Intelligent color-changing absorbable suture and method of making same

Abstract

The present application relates to a kind of intelligent color-changing absorbable suture and its preparation method, belong to medical instrument field.The suture includes inner layer support layer, response layer, drug release system and outer layer encapsulation layer.The inner layer support layer is made of absorbable polymer;Response layer includes pH response unit and enzyme response unit, can produce identifiable color change under tissue infection microenvironment;Drug release system is loaded with antibacterial drug by mesoporous nano-carrier and is modified with polyelectrolyte gate layer, triggers drug burst release under microenvironment change;Outer layer encapsulation layer is at least partially degradable, to expose response layer after predetermined time.The suture realizes phased degradation by three-layer structure: outer layer encapsulation layer is preferentially degraded to expose response layer, response layer degradation provides infection monitoring window period, and inner layer support layer is lastly degraded to maintain mechanical support, realizes the synergistic function of infection monitoring, drug release and tissue repair.

Description

Technical Field

[0001] This invention relates to the field of medical devices, specifically to a smart color-changing absorbable suture and its preparation method. Background Technology

[0002] With the continuous development of surgical techniques, sutures, as indispensable medical devices in surgery, are constantly improving in performance and function. Absorbable sutures, because they can degrade naturally in the body without the need for secondary surgery, have been widely used in various surgical procedures. However, postoperative infection remains one of the main factors affecting surgical success rates, and traditional sutures have significant shortcomings in infection monitoring and treatment.

[0003] Traditional absorbable sutures rely primarily on postoperative symptoms or laboratory tests for infection monitoring, which can lead to monitoring delays, treatment delays, and compromised surgical outcomes. While some absorbable sutures feature silver ion antibacterial coatings or pH-sensitive dye coatings, these coatings are prone to peeling and rapid loss, making them unsuitable for practical applications. Summary of the Invention

[0004] To address the technical problems of traditional absorbable sutures, such as delayed infection monitoring and insufficient durability of antibacterial effects, this invention provides an intelligent color-changing absorbable suture that not only has enhanced antibacterial function but also enables real-time intraoperative infection monitoring.

[0005] The technical solution adopted by this invention to solve its technical problem is: to provide an intelligent color-changing absorbable suture, comprising:

[0006] An inner support layer is used to provide mechanical support during the degradation cycle;

[0007] A response layer, which covers the inner support layer, includes at least two types of stimulus response units, which produce recognizable color changes in response to changes in the microenvironment caused by tissue infection.

[0008] A drug delivery system, embedded in the response layer, triggers a burst release of the drug in response to changes in the microenvironment.

[0009] An outer encapsulation layer covers the response layer, and the outer encapsulation layer is at least partially degradable to expose the response layer after a predetermined time.

[0010] Preferably, the inner support layer is made of an absorbable polymer, and the absorbable polymer is polycaprolactone (PCL); the absorbable polymer has a fiber diameter of 50-100 μm and a tensile strength greater than 40 N.

[0011] Preferably, the stimulus response unit includes a pH response unit and an enzyme response unit, wherein the pH response unit changes color when the pH value is 5.2-6.8, and the enzyme response unit changes color upon contact with infection-related enzymes.

[0012] Preferably, the pH response unit uses a gelatin-bromocresol purple complex, and the enzyme response unit uses a silk fibroin-alizarin red complex, which turns orange-red upon contact with neutrophil elastase.

[0013] Preferably, the drug delivery system includes a mesoporous nanocarrier loaded with an antibacterial drug, the surface of which is modified with a polyelectrolyte-gated layer, which disintegrates under changes in the microenvironment to release the drug; the antibacterial drug is selected from ciprofloxacin, levofloxacin, cephalosporins, or combinations thereof; the mesoporous nanocarrier uses mesoporous silica nanoparticles with a pore size of 5 nm.

[0014] Preferably, the outer encapsulation layer is a nanofiber film prepared by electrospinning polylactic acid-glycolic acid copolymer (PLGA); the thickness of the film is 5 μm; the polylactic acid-glycolic acid copolymer (PLGA) is a biodegradable copolymer formed by ring-opening copolymerization of two monomers, lactide (LA) and glycolide (GA), with a molar ratio of LA:GA = 85:15.

[0015] Preferably, the surface of the outer encapsulation layer is further coated with an anti-stick coating, the anti-stick coating being selected from zwitterionic polymers; the zwitterionic polymer is sulfobetaine.

[0016] Preferably, the degradation cycle of the suture includes three stages: the outer encapsulation layer degrades preferentially to expose the response layer, the response layer degrades to provide an infection monitoring window, and the inner support layer degrades last to maintain mechanical support.

[0017] In addition, the present invention also provides a method for preparing absorbable sutures as described in any of the preceding claims, comprising:

[0018] A three-layer structure consisting of an inner support layer, a response layer, and an outer encapsulation layer is formed by coaxial electrospinning.

[0019] Mesoporous nanocarriers loaded with antibacterial drugs are dispersed in the spinning solution of the responsive layer;

[0020] An anti-stick coating is applied to the surface of the outer encapsulation layer and then cured.

[0021] The beneficial effects of this invention are as follows:

[0022] (1) The present invention adopts a three-layer architecture. The outer encapsulation layer is degraded preferentially to expose the response layer containing dual-stimulation response units. When the infection microenvironment causes the pH to drop and the enzyme activity to rise, the two response units superimpose to produce a color switch that can be seen by the naked eye. Doctors and patients can detect the infection at the bedside or at home without equipment. This is several days earlier than the traditional "symptom-test" path, reducing the risk of delay and significantly reducing the probability of a second surgery due to diagnostic delay.

[0023] (2) This invention achieves real-time intraoperative infection monitoring through a pH / enzyme dual-response color-changing system, overcoming the monitoring lag problem caused by traditional sutures relying on postoperative symptoms or laboratory tests. When tissue infection occurs, the local microenvironment pH value decreases and releases specific enzymes, triggering color changes in bromocresol purple and alizarin red in the color-changing response layer. This allows medical staff to directly observe the infection status, greatly improving the accuracy and timeliness of infection detection, and facilitating early detection and timely treatment of potential infections.

[0024] (3) The response layer of the present invention integrates two independent response units, pH and enzyme. Significant color change only occurs when infection-related "acidity + protease" dual signals appear simultaneously. Single physiological fluctuations (such as transient acidic food, mild inflammation) are insufficient to activate the two types of units at the same time, thereby reducing the false positive rate, ensuring the clinical credibility of the warning information, and avoiding unnecessary antibiotic use and over-treatment.

[0025] (4) The drug release system of the present invention is embedded in the response layer and shares the same "infection signal" with the color-changing unit; the microenvironmental change triggers the color change and directly releases the drug controlled release mechanism, so that the antibacterial agent can be released in time, forming a high concentration "pulse" in the infection focus, while the systemic blood drug concentration remains low, which not only enhances the bactericidal effect, but also avoids the risk of liver and kidney toxicity and drug resistance caused by high doses of systemic administration.

[0026] (5) The present invention adopts a gradient degradation structure design, including an outer PLGA layer, a color-changing gelatin-silk fibroin layer, and a core PCL, which realizes adaptive degradation to different tissue environments. Compared with the sutures made of a single material in the prior art, the three-layer structure of the present invention can adjust the degradation rate according to different tissue environments. The outer PLGA layer degrades first to expose the color-changing response layer, while the core PCL provides long-term mechanical support, effectively solving the problem that the degradation rate of existing materials is difficult to control precisely in different tissue environments, and improving the applicability and reliability of the suture.

[0027] (6) This invention achieves infection-triggered intelligent drug release by embedding mesoporous silica nanoparticles in the color-changing layer and loading ciprofloxacin. When the local microenvironment pH value decreases, the polyelectrolyte gated layer disintegrates, triggering drug release. Compared with the prior art of directly coating non-degradable antibacterial coatings, this invention significantly improves the drug release efficiency and durability, without affecting the mechanical properties of the suture.

[0028] (7) The present invention coats the outer layer with sulfobetaine to form an anti-adhesion coating, which effectively reduces the bacterial adhesion rate and enhances the antibacterial properties and tissue compatibility of the suture. Compared with the suture without anti-adhesion coating, the suture of the present invention greatly reduces the adhesion rate of Staphylococcus aureus and Escherichia coli, and is particularly suitable for surgical environments with high infection risk.

[0029] (8) The present invention uses coaxial electrospinning process to prepare sandwich structure, forming inner support layer with good mechanical properties, ensuring the overall strength of suture, and realizing tight bonding between functional layers, improving product consistency and stability, and meeting the needs of most surgical suturing.

[0030] (9) All functions of the present invention (support, early warning, drug delivery) are integrated into a single suture. Surgeons can tie the knot using conventional methods without the need for secondary implantation of sensor strips or drug-loaded tablets, and the dosage will not be reduced due to coating friction. Clinical comparison shows that the operation time is no different from that of traditional sutures, but it can simultaneously complete the triple tasks of "suturing + infection monitoring + local antibacterial", significantly reducing the risk of medical errors caused by additional operations or missed steps. Attached Figure Description

[0031] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other embodiments can be obtained based on these drawings without creative effort.

[0032] Figure 1 This is a schematic diagram of the structure of a smart color-changing absorbable suture according to the present invention.

[0033] In the diagram: 10 - Inner support layer; 20 - Response layer; 21 - Drug release system; 30 - Outer encapsulation layer; 40 - Anti-stick coating. Detailed Implementation

[0034] The present invention will now be described in detail with reference to the accompanying drawings and embodiments.

[0035] Example 1

[0036] like Figure 1 As shown, this embodiment provides an intelligent color-changing absorbable suture composed of an inner support layer, a response layer, and an outer encapsulation layer, with a drug release system embedded in the response layer, forming a collaborative intelligent suture system.

[0037] (1) Inner support layer:

[0038] The inner support layer is made of an absorbable polymer, including polycaprolactone, polylactic acid-glycolic acid copolymer, polylactic acid, or combinations thereof.

[0039] When the absorbable suture is used for intestinal anastomosis sutures, the inner support layer is made of polycaprolactone (PCL) fibers with a diameter of 50-100 μm, a tensile strength ≥40 N, a weight-average molecular weight (Mw) of 80 kDa, a tensile strength of 40–60 MPa, and an in vivo degradation time of 6-12 months, matching the collagen maturation cycle and meeting the requirement that the suture "remains >15 N after 4 weeks." Therefore, polycaprolactone has good mechanical properties and a controllable degradation rate, enabling it to maintain the necessary tensile strength throughout the suture degradation cycle, providing basic support for the suture. In this embodiment, the diameter of the inner support layer is 0.1-0.5 mm, preferably 0.2 mm, a size that ensures sufficient strength without causing excessive tissue irritation.

[0040] When the absorbable suture is used in orthopedic sutures, the inner support layer is made of polycaprolactone (PCL) fibers and nano-hydroxyapatite (nHA) in a mass ratio of PCL / nHA = 9:1; wherein the nano-hydroxyapatite has a particle size of 50-200 nm. Orthopedic sutures need to withstand high tension and cutting forces from tendons, ligaments, or periosteum. Pure PCL has a modulus of only 200–300 MPa, which is relatively soft. After introducing 10% nHA, physical-chemical bonds are formed between the particles and the PCL molecular chains, increasing the elastic modulus by 1.5–2 times (≈400–600 MPa), improving bending and creep resistance, and maintaining a tensile strength of over 40 MPa. At the same time, the stiffness (resistance to deformation) is significantly improved, making the orthopedic suture harder and more resistant to cutting, in order to match the high-tension environment of the bone surface.

[0041] In a preferred embodiment, the inner support layer may be selectively supplemented with anti-inflammatory drugs or growth factors, such as methylprednisolone or β-transfer factor, with the total amount added not exceeding 5%.

[0042] (2) Response layer:

[0043] The responsive layer, surrounding the inner support layer, contains at least two types of stimulus-response units that produce identifiable color changes in response to microenvironmental changes resulting from tissue infection. Specifically, the responsive layer includes pH-responsive units and enzyme-responsive units. The pH-responsive units change color at pH values ​​of 5.2–6.8, while the enzyme-responsive units change color upon contact with infection-related enzymes. The pH-responsive unit includes a gelatin-bromocresol purple complex, which turns bright yellow at pH < 5.2 and deep purple at pH > 6.8; when the tissue microenvironment pH drops to the 5.2–6.8 range, bromocresol purple changes from purple to yellow, indicating early signs of inflammation or infection. The enzyme-responsive unit includes a silk fibroin-alizarin red complex, which changes from orange-red to deep red upon contact with specific proteases released during bacterial infection. This combination of response units allows the suture to respond to different types of infection markers, improving the accuracy and sensitivity of detection. The thickness of the responsive layer is 0.05-0.2 mm, preferably 0.1 mm, to ensure sufficient loading of responsive material without affecting the flexibility of the suture.

[0044] In a preferred embodiment, the color-changing responsive layer comprises, from the inside out, a gelatin-bromocresol purple complex and a silk fibroin-alizarin red complex, with a thickness of 2-5 μm, and is coated on the surface of the inner support layer. Further, in the color-changing responsive layer, the mass ratio of the gelatin-bromocresol purple complex is 1:0.03-0.1, preferably 1:0.05, for pH-responsive color change; the mass ratio of the silk fibroin-alizarin red complex is 1:0.01-0.05, preferably 1:0.03, for enzyme-responsive color change.

[0045] The drug delivery system is embedded in a response layer, comprising mesoporous nanocarriers loaded with antibacterial drugs. The surface of the mesoporous nanocarriers is modified with a polyelectrolyte-gated layer, which disintegrates under changes in the microenvironment to release the drug. The mesoporous nanocarriers utilize mesoporous silica nanoparticles with a particle size of 50-200 nm, a pore size of 2-10 nm (preferably 5 nm), and a specific surface area of ​​600-1000 m² / g, enabling effective loading of drug molecules. The antibacterial drug is selected from ciprofloxacin, levofloxacin, cephalosporins, or combinations thereof. In a preferred embodiment, the drug delivery system primarily loads ciprofloxacin, with a loading amount of 10-20% of the carrier weight, preferably 15%. The polyelectrolyte-gated layer is formed by alternating assembly of polyacrylic acid and polylysine. Under conditions of pH decrease or the presence of specific enzymes, the polyelectrolyte layer structure is disrupted, releasing the drug from the mesopores, achieving targeted therapy to the site of infection.

[0046] Performance verification results showed that under infected conditions, the sutures could change from purple to yellow within 2 minutes, and further turn orange-red within 25 minutes after enzyme activation, achieving rapid visual early warning. At the same time, the drug release system responded to the infection signal, and the ciprofloxacin release reached 82% within 24 hours, significantly higher than the 21% under normal conditions, showing obvious infection-triggered burst release characteristics. In vitro antibacterial experiments showed that the inhibition zone diameter against Escherichia coli under infected conditions reached 28 mm, demonstrating strong antibacterial ability.

[0047] When the absorbable suture is used as an orthopedic suture, a calcium ion indicator is also added to the responsive layer. The added calcium ion indicator is loaded onto mesoporous silica nanoparticles via a sol-gel method, and then electrospun together with a pH / enzyme dye.

[0048] Early postoperative infection in orthopedic surgery is often accompanied by periosteal / cortical bone resorption, and local calcium deficiency. 2+ The concentration increased rapidly (>2.5 mmol / L). After introducing calcium ion indicators (such as Fluo-3, Rhod-5N, or azo-arsenazo dyes) into the suture response layer, the indicator reacted with Ca... 2+ Upon binding, a color or fluorescence change occurs, forming a "third signal" in conjunction with the existing pH / enzyme dual response. This occurs when infection leads to a decrease in pH, an increase in elastase, and a rise in Ca2+. 2+ During the ascent, the three-line signal is triggered simultaneously, and the suture shows obvious tri-color composite color change (e.g., purple → yellow → orange-red + the appearance of fluorescent spots). Through cross-validation, the false positive rate can be further reduced and the specificity for infectious osteitis can be improved.

[0049] In a preferred embodiment, the surface of the drug-loaded nanoparticles is modified by silanization to increase their stability, and a chitosan / sodium alginate polyelectrolyte gated layer is formed on the surface, with a gated layer thickness of 2-5 nm.

[0050] (3) Outer encapsulation layer:

[0051] The outer encapsulation layer covers the responsive layer and is composed of polylactic acid-glycolic acid copolymer, with a thickness of 0.03-0.1 mm, preferably 0.05 mm. The outer encapsulation layer is at least partially degradable, designed to begin degrading 3-5 days after implantation and fully expose the responsive layer after 7-10 days. The surface of the outer encapsulation layer is further coated with an anti-adhesion coating selected from zwitterionic polymers, such as phosphatidylcholine polymers, with a thickness of 5-20 micrometers. This anti-adhesion coating reduces protein adsorption and cell adhesion, decreases friction between the suture and tissue, and improves the biocompatibility of the suture.

[0052] In a preferred embodiment, the outer layer is made of an electrospun polylactic acid-glycolic acid copolymer (PLGA) film. The outer encapsulation layer is a nanofiber film prepared by electrospinning polylactic acid-glycolic acid copolymer (PLGA) with a thickness of 5-10 μm (preferably 5 μm). The polylactic acid-glycolic acid copolymer (PLGA) is a biodegradable copolymer formed by ring-opening copolymerization of lactide (LA) and glycolide (GA), with a molar ratio of LA:GA = 85:15.

[0053] (4) Anti-stick coating:

[0054] In a preferred embodiment, the outer surface is coated with a sulfobetaine anti-stick coating, the concentration of sulfobetaine is 2-5%, and it is cured by dip coating at a temperature of 50-70°C (preferably 60°C) for 2 hours.

[0055] The entire degradation cycle of the suture consists of three phases: Phase 1 (0-10 days), the outer encapsulation layer degrades preferentially to expose the response layer; Phase 2 (10-30 days), the response layer degrades to provide an infection monitoring window; and Phase 3 (30-90 days), the inner support layer degrades last to maintain mechanical support. This phased degradation design ensures that the suture maintains the necessary mechanical properties throughout its in vivo degradation cycle, while simultaneously achieving the synergistic functions of infection monitoring, drug release, and tissue repair.

[0056] During suture use, when a wound becomes infected, the tissue microenvironment changes, including a decrease in pH and the release of specific enzymes. These changes trigger color changes in the stimulus-response units within the suture layer, allowing healthcare professionals to promptly detect signs of infection by observing these color shifts. Simultaneously, these microenvironmental changes also trigger the disintegration of the polyelectrolyte-gated layer in the drug delivery system, leading to the release of antibacterial drugs from the mesoporous nanocarrier for localized treatment of the infected site and inhibition of bacterial growth. Over time, the suture layers gradually degrade and are eventually completely absorbed by the body, eliminating the need for a secondary surgical removal.

[0057] The intelligent color-changing absorbable suture in this embodiment, through its multi-layered structural design and stimulus response mechanism, enables early monitoring and timely treatment of wound infection, significantly reducing the risk of postoperative infection and improving the quality of wound healing.

[0058] Example 2

[0059] This embodiment provides a method for preparing a smart color-changing absorbable suture. This method corresponds to the suture structure described in Embodiment 1, but employs a different preparation process.

[0060] The method includes the following steps:

[0061] (1) A three-layer structure consisting of an inner support layer, a response layer, and an outer encapsulation layer is formed by coaxial electrospinning.

[0062] Coaxial electrospinning is an advanced process capable of simultaneously spinning multilayer structures, allowing for precise control of the thickness and composition of each layer. In this method, the process parameters for coaxial electrospinning are: inner layer voltage 15-20 kV, middle layer voltage 18-22 kV, outer layer voltage 20-25 kV, collection distance 150-200 mm, and flux 0.1-0.5 mL / min.

[0063] The inner layer voltage is 15-18kV, the middle layer voltage is 18-20kV, and the outer layer voltage is 20-22kV. This voltage gradient design ensures the stable formation of the three-layer structure and good interfacial bonding. The inner support layer uses the polycaprolactone material described in Example 1, the responsive layer contains a pH-responsive gelatin-bromocresol purple complex and an enzyme-responsive silk fibroin-alizarin red complex, and the outer encapsulation layer uses polylactic acid-glycolic acid copolymer.

[0064] (2) Disperse the mesoporous nanocarrier loaded with antibacterial drugs in the spinning solution of the response layer.

[0065] In this step, mesoporous silica nanocarriers are first prepared and then loaded with antibacterial drugs (such as ciprofloxacin, levofloxacin, or cephalosporins) via impregnation. Next, a polyelectrolyte-gated layer is modified onto the carrier surface to form a complete drug release system. Finally, these drug-loaded nanocarriers are uniformly dispersed in the spinning solution of the response layer, ensuring that the nanocarriers are evenly distributed within the response layer during electrospinning.

[0066] (3) Apply an anti-stick coating to the surface of the outer encapsulation layer and cure it.

[0067] After spinning, an amphoteric polymer anti-adhesion coating, such as phosphatidylcholine polymer, is coated onto the outer layer of the suture. The coated suture is then cured at 60°C to ensure the anti-adhesion coating adheres firmly to the surface of the outer encapsulation layer. This anti-adhesion coating reduces protein adsorption and cell adhesion, decreases friction between the suture and tissue, and improves the biocompatibility of the suture.

[0068] In a preferred embodiment, the specific parameters of coaxial electrospinning can be set as follows: inner layer voltage 16kV, middle layer voltage 19kV, and outer layer voltage 21kV. This set of parameters can obtain the best interlayer bonding strength and morphological structure.

[0069] The sutures prepared by this method possess the structural features and functional properties described in Example 1, enabling synergistic functions of infection monitoring, drug release, and tissue repair. Through coaxial electrospinning technology, the thickness and composition of each layer can be precisely controlled, ensuring that the sutures have ideal mechanical properties and biodegradability.

[0070] The above description is merely a preferred embodiment of the present invention, and the present invention is not limited to the above embodiments. It is understood that other improvements and variations that are directly derived or conceived by those skilled in the art without departing from the spirit and concept of the present invention should be considered to be included within the protection scope of the present invention.

Claims

1. A smart color-changing absorbable suture, characterized in that, include: An inner support layer is used to provide mechanical support during the degradation cycle; A response layer, encapsulating the inner support layer, comprises at least two types of stimulus-response units. These units produce identifiable color changes in response to microenvironmental changes caused by tissue infection. The stimulus-response units include a pH-response unit and an enzyme-response unit. The pH-response unit changes color at a pH of 5.2-6.8, and the enzyme-response unit changes color upon contact with infection-related enzymes. The pH-response unit uses a gelatin-bromocresol purple complex, and the enzyme-response unit uses a silk fibroin-alizarin red complex, turning orange-red upon contact with neutrophil elastase. A drug delivery system, embedded in the response layer, triggers a burst release of the drug in response to changes in the microenvironment. An outer encapsulation layer covers the response layer, and the outer encapsulation layer is at least partially degradable to expose the response layer after a predetermined time.

2. The absorbable suture according to claim 1, characterized in that, The inner support layer is made of an absorbable polymer, specifically polycaprolactone (PCL); the absorbable polymer fibers have a diameter of 50-100 μm and a tensile strength greater than 40 N.

3. The absorbable suture according to claim 1, characterized in that, The drug delivery system includes a mesoporous nanocarrier loaded with an antibacterial drug. The surface of the mesoporous nanocarrier is modified with a polyelectrolyte-gated layer, which disintegrates under changes in the microenvironment to release the drug. The antibacterial drug is selected from ciprofloxacin, levofloxacin, cephalosporins, or combinations thereof. The mesoporous nanocarrier uses mesoporous silica nanoparticles with a pore size of 5 nm.

4. The absorbable suture according to claim 1, characterized in that, The outer encapsulation layer is a nanofiber film prepared by electrospinning polylactic acid-glycolic acid copolymer (PLGA); the thickness of the film is 5 μm; the polylactic acid-glycolic acid copolymer (PLGA) is a biodegradable copolymer formed by ring-opening copolymerization of two monomers, lactide (LA) and glycolide (GA), with a molar ratio of LA:GA = 85:

15.

5. The absorbable suture according to claim 1 or 4, characterized in that, The outer encapsulation layer is further coated with an anti-stick coating, which is selected from zwitterionic polymers; the zwitterionic polymer is sulfobetaine.

6. The absorbable suture according to claim 1, characterized in that, The degradation cycle of the suture consists of three stages: the outer encapsulation layer degrades preferentially to expose the response layer, the response layer degrades to provide an infection monitoring window, and the inner support layer degrades last to maintain mechanical support.

7. A method for preparing the absorbable suture as described in any one of claims 1-6, characterized in that, include: A three-layer structure consisting of an inner support layer, a response layer, and an outer encapsulation layer is formed by coaxial electrospinning. Mesoporous nanocarriers loaded with antibacterial drugs are dispersed in the spinning solution of the responsive layer; An anti-stick coating is applied to the surface of the outer encapsulation layer and then cured.

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