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CN-122005901-A - M2 membrane camouflage magnetic nanoparticle composite hydrogel and preparation method and application thereof in tissue repair

CN122005901ACN 122005901 ACN122005901 ACN 122005901ACN-122005901-A

Abstract

The invention discloses an M2 membrane camouflage magnetic nanoparticle composite hydrogel, a preparation method thereof and application thereof in tissue repair. The magnetic nanoparticle composite hydrogel comprises a double-network polymer matrix formed by gallic acid modified collagen and oxidized methacrylic acid hyaluronic acid, wherein M2 membrane camouflage magnetic nanoparticles are arranged in the double-network polymer matrix, and the magnetic nanoparticles are wrapped by a membrane from M2 macrophages. The invention constructs a multifunctional integrated magnetic response composite hydrogel, which comprises a double-network polymer matrix formed by collagen modified by gallic acid and oxidized methacrylic acid hyaluronic acid, wherein magnetic nano particles are embedded in the matrix, and a membrane from M2 phenotype macrophages is wrapped. The three core functions of antioxidation and scavenging Reactive Oxygen Species (ROS), active immunoregulation and non-contact dynamic mechanical stimulation are integrated into a single system, so that the problems of single function and insufficient synergistic effect of the existing dressing are solved.

Inventors

  • YAN PENGFEI
  • ZHENG HUI
  • WANG ZUYONG
  • ZHANG RUIXING

Assignees

  • 湖南大学

Dates

Publication Date
20260512
Application Date
20251229

Claims (10)

  1. 1. The M2 membrane camouflage magnetic nanoparticle composite hydrogel is characterized by comprising a double-network polymer matrix formed by gallic acid modified collagen and oxidized methacrylic acid hyaluronic acid, wherein the double-network polymer matrix is provided with M2 membrane camouflage magnetic nanoparticles, and the magnetic nanoparticles are wrapped by a membrane from M2 macrophages.
  2. 2. The M2 membrane camouflage magnetic nanoparticle composite hydrogel of claim 1, wherein the magnetic nanoparticle comprises a superparamagnetic iron oxide core and the M2-type macrophage membrane is derived from interleukin-4 polarized macrophages.
  3. 3. The M2 film camouflage magnetic nanoparticle composite hydrogel of claim 1 or 2, wherein the concentration of M2 film camouflage magnetic nanoparticles in the dual network polymer matrix is 400-800 μg/mL.
  4. 4. A method for preparing the M2 film camouflage magnetic nanoparticle composite hydrogel according to any one of claims 1-3, comprising the steps of: S1, extracting an M2 type macrophage membrane, and preparing the M2 membrane camouflage magnetic nano particles with the iron nano particles by an extrusion method; S2, preparing gallic acid modified collagen from I-type collagen extracted from tilapia skin and gallic acid through EDC/NHS crosslinking, preparing a mixture by oxidizing hyaluronic acid and sodium periodate under a light-proof condition, sequentially dialyzing and freeze-drying the mixture to obtain oxidized hyaluronic acid solid, preparing the prepared oxidized hyaluronic acid solid into a solution, adding methacrylic anhydride to react under an ice water bath condition, regulating the pH value of a reaction system to be 8.0, sequentially dialyzing and freeze-drying the mixed solution after the reaction is finished to obtain oxidized methacrylic acylated hyaluronic acid solid, dissolving the gallic acid modified collagen in 0.01-0.03-M of acetic acid to prepare a solution with the concentration of 8-12 mg/mL, regulating the pH value to be neutral, obtaining a solution A, dissolving the oxidized methacrylic acylated hyaluronic acid solid in water to prepare a solution B with the concentration of 140-150 mg/mL, dissolving M2 membrane camouflage magnetic nanoparticles obtained in the step S1 in PBS (PBS-12) to obtain a solution with the concentration of mg ℃ and then uniformly irradiating the magnetic membrane camouflage magnetic nanoparticles with light at the temperature of 3-37 ℃ under the conditions of PBS (light-3 ℃ and the magnetic phosphine) to form a three-phase magnetic composite magnetic membrane with the three-phase magnetic membrane.
  5. 5. The preparation method according to claim 4, wherein the step S1 specifically comprises the steps of: s11, stimulating RAW264.7 macrophages by using interleukin-4, and inducing polarization of the RAW264.7 macrophages into an M2 phenotype with anti-inflammatory and repair promoting functions; S12, breaking cells, separating and purifying M2 cell membrane vesicles, mixing the purified M2 cell membrane with iron nanoparticles to obtain a mixed solution, and extruding the mixed solution polycarbonate membrane for a plurality of times to form the M2 membrane camouflage magnetic nanoparticle Fe-M 2 NPs with a stable structure.
  6. 6. The method according to claim 5, wherein in step S12, the amount of the iron nanoparticles in the M2 film camouflage magnetic nanoparticles is 3-5 mg iron nanoparticles per mg of the film protein, and the mixture is extruded several times through the polycarbonate film with the pore diameters of 400nm and 200 nm.
  7. 7. Use of the M2 film camouflage magnetic nanoparticle composite hydrogel of any one of claims 1-3 or the M2 film camouflage magnetic nanoparticle composite hydrogel obtained by the preparation method of any one of claims 4-6 in the preparation of a pharmaceutical formulation for tissue repair.
  8. 8. A pharmaceutical preparation for tissue repair, characterized in that the M2 membrane camouflage magnetic nanoparticle composite hydrogel obtained by the preparation method of any one of claims 1 to 3 or any one of claims 4 to 6 is used as an active ingredient.
  9. 9. The method of using a pharmaceutical formulation for tissue repair of claim 8, wherein the pharmaceutical formulation for tissue repair is co-administered with an external dynamic magnetic field.
  10. 10. The method of claim 9, wherein the external dynamic magnetic field has a magnetic flux density of 400-600 mt and an oscillation frequency of 0.5-1.0 Hz.

Description

M2 membrane camouflage magnetic nanoparticle composite hydrogel and preparation method and application thereof in tissue repair Technical Field The invention relates to the technical field of biomedical materials, in particular to M2 membrane camouflage magnetic nanoparticle composite hydrogel, a preparation method thereof and application thereof in tissue repair. Background Difficult healing of diabetic wounds is a significant challenge in clinical practice, with the core pathological mechanisms consisting in persistent inflammation induced by hyperglycemia, blocked neovascularization, and imbalance in extracellular matrix (ECM) remodeling. This pathological microenvironment is closely related to intracellular calcium ion (ca2+) signal disorders-ca2+ is a key second messenger regulating cell migration, proliferation and angiogenesis, and its imbalance in homeostasis severely affects the function of the repaired cells. Recent studies have further revealed that mechanically sensitive channels such as Piezo1 and TRPV4 and their downstream effector molecules Yes-related proteins (YAPs) play a central role in sensing microenvironment mechanical signals and converting into ca2+ influx and regenerating gene expression. However, diabetic wounds can lead to impaired ca2+ homeostasis, thereby disrupting mechanical transduction pathways including RhoA/ROCK, leading to reduced YAP activity, ultimately leading to reduced transduction efficiency of mechanical signals into regenerative signals, and wound repair arrest. The current clinical strategies in common use have the following significant limitations: 1. The intelligent response type hydrogel has the limitation that the temperature-sensitive, pH response or enzyme triggering type hydrogel can realize the controlled release of the medicine or the micro-environment regulation, but the action mechanism is mainly passive response, and lacks the active and dynamic regulation capability on the micro-environment of cell mechanics. Such materials often fail to mimic the dynamic mechanical stimulus experienced by cells in physiological conditions, making it difficult to activate critical mechanically sensitive signal pathways. 2. Cell therapy has the limitations that although it promotes re-epithelialization and paracrine action, the transplanted cells have low survival rate in the microenvironment where the diabetic wound is severe, the functions are easily affected, and the problems of immune rejection, ethical limitation, high cost and the like exist. 3. The disadvantage of Negative Pressure Wound Therapy (NPWT) is that although devices such as NPWT can apply mechanical stimulation, the mechanism of action is not clear, and the devices are contact physical stimulation, which may cause discomfort to patients, and are difficult to act on deep tissues, and more importantly, accurate mechanical regulation at the cell level cannot be realized. 4. The limitation of the existing magnetic response material is that the combination of the magnetic response hydrogel and the noninvasive magnetic field opens up a new path for wireless mechanical regulation, but the current research focuses on thermal effect or drug targeted delivery, and the research of directly regulating cell behaviors by utilizing non-thermodynamic signals is not enough. Most magnetically responsive materials either act only as drug carriers or rely on the magnetocaloric effect, lacking the ability to specifically activate the cellular machinery signal pathways. 5. The existing treatment strategies are often only aimed at a single link of wound healing, and lack comprehensive capability of simultaneously solving multiple pathological factors such as oxidative stress, chronic inflammation, angiogenesis disorder, mechanical signal disorder and the like. Especially, the existing materials have insufficient synergistic ability in terms of antioxidation, immunoregulation and mechanical signal transmission, and are difficult to effectively reverse the healing disorder of the diabetes wound. 6. Mechanical biological mechanisms are underutilized-cell behaviors critical to wound healing, such as migration, proliferation and matrix secretion, are themselves highly mechanically sensitive processes. However, existing treatments fail to effectively utilize mechanochemical principles and fail to activate endogenous repair procedures by controllable mechanical stimulation. Therefore, developing an intelligent material system capable of realizing the cooperation of the multiple functions of antioxidation, immunoregulation and mechanical stimulation at the same time, and accurately regulating and controlling the microenvironment of the diabetes wound in a non-contact mode becomes a technical bottleneck to be broken through in the current field. Disclosure of Invention In order to solve the problem that the existing diabetes wound is difficult to heal, the invention provides an M2 membrane camouflage magnetic nanoparticle composite