Skin-adhesive intelligent air-permeable bandage

Abstract

The invention provides an intelligent breathable bandage capable of being adhered to skin. The intelligent breathable bandage capable of being adhered to skin comprises an antibacterial bioelectric interface film capable of being adhered in a stretching mode; the waterproof moisture-permeable protective film is used for protecting the wound from external pollution; and a stretchable breathable circuit assembly disposed between the bioelectrical interface film and the protective film. A permeable stretchable circuit assembly includes: a permeable stretchable circuit board; the biosensor is constructed on the permeable and stretchable circuit board; and an electronic component assembled on the permeable stretchable circuit board. The electronic assembly includes: a physiological signal processing module electrically coupled to the biosensor for in situ wound monitoring; and a drug delivery actuation module electrically coupled to the bioelectrical interface membrane for adaptive drug delivery for wound therapy. The provided bandage is more convenient, comfortable and efficient, does not require a large amount of dressing, and thus does not hinder the daily activity and living quality of the patient.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202511074371.9 (22) Application Date 2025.08.01 (30) Priority Data 63 / 678,566 2024.08.02 US (71) Applicant City University of Hong Kong Address Tat Chee Road, Kowloon, Hong Kong, China (72) Inventors Yu Xingge Huang Xingcan Zhang Qiang Yang Yawen Zou Long (74) Patent Agency Shenzhen Yibao Intellectual Property Agency (General Partnership) 44588 Patent Attorney Wang Qin Cao Yucun (51) Int.Cl. A61F 13 / 01 (2024.01) A61F 13 / 00 (2024.01) A61B 5 / 01 (2006.01) A61B 5 / 145 (2006.01) (54) Invention Title: Skin-Adhesive Smart Breathable Bandage (57) Abstract: This invention provides a skin-adhesive smart breathable bandage comprising: a stretchable, adhesive antibacterial bioelectric interface membrane; a waterproof and breathable protective membrane for protecting wounds from external contamination; and a stretchable and breathable circuit assembly disposed between the bioelectric interface membrane and the protective membrane. The permeable and stretchable circuit assembly comprises: a permeable and stretchable circuit board; a biosensor constructed on the permeable and stretchable circuit board; and electronic components assembled on the permeable and stretchable circuit board. The electronic components include: a physiological signal processing module electrically coupled to the biosensor for in-situ wound monitoring; and a drug delivery actuation module electrically coupled to the bioelectric interface membrane for adaptive drug delivery for wound treatment. The provided bandage is more convenient, comfortable, and efficient, requiring less dressing and thus not hindering the patient's daily activities and quality of life. Claims (3 pages), Description (12 pages), Drawings (33 pages), CN 121445557 A 2026.02.03 CN 1 21 44 55 57 A 1. A skin-adhesive smart breathable bandage comprising: a stretchable adhesive antimicrobial bioelectric interface membrane, said stretchable adhesive antimicrobial bioelectric interface membrane being made of stretchable adhesive antimicrobial fibers; a waterproof and breathable protective membrane for protecting a wound from external contamination; and a permeable and stretchable circuit assembly disposed between said bioelectric interface membrane and said protective membrane; wherein said permeable and stretchable circuit assembly comprises: a permeable and stretchable circuit board; one or more biosensors built on said permeable and stretchable circuit board; and electronic components assembled on said permeable and stretchable circuit board, and comprising: a physiological signal processing module electrically coupled to said one or more biosensors to...1. For in-situ wound monitoring; and a drug delivery actuation module electrically coupled to the bioelectric interface membrane for adaptive drug delivery for wound treatment. 2. The smart adhesive permeable bandage of claim 1, wherein the stretchable adhesive antibacterial bioelectric interface membrane is a fiber membrane prepared by co-electrospinning styrene-ethylene-butene-styrene (SEBS) fibers and antibiotic-loaded gelatin methacrylate (GelMA) fibers. 3. The skin-adhesive smart breathable bandage of claim 1, wherein the weight ratio of SEBS fibers to GelMA fibers is 1:1. 4. The skin-adhesive smart breathable bandage of claim 1, wherein the bioelectric interface membrane is modified with tannins, contains catechol and pyrogallol, and adheres to the skin through multiple synergistic reactions including hydrogen bonding and Schiff base / Michael addition reactions, electrostatic attraction, and cation-π interactions. 5. The skin-adhesive smart breathable bandage of claim 1, wherein the fiber membrane is loaded with conductive nanoparticles. 6. The skin-adhesive smart breathable bandage of claim 5, wherein the conductive nanoparticles are silver nanoparticles. 7. The skin-adhesive smart breathable bandage of claim 1, further comprising a wireless power harvesting and communication module, the wireless power harvesting and communication module being configured to enable the skin-adhesive smart breathable bandage to communicate with a remote device to facilitate battery-free remote diagnosis and treatment of wounds. 8. The skin-adhesive smart breathable bandage of claim 1, wherein the drug delivery actuation module comprises: at least one pair of drug delivery electrodes for applying a drug delivery voltage to the bioelectric interface membrane; and a switch connected to the drug delivery electrodes and configured to turn the drug delivery voltage on / off. 9. The skin-adhesive smart breathable bandage of claim 8, further comprising a microcontroller unit electrically connected to the drug delivery actuation module and configured to adjust the drug delivery amount by controlling the duration of the drug delivery voltage being turned on. 10. The skin-adhesive smart breathable bandage of claim 1, wherein the one or more biosensors include a glucose sensor having at least one stretchable working electrode, the at least one stretchable working electrode being attached to the permeable stretchable circuit board; and the working electrode having a layered structure comprising: a stretchable substrate; a mediator layer deposited on the stretchable substrate; and a glucose sensing element layer deposited on the mediator material layer;11. The skin-adhesive smart breathable bandage of claim 1, wherein the one or more biosensors include a pH sensor having at least one stretchable working electrode attached to the permeable stretchable circuit board; and the working electrode has a layered structure including: a stretchable substrate; and a pH sensing element layer deposited on the stretchable substrate. 12. The skin-adhesive smart breathable bandage of claim 1, wherein the one or more biosensors include a thermal sensor attached to the permeable stretchable circuit board. 13. A method for manufacturing the skin-adhesive smart breathable bandage of claim 1, the method comprising: manufacturing the bioelectric interface membrane; manufacturing the stretchable circuit assembly; attaching the bioelectric interface membrane to the bottom side of the stretchable circuit assembly; and covering the top side of the stretchable circuit assembly with a protective film. 14. The method of claim 13, wherein the bioelectric interface membrane is manufactured by: preparing a first syringe containing an SEBS precursor solution and a second syringe containing a GelMA solution loaded with a drug; connecting the first syringe and the second syringe to a dual-channel injection pump to simultaneously eject SEBS fibers and GelMA fibers; co-electrospinning the SEBS fibers and the GelMA fibers onto a metal foil covering a rotating drum to form a fiber membrane composed of the SEBS fibers and the GelMA fibers; immersing the fiber membrane in a solution of 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone under UV light to crosslink the GelMA fibers in the fiber membrane; peeling the fiber membrane off the metal foil; immersing the fiber membrane in a solution of silver nanoparticles to load silver nanoparticles into the fiber membrane; and immersing the fiber membrane in tannic acid to form the bioelectric interface membrane; The bioelectric interface membrane is modified with tannins, contains catechol and pyrogallol, and adheres to the skin through multiple synergistic reactions, including hydrogen bonding and Schiff base / Michael addition reactions, electrostatic attraction, and cation-π interactions. 15. The method of claim 13, wherein the stretchable circuit assembly is manufactured by: forming a stretchable SEBS / Au electrode; forming a sensor electrode based on the stretchable SEBS / Au electrode; and bonding the sensor electrode and the electronic component to the stretchable circuit board; wherein the stretchable SEBS / Au electrode is formed by: pre-stretching a SEBS film; depositing a first layer of Cr / Au on the SEBS film; and peeling off the SEBS film;A second Cr / Au layer is deposited on the first Cr / Au layer to form a stretchable SEBS / Au layer; and the stretchable SEBS / Au layer is patterned to form the stretchable SEBS / Au electrode. Claims 2 / 3, page 3, CN 121445557 A Skin-Adhesive Smart Breathable Bandage Technology Field

[0001] This invention generally relates to smart wound management technology. More specifically, this invention relates to a smart skin-adhesive, highly integrated, permeable electronic bandage. Background Art

[0002] Chronic wounds are often caused by diabetic ulcers, unhealed surgical incisions, and venous ulcers, frequently resulting in severe bacterial infection and impaired healing, leading to unbearable pain and a significant financial burden for patients. The healing of chronic wounds involves several stages of hemostasis, inflammation, new tissue formation, and remodeling, and each stage can be affected by a variety of environmental and physiological factors. Typically, these factors and the state of wound healing can be inferred from the dynamic changes in wound exudate. For example, studies have shown that wound healing is accompanied by a decrease in the pH of the exudate from alkaline to neutral, and that the skin temperature around acute wounds rises in the first few days after infection. Furthermore, monitoring the glucose concentration in wound exudate helps regulate blood sugar in diabetic patients, thereby reducing the risk of infection.

[0003] Clinically, various wound dressings (such as gauze dressings, foam dressings, alginate dressings) are always prepared to meet a variety of needs, including absorbing excess wound exudate, maintaining a moist environment, preventing wound infection, and wearing comfort. Although these wound dressings can meet the needs of various types of wounds, it is inevitable to combine multiple wound dressings for complex wounds, which will greatly increase medical costs and healing time. In addition, patients with severe open ulcers (such as venous ulcers, diabetic ulcers, and pressure ulcers) may not respond to conventional treatments, thus requiring additional interventions, such as skin grafts, to achieve wound healing. Current digital wound dressings have integrated wireless communication and biosensors, but these wireless communication and biosensors are always characterized by large size, poor mechanical properties, and the stretchability of rigid batteries. While these commonly used batteries (such as lithium-ion batteries) can provide sufficient power for remote communication and data processing, rigid packaging and potential safety risks limit their application in epidermal, soft, and bio-integrated electronic devices. Most digital wound dressings have a single functional mechanism, monitoring or promoting healing. These effects are typically passive and cannot respond to or adjust to dynamic changes in the wound microenvironment. Summary of the Invention

[0004] To address the above needs, the present invention provides an ultra-thin, battery-free, skin-adhesive, permeable, waterproof,A stretchable, antibacterial, and multifunctional electronic intelligent wound management system is available, capable of in-situ wound monitoring, accelerated wound healing, and intelligent wound treatment. The intelligent wound management system provided by this invention is ultra-thin, with a thickness similar to the epidermis and excellent skin adhesion, adapting to skin deformation. The intelligent wound management system not only exhibits the same functions as human skin in terms of permeability, stretchability, and adaptability, but also encompasses properties including antibacterial capabilities, hemostasis, water retention, and healing promotion. Powered by wireless communication and near-field communication (NFC), the battery-free intelligent wound management system can monitor wound conditions in real time and in situ by combining stretchable, state-of-the-art biosensors to assess glucose levels, pH, and temperature (Tem) in wound exudate, and thus simultaneously adjust treatment to avoid wound infection. Extensive in vitro and in vivo evaluations have demonstrated the intelligent wound management system's ability to monitor wound conditions and accelerate wound healing.

[0005] Utilizing a cutting-edge bioelectronic integration strategy, NFC technology, and microelectronic manufacturing methods, the intelligent wound management system can adhere to the wound site and achieve wireless communication and data transmission with intelligent terminals (such as smartphones) without any battery power source. The bioelectric interface membrane integrates basic bioactive properties, including biocompatibility, skin adhesion, antibacterial activity, hemostasis, breathability, and waterproofness, all of which passively enhance wound healing and infection prevention. Biosensors monitor the wound's glucose, pH, and temperature in situ, providing crucial insights into the wound's condition. Simultaneously, a smart terminal can power the intelligent wound management system for intelligent adaptive, on-demand drug delivery and wound treatment in the event of wound infection.

[0006] When a wound becomes infected, the intelligent wound management system can achieve adaptive drug delivery and on-demand treatment by assessing the wound infection status. Furthermore, the intelligent wound management system incorporates significant features including permeability, adaptability, biocompatibility, skin adhesion, hemostasis, antibacterial properties, and waterproofness to prevent wound infection and improve wearing comfort, water retention, hydrophilicity, and accelerated cell migration properties to maintain a moist wound environment and promote wound healing.

[0007] According to a first aspect of the invention, a skin-adhesive intelligent breathable bandage is provided. The bandage comprises: a stretchable, adhesive antimicrobial bioelectric interface membrane made of stretchable, adhesive antimicrobial fibers; a waterproof and breathable protective membrane for protecting the wound from external contamination; and a permeable and stretchable circuit assembly disposed between the bioelectric interface membrane and the protective membrane. The permeable and stretchable circuit assembly comprises: a permeable and stretchable circuit board; one or more biosensors.The one or more biosensors are constructed on the permeable and stretchable circuit board; and electronic components are assembled on the permeable and stretchable circuit board. The electronic components include: a physiological signal processing module electrically coupled to the one or more biosensors for in-situ wound monitoring; and a drug delivery actuation module electrically coupled to the bioelectric interface membrane for adaptive drug delivery for wound treatment.

[0008] Preferably, the stretchable and adhesive antimicrobial bioelectric interface membrane is a fiber membrane, which is made by co-electrospinning styrene-ethylene-butene-styrene (SEBS) fibers and antibiotic-loaded gelatin methacrylate (GelMA) fibers.

[0009] Preferably, the weight ratio of the SEBS fibers to the GelMA fibers is 1:1.

[0010] Preferably, the bioelectric interface membrane is modified with tannic acid, contains catechol and pyrogallol, and adheres to the skin through multiple synergistic reactions, including hydrogen bonding and Schiff base / Michael addition reactions, electrostatic attraction, and cation-π interactions.

[0011] Preferably, the fiber membrane is loaded with conductive nanoparticles.

[0012] Preferably, the conductive nanoparticles are silver nanoparticles.

[0013] Preferably, the bandage further includes a wireless energy harvesting and communication module for enabling the skin-adhesive smart breathable bandage to communicate with a remote device to facilitate battery-free remote diagnosis and treatment of wounds.

[0014] Preferably, the drug delivery actuation module includes: at least one pair of drug delivery electrodes for applying a drug delivery voltage to the bioelectric interface membrane; and a switch connected to the drug delivery electrodes and configured to turn the drug delivery voltage on / off.

[0015] Preferably, the bandage further includes a microcontroller unit electrically connected to the drug delivery actuation module and configured to adjust the drug delivery amount by controlling the duration of the drug delivery voltage being applied.

[0016] Preferably, the one or more biosensors include a glucose sensor having at least one stretchable working electrode attached to the permeable stretchable circuit specification page 2 / 12 6 CN 121445557 A plate; the working electrode has a layered structure comprising: a stretchable substrate; a mediator layer deposited on the stretchable substrate; a glucose sensing element layer deposited on the mediator layer; and a retention material layer deposited on the glucose sensing element layer.

[0017] Preferably, the one or more biosensors include a pH sensor having at least one stretchable working electrode attached to the permeable stretchable circuit board; and the working electrode has a layered structure including: a stretchable substrate; and a pH sensing element layer deposited on the stretchable substrate.

[0018] Preferably, the one or more biosensors include a thermal sensor attached to the permeable stretchable circuit board.

[0019] According to a second aspect of the invention, a method for manufacturing a skin-adhesive smart breathable bandage according to the first aspect is provided. The method includes: manufacturing the bioelectric interface membrane; manufacturing the stretchable circuit assembly; attaching the bioelectric interface membrane to the bottom side of the stretchable circuit assembly; and covering the top side of the stretchable circuit assembly with a protective film.

[0020] Preferably, the bioelectric interface membrane is manufactured by: preparing a first syringe containing an SEBS precursor solution and a second syringe containing a GelMA solution loaded with a drug; connecting the first and second syringes to a dual-channel injection pump to simultaneously eject SEBS fibers and GelMA fibers; electrospinning the SEBS fibers and the GelMA fibers onto a metal foil covering a rotating drum to form a fiber membrane composed of the SEBS fibers and GelMA fibers; and immersing the fiber membrane in a 2-hydroxy-4'- ionomer solution under UV light. In a solution of (2-hydroxyethoxy)-2-methylphenylacetone, GelMA fibers in the fiber membrane are crosslinked; the fiber membrane is peeled off from the metal foil; the fiber membrane is immersed in a solution of silver nanoparticles to load silver nanoparticles onto the fiber membrane; and the fiber membrane is immersed in tannic acid to form the bioelectric interface membrane; the bioelectric interface membrane is modified with tannic acid, contains catechol and pyrogallol, and adheres to the skin through multiple synergistic reactions including hydrogen bonding and Schiff base / Michael addition reaction, electrostatic attraction, and cation-π interaction.

[0021] Preferably, the stretchable circuit assembly is manufactured by: forming a stretchable SEBS / Au electrode; forming a sensor electrode based on the stretchable SEBS / Au electrode; and combining the sensor electrode and the electronic component on the stretchable circuit board. Preferably, the stretchable SEBS / Au electrode is formed by: pre-stretching a SEBS film; depositing a first Cr / Au layer on the SEBS film; peeling off the SEBS film; depositing a second Cr / Au layer on the first Cr / Au layer to form a stretchable SEBS / Au layer; and patterning the stretchable SEBS / Au layer to form the stretchable SEBS / Au electrode.

[0022] Compared to conventional wound dressing methods, especially for complex wounds at joint locations, the application of the intelligent wound management system is more convenient, comfortable, and efficient, eliminating the need for bandages and large amounts of dressings, thus not hindering the patient's daily activities and quality of life.

[0023] Due to its skin-adhesive and ultra-thin characteristics, the intelligent wound management system can seamlessly adhere to different body locations, particularly joints (such as the wrist) and bones (such as the scapula), and achieves conformal contact and arbitrary deformation with the skin through sensor data acquisition, wireless communication, and programmed voltage modulation using NFC technology for in-situ wound monitoring and adaptive treatment. Since each component layer is stretchable, the intelligent wound management system can be bent, twisted, and stretched to adapt to real-world body monitoring. Specification 3 / 12 Page 7 CN 121445557 A Brief Description of the Drawings

[0024] Embodiments of the invention are described in more detail below with reference to the accompanying drawings, in which:

[0025] FIG1A shows a schematic diagram of an intelligent wound management (iSAFE) system (or intelligent adhesive bandage) according to an embodiment of the invention, the iSAFE system being adhered to the skin and operated by a remote device; and FIG1B shows a schematic diagram demonstrating how a drug is released into the wound through a bioactive interface membrane (SA2EF).

[0026] FIG2 is a block diagram showing the key components of the intelligent wound management system.

[0027] FIG3 shows an exploded view showing the layered structure of the intelligent wound management system.

[0028] FIGS4A to 4C show the layout of a stretchable conductive trace layer of a permeable stretchable circuit board according to an embodiment.

[0029] FIG5 shows the electrode layout of the working electrodes (i.e., thermal sensors, pH sensors, and glucose sensors), the counter electrode (CE), and the reference electrode (RE).

[0030] Figures 6A to 6C show the layered structures of the working electrode and reference electrode of the glucose sensor and pH sensor, respectively.

[0031] Figure 7 shows a flowchart of a method for manufacturing an intelligent wound management system according to an embodiment of the present invention.

[0032] Figure 8 shows a schematic diagram of the manufacturing process flow of a bioelectric interface membrane according to an embodiment of the present invention.

[0033] Figure 9A shows the front plane of a vertical integration method for manufacturing a stretchable circuit assembly. Figures 9B and 9C show the front plane and bottom view of the connection point between the Cu trace and the sensor electrode.

[0034] Figure 10 shows an optical image of a prototype of the stretchable circuit assembly.

[0035] Figure 11 shows a schematic diagram of the manufacturing process for the stretchable electrode used in the subsequent construction of a biosensor.

[0036] Figure 12 shows the XRD patterns of SEBS, GelMA, SEBS / GelMA, and SA2EF electrospun membranes;

[0037] Figure 13 shows the electrical conductivity of SA2EF with different SEBS and GelMA ratios.

[0038] Figure 14A shows the stress-strain curves of electrospun films of blends with different SEBS and GelMA ratios and optimized SA2EF; Figure 14B shows the stress-strain curves of S / G fibers with GelMA and a content ratio of 1:1.

[0039] Figure 15A shows the resistivity response of BEWI subjected to 10%, 30%, and 50% strain over time; Figure 15B shows the time-dependent resistivity response of BEWI under more than 600 repeated 50% cyclic stretching;

[0040] Figure 16A shows the mass loss of electrospun SEBS, GelMA, SEBS / GelMA, and SA2EF films; Figure 16B shows the water vapor transmission rate of electrospun SEBS, GelMA, SEBS / GelMA, and SA2EF films; Figure 16C shows the water loss of electrospun SEBS, GelMA, SEBS / GelMA, and SA2EF films; Figure 16D shows a schematic diagram of the principle of skin adhesion of SA2EF.

[0041] Figures 17A and 17B show optical images and schematic diagrams of peel and shear tests; Figures 17C and 17D show a comparison of peel strength and shear stress between SA2EF and commercial fibrin glue.

[0042] Figure 18 shows live / dead staining of NIH / 3T3 cells cultured for 24, 48, and 72 hours using control material, SEBS / GelMA, and SA2EF.

[0043] Figure 19A shows cell viability calculated based on live / dead staining images; Figure 19B shows cell proliferation assessment by CCK-8 assay.

[0044] Figure 20 shows scratch assay analysis of the migration ability of NIH / 3T3 cells pretreated with SA2EF.

[0045] Figures 21A and 21B show images of E. coli and Staphylococcus aureus colonies cultured with different materials on LB agar plates.

[0046] Figures 22A and 22B show quantitative assessments of bacterial colonies and antibacterial rates for various materials. Instruction manual, page 4 / 12, CN 121445557 A

[0047] Figure 23A shows a comparison of the resistance response between a normal SEBS / Au electrode and a pre-stretched SEBS / Au electrode at different strain levels; Figure 23B shows the time-dependent resistance response of a stretchable SEBS / Au electrode subjected to 500 cycles of continuous 30% strain.

[0048] Figure 24A shows the time-dependent rate of change of resistance of the SEBS / Au electrode subjected to continuous friction with a glass rod; Figure 24B shows the resistance value of the SEBS / Au electrode as a function of friction cycles. After continuous dynamic friction, the resistance value of the electrode changes with the initial resistance.The initial resistance values ​​were basically the same, thus proving the stability of the conductive SEBS / Au electrode.

[0049] Figures 25A to 25C show the responses of the glucose sensor, pH sensor, and temperature sensor over time, respectively.

[0050] Figures 26A to 26C show the corresponding calibration curves of the glucose sensor, pH sensor, and temperature sensor.

[0051] Figure 27A shows the live / dead staining of NIH / 3T3 cells cultured for 24, 48, and 72 hours using the pH sensor, glucose sensor, and temperature sensor; Figure 27B shows the cell viability calculated based on the live / dead staining images; Figure 27C shows the cell proliferation assessment by the CCK-8 assay.

[0052] Figure 28A shows optical images of iSAFE adhered to rats with chronic wounds on their backs for in situ wound monitoring and to accelerate wound healing; Figure 28B shows a timeline of in vivo studies of the wound infection model; Figure 28C shows optical images and schematic diagrams of infected wounds in diabetic rats using three different wound dressings; Figure 28D shows the change in relative wound size over days in diabetic rats using three different wound dressings; Figures 28E to 28G show the changes in glucose concentration, pH, and temperature over days in wound exudate from diabetic rats using three different wound dressings; Figure 28H shows optical images of colonies from infected wounds in diabetic rats.

[0053] Figure 29A shows optical images of hematoxylin and eosin (H&E) staining and Masson's trichrome (MT) staining of wounds in diabetic rats using three different wound dressings after 14 days of treatment. Figures 29B to 29D show epidermal thickness, wound area length, and epithelial regeneration of wounds using three different wound dressings after 6-day and 14-day treatment, and quantitative analysis of H&E staining after 14 days; Figures 29E to 29G show appendage counts, scar elevation index, and collagen density of wounds using three different wound dressings after 14-day treatment, and quantitative analysis of MT staining; Figures 29H and 29I show optical images of wounds using three different wound dressings after 6-day treatment with IHC staining; Figures 29J and 29K show quantitative analysis of IHC staining. Detailed Description

[0054] In the following description, details of the invention are set forth as preferred embodiments. It will be apparent to those skilled in the art that modifications, including additions and / or substitutions, can be made without departing from the scope and spirit of the invention. Specific details may be omitted so as not to obscure the invention; however, this disclosure is prepared to enable those skilled in the art to practice the teachings herein without requiring extensive experimentation.

[0055] Figure 1A illustrates an intelligent wound management (iSAFE) system (or intelligent adhesion) according to an embodiment of the present invention.Figure 1A is a schematic diagram of a bandage, wherein the iSAFE system adheres to the skin and is operated by a remote device; and Figure 1B shows a schematic diagram illustrating how medication is released into the wound through the intelligent wound management system. Figure 2 is a block diagram illustrating the key components of the intelligent wound management system. Figure 3 shows an exploded view illustrating the layered structure of the intelligent wound management system.

[0056] The intelligent wound management system is characterized by an ultra-thin, highly adhesive, multi-layered stacked structure, including a bioelectric interface layer 101; a waterproof and breathable protective membrane 102; and a permeable and stretchable circuit assembly 103 disposed between the bioelectric interface membrane 101 and the protective membrane 102.

[0057] In some embodiments, the bioelectric interface membrane 101 is a stretchable and adhesive antibacterial membrane, which is made by co-electrospinning styrene-ethylene-butene-styrene (SEBS) fibers and gelatin methacrylate (GelMA) fibers loaded with antibiotics and conductive nanoparticles. Preferably, the GelMA fibers in the stretchable, adhesive antimicrobial electrospun fibers contain hydroxyl groups, which are crosslinked with amine groups in the skin via hydrogen bonds. Preferably, the weight ratio of SEBS to GelMA is 1:1 to achieve a balanced mechanical and biological performance. Preferably, the conductive nanoparticles may be, but are not limited to, silver, gold, or platinum nanoparticles.

[0058] The permeable and stretchable circuit assembly 103 includes a permeable and stretchable circuit board; and one or more biosensors 104 constructed on the permeable and stretchable circuit board. In some embodiments, the one or more biosensors may include a glucose sensor 401, a pH sensor 402, and a thermal sensor 403 for in-situ monitoring of glucose, pH, and / or temperature (Tem) of the wound, thereby providing key insights into the wound condition.

[0059] The permeable and stretchable circuit assembly 103 further includes electronic components 105 assembled on the permeable and stretchable circuit board 103. The key electronic components 105 of the intelligent wound management system include a microcontroller unit (MCU) 501, a memory (not shown), a wireless power harvesting and communication module 502, a drug delivery actuation module 503 electrically coupled to a bioelectric interface membrane for adaptive drug delivery to treat wounds, and a physiological signal processing module 504 electrically coupled to one or more biosensors 104 for in-situ wound monitoring.

[0060] The MCU 501 can communicate with the memory and is configured to process and store data acquired from the biosensors 104. The power harvesting and communication module 502 may include an NFC circuit chip for enabling battery-free wireless power and data transmission, thereby allowing the entire circuit to be activated simultaneously and facilitating remote diagnosis and treatment of wounds when a smartphone is near the intelligent wound management system.

[0061] The drug delivery actuation module 503 may include at least one pair of drug delivery electrodes and a switch for switching on / off a drug delivery voltage applied to the bioelectric interface membrane 101 through the drug delivery electrodes for adaptive therapy and drug delivery. In some embodiments, the switch may be a semiconductor switching device, such as, but not limited to, an N-type MOSFET (BSS138BKVL, Nexperia).

[0062] Figures 4A to 4C show the layout of a stretchable conductive trace layer of a permeable stretchable circuit board according to one embodiment. The first and second trace layouts are traces for connecting and routing battery-free functional circuitry for intelligent wound monitoring and therapy. The third trace layout is a trace for connecting and routing drug delivery electrodes, sensor electrodes, and electronic components. The entire circuit board is small, measuring 51.69 mm × 28.05 mm.

[0063] Referring to Figure 5, the glucose sensor may include a working electrode (WE1), a counter electrode (CE), and a reference electrode (RE), configured to generate a current output related to the glucose concentration in the wound. The pH sensor may include a working electrode (WE2) and share a reference electrode with the glucose sensor, and is configured to generate a voltage output related to the pH value of the wound; and the thermal sensor may be implemented using a resistance temperature detector (RTD) (e.g., NCP15WF104F03RC).

[0064] Referring to FIG6A, the working electrode (WE1) of the glucose sensor may have a layered structure comprising: a stretchable substrate 601; a mediator layer 602 deposited on the stretchable substrate 601; a glucose sensing element 603 layer deposited on the mediator layer 602; and a retention material 604 layer deposited on the glucose sensing element 603 layer. Referring to FIG6B, the working electrode (WE2) of the pH sensor may have a layered structure comprising: a stretchable substrate 601; and a pH sensing element 605 layer deposited on the stretchable substrate 601. The reference electrode may have a stretchable layered structure comprising: a stretchable substrate 601; and an Ag / AgCl layer 606 deposited on the stretchable substrate 601.

[0065] In some embodiments, the stretchable substrate electrode 601 may be made of any suitable type of stretchable material, such as, but not limited to, SEBS, and coated with a conductive material, such as gold, silver, copper, or platinum. The mediator layer 602 may be made of any suitable type of mediator material suitable for implantable devices, such as, but not limited to, Prussian blue (see specification page 6 / 12, 10 CN 121445557 A), carbon nanomaterials (such as graphene, carbon nanotubes). The glucose sensing element 603 may be a glucose desaturation...The hydrogenase is glucose oxidase. The retention material 604 can be chitosan or any suitable type of retention material suitable for implantable devices. The pH sensing element 605 can be made of IrOx, polyaniline, or any suitable type of pH sensing element having excellent biocompatibility for implantable or clinical applications.

[0066] Measurements of glucose concentration, pH, and temperature are performed based on potentiostatic methods, open-circuit voltage (OCV) methods, and voltage divider methods, respectively. More specifically, the physiological signal processing module 504 may include a potentiostat, which is a three-electrode electrochemical interface enabling rapid detection of glucose potency.

[0067] In one embodiment, the potentiostat interface (or physiological signal processing module) 504 may be constructed using a dual operational amplifier (e.g., AD8606, Analog Devices) and a digital-to-analog converter (DAC) (e.g., MCP47CVB12-E / MF, Microchip Technology). The dual operational amplifier is used to implement three-electrode system performance and current-to-voltage conversion. Simultaneously, the DAC enables the differential pulse voltammetry (DPV) dynamic excitation signal to bias the reference electrode and the working electrode. The analog signal from the sensor is then converted into a digital signal by the analog-to-digital converter (ADC) 505 inside the MCU 501. When the sensor results are delivered from the MCU via the internal integrated circuit, the NFC chip can transmit the data to the smartphone via the radio frequency (RF) interface when the smartphone is near.

[0068] Referring back to FIG1B, when an infection occurs and is detected by the biosensor, the anti-infective drug (such as antibiotic) contained in the intelligent wound management system is released into the wound by applying a voltage to the bioelectric interface through the drug delivery electrode. The amount of drug released / delivered can be adjusted by the (MCU) by controlling the product of the applied voltage and the time period during which the applied voltage is on, while when no voltage is applied, the amount is negligible. In this way, the amount released can be intelligently controlled by the wound condition assessed by the biosensor, and thus prevents the overuse and abuse of drugs.

[0069] FIG7 shows a flowchart of a method S100 for manufacturing an intelligent wound management system according to an embodiment of the present invention. Method S100 includes:

[0070] S101: preparing a bioelectric interface membrane;

[0071] S102: manufacturing a stretchable circuit assembly;

[0072] S103: attaching the bioelectric interface membrane to the bottom side of the stretchable circuit assembly; and

[0073] S105: covering the top side of the stretchable circuit assembly with a protective film.

[0074] A plurality of holes (as shown in FIG. 5) corresponding to the positions of the working electrodes of the sensor are formed (e.g., by laser cutting) on ​​the bioelectric interface membrane 101 to expose the working electrodes so that the working electrodes can directly contact wound exudate without...This negatively impacts the functionality of SA2EF. A pore can be formed on the bioelectric interface membrane before it is attached to the stretchable circuit assembly.

[0075] Figure 8 shows a schematic diagram of the manufacturing process flow of a bioelectric interface membrane according to an embodiment of the present invention. As shown in the figure, the manufacturing process includes the following steps:

[0076] S201: Prepare a first syringe containing a SEBS precursor solution and a second syringe containing a GelMA solution loaded with the drug; connect the first syringe and the second syringe to a dual-channel injection pump to simultaneously eject SEBS fibers and GelMA fibers; and co-electrospin the SEBS fibers and GelMA fibers onto a metal foil covering a rotating drum to obtain a fiber membrane composed of SEBS fibers and GelMA fibers;

[0077] S202: Under UV light irradiation, immerse the fiber membrane in a solution of 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone (photoinitiator 2959, 8 wt.%) to crosslink the GelMA fibers; and then peel the fiber membrane off from the metal foil;

[0078] S203: Immerse the S / G fiber membrane in a silver nanoparticle solution (e.g., Ag NO3) to load the silver nanoparticles onto the cured S / G fiber membrane; Specification 7 / 12 pages 11 CN 121445557 A

[0079] S204: Immersing an S / G fiber membrane loaded with silver nanoparticles in a polyphenol solution (e.g., tannic acid) to form a bioelectric interface membrane, wherein the bioelectric interface membrane is modified with tannic acid, contains catechol and pyrogallol, and adheres to the skin through multiple synergistic reactions including hydrogen bonding and Schiff base / Michael addition reactions, electrostatic attraction, and cation-π interactions.

[0080] More specifically, the SEBS precursor solution is obtained by dissolving SEBS (80 wt.%) and F127 (20 wt.%) in chloroform (80 wt.%) and toluene (20 wt.%). The drug-loaded GelMA solution is a GelMA / antibiotic solution containing 10 wt.% GelMA and 0.2 wt.% penicillin sodium in hexafluoroisopropanol.

[0081] Both syringes have a capacity of 20 mL and are equipped with 21G metal nozzles. SEBS fibers and GelMA fibers are ejected from the syringes at flow rates of 0.8 ml / h and 1.0 ml / h, respectively. The nozzles of both syringes are configured to have a lateral (x-axis) sliding speed between 10 mm / s and 12 mm / s to ensure uniform distribution of the fiber pads.

[0082] For the co-electrospinning of SEBS and GelMA fibers, a positive electrode is attached to the nozzles of the two syringes to respectively...The SEBS precursor solution and the drug-loaded GelMA solution are subjected to a voltage ranging from 18kV to 23kV. The metal foil is aluminum foil. The rotating drum has a diameter of 10cm and is set to rotate at a speed of 90 to 100 rpm, and is positioned 15cm from the nozzle tip. The entire electrospinning process takes more than 12 hours.

[0083] Figure 9A shows the front plane of the vertical integration method for manufacturing the stretchable circuit assembly. Figures 9B and 9C show the front plane and bottom view of the connection point between the Cu trace and the sensor electrode. The three-layer circuit and electrode are vertically connected by advanced manufacturing techniques for highly integrated, small-size and ultra-thin skin electronics with permeable and waterproof encapsulation, resulting in a stretchable circuit assembly with excellent flexibility and an ultra-thin thickness of 140μm (Figure 10).

[0084] More specifically, the manufacturing process of the stretchable circuit assembly may include the following steps:

[0085] S301: forming a first Tegaderm / Cu trace layer having a first Cu trace layout (e.g., the Cu trace layout shown in FIG. 4A);

[0086] S302: forming a second Tegaderm / Cu trace layer having a second Cu trace layout (e.g., the Cu trace layout shown in FIG. 4B);

[0087] S303: bonding the first Tegaderm / Cu trace layer and the second Tegaderm / Cu trace layer to form a stretchable circuit board having a first Cu trace on its top surface and a second Cu trace on its bottom surface (FIG. 9A); and forming connection holes on the stretchable circuit board to provide electrical interconnection between the first Cu trace and the second Cu trace; wherein the connection holes may be formed by laser cutting, thereby filling the laser-cut holes with Ag paste; and applying a Sil-Poxy protective layer onto the filled Ag paste;

[0088] S304: Deposit PI / Cu sheet onto an aqueous strip; laser cut PI / Cu sheet to form a third conductive trace and repair hole; fill the repair hole with Ag paste for subsequent connection between Cu trace and sensor; apply Sil-Poxy protective layer onto the filled Ag paste;

[0089] S305: Transfer the third conductive trace onto the bottom surface of the stretchable circuit board;

[0090] S306: Combine and electrically connect (e.g., via low-temperature solder joints) the stretchable sensor electrodes (FIGs 9B and 9C) and electronic components on the stretchable circuit board; and attach a Tegaderm encapsulation layer to the top of the electronic components.

[0091] The fabrication process of each Tegaderm / Cu trace layer may include the following steps:

[0092] S401: Attach a Tegaderm layer onto a support substrate;

[0093] S402: Deposit PI / Cu sheet onto a first Tegaderm layer;

[0094] S403: The PI / Cu sheet is patterned by photolithography and wet etching to obtain a Tegaderm / Cu trace layer.

[0095] The stretchable sensor electrode is fabricated by using a pre-stretching strategy on an electrospun SEBS fiber film to ensure that the electrode is conductive even in a stretched state. Figure 11 shows a schematic diagram of the fabrication process for the stretchable electrode used in the subsequent construction of the biosensor. First, the electrospun SEBS fiber film is pre-stretched (e.g., 50%), and then a first layer of Cr (10 nm) / Au (100 nm) is deposited by sputtering. Next, the pre-stretched film is peeled off, and then a second layer of Cr / Au is deposited (on top of the first layer of Cr / Au) to form a stretchable SEBS / Au layer. Then, the SEBS / gold layer is patterned by laser cutting to form a stretchable SEBS / Au electrode.

[0096] Modifying the corresponding SEBS / Au electrode into a working electrode for a glucose biosensor includes the following steps:

[0097] S501: In a mixed solution of 2.5 mM ferric chloride (FeCl3), 100 mM potassium chloride (KCl), 2.5 mM potassium ferricyanide (K3Fe(CN)6), and 100 mM hydrogen chloride (HCl), a layer of Prussian blue is electrodeposited onto the corresponding SEBS / Au electrode by cyclic voltammetry at 0 V to 0.5 V for 5 cycles;

[0098] S502: A mixture of 2 μL GOx (5 U / μl), 1 μL bovine serum albumin (BSA, 2 mg / mL), and 2 μL glutaraldehyde (GA, 2%) is impregnated onto the electrode;

[0099] S503: The electrode is stored overnight in a refrigerator at 4 °C; and

[0100] S504: Drop 2 μL of chitosan (2%) onto the electrode used for enzyme immobilization.

[0101] Modify the corresponding SEBS / Au electrode into the working electrode of the pH sensor by electrodeposition electrolyte, and electrodeposit IrOx onto the SEBS / Au electrode at a constant voltage of 0.7 V for 45 minutes. The electrodeposition electrolyte was prepared as follows:

[0102] S601: 300 mg iridium tetrachloride was dissolved in 200 mL deionized (DI) water to form the existing solution;

[0103] S602: 2 mL hydrogen peroxide (H2O2) was added to the existing solution with continuous stirring;

[0104] S603: 1000 mg oxalate dihydrate was added with continuous stirring;

[0105] S604: A small amount of anhydrous potassium carbonate was introduced into the continuously stirred solution to adjust the pH of the solution to 10.5;

[0106] S605: The pH-adjusted solution was stored at ambient room temperature for 48 hours to stabilize.

[0107] Modifying the corresponding SEBS / Au electrode into a reference electrode included adding 10 μL of...0.1M FeCl3 was injected onto the electrode to obtain an Ag / AgCl layer on the SEBS / gold electrode.

[0108] Characterization of the bioelectric interface membrane (SA2EF)

[0109] As shown in Figure 12, X-ray diffraction (XRD) analysis showed that characteristic diffraction peaks at 38.1, 44.3, and 64.6 corresponding to the (111), (200), and (220) crystal planes were present in the SA2EF, indicating that tannic acid-mediated AgNP was successfully synthesized.

[0110] To optimize the performance of SA2EF, the effect of the SEBS to GelMA fiber ratio on conductivity was explored. As shown in Figure 13, all SA2EFs with different SEBS to GelMA ratios showed a high conductivity of approximately 0.52 S / m, indicating that the conductivity depends mainly on the loading of Ag NP, rather than the SEBS / GelMA (S / G) ratio.

[0111] Figures 14A and 14B show the stress-strain curves of GelMA, S / G fibers with different content ratios, and SA2EF. Clearly, the co-electrospinning strategy greatly improves the fiber's stretchability, and the stretchability increases with increasing SEBS content. Furthermore, the mechanical strength and stretchability of SA2EF (SEBS:GelMA 1:1) are further increased due to the enhanced intermolecular interactions caused by tannic acid.

[0112] Tannic acid is a polyphenolic compound that allows hydroxyl groups in the GelMA polymer chain to crosslink with amine groups in the skin via strong hydrogen bonds. Tannic acid contains catechol and pyrogallol, which form numerous hydrogen bonds with amine (-NH2), amide (-CONH-), and hydroxyl (-OH) groups in skin surface proteins (such as keratin). The amine (-NH2) and hydroxyl (-OH) groups of GelMA can form hydrogen bonds with the phenolic hydroxyl groups of tannic acid (similar to the role of skin proteins), making the tannic acid more stably anchored in the GelMA network. This additional crosslinking via hydrogen bonding produces a denser network structure, thereby improving mechanical properties such as higher tensile strength and stretchability. Specification 9 / 12 pages 13 CN 121445557 A

[0113] Furthermore, the resistance response of the optimized SA2EF under a stretch configuration was tested. As shown in Figures 15A and 15B, the resistance change was negligible at 10% and 30% stretching. Although the resistance of SA2EF changed when stretched to 50%, it recovered to its initial state, and the small fluctuations were insufficient to affect the electrical properties of SA2EF. Furthermore, even after undergoing more than 600 cycles of consecutive 50% stretch deformation, the resistance still exhibited stable recovery.

[0114] In addition, SA2EF showed appropriate biodegradability (approximately 40% mass loss during a 14-day test), water evaporation...Gas permeability (WVTR) (approximately 50 g / m² / h) and swelling capacity (approximately 300%) (Figures 16A to 16C). Due to multiple synergistic interactions including hydrogen bonding and Schiff-base / Michael addition reaction, electrostatic attraction, and cation-π interaction (Figure 16D), SA2EF exhibits good tissue adhesion, conformally attaching to the skin surface even under twisting and bending.

[0115] Quantitative analysis showed that the shear strength and peel strength of SA2EF were significantly higher than those of commercial fibrin glue, thus demonstrating its potential for clinical application (Figures 17A to 17D).

[0116] Next, the in vitro bioactivity of SA2EF was evaluated. First, live / dead staining and cell counting kit-8 (CCK-8) analysis showed favorable biocompatibility of SA2EF, which could promote cell survival and proliferation (Figures 18, 19A, and 19B). Wound healing assays, also known as cell scratch tests, further demonstrated that SA2EF can promote cell migration and accelerate wound healing rates (Fig. 20). Additionally, such composite membranes were found to support cell adhesion and exhibit excellent antibacterial activity (Figs. 21A and 21B, Figs. 22A and 22B), indicating that they can create a beneficial microenvironment for cell growth and showing promising potential as anti-infective wound dressings.

[0117] Characterization of Stretchable Biosensors

[0118] In the conventional design of stretchable biosensors, the connection between the serpentine and the electrode patch is always constructed using an island bridge structure. Although island bridge designs can withstand repeated stretching and bending cycles without risk of breakage, there is always significant strain at the electrode patch site. For high-sensitivity biosensors, even small deformations of the electrode substrate can lead to significant signal fluctuations and potential sensor failure. Due to the superior durability and resistance to physical deformation of stretchable conductive electrodes, their function is biased towards high reliability even under a wide range of dynamic stress conditions; therefore, constructing biosensors for epidermal electronic devices on stretchable conductive electrodes would be an option.

[0119] Based on the pre-stretching strategy, since the conductive fibers remain connected during stretching, electrospun SEBS fibers can maintain stable conductivity during stretching after two sputtering cycles, thereby enhancing the stretchability of multiple biosensors. Even after 500 consecutive stretching cycles, the decrease in conductivity is negligible, and the function of the electrodes will not be affected.

[0120] As shown in Figures 23A and 23B, compared with normally sputtered SEBS fibers, pre-stretched SEBS enables stable resistance even under continuous stretching and friction. Although the resistance value fluctuates during dynamic friction, the sputtering...The conductivity of the laser-cut SEBS fibers remains relatively stable even after 400 cycles, and the resistance remains essentially stable even under tension. The conductive SEBS fiber membrane can be laser-cut into electrodes of different shapes and sizes. In general, such electrodes exhibit excellent durability and resistance to physical deformation, thus maintaining high reliability even under a wide range of dynamic stress conditions.

[0121] Therefore, the glucose sensor and pH sensor modified on the electrodes both exhibit good stretchability and stable output under 30% tension (Figures 24A and 24B). Thanks to the superior performance of the GOx sensing element, the current output of the glucose sensor is linearly correlated with the glucose concentration in the electrolyte. The coefficient of determination (R²) can reach 0.989 in IrOx. Similarly, the IrOx-modified pH sensor can sensitively detect changes in hydrogen ion concentration in the electrolyte, where R² is 0.996. Furthermore, the glucose sensor and pH sensor exhibit excellent anti-interference capability and stability. Instruction manual, pages 10 / 12, 14 CN 121445557 A

[0122] Figures 25A to 25C show the responses of the glucose sensor, pH sensor, and Tem sensor over time, and Figures 26A to 26C show their corresponding calibration curves. As shown in Figures 25A and 26A, at a constant voltage of -0.1V, the current response of the glucose sensor increases with the increase of glucose concentration in the electrolyte, and there is a large linear relationship between the glucose concentration in the electrolyte and the current output of the glucose sensor.

[0123] Since these sensors are designed to monitor wound exudate and will be in direct contact with open tissue, biocompatibility is a primary factor that must be considered first. As shown in Figures 27A to 27C, the NIH / 3T3 cell co-culture results showed that the sensing elements, electrodes, and other components of the glucose sensor, pH sensor, and Tem sensor had no significant cytotoxicity. It is worth mentioning that IrOx was the best choice for the sensing element of the pH sensor compared to inexpensive polyaniline, which has a risk of cytotoxicity, mainly due to its excellent biocompatibility.

[0124] In vivo preclinical studies

[0125] Figures 28A to 28H show the in vivo preclinical evaluation in diabetic rats to test the robustness and efficacy of the intelligent wound management system in wound monitoring and accelerated wound healing. As shown in Figure 28A, the intelligent wound management system can be seamlessly attached to the back of the rat, and the developed state-of-the-art biosensors are able to monitor the wound status via a GUI (Figure 28A). For diabetic rats, bilateral full-thickness excision wounds and E. coli infection (20 μl, 106 CFU / mL) were performed on day -1 (Figure 28B). Here, three different groups were tested to validate the effectiveness of the intelligent wound management system: control group and control group.The groups included a Tegaderm dressing with no controlled drug release, an S / G / P dressing with co-electrospun SEBS / GelMA / drug dressing with no controlled drug release, and a smart wound management system group.

[0126] From day 0 to day 6, glucose levels, pH, and Tem in wound exudate were measured, and wound dressings were changed every two days for each group. For the smart wound management system group, medication was delivered simultaneously if wound infection occurred during measurement. In the early stages, drug treatment and wound dressings played a role in eliminating bacterial infection and modulating the immune response.

[0127] After day 6, a small amount of wound exudate was observed, and sensing and drug treatment were therefore withdrawn. Wound dressings were used to accelerate cell migration and wound healing in the next stage. As shown in Figures 28C and 28D, the highest wound closure rate was observed in the smart wound management system group, while the wound closure rate in the S / G / P group was higher than that in the control group, thus demonstrating the effectiveness of the smart wound management system in promoting healing. The healing-promoting performance of the S / G / P group may be attributed to the presence of GelMA and the drug.

[0128] As shown in Figure 28E, glucose levels in all diabetic rats were stable for the first 6 days. It can be seen that the overall trend of pH and Tem values ​​in the three groups decreased (Figures 28F and 28G), which indicates the emergence of wound healing. The values ​​in the intelligent wound management system group decreased significantly compared to the other groups, demonstrating the excellent antibacterial and healing-promoting capabilities of the intelligent wound management system. Furthermore, compared to the other two groups, mixed bacterial colony cultures of wounds from the three different groups on LB agar plates showed a significant reduction in bacterial growth in the intelligent wound management system group, thus demonstrating the excellent antibacterial properties of SA2EF and the intelligent wound management system (Figure 28H).

[0129] The hemostatic effect of SA2EF was further evaluated using tail and liver hemostasis models. Compared to the control group (without SA2EF), the blood loss in both the tail and liver hemostasis models was much lower, revealing the good hemostatic effect of SA2EF.

[0130] Evaluation of Healing Effect

[0131] To evaluate the healing effect of the three groups of wound dressings, the wounds were stained with hematoxylin and eosin (H&E), massen trichrome (MT), and immunocytochemically analyzed at 6 and 14 days, respectively. On day 14, the wounds in the intelligent wound management system group were almost healed, while partial tissue defects were observed in the other two groups (Fig. 29A). In the H&E staining results of the intelligent wound management system group, mature epithelium, higher epidermal thickness and epithelial regeneration, and shorter wound area were observed (Figs. 29B to 29D). For the quantitative analysis of H&E staining on day 6, it is obvious that the intelligent wound management system group...The wound index of epidermal thickness was significantly higher than that of the control group and the S / G / P group, while the wound area length of the intelligent wound management system group was smaller than that of the other two groups (Figs. 29B and 29C). MT staining images and quantitative analysis results (Figs. 29A and 29E to 29G) showed that the intelligent wound management system group had significantly higher dermal appendage counts and collagen density and lower scar elevation index compared with the other two groups, thus demonstrating granulation tissue formation and uniform dermal repair. Immunohistochemical staining (IHC) analysis (Figs. 29H and 29I) and quantitative analysis results (Figs. 29J and 29K) further demonstrated antibacterial, accelerated cell migration and wound healing capabilities.

[0132] The functional units and modules of the [devices, apparatus, systems, compounds, materials and / or methods] according to the embodiments disclosed herein can be implemented using computing devices, computer processors or electronic circuit systems, including but not limited to application-specific integrated circuits (ASICs), field-programmable gate arrays (FPGAs), microcontrollers and other programmable logic devices configured or programmed according to the teachings of this disclosure. Based on the teachings of this disclosure, those skilled in the art of software or electronics can readily prepare computer instructions or software code to run in a computing device, computer processor, or programmable logic device.

[0133] All or part of the methods according to the embodiments can be performed in one or more computing devices, including server computers, personal computers, laptop computers, mobile computing devices such as smartphones, and tablet computers.

[0134] Embodiments may include computer storage media, transient and non-transient memory devices in which computer instructions or software code are stored, which can be used to program or configure computing devices, computer processors, or electronic circuit systems to perform any of the processes of the present invention. Storage media, transient and non-transient memory devices may include, but are not limited to, floppy disks, optical disks, Blu-ray discs, DVDs, CD-ROMs and magneto-optical disks, ROMs, RAMs, flash memory devices, or any type of medium or device suitable for storing instructions, code, and / or data.

[0135] Each of the functional units and modules according to various embodiments may also be implemented in a distributed computing environment and / or cloud computing environment, wherein all or part of the machine instructions are executed in a distributed manner by one or more processing devices interconnected via a communication network such as an intranet, a wide area network (WAN), a local area network (LAN), the Internet, and other forms of data transmission media.

[0136] Although the present disclosure has been described and illustrated with reference to specific embodiments thereof, such descriptions and illustrations are not limiting. Illustrations may not necessarily be drawn to scale. Due to manufacturing processes and tolerances, artistic representations in this disclosure may differ from actual embodiments.Differences may exist between actual devices. Other embodiments of this disclosure may exist that are not specifically shown. Modifications may be made to suit particular circumstances, materials, composition, methods, or processes to the objectives and scope of this disclosure. All such modifications are intended to fall within the scope of the appended claims. While the methods disclosed herein have been described with reference to specific operations performed in a particular order, it should be understood that these operations may be combined, subdivided, or reordered to form equivalent methods without departing from the teachings of this disclosure. Therefore, the order and grouping of operations are not limiting unless expressly indicated herein. Instruction Manual Page 12 / 12, 16 CN 121445557 A, Figure 1A; Instruction Manual Figure 1 / 33, 17 CN 121445557 A, Figure 1B, Figure 2; Instruction Manual Figure 2 / 33, 18 CN 121445557 A, Figure 3, Figure 4A, Figure 4B; Instruction Manual Figure 3 / 33, 19 CN 121445557 A, Figure 4C, Figure 5, Figure 6A; Instruction Manual Figure 4 / 33, 20 CN 121445557 A, Figure 6B, Figure 6C, Figure 7; Instruction Manual Figure 5 / 33, 21 CN 121445557 A, Figure 8; Instruction Manual Figure 6 / 33, 22 CN 121445557 A, Figure 9A, Figure 9B, Figure 9C, Figure 10; Instruction Manual Figure 7 / 33, 23 CN 121445557 A, Figure 11; Instruction Manual Figure 8 / 33, 24 CN 121445557 Figure 12 Figure 13 Figure 14A Instruction Manual Drawings 9 / 33 Page 25 CN 121445557 Figure 14B Figure 15A Instruction Manual Drawings 10 / 33 Page 26 CN 121445557 Figure 15B Figure 16A Figure 16B Instruction Manual Drawings 11 / 33 Page 27 CN 121445557 Figure 16C Figure 16D Figure 17A Instruction Manual Drawings 12 / 33 Page 28 CN 121445557 Figure 17B Figure 17C Instruction Manual Drawings 13 / 33 Page 29 CN 121445557 Figure 17D Figure 18 Instruction Manual Drawings 14 / 33 Page 30 CN 121445557 Figure 19A Figure 19B Instruction Manual Drawings 15 / 33 Page 31 CN 121445557 Figure 20 Figure 21A Figure 21B Figure 22A Instruction manual drawings, page 16 / 33, CN 121445557 A, Figure 22B, Figure 23A, Figure 23B.Page 17 / 33, 33 CN 121445557 A, Figure 24A, Figure 24B, Instruction Manual Drawings; Page 18 / 33, 34 CN 121445557 A, Figure 25A, Figure 25B, Instruction Manual Drawings; Page 19 / 33, 35 CN 121445557 A, Figure 25C, Figure 26A, Instruction Manual Drawings; Page 20 / 33, 36 CN 121445557 A, Figure 26B, Figure 26C, Instruction Manual Drawings; Page 21 / 33, 37 CN 121445557 A, Figure 27A, Figure 27B, Instruction Manual Drawings; Page 22 / 33, 38 CN 121445557 A, Figure 27C, Figure 28A, Instruction Manual Drawings; Page 23 / 33, 39 CN 121445557 A, Figure 28B, Figure 28C, Instruction Manual Drawings; Page 40 CN 121445557 A, Figure 28D, Figure 28E. Instruction manual figures 25 / 33, page 41, CN 121445557 A, Figure 28F, Figure 28G; Instruction manual figures 26 / 33, page 42, CN 121445557 A, Figure 28H; Instruction manual figures 27 / 33, page 43, CN 121445557 A, Figure 29A; Instruction manual figures 28 / 33, page 44, CN 121445557 A, Figure 29B, Figure 29C; Instruction manual figures 29 / 33, page 45, CN 121445557 A, Figure 29D, Figure 29E; Instruction manual figures 30 / 33, page 46, CN 121445557 A, Figure 29F, Figure 29G; Instruction manual figures 31 / 33, page 47, CN 121445557 A, Figure 29H, Figure 29I; Instruction manual figures 32 / 33, page 48, CN 121445557 A, Figure 29J, Figure 29K. Figure 33 / 33 of the specification, page 49 CN 121445557 A Abstract Abdominal ultrasound examination method, system and device The present invention provides a skin-adhesive intelligent air-permeable bandage consisting of: a stretchable adhesive antibacterial bioelectrical interface film; a waterproofmoisture-permeable protective film for protecting the wound from external contaminants; and a permeable stretchable circuit assembly arranged between the bioelectrical interface film and the protective film. The permeable stretchable circuit assembly comprises: a permeable stretchable circuit board; biosensors constructed on the permeable stretchable circuit board; and electronic components assembled on the permeable stretchable circuit board. The electronic components include: a physiological signal processing module electrically coupled to the biosensors for in-situ wound monitoring; and a drug delivery actuation module electrically coupled to the bioelectrical interface film for adaptive drug delivery for wound treatment. The provided bandage is more convenient, comfortable and efficient without numerous dressings, thereby not hindering the daily activities and life quality of patients.

Claims

1. A skin-adhesive smart breathable bandage, comprising: A stretchable and adhesive antimicrobial bioelectric interface membrane, said stretchable and adhesive antimicrobial bioelectric interface membrane being made of stretchable and adhesive antimicrobial fibers; A waterproof and breathable protective membrane, used to protect wounds from external contamination; as well as A permeable and stretchable circuit assembly disposed between the bioelectric interface membrane and the protective membrane; The permeable and stretchable circuit assembly comprises: Permeable and stretchable circuit board; One or more biosensors, said one or more biosensors being constructed on the permeable and stretchable circuit board; as well as An electronic component, assembled on the permeable and stretchable circuit board, and comprising: A physiological signal processing module, which is electrically coupled to the one or more biosensors for in-situ wound monitoring; as well as A drug delivery actuation module electrically coupled to the bioelectric interface membrane for adaptive drug delivery to treat wounds.

2. The smart adhesive permeable bandage according to claim 1, wherein the stretchable adhesive antibacterial bioelectric interface membrane is a fiber membrane, the fiber membrane being made by co-electrospinning styrene-ethylene-butene-styrene (SEBS) fibers and gelatin methacrylate (GelMA) fibers loaded with antibiotics.

3. The skin-adhesive smart breathable bandage according to claim 1, wherein the weight ratio of the SEBS fibers to the GelMA fibers is equal to 1:

1.

4. The skin-adhesive smart breathable bandage according to claim 1, wherein the bioelectric interface membrane is modified with tannic acid, contains catechol and pyrogallol, and adheres to the skin through multiple synergistic reactions, including hydrogen bonding and Schiff base / Michael addition reactions, electrostatic attraction, and cation-π interactions.

5. The skin-adhesive smart breathable bandage according to claim 1, wherein the fiber membrane is loaded with conductive nanoparticles.

6. The skin-adhesive smart breathable bandage according to claim 5, wherein the conductive nanoparticles are silver nanoparticles.

7. The skin-adhesive smart breathable bandage according to claim 1, further comprising a wireless energy harvesting and communication module, the wireless energy harvesting and communication module being used to enable the skin-adhesive smart breathable bandage to communicate with a remote device to facilitate battery-free remote diagnosis and treatment of wounds.

8. The skin-adhesive smart breathable bandage according to claim 1, wherein the drug delivery actuation module comprises: At least one pair of drug delivery electrodes, said at least one pair of drug delivery electrodes being used to apply a drug delivery voltage onto the bioelectric interface membrane; And a switch connected to the drug delivery electrode and configured to turn the drug delivery voltage on / off.

9. The skin-adhesive smart breathable bandage of claim 8, further comprising a microcontroller unit electrically connected to the drug delivery actuation module and configured to adjust the drug delivery amount by controlling the duration of the drug delivery voltage being applied.

10. The skin-adhesive smart breathable bandage according to claim 1, wherein... The one or more biosensors include a glucose sensor having at least one stretchable working electrode attached to the permeable stretchable circuit board. and The working electrode has a layered structure, which includes: a stretchable substrate; a mediator layer deposited on the stretchable substrate; a glucose sensing element layer deposited on the mediator layer; and a retention material layer deposited on the glucose sensing element layer.

11. The skin-adhesive smart breathable bandage according to claim 1, wherein... The one or more biosensors include a pH sensor having at least one stretchable working electrode attached to the permeable stretchable circuit board. and The working electrode has a layered structure, the layered structure comprising: Stretchable substrate; And a pH sensing element layer, which is deposited on the stretchable substrate.

12. The skin-adhesive smart breathable bandage of claim 1, wherein the one or more biosensors include a thermal sensor attached to the permeable and stretchable circuit board.

13. A method for manufacturing a skin-adhesive smart breathable bandage according to claim 1, the method comprising: manufacturing the bioelectric interface membrane; Manufacture the stretchable circuit assembly; The bioelectric interface membrane is attached to the bottom side of the stretchable circuit assembly; as well as The top side of the stretchable circuit assembly is covered with a protective film.

14. The method of claim 13, wherein the bioelectric interface membrane is manufactured by: Prepare a first syringe containing a SEBS precursor solution and a second syringe containing a GelMA solution loaded with the drug; Connect the first syringe and the second syringe to a dual-channel injection pump to simultaneously eject SEBS fibers and GelMA fibers; The SEBS fibers and the GelMA fibers are electrospun together on a metal foil covering a rotating drum to form a fiber membrane composed of the SEBS fibers and the GelMA fibers. Under UV light irradiation, the fiber membrane is immersed in a solution of 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone to crosslink the GelMA fibers in the fiber membrane. Peel the fiber membrane off the metal foil; The fiber membrane is immersed in a silver nanoparticle solution to load the silver nanoparticles onto the fiber membrane; as well as The fiber membrane is immersed in tannic acid to form the bioelectric interface membrane; The bioelectric interface membrane is modified with tannins, contains catechol and pyrogallol, and adheres to the skin through multiple synergistic reactions, including hydrogen bonding and Schiff base / Michael addition reactions, electrostatic attraction, and cation-π interactions.

15. The method of claim 13, wherein the stretchable circuit assembly is manufactured by: Forming a stretchable SEBS / Au electrode; A sensor electrode is formed based on the stretchable SEBS / Au electrode; and The sensor electrodes and the electronic components are bonded to the stretchable circuit board; The stretchable SEBS / Au electrode is formed by the following: Pre-stretched SEBS membrane; The first Cr / Au layer is deposited on the SEBS membrane; Peel off the SEBS film; A second Cr / Au layer is deposited on top of the first Cr / Au layer to form a stretchable SEBS / Au layer; and The stretchable SEBS / Au layer is patterned to form the stretchable SEBS / Au electrode.

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