Micrometer motor with sterilization and anti-inflammatory synergism, and preparation method and application thereof

Abstract

The invention relates to the technical field of wound healing materials, in particular to a micron motor with sterilization and anti-inflammatory synergy and a preparation method and application thereof. The micron motor is of a core-shell structure, the core is magnesium particles, the shell is a composite coating layer, and the composite coating layer comprises a polylactic acid-glycolic acid copolymer layer and a polydopamine layer; the polylactic acid-glycolic acid copolymer layer partially coats the surfaces of the magnesium particles so as to form openings in the surfaces of the magnesium particles; the width of the opening is not less than 5 [mu] m; the polydopamine layer is completely coated on the surface of the polylactic acid-glycolic acid copolymer layer. According to the micron motor, the magnesium particles serve as the core, the polylactic acid-glycolic acid copolymer layer and the polydopamine layer serve as the composite coating layer, through the synergistic effect of the structures, the performance of the micron motor in the aspects of rapid sterilization, biological membrane removal and inflammation resistance can be improved at the same time, and therefore the healing process of bacterial infectious chronic wounds is accelerated.

Description

Technical Field

[0001] This application relates to the technical field of wound healing materials, and particularly to a micromotor with synergistic bactericidal and anti-inflammatory effects, a preparation method thereof, and an application thereof. Background Art

[0002] Diabetes complications are extremely common, and chronic non-healing wounds are one of these complications. Chronic non-healing wounds are commonly found in diabetic foot ulcers, which occur in up to 25% of the diabetic patient population, and the recurrence rate of this symptom is as high as 40%. The chronic and difficult-to-heal nature of chronic non-healing wounds at the present stage is attributed to multiple factors: (1) The hyperglycemic environment can damage the extracellular matrix and affect wound healing; (2) The hyperglycemic environment can provide favorable conditions for bacterial colonization and increase the risk of bacterial infection; (3) The hyperglycemic environment can promote an increase in the body's oxidative stress level and produce a persistent inflammatory response; (4) The hyperglycemic environment can lead to hypoxia in the body due to insufficient angiogenesis, affecting cell proliferation and migration. Among these numerous factors, bacterial infection is one of the main reasons for the difficulty in healing diabetic chronic wounds. In addition, the hyperglycemic environment can provide favorable conditions for the growth and reproduction of bacteria, and at the same time enhance the ability of bacteria to form biofilms. Moreover, bacteria in diabetic chronic wounds usually exhibit multi-drug resistance, which undoubtedly limits the therapeutic effect of antibiotics, and it is difficult for antibiotics to effectively remove biofilms. Therefore, there is an urgent need to develop an antibacterial method to replace antibiotic bactericidal action, so as to break through bacterial biofilms for sterilization under the limitation of bacterial drug resistance.

[0003] Micro / Nanomotors are a type of microdevice that can convert chemical energy, light energy, electrical energy, or magnetic energy into mechanical motion at the microscale, and have good development potential in targeted drug delivery, environmental remediation, and biosensing. Micro / Nanomotors have good biodegradability, and the reaction environment is easily obtained. Micro / Nanomotors mainly rely on hydrogen gas generated by the reaction of magnesium with the water environment as an efficient driving force. In addition, Mg generated by the hydrolysis of magnesium 2+ plays an important role in cell proliferation, differentiation, and migration. In addition, the degradation products of micro / nanomotors have good biocompatibility in the body, and the generated Mg 2+ is an essential trace element for the human body. In addition, micro / nanomotors can use poly(lactic-co-glycolic acid) as the outer shell, and poly(lactic-co-glycolic acid) can be hydrolyzed into lactic acid and glycolic acid in the body, both of which are natural substances for human metabolism and can be decomposed into water and carbon dioxide through the tricarboxylic acid cycle of the body and excreted from the body.

[0004] As a new anti-inflammatory agent, hydrogen gas (H2) has various properties such as excellent biocompatibility, selective antioxidant activity, regulation of inflammatory signaling pathways, and immune cell functions. Hydrogen can selectively scavenge strongly oxidizing free radicals (such as hydroxyl radicals and peroxynitrite) without affecting ROS with signaling functions (such as hydrogen peroxide and nitric oxide). Therefore, hydrogen can inhibit the excessive activation of neutrophils and reduce the differentiation of macrophages into pro-inflammatory phenotypes (M1 type) to reduce the production of mitochondrial ROS, thereby alleviating inflammation and oxidative stress. However, due to the short residence time and extremely low solubility of H2 in body fluids, this greatly limits the effect of H2 in anti-inflammatory work. In addition, current micro-motors are difficult to achieve effective sterilization, and direct use is difficult to meet the sterilization requirements of chronically non-healing wounds. Therefore, the anti-inflammatory and sterilization effects of current micro-motors are still not ideal, making the healing process of bacterially infected chronic wounds relatively long. Summary of the Invention

[0005] The present application provides a micro-motor with synergistic bactericidal and anti-inflammatory effects, a preparation method, and an application to solve the following technical problems: how to simultaneously improve the bactericidal and anti-inflammatory effects of the micro-motor to accelerate the healing of bacterially infected chronic wounds.

[0006] In a first aspect, an embodiment of the present application provides a micro-motor with synergistic bactericidal and anti-inflammatory effects. The micro-motor has a core-shell structure, with a magnesium particle core and a composite coating layer as the shell. The composite coating layer includes a poly(lactic-co-glycolic acid) layer and a polydopamine layer;

[0007] The poly(lactic-co-glycolic acid) layer partially coats the surface of the magnesium particle to form an opening on the surface of the magnesium particle; the width of the opening ≥ 5 μm;

[0008] The polydopamine layer completely coats the surface of the poly(lactic-co-glycolic acid) layer.

[0009] Optionally, the width of the opening is 5 μm to 15 μm.

[0010] Optionally, the average particle size of the magnesium particles is 15 μm to 20 μm.

[0011] Optionally, the average particle size of the micro-motor is 25 μm to 30 μm.

[0012] In a second aspect, an embodiment of the present application provides a method for preparing the micro-motor described in the first aspect. The method includes:

[0013] Using an organic solvent to disperse and extract magnesium particles in sequence to obtain a single-layer magnesium particle layer;

[0014] Coat one side of the layer of magnesium particles with a poly(lactic-co-glycolic acid) solution so that the poly(lactic-co-glycolic acid) solution partially coats the magnesium particles to obtain coated core particles;

[0015] Immerse the coated core particles in a polydopamine solution and perform vacuum drying so that the polydopamine solution coats the surface of the poly(lactic-co-glycolic acid) to obtain polydopamine-coated micro-nano particles;

[0016] Scrape the polydopamine-coated micro-nano particles into a single layer so that the bottom opening of the polydopamine-coated micro-nano particles is exposed to obtain micro motors.

[0017] Optionally, the mass m1 of the magnesium particles and the volume V1 of the organic solvent satisfy the relationship: m1:V1 = 1:1. If the unit of m1 is mg, then the unit of V1 is mL; and / or

[0018] The mass concentration of the poly(lactic-co-glycolic acid) solution is 15 mg / mL, and the molecular weight of the poly(lactic-co-glycolic acid) in the poly(lactic-co-glycolic acid) solution is 10 kDa.

[0019] Optionally, the preparation steps of the polydopamine solution are as follows:

[0020] Perform a polymerization reaction on dopamine hydrochloride and a tris(hydroxymethyl)aminomethane hydrochloride solution to obtain polydopamine;

[0021] Ultrasonically disperse the polydopamine in deionized water to obtain a polydopamine solution.

[0022] Optionally, the mass m2 of the dopamine hydrochloride and the volume V2 of the tris(hydroxymethyl)aminomethane hydrochloride solution satisfy the relationship: m2:V2 = 2:1. If the unit of m2 is mg, then the unit of V2 is mL; and / or

[0023] The mass concentration of the tris(hydroxymethyl)aminomethane hydrochloride solution is 50 mmol / L; and / or

[0024] The mass m3 of the polydopamine and the volume V3 of the deionized water satisfy the relationship: m3:V3 = 5:1. If the unit of m3 is mg, then the unit of V3 is mL.

[0025] In a third aspect, an embodiment of the present application provides a wound healing material. The wound healing material includes the micro motors described in the first aspect, and the wound healing material is used in the preparation of a healing reagent for diabetic chronic wounds.

[0026] In a fourth aspect, an embodiment of the present application provides a biomedical material. The biomedical material includes the micro motors described in the first aspect.

[0027] The above technical solution provided by the embodiments of the present application has the following advantages compared with the prior art:

[0028] A micro motor with synergistic bactericidal and anti-inflammatory effects provided by an embodiment of the present application uses magnesium particles as the core and a poly (lactic-co-glycolic acid) layer and a polydopamine layer as a composite coating layer. Through the partial coating effect of the poly (lactic-co-glycolic acid), openings with a width of more than 5 μm are formed on the magnesium particles. These openings allow the magnesium particles to partially contact water. Based on the biodegradability and excellent biocompatibility of the poly (lactic-co-glycolic acid) layer, the micro motor can gradually expand the opening width of the magnesium particles to control the oxidation reaction process of the magnesium particles, thereby slowly generating hydrogen. The slowly released hydrogen can increase the residence time and solubility of the hydrogen in the body fluid. On the one hand, the hydrogen can be used as a power source to drive the micro motor to penetrate tissues and reach the target area. On the other hand, the hydrogen can be used as an anti-inflammatory agent to selectively scavenge excessive strong oxidative free radicals and down-regulate the expression level of inflammatory factors, thereby improving the anti-inflammatory effect of the micro motor; In addition, polydopamine, as a photothermal agent, can generate local high temperatures under infrared light irradiation. The areas with these local high temperatures can destroy the bacterial protein structure through thermal effects to kill bacteria through physical mechanisms, thereby avoiding the generation of bacterial drug resistance and improving the bactericidal effect of the micro motor; Therefore, the micro motor uses magnesium particles as the core and a poly (lactic-co-glycolic acid) layer and a polydopamine layer as a composite coating layer. Through the synergistic effect of these structures, the performance of the micro motor in rapid sterilization, biofilm removal and anti-inflammatory can be improved simultaneously, thereby accelerating the healing process of bacterial infectious chronic wounds through the micro motor. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] The drawings herein are incorporated into the specification and form a part of the specification, showing embodiments consistent with the present application and used together with the specification to explain the principles of the present application.

[0030] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art. Obviously, for those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0031] Figure 1 Schematic structural diagram of a micro motor with synergistic bactericidal and anti-inflammatory effects provided by an embodiment of the present application;

[0032] Figure 2 Scanning electron microscope schematic diagram of a micro motor with synergistic bactericidal and anti-inflammatory effects provided by an embodiment of the present application;

[0033] Figure 3 Schematic flow chart of a method for preparing a micromotor provided by an embodiment of the present application;

[0034] Figure 4 Detailed flow chart of a method for preparing a micromotor provided by an embodiment of the present application;

[0035] Figure 5 Fluorescence detection result diagram of a micromotor with antibacterial and anti-inflammatory synergy provided by an embodiment of the present application, where Figure 5 A is the result diagram of an inverted fluorescence microscope in the bright field area, Figure 5 B is the rhodamine staining result diagram of an inverted fluorescence microscope;

[0036] Figure 6 Statistical comparison result diagram of the particle size of magnesium ball particles and M@P@PDA micromotors provided by the present application;

[0037] Figure 7 Hydrogen release performance result diagram of magnesium ball particles and M@P@PDA micromotors provided by the present application, where Figure 7 A is the hydrogen release performance result diagram of magnesium ball particles, Figure 7 B is the hydrogen release performance result diagram of M@P@PDA micromotors;

[0038] Figure 8 Photothermal performance result diagram of M@P@PDA micromotors provided by an embodiment of the present application, where Figure 8 A is the photothermal curve diagram of M@P@PDA micromotors, Figure 8 B is the temperature cycle curve of M@P@PDA micromotors;

[0039] Figure 9 Antibacterial performance result diagram of M@P@PDA micromotors provided by an embodiment of the present application.

[0040] Figure 10 Biofilm removal result diagram of M@P@PDA micromotors provided by an embodiment of the present application.

[0041] Figure 11 Cell compatibility result diagram of M@P@PDA micromotors provided by an embodiment of the present application, where Figure 11 A is the statistical result diagram of cell viability after co-incubation of M@P@PDA micromotors with cells for 6 h and 24 h, Figure 11 B is the staining result diagram of live / dead cells after co-incubation of M@P@PDA micromotors with cells for 24 h;

[0042] Figure 12 Anti-inflammatory performance result diagram of M@P@PDA micromotors provided by an embodiment of the present application;

[0043] Figure 13 This is the result graph of the cell migration promotion performance of the M@P@PDA micromotor provided by the embodiments of the present application;

[0044] Figure 14 This is the result graph of the wound healing promotion performance of the M@P@PDA micromotor provided by the embodiments of the present application, where, Figure 14 A is the physical change graph of the wound of diabetic mice promoted by the M@P@PDA micromotor, Figure 14 B is the wound healing rate of the wounds of diabetic mice;

[0045] Figure 15 This is the result graph of the histological changes of the wound surface of the M@P@PDA micromotor promoting the wounds of diabetic mice provided by the embodiments of the present application;

[0046] Figure 16 This is the graph of the change in the collagen content of the wound surface tissue promoted by the M@P@PDA micromotor provided by the embodiments of the present application. Detailed implementation manners

[0047] To make the objectives, technical solutions, and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present application. Obviously, the described embodiments are some, but not all, of the embodiments of the present application. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present application without creative efforts shall fall within the scope of protection of the present application.

[0048] The various embodiments of the present application may exist in the form of a range; it should be understood that the description in the form of a range is only for convenience and brevity and should not be construed as a rigid limitation on the scope of the present application; therefore, it should be considered that the described range description has specifically disclosed all possible sub-ranges and single values within that range; for example, it should be considered that the range description from 1 to 6 has specifically disclosed sub-ranges, such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., and single numbers within that range, such as 1, 2, 3, 4, 5, and 6, regardless of what the range is; in addition, whenever a numerical range is indicated herein, it means including any cited number (fraction or integer) within the indicated range.

[0049] In this text, terms such as "including" mean "including but not limited to". Relative terms such as "first" and "second" are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. "And / or", which describes the association relationship of associated objects, indicates that there can be three relationships. For example, A and / or B can represent: A exists alone, A and B exist simultaneously, and B exists alone; where A and B can be singular or plural. "At least one" means one or more, and "multiple" means two or more; "at least one kind", "at least one of the following items (pieces)" or similar expressions refer to any combination of these items, including any combination of single item (piece) or plural items (pieces); for example, "at least one of a, b, or c", or, "at least one of a, b, and c" can both represent: a, b, c, a-b (that is, a and b), a-c, b-c, or a-b-c, where a, b, and c can be single or multiple respectively. "Parts representation method" such as parts by weight, parts by mass, etc. represents the proportional relationship between each component. In the proportional relationships involved in this text, the parameters that need to be described by proportion should be understood as the antecedents of the proportion formula in the order of description, and the proportional numbers should be understood as the consequents of the proportion formula. For example, if the mass ratio of substance A, substance B, and substance C is 1:2:3, then substance A, substance B, and substance C should correspond one by one with the proportional numbers in the proportion formula in the order of description, that is, the mass of substance A: the mass of substance B: the mass of substance C = 1:2:3.

[0050] Unless otherwise specifically stated, various raw materials, reagents, instruments, equipment, etc. used in this text can be obtained through market purchase or can be prepared by existing methods.

[0051] It should be noted that hydrogen (H2) is a new type of anti-inflammatory agent with excellent biocompatibility, selective antioxidant, regulation of inflammatory signaling pathways, and immune cell functions. Hydrogen can selectively scavenge strongly oxidizing free radicals (such as hydroxyl radicals and peroxynitrite), without affecting ROS with signaling functions (such as hydrogen peroxide and nitric oxide). Thereby, it can inhibit the over-activation of neutrophils and reduce the differentiation of macrophages into pro-inflammatory phenotypes (M1 type), so as to reduce the production of mitochondrial ROS, thereby reducing the body's inflammation and oxidative stress. However, due to the short residence time and extremely low solubility of H2 in body fluids, it has great limitations in anti-inflammatory work. The nano-micro motor of the embodiment of this application provides a huge convenience for the anti-inflammatory work of the micro motor by setting an opening so that magnesium particles can react with the water environment to continuously release H2 for a long time.

[0052] Photothermal Antibacterial Therapy (PTT) is a novel antibacterial strategy that utilizes a photothermal agent to convert light energy into heat energy under light irradiation and kill bacteria through local high temperature. As a photothermal agent, polydopamine is a biomimetic polymer material inspired by mussel adhesive protein. Generally, polydopamine is a product formed by the self-polymerization of dopamine monomers under alkaline conditions. Polydopamine generates local high temperature under near-infrared light irradiation, and these high-temperature heats will rapidly damage the cell membrane and protein structure of bacteria, leading to bacterial death. The strategy of sterilization through this physical mechanism is not likely to cause bacterial drug resistance. Moreover, polydopamine can form a uniform coating on almost all material surfaces, with excellent adhesion and good biocompatibility, making it an outstanding antibiotic alternative.

[0053] Figure 1 Exemplarily shown is a schematic structural diagram of a micromotor with synergistic antibacterial and anti-inflammatory effects provided by an embodiment of the present application;

[0054] Figure 2 Exemplarily shown is a scanning electron microscope schematic diagram of a micromotor with synergistic antibacterial and anti-inflammatory effects provided by an embodiment of the present application;

[0055] As Figure 1 and Figure 2 shown, an embodiment of the present application provides a micromotor with synergistic antibacterial and anti-inflammatory effects. The micromotor has a core-shell structure, with a magnesium particle as the core and a composite coating layer as the shell. The composite coating layer includes a poly(lactic-co-glycolic acid) layer and a polydopamine layer;

[0056] The poly(lactic-co-glycolic acid) layer partially coats the surface of the magnesium particle to form an opening on the surface of the magnesium particle; the width of the opening ≥ 5 μm;

[0057] The polydopamine layer completely coats the surface of the poly(lactic-co-glycolic acid) layer.

[0058] It should be noted that the diameter of the magnesium particle should be greater than the width of the opening to avoid excessive oxidation reaction of the magnesium particle due to too large an opening and generate a large amount of hydrogen.

[0059] It should be noted that an embodiment of the present application provides a micromotor with synergistic antibacterial and anti-inflammatory effects. This micromotor realizes the synchronous improvement of antibacterial and anti-inflammatory effects through the synergistic action of multiple components and a unique structural design. The specific mechanism is as follows:

[0060] 1. Magnesium core-driven autonomous movement and optimization of multiple functions of the magnesium core:

[0061] (1) Driving mechanism: Magnesium particles undergo an oxidation reaction in water or body fluids (Mg + 2H2O → Mg(OH)2 + H2↑), and the hydrogen gas bubbles generated can drive the autonomous movement of the micromotor, enhancing the tissue penetration of the micromotor and enabling the micromotor to effectively penetrate the bacterial biofilm, so that the effective components of the micromotor can effectively act on bacteria.

[0062] (2) Antibacterial synergy: During the oxidation reaction process, the local pH increases (alkaline environment) and magnesium ions are released (Mg 2+ ), and the oxidation reaction process can damage the cell membrane integrity of some bacteria and inhibit biofilm formation.

[0063] (3) Anti-inflammatory regulation: The released magnesium ions can reduce the expression of pro-inflammatory factors (TNF-α, IL-6) in cells by regulating macrophage polarization (promoting the M2 anti-inflammatory phenotype) and inhibiting the NF-κB pathway.

[0064] (4) Promote healing: The released magnesium ions have the characteristics of promoting angiogenesis and cell migration, and can promote wound healing.

[0065] 2. Functional design of the PLGA layer structure:

[0066] (1) Directional drug release: The opening with a diameter of ≥5μm formed by partial coating of the micromotor can achieve "reaction-release" coupling: the hydrogen microflow generated by the oxidation reaction of magnesium can accelerate the diffusion of the micromotor, while the biodegradation of poly(lactic-co-glycolic acid) (PLGA) can control the sustained release of the hydrogen gas generated by the magnesium oxidation reaction.

[0067] (2) Surface modification: The carboxyl terminal of PLGA can adsorb positively charged antimicrobial peptides (such as LL-37) through electrostatic interaction to form a local high-concentration sterilization area.

[0068] (3) Harmlessness of degradation: The products of PLGA degradation in the body are generally lactic acid, etc. Lactic acid can participate in the body's metabolic process as an intermediate product of the tricarboxylic acid cycle to avoid the impact of the micromotor on the body.

[0069] 3. Multiple functions of the polydopamine layer:

[0070] (1) Photothermal antibacterial: Under near-infrared light irradiation (808nm), polydopamine generates a local high temperature of up to 42°C - 50°C. These local high-temperature regions can damage the protein structure of bacteria through the thermal effect, and the photothermal conversion efficiency of polydopamine can reach 35% - 40%.

[0071] (2) Reactive oxygen species scavenging: The catechol groups of polydopamine can efficiently scavenge reactive oxygen species (ROS) and inhibit the inflammatory cascade reaction induced by oxidative stress.

[0072] (3) Targeted adhesion: The catechol groups of polydopamine can mediate the adhesion ability on the bacterial surface to increase the local concentration of the bactericide.

[0073] 4. Spatiotemporal synergy mechanism

[0074] (1) Enhanced motility for penetration: The autonomous movement speed of the hydrogen-driven micromotor can reach 120 μm / s - 200 μm / s, which can improve the passive diffusion efficiency by 5 - 8 times compared with traditional biological carriers, and can promote the drug to penetrate deep into the infection site.

[0075] (2) Cascade reaction regulation: In the initial stage of magnesium reaction, the environment can be rapidly alkalized to destroy the bacterial biofilm. Subsequently, PLGA slowly releases drugs to maintain the long-term bactericidal effect of the micromotor, while polydopamine can simultaneously eliminate excessive ROS.

[0076] (3) Intelligent response design: The synergy of pH response (the acidic environment at the infection site can accelerate the degradation of PLGA) and photothermal response (triggering high-temperature sterilization as needed) can achieve precise treatment of the micromotor.

[0077] Therefore, the embodiments of the present application provide a micromotor with synergistic bactericidal and anti-inflammatory effects. Through the multi-modal synergy strategy among magnesium particles, poly(lactic-co-glycolic acid) layer, and polydopamine layer, the micromotor breaks through the limitation that traditional antibacterial materials cannot take into account the anti-inflammatory function, provides a new idea for the comprehensive treatment of infectious inflammation, and can accelerate the healing of chronic wounds infected with bacteria.

[0078] In some alternative embodiments, the width of the opening is 5 μm - 15 μm.

[0079] In these embodiments, the width of the opening can be 5 μm - 15 μm, such that the surface of the micromotor has a wide enough opening, which can control the degree of the oxidation reaction of magnesium particles, so that magnesium particles can slowly release hydrogen, can increase the residence time and solubility of hydrogen in body fluids, and thus can improve the anti-inflammatory effect of the micromotor.

[0080] The width of the opening can be 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, 10 μm, 11 μm, 12 μm, 13 μm, 14 μm or 15 μm.

[0081] In some alternative embodiments, the average particle size of the magnesium particles is 15 μm - 20 μm.

[0082] In these embodiments, the average particle size of the magnesium particles can be 15 μm to 20 μm, such that the magnesium particles have a large enough diameter to fit the opening and control the rate of hydrogen release from the magnesium particles, thereby increasing the residence time and solubility of hydrogen in body fluids, and thus improving the anti-inflammatory effect of the micromotors.

[0083] The average particle size of the magnesium particles can be 15 μm, 16 μm, 17 μm, 18 μm, 19 μm or 20 μm.

[0084] In some alternative embodiments, the average particle size of the micromotors is 25 μm to 30 μm.

[0085] In these embodiments, the average particle size of the micromotors can be 25 μm to 30 μm, such that the micromotors have a large enough particle size, and the micromotors with a large enough particle size can have a sufficient thickness of poly(lactic-co-glycolic acid) layer and polydopamine layer. These sufficient thickness of poly(lactic-co-glycolic acid) layer and polydopamine layer can adopt a multimodal synergistic strategy with the magnesium particles, so that the bactericidal and anti-inflammatory effects of the micromotors can be improved synchronously through the synergistic effect of these structures, and the healing of bacterial infectious chronic wounds can be accelerated.

[0086] The average particle size of the micromotors can be 25 μm, 26 μm, 27 μm, 28 μm, 29 μm or 30 μm.

[0087] Figure 3 Exemplarily, a schematic flow chart of a method for preparing a micromotor provided by an embodiment of the present application is shown;

[0088] Based on a general inventive concept, as Figure 3 shown, an embodiment of the present application provides a method for preparing the micromotor, the method comprising:

[0089] S1. Using an organic solvent to disperse and extract magnesium particles in sequence to obtain a monolayer of magnesium particle layer;

[0090] S2. Coating a poly(lactic-co-glycolic acid) copolymer solution on one side of the monolayer of magnesium particle layer, so that the poly(lactic-co-glycolic acid) copolymer solution partially coats the magnesium particles to obtain coated core particles;

[0091] S3. Immersing the coated core particles in a polydopamine solution and performing vacuum drying, so that the polydopamine solution coats the surface of the poly(lactic-co-glycolic acid) copolymer to obtain polydopamine-coated micro-nano particles;

[0092] S4. Scraping the polydopamine-coated micro-nano particles into a monolayer, so that the bottom opening of the polydopamine-coated micro-nano particles is exposed to obtain micromotors.

[0093] This method is for the preparation method of the above-mentioned micro motor. For the specific structure and specific composition of the micro motor, reference can be made to the above-mentioned embodiments. Since this method adopts some or all of the technical solutions of the above-mentioned embodiments, it has at least all the beneficial effects brought by the technical solutions of the above-mentioned embodiments, which will not be elaborated one by one here.

[0094] It should be noted that dispersing magnesium particles to form a single-layer magnesium particle layer can facilitate the subsequent partial coating of poly(lactic-co-glycolic acid) on the surface of the single-layer magnesium particles. Subsequently, the core particles are coated by soaking in a polydopamine solution, so that the polydopamine solution is coated on the surface of the poly(lactic-co-glycolic acid). Finally, by scraping in a single layer, the uncoated area of the magnesium particles can be retained to form an open structure to facilitate the smooth release of hydrogen gas from the magnesium particles.

[0095] In some optional embodiments, the mass m1 of the magnesium particles and the volume V1 of the organic solvent satisfy the relationship: m1:V1 = 1:1. If the unit of m1 is mg, then the unit of V1 is mL; and / or

[0096] The mass concentration of the poly(lactic-co-glycolic acid) solution is 15 mg / mL, and the molecular weight of the poly(lactic-co-glycolic acid) in the poly(lactic-co-glycolic acid) solution is 10 kDa.

[0097] In these embodiments, the mass m1 of the magnesium particles and the volume V1 of the organic solvent can satisfy the relationship: m1:V1 = 1:1, which can promote the magnesium particles to be fully dispersed in the organic solvent to form a uniformly distributed single-layer magnesium particle layer. These single-layer magnesium particle layers can facilitate the subsequent partial coating of poly(lactic-co-glycolic acid) and polydopamine solution.

[0098] In addition, the mass concentration of the poly(lactic-co-glycolic acid) solution can be 15 mg / mL, and the molecular weight of the poly(lactic-co-glycolic acid) in the poly(lactic-co-glycolic acid) solution can be 10 kDa, so that the poly(lactic-co-glycolic acid) solution has a sufficient mass concentration and a sufficient molecular weight to facilitate the coating of the poly(lactic-co-glycolic acid) on one side of the single-layer magnesium particle layer.

[0099] Figure 4 Exemplarily shows a detailed process schematic diagram of a method for preparing a micro motor provided by an embodiment of the present application;

[0100] In some optional embodiments, as Figure 4 shown, the preparation steps of the polydopamine solution are:

[0101] S201. Polymerize dopamine hydrochloride and tris(hydroxymethyl)aminomethane hydrochloride solution to obtain polydopamine;

[0102] S202. Ultrasonically disperse the polydopamine in deionized water to obtain a polydopamine solution.

[0103] In these embodiments, using dopamine hydrochloride as a raw material, through the dispersion of tris(hydroxymethyl)aminomethane hydrochloride solution, dopamine hydrochloride can undergo a polymerization reaction to form polydopamine particles, and then the polydopamine particles are dispersed by ultrasonic dispersion to form a polydopamine solution.

[0104] In some alternative embodiments, the mass m2 of the dopamine hydrochloride and the volume V2 of the tris(hydroxymethyl)aminomethane hydrochloride solution satisfy the relationship: m2:V2 = 2:1. If the unit of m2 is mg, then the unit of V2 is mL; and / or

[0105] The mass concentration of the tris(hydroxymethyl)aminomethane hydrochloride solution is 50 mmol / L; and / or

[0106] The mass m3 of the polydopamine and the volume V3 of the deionized water satisfy the relationship: m3:V3 = 5:1. If the unit of m3 is mg, then the unit of V3 is mL.

[0107] In these embodiments, the mass m2 of dopamine hydrochloride and the volume V2 of the tris(hydroxymethyl)aminomethane hydrochloride solution can satisfy the relationship: m2:V2 = 2:1, and the mass concentration of the tris(hydroxymethyl)aminomethane hydrochloride solution can be 50 mmol / L, so that dopamine hydrochloride can be uniformly dispersed in the tris(hydroxymethyl)aminomethane hydrochloride solution to facilitate the subsequent polymerization reaction to form a sufficient amount of polydopamine. In addition, the mass m3 of the polydopamine and the volume V3 of the deionized water can satisfy the relationship: m3:V3 = 5:1, so that the polydopamine can be uniformly dispersed in the deionized water, thereby obtaining a uniformly dispersed polydopamine solution.

[0108] Based on a general inventive concept, an embodiment of the present application provides a wound healing material, and the wound healing material includes the micro motor, and the wound healing material is used in the preparation of a healing reagent for diabetic chronic wounds.

[0109] The wound healing material is realized based on the above micro motor. The specific structure and specific composition of the micro motor can be referred to the above embodiments. Since the wound healing material adopts some or all of the technical solutions of the above embodiments, it has at least all the beneficial effects brought by the technical solutions of the above embodiments, which will not be elaborated here one by one.

[0110] Based on a general inventive concept, an embodiment of the present application provides a biomedical material, and the biomedical material includes the micro motor.

[0111] The biomedical material is realized based on the above-mentioned micromotor. For the specific structure and specific composition of the micromotor, reference can be made to the above-mentioned embodiments. Since the biomedical material adopts some or all of the technical solutions of the above-mentioned embodiments, it has at least all the beneficial effects brought by the technical solutions of the above-mentioned embodiments, which will not be elaborated one by one here.

[0112] The following further elaborates the present application in conjunction with specific embodiments. For the experimental methods without specific conditions indicated in the following embodiments, they are generally determined according to national standards / industry standards; if there are no corresponding national standards / industry standards, they are carried out according to general international standards, conventional conditions or according to the conditions recommended by the manufacturer.

[0113] Example 1

[0114] As Figure 1 shown, a micromotor with synergistic bactericidal and anti-inflammatory effects, the micromotor is a core-shell structure, the core is magnesium particles, and the shell is a composite coating layer. The composite coating layer includes a poly(lactic-co-glycolic acid) layer and a polydopamine layer;

[0115] The poly(lactic-co-glycolic acid) layer partially coats the surface of the magnesium particles to form an opening on the surface of the magnesium particles; the width of the opening ≥ 5 μm;

[0116] The polydopamine layer completely coats the surface of the poly(lactic-co-glycolic acid) layer.

[0117] The width of the opening is 5 μm to 15 μm.

[0118] The average particle size of the magnesium particles is 15 μm to 20 μm.

[0119] The average particle size of the micromotor is 25 μm to 30 μm.

[0120] As Figure 4 shown, a method for preparing a micromotor includes:

[0121] S1. Using an organic solvent to disperse and extract magnesium particles in sequence to obtain a single-layer magnesium particle layer;

[0122] S2. Coating the poly(lactic-co-glycolic acid) solution on one side of the single-layer magnesium particle layer so that the poly(lactic-co-glycolic acid) solution partially coats the magnesium particles to obtain coated core particles;

[0123] S201. Polymerizing hydrochloric acid dopamine and tris(hydroxymethyl)aminomethane hydrochloride solution to obtain polydopamine;

[0124] S202. Ultrasonically dispersing polydopamine in deionized water to obtain a polydopamine solution;

[0125] S3. Immerse the coated core particles in a polydopamine solution and conduct vacuum drying so that the polydopamine solution coats the surface of the poly(lactic-co-glycolic acid) to obtain polydopamine-coated micro-nano particles;

[0126] S4. Scrape out a single layer of the polydopamine-coated micro-nano particles to expose the bottom opening of the polydopamine-coated micro-nano particles, thereby obtaining the micro motors.

[0127] The mass m1 of the magnesium particles and the volume V1 of the organic solvent satisfy the relationship: m1:V1 = 1:1. If the unit of m1 is mg, then the unit of V1 is mL;

[0128] The mass concentration of the poly(lactic-co-glycolic acid) solution is 15 mg / mL, and the molecular weight of the poly(lactic-co-glycolic acid) in the poly(lactic-co-glycolic acid) solution is 10 kDa.

[0129] The mass m2 of dopamine hydrochloride and the volume V2 of the tris(hydroxymethyl)aminomethane hydrochloride solution satisfy the relationship: m2:V2 = 2:1. If the unit of m2 is mg, then the unit of V2 is mL;

[0130] The mass concentration of the tris(hydroxymethyl)aminomethane hydrochloride solution is 50 mmol / L;

[0131] The mass m3 of polydopamine and the volume V3 of deionized water satisfy the relationship: m3:V3 = 5:1. If the unit of m3 is mg, then the unit of V3 is mL.

[0132] The specific process of the above method is as follows:

[0133] Step 1: Pretreat the purchased magnesium ball particles. Weigh 1 g of magnesium ball particles with a particle size of about 15 μm and disperse them in acetone, then perform ultrasonic treatment for 5 min, and then centrifuge at 4000 rpm for 2 min to separate the acetone supernatant and deposit the magnesium ball particles. After washing 3 times, wash 3 times with absolute ethanol in the same manner. Finally, successfully disperse the magnesium ball particles in absolute ethanol to form a magnesium ball particle solution with a mass concentration of 1 mg / mL. Perform leaching on the magnesium ball particle solution (the specific leaching method is to immerse a glass slide into the magnesium ball particle solution and then lift it), and use the glass slide to carry the dispersed magnesium ball particles to obtain a single-layer magnesium ball particle layer.

[0134] Step 2: Weigh 0.3 g of poly(lactic-co-glycolic acid) (PLGA) precisely and dissolve the PLGA in ethyl acetate to form a PLGA solution with a mass concentration of 15 mg / mL. Similarly, use the leaching method to coat a layer of PLGA solution on the surface of the single-layer magnesium ball particle layer, and then volatilize the coated core particles overnight at room temperature to obtain the coated core particles Mg@PLGA.

[0135] Step 3: Disperse 20 mg of dopamine hydrochloride in a tris(hydroxymethyl)aminomethane hydrochloride solution (Tris-HCl buffer solution) to form a mixed solution with a mass concentration of 2 mg / mL and a pH of 8.5. Then, stir the mixed solution at 25 °C for 5 h for a polymerization reaction, and then centrifuge at 6000 rpm for 5 min. Wash the centrifuged product three times with deionized water and vacuum dry it overnight at 37 °C to obtain polydopamine (PDA) with a particle size of 500 nm. Ultrasonically disperse the polydopamine in deionized water to form a polydopamine solution with a mass concentration of 5 mg / mL. Immerse the glass slide carrying the coated core particles Mg@PLGA obtained in Step 2 in the polydopamine solution for 2 min, and then vacuum dry it overnight at 37 °C to obtain polydopamine-coated micro-nano particles. Then, under a stereomicroscope, scrape off the polydopamine-coated micro-nano particles M@P@PDA obtained on the glass slide in a single layer to obtain M@P@PDA micromotors with at least one notch.

[0136] Comparative Example 1

[0137] On the basis of the content disclosed in Example 1, the following further modifications are made:

[0138] Only use magnesium sphere particles.

[0139] Comparative Example 2

[0140] On the basis of the content disclosed in Example 1, the following further modifications are made:

[0141] Only use magnesium particles coated with poly(lactic-co-glycolic acid) (Mg@PLGA).

[0142] Related experiments and data:

[0143] 1. Morphology test of M@P@PDA micromotors:

[0144] (1) SEM characterization: The morphology of the prepared M@P@PDA micromotors was characterized by SEM. The results are as Figure 2 shown. It can be seen that there is one notch on the surface of the M@P@PDA micromotors, which enables the magnesium particles to come into contact with the outside world and undergo an oxidation reaction to produce hydrogen.

[0145] (2) Fluorescence detection: To verify the asymmetric PLGA distribution, Mg@PLGA micromotors were stained with rhodamine. Due to the hydrophobicity of the PLGA coating, rhodamine will be loaded into the PLGA shell, thus producing red fluorescence. An inverted fluorescence microscope was used to take comparative pictures of the rhodamine-stained Mg@PLGA micromotors. The results are as Figure 5 shown.

[0146] (3) Particle size analysis: Statistical analysis was carried out on the particle sizes of the purchased magnesium balls and M@P@PDA micromotors. The results are as Figure 6 shown.

[0147] 2. Hydrogen release performance test of M@P@PDA micromotors:

[0148] The release of hydrogen was detected using methylene blue-platinum probe solution. Due to the influence of the covalent bond of hydrogen itself, hydrogen is difficult to react with methylene blue at room temperature. However, in the presence of platinum, methylene blue can undergo a redox reaction with an equimolar amount of hydrogen. During the reaction stage, the blue oxidized methylene blue (MB) can be changed into colorless reduced methylene blue (leucoMB). Based on this color change, information such as the hydrogen production can be quantified.

[0149] Magnesium ball particles with a mass concentration of 50 μg / mL and M@P@PDA micromotors with an equimolar amount of magnesium were respectively added to the methylene blue-platinum probe solution containing 0.3 M NaHCO3 (final volume 2 mL). The absorbance was measured at a wavelength of 664 nm by UV2600. The results are as Figure 7 shown. Figure 7 A shows the change of methylene blue with the hydrogen release of magnesium ball particles within 40 min, Figure 7 B shows the change of methylene blue with the hydrogen release of M@P@PDA micromotors within 40 min.

[0150] According to Figure 7 the results of A, magnesium ball particles can exhibit rapid H2 release behavior, and the absorbance of MB changes rapidly, decreasing rapidly within 20 min, while M@P@PDA micromotors provide a lower and continuous hydrogen release curve in PBS ( Figure 7 B). This indicates that the hydrogen release of M@P@PDA micromotors is longer and can be effectively controlled. This is because there is only a small notch in the M@P@PDA micromotor, resulting in a small contact area between the magnesium particles and the outside world, thus causing the oxidation reaction of the magnesium particles to be relatively slow, and the hydrogen release can be extended and controlled through this opening.

[0151] 3. Photothermal performance test of M@P@PDA micromotors:

[0152] Mg@PLGA micromotors and M@P@PDA micromotors were irradiated with a near-infrared light source with a wavelength of 808 nm, and an infrared thermal imager was used to monitor at an optical density of 1.0 W / cm 2And the temperature changes of Mg@PLGA micromotors and M@P@PDA micromotors at different times under the irradiation of a laser with a wavelength of 808 nm are as follows Figure 8 as shown. Figure 8 A shows the temperature curves of M@P@PDA micromotors at different times under the irradiation of a 1.0 W / cm 2 and 808 nm laser. In the repeated heating and cooling cycle experiment, after 5 "ON / OFF" cycles, the results are as Figure 8 shown in B, which indicates that the M@P@PDA micromotor has good photothermal stability.

[0153] Figure 8 As shown in A, with the increase of the near-infrared light irradiation time, the temperature of the Mg@PLGA micromotor remains basically unchanged, while the temperature of the M@P@PDA micromotor increases with time. Figure 8 As shown in B, after 5 "ON / OFF" cycles, the highest temperature that the M@P@PDA micromotor can reach remains unchanged at the same temperature level, showing good photothermal reversibility.

[0154] 4. Antibacterial performance test of M@P@PDA micromotors:

[0155] The plate counting method was used to detect the effect of the near-infrared light irradiation duration on the killing of Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) by M@P@PDA micromotors. The Mg@PLGA and M@P@PDA micromotors were mixed with the bacterial suspension to obtain a mixed treatment solution; the mixed treatment solution was irradiated with near-infrared light (wavelength 808 nm, optical density 1 W / cm 2 ) and incubated for 3 h, and the results are as Figure 9 shown. It can be Figure 9 seen that compared with the control group, the bacteria co-incubated with the M@P@PDA micromotor will show a smaller number, indicating that the M@P@PDA micromotor has good bactericidal effect.

[0156] 5. Biofilm removal performance test of M@P@PDA micromotors:

[0157] The dense biofilm formed by Staphylococcus aureus in tryptic soy broth medium was used to evaluate the elimination effect of M@P@PDA micromotors on the dense biofilm structure. The prepared bacterial suspension (10 7(CFU / mL) were inoculated into 96-well plates and cultured at 37 °C for 48 h to form a dense biofilm from the bacterial suspension. Then, Mg@PLGA and Mg@P@PDA micromotors were used to treat the biofilm. The remaining biofilm at the bottom of the 96-well plates was fixed with 4% paraformaldehyde and stained with crystal violet. The residual dye was washed with 30% acetic acid, and the eluate was measured at a wavelength of 590 nm on an enzyme-labeling instrument. The results are as Figure 10 shown. As can be seen from Figure 10 Figure 10 , the absorbance value of the Mg@P@PDA micromotor group was significantly lower than that of the Mg@PLGA biofilm compared to the control group, indicating that Mg@P@PDA micromotors have a good effect on clearing biofilms.

[0158] 6. Biocompatibility test of M@P@PDA micromotors:

[0159] The M@P@PDA micromotors prepared in Example 1 were co-cultured with L929 cells for 6 h to 24 h, and CCK-8 was used to detect cell viability to evaluate the cytocompatibility of M@P@PDA micromotors. The results are as Figure 11 shown in A. As shown in Figure 11 A, after co-incubating M@P@PDA micromotors with cells for 24 h, the cells were stained with live / dead fluorescence. The results are as Figure 11 shown in B. As can be seen from Figure 11 B, the cells of M@P@PDA micromotors all maintained cell viability comparable to that of the control group, indicating that M@P@PDA micromotors are not toxic to cells, and most of the L929 cells are in a healthy growth state (green indicates live cells), and there are almost no dead cells (red indicates dead cells). The above results show that M@P@PDA micromotors have good cytocompatibility.

[0160] 7. Anti-inflammatory performance test of M@P@PDA micromotors:

[0161] ROS was detected using the ROS fluorescent probe CellROX Green reagent. Cells treated with 10 μM H2O2 alone were used as the positive control. In the experimental group, 10 μM H2O2 was mixed with M@P@PDA micromotors and then incubated with cells. Then, the cells were fluorescently stained with CellROX Green and DAPI. The results are as Figure 12 shown, Figure 12 showing the fluorescence in the cells, where the green fluorescence comes from CellROX Green, which represents that the reagent has bound to ROS, and the blue fluorescence comes from DAPI, representing the cell nucleus. As can be seen from Figure 12It can be seen that the green fluorescence intensity of the M@P@PDA micromotor is significantly reduced compared with the H2O2 positive control, demonstrating that the M@P@PDA micromotor has good anti-inflammatory effects.

[0162] 8. Assay for the cell migration-promoting performance of the M@P@PDA micromotor:

[0163] The cell migration-promoting performance of the M@P@PDA micromotor was detected by the cell scratch assay on HUVEC cells. The HUVEC cells were seeded in 24-well plates at a cell seeding density of 5×10 5 cells / well and cultured using complete medium containing 10% fetal bovine serum (FBS) by mass concentration. After culturing for 16 h to 24 h to form a monolayer of cells, a straight line was scratched with the tip of a 200-μL pipette. Then, it was rinsed 3 times with sterile PBS to remove cell debris, and the sterilized M@P@PDA micromotor was placed into the well plate. The well plate without the M@P@PDA micromotor was used as the control group. It was cultured at 37 °C and under a condition of 5% CO2 by volume concentration for 48 h. Then, the culture medium, the M@P@PDA micromotor, and cell debris were removed. The inverted microscope was used to take pictures of the cell scratch, and the results are as Figure 13 shown. It can be Figure 13 seen that after culturing for 24 h, the cells migrated towards the middle scratch. Compared with the control group, the scratch of the M@P@PDA micromotor basically disappeared completely, indicating that the M@P@PDA micromotor has the ability to promote cell migration.

[0164] 9. Assay for the wound healing-promoting performance of the M@P@PDA micromotor:

[0165] (1) Establish a model of diabetic mice. Select Bacl-c mice and randomly divide them into two groups with eight mice in each group. They were allowed to adapt to the environment with normal diet and water for one week before modeling. Before modeling, they were fasted for 8 h, and streptozotocin (STZ, dissolved in sodium citrate buffer with pH = 4.5) was intraperitoneally injected into the mice at a dose of 45 mg / Kg of mouse body weight every day. A high-sugar and high-fat diet was used during the modeling process. When the fasting blood glucose value ≥ 16.7 mM, it was regarded as successful modeling.

[0166] The diabetic mouse model was shaved, and then a full-thickness wound of about 10 mm was created on its back skin. Staphylococcus aureus (at a concentration of 10 8 CFU / mL) was inoculated into the full-thickness wound for 2 days to wait for the completion of the construction of diabetic chronic wounds. The M@P@PDA micromotor was applied to the mouse wounds in an alternate-day dosing manner, and the wound healing situation of the mice and histological analysis were observed. The results are respectively as Figure 14 , Figure 15 and Figure 16 shown. Among them, Figure 14Shows the wound pictures and conditions of mice, Figure 15 Shows the HE staining pictures of the wound skin of mice after 14 days of treatment, Figure 16 Shows the Masson staining pictures of the wound skin of mice.

[0167] It can be seen from Figure 14 that as the treatment time of the M@P@PDA micromotor increases, the wound area of the mice with the M@P@PDA micromotor gradually decreases, and the healing conditions at each time are significantly better than those of the control group. It can be seen from Figure 14 B that the wound healing rate of the mice is relatively fast. After 14 days, the M@P@PDA micromotor has basically completely healed, which shows that the mice have a good ability to promote wound healing in mice.

[0168] HE staining was performed on the wound tissue to analyze the histological changes at the wound site. It can be seen from Figure 15 that in the control group, the emergence of new epidermis was not shown, the healing signs were not obvious, and there were a large number of inflammatory cells, indicating that the mice were still in an inflammatory state. While the M@P@PDA micromotor has almost completed tissue remodeling, there are almost no inflammatory cells, showing an epidermal thickness close to normal skin, a narrower dermal space, a dermis layer with a relatively normal structure, and more hair follicle structures.

[0169] The Masson trichrome staining method was used to analyze the content of collagen in the wound tissue, and the results are as Figure 16 shown. In the control group, only a small amount of collagen deposition was observed. While in the M@P@PDA micromotor and the NIR group, it was possible to observe that the collagen fibers showed a more orderly bundle arrangement (blue), and there was obvious collagen fiber deposition in the granulation tissue, and the collagen distribution was relatively uniform, indicating that the wound healing process was basically completed.

[0170] In summary, a micromotor with synergistic bactericidal and anti-inflammatory effects provided by the embodiments of the present application. This micromotor uses magnesium particles as the core and poly(lactic-co-glycolic acid) layer and polydopamine layer as the composite coating layer. Through the synergistic effect of these structures, the bactericidal and anti-inflammatory effects of the micromotor can be improved synchronously. In actual experiments, this micromotor has shown good antibacterial, anti-inflammatory, and wound healing promotion abilities. This micromotor realizes its antibacterial, anti-inflammatory, and wound healing promotion processes through the hydrogen continuously generated by magnesium particles and the photothermal therapy of polydopamine, demonstrating the application potential of the micromotor as a biomedical material.

[0171] In addition, a method for preparing a micromotor provided by the embodiments of the present application. This method only requires a polymerization reaction and a coating process under mild conditions. The overall process of the method is simple and easy to operate, and can be applied on a large scale in industrial production.

[0172] In addition, a wound healing material provided by an embodiment of the present application. Based on the antibacterial, anti-inflammatory, and wound healing effects of the micromotor, this wound healing material can provide a new biomaterial solution for the treatment of diabetic chronic wounds, which integrates high-efficiency antibacterial, inflammation regulation, and tissue regeneration.

[0173] The above are only specific embodiments of the present application, enabling those skilled in the art to understand or implement the present application. Various modifications to these embodiments will be obvious to those skilled in the art. The general principles defined in the present application can be implemented in other embodiments without departing from the spirit or scope of the present application. Therefore, the present application will not be limited to these embodiments shown in the present application, but rather to the broadest scope consistent with the principles and novel features claimed in the present application.

Claims

1. A micromotor with synergistic bactericidal and anti-inflammatory properties, wherein the micromotor is a core-shell structure, the core is a magnesium particle, the shell is a composite coating layer, and the composite coating layer includes a polylactic acid-glycolic acid copolymer layer and a polydopamine layer; The polylactic acid-glycolic acid copolymer layer partially covers the surface of the magnesium particles to form an opening on the surface of the magnesium particles; the width of the opening is ≥5 μm; The polydopamine layer completely covers the surface of the polylactic acid-glycolic acid copolymer layer. 2 . The micromotor according to claim 1 , wherein a width of the opening is 5 μm to 15 μm. 3 . The micromotor according to claim 1 , wherein the average particle size of the magnesium particles is 15 μm to 20 μm. The micro-motor according to claim 1 , wherein the average particle size of the micro-motor is 25 μm to 30 μm.

5. A method for preparing the micromotor according to any one of claims 1 to 4, the method comprising: The magnesium particles are sequentially dispersed and leached using an organic solvent to obtain a single layer of magnesium particles; Coating a polylactic acid-co-glycolic acid copolymer solution on one side of the single-layer magnesium particle layer so that the polylactic acid-co-glycolic acid copolymer solution partially covers the magnesium particles to obtain coated core particles; The coated core particles are immersed in a polydopamine solution and vacuum dried so that the polydopamine solution is coated on the surface of the polylactic acid-glycolic acid copolymer to obtain polydopamine-coated micro-nanoparticles; The polydopamine coated micro-nanoparticles are scraped out in a single layer to expose the bottom openings of the polydopamine coated micro-nanoparticles, thereby obtaining a micro-motor.

6. The method according to claim 5, wherein the mass m1 of the magnesium particles and the volume V1 of the organic solvent satisfy the relationship: m1:V1=1:1, if the unit of m1 is mg, the unit of V1 is mL; and / or The mass concentration of the polylactic acid-co-glycolic acid solution is 15 mg / mL, and the molecular weight of the polylactic acid-co-glycolic acid solution is 10 kDa.

7. The method according to claim 5, wherein the polydopamine solution is prepared by: The dopamine hydrochloride and tris(hydroxymethyl)aminomethane hydrochloride) solution are polymerized to obtain polydopamine; The polydopamine is ultrasonically dispersed in deionized water to obtain a polydopamine solution.

8. The method according to claim 7, wherein the mass m2 of the dopamine hydrochloride and the volume V2 of the tris(hydroxymethyl)aminomethane hydrochloride solution satisfy the relationship: m2:V2=2:1, if the unit of m2 is mg, the unit of V2 is mL; and / or The mass concentration of the tris(hydroxymethyl)aminomethane hydrochloride solution is 50mmol / L; and / or The mass m3 of the polydopamine and the volume V3 of the deionized water satisfy the relationship: m3:V3=5:

1. If the unit of m3 is mg, the unit of V3 is mL.

9. A wound healing material, comprising the micromotor according to any one of claims 1 to 4, wherein the wound healing material is used for preparing a healing agent for diabetic chronic wounds.

10. A biomedical material, comprising the micromotor according to any one of claims 1 to 4.

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