Self-powered microneedle patch for repairing hypertrophic scars and preparation method and use thereof

Abstract

The application provides a self-powered microneedle patch for repairing hypertrophic scars, a preparation method and application thereof. The self-powered microneedle patch comprises a friction nanogenerator for generating an electric current; a conductive drug-loaded microneedle patch connected with the friction nanogenerator; the conductive drug-loaded microneedle patch comprises a conductive microneedle patch and a cross-linked gelatin-cross-linked hyaluronic acid microneedle loaded with Sb4; the surface of the conductive microneedle patch is provided with a metal coating for mediating the electric current generated by the friction nanogenerator and applying transdermal electrical stimulation; and the cross-linked gelatin-cross-linked hyaluronic acid microneedle is coated on the tip of the conductive microneedle patch. The self-powered microneedle patch of the application can convert the myofibroblasts of the hypertrophic scar into adipocytes by providing transdermal electrochemical stimulation, inhibit the release of inflammatory factors, reshape the tissue microenvironment, thereby reversing the hypertrophic scar and realizing skin repair and tissue regeneration.

Description

Technical Field

[0001] This application relates to the field of scar repair technology, specifically to a self-powered microneedle patch for repairing hypertrophic scars, its preparation method, and its uses. Background Technology

[0002] Hypertrophic scars are a pathological phenomenon caused by excessive inflammatory response and abnormal proliferation and activation of myofibroblasts, manifesting as raised, hardened, and pigmented scars. Currently, commonly used clinical treatments include medication, laser therapy, and surgery; however, these methods have many limitations, such as significant side effects, unsatisfactory treatment outcomes, and reliance on specialized equipment.

[0003] Reprogramming refers to the process of transforming differentiated somatic cells into other cell types through external factors, providing new methods for tissue repair and regeneration. Among these, chemical reprogramming mediated by small molecule compounds offers advantages such as high controllability and ease of optimization, holding promise for developing scalable and standardized therapeutic reprogramming strategies. Recent research has found that myofibroblasts possess a certain degree of plasticity, which can be activated...

[0004] The BMP4-p-SMAD1 / 5 / 8 signaling pathway can promote fate reprogramming of myofibroblasts. Sb4, a potent benzoxazole bone morphogenetic protein 4 (BMP4) signaling agonist, activates BMP signaling transduction by stabilizing intracellular p-SMAD1 / 5 / 8, demonstrating great potential as a therapeutic agent for hypertrophic scars. However, there are some challenges in the application of Sb4 in the treatment of hypertrophic scars: for example, local administration must overcome the thickened epidermal barrier of hypertrophic scars, which may limit drug penetration and reduce its local concentration at the target site; while intralesional injection must penetrate dense and hard scar tissue, causing significant pain and resulting in uneven drug distribution; in addition, the efficiency of chemical reprogramming needs to be further improved.

[0005] Related studies have shown that electric fields can upregulate the expression of receptors in various cells, promote signal transduction, and potentially improve the efficiency of chemical reprogramming. Furthermore, electrical stimulation has been shown to expand intercellular spaces and gaps by enhancing venous and lymphatic return, thus aiding in the softening and loosening of scar tissue. Microneedles are widely used for transdermal drug delivery due to their advantages such as non-selective loading capacity, minimally invasive nature, ease of operation, and good biocompatibility. Moreover, microneedles can be made from various materials and customized to specific lengths, allowing for the development of conductive drug-loaded microneedles based on the histological characteristics of hypertrophic scars, achieving transdermal electrical stimulation and drug delivery. Based on this, a self-powered microneedle patch for repairing hypertrophic scars was designed and fabricated. The fabricated microneedles simultaneously serve as electrodes and drug delivery platforms, and through self-driven transdermal electrochemical stimulation using triboelectric nanogenerators, they can reduce scar elevation, promote adipose tissue regeneration, inhibit inflammatory responses, and reshape the pathological microenvironment, thereby promoting skin repair and tissue regeneration. Summary of the Invention

[0006] The purpose of this application is to provide a self-powered microneedle patch for repairing hypertrophic scars, its preparation method, and its uses.

[0007] To achieve the above objectives, the embodiments of this application propose the following technical solutions:

[0008] In a first aspect, embodiments of this application propose a self-powered microneedle patch for repairing hypertrophic scars, the self-powered microneedle patch comprising:

[0009] Triboelectric nanogenerators are used to generate electric current.

[0010] A conductive drug-loaded microneedle patch, wherein the conductive drug-loaded microneedle patch is connected to a triboelectric nanogenerator;

[0011] The conductive drug-loaded microneedle patch includes a conductive microneedle patch and cross-linked gelatin-cross-linked hyaluronic acid microneedles carrying Sb4.

[0012] The conductive microneedle patch has a metal coating on its surface to mediate the current generated by the triboelectric nanogenerator and to apply transdermal electrical stimulation; the cross-linked gelatin-cross-linked hyaluronic acid microneedles are coated on the tips of the conductive microneedle patch.

[0013] In one embodiment, the triboelectric nanogenerator is a freestanding-sliding triboelectric nanogenerator.

[0014] In one embodiment, the Sb4 is located on the outer surface of the cross-linked gelatin-cross-linked hyaluronic acid microneedles or dispersed inside the cross-linked gelatin-cross-linked hyaluronic acid microneedles.

[0015] In one embodiment, the metal coating of the conductive microneedle patch is selected from one or more of gold, silver, titanium, tungsten, copper, and aluminum.

[0016] Secondly, embodiments of this application propose a method for preparing a self-powered microneedle patch as described in the first aspect, the method comprising:

[0017] Preparation of Sb4-loaded cross-linked gelatin-cross-linked hyaluronic acid microneedles;

[0018] The conductive microneedle patch was assembled with cross-linked gelatin-cross-linked hyaluronic acid microneedles to obtain a conductive drug-loaded microneedle patch;

[0019] By connecting a conductive drug-loaded microneedle patch to a triboelectric nanogenerator, a self-powered microneedle patch is obtained.

[0020] As one embodiment, the preparation of Sb4-supported crosslinked gelatin-crosslinked hyaluronic acid microneedles includes:

[0021] Preparation of cross-linked gelatin and cross-linked hyaluronic acid microparticles;

[0022] Cross-linked hyaluronic acid microparticles were soaked in Sb4 solution to obtain drug-loaded cross-linked hyaluronic acid microparticles;

[0023] Cross-linked gelatin was dissolved in genipin solution to obtain a cross-linked gelatin solution;

[0024] Add drug-loaded cross-linked hyaluronic acid microparticles and Sb4 to the cross-linked gelatin solution and stir until homogeneous to obtain a cross-linked gelatin-cross-linked hyaluronic acid drug solution;

[0025] A cross-linked gelatin-cross-linked hyaluronic acid drug solution was added to a PDMS template and impregnated under vacuum to obtain Sb4-loaded cross-linked gelatin-cross-linked hyaluronic acid microneedles.

[0026] As one embodiment, the method for preparing the cross-linked hyaluronic acid microparticles includes:

[0027] Hyaluronic acid and a cross-linking agent are added to a NaOH solution. After mixing and reacting, the cross-linking agent and uncross-linked hyaluronic acid fragments are removed to obtain a cross-linked hyaluronic acid gel.

[0028] Cross-linked hyaluronic acid gel is ground and filtered to obtain cross-linked hyaluronic acid microparticles.

[0029] In one embodiment, the crosslinking agent is 1,4-butanediol diglycidyl ether.

[0030] Thirdly, embodiments of this application propose the use of the self-powered microneedle patch according to the first aspect in the preparation of a product for treating hypertrophic scars.

[0031] In one embodiment, the product is used to transdifferentiate myofibroblasts of hypertrophic scars into adipocytes, and / or, the product is used to reduce the height and hardness of scars.

[0032] Compared with the prior art, the embodiments of this application have at least the following beneficial effects:

[0033] This application combines a conductive drug-loaded microneedle patch loaded with Sb4 with a triboelectric nanogenerator to obtain a self-powered microneedle patch. The triboelectric nanogenerator offers advantages in portability and self-powered operation, converting mechanical energy generated by human movement into electrical energy to provide a continuous and stable power source for electrical stimulation. Sb4, as a selective small molecule agonist, activates BMP signal transduction by stabilizing intracellular p-SMAD1 / 5 / 8. However, the application of Sb4 in scar treatment faces some challenges. In the self-powered microneedle patch provided by this application, firstly, the electrical stimulation provided by the triboelectric nanogenerator further promotes BMP4 activation, increases transdifferentiation efficiency, and thus promotes adipogenesis. Secondly, the electrical stimulation exerts an anti-inflammatory effect, creating a microenvironment conducive to Sb4's scar repair function. In this microenvironment, Sb4 can better transdifferentiate myofibroblasts in hypertrophic scars into adipocytes, thereby effectively reversing hypertrophic scars and achieving skin repair and tissue regeneration. This microneedle patch provides a minimally invasive, convenient, and efficient strategy for the clinical treatment of burn / traumatic scar repair and fibrotic diseases, and is expected to further promote the development of the field of tissue repair and regeneration.

[0034] Additional aspects and advantages of this application will be set forth in part in the description which follows, and will become apparent from the description or may be learned by practice of this application. Attached Figure Description

[0035] Figure 1 A schematic diagram of the self-powered microneedle patch of this embodiment is shown;

[0036] Figure 2 A schematic diagram of the self-powered microneedle patch of this embodiment is shown;

[0037] Figure 3 A schematic diagram showing the results of the scar penetration ability study in Example 2 is shown;

[0038] Figure 4 A schematic diagram showing the results of the scar penetration ability study in Example 2 is shown;

[0039] Figure 5 A schematic diagram showing the electrical parameter characterization results of the self-powered microneedle patch of Example 3 is shown;

[0040] Figure 6 A schematic diagram of the test results of the in vitro sustained-release experiment in Example 4 is shown;

[0041] Figure 7 A schematic diagram of the rabbit ear hypertrophic scar model after modeling in Example 5 is shown;

[0042] Figure 8 A schematic diagram of the rabbit ear hypertrophic scar model in Example 5 after treatment is shown;

[0043] Figure 9 A schematic diagram of the VSS score results of the scar tissue in Example 5 is shown;

[0044] Figure 10 A schematic diagram of the test results of H&E staining analysis in Example 6 is shown;

[0045] Figure 11 A schematic diagram of the SEI analysis results of the scar tissue in Example 6 is shown;

[0046] Figure 12 A schematic diagram of the test results of immunofluorescence staining in Example 7 is shown;

[0047] Figure 13 A schematic diagram of the test results for inhibiting the inflammatory response in Example 8 is shown;

[0048] Figure 14 A schematic diagram of the test results for inhibiting the inflammatory response in Example 8 is shown. Detailed Implementation

[0049] The technical solutions in the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the embodiments described below are only a part of the embodiments of this application, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this application without creative effort are within the scope of protection of this application.

[0050] It should be understood that, when used in this specification and the appended claims, the terms "comprising" and "including" indicate the presence of the described features, integrals, steps, operations, elements and / or components, but do not exclude the presence or addition of one or more other features, integrals, steps, operations, elements, components and / or collections thereof.

[0051] It should also be understood that the terminology used in this specification is for the purpose of describing particular embodiments only and is not intended to limit the embodiments of this application. As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” are intended to include the plural forms unless the context clearly indicates otherwise.

[0052] Below, we will first explain some of the terms and materials used in this embodiment to facilitate understanding by those skilled in the art.

[0053] Reprogramming: refers to the transformation of a specific type of cell into another cell type through external factors; for example, transforming myofibroblasts in hypertrophic scars into adipocytes.

[0054] Chemical reprogramming: This involves inducing cell reprogramming through the use of small chemical molecules. For example, some small molecules can activate pluripotency-related genes or inhibit the expression of genes related to cell differentiation. Chemically induced reprogramming avoids the risks of genome integration that can occur with gene delivery. Furthermore, small chemical molecules can be precisely targeted to specific cells using drug delivery systems.

[0055] cGel: cross-linked gelatin.

[0056] cHA: cross-linked hyaluronic acid.

[0057] cGel-cHA: cross-linked gelatin-cross-linked hyaluronic acid.

[0058] Sb4@Sb4-carrying cross-linked gelatin-cross-linked hyaluronic acid microneedles: Sb4-carrying cross-linked gelatin-cross-linked hyaluronic acid microneedles.

[0059] TENG: Triboelectric nanogenerator.

[0060] sf-TENG: Stand-alone sliding friction nanogenerator.

[0061] EF: electric field, intrinsic electric field.

[0062] VSS: Vancouver Scar Scale.

[0063] H&E: Hematoxylin and eosin staining method.

[0064] SEI: Scar Elevation Index.

[0065] PLIN: Perilipin.

[0066] The self-powered microneedle patch for repairing hypertrophic scars in this embodiment, its preparation method, and its uses will be described in detail below.

[0067] First, let me explain the self-powered microneedle patch of the first aspect of this embodiment.

[0068] Self-powered microneedle patch

[0069] While existing microneedle patches can provide some electrical stimulation, they typically rely on an external power source, such as a battery or charging device. First, this dependence makes the devices less portable and requires additional support during use, increasing operational complexity and limiting their application in routine medical settings. Due to the limited battery capacity, the devices usually cannot provide a stable, long-term power supply, affecting the sustainability of treatment effects. Second, the limited flexibility of the devices necessitates additional auxiliary equipment during treatment, requiring patients to adapt to complex procedures, impacting the convenience and comfort of the treatment. More importantly, conventional microneedle patches have limited effectiveness in treating and repairing hypertrophic scars.

[0070] In view of this, this embodiment provides a self-powered microneedle patch for repairing hypertrophic scars. Please refer to [link to relevant documentation]. Figure 1 , Figure 1 This embodiment illustrates a self-powered microneedle patch; the self-powered microneedle patch includes:

[0071] A triboelectric nanogenerator is used to generate an electric current; a conductive drug-loaded microneedle patch is connected to the triboelectric nanogenerator; the conductive drug-loaded microneedle patch includes a conductive microneedle patch and cross-linked gelatin-cross-linked hyaluronic acid microneedles carrying Sb4; the surface of the conductive microneedle patch has a metal coating for mediating the current generated by the triboelectric nanogenerator and applying transdermal electrical stimulation; the cross-linked gelatin-cross-linked hyaluronic acid microneedles are coated on the tip of the conductive microneedle patch.

[0072] It is understood that the Sb4 (CAS: 100874-08-6) selected in this embodiment is an effective benzoxazole bone morphogenetic protein 4 (BMP4) signaling agonist. As a selective small molecule agonist, it can activate BMP signal transduction by stabilizing intracellular p-SMAD.

[0073] However, there are some challenges in the application of Sb4 in the treatment of hypertrophic scars. First, local administration must overcome the thickened epidermal barrier of hypertrophic scars, which may limit drug penetration and reduce its local concentration at the target site. Second, intralesional injection must penetrate dense and hard scar tissue, causing significant pain and resulting in uneven drug distribution. In addition, Sb4 has a short half-life, requiring multiple administrations, but frequent administration may cause serious side effects such as vasculitis, pigmentation, erythema, purpura, and burning sensation. At the same time, the chemical reprogramming efficiency of Sb4 needs to be further improved.

[0074] It is understood that the triboelectric nanogenerator in the self-powered microneedle patch provided in this embodiment has the advantages of portability and self-powering, and can convert the mechanical energy generated by human movement into electrical energy, providing a continuous and stable power source for electrical stimulation. Compared with the prior art, the self-powered microneedles prepared in this embodiment can penetrate thickened and rigid scar tissue and directly reach the low-resistance dermis, thereby realizing transdermal electrical stimulation and drug delivery.

[0075] Specifically, in the self-powered microneedle patch's operating mode, by contacting Sb4-carrying cross-linked gelatin-hyaluronic acid microneedles with the hypertrophic scar, a triboelectric nanogenerator generates an electric current under external force. This current, mediated by the conductive microneedle patch, is then applied via transdermal electrical stimulation. Under this electrical stimulation, an immune microenvironment conducive to tissue repair is established. In this embodiment, the self-powered microneedle patch activates the p-SMAD1 / 5 / 8 signaling pathway, promoting the reprogramming of myofibroblasts into adipocytes and reshaping the microenvironment, thereby effectively reversing hypertrophic scars and achieving skin repair and tissue regeneration.

[0076] In other words, under the action of electrical stimulation, BMP4 activation can be further promoted, improving transdifferentiation efficiency and thus promoting adipogenesis. On the other hand, electrical stimulation can exert an anti-inflammatory effect, creating a microenvironment conducive to Sb4's scar repair function. In this microenvironment, Sb4 can better transdifferentiate myofibroblasts in hypertrophic scars into adipocytes. In other words, this embodiment combines a conductive drug-loaded microneedle patch loaded with Sb4 with a triboelectric nanogenerator, which can penetrate thickened and rigid scar tissue and directly reach the low-resistance dermis, thereby achieving transdermal electrical stimulation and drug delivery. Among them, the current generated by the triboelectric nanogenerator can significantly promote the transdifferentiation of myofibroblasts in hypertrophic scars into adipocytes by Sb4, thereby better reversing hypertrophic scars and achieving skin repair and tissue regeneration. At the same time, this embodiment can also achieve sustained release of Sb4.

[0077] Therefore, this embodiment improves reprogramming efficiency by combining the conductive drug-loaded microneedle patch and the triboelectric nanogenerator, which can better transdifferentiate myofibroblasts in hypertrophic scars into adipocytes, reshape the scar microenvironment, and thus effectively reverse hypertrophic scars, achieving skin repair and tissue regeneration.

[0078] As a preferred embodiment, the triboelectric nanogenerator used in this embodiment is a freestanding-sliding triboelectric nanogenerator.

[0079] In this embodiment, Sb4 is loaded onto cross-linked gelatin-cross-linked hyaluronic acid microneedles. Therefore, under the stimulation of electric current, Sb4 can act more effectively on the target location (hypertrophic scar). In a preferred embodiment, Sb4 is located on the outer surface of the cross-linked gelatin-cross-linked hyaluronic acid microneedles or dispersed inside the cross-linked gelatin-cross-linked hyaluronic acid microneedles.

[0080] In a preferred embodiment, the metal coating of the conductive microneedle patch is selected from one or more of gold, silver, titanium, tungsten, copper, and aluminum. In a more preferred embodiment, the metal coating of the conductive microneedle patch is selected from gold (Au).

[0081] In summary, this embodiment combines a conductive drug-loaded microneedle patch with Sb4 and a triboelectric nanogenerator to obtain a self-powered microneedle patch. The triboelectric nanogenerator offers the advantages of portability and self-powered operation, converting mechanical energy generated by human movement into electrical energy to provide a continuous and stable power source for electrical stimulation. Sb4, as a selective small-molecule agonist, activates BMP signal transduction by stabilizing intracellular p-SMAD. Based on the combined action of the conductive drug-loaded microneedle patch and the triboelectric nanogenerator, this self-powered microneedle patch can establish an immune microenvironment conducive to tissue repair by inhibiting the release of pro-inflammatory factors. More importantly, it promotes the reprogramming of myofibroblasts into adipocytes and remodels the microenvironment by activating the p-SMAD1 / 5 / 8 signaling pathway, thereby effectively reversing hypertrophic scarring and achieving skin repair and tissue regeneration.

[0082] Therefore, the self-powered microneedle patch of this embodiment provides a minimally invasive, convenient, and efficient strategy for the clinical treatment of burn / traumatic scar repair and fibrotic diseases, and is expected to further promote the development of the field of tissue repair and regeneration.

[0083] Next, the preparation method of the second aspect of this embodiment will be described.

[0084] Preparation method

[0085] This embodiment proposes a method for preparing a self-powered microneedle patch, which includes the following steps:

[0086] (1) Preparation of cross-linked gelatin-cross-linked hyaluronic acid microneedles carrying Sb4.

[0087] It is understandable that the cross-linked gelatin-cross-linked hyaluronic acid microneedles carrying Sb4 are the core components of this embodiment. They can act on hypertrophic scars under the stimulation of the current generated by the triboelectric nanogenerator. In step (1), the purpose is to prepare cross-linked gelatin-cross-linked hyaluronic acid microneedles carrying Sb4 so as to realize the subsequent assembly with conductive microneedle patches.

[0088] (2) The conductive microneedle patch is assembled with cross-linked gelatin-cross-linked hyaluronic acid microneedles to obtain a conductive drug-loaded microneedle patch.

[0089] In step (2), the conductive microneedle patch can be prepared using the following method:

[0090] A 50nm thick layer of Au was uniformly coated onto the surface of a PLA microneedle patch using sputtering technology to obtain a conductive microneedle patch.

[0091] Next, the conductive microneedle patch was assembled with cross-linked gelatin-cross-linked hyaluronic acid microneedles to obtain a conductive drug-loaded microneedle patch. The conductive drug-loaded microneedle patch can mediate the current generated by the triboelectric nanogenerator and significantly promote the function of Sb4 through the current.

[0092] (3) Connect the conductive drug-loaded microneedle patch to the triboelectric nanogenerator to obtain a self-powered microneedle patch.

[0093] In step (3), a self-powered microneedle patch can be obtained by simply assembling the conductive drug-loaded microneedle patch with the triboelectric nanogenerator.

[0094] The above steps will be explained in further detail below.

[0095] In step (1), the preparation of Sb4-supported cross-linked gelatin-cross-linked hyaluronic acid microneedles specifically includes:

[0096] (1.1) Preparation of cross-linked gelatin and cross-linked hyaluronic acid microparticles;

[0097] (1.2) Cross-linked hyaluronic acid microparticles were soaked in Sb4 solution to obtain drug-loaded cross-linked hyaluronic acid microparticles;

[0098] (1.3) Dissolve cross-linked gelatin in genipin solution to obtain cross-linked gelatin solution;

[0099] (1.4) Add drug-loaded cross-linked hyaluronic acid microparticles and Sb4 to the cross-linked gelatin solution and stir until homogeneous to obtain a cross-linked gelatin-cross-linked hyaluronic acid drug solution;

[0100] (1.5) Add cross-linked gelatin-cross-linked hyaluronic acid drug solution to PDMS template and impregnate in vacuum environment to obtain cross-linked gelatin-cross-linked hyaluronic acid microneedles carrying Sb4.

[0101] In step (1.2), the obtained cross-linked hyaluronic acid microparticles are immersed in an Sb4 solution (1 mg / mL, 1 mL). After the microparticles swell sufficiently, drug-loaded cross-linked hyaluronic acid microparticles are obtained. Then, the Sb4 powder and the drug-loaded cross-linked hyaluronic acid microparticles containing Sb4 are magnetically stirred with the cross-linked gelatin solution at room temperature to mix evenly, resulting in a cross-linked gelatin-cross-linked hyaluronic acid drug solution containing Sb4.

[0102] Cross-linked gelatin and cross-linked hyaluronic acid microparticles serve as matrix materials for microneedles, used to encapsulate SB4.

[0103] In this embodiment, the cross-linked gelatin can be prepared using the following method:

[0104] (1) Dissolve 4g of gelatin in 8mL of deionized water and stir magnetically at 50℃ and 200r / min for 1h to obtain a 40% (w / v) gelatin solution.

[0105] (2) Dissolve 10 mg of genipin in deionized water containing 10% alcohol, and slowly add the genipin solution (200 μL, 300 μL or 400 μL, preferably 300 μL) dropwise into the prepared gelatin solution. Stir magnetically at 40°C for 96 h to allow the gelatin molecules to fully crosslink and obtain crosslinked gelatin.

[0106] It is understood that the PDMS template is a micro-nano structure mold made of a flexible polymer material, polydimethylsiloxane (PDMS); in this embodiment, Sb4 is supported (loaded) by injecting a cross-linked gelatin-cross-linked hyaluronic acid drug solution into the PDMS micropores.

[0107] This embodiment demonstrates through relevant experiments that the volume of the genipin solution and the content of cross-linked hyaluronic acid microparticles in the cross-linked gelatin-cross-linked hyaluronic acid drug solution affect the sustained-release time of the self-powered microneedle patch.

[0108] In a preferred embodiment, the cross-linked gelatin-cross-linked hyaluronic acid drug solution contains a genipin solution volume of 300 μL and a cross-linked hyaluronic acid microparticle content of 40%.

[0109] In this embodiment, the drug release rate decreased with increasing genipin solution volume, while the sustained release time increased. Specifically, the microneedles prepared using 300 μL of genipin solution were able to release the drug continuously for an extended period.

[0110] Secondly, by adding cross-linked hyaluronic acid microparticles to cross-linked gelatin, the drug release time of the microneedles can be further adjusted. Specifically, as the content of cross-linked hyaluronic acid microparticles in the cross-linked gelatin increases, the drug release rate actually slows down. When the content of cross-linked hyaluronic acid microparticles is 40%, the drug can be continuously released within 24 hours.

[0111] Step (1.1), the method for preparing the cross-linked hyaluronic acid microparticles, includes:

[0112] (1.1.1) Hyaluronic acid and cross-linking agent are added to NaOH solution, and after mixing and reaction, the cross-linking agent and uncross-linked hyaluronic acid fragments are removed to obtain cross-linked hyaluronic acid gel;

[0113] (1.1.2) Cross-linked hyaluronic acid gel was ground and filtered to obtain cross-linked hyaluronic acid microparticles.

[0114] In this embodiment, the hyaluronic acid used has a molecular weight of approximately 20,000 to 400,000 Da.

[0115] For example, the method for preparing cross-linked hyaluronic acid microparticles specifically includes:

[0116] 1 g of HA (molecular weight approximately 20,000–400,000 Da) and 200 μL of crosslinking agent were added to a 0.25 M NaOH solution (pH = 13) of 9.8 mL. The solution was then thoroughly mixed and reacted at 65 °C and 100 rpm for 3 h. After the reaction, 95% ethanol was added to remove excess NaOH, crosslinking agent, and uncrosslinked HA fragments, yielding cHA gel.

[0117] Next, the cHA gel was thoroughly ground for 20 minutes and then filtered through a 500-mesh sieve to obtain cross-linked hyaluronic acid microparticles.

[0118] In a preferred embodiment, the crosslinking agent is 1,4-butanediol diglycidyl ether.

[0119] Next, the use of the third aspect of this embodiment will be explained.

[0120] use

[0121] As described in the first aspect, this embodiment combines a conductive drug-loaded microneedle patch loaded with Sb4 with a triboelectric nanogenerator. The current generated by the triboelectric nanogenerator can significantly promote the transdifferentiation of myofibroblasts in hypertrophic scars into adipocytes by Sb4, thereby better reversing hypertrophic scars and achieving skin repair and tissue regeneration. Simultaneously, this embodiment can also achieve sustained release of Sb4.

[0122] Therefore, the self-powered microneedle patch of this embodiment can be used to manufacture products for treating hypertrophic scars. For example, a self-driven hypertrophic scar repair patch.

[0123] The present application will be further described below with reference to specific embodiments. It should be understood that these embodiments are for illustration / explanation only and are not intended to limit the scope of the present application.

[0124] Unless otherwise specified, all materials, reagents and instruments used in the following embodiments are commercially available.

[0125] Example 1: Preparation of matrix material.

[0126] This embodiment uses a chemical cross-linking method to prepare cross-linked gelatin and a cross-linked gelatin-cross-linked hyaluronic acid drug solution; the specific preparation method includes the following steps:

[0127] 1.1 Preparation of gelatin solution: Dissolve 4g of gelatin in 8mL of deionized water and stir magnetically at 50℃ and 200r / min for 1h to obtain a 40% (w / v) gelatin solution.

[0128] 1.2 Preparation of cross-linked gelatin: Dissolve 10 mg of genipin in deionized water containing 10% alcohol, and slowly add the genipin solution (200 μL, 300 μL or 400 μL) dropwise into the gelatin solution prepared in step (1.1). Stir magnetically at 40°C for 96 h to allow the gelatin molecules to fully cross-link, and obtain cross-linked gelatin with different degrees of cross-linking.

[0129] 1.3 Preparation of cross-linked hyaluronic acid gel: 1 g of HA (purchased from Sigma-Aldrich) with a molecular weight of approximately 20,000–400,000 Da and 200 μL of 1,4-butanediol diglycidyl ether were added to a 0.25 M NaOH solution with pH = 13. The solution was then thoroughly mixed and reacted at 65 °C for 3 h. After the reaction was complete, 95% ethanol was added to remove excess NaOH, 1,4-butanediol diglycidyl ether, and uncross-linked HA fragments, thus obtaining cross-linked hyaluronic acid gel.

[0130] 1.4 Preparation of cross-linked hyaluronic acid microparticles: After thoroughly grinding the cross-linked hyaluronic acid gel obtained in step (1.3) for 20 minutes, filter it through a 500-mesh sieve to obtain cross-linked hyaluronic acid microparticles.

[0131] 1.5 Preparation of drug-loaded cross-linked hyaluronic acid microparticles:

[0132] The cross-linked hyaluronic acid microparticles obtained in step 1.4 were thoroughly soaked in an Sb4 solution with a concentration of 1 mg / mL and a volume of 1 mL to form drug-loaded cross-linked hyaluronic acid microparticles.

[0133] 1.6 Preparation of cross-linked gelatin-cross-linked hyaluronic acid drug solution: The drug-loaded cross-linked hyaluronic acid microparticles and Sb4 solution (1 mg / mL, 1 mL) were added to the cross-linked gelatin obtained in step 1.2. The mixture was then thoroughly stirred with magnetic force at room temperature to prepare a cross-linked gelatin-cross-linked hyaluronic acid drug solution containing Sb4.

[0134] Next, the Sb4-loaded conductive microneedle patch (conductive drug-loaded microneedle patch) is prepared, including the following steps:

[0135] 2.1 PLA microneedle patches were prepared using thermoforming and PDMS template.

[0136] 2.2 A 50nm thick layer of Au was uniformly coated on the surface of the PLA microneedle patch using sputtering technology to obtain a conductive microneedle patch.

[0137] 2.3 Add a cross-linked gelatin-cross-linked hyaluronic acid drug solution containing Sb4 to the surface of the PDMS template and place it in a vacuum environment of -85kPa for 30 minutes to fully impregnate it.

[0138] 2.4 Remove the cross-linked gelatin-cross-linked hyaluronic acid drug solution residue from the PDMS template surface, and precisely align and press the conductive microneedle patch into the drug cavity.

[0139] 2.5 After drying at room temperature for 12 hours, a conductive drug-loaded microneedle patch loaded with Sb4 was successfully constructed.

[0140] 2.6. The Sb4-loaded ordinary microneedle patch is prepared using PLA microneedle patches as substrates and the same method.

[0141] 3. The following will describe the preparation of the self-powered microneedle patch in this embodiment:

[0142] The self-powered microneedle patch consists of the aforementioned conductive drug-loaded microneedle patch and sf-TENG. The sf-TENG is composed of a triboelectric layer (PI), a dielectric layer (PTFE), and an electrode (EMNP, conductive drug-loaded microneedle patch).

[0143] 3.1 The triboelectric layer is made of polyimide (PI) film (30mm×70mm) and the dielectric layer is made of polytetrafluoroethylene (PTFE) (13mm×13mm). The conductive drug-loaded microneedle patch obtained in step (2.5) is used as the electrode of the self-powered microneedle patch to prepare sf-TENG.

[0144] 3.2 Cover the Al sheet with PTFE and ground it with a wire. Apply a 2WV polarization voltage to the PTFE film with a corona needle for 20 minutes to increase the surface charge density of the PTFE dielectric layer through corona discharge.

[0145] Please see Figure 1 , Figure 1 A schematic diagram of the self-powered microneedle patch of this embodiment is shown. Figure 2 A schematic diagram of the self-powered microneedle patch of this embodiment is shown; combined with Figure 1 As shown, Sb4-carrying cross-linked gelatin-cross-linked hyaluronic acid microneedles are coated on the tip of a conductive microneedle patch.

[0146] The following examples will verify the effectiveness of the self-powered microneedle patch prepared in Example 1.

[0147] Example 2: Study on scar penetration ability.

[0148] To verify whether the microneedle patch could penetrate hypertrophic scars, Example 2 conducted a penetration experiment on ex vivo hypertrophic scars in rabbit ears. The specific experimental method is as follows:

[0149] 1. Free the hypertrophic scar tissue of rabbit ears. Insert a microneedle loaded with yellow chromogenic agent into the hypertrophic scar tissue with a force of 20N, hold for 20 seconds, and then peel it off.

[0150] 2. After gently removing excess dye from the scar surface, observe the arrangement of pinholes on the hypertrophic scar tissue.

[0151] 3. Fix the hypertrophic scar tissue that had been previously penetrated by microneedles with 4% paraformaldehyde, prepare paraffin sections, stain with hematoxylin and eosin (H&E), and observe the penetration depth of the microneedles under a microscope.

[0152] To visually observe the ability of microneedle patches to penetrate hypertrophic scars, we first inserted the microneedle patches into rabbit ear scars. Figure 3 As shown at point A, a 10×10 array immediately appears on the scarred skin. Subsequently, in this embodiment, a microneedle patch with a yellow developer loaded on the needle tip is inserted into the rabbit ear scar skin, and the ability of the microneedle patch to penetrate the scar is evaluated by the number of yellow pores left in the skin. According to... Figure 3 The results at point B showed that after removing the microneedle patch, a 10×10 array of yellow pinholes was clearly visible on the rabbit ear scar tissue, proving that the microneedles could completely penetrate the scar tissue.

[0153] To further determine the penetration depth of the microneedles, the example involved H&E staining of pretreated rabbit ear scar skin to observe the depth of microneedle insertion into the scar. According to... Figure 4 Test results show that microneedles can successfully create microchannel arrays that penetrate the epidermal layer of scars and reach the dermal region, with a penetration depth of approximately 800 μm.

[0154] Based on the above test results, it is demonstrated that the microneedle patch of this embodiment has sufficient mechanical force to penetrate the epidermal barrier of the scar, laying the foundation for subsequent percutaneous drug delivery and electrical stimulation.

[0155] Example 3: Study on electrical output performance.

[0156] After successfully fabricating the sf-TENG, we drove it with a finger at a frequency of 2Hz and connected an electrometer and oscilloscope to measure its electrical output parameters. Please refer to [link to documentation]. Figure 5 , Figure 5A schematic diagram illustrating the electrical parameter characterization results of the self-powered microneedle patch of this embodiment is shown; according to Figure 5 The test results show that the peak open-circuit voltage (Voc) of the sf-TENG is about 10.5V, the peak short-circuit current (Isc) is about 1μA, and the short-circuit transferred charge (Qsc) is about 9nC.

[0157] Example 4: In vitro drug release performance study.

[0158] To achieve sustained treatment, this embodiment controlled the sustained-release time of the self-powered microneedle patch to 24 hours by adjusting the volume of the genipin solution and the content of cross-linked hyaluronic acid microparticles in the Sb4-carrying cross-linked gelatin-cross-linked hyaluronic acid microneedles. First, this embodiment investigated the effect of the added volume of genipin solution in the self-powered microneedle patch on the Sb4 release kinetics in vitro. Since Sb4 (320.2 Da) has a similar molecular weight and hydrodynamic radius to the small molecule compound fluorescein sodium (332.0 Da), this embodiment used fluorescein sodium to simulate the release behavior of Sb4 in the self-powered microneedle patch.

[0159] Please see Figure 6 This embodiment is based on the standard concentration solution of Fluorescein sodium and OD 480 The relationships between them were drawn Figure 6 The standard curve is shown at point A in the diagram. In this embodiment, the release curve of Fluorescein sodium from the self-powered microneedle patch was obtained based on the standard curve. Figure 6 The release curve shown at point B.

[0160] The results showed that the release rate of Fluorescein sodium decreased with increasing genipin solution volume, while the duration of sustained release increased. Specifically, the self-powered microneedle patch prepared using 300 μL of genipin solution demonstrated sustained drug release. Therefore, 300 μL of genipin solution was selected for this study.

[0161] This embodiment further adjusts the drug release time of a self-powered microneedle patch by adding cross-linked hyaluronic acid microparticles to cross-linked gelatin. Subsequently, this embodiment investigates the effect of different cross-linked hyaluronic acid microparticle contents on Sb4 release kinetics. According to... Figure 6The test results at point C showed that the release rate of Fluorescein sodium decreased with increasing cross-linked hyaluronic acid microparticle content in the cross-linked gelatin. Specifically, when the cross-linked hyaluronic acid microparticle content was 40%, the drug could be continuously released within 24 hours. Therefore, the Sb4-supported cross-linked gelatin-cross-linked hyaluronic acid microneedles consist of cross-linked gelatin containing 300 μL of genipin and 40% cross-linked hyaluronic acid microparticles.

[0162] Subsequently, this embodiment further explored the effect of EF generated by sf-TENG on the molecular motion behavior of drugs. According to Figure 6 The test results at point D showed that the in vitro drug release kinetics indicated no difference in drug release rate between the self-powered microneedle patch and the Sb4-supported cross-linked gelatin-hyaluronic acid microneedles. This means that the current has almost no effect on the drug release process. Based on the above research, the self-powered microneedle patch can continuously release Sb4 within 24 hours.

[0163] Example 5: Self-powered microneedle patch inhibits hypertrophic scars.

[0164] This embodiment uses a New Zealand white rabbit to establish a rabbit ear hypertrophic scar model as a preclinical animal model for the treatment system. Please refer to [link to previous text]. Figure 7 A puncture site was created on the rabbit ear using a piercing device. Twenty-eight days post-surgery, a significantly thickened scar formed at the puncture site; the scar was red and hard, thus establishing a rabbit ear hypertrophic scar model. The experiment was divided into three groups: a normal group, a scar group, and a treatment group.

[0165] In this study, the normal group received no trauma treatment, the scar group received no treatment, while the treatment group received scar treatment using a self-powered drug-loaded microneedle patch (outputting 1 μA current). In subsequent experiments (lasting 14 days), the scar repair effects and histological changes in the rabbit ears of each group were closely observed to assess the impact of different interventions on scar tissue.

[0166] Please refer to Table 1 for the evaluation content and scoring criteria for the test results of this embodiment.

[0167] Please see Figure 8 , Figure 8 A schematic diagram of a rabbit ear hypertrophic scar model after treatment is shown (including a normal group, a scar group, and a treatment group). The appearance of the scars significantly improved after treatment with self-powered microneedle patches. Compared to the scar group, the scar height in the treatment group was significantly reduced, approaching that of the normal group, and the surface became smoother. Furthermore, the scar hardness in the treatment group decreased, becoming easily movable with gentle pressure, while the scar in the scar group was hard and showed whitening upon stretching. Subsequently, the overall condition of the scars was assessed using the Vancouver Scar Scale (VSS). The test results can also be found in [link to test results]. Figure 9 , Figure 9 The VSS scores for the scar group and the treatment group are also shown.

[0168] according to Figure 9 The test results showed that the VSS score of the treatment group was significantly lower than that of the scar group, indicating that the appearance of the scar was significantly improved after treatment with self-powered microneedle patches.

[0169] Table 1

[0170]

[0171]

[0172] Example 6: Self-powered microneedle patches reduce scar elevation index.

[0173] To further investigate the effect of self-powered microneedle patches on the pathological characteristics of scar tissue, this embodiment also performed hematoxylin and eosin (H&E) staining analysis on the rabbit ear hypertrophic scar model (day 14) after treatment in Example 5.

[0174] HE staining methods include:

[0175] 1. Dewaxing: The paraffin sections of rabbit ear scar tissue were successively immersed in xylene I and xylene II containers for 15 minutes in each container.

[0176] 2. Rehydration: After removing the paraffin, the rabbit ear scar tissue sections need to be gradually replaced with water by passing xylene solvent through ethanol solutions of different concentrations. The ethanol solution concentrations are: 100%, 95%, 90%, 80%, and 70%. The sections are treated in each concentration for 8 minutes, and finally washed with distilled water for 8 seconds.

[0177] 3. Staining: After staining the sections with hematoxylin solution for 5 minutes, rinse three times with distilled water, then perform rapid differentiation with 1% hydrochloric acid ethanol, rinse three more times with distilled water, and after blueing with 0.6% ammonia solution, rinse thoroughly with running water. Finally, stain with eosin solution for 3 minutes.

[0178] 4. Dehydration and Clearing: Immerse the sections sequentially in containers of 70%, 95%, and 100% ethanol solutions, immersing each in 5 minutes. Then, immerse the sections sequentially in two xylene containers, immersing each in 5 minutes, thus completing the dehydration and clearing process.

[0179] 5. Mounting: Use neutral resin to mount the slightly dried slides onto a glass slide, avoiding air bubbles. Allow the mounted slides to dry completely, then observe and record the observations under an optical microscope.

[0180] Please see Figure 10 , Figure 10 A schematic diagram of the test results for H&E staining analysis is shown; Figure 10 The test results showed that, compared with the normal group, the scar group had significantly increased tissue thickness, indicating that the scar tissue in this group underwent a significant proliferative response, further demonstrating that the scar tissue experienced an abnormal repair process. After treatment with self-powered microneedle patches, the epidermal and dermal thickness of the scar tissue in the treatment group significantly decreased, returning to levels close to normal skin, demonstrating the potential of self-powered microneedle patches in inhibiting scar hyperplasia and promoting tissue repair.

[0181] In this embodiment, the scar elevation index (SEI) of the scar tissue is analyzed simultaneously. The SEI is calculated using the following formula: SEI = H / H0; where H represents the height from the highest point of the scar to the cartilage surface, and H0 represents the height from the stratum corneum at the bottom of the scar to the cartilage surface.

[0182] SEI analysis results are as follows Figure 11 As shown; according to Figure 11 The analysis results showed that, compared with the scar group, the SEI of the treatment group was significantly reduced after treatment with self-powered microneedle patches.

[0183] Example 7: Experiment on the effect of self-powered microneedle patches on fat regeneration.

[0184] Perilipins (PLINs) are a group of proteins located on the surface of lipid droplets that regulate fat storage and metabolism. To investigate the effect of self-powered charged Sb4 microneedle patches on fat regeneration, this study simultaneously detected the expression of PLIN1 in different treatment groups (normal group, scar group, and treatment group) using immunofluorescence staining.

[0185] The immunofluorescence staining methods include:

[0186] 1. Dewaxing: The paraffin sections of rabbit ear scar tissue were successively immersed in xylene I and xylene II containers for 15 minutes in each container.

[0187] 2. Rehydration: After removing the paraffin, the rabbit ear scar tissue sections need to be gradually replaced with water by passing xylene solvent through ethanol solutions of different concentrations. The ethanol solution concentrations are: 100%, 95%, 90%, 80%, and 70%. The sections are treated in each concentration for 8 minutes, and finally washed with distilled water for 8 seconds.

[0188] 3. Antigen retrieval: Immerse the slides in antigen retrieval solution, incubate overnight in a 70°C water bath, and then wash three times with PBS solution after naturally cooling to room temperature.

[0189] 4. Permeability and sealing: Circle the tissue with a water-resistant pen, add 0.2% Triton to the tissue for permeability treatment for 5 minutes, wash 3 times with PBS solution, and then block with 10% goat serum for 30 minutes.

[0190] 5. Primary antibody incubation: Place the slides in a humidified chamber and incubate overnight at 4°C. After incubation, wash three times with PBS solution.

[0191] 6. Secondary antibody incubation: Incubate the secondary antibody at room temperature in the dark for 2 hours, wash 3 times with PBS solution, and mount with mounting medium containing DAPI.

[0192] Figure 12 The diagram shows the test results of the normal group, scar group, and treatment group after immunofluorescence staining. Figure 12 The results showed that the normal group contained a large number of PLIN1-positive adipocytes, exhibiting a strong green fluorescent signal. In contrast, the scar group showed almost no PLIN1-positive green fluorescent signal, indicating that both the number and function of adipocytes were suppressed, which is closely related to the progression of tissue fibrosis. After treatment with self-powered microneedle patches, PLIN1-positive adipocytes appeared in the tissue, demonstrating that self-powered microneedle patches can effectively promote adipocyte regeneration.

[0193] Example 7 demonstrates that the self-powered microneedle patch of this embodiment can inhibit scar formation by promoting the transdifferentiation of myofibroblasts into adipocytes and soften scars by promoting fat regeneration, thereby further improving the efficacy of anti-scar treatment. Through this mechanism, this embodiment not only provides a more effective treatment plan for scar treatment but also has high clinical application value, promoting natural skin repair and regeneration during treatment and further improving the appearance of scars.

[0194] Example 8: Self-powered drug-loaded microneedle patch inhibits inflammatory response.

[0195] TNF-α is an important pro-inflammatory cytokine. In order to evaluate the effect of self-powered drug-loaded microneedle patches on tissue inflammation, this embodiment simultaneously detected the expression of TNF-α in different treatment groups (normal group, scar group and treatment group) by immunofluorescence staining.

[0196] The immunofluorescence staining method in Example 8 is the same as that in Example 7.

[0197] Figure 13 and Figure 14 This diagram illustrates the test results of the normal group, scar group, and treatment group after immunofluorescence staining; based on Figure 13 and Figure 14The test results showed that strong TNF-α positive red fluorescence signals appeared in the scar group. After treatment with self-powered drug-loaded microneedle patches, the expression level of TNF-α in the tissue was significantly reduced, approaching the level of normal skin tissue. This indicates that self-powered microneedle patches effectively improve the infiltration of inflammatory factors, reduce inflammatory response, and rebuild an immune microenvironment conducive to tissue repair.

[0198] In summary, the self-powered microneedle patch provided in this embodiment promotes the reprogramming of myofibroblasts into adipocytes by providing transdermal electrochemical stimulation, rebuilds the pro-regenerative microenvironment, and further regulates the immune microenvironment by inhibiting the release of pro-inflammatory factors, thereby effectively reversing hypertrophic scars and achieving skin repair and tissue regeneration.

[0199] The technical solutions provided by the embodiments of this application have been described in detail above. Specific examples have been used in this document to illustrate the principles and implementation methods of the embodiments of this application. The descriptions of the embodiments above are only for helping to understand the principles of the embodiments of this application. At the same time, for those skilled in the art, there will be changes in the specific implementation methods and application scope based on the embodiments of this application. Therefore, the content of this specification should not be construed as a limitation of this application.

Claims

1. A self-powered microneedle patch for repairing hypertrophic scars, characterized in that, The self-powered microneedle patch includes: Triboelectric nanogenerators are used to generate electric current. A conductive drug-loaded microneedle patch, wherein the conductive drug-loaded microneedle patch is connected to a triboelectric nanogenerator; The conductive drug-loaded microneedle patch includes a conductive microneedle patch and cross-linked gelatin-cross-linked hyaluronic acid microneedles loaded with Sb4; the CAS number of the Sb4 is 100874-08-6; The conductive microneedle patch has a metal coating on its surface to mediate the current generated by the triboelectric nanogenerator and to apply transdermal electrical stimulation; the cross-linked gelatin-cross-linked hyaluronic acid microneedles are coated on the tips of the conductive microneedle patch; The current generated by the triboelectric nanogenerator can promote the transdifferentiation of myofibroblasts in hypertrophic scars into adipocytes by Sb4. The method for preparing the self-powered microneedle patch includes: Preparation of Sb4-loaded crosslinked gelatin-crosslinked hyaluronic acid microneedles; The conductive microneedle patch was assembled with cross-linked gelatin-cross-linked hyaluronic acid microneedles to obtain a conductive drug-loaded microneedle patch; By connecting a conductive drug-loaded microneedle patch to a triboelectric nanogenerator, a self-powered microneedle patch is obtained. The preparation of Sb4-loaded crosslinked gelatin-crosslinked hyaluronic acid microneedles includes: Preparation of cross-linked gelatin and cross-linked hyaluronic acid microparticles; Cross-linked hyaluronic acid microparticles were soaked in Sb4 solution to obtain drug-loaded cross-linked hyaluronic acid microparticles; Cross-linked gelatin was dissolved in genipin solution to obtain a cross-linked gelatin solution; Add drug-loaded cross-linked hyaluronic acid microparticles and Sb4 to the cross-linked gelatin solution and stir until homogeneous to obtain a cross-linked gelatin-cross-linked hyaluronic acid drug solution; A cross-linked gelatin-cross-linked hyaluronic acid drug solution was added to a PDMS template and impregnated under vacuum to obtain Sb4-loaded cross-linked gelatin-cross-linked hyaluronic acid microneedles.

2. The self-powered microneedle patch according to claim 1, characterized in that, The triboelectric nanogenerator is a freestanding sliding triboelectric nanogenerator.

3. The self-powered microneedle patch according to claim 1, characterized in that, The Sb4 is dispersed inside the cross-linked gelatin-cross-linked hyaluronic acid microneedles.

4. The self-powered microneedle patch according to claim 1, characterized in that, The metal coating of the conductive microneedle patch is selected from one or more of gold, silver, titanium, tungsten, copper, and aluminum.

5. The self-powered microneedle patch according to claim 1, characterized in that, The method for preparing the cross-linked hyaluronic acid microparticles includes: Hyaluronic acid and a cross-linking agent are added to a NaOH solution. After mixing and reacting, the cross-linking agent and uncross-linked hyaluronic acid fragments are removed to obtain a cross-linked hyaluronic acid gel. Cross-linked hyaluronic acid gel is ground and filtered to obtain cross-linked hyaluronic acid microparticles.

6. The self-powered microneedle patch according to claim 5, characterized in that, The crosslinking agent is 1,4-butanediol diglycidyl ether.

7. Use of the self-powered microneedle patch according to any one of claims 1-6 in the preparation of a medicament for treating hypertrophic scars.

8. The use according to claim 7, characterized in that, The drug is used to transdifferentiate myofibroblasts of hypertrophic scars into adipocytes, and / or the drug is used to reduce the height and hardness of scars.

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