Silk fibroin-polyethylene glycol composite hydrogel material, and preparation method and application thereof

Abstract

The application discloses a silk fibroin-polyethylene glycol composite hydrogel material and a preparation method and application thereof. The composition of the silk fibroin-polyethylene glycol composite hydrogel material comprises a silk fibroin-polyethylene glycol composite hydrogel matrix and magnetic nanoparticles dispersed in the silk fibroin-polyethylene glycol composite hydrogel matrix. The silk fibroin-polyethylene glycol composite hydrogel material has excellent biocompatibility, biodegradability, mechanical flexibility and water retention, and can realize target positioning, uniform coverage of a wound surface and local delivery of a therapeutic agent to damaged tissue under the guidance of a magnetic field. Compared with traditional wound dressings, the silk fibroin-polyethylene glycol composite hydrogel material has higher targeting, stronger drug retention capacity, more controllable drug release effect, faster tissue regeneration speed and lower infection and inflammation reaction, and is suitable for large-scale industrial production and application.

Description

Technical Field

[0001] This invention belongs to the field of drug targeted delivery technology, specifically relating to a silk fibroin-polyethylene glycol composite hydrogel material, its preparation method, and its application. Background Technology

[0002] Burns are among the most common traumatic tissue injuries. Severe burn wounds are often accompanied by excessive fluid loss, bacterial infection, persistent inflammation, delayed angiogenesis, impaired tissue regeneration, and extensive scarring. Currently, rapid and effective treatment of burns remains a significant clinical challenge, especially for deep or irregularly shaped burn wounds. Traditional burn wound treatments typically rely on passive dressings, topical ointments, skin substitutes, or systemic drug administration. While these methods provide temporary protection and maintain a moist wound environment, they also have many limitations. For example, traditional dressings cannot actively deliver medication to specific areas of the wound, resulting in uneven drug distribution and requiring repeated dressing changes. Furthermore, dressings cannot dynamically adapt to complex wound shapes. Systemic drug administration may reduce the effectiveness of wound treatment and also carries the risk of increased systemic side effects. Therefore, there is an urgent need to develop advanced treatment systems that can accelerate wound healing and reduce infection, inflammation, and long-term tissue damage.

[0003] In recent years, hydrogel-based biomaterials have attracted widespread attention in the field of wound healing due to their high water content, excellent biocompatibility, superior flexibility, and ability to promote cell adhesion and tissue regeneration. However, existing hydrogel materials mainly function as passive dressings, typically fixed at the dressing site after drug administration. These therapeutic systems lack the ability to actively move, remotely control, target, or navigate in complex wound environments. Therefore, incorporating therapeutic agents into these hydrogel materials makes it impossible to selectively deliver them to poorly healing or infected areas of burn wounds, resulting in suboptimal treatment outcomes. Furthermore, these hydrogel materials have poor adaptability to heterogeneous wound surfaces, failing to fully meet the needs of practical applications.

[0004] Therefore, it is of great significance to develop a hydrogel material that can achieve active wound coverage, local drug delivery, controlled drug release, and accelerated burn wound healing. Summary of the Invention

[0005] The purpose of this invention is to provide a silk fibroin-polyethylene glycol composite hydrogel material, its preparation method, and its application.

[0006] The technical solution adopted in this invention is: A silk fibroin-polyethylene glycol composite hydrogel material, comprising a silk fibroin-polyethylene glycol composite hydrogel matrix and magnetic nanoparticles dispersed in the silk fibroin-polyethylene glycol composite hydrogel matrix.

[0007] Preferably, the silk fibroin-polyethylene glycol composite hydrogel material contains 5% to 10% by mass of silk fibroin, 80% to 90% by mass of polyethylene glycol, and 5% to 10% by mass of magnetic nanoparticles (MNPs) (the weight of silk, PEG, or MNPs as a percentage of the total weight of silk, PEG, and MNPs).

[0008] Preferably, the number-average molecular weight of the polyethylene glycol is 200 g / mol to 600 g / mol.

[0009] Preferably, the magnetic nanoparticles are at least one of Fe3O4 nanoparticles and γ-Fe2O3 nanoparticles.

[0010] Preferably, the magnetic nanoparticles have a particle size of 50 nm to 250 nm.

[0011] Preferably, the silk fibroin-polyethylene glycol composite hydrogel material is in the form of spheres, cylinders, spirals, tubes, discs, stars, or irregular shapes.

[0012] Preferably, the size of the silk fibroin-polyethylene glycol composite hydrogel material is 10µm to 1000µm.

[0013] Preferably, the composition of the silk fibroin-polyethylene glycol composite hydrogel material further includes an imaging agent (the addition of the imaging agent enables the silk fibroin-polyethylene glycol composite hydrogel material to be visualized through fluorescence imaging, nuclear magnetic resonance imaging, ultrasound imaging, photoacoustic imaging or optical imaging).

[0014] A method for preparing a silk fibroin-polyethylene glycol composite hydrogel material as described above includes the following steps: 1) Disperse silk fibroin, polyethylene glycol and magnetic nanoparticles in water and then incubate to obtain a composite hydrogel dispersion; 2) The composite hydrogel dispersion was loaded into a precision dispensing syringe for controlled extrusion, then immersed in PBS buffer solution for soaking, and then separated and dried to obtain silk fibroin-polyethylene glycol composite hydrogel material.

[0015] A dressing for treating burn wounds, comprising the aforementioned silk fibroin-polyethylene glycol composite hydrogel material and a drug for treating burns.

[0016] Preferably, the drug for treating burns includes at least one of antibacterial agents, anti-inflammatory agents, growth factors, angiogenesis factors, antioxidants, and analgesics.

[0017] A targeted drug comprising the aforementioned silk fibroin-polyethylene glycol composite hydrogel material and an active drug.

[0018] The beneficial effects of this invention are: the silk fibroin-polyethylene glycol composite hydrogel material of this invention has excellent biocompatibility, biodegradability, mechanical flexibility and water retention, and under the guidance of a magnetic field, it can actively navigate and achieve targeted positioning, uniform coverage of the wound, and local delivery of therapeutic agents to the damaged tissue. Compared with traditional wound dressings, it has higher targeting, stronger drug retention capacity, more controllable drug release effect, faster tissue regeneration speed, and lower infection and inflammatory response, making it suitable for large-scale industrial production and application.

[0019] Specifically: 1) The matrix of the silk fibroin-polyethylene glycol composite hydrogel material of the present invention is a silk fibroin-polyethylene glycol composite hydrogel, which has excellent biocompatibility, biodegradability, mechanical flexibility and water retention (polyethylene glycol can improve the flexibility, hydration, swelling, mechanical stability and biodegradability of the hydrogel matrix). 2) The silk fibroin-polyethylene glycol composite hydrogel material of the present invention contains magnetic nanoparticles, which can achieve remote magnetic drive and precise navigation of the silk fibroin-polyethylene glycol composite hydrogel material under the action of an external magnetic field (including a rotating magnetic field, an oscillating magnetic field, a gradient magnetic field, a uniform magnetic field or a combination thereof), thereby enabling targeted positioning, uniform coverage of the wound surface and local delivery of therapeutic agents to the damaged tissue. 3) The silk fibroin-polyethylene glycol composite hydrogel material of the present invention will gradually biodegrade after treatment, so it does not need to be removed from the wound surface, making it more convenient to use; 4) The preparation process of the silk fibroin-polyethylene glycol composite hydrogel material of the present invention is simple and the production cost is low, making it suitable for large-scale industrial applications in fields such as burn wound management, regenerative medicine, intelligent wound dressings, targeted drug delivery, biomedical engineering, and soft microrobots. Attached Figure Description

[0020] Figure 1 This is a flowchart illustrating the preparation process of the silk fibroin-polyethylene glycol composite hydrogel material in Example 1.

[0021] Figure 2 This is a SEM image of the silk fibroin-polyethylene glycol composite hydrogel material from Example 1.

[0022] Figure 3The magnetic hysteresis curves of the silk fibroin-polyethylene glycol composite hydrogel material and Fe3O4 nanoparticles in Example 1 are shown.

[0023] Figure 4 This is the EDX elemental mapping diagram of the silk fibroin-polyethylene glycol composite hydrogel material of Example 1.

[0024] Figure 5 The figure shows the test results of the drug loading performance of the silk fibroin-polyethylene glycol composite hydrogel material in Example 1.

[0025] Figure 6 This is an optical microscope image of the silk fibroin-polyethylene glycol composite hydrogel material of Example 2. Detailed Implementation

[0026] The present invention will be further explained and described below with reference to specific embodiments.

[0027] Example 1: A silk fibroin-polyethylene glycol composite hydrogel material is prepared by the following method (preparation process as follows). Figure 1 (as shown) 1) Silk fibroin was stirred and dispersed in deionized water to prepare a 15% (w / v) silk fibroin dispersion. Polyethylene glycol (number average molecular weight of 400 g / mol) was added and dispersed evenly. Fe3O4 nanoparticles (particle size of 50 nm to 250 nm) were added and stirred evenly. The mass ratio of silk fibroin, polyethylene glycol and Fe3O4 nanoparticles was 15:80:5. The mixture was then placed in an oven and incubated at 37°C for 30 h to obtain a composite hydrogel dispersion. 2) The composite hydrogel dispersion was loaded into a precision dispensing syringe and extruded in a controlled manner to form discrete droplets. The nozzle inner diameter of the precision dispensing syringe was 10 μm. The mixture was then immersed in PBS buffer solution for 30 min, filtered, and the solid was placed in an oven at 37 °C for 30 h to obtain the silk fibroin-polyethylene glycol composite hydrogel material (denoted as MMR).

[0028] Performance testing: 1) The scanning electron microscope (SEM) image of the silk fibroin-polyethylene glycol composite hydrogel material in this embodiment is shown below. Figure 2 As shown.

[0029] Depend on Figure 2 It can be seen that the silk fibroin-polyethylene glycol composite hydrogel material is a regular sphere with a diameter of about 200µm and a smooth surface.

[0030] 2) The hysteresis curves of the silk fibroin-polyethylene glycol composite hydrogel material (MMR) and Fe3O4 nanoparticles in this embodiment are as follows: Figure 3 As shown.

[0031] Depend on Figure 3 It can be seen that the magnetization intensity of MMR increases rapidly after a magnetic field is applied, exhibiting superparamagnetic behavior. This indicates that the incorporation of Fe3O4 nanoparticles gives the hydrogel material a high degree of magnetic responsiveness, which can then be effectively manipulated by an external magnetic field to achieve remote magnetic drive and precise navigation, making it suitable for targeted drug delivery.

[0032] 3) The energy dispersive X-ray (EDX) elemental mapping diagram of the silk fibroin-polyethylene glycol composite hydrogel material in this embodiment is shown below. Figure 4 As shown.

[0033] Depend on Figure 4 It can be seen that: Fe3O4 nanoparticles were successfully incorporated into the hydrogel matrix and were uniformly distributed; the mapping image of oxygen (O) revealed the presence and uniform dispersion of oxygen-containing components, corresponding to the Fe3O4 phase and the polymer matrix; the mapping image of iron (Fe) confirmed the uniform distribution of iron elements throughout the hydrogel material, thus verifying the successful loading of Fe3O4 nanoparticles.

[0034] 4) The silk fibroin-polyethylene glycol composite hydrogel material of this embodiment was immersed in ibuprofen solutions of different concentrations (5 mg / mL to 70 mg / mL) for drug loading. The drug loading performance test results of the obtained silk fibroin-polyethylene glycol composite hydrogel material are as follows: Figure 5 As shown (drug loading is expressed as the weight of ibuprofen loaded onto a single silk fibroin-polyethylene glycol composite hydrogel material).

[0035] Depend on Figure 5 It is known that silk fibroin-polyethylene glycol composite hydrogel materials have strong drug loading capacity. Hydrogels can serve as effective drug carriers, thereby enabling the delivery of burn wound healing drugs in a controllable and continuous manner.

[0036] Example 2: A silk fibroin-polyethylene glycol composite hydrogel material is identical to Example 1 except that in step 2), the process of preparing the material is changed from "loading the composite hydrogel dispersion into a precision dispensing syringe for controlled extrusion to form discrete droplets" to "loading the composite hydrogel dispersion into a precision dispensing syringe for controlled extrusion to form a continuous deposit".

[0037] Performance testing: 1) An optical microscope image of the silk fibroin-polyethylene glycol composite hydrogel material in this embodiment is shown below. Figure 6 As shown.

[0038] Depend on Figure 6 It can be seen that the silk fibroin-polyethylene glycol composite hydrogel material is an irregular sphere with a diameter of about 450µm, and is black in color due to the presence of Fe3O4 nanoparticles.

[0039] 2) After testing (testing method is the same as in Example 1), the silk fibroin-polyethylene glycol composite hydrogel material of this example also has high magnetic responsiveness, uniform element distribution, excellent drug loading performance and controllable and continuous drug delivery capability, making it suitable for targeted drug delivery.

[0040] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A silk fibroin-polyethylene glycol composite hydrogel material, characterized in that, The composition includes a silk fibroin-polyethylene glycol composite hydrogel matrix and magnetic nanoparticles dispersed in the silk fibroin-polyethylene glycol composite hydrogel matrix.

2. The silk fibroin-polyethylene glycol composite hydrogel material according to claim 1, characterized in that: The silk fibroin-polyethylene glycol composite hydrogel material contains 5%–10% silk fibroin by mass, 80%–90% polyethylene glycol by mass, and 5%–10% magnetic nanoparticles by mass.

3. The silk fibroin-polyethylene glycol composite hydrogel material according to claim 1 or 2, characterized in that: The number-average molecular weight of the polyethylene glycol is 200 g / mol to 600 g / mol.

4. The silk fibroin-polyethylene glycol composite hydrogel material according to claim 1 or 2, characterized in that: The magnetic nanoparticles are at least one of Fe3O4 nanoparticles and γ-Fe2O3 nanoparticles.

5. The silk fibroin-polyethylene glycol composite hydrogel material according to claim 1 or 2, characterized in that: The magnetic nanoparticles have a particle size of 50 nm to 250 nm.

6. The silk fibroin-polyethylene glycol composite hydrogel material according to claim 1 or 2, characterized in that: The silk fibroin-polyethylene glycol composite hydrogel material is in the form of spheres, cylinders, spirals, tubes, discs, stars, or irregular shapes.

7. The silk fibroin-polyethylene glycol composite hydrogel material according to claim 6, characterized in that: The size of the silk fibroin-polyethylene glycol composite hydrogel material is 10µm to 1000µm.

8. A method for preparing a silk fibroin-polyethylene glycol composite hydrogel material as described in any one of claims 1 to 7, characterized in that, Includes the following steps: 1) Disperse silk fibroin, polyethylene glycol and magnetic nanoparticles in water and then incubate to obtain a composite hydrogel dispersion; 2) The composite hydrogel dispersion was loaded into a precision dispensing syringe for controlled extrusion, then immersed in PBS buffer solution for soaking, and then separated and dried to obtain silk fibroin-polyethylene glycol composite hydrogel material.

9. A dressing for treating burn wounds, characterized in that, The composition includes the silk fibroin-polyethylene glycol composite hydrogel material as described in any one of claims 1 to 7 and a drug for treating burns.

10. A targeted drug, characterized in that, The composition includes the silk fibroin-polyethylene glycol composite hydrogel material as described in any one of claims 1 to 7 and the active pharmaceutical ingredient.

Images