ratio of lactic acid to glycolic acid in the range of 50:50 to 85:15, the degradation period can be controlled in the range of 2 to 6 months. Its amorphous structure is conducive to the penetration of extracellular matrix. Polylactic acid (PLA) refers to a thermoplastic polyester formed by polymerization of lactic acid monomers. It can be implemented by using levorotatory polylactic acid PLLA or racemic polylactic acid PDLA. Its glass transition temperature is 50-60℃, and the lactic acid generated during the degradation process can adjust the local microenvironment pH value.

[0034] Specifically, the slow degradation characteristics of polycaprolactone (PCL) can maintain the structural integrity of the scaffold in the early stage of dental pulp regeneration, avoiding premature collapse that hinders cell migration. By adjusting the copolymerization ratio, poly(lactic-co-glycolic acid) (PLGA) can achieve dynamic matching of the degradation rate and the proliferation rate of dental pulp stem cells. For example, when the glycolic acid content is increased to 50%, the degradation period can be shortened to 3 months, which is consistent with the key period of dental pulp vascularization. The lactic acid monomer released during the degradation of polylactic acid (PLA) can form a slightly acidic environment, which can activate the TRPV1 ion channel of dental pulp stem cells and promote the expression of nerve differentiation marker β3-tubulin. After the three types of materials are compounded with piezoelectric ceramics, their different crystallinities affect the dispersion state of the piezoelectric phase. The amorphous structure of PLGA is conducive to the uniform distribution of piezoelectric particles, while the semi-crystalline structure of PCL can form stress concentration points to enhance the piezoelectric response.

[0035] Optionally, the piezoelectric ceramic is BaTiO3 or ZnO.

[0036] In this optional embodiment, barium titanate and zinc oxide exhibit stable chemical inertness in a physiological environment, promoting the electrophysiological activity of neural precursor cells by optimizing the charge generation capacity and surface potential distribution, while accelerating the formation of vascular networks using the biocompatibility of material degradation products, thereby improving the speed of pulp regeneration and the effect of tissue functional reconstruction. A directional arrangement of BaTiO3 nanofiber arrays is used to optimize the piezoelectric coefficient through interface polarization engineering to match the electrophysiological parameters of pulp development.

[0037] Specifically, barium titanate refers to a ferroelectric ceramic material with a perovskite crystal structure, which can be prepared by sol-gel method or hydrothermal synthesis method. Its high dielectric constant and piezoelectric coefficient can enhance the charge generation capacity of the scaffold under stress. Zinc oxide refers to a semiconductor piezoelectric material with a wurtzite structure, which can be prepared by chemical vapor deposition or electrochemical deposition. Its nanowire morphology can increase the surface roughness to promote cell adhesion.

[0038] Specifically, the piezoelectric response of barium titanate can generate a stable surface potential under external mechanical stimulation, promoting the directional extension of neural synapses by regulating cell membrane potential. The semiconductor properties of zinc oxide form a local potential gradient in the body fluid environment, accelerating calcium ion influx to activate neural differentiation-related pathways. Metal ions released during the degradation of the two materials can participate in cell metabolism, further supporting the migration and lumen formation of vascular endothelial cells.

[0039] Optionally, the porosity of the three-dimensional porous scaffold 1 is ≥70%.

[0040] In this optional embodiment, the porosity range is defined to construct a high-connectivity pore network, significantly improving the migration efficiency of vascular endothelial cells and the permeability of nutrients, while avoiding the risk of structural collapse caused by excessively high porosity. It solves the problem of limited blood supply caused by insufficient vascularization during pulp regeneration, promoting the rapid formation of new blood vessels to maintain the survival rate of regenerated tissues; at the same time, high porosity provides sufficient space conditions for stem cell proliferation and differentiation, accelerating the pulp tissue regeneration process to meet the rapid repair needs of young permanent teeth.

[0041] Specifically, porosity refers to the proportion of pore volume inside the material to the total volume, which can be achieved by adjusting the spacing, layer thickness and filling density parameters of the printing path, such as the periodic alternating path arrangement strategy in 4D printing technology. The parameter is set to no less than 70% to construct a high-permeability structure, promoting cell migration and material exchange. The lower limit of porosity control can avoid the blockage of cell infiltration caused by excessively small pores, while maintaining the mechanical support performance of the scaffold.

[0042] Specifically, the high porosity three-dimensional porous scaffold 1 forms a network of interconnected channels inside, providing sufficient growth space for cells and diffusion paths for nutrients. The dense and interconnected pore structure accelerates the directional migration of vascular endothelial cells and the formation of new blood vessels, while increasing the specific surface area of the scaffold to improve the loading efficiency of bioactive factors, promoting the adhesion, proliferation and differentiation of stem cells. The balance between porosity and mechanical properties is achieved by optimizing the printing parameters, for example, when using an inner hexagonal lattice topology, by adjusting the unit cell size and wall thickness ratio, the porosity is maintained while the structural stability is maintained.

[0043] Optionally, the three-dimensional porous scaffold 1 is an inner hexagonal lattice, and the unit cell size of the inner hexagonal lattice is 1-3 mm, and the wall thickness is 100-300 μm.

[0044] In this optional embodiment, the anisotropic pore arrangement of the inner hexagonal lattice can simulate the fiber bundle orientation of the natural dental pulp tissue, and its negative Poisson's ratio property makes the scaffold expand laterally when subjected to compressive load, thereby actively fitting the irregular dental pulp cavity wall. In addition, the stiffness distribution optimization achieved by the wall thickness gradient design can match the elastic modulus difference between dentin and new tissue. It can improve the adaptability of the scaffold to the shape of the dental pulp cavity, promote the directional migration of neural crest stem cells along the pore channel and differentiate into functional neurons, accelerate the formation of vascular endothelial cells into a through-hole structure, and reduce the risk of mechanical damage to the new tissue under functional load through the optimized stiffness distribution. Finally, it realizes the efficient reconstruction of nerve function and vascular network in the process of dental pulp regeneration.

[0045] Specifically, the inner hexagonal lattice refers to a three-dimensional network structure composed of periodically arranged inner hexagonal cells, which can be realized by computer-aided design modeling combined with 4D printing technology. Its negative Poisson's ratio property can enhance the stress dispersion ability of the scaffold under dynamic load. The unit cell size refers to the geometric size range of a single inner hexagonal cell in three-dimensional space, which can be controlled by adjusting the printing path parameters. This size range can balance the overall mechanical strength and pore connectivity of the scaffold. The wall thickness refers to the thickness of the solid structure that constitutes the inner hexagonal lattice, which can be achieved by adjusting the extrusion amount of the printing material. This thickness range can maintain the porosity while optimizing the local stiffness distribution.

[0046] Specifically, the periodic arrangement of pores in the concave hexagonal lattice forms a network of directional channels, providing spatial guidance for cell migration. Simultaneously, the local curvature changes generated by its concave geometry promote the directional deposition of extracellular matrix proteins. The specific cell size ensures continuous nutrient diffusion pathways between adjacent pores, preventing insufficient cell adhesion substrate area due to excessively large pores. The synergistic design of the wall thickness allows the scaffold to absorb energy through elastic deformation of the lattice walls under pressure, preventing stress concentration and mechanical damage to newly formed tissue. Thus, this structure activates intracellular mechanotransduction pathways by regulating the spatial distribution of microscale mechanical stimuli, promoting the expression of neuronal markers in neural crest stem cells.

[0047] Optionally, the nozzle temperature of the 4D printing method is 150 to 200 °C, and the printing speed is 2 to 8 mm / s.

[0048] In this optional embodiment, by establishing a temperature-velocity coordinated control model, dynamic matching between material rheological properties and structural forming requirements is achieved, resolving the contradiction between structural deformation during high-speed printing and insufficient porosity during low-temperature printing. This effectively maintains the periodic arrangement of pores in the three-dimensional porous scaffold 1, ensuring accurate forming of the negative Poisson's ratio structure, while avoiding piezoelectric performance degradation due to improper processing parameters. This provides a scaffold carrier with stable mechanical properties and electroactive response for pulp regeneration devices.

[0049] Specifically, nozzle temperature refers to the temperature range at which material is extruded from the nozzle during the printing process. This temperature range can be achieved by adjusting the power of the heating module. This temperature range ensures that the mixture of biodegradable polymers and piezoelectric ceramics has appropriate fluidity while preventing thermal decomposition of the material. Printing speed refers to the rate at which the nozzle moves across the printing plane. This speed range can be achieved by adjusting the drive frequency of the stepper motor. This speed range can balance the curing time of the extruded slurry with the structural forming accuracy.

[0050] Specifically, during 4D printing, when the nozzle temperature is below 150°C, the viscosity of the slurry mixture of biodegradable polymers and piezoelectric ceramics is too high, leading to filament breakage or uneven pore filling during extrusion. When the temperature exceeds 200°C, the polymer chain segments undergo thermal degradation, affecting the mechanical properties of the scaffold. When the printing speed is below 2 mm / s, the molten slurry remains for too long after deposition, resulting in excessive fusion between adjacent layers and a decrease in porosity. When the speed exceeds 8 mm / s, the slurry is covered by subsequent layers before it can be fully extended, leading to uneven lattice wall thickness. By controlling the temperature and speed within the above-mentioned ranges, the molten slurry can quickly form a stable shape after extrusion, maintaining the preset concave hexagonal lattice structure, while ensuring the uniform dispersion of piezoelectric ceramic particles in the slurry, providing a foundation for subsequent polarization treatment.

[0051] Optionally, between step S1 and step S2, there is also a step: S11: heat treating the three-dimensional porous scaffold 1 at 50-70°C for 0.5-1.5 h to trigger the shape memory effect of the three-dimensional porous scaffold 1, so that the three-dimensional porous scaffold 1 spontaneously shrinks by 10%-30% to adapt to the dental pulp cavity; S12: applying a direct current electric field of 1-3 kV / mm to the three-dimensional porous scaffold 1 at 70-90°C for 20-40 min to make the piezoelectric ceramic particles directionally arrange to improve the piezoelectric coefficient.

[0052] In this optional embodiment, the morphology adaptation and function enhancement are completed before the three-dimensional porous scaffold 1 is implanted through a staged regulation strategy, which not only avoids the risk of secondary surgery adjustment, but also significantly improves the stability of electric signal output through the ordered arrangement of particles. The morphology of the three-dimensional porous scaffold 1 is self-adapted to the dental pulp cavity, which provides an optimized spatial support structure for cell proliferation, and a stable electric stimulation microenvironment is formed through the directional arrangement of piezoelectric ceramics, which effectively promotes nerve differentiation and tissue regeneration.

[0053] Specifically, the heat treatment triggering the shape memory effect refers to activating the morphology memory ability of the biodegradable polymer by temperature stimulation, which can be realized by incubating in a thermostat at a set temperature range. This process makes the three-dimensional porous scaffold 1 spontaneously shrink and deform, so as to form a spatial adaptation with the irregular dental pulp cavity. The application of a direct current electric field to promote the directional arrangement of particles refers to using electric field force to drive the piezoelectric ceramic particles to arrange in a specific direction. Specifically, a uniform electric field can be applied in a heated environment by a high-voltage power supply to realize this operation, which can optimize the polarization direction of the piezoelectric material and enhance the overall piezoelectric response performance.

[0054] Specifically, after the scaffold is formed, heat treatment is first performed. When the temperature reaches the critical point of material phase transition, the conformation of the polymer chain segment is reorganized, which promotes the controllable shrinkage of the overall scaffold volume. This self-deformation mechanism without external intervention can avoid the destruction of the pore structure caused by traditional mechanical compression, and at the same time realize the morphology matching with the dental pulp cavity. Then a direct current electric field is applied under high temperature conditions. At this time, the interface potential barrier of the piezoelectric ceramic particles is reduced, and under the driving of the electric field, a chain-like arrangement structure is formed along the field intensity direction. This directional arrangement effectively improves the density of piezoelectric active sites in unit volume.

[0055] Optionally, the thickness of the piezoelectric material film 2 is 20-100 μm.

[0056] In this optional embodiment, the piezoelectric material film 2 is too thin to be easily broken, and too thick to reduce flexibility and electrical signal sensitivity. The thickness range can ensure that the piezoelectric layer remains stable under dynamic stress, while avoiding the problem of insufficient electrical signal output due to being too thin or stress concentration caused by being too thick. By limiting the thickness range, a balance is established between dynamic stress response and cell permeability, solving the contradiction in traditional methods that electrical stimulation efficiency and mechanical adaptability are difficult to balance. It can promote the directional differentiation of nerve cells on the surface of the piezoelectric material film 2, enhance the ability of the regenerated dental pulp tissue to form a vascular network, and at the same time maintain the mechanical adaptability of the scaffold-dentin interface, avoiding the problem of microcrack propagation caused by a sudden change in rigidity.

[0057] Specifically, when the film thickness reaches the lower limit, the piezoelectric material can form a continuous covering layer, generating sufficient surface potential gradient in the dental pulp cavity microenvironment, promoting directional migration of nerve cells and axon extension. When the thickness is controlled within the upper limit, the difference in elastic modulus between the film and the porous scaffold is limited to an adaptable range, avoiding interface peeling under the action of masticatory force cycles. This thickness range also matches the mechanical properties of the dentin wall, allowing the scaffold-film composite to form a gradual stress transfer with the surrounding tissue after implantation, thereby maintaining the sustained effectiveness of the electrical-mechanical coupling stimulation.

[0058] Optionally, the piezoelectric material film 2 attached to the surface of the three-dimensional porous scaffold 1 includes: In-situ electrospinning: In-situ electrospinning of PVDF-TrFE composite material on the surface of the three-dimensional porous scaffold 1, with fiber diameter of 500 nm to 2 μm, thickness of the piezoelectric material film 2 of 20 to 50 μm, annealing at 80 to 100 °C and polarization at 90 to 110 MV / m to obtain a β phase content of more than 80%; or Solution casting + hot pressing: Pouring a BaTiO3-PVDF composite solution onto the surface of the three-dimensional porous scaffold 1, evaporating the solvent at 50 to 70 °C, hot pressing at 90 to 110 °C for 5 to 15 min to obtain a piezoelectric material film 2 with a thickness of 50 to 100 μm; or Using multi-jet 4D printing, uniformly extruding the slurry and PVDF-graphene composite ink simultaneously to integrally build the three-dimensional porous scaffold 1 and the piezoelectric material film 2.

[0059] In this optional embodiment, the controllable construction of the interface microstructure is achieved by an in-situ forming process, avoiding the influence of secondary processing on the mechanical properties of the three-dimensional porous scaffold 1. The existing piezoelectric material film 2 preparation is mostly prepared by a single process, which is difficult to balance the biocompatibility and the strength of the piezoelectric response. The present scheme optimizes the material composition and process through synergistic optimization, maintains the cell proliferation space while improving the electric stimulation efficiency. The neural differentiation induction efficiency of the piezoelectric material film 2 is effectively improved, and the directional growth of the nerve synapse is promoted by the continuous and stable piezoelectric signal output. The composite preparation cycle of the three-dimensional porous scaffold 1 and the piezoelectric material film 2 is significantly shortened, avoiding the pollution risk caused by traditional multi-process operation. The interface bonding reliability of the functional layer and the three-dimensional porous scaffold 1 is enhanced, the structural integrity is maintained under dynamic chewing load, and the long-term stability of the regenerated tissue is ensured.

[0060] Specifically, the electrospinning in-situ deposition refers to stretching the polymer solution into nanofibers by a high-voltage electric field and directly depositing on the scaffold surface. Specifically, an electrospinning equipment with a rotating collection device can be used to achieve this. This method promotes the directional distribution of piezoelectric properties through fiber orientation control. Among them, solution casting combined with hot pressing refers to eliminating interface defects after coating the piezoelectric composite material solution through temperature gradient. Specifically, a laminator with temperature control function can be used to achieve this. This method enhances the interfacial bonding force through the interpenetration of high molecular chains in the molten state. Among them, multi-nozzle 4D printing refers to synchronously extruding different functional materials through independently controlled printing nozzles. Specifically, a biological 3D printer with a multi-axis motion system can be used to achieve this. This method eliminates the structural misalignment caused by secondary assembly through in-situ forming.

[0061] Specifically, in the electrospinning process, the PVDF-TrFE fiber forms a high proportion of β crystal phase after polarization treatment, and its piezoelectric response can simulate the biological electric signal environment to promote the growth of nerve cell synapses. In the solution casting process, the interpenetrating network structure is formed between the PVDF molecular chain and the scaffold surface polymer during the hot pressing stage, avoiding the peeling of the film under dynamic load. Multi-nozzle printing controls the material extrusion path in a coordinated manner, so that the piezoelectric material film 2 and the scaffold pore structure form a mechanically adaptive gradient interface, maintaining the negative Poisson's ratio characteristics without being damaged.

[0062] Specifically, the electrospinning process can be combined with the shrinkage morphology of the scaffold after heat treatment for curved surface deposition, so that the fiber arrangement direction is consistent with the stress direction of the scaffold. The solution casting process can apply ultrasonic vibration during the solvent evaporation stage to promote the uniform dispersion of BaTiO3 particles in the PVDF matrix. Multi-nozzle printing can set a gradient distribution of graphene content to form a conductive network on the surface of the film to enhance the charge collection efficiency.

[0063] A directional array of BaTiO3 nanofibers is adopted, and the piezoelectric coefficient is optimized through interface polarization engineering to match the electrophysiological parameters of dental pulp development The piezoelectric functional layer is composed of polarized PVDF-TrFE (β phase content ≥ 70%) or BaTiO3 / PCL composite (piezoelectric constant d 33 ≥ 50 pC / N), which can convert the chewing force (110 MPa) into a physiologically effective electrical signal (0.110 mV / cm); the frequency of the electrical signal (1100 Hz) matches the electrical physiological activity of the nerve, significantly improving the efficiency of nerve differentiation (23 times) and the degree of dentin matrix mineralization (40% to 60% increase in calcium deposition) 4D printing realizes individualized adaptation, and the integrated piezoelectric-scaffold composite simplifies the surgical procedure (operation time is shortened by 30% to 50%).

[0064] Another embodiment of the present application provides a dental pulp regeneration structure based on piezoelectric intelligent material, which is made by the preparation method of the dental pulp regeneration structure based on piezoelectric intelligent material according to any one of the above.

[0065] The present application will be further described below in combination with specific embodiments.

[0066] Embodiment 1, preparation method of dental pulp regeneration structure based on piezoelectric intelligent material.

[0067] Material selection: biodegradable high molecular weight polylactic acid (PLA) and piezoelectric ceramic BaTiO3 are used to ensure that the mechanical properties (Young's modulus 0.5 to 3 GPa) and electrical activity are matched.

[0068] 4D printing (fused deposition modeling FDM + electric field assisted polarization): printing material preparation, PLA + BaTiO3 nanoparticles (20 wt%) are mixed in a solvent chloroform to form a uniform slurry, and the extrusion diameter is 0.3 mm.

[0069] Printing parameters: nozzle temperature 180°C, printing speed 5 mm / s.

[0070] 4D printing three-dimensional porous scaffold 1 scaffold, structure design: using an inner concave hexagonal lattice, the size of the unit cell is 2 mm, and the wall thickness is 200 μm, to realize the negative Poisson's ratio effect.

[0071] Dynamic deformation, after printing, heat treatment at 60°C for 1h, trigger shape memory effect, three-dimensional porous scaffold 1 spontaneously shrinks by 20% to adapt to the pulp cavity.

[0072] Polarization treatment, 2 kV / mm direct current electric field is applied at 80°C for 30 min, so that the BaTiO3 particles are oriented and arranged, and the piezoelectric coefficient is improved.

[0073] A thin film of piezoelectric material 2 is attached to the outer surface of the three-dimensional porous scaffold 1: electrospinning in situ deposition, electrospinning PVDF-TrFE (piezoelectric polymer) on the surface of the three-dimensional porous scaffold 1, fiber diameter 1 μm, thickness 30 μm, high β phase content (>80%) after 90°C annealing and 100 MV / m polarization.

[0074] The elastic modulus (1 to 5 GPa) of the thin film of piezoelectric material 2 needs to be close to that of the three-dimensional porous scaffold 1 (0.5 to 3 GPa) to avoid interfacial peeling.

[0075] When the thickness of the thin film of piezoelectric material 2 is 50 μm, a bite force (1 N) can generate a voltage of 0.8 to 1.2 V, which can meet the demand for cell electrical stimulation.

[0076] Example 2, preparation method of a dental pulp regeneration structure based on piezoelectric smart materials.

[0077] Material selection: biodegradable high molecular weight polylactic acid (PLA) and piezoelectric ceramic BaTiO3 are used to ensure that the mechanical properties (Young's modulus 0.5 to 3 GPa) and electrical activity are matched.

[0078] 4D printing (fused deposition modeling FDM + electric field assisted polarization): printing material preparation, PLA + BaTiO3 nanoparticles (20 wt%) are mixed in a solvent chloroform to form a uniform slurry, and the extrusion diameter is 0.3 mm.

[0079] Printing parameters: nozzle temperature 180°C, printing speed 5 mm / s.

[0080] 4D printing of the three-dimensional porous scaffold 1 scaffold, structure design: a concave hexagonal lattice is used, the unit cell size is 2 mm, and the wall thickness is 200 μm to realize the negative Poisson's ratio effect.

[0081] Dynamic deformation, after printing, heat treatment at 60°C for 1 h to trigger the shape memory effect, the three-dimensional porous scaffold 1 spontaneously shrinks by 20% to adapt to the pulp cavity.

[0082] Polarization treatment, 2 kV / mm direct current electric field is applied at 80°C for 30 min to make the BaTiO3 particles orient and arrange, and the piezoelectric coefficient is improved.

[0083] A thin film of piezoelectric material 2 is attached to the outer surface of the three-dimensional porous scaffold 1: solution casting + hot pressing, BaTiO3 / PVDF solution (mass ratio 1:4) is poured onto the surface of the three-dimensional porous scaffold 1, after volatilizing the solvent at 60°C, hot pressing at 100°C for 10 min to form a dense film (thickness 80 μm).

[0084] Example 3, preparation method of a dental pulp regeneration structure based on piezoelectric smart materials.

[0085] Material selection: Biodegradable polymer polylactic acid (PLA) and piezoelectric ceramic BaTiO3 are used to ensure the matching of mechanical properties (Young's modulus 0.5-3 GPa) and electrical activity.

[0086] 4D printing (FDM + electric field assisted polarization): printing material preparation, PLA + BaTiO3 nanoparticles (20 wt%) are mixed in solvent chloroform to form a uniform slurry, and the filament diameter is 0.3 mm.

[0087] Printing parameters: nozzle temperature 180°C, printing speed 5 mm / s.

[0088] 4D printing of three-dimensional porous scaffold 1: the structure is designed to be a concave hexagonal lattice, the unit cell size is 2 mm, and the wall thickness is 200 μm, so as to realize the negative Poisson's ratio effect.

[0089] Dynamic deformation, after printing, heat treatment at 60°C for 1h, trigger shape memory effect, three-dimensional porous scaffold 1 spontaneously shrinks by 20% to adapt to the medullary cavity.

[0090] Polarization treatment: a direct current electric field of 2 kV / mm is applied at 80°C for 30 min to make the BaTiO3 particles arrange in a certain direction and improve the piezoelectric coefficient.

[0091] Attaching a piezoelectric material film 2 on the outer surface of the three-dimensional porous scaffold 1: 3D printing co-extrusion, using multi-nozzle printing, synchronously extruding the uniform slurry of the three-dimensional porous scaffold 1 and the piezoelectric ink (PVDF + graphene), realizing integrated forming.

[0092] Although the present application is disclosed as above, the protection scope of the present application is not limited to this. Those skilled in the art can make various changes and modifications without departing from the spirit and scope of the present application, and these changes and modifications shall fall within the protection scope of the present application.

Claims

1. A method for preparing a dental pulp regeneration structure based on piezoelectric smart materials, characterized in that, Includes the following steps: S1: Take biodegradable polymer and piezoelectric ceramic and mix them in chloroform to form a uniform slurry. Use 4D printing to construct a three-dimensional porous scaffold (1) with periodically arranged pores. The Poisson's ratio of the three-dimensional porous scaffold (1) is -0.3 to -0.

8. S2: A piezoelectric material film (2) is attached to the surface of the three-dimensional porous support (1).

2. The method for preparing a pulp regeneration structure based on piezoelectric smart materials according to claim 1, characterized in that, The biodegradable polymer is polycaprolactone, polylactic acid-hydroxyacetic acid copolymer, or polylactic acid.

3. The method for preparing a pulp regeneration structure based on piezoelectric smart materials according to claim 1, characterized in that, The piezoelectric ceramic is BaTiO3 or ZnO.

4. The method for preparing a pulp regeneration structure based on piezoelectric smart materials according to claim 1, characterized in that, The porosity of the three-dimensional porous scaffold (1) is ≥70%.

5. The method for preparing a pulp regeneration structure based on piezoelectric smart materials according to claim 1, characterized in that, The three-dimensional porous scaffold (1) is a concave hexagonal lattice with a unit cell size of 1 to 3 mm and a wall thickness of 100 to 300 μm.

6. The method for preparing a pulp regeneration structure based on piezoelectric smart materials according to claim 1, characterized in that, The nozzle temperature of the 4D printing method is 150 to 200 °C, and the printing speed is 2 to 8 mm / s.

7. The method for preparing a pulp regeneration structure based on piezoelectric smart materials according to claim 1, characterized in that, The steps between step S1 and step S2 include: S11: The three-dimensional porous framework (1) is heat-treated at 50 to 70°C for 0.5 to 1.5 h to trigger the shape memory effect of the three-dimensional porous framework (1), causing the three-dimensional porous framework (1) to spontaneously shrink by 10% to 30% to adapt to the pulp cavity; S12: Apply a DC electric field of 1 to 3 kV / mm at 70 to 90°C to the three-dimensional porous support (1) for 20 to 40 min to orient the piezoelectric ceramic particles to improve the piezoelectric coefficient.

8. The method for preparing a pulp regeneration structure based on piezoelectric smart materials according to claim 1, characterized in that, The thickness of the piezoelectric material film (2) is 20 to 100 μm.

9. The method for preparing a pulp regeneration structure based on piezoelectric smart materials according to claim 1, characterized in that, The piezoelectric material film (2) attached to the surface of the three-dimensional porous scaffold (1) includes: In-situ electrospinning deposition: PVDF-TrFE composite material is deposited in-situ on the surface of the three-dimensional porous scaffold (1) by electrospinning, with fiber diameters ranging from 500 nm to 2 μm, and the thickness of the piezoelectric material film (2) is 20 to 50 μm. The film is then annealed at 80 to 100 °C and polarized at 90 to 110 MV / m to obtain a β-phase content exceeding 80%; or Solution casting + hot pressing: The BaTiO3-PVDF composite solution is cast onto the surface of the three-dimensional porous scaffold (1), the solvent is evaporated at 50 to 70 °C, and hot pressing is performed at 90 to 110 °C for 5 to 15 min to obtain the piezoelectric material film (2) with a thickness of 50 to 100 μm; or Using multi-nozzle 4D printing, the uniform slurry and PVDF-graphene composite ink are extruded simultaneously to construct the three-dimensional porous scaffold (1) and the piezoelectric material film (2) in an integrated manner.

10. A dental pulp regeneration structure based on piezoelectric smart materials, characterized in that, The dental pulp regeneration structure based on piezoelectric smart materials was prepared using the method described in any one of claims 1-9.

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