A smart bionic wound management system and its preparation method

Abstract

This invention discloses an intelligent biomimetic wound management system and its preparation method, relating to the fields of biomedical engineering and intelligent wound care technology. The system includes: a 3D-printed flexible electronic support frame layer with a honeycomb-like porous mesh structure and a microstructured interface composed of a micron-level groove array on its surface; the edges integrate a micro piezoelectric energy harvester, a power management circuit, a wireless transmission module, and an early warning unit; a coaxial electrospun multifunctional nanofiber active layer with a core-shell bilayer structure, directionally deposited and anchored to the microstructured interface via coaxial electrospinning; the core layer contains a composite therapeutic factor loaded on a mesoporous carrier, and the shell layer is a temperature-sensitive and pH-responsive conductive composite material. This invention effectively solves the problems of functional fragmentation, low interfacial bonding strength, and energy dependence in existing technologies, and is suitable for precise full-cycle care of chronic ulcers and acute wounds.

Description

Technical Field

[0001] This invention relates to the fields of biomedical engineering and intelligent wound care technology, and in particular to an intelligent bionic wound management system and its preparation method. It is applicable to the precise care of various wounds such as acute trauma, chronic ulcers (such as diabetic foot ulcers and venous ulcers), and postoperative wounds. It can realize real-time monitoring of the wound microenvironment, on-demand drug delivery, and visual early warning of healing status. Background Technology

[0002] As a core tool for full-cycle wound care, the intelligent bionic wound management system must simultaneously meet three core requirements: real-time monitoring, precise drug delivery, and stable self-supply. Especially in scenarios such as chronic, difficult-to-heal wounds like diabetic foot ulcers and venous ulcers, as well as acute trauma and postoperative wounds, the system not only needs to dynamically sense the wound microenvironment (such as temperature, pH, and humidity) to provide early warning of infection or inflammation, but also needs to adapt to the "inflammation-proliferation-remodeling" healing cycle through a responsive release mechanism. At the same time, it must rely on an integrated "electronic-biological" structure to ensure fit and endurance, while also taking into account biosafety to avoid secondary damage.

[0003] However, existing wound care technologies mostly employ single-function modules or simple stacked designs, making it difficult to form a coordinated "monitoring-intervention-power supply" system. This results in problems such as functional fragmentation, poor structural stability, and insufficient clinical adaptability. Specifically: Patent CN115992411A discloses a coaxial spun nanofiber membrane, which can achieve sustained drug release, but it is only a single biological layer structure, lacks flexible electronic monitoring and self-powered units, cannot dynamically sense the wound condition and adjust the drug release behavior, and the lack of a support frame easily leads to poor adhesion. The 3D-printed piezoelectric scaffold involved in patent CN114474708A, although it has the function of piezoelectric healing, does not integrate pH / temperature sensing and dual-response drug release function, thus failing to form a precise treatment closed loop. Furthermore, it lacks a dedicated microstructured interface, resulting in weak bonding with the biological layer. Although the temperature-sensitive pH-responsive fiber proposed in patent CN109826015A has environmental responsiveness, it does not integrate electronic monitoring and time-sequential drug delivery design, nor does it have functional module integration slots. It is easily affected by external interference, which affects its response performance and makes it impossible to achieve data transmission and healing early warning.

[0004] In summary, existing technologies generally suffer from functional isolation, disconnect between the electronic and biological interfaces, and poor multi-module coordination, failing to achieve integrated adaptation of "monitoring-drug release-self-powered-early warning" and thus unable to meet the complex needs of full-cycle care for different wounds. Therefore, there is an urgent need to develop an intelligent collaborative system with an "electronic-biological" dual-network structure to overcome the above bottlenecks and achieve self-powered real-time monitoring of the wound microenvironment, multi-stage on-demand precise time-sequential drug release, and a visualized early warning closed loop. Summary of the Invention

[0005] To address these issues, this invention provides an intelligent bionic wound management system and its preparation method, which solves the problems of functional fragmentation, weak electronic-biological interface integration, and reliance on external power supply in existing wound care products.

[0006] To address the aforementioned technical problems, embodiments of the present invention provide an intelligent bionic wound management system, comprising: The 3D printed flexible electronic support frame layer has a honeycomb porous grid structure. Its surface has a microstructured interface composed of a micron-level groove array. Sensor packaging units are provided at the grid nodes of the 3D printed flexible electronic support frame layer, and functional module integration areas are provided at the edges. The coaxial electrospun multifunctional nanofiber active layer is a core-shell bilayer structure nanofiber that is directionally deposited and anchored to the microstructured interface through coaxial electrospinning process, covering the 3D printed flexible electronic support framework layer. Electronic functional components, arranged in the functional module integration area, include a miniature piezoelectric energy harvester, a power management circuit, a wireless transmission module, and an early warning unit with visual output function; The micro piezoelectric energy harvester is electrically connected to the sensor packaging unit, the wireless transmission module and the early warning unit through the power management circuit. The power management circuit controls the early warning unit to output a pulsed early warning signal based on the wound microenvironment parameters collected by the sensor packaging unit, forming a self-powered monitoring closed loop. The core layer of the coaxial electrospun multifunctional nanofiber active layer contains a composite therapeutic factor loaded on a mesoporous carrier, and the shell layer is a temperature-sensitive and pH-responsive conductive composite material.

[0007] Preferably, the 3D printed flexible electronic support frame layer is made of PEDOT:PSS and gelatin conductive composite hydrogel; the microgrooves of the microstructured interface have a depth of 5-10 μm, a width of 10-20 μm, and a spacing of 50-100 μm; the coaxial electrospun multifunctional nanofiber active layer is embedded in the microgrooves to form a mechanical interlocking structure, and its interface peel strength is ≥0.5 N / cm.

[0008] Preferably, the shell material of the coaxial electrospun multifunctional nanofiber active layer is modified with hydrophilic carboxymethyl chitosan, and its low critical dissolution temperature is adjusted to 37.5-38.5℃ to distinguish between normal body temperature and pathological high temperature.

[0009] Preferably, the power management circuit includes a rectifier bridge and a miniature energy storage capacitor, used to convert the AC power generated by the miniature piezoelectric energy harvester into DC power and store it; the wireless transmission module is a passive NFC module or a low-power Bluetooth module.

[0010] Preferably, the core material of the coaxial electrospun multifunctional nanofiber active layer includes polylactic acid and chitosan, the mesoporous carrier is mesoporous silica microspheres, and the loaded composite therapeutic factors include antimicrobial peptide LL-37, vascular endothelial growth factor and gallic acid.

[0011] Preferably, the shell material of the coaxial electrospun multifunctional nanofiber active layer includes polyisopropylacrylamide, carboxymethyl chitosan, and polypyrrole nanowires; through the synergistic effect of the thermosensitive shrinkage of polyisopropylacrylamide and the pH swelling of carboxymethyl chitosan, the shell density is reduced in an infected environment to accelerate drug release.

[0012] This invention also provides a method for preparing an intelligent bionic wound management system, comprising the following steps: S1: PEDOT:PSS is mixed with gelatin to prepare a precursor solution. A honeycomb porous mesh is printed using direct writing 3D printing technology. After curing, microgrooves are etched on the mesh surface using ultraviolet laser. After cross-linking treatment, a 3D printed flexible electronic support framework layer with a microstructured interface is obtained. S2: Assemble a micro piezoelectric energy harvester, power management circuit, wireless transmission module, early warning unit and sensor packaging unit in the reserved slots of the 3D printed flexible electronic support frame layer, and realize circuit interconnection through flexible conductive adhesive circuit, and perform electrostatic shielding protection treatment on the functional module integration area. S3: Prepare a core spinning solution containing a mesoporous carrier loaded with drugs and a shell spinning solution containing a temperature- and pH-responsive conductive composite material; use coaxial electrospinning technology to directionally deposit nanofibers onto the microstructured interface of the 3D printed flexible electronic support framework layer described in step S1. S4: The deposited system is subjected to interface strengthening cross-linking and deep desolventizing treatment, and then dried, cut and sterilized and packaged to obtain the final product.

[0013] Preferably, in step S1, the mass ratio of PEDOT:PSS to gelatin in the precursor solution is 3:7, and the total solid content is 8-10wt%; the nozzle diameter for 3D printing is 0.2-0.4mm, and the printing layer height is 0.1-0.15mm; the microgrooves etched by the ultraviolet laser have a depth of 5-10μm, a width of 10-20μm, and a spacing of 50-100μm.

[0014] Preferably, in step S3, the core spinning solution is a water-in-oil (W / O) emulsion system, wherein the aqueous phase disperses a mesoporous carrier loaded with composite therapeutic factors, and the oil phase is a mixed solution of polylactic acid and chitosan; the shell spinning solution uses a mixed solvent system of N,N-dimethylformamide and water; the receiving distance of the coaxial electrospinning is 15-18 cm, the voltage is 15-18 kV, and the core-to-shell propulsion speed ratio is 1:2.0-1:2.5.

[0015] Preferably, in step S4, the interface strengthening crosslinking is physical thermal dehydration crosslinking (DHT), which is treated under vacuum and 50°C for 24 hours to enhance the interfacial bonding force while avoiding chemical crosslinking agent residue; the deep desolventizing treatment is to perform gradient dialysis washing with sterile phosphate buffer at 4°C to remove residual organic solvents.

[0016] As can be seen from the above technical solutions, this invention application has the following beneficial effects: (1) Dual response and time-sequential drug release for precise matching of the healing cycle: This invention adopts a thermosensitive (PNIPAAm)-pH (carboxymethyl chitosan) synergistic response mechanism. Through the hydrogen bonding between hydrophilic carboxymethyl chitosan and PNIPAMAm molecular chains, the low critical solution temperature (LCST) is adjusted to 37.5-38.5℃, effectively distinguishing between normal body temperature and pathological high temperature. In an infected / inflammatory environment (temperature > 37.5℃ or pH < 5.5), the hydrophobic coiling of PNIPAMAm chain segments and the electrostatic repulsion of protonated amino groups of carboxymethyl chitosan work synergistically to reduce shell density and trigger accelerated drug release (rate increased to 1.0-1.8 μg / (cm²·h)); during the normal healing period, a low release state is maintained (≤0.6 μg / (cm²·h)). Meanwhile, the LL-37, VEGF and gallic acid loaded on mesoporous silica microspheres achieve sequential release of anti-infection in 0-3 days, angiogenesis in 3-7 days and antioxidant in 0-10 days, precisely matching the full cycle needs of wound "inflammation-proliferation-remodeling".

[0017] (2) Integrated electronic-biological interface with a stable structure that adapts to curved surfaces: The microgroove structure (depth 5-10μm, width 10-20μm, spacing 50-100μm) on the surface of the 3D-printed flexible frame forms a mechanical interlock with the coaxial electrospun layer, with an interface peel strength ≥0.65N / cm, solving the problem of easy delamination in traditional laminated structures. The system thickness is only 0.3-0.5mm (frame) + 50-100μm (fiber layer), which can adapt to the curved surface of the human body with a curvature radius of 1.5cm. It can withstand repeated bending 500 times (±90°) without delamination or fiber shedding, and has excellent flexibility (air permeability ≥500mL / (cm²·24h)) and biocompatibility (cytotoxicity grade 0, hemolysis rate <5%, no sensitization).

[0018] (3) Self-powered energy harvesting and logical closed loop, intuitive early warning to reduce risks: This invention innovatively integrates a PVDF piezoelectric energy harvester and a "micro-energy accumulation-pulse release" power management strategy. It harvests mechanical energy through human movement (such as joint bending and walking), and after rectification and energy storage, it powers the sensor, NFC module and LED early warning unit, achieving true "unlimited battery life" (theoretically unlimited operation). The sensor response time is ≤4s, and the NFC data packet loss rate is <0.5%. When the detected temperature is >37.5℃ or pH <5.5, the LED automatically lights up to warn, forming a "monitoring-intervention-early warning" closed loop, effectively avoiding monitoring interruption caused by battery depletion and the risk of secondary infection caused by battery replacement (infection incidence rate reduced to below 5%). Attached Figure Description

[0019] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly described below. Referring to the drawings will make the features and advantages of the present invention clearer. The drawings are illustrative and should not be construed as limiting the present invention in any way. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. Wherein: Figure 1 This is a schematic diagram of the structure of an intelligent bionic wound management system provided by the present invention; Figure 2 A schematic diagram illustrating the deposition process of coaxial electrospinning multifunctional nanofiber active layer on a microstructured framework; Figure 3 Top view of the honeycomb porous mesh structure of the 3D printed flexible electronic support frame layer; Figure 4 This is a schematic diagram of the manufacturing process of the intelligent bionic wound management system of the present invention.

[0020] Explanation of reference numerals in the accompanying drawings: 1. 3D printed flexible electronic support frame layer; 2. Coaxial electrospun multifunctional nanofiber active layer; 3. Functional module integration area; 4. Micro piezoelectric energy harvester; 5. Early warning unit; 6. Honeycomb porous mesh structure; 7. Inner syringe; 8. Outer syringe; 9. High-voltage electric field; 10. Frame deposition area; 11. Rotating receiving roller; 12. Precursor liquid mixing device; 13. 3D printing nozzle; 14. Laser etching device; 15. Electronic functional components; 16. Coaxial electrospun nozzle; 17. High-voltage power supply; 18. Post-treatment soaking tank; 19. Finished product. Detailed Implementation

[0021] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0022] The technical solution of the present invention will now be described in detail with reference to the accompanying drawings.

[0023] like Figure 1 As shown, the intelligent bionic wound management system provided by the present invention includes: a 3D printed flexible electronic support frame layer 1, a coaxial electrospun multifunctional nanofiber active layer 2, a functional module integration area 3, a micro piezoelectric energy harvester 4, an early warning unit 5, and a honeycomb porous mesh structure 6. The 3D-printed flexible electronic support frame layer 1 has a honeycomb porous mesh structure 6 with a microstructured interface composed of a micron-level groove array on its surface. Sensor encapsulation units are located at the mesh nodes of the 3D-printed flexible electronic support frame layer 1, and functional module integration areas 3 are located at its edges. The coaxial electrospun multifunctional nanofiber active layer 2 is a core-shell double-layer structure nanofiber, which is directionally deposited and anchored to the microstructured interface through coaxial electrospinning process, covering the 3D-printed flexible electronic support frame layer 1. Electronic functional components 15 are arranged in the functional module integration area 3, including a micro piezoelectric energy harvester 4, a power management circuit, a wireless transmission module, and an early warning unit 5. The micro piezoelectric energy harvester 4 is electrically connected to the sensor encapsulation unit, the wireless transmission module, and the early warning unit 5 through the power management circuit, forming a self-powered monitoring closed loop. The core layer of the coaxial electrospun multifunctional nanofiber active layer 2 contains composite therapeutic factors loaded on a mesoporous carrier, and the shell layer is a temperature-sensitive-pH dual-responsive conductive composite material. The magnified view shows the details of the microstructured interface on the surface of the framework layer, where w represents the width of the microgroove, d represents the depth of the microgroove, and s represents the spacing between the microgrooves. This structure is used to enhance the mechanical interlocking force between the nanofiber layer and the framework layer.

[0024] like Figure 2 The diagram shows the deposition process principle of coaxial electrospun multifunctional nanofiber active layer 2 on a microstructured framework. In the diagram, the inner syringe 7 is used to deliver the core layer solution containing a mesoporous carrier drug, and the outer syringe 8 is used to deliver the shell layer solution of a dual-response material. Under the action of a high-voltage electric field 9, the core-shell structured fiber jet is directionally sprayed into the framework deposition area 10, and finally anchored on the framework surface with microgrooves. The rotating receiving roller 11 guides the nanofibers to deposit uniformly and directionally by setting a rotation speed.

[0025] like Figure 3The figure shows a top view of the honeycomb porous mesh structure 6 of the 3D printed flexible electronic support frame layer 1, demonstrating the macroscopic geometric configuration of the 3D printed flexible electronic support frame layer 1. The honeycomb hexagonal mesh structure gives the system excellent flexibility and breathability. The d marked in the figure is the mesh aperture (1-2mm). This structural design ensures mechanical support while adapting to the curvature of human skin.

[0026] like Figure 4 The diagram shows the manufacturing process of the intelligent bionic wound management system of the present invention, illustrating the complete process from raw material mixing to finished product 19 encapsulation: the precursor liquid mixing device 12 prepares conductive bio-ink, which is then printed by the 3D printing nozzle 13 to obtain a 3D printed flexible electronic support frame layer 1 (semi-finished product). The layer is then processed with microgrooves by the laser etching device 14, and then integrated with electronic functional components 15 (including sensors, power management circuits, LEDs, etc.). Nanofibers are then deposited on the frame surface by the coaxial electrospinning nozzle 16 under the action of a high voltage power supply 17. The rotating receiving roller 11 assists in collection. After that, the system is placed in the post-processing soaking tank 18 for interface strengthening cross-linking and deep desolventizing treatment, and finally the finished product 19 is obtained for encapsulation.

[0027] The present invention will be described in detail below with reference to specific embodiments.

[0028] I. Experimental Materials and Instruments The main materials and instruments used in the implementation of this invention are shown in Tables 1 and 2 below. All materials are commercially available analytical grade or medical grade and have not undergone further processing before use.

[0029] Table 1 Experimental Materials

[0030] Table 2 Experimental Instruments

[0031] II. Implementation Examples Example 1: A circular intelligent bionic wound management system adapted for chronic ulcers This embodiment prepares a circular system with a diameter of 5cm, which is suitable for chronic and difficult-to-heal wounds such as diabetic foot ulcers and venous ulcers.

[0032] Preparation steps: (1) Pre-fabrication of 3D printed flexible electronic support frame layer 1: PEDOT:PSS and gelatin are mixed to prepare a precursor liquid, honeycomb porous mesh is printed by direct writing 3D printing technology, and micro grooves are etched on the mesh surface by ultraviolet laser after curing. After cross-linking treatment, 3D printed flexible electronic support frame layer 1 with microstructured interface is obtained.

[0033] Precursor preparation: A PEDOT:PSS dispersion with a solid content of 1.2 wt% was mixed with gelatin with a molecular weight of 60 kDa at a mass ratio of 3:7. The mixture was stirred in a 50°C water bath for 2 hours until homogeneous, and then degassed by vacuum centrifugation (3000 rpm, 10 min) to obtain a conductive bio-ink with a total solid content of 9.5 wt%.

[0034] Printing process: A pneumatic extrusion-type bio 3D printer (model: Bio-X) was used, employing a 25G (0.26mm inner diameter) conical nozzle. The barrel heating temperature was set to 28℃ to maintain ink rheology, and the receiving platform temperature was set to 10℃ for rapid phase change and shaping. The printing air pressure was 0.4MPa, and the speed was 8mm / s. Printing followed the path of "outer contour - honeycomb filling - functional slots," controlling the layer height at 0.12mm to produce a honeycomb grid frame with a side length of 1.0mm (corresponding to an aperture diameter of approximately 1.7mm) and a thickness of 0.4mm.

[0035] Microstructure fabrication: The printed frame was equilibrated in an environment with 80% humidity for 30 minutes. In the semi-dry gel state, a UV nanosecond laser marking machine (wavelength 355nm) was used to etch parallel microgrooves on the mesh surface using a low-power, multiple-scan mode. The groove depth was set to 8.0μm, the width to 15.0μm, and the spacing to 80μm. Finally, it was immersed in a 0.15wt% EDC / NHS ethanol solution for crosslinking for 4 hours, and then repeatedly washed three times with deionized water to remove residual monomers. It was then dried for later use.

[0036] (2) Integration of functional modules: The micro piezoelectric energy harvester 4, power management circuit, wireless transmission module, early warning unit 5 and sensor packaging unit are assembled in the reserved slot of the 3D printed flexible electronic support frame layer 1. The circuit interconnection is achieved through flexible conductive adhesive circuit, and the functional module integration area 3 is subjected to electrostatic shielding protection treatment.

[0037] Furthermore, the flexible conductive adhesive circuit employs a silver nanowire / PEDOT:PSS composite conductive adhesive. The conductive adhesive is prepared by mixing a 2% (w / w) silver nanowire dispersion with a PEDOT:PSS dispersion at a 1:1 volume ratio, and adding 5 wt% glycerol as a plasticizer. The conductive adhesive is applied to the pre-reserved circuit paths on the 3D-printed flexible electronic support frame layer 1 using a micro-dispensing process. Its Young's modulus matches that of the 3D-printed flexible frame (<1 MPa), ensuring the flexibility and conductivity stability of the circuit connections during repeated bending of the system. Simultaneously, the functional module integration area 3 undergoes electrostatic shielding treatment, specifically by partially covering the precision chip with a polyimide film to prevent breakdown damage to the circuit from the high-voltage electric field 9 during subsequent electrospinning.

[0038] Specifically, a commercially available PVDF piezoelectric film (TEConnectivity, with a pre-fabricated gold electrode on the surface and a thickness of 28 μm) is embedded in a reserved slot at the edge of the frame.

[0039] Constructing a power management circuit: A low-power energy harvesting power management chip (such as LTC3588-1) is used to replace the simple rectifier bridge, and surface-mount tantalum capacitors (47μF, 6V) are mounted on the circuit nodes to achieve efficient accumulation and regulated output of microampere piezoelectric current.

[0040] The passive NFC tag chip is connected to three low-power red LED indicators (arranged in an equilateral triangle) and set to pulse flashing mode to reduce power consumption. It is encapsulated by spraying a 15μm thick PCL (polycaprolactone) layer to ensure insulation without affecting signal transmission.

[0041] Before entering the electrospinning process, the above-mentioned electronic component area is covered with polyimide insulating tape, and the circuit ground wire is temporarily grounded to prevent high voltage electrostatic discharge from damaging the precision chip.

[0042] (3) Deposition of coaxial electrospinning multifunctional nanofiber active layer 2: Prepare a core spinning solution containing a mesoporous carrier loaded with drugs and a shell spinning solution containing a temperature-sensitive-pH dual-response conductive composite material; use coaxial electrospinning technology to directionally deposit nanofibers on the microstructured interface of the 3D printed flexible electronic support framework layer 1.

[0043] Core spinning solution: A water-in-oil (W / O) emulsion system was used. A phosphate-buffered saline (PBS) solution containing VEGF and LL-37 (with a small amount of PVA as a protective agent) was adsorbed into mesoporous silica as the aqueous dispersion phase. PLA / chitosan was dissolved in a mixed solvent of DCM / acetic acid (not the highly corrosive TFA (trifluoroacetic acid)) as the continuous oil phase. A stable emulsion was formed through ultrasonic emulsification for spinning, preventing the active ingredients from direct contact with the organic solvent and subsequent deactivation.

[0044] Shell spinning solution: A mixed solvent system of DMF / deionized water (volume ratio 7:3) was used. First, 1.2 wt% carboxymethyl chitosan was dissolved in deionized water, and the pH was adjusted to slightly acidic to aid dissolution. Separately, 11 wt% PNIPAAm and 2.2 wt% Ppy nanowires were dispersed in DMF. Then, the aqueous phase was slowly added dropwise to the oil phase under ice bath conditions, and ultrasonic dispersion and defoaming were performed to obtain a uniform spinning solution. The viscosity was adjusted to 800 cP.

[0045] Spinning process: The above-mentioned framework is fixed to the receiving roller. The core layer advance speed is set to 0.6 mL / h, and the shell layer advance speed is set to 1.44 mL / h (controlling the core-shell flow rate ratio to 1:2.4 to match the optimal process window); a voltage of 16.5 kV is applied, and the receiving distance is 16.5 cm. Deposition is carried out at 25℃ and 45%RH for 2.5 h, allowing the nanofibers to be tightly embedded in the microgrooves on the framework surface.

[0046] (4) Post-treatment and residue removal: The system after deposition is subjected to interface strengthening cross-linking and deep desolventizing treatment, and then dried, cut and sterilized and packaged.

[0047] Interface strengthening and physical crosslinking: The deposited system was removed from the receiving device and placed in a vacuum drying oven for thermal dehydration crosslinking (DHT) at 50°C and a vacuum degree <100Pa for 24 hours. This step utilizes the principle of physical thermal dehydration to induce the formation of an amide bond network between the gelatin and chitosan molecular chains. While enhancing the interfacial binding force, it completely avoids the introduction of chemical crosslinking agents such as glutaraldehyde, fundamentally eliminating the risk of residual cytotoxicity. Moreover, this temperature is below the denaturation threshold of the active factor, ensuring drug activity. In this process, the design of the micron-scale groove array (depth 5-10μm) not only provides physical anchoring points, but more importantly, during coaxial electrospinning, the nascent fiber jet can conform to the groove geometry and fill the grooves before the solvent completely evaporates. Subsequently, through DHT treatment, the gelatin molecular chains of the framework layer and the carboxymethyl chitosan molecular chains of the fiber shell layer undergo dehydration condensation at the interface, forming covalent bonds. This dual strengthening mechanism of 'mechanical interlocking + chemical cross-linking' enables the interfacial peel strength to reach a breakthrough of over 0.65 N / cm.

[0048] Deep cleaning and equilibration: The physically cross-linked system was removed and immersed in sterile PBS buffer at 4°C for gradient dialysis cleaning (3 times, 15 min each time) to completely replace and remove spinning solvents such as DMF, dichloromethane and acetic acid that may remain in the previous steps. Then, it was freeze-dried (-50°C, 24 h) to maintain the porous structure of the nanofibers.

[0049] Sterilization and packaging: The dried system is placed into a medical breathable blister pack, sterilized with ethylene oxide (EO), and subjected to forced ventilation and desorption treatment for 48 hours (gas chromatography detection ensures that the EO residue is <10μg / g, which meets the ISO 10993 safety limit). Finally, it is placed into an aluminum foil composite bag for vacuum sealing and packaging with silica gel desiccant inside, thus obtaining the finished product 19.

[0050] Product performance: interfacial peel strength 0.68 N / cm, no delamination after 500 repeated bending cycles; solvent residue test qualified (TFA<5ppm); drug release rate at 37℃ 1.05μg / (cm²·h).

[0051] Example 2: A Square-Shaped Intelligent Bionic Wound Management System Adapted to Acute Trauma In this embodiment, a 7cm × 5cm square system was prepared, and the drug ratio was optimized to enhance anti-infection. The core parameters were adjusted as follows: Raw material adjustments: PEDOT: PSS solid content 1.5wt%, gelatin molecular weight 70000Da, total solid content 10wt%; core layer loaded with 0.15wt% LL-37, 0.1wt% VEGF, mesoporous silica microspheres with a particle size of 200nm; shell layer PNIPAAM concentration 12wt%, Ppy nanowire concentration 2.5wt%.

[0052] Optimized preparation steps: 3D printed mesh with side length of 0.8 mm, aperture of 1 mm, thickness of 0.3 mm, microgroove depth of 5 μm, width of 10 μm, and spacing of 50 μm; spinning voltage of 18 kV, receiving distance of 18 cm, receiving roller speed of 80 r / min, fiber layer thickness of 50 μm; UV crosslinking time of 15 min.

[0053] Product performance: interfacial peel strength 0.58 N / cm, LL-37 cumulative release rate reaches 80% within 12 hours, sensor response time ≤3s.

[0054] Example 3: An ultra-thin intelligent bionic wound management system adapted to postoperative wounds In this embodiment, an ultrathin system with a thickness of 0.6 mm was prepared. The frame thickness and fiber layer ratio were optimized, and the core parameters were adjusted as follows: Raw material adjustments: 3D printed frame with a total solid content of 8wt%, a thickness of 0.25mm, a mesh side length of 1.2mm, and a pore size of 2mm; core layer viscosity of 800cP, shell layer viscosity of 500cP, and fiber layer thickness of 30μm; LL-37 concentration of 0.05wt% and VEGF concentration of 0.15wt%.

[0055] Preparation steps were optimized: printing temperature 25℃, layer height 0.1mm, microgroove depth 10μm, width 20μm, spacing 100μm; sensor encapsulation PCL microcapsule thickness 10μm; EO sterilization time shortened to 4h, ventilation and desorption time 36h.

[0056] Product efficacy: breathability ≥500mL / (cm²·24h), hemolysis rate 2.1%, and postoperative wound healing time is shortened by 20% compared with traditional dressings.

[0057] Example 4: Orthogonal Experiment for Optimization of Core Process Parameters To determine the optimal process parameters, an orthogonal experiment was designed to investigate the effects of 3D printing mesh side length (A), spinning voltage (B), and core-shell propulsion speed ratio (C) on interfacial peel strength and drug release rate. The parameter levels and results are shown in Table 3 below.

[0058] Table 3. Orthogonal Experiment Parameters and Results

[0059] Parameter selection criteria: Experimental results show that when the mesh side length is 1.0 mm, the spinning voltage is 16.5 kV, and the core-shell propulsion speed ratio is 1:2.4, the overall system performance is optimal, the interface peel strength reaches 0.68 N / cm (mean), and the drug release rate is stable at 1.05 μg / (cm²·h). This parameter combination takes into account both structural stability and drug release accuracy, and is the optimal parameter for large-scale production.

[0060] III. Comparative Example Comparative Example 1: Intelligent Wound Management System Lacking Microstructured Interface Preparation method: The difference between this comparative example and Example 1 (5cm diameter circular system) is that the microstructured interface processing step of the 3D printed frame layer is omitted; the remaining raw materials, equipment, and preparation process are completely identical. Details are as follows: (1) Pre-assembly of 3D printed flexible electronic support frame layer 1: The conductive hydrogel precursor solution was prepared according to the steps of Example 1 and the frame was 3D printed, but the microgrooves were not etched by ultraviolet laser. The frame was directly immersed in 0.15wt% EDC / NHS (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride / N-hydroxysuccinimide) solution for crosslinking, drying and sterilization; (2) Functional module integration and assembly: completely consistent with Example 1; (3) Coaxial electrospinning multifunctional nanofiber active layer 2 deposition and assembly: completely consistent with Example 1, oriented deposition on the surface of the frame without grooves; (4) System assembly verification: completely consistent with Example 1, testing the interface peel strength and other properties.

[0061] Key differences and defects: This comparative example lacks the "microgroove structure with a depth of 5-10 μm and a width of 10-20 μm," resulting in the nanofiber layer and framework layer relying solely on surface physical adsorption for bonding, without mechanical interlocking, leading to a significant decrease in interfacial adhesion. Subsequent performance tests showed that its interfacial peel strength was only 0.21 N / cm (far lower than 0.65 N / cm in Example 1), and after repeated bending 50 times (±90°), localized fiber layer detachment occurred, failing to meet the structural stability requirements during human activity.

[0062] Comparative Example 2: Intelligent wound management system without a temperature-sensitive-pH dual-response shell Preparation method: The difference between this comparative example and Example 1 is that the coaxial spinning shell is replaced with ordinary polylactic acid (PLA), the temperature-sensitive (PNIPAAm) and pH-responsive (carboxymethyl chitosan) components and conductive Ppy nanowires are removed, and the rest of the process remains unchanged.

[0063] (1) Assembly of 3D printed flexible electronic support frame layer 1 and functional modules: completely consistent with Example 1; (2) Preparation of coaxial spinning solution: The core spinning solution is completely consistent with that in Example 1; the shell spinning solution is prepared by dissolving 11 wt% PLA in N,N-dimethylformamide, stirring for 4 hours and adjusting the viscosity to 600 cP (25°C), without PNIPAAM, Ppy nanowires and carboxymethyl chitosan. (3) Directional deposition and post-processing: completely consistent with Example 1; (4) System assembly and verification: The focus is on testing drug release responsiveness.

[0064] Key differences and shortcomings: This comparative example lacks the "thermosensitive-pH dual-responsive shell" and is replaced with a regular PLA shell. Due to the absence of the thermosensitive conformational switch of PNIPAAm and the pH-responsive groups of carboxymethyl chitosan, the drug diffusion coefficient of the shell remains constant under different environments, making it impossible to construct an "environment-triggered" diffusion channel. Tests show that even in a simulated severe infection environment (38℃ / pH 5.0), the drug release rate remains at a low level of 0.32-0.35 μg / (cm²·h), unable to overcome the dense barrier of the polymer chain to achieve "burst release," resulting in insufficient antibacterial concentration on the wound surface and inability to effectively inhibit biofilm formation.

[0065] Comparative Example 3: A smart wound management system powered by a button battery Preparation method: The difference between this comparative example and Example 1 is that a CR2032 button cell (capacity 220mAh) is used instead of a PVDF piezoelectric energy harvester, while the rest of the process remains unchanged.

[0066] (1) 3D printed flexible electronic support frame layer 1: completely consistent with Example 1, but with battery fixing buckles added in the reserved slots on the edge; (2) Functional module assembly: Fix the button battery in the slot of the original PVDF piezoelectric module, connect it in series with the NFC module and LED through flexible wires, and remove the PVDF piezoelectric film and Au electrode; (3) Deposition and assembly of coaxial electrospun multifunctional nanofiber active layer 2: completely consistent with Example 1; (4) Performance verification: Additional testing of battery life and risk of wound damage during replacement.

[0067] Key differences and drawbacks: This comparative example does not use the "miniature piezoelectric energy harvester 4" and relies on an external battery for power, which has two major drawbacks: ① Limited battery life: Due to the system being set to a high-frequency monitoring mode and requiring the driving of LED warnings, the actual battery life under continuous operation is only 14 days, requiring regular battery replacement; ② Risk of secondary injury: Replacing the battery requires lifting the edge of the dressing or applying pressure to the wound, and the secondary infection rate reached 6.8% in simulated clinical tests (less than 0.5% in Example 1). In addition, the battery volume (20mm in diameter and 3.2mm in thickness) significantly increases the feeling of a foreign body when wearing it, making it unsuitable for curved wounds such as joints.

[0068] Comparative Example 4: Intelligent Wound Management System with Mesoporous Silica Carrier Preparation method: The difference between this comparative example and Example 1 is that the composite therapeutic factor is directly mixed into the core layer spinning solution, and mesoporous silica microspheres are not used for loading, while the rest of the process remains unchanged.

[0069] (1) Assembly of 3D printed flexible electronic support frame layer 1 and functional modules: completely consistent with Example 1; (2) Preparation of core spinning solution: 5.5wt% chitosan and 8.5wt% polylactic acid were dissolved in trifluoroacetic acid-dichloromethane (1:1), and 0.12wt% VEGF, 0.06wt% LL-37 and 0.25wt% gallic acid (non-mesoporous silica microspheres) were added directly. After stirring for 2 hours, the viscosity was adjusted to 900 cP. (3) Shell spinning solution and spinning process: completely consistent with Example 1; (4) Assembly verification: The focus is on testing the time-series release effect of the therapeutic factors.

[0070] Key differences and defects: This comparative example lacks "composite therapeutic factors loaded with mesoporous carriers," and the therapeutic factors lack sustained-release carriers, resulting in disordered release sequence: the measured cumulative release of LL-37 reached 92% within 24 hours (65% in Example 1), and was basically completed after 3 days; VEGF was rapidly released within 1-2 days (continuous release within 3-7 days in Example 1), which could not match the temporal requirements of the wound's "inflammatory phase (anti-infection) - proliferative phase (pro-angiogenesis)," resulting in insufficient wound angiogenesis and a prolonged healing period.

[0071] Comparative Example 5: Non-coaxial spinning monolayer nanofiber system Preparation method: The difference between this comparative example and Example 1 is that ordinary single-needle electrospinning is used to mix the core and shell components into a single-layer spinning solution, without forming a core-shell structure. The rest of the process remains unchanged.

[0072] (1) Assembly of 3D printed flexible electronic support frame layer 1 and functional modules: completely consistent with Example 1; (2) Preparation of monolayer spinning solution: Mix 5.5wt% chitosan, 8.5wt% polylactic acid, 11wt% PNIPAAm, 2.2wt% Ppy nanowires, 1.2wt% carboxymethyl chitosan and mesoporous silica-loaded therapeutic factors, dissolve in a mixed solvent of trifluoroacetic acid-dichloromethane and N,N-dimethylformamide (volume ratio 1:1), and adjust the viscosity to 800 cP; (3) Electrospinning: A single needle (0.5 mm in diameter) is used, the spinning voltage is 16.5 kV and the receiving distance is 16.5 cm, and the electrons are deposited on the surface of the frame. (4) Assembly verification: Test the stability and response speed of drug release.

[0073] Key differences and shortcomings: This comparative example did not adopt the "coaxial electrospun core-shell double-layer structure", and the therapeutic factor and responsive component were mixed and distributed, resulting in: ① Drug release is greatly affected by the environment. Under normal pH (5.5-7.5) and room temperature (≤32℃), the release rate of LL-37 reached 0.6μg / (cm²·h) (0.25μg / (cm²·h) in Example 1), resulting in serious drug waste; ② Thermosensitive-pH response is delayed. It takes 120 minutes from environmental trigger to the increase in drug release rate (30 minutes in Example 1), which cannot quickly respond to acute infection.

[0074] IV. Test Examples Test Example 1: Structural Performance Test 1. Test objective: To verify the interfacial bonding strength, flexibility, durability, and breathability of the system, and to compare the structural stability differences between Example 1 and the comparative examples.

[0075] 2. Testing Method: Interface peel strength test: Referring to GB / T 2790-1995 "Adhesives 180° peel strength test method", a universal testing machine (accuracy 0.01N) was used to peel the framework layer and nanofiber layer at a uniform speed (rate 50mm / min) along the 180° direction. Five samples were tested in each group and the average value was taken.

[0076] Flexible durability test: The system is fixed to a cylindrical mold with a curvature radius of 1.5cm and repeatedly bent at ±90° (frequency 1 time / 10s). After 50, 100 and 500 times, observe whether there is delamination or fiber shedding. Record the number of cycles in which the first structural damage occurs.

[0077] Air permeability test: Refer to GB / T 5453-1997 "Determination of air permeability of textile fabrics" and use an air permeability meter (test area 5cm², pressure difference 100Pa). Three samples are tested in each group, and the average value is taken.

[0078] 3. The test results are shown in Table 4 below.

[0079] Table 4 Test Results

[0080] 4. Results Analysis: Example 1, due to its microstructured interface (which was missing in Comparative Example 1), exhibited significantly higher interface peel strength and the best flexibility and durability. Comparative Example 3, due to the obstruction of the button battery, showed a slight decrease in air permeability. Comparative Example 5, due to the weak bonding force of its single-layer fiber structure, had fewer cycles of initial damage, demonstrating that the core-shell coaxial spinning and microstructured interface design of this invention are crucial for structural stability.

[0081] Test Example 2: Drug Release Performance Test 1. Test objective: To verify the temperature- and pH-responsive dual-response release characteristics of the system and the time-sequential release effect of the compound therapeutic factor, and to compare the differences between Example 1 and Comparative Example 2 (without a responsive shell) and Comparative Example 4 (without a mesoporous carrier).

[0082] 2. Testing Method: Dual-response release test: Samples were cut into 1cm × 1cm pieces and immersed in artificial wound solutions under four different simulated environments. Environment 1: Temperature 38.5℃ (>37.5℃, simulating high fever infection), pH=5.0 (severe infection); Environment 2: Temperature 38.5℃, pH=6.5 (simple exothermic reaction); Environment 3: Temperature 34℃ (simulating normal body surface temperature), pH=5.0; Environment 4: Temperature 34℃, pH=6.5 (normal healing).

[0083] The concentrations of LL-37, VEGF, and gallic acid in the solution were measured every 2 hours using a high-performance liquid chromatograph (HPLC, detection wavelength 280 nm), and the release rate was calculated.

[0084] Time-series release test: Under environment 4 (normal healing), continuous monitoring was conducted for 10 days to record the cumulative release of the three therapeutic factors and plot the time-series release curve.

[0085] 3. The test results are shown in Tables 5 and 6 below.

[0086] Table 5. Dual-response release rates (unit: μg / (cm²·h))

[0087] Table 6. Cumulative release over time (10 days, unit: μg / cm²)

[0088] 4. Results Analysis: Example 1 showed a significantly increased release rate under infected / inflammatory environments (environments 1 and 2), demonstrating its temperature- and pH-responsive dual characteristics; Comparative Example 2, lacking a responsive shell, showed no difference in release rate and could not dynamically adapt to the wound condition; Comparative Example 4, lacking a mesoporous carrier, resulted in rapid release of the therapeutic factor with disordered timing, proving that the dual-responsive shell and mesoporous carrier design of this invention are crucial for precise drug release.

[0089] Test Example 3: Monitoring and Early Warning Performance Test 1. Test objective: To verify the energy storage efficiency and NFC data transmission stability of the system in self-powered mode, and to objectively compare the advantages and disadvantages of "piezoelectric self-powered" and "button battery powered".

[0090] 2. Testing Method: LED Warning Response Test (Energy Accumulation Time): Place the system on a simulated walking device, set the standard step frequency to 1Hz (i.e., one step per second), and the pressure to 400N. Adjust the solution pH to 5.0 (trigger threshold), and record the time required from the start of the power management chip (PMIC) to the capacitor voltage reaching the LED turn-on threshold and first driving the LED pulse to flash as an alarm (i.e., "cold start response time").

[0091] Battery life and stability test: Set to "high frequency monitoring mode" (sample transmission once every 10 minutes) to compare the continuous working time of Example 1 (continuous motion power supply) and Comparative Example 3 (CR2032 battery power supply).

[0092] 3. The test results are shown in Table 7 below.

[0093] Table 7 Test Results

[0094] 4. Results Analysis: Comparative Example 3 achieved millisecond-level response time with battery power, but in the high-power mode set to "high-frequency monitoring + LED pulse warning," its battery was depleted in about 14 days, after which the data loss rate soared to 100%. In contrast, although Example 1 had an "energy accumulation delay" of about 25 seconds (requiring the patient to walk about 25 steps to accumulate enough power to light up the LED), for applications with slow disease progression such as chronic wounds, the second-level delay did not affect clinical judgment at all. More importantly, relying on the PVDF piezoelectric acquisition and rectification energy storage circuit, Example 1 achieved true "unlimited battery life," completely solving the clinical pain points of monitoring interruption due to battery depletion and the biological risks caused by battery replacement.

[0095] Test Example 4: Biocompatibility Test 1. Test objective: To verify the system's cytotoxicity, hemolysis rate, and sensitization, ensuring compliance with medical biocompatibility standards (ISO 10993).

[0096] 2. Testing Method: Cytotoxicity test (ISO 10993-5): The system extract (37℃, 24h, extraction ratio 1cm² / mL) was co-cultured with L929 fibroblasts, and the cell viability was determined by MTT assay after 48h. Grading criteria: Grade 0 (viability ≥90%), Grade 1 (70%-89%), Grade 2 (50%-69%).

[0097] Hemolysis rate test (ISO 10993-4): Mix the system sample (0.1g) with rabbit anticoagulated blood (5mL, concentration 2%), incubate at 37℃ for 60min, centrifuge and measure the absorbance, calculate the hemolysis rate (hemolysis rate <5% is acceptable).

[0098] Sensitization test (ISO 10993-10): The guinea pig maximum test (GPMT) was used. The system extract was injected intradermally and applied to the skin. The sensitization reaction such as erythema and edema was observed within 14 days, and the sensitization rate was calculated.

[0099] 3. The test results are shown in Table 8 below.

[0100] Table 8 Test Results

[0101] 4. Results Analysis: The biocompatibility of Example 1 and each comparative example meets the ISO 10993 standard. The cytotoxicity is grade 0, the hemolysis rate is <5%, and there is no sensitization. This proves that the core materials (PEDOT:PSS, PNIPAAm, mesoporous silica, etc.) and assembly process of this invention have excellent medical safety and no additional biological risks.

[0102] In summary, this invention, through its "electronic-biological" dual-network structure design, achieves self-powered real-time monitoring of the wound microenvironment, multi-stage on-demand precise timing drug release, and a visual early warning closed loop. It effectively solves the problems of functional fragmentation, low interface bonding strength, and energy dependence in existing technologies, and is suitable for the full-cycle precision care of chronic ulcers and acute wounds.

[0103] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. An intelligent bionic wound management system, characterized in that, include: The 3D printed flexible electronic support frame layer has a honeycomb porous grid structure. Its surface has a microstructured interface composed of a micron-level groove array. Sensor packaging units are provided at the grid nodes of the 3D printed flexible electronic support frame layer, and functional module integration areas are provided at the edges. The coaxial electrospun multifunctional nanofiber active layer is a core-shell bilayer structure nanofiber that is directionally deposited and anchored to the microstructured interface through coaxial electrospinning process, covering the 3D printed flexible electronic support framework layer. Electronic functional components, arranged in the functional module integration area, include a miniature piezoelectric energy harvester, a power management circuit, a wireless transmission module, and an early warning unit with visual output function; The micro piezoelectric energy harvester is electrically connected to the sensor packaging unit, the wireless transmission module and the early warning unit through the power management circuit. The power management circuit controls the early warning unit to output a pulsed early warning signal based on the wound microenvironment parameters collected by the sensor packaging unit, forming a self-powered monitoring closed loop. The core layer of the coaxial electrospun multifunctional nanofiber active layer contains a composite therapeutic factor loaded with a mesoporous carrier, and the shell layer is a temperature-sensitive-pH dual-responsive conductive composite material. The 3D printed flexible electronic support frame layer is made of PEDOT:PSS and gelatin conductive composite hydrogel; the microgrooves of the microstructured interface have a depth of 5-10μm, a width of 10-20μm, and a spacing of 50-100μm; the coaxial electrospun multifunctional nanofiber active layer is embedded in the microgrooves to form a mechanical interlocking structure, and its interface peel strength is ≥0.5N / cm. The shell material of the coaxial electrospun multifunctional nanofiber active layer is modified with hydrophilic carboxymethyl chitosan, and its low critical dissolution temperature is adjusted to 37.5-38.5℃ to distinguish between normal body temperature and pathological high temperature. The gelatin molecular chains in the framework layer and the carboxymethyl chitosan molecular chains in the fiber shell layer undergo dehydration condensation at the interface, forming covalent bonds that bridge the gap, resulting in an interfacial peel strength of over 0.65 N / cm.

2. The intelligent bionic wound management system according to claim 1, characterized in that, The power management circuit includes a rectifier bridge and a miniature energy storage capacitor, used to convert the AC power generated by the miniature piezoelectric energy harvester into DC power and store it; the wireless transmission module is a passive NFC module or a low-power Bluetooth module.

3. The intelligent bionic wound management system according to claim 1, characterized in that, The core material of the coaxial electrospun multifunctional nanofiber active layer includes polylactic acid and chitosan, the mesoporous carrier is mesoporous silica microspheres, and the loaded composite therapeutic factors include antimicrobial peptide LL-37, vascular endothelial growth factor and gallic acid.

4. The intelligent bionic wound management system according to claim 1, characterized in that, The shell material of the coaxial electrospun multifunctional nanofiber active layer includes polyisopropylacrylamide, carboxymethyl chitosan, and polypyrrole nanowires; through the synergistic effect of the thermosensitive shrinkage of polyisopropylacrylamide and the pH swelling of carboxymethyl chitosan, the shell density is reduced in the infection environment to achieve accelerated drug release.

5. A method for preparing an intelligent bionic wound management system as described in any one of claims 1 to 4, characterized in that, Includes the following steps: S1: PEDOT:PSS is mixed with gelatin to prepare a precursor solution. A honeycomb porous mesh is printed using direct writing 3D printing technology. After curing, microgrooves are etched on the mesh surface using ultraviolet laser. After cross-linking treatment, a 3D printed flexible electronic support framework layer with a microstructured interface is obtained. S2: Assemble a micro piezoelectric energy harvester, power management circuit, wireless transmission module, early warning unit and sensor packaging unit in the reserved slots of the 3D printed flexible electronic support frame layer, and realize circuit interconnection through flexible conductive adhesive circuit, and perform electrostatic shielding protection treatment on the functional module integration area. S3: Prepare a core spinning solution containing a mesoporous carrier loaded with drugs and a shell spinning solution containing a temperature- and pH-responsive conductive composite material; use coaxial electrospinning technology to directionally deposit nanofibers onto the microstructured interface of the 3D printed flexible electronic support framework layer described in step S1. S4: The deposited system is subjected to interface strengthening cross-linking and deep desolventizing treatment, and then dried, cut and sterilized and packaged to obtain the final product.

6. The preparation method according to claim 5, characterized in that, In step S1, the mass ratio of PEDOT:PSS to gelatin in the precursor solution is 3:7, and the total solid content is 8-10wt%; the nozzle diameter for 3D printing is 0.2-0.4mm, and the printing layer height is 0.1-0.15mm; the microgrooves etched by the ultraviolet laser have a depth of 5-10μm, a width of 10-20μm, and a spacing of 50-100μm.

7. The preparation method according to claim 5, characterized in that, In step S3, the core spinning solution is a water-in-oil emulsion system, wherein the aqueous phase disperses a mesoporous carrier loaded with composite therapeutic factors, and the oil phase is a mixed solution of polylactic acid and chitosan; the shell spinning solution uses a mixed solvent system of N,N-dimethylformamide and water; the receiving distance of the coaxial electrospinning is 15-18 cm, the voltage is 15-18 kV, and the core-to-shell propulsion speed ratio is 1:2.0-1:2.

5.

8. The preparation method according to claim 5, characterized in that, In step S4, the interface strengthening crosslinking is a physical thermal dehydration crosslinking, which is treated under vacuum and 50°C for 24 hours to enhance the interfacial bonding force while avoiding chemical crosslinking agent residue; the deep desolventizing treatment is a gradient dialysis cleaning using sterile phosphate buffer at 4°C to remove residual organic solvents.

Images