Mechanical performance adjustable fast photodegradation wound healing patch and preparation method thereof

Abstract

The present application relates to the technical field of fast-degradable intelligent adhesive healing patch elastomer materials, in particular to a fast photodegradable wound healing patch with adjustable mechanical strength and a preparation method thereof. Aliphatic polycarbonate containing terminal photoreactive groups is used as a matrix, a drug promoting wound healing is added, and a fast-degradable intelligent healing patch with photothermal response is prepared by electrospinning technology. In vitro degradation and intelligent wound adhesion animal experiments show that, compared with traditional wound healing medical materials, the aliphatic polycarbonate elastomer containing terminal photoreactive groups synthesized in the present application has a fast degradation behavior, and as an intelligent healing patch, it can effectively close the wound. The healing patch containing traditional Chinese medicine has great potential in promoting wound healing, anti-inflammatory and skin regeneration, and can reduce medical waste, and has very good application prospect.

Description

Technical Field

[0001] This invention belongs to the field of rapidly degradable smart healing patch technology, specifically relating to a photodegradable smart healing patch material with mechanical controllability and its preparation method. Background Technology

[0002] Polymer products are widely used in many fields, such as consumer goods, medical, and industrial sectors, due to their unique physicochemical properties. It is estimated that global polymer product production has reached 300 million tons per year. Because they are not recyclable after use and are discarded in large quantities, and the materials themselves cannot effectively degrade, it is projected that by 2025, there will be 11 billion tons of polymer product waste in the global environment, severely polluting the global environment and putting the Earth under excessive strain. Aliphatic polycarbonate materials have a simple preparation process, environmentally friendly monomers, require no solvents, have no complicated post-processing steps, and have a mild reaction temperature. Furthermore, as an important class of biomedical materials, aliphatic polycarbonate materials themselves and their degradation products are non-toxic. They are highly functionalized, and their physicochemical properties can be controlled by introducing functional groups to meet their applications in medicine, industry, and other fields. However, the simple structure and poor mechanical strength of these materials severely limit their application in medical and other fields. Among existing patent publications, CN101348605A discloses a biodegradable aliphatic polycarbonate film that effectively balances its thermal, mechanical, and degradation properties. CN101717567A discloses improving the overall properties of aliphatic polycarbonate by adding suitable modifiers, compatibilizers, antioxidants, and fillers, resulting in a biodegradable aliphatic polycarbonate composite film with good mechanical strength. However, existing patents fail to provide an aliphatic polycarbonate material that is both rapidly degradable and possesses controllable mechanical strength while also being multifunctional. In particular, research on the molecular regulation, response mechanism, and application as a smart healing patch of functionalized aliphatic polycarbonate materials with rapid degradation is largely absent. Summary of the Invention

[0003] To address the problems of slow degradation, poor mechanical strength, and limited structural functionality of current aliphatic polycarbonate materials, the purpose of this invention is to provide a physically cross-linked, energy-driven aliphatic polycarbonate elastomer healing patch that achieves rapid degradation, thus solving the problems of current medical dressings' inability to intelligently adhere and promote healing, and the resulting dressing waste.

[0004] This invention uses photoresponsive units (including but not limited to azobenzene and its derivatives, stilbene, Schiff bases, and other photoresponsive compounds) as initiators and aliphatic polycarbonate as the polymer backbone. A driveable aliphatic polycarbonate chain elastic network was designed, and a novel wound-healing material with tunable mechanical strength, rapid photodegradation, and smart adhesion was successfully prepared. The driveable aliphatic polycarbonate elastomer exhibits excellent smart adhesion response to strain and temperature changes. Further compounding with traditional Chinese medicine and utilizing the fiber network formed by electrospinning, it can be used as a smart healing wound dressing to rapidly promote wound healing, demonstrating its great application potential in wound healing.

[0005] The aliphatic polycarbonate monomers involved in this invention are commercially widely used and patented aliphatic polycarbonate monomers (e.g., those reported in Chinese Invention Patent ZL 201310363003.7). Ring-opening polymerization (ROP) of cyclic carbonate monomers is the most efficient and convenient method for preparing high molecular weight polycarbonates with low dispersion coefficients. Trimethylene carbonate (TMC) is one of the most studied cyclic carbonate monomers. To optimize its performance and expand its applications in biomedicine, various functional groups, such as hydroxyl, carboxyl, and amino groups, are often introduced into its outer ring through chemical modification, resulting in a variety of functionalized cyclic carbonate monomers, the general structural formula of which is shown in Formula I.

[0006]

[0007] In the aliphatic carbonate monomers shown in Formula I, M1 is a hydrogen atom or a methyl group; M2 is selected from hydrogen atom, cyano, carboxyl, ester, substituted or unsubstituted C1-C15 alkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C1-C15 alkoxy, substituted or unsubstituted C1-C15 heteroalkyl, substituted or unsubstituted C6-C20 heteroaryl, wherein the heteroalkyl is at least one C-substituted alkyl or cycloalkyl group, and the alkyl, aryl, alkoxy, heteroalkyl, and heteroaryl groups may have one or more substituents, including but not limited to hydroxyl, cyano, carboxyl, mercapto, carbonyl, ester, and phenyl.

[0008] The aliphatic carbonate monomers used in this invention include, but are not limited to, trimethylene carbonate (TMC), 5-methyl-5-benzyloxycarbonyl trimethylene carbonate (MBC), 5-benzyloxy-trimethylene carbonate (BTMC), and 5-methyl-5-carboxyl-trimethylene carbonate (MCC), as shown below:

[0009]

[0010] The photoresponsive groups involved in this invention include, but are not limited to, stilbene, azobenzene, Schiff bases, and other compounds that can undergo cis-trans isomerization under light of a certain wavelength or at a specific temperature, as shown in Formulas II to IV:

[0011]

[0012] In the stilbene-based photoresponsive compounds represented by Formula ⅠⅠ, the azobenzene-based photoresponsive compounds represented by Formula Ⅲ, and the Schiff base-based photoresponsive compounds represented by Formula Ⅳ, R1 is a hydrogen atom or a C1-C12 alkyl group; the terminal group R2 is a para-substituted C1-C12 n-alkyl or n-alkoxy, nitro, cyano, or carboxyl group; and R3 is a hydrogen atom or a cyano group.

[0013] This invention uses photoresponsive groups to initiate the ring-opening polymerization of aliphatic carbonate monomers to prepare aliphatic polycarbonate elastomers with photoresponsive groups at the terminal positions, the structures of which are shown in Formula V-Formula VⅠⅠ.

[0014]

[0015] In aliphatic polycarbonate elastomers of formulas V-VII containing photoresponsive groups at their terminal positions, M1 is a hydrogen atom or a methyl group; M2 is a hydrogen atom, a cyano group, a carboxyl group, an ester group, a substituted or unsubstituted C1-C15 alkyl group, a substituted or unsubstituted C6-C20 aryl group, a substituted or unsubstituted C1-C15 alkoxy group, a substituted or unsubstituted C1-C15 heteroalkyl group, or a substituted or unsubstituted C6-C20 heteroaryl group, wherein the heteroalkyl group is at least one C with an O The alkyl or cycloalkyl group may be S- or N-substituted, and the alkyl, aryl, alkoxy, heteroalkyl, or heteroaryl group may have one or more substituents, including but not limited to hydroxyl, cyano, carboxyl, mercapto, carbonyl, ester, and phenyl groups; n represents the degree of polymerization (number of repeating units), preferably an integer from 107 to 300, i.e., the polymer molecular weight is between 30,000 and 90,000; the terminal group R2 is a para-substituted C1-C12 n-alkyl or n-alkoxy, nitro, cyano, or carboxyl group.

[0016] This invention selects a photoresponsive group as an initiator to initiate the ring-opening polymerization of aliphatic carbonate monomers of formula I, forming an aliphatic polycarbonate elastomer with a photoresponsive group at the end. The dynamic bonds constituting the elastomer include, but are not limited to, hydrogen bonding, disulfide bonds, Diels-Alde bonds, hydrophobic association, host-guest interactions, and boron-oxygen bonds. The polymerization reaction steps are generally similar to the preparation method disclosed in Chinese invention patent application CN201310363003.7.

[0017] Using an elastic network composed of aliphatic polycarbonate with photoresponsive groups at the ends as a matrix, this invention provides a rapidly photodegradable wound healing patch, the preparation and application methods of which are as follows:

[0018] (1) Preparation of aliphatic polycarbonate elastomers with end-position photoresponsive groups

[0019] A certain amount of photoresponsive groups are used as initiators to initiate the ring-opening polymerization of aliphatic carbonate monomers, thereby preparing a target aliphatic polycarbonate elastomer network that can be driven. Generally, the molar ratio of aliphatic carbonate monomer to photoresponsive initiator is in the range of 10:1 to 1000:1, the reaction temperature is in the range of 80 to 130℃, the reaction time is in the range of 24 to 48 h, and organic solvents such as tetrahydrofuran, dichloromethane, ethanol, and methanol can be used.

[0020] (2) Preparation of aliphatic polycarbonate healing patches with terminal photoresponsive groups

[0021] To enable aliphatic polycarbonate elastomers containing photoresponsive groups to promote wound healing in practical applications, a certain mass of the elastomer sample prepared in step (1) was mixed with a drug solution that promotes wound healing and then prepared into a patch using electrospinning technology. The drug can be Western medicine or traditional Chinese medicine, including but not limited to honeysuckle, houttuynia cordata, isatis root, indigo leaf, purslane, and glycyrrhizic acid. These are mixed using a solution ultrasonic blending method, and then a healing patch with wound-healing capabilities is prepared using electrospinning technology. Generally, the proportion of traditional Chinese medicine contained in the prepared healing patch is 0.2% to 4% (by mass).

[0022] The present invention provides a mechanically adjustable, photothermally responsive, and rapidly degradable smart healing patch, prepared using aliphatic polycarbonate as the polymer backbone and photoresponsive groups as initiators via electrospinning technology. In vitro degradation and animal experiments demonstrating smart wound adhesion show that, compared to traditional wound healing medical materials, the synthesized elastomer exhibits rapid degradation behavior and can effectively close wounds as a smart healing patch. Specifically, the present invention has the following advantages compared to existing inventions:

[0023] 1. The preparation method of this invention is simple and easy to implement, and the raw material resources are abundant, which is conducive to realizing industrial production.

[0024] 2. The aliphatic polycarbonate involved in the preparation process of this invention has good biocompatibility and no acidic substances are generated during the degradation process, which can significantly improve the biocompatibility of wound healing.

[0025] 3. The elastomer prepared by this invention can achieve controllable mechanical properties of aliphatic polycarbonate segments by adjusting the content of azobenzene, so that this type of healing patch can meet the needs of the medical field.

[0026] 4. The elastomer material prepared by this invention can achieve photothermal equivalent degradation behavior, that is, it can achieve photo-responsive degradation as well as rapid thermal response degradation.

[0027] 5. The elastomer prepared by this invention can be made into a fiber healing patch through electrospinning technology, which gives it a large specific surface area and porosity. During wound healing, it can be intelligently adhered to the wound surface, which will accelerate the patient's wound healing and reduce the adverse effects of complications. Attached Figure Description

[0028] Figure 1 This is a reaction mechanism diagram of the aliphatic polycarbonate elastomer prepared in Example 1 of the present invention.

[0029] Figure 2 This document demonstrates the mechanical properties of the aliphatic polycarbonate elastomer prepared in Example 2 of the present invention. Specifically, a represents the stress-strain curves of the elastomer at different temperatures, b represents the stress-time curve of the elastomer under stress relaxation in a universal tensile testing machine, c represents the crosslinking density of the cis and trans structures of the elastomer, d represents the constant volume free energy simulation of the elastomer's energy-driven properties, e represents the stress-strain curve of the elastomer, and f represents the cyclic tensile properties of the elastomer.

[0030] Figure 3 The above are the photothermal degradation curves of the aliphatic polycarbonate elastomer prepared in Example 3 of the present invention, where a is the mass loss curve of the elastomer at different temperatures and b is the mass loss curve of the elastomer under different light intensities.

[0031] Figure 4 This is a diagram demonstrating the degradation mechanism of the aliphatic polycarbonate elastomer prepared in Example 4 of the present invention. In the diagram, a shows the products before and after the degradation of the elastomer, and b shows the dipole moment and electron cloud density of the elastomer based on Gaussian simulation.

[0032] Figure 5 This is a schematic diagram of the fiber healing patch produced by electrospinning technology in Embodiment 5 of the present invention. (a) shows the process of producing the fiber healing patch by electrospinning technology after mixing elastomer and traditional Chinese medicine. (b) shows the formation process of the cis and trans structures of the elastomer. (c) shows the structure of glycyrrhizic acid, a traditional Chinese medicine. (d) shows the surface morphology of the healing patch after spinning.

[0033] Figure 6 Example 6 of the present invention is an intelligent healing patch used for wound healing in animals. In this example, a shows the surface healing of the wound when the healing patch heals the wound, b shows the healing rate, c shows the wound healing distance of control group 1, d shows the wound healing distance of control group 2, and e shows the wound healing distance of the experimental group.

[0034] Figure 7This is a demonstration of the inflammatory response of an animal wound healing using the intelligent healing patch of Embodiment 7 of the present invention. The left side shows H&E staining, and the right side shows Masson staining. Detailed Implementation

[0035] The present invention will now be described in detail with reference to the accompanying drawings, but the scope of protection of the present invention is not limited to the embodiments.

[0036] Example 1

[0037] A method for preparing a rapidly photodegradable wound healing patch, comprising the following specific steps:

[0038] 1. Selection of photoresponsive initiator materials

[0039]

[0040] The photoresponsive initiator used in this embodiment is n-butylazophenol as shown in the above formula. The synthesis process is as follows: p-n-butylaniline is dissolved in a hydrochloric acid solution of a certain concentration and stirred in an ice-water bath; then, sodium nitrite is dissolved in deionized water and added dropwise to the above solution to generate a diazonium salt; then, a certain mass of sodium hydroxide particles is dissolved in deionized water, and after dissolution, a certain mass of phenol solution is added to the sodium hydroxide solution; finally, the mixed solution is added dropwise to the reaction system; after the reaction is completed, hydrochloric acid solution is added dropwise to make the pH of the system 3-5, filtered, dried by blowing air and then vacuum dried for 24-48 hours to synthesize n-butylazophenol.

[0041] 2. Preparation of aliphatic polycarbonate elastomers with terminal azophenyl groups

[0042] 10 g (40 mmol) of aliphatic carbonate monomer 5-methyl-5-benzyloxycarbonyltrimethylene carbonate (MBC) was placed into a dry and clean silanization polymerization tube. Then, 0.08–4 mmol of initiator n-butylazophenol was added to the polymerization tube (multiple parallel experiments were conducted within a molar ratio of n-butylazophenol to aliphatic carbonate monomer of 1:500–1:10). Following this, 10 μL of catalyst stannous octoate solution was added dropwise. The polymerization tube was evacuated, purged four times with nitrogen, sealed, and reacted in an oil bath at 130 °C for 30 h. After polymerization, the prepared sample was placed in a large amount of dichloromethane solvent for 48 h to dissolve unreacted monomers, with fresh dichloromethane solvent replaced every 24 h. Subsequently, the sample was deswollen with ethanol, and the deswollen sample was dried in a vacuum oven for four days to constant weight, yielding a pale yellow solid material.

[0043] 3. Preparation and application of aliphatic polycarbonate healing patches with terminal azophenyl groups

[0044] Traditional Chinese medicines (including but not limited to honeysuckle, houttuynia cordata, isatis root, indigo leaf, purslane, and glycyrrhizic acid) are mixed with the obtained materials to prepare a mixed solution using a solution ultrasonic blending method. Subsequently, a healing patch is prepared using electrospinning technology. Specifically: 10g of the elastomer prepared in step 2 is placed in a centrifuge tube and then dissolved in an organic solvent, including but not limited to dichloromethane, tetrahydrofuran, ethyl acetate, and acetone. After complete dissolution, a 0.1%–10% glycyrrhizic acid (GA) solution is added. The mixture is then placed in an ultrasonic machine for ultrasonic vibration for 5–60 minutes. Finally, the mixed solution is transferred to an electrospinning machine to prepare the fiber healing patch.

[0045] like Figure 1 As shown, in order to achieve a rapidly degradable aliphatic polycarbonate (APC) chemical structure, a photoresponsive azobenzene was first used as an initiator to synthesize a polymer network through ring-opening polymerization of aliphatic carbonate (2-methyl-2-benzyloxycarbonyl propylene carbonate) monomer (MBC). The material design concept of this invention includes: (1) constructing hydrophobic interactions to obtain moderate crosslinking force, providing higher bonding strength and directional bonding performance for the elastomer; (2) by adjusting the ratio of azobenzene in the structure (10:1 to 1000:1), the degradation behavior and mechanical properties of the material can be balanced; (3) azobenzene compounds, as a special functional initiator, have photoisomerization properties and can react to light or heat, driving the transformation of the obtained polymer condensate state, thereby realizing the multifunctionality of the material.

[0046] Example 2

[0047] 1. Same as step 1 in Example 1;

[0048] 2. Same as step 2 in Example 1.

[0049] The mechanical properties of the synthesized aliphatic polycarbonate elastomer were tested using a universal tensile testing machine. The crosslinking density test procedure is as follows:

[0050] The prepared elastomer was subjected to equilibrium swelling experiments in diethyl ether solvent, and the density of crosslinking sites within its network was calculated using the Flory-Rehner equation. Pre-weighed elastomer material was immersed in diethyl ether for 72 hours, with the solvent replaced every 24 hours. After swelling, the solvent on the sample surface was quickly wiped off with filter paper, and the sample was immediately weighed and then dried to constant weight in a vacuum oven at 25°C. Each sample was tested in at least three parallel trials.

[0051] The Flory-Rehner equation is used to calculate the crosslinking density of elastomers:

[0052]

[0053] Where V e χ is the crosslinking density of the elastomer, and χ is the solvent interaction parameter of the Flory-Huggins polymer.

[0054] V s V is the molar volume of the solvent. r This is the volume fraction of elastomers in toluene:

[0055]

[0056] Where m d It is the mass of the sample before swelling, m s It is the weight of the sample at equilibrium swelling, ρ s and ρ p These are the densities of the solvent and the elastomer, respectively.

[0057] like Figure 2 As shown, the synthesized aliphatic polycarbonate elastomer materials P1–P4, with aliphatic carbonate monomers to n-butylazophenol molar ratios of 10:1, 50:1, 250:1, and 500:1 respectively, exhibited good mechanical and thermodynamic properties, including strength (1.30–3.18 MPa) and elongation at break (495%–715%), without complete loss of tensile strength (0.01–1.3 MPa) within a temperature range of 25–50 °C. This is attributed to the dense crosslinking density within the network. Figure 2 (c)

[0058] Secondly, the obtained materials also exhibit excellent stress relaxation resistance (0.05–10.1 MPa) and cycling ability, enabling them to operate in harsh environments for extended periods. At temperatures up to 50°C, with sustained loading >1% for over 1800 s, the stress in the materials was not fully relaxed (>0.05 MPa), indicating that the orientation of the entire chain motion was limited by the crosslinking points and not fully oriented. It is noteworthy that the temperature was adjusted using constant-volume free energy. and strain Double partial derivatives, constructed using the Flory plot, show a highly linear relationship between stress and temperature when the stretching ratio is fixed between 0 and 5. This is because the intercept of the straight line contributes to... The slope is the entropy contribution. This indicates that the elasticity of the obtained network structure comes from energy-driven rather than entropy-driven (energy contributes 80% to 100%). Therefore, this type of elastomer can also be called an energy elastomer. It has a high modulus and a small reversible deformation value, which contrasts with the steadily increasing reversible deformation of elastomers contributed by entropy, but is more in line with the mechanical performance test results.

[0059] Example 3

[0060] 1. Same as step 1 in Example 1;

[0061] 2. Same as step 2 in Example 1.

[0062] The in vitro degradation experiment was conducted as follows: In vitro degradation experiments were performed under different temperatures (25, 37, 50℃) and different light intensities (50, 75, 100W), using hydrogen peroxide solution as the degradation solution. Samples were cut into cubic structures (approximately 2cm (length) × 2cm (width) × 2cm (height)) and placed in clean, transparent colorimetric tubes. 200μL of hydrogen peroxide solution was then added, and the solution was replaced with fresh hydrogen peroxide every 3 days. Finally, the colorimetric tubes were placed in a constant temperature incubator (25, 37, 50℃) and a constant temperature incubator with different light intensities (25℃) for continuous shaking incubation. Furthermore, the degree of degradation was expressed as a percentage of weight loss. Weight loss percentage (%) = (m d -m i ) / m i , where m d m represents the constant weight of the sample after degradation. i This represents the initial mass.

[0063] like Figure 3 As shown, PC represents aliphatic polycarbonate materials without azophenyl groups at the terminal sites, and P1 to P4 represent aliphatic polycarbonate elastomer materials with azophenyl groups at the terminal sites (as described in Example 2). This invention achieves for the first time rapid and controllable degradation of aliphatic polycarbonate in hydrogen peroxide as the degradation solution. To evaluate the biodegradability of the obtained elastomers, the relationship between actual residual weight (W%) and degradation time (0–20 days) was examined. Within a wide temperature range, the degradation weight loss rate of samples obtained after 20 days gradually increased with increasing temperature (0–18.9%), while the UV irradiation time (0–30 min) and light intensity (0–100 W) required to achieve a similar weight loss rate also increased. Compared with traditional APC degradation, this type of elastomer exhibits very rapid photothermal equivalent degradation behavior.

[0064] Example 4

[0065] 1. Same as step 1 in Example 1;

[0066] 2. Same as step 2 in Example 1.

[0067] The molecular spin density map of the elastomer was obtained using Gaussian and GaussView simulations. The steps involved included:

[0068] First, the molecular structure is optimized in Gaussian. Then, using the optimized molecule as the initial structure, GaussView single-point energy calculations are performed with a larger basis set to obtain the wavefunction and spin density map of the molecular ground state. Typically, Gaussian uses 128 cores, requires 300GB of memory, and outputs a .chk file.

[0069] like Figure 4 As shown, further research on the degradation mechanism of the obtained elastomers revealed that the weight loss rate of such elastomers increased with the increase of the dipole moment value (0.82–4.95) (3.12%–14.84%).

[0070] Example 5

[0071] 1. Same as step 1 in Example 1;

[0072] 2. Same as step 2 in Example 1;

[0073] 3. Same as step 3 in Example 1.

[0074] Take 10g of elastomer and place it in a centrifuge tube. Then, dissolve it in 15mL of dichloromethane. After complete dissolution, add a 0.2% glycyrrhizic acid solution. Next, place the mixture in an ultrasonic machine for ultrasonic vibration for 60 minutes. Finally, transfer the mixture to an electrospinning machine to prepare the fiber healing patch. Figure 5 As shown, we used electrospinning technology to fabricate a mixture (elastomer and GA, denoted as AP-GA) with high porosity (e.g., ...). Figure 5 (d) and fiber dressings with large specific surface area.

[0075] Example 6

[0076] 1. Same as step 1 in Example 1;

[0077] 2. Same as step 2 in Example 1;

[0078] 3. Same as step 3 in Example 1.

[0079] The specific steps of the wound healing experiment are as follows: Thirty 6-8 week old mice were acclimatized for one week. Generally, all surgical instruments and consumables involved in the experiment were sterilized / disinfected in advance and placed in a barrier facility, and then placed in a biosafety cabinet for ultraviolet irradiation disinfection again before the experiment began. Subsequently, the 30 mice were randomly divided into two groups and ear-tagged. One mouse was placed in the anesthesia induction box of the anesthesia machine for isoflurane gas anesthesia. When the mouse showed no behavioral activity and muscle tension and reflex response decreased, it was removed from the induction box and placed on the operating table of the biosafety cabinet. The face was aligned with the ventilator mask for continued inhalation anesthesia. After the mouse showed no response to external stimuli, the surgical procedure began. The back of the mouse was shaved and the skin was prepared. The skin surface was first disinfected with 75% alcohol using a cotton swab, and then disinfected with iodine using a cotton swab. Then, ophthalmic forceps and ophthalmic scissors were used to cut off the skin tissue on the back of the mouse, in a square shape with an area of ​​about 1cm × 1cm. The size of the mouse skin wound was measured with a steel ruler and recorded in the table according to the corresponding number. Simultaneously, the wound condition of the numbered mice was photographed and recorded. Appropriately sized wound dressings were applied to the mouse skin wounds. Subsequently, the mice were injected intramuscularly with meloxicam 10μl / 10g for analgesia (continuous injection for 3 days). Wound dressing changes and observation: During the 15-day experimental period, the mice's condition was observed daily. Wound measurements were taken on Day 1, Day 3, Day 5, Day 10, and Day 15. Wound changes were photographed and recorded. Wound dressings were changed (gas anesthesia and analgesia were performed), and necessary tissue samples were taken (euthanasia for pathological observation). Figure 6 As shown, within 0–15 days, the wound area of ​​the AP-GA-treated experimental groups was significantly smaller than that of the control groups 1 (gauze treatment) and 2 (elastomer treatment). Furthermore, after 15 days, the wound shrinkage rate of the AP-GA healing dressing-treated experimental groups reached 100%, while the wound shrinkage rates of control groups 1 and 2 were 77.8% and 85.0%, respectively.

[0080] Example 7

[0081] 1. Same as step 1 in Example 1;

[0082] 2. Same as step 2 in Example 1;

[0083] 3. Same as step 3 in Example 1.

[0084] The steps for H&E staining of paraffin sections are as follows:

[0085] Dewaxing: Immerse in xylene 1, xylene 2, and xylene 3 for 10 minutes each. Rehydrate with a gradient of alcohols (100%, 100%, 100%, 95%, 80%, 75%) for 5 minutes each. Washing: Wash three times with 1×PBS, 5 minutes each time. Hematoxylin staining: Stain with hematoxylin for 30 seconds to 1 minute, then stop staining with tap water. Differentiation: Differentiate with 1% hydrochloric acid alcohol for 1 to 5 seconds. Bluing: Place the differentiated slides in tap water and bluing for 10 to 30 minutes. Eosin staining: Stain with eosin for 30 seconds to 1 minute, then soak in deionized water for 20 minutes, observing constantly. Once the staining is suitable, place in 95% alcohol and prepare for mounting. Dehydration and clearing: Dehydrate in a fume hood using a gradient of alcohols (75%, 85%, 95% for desaturation, 95% for desaturation, 95%, 100%, 100%, 100%) for 30 seconds each, then clear with xylene 1, xylene 2, and xylene 3 for 3 minutes each. Mounting: Mount with neutral resin. Air dry in a fume hood (1-2 days). Store at room temperature in a slide box. Ensure completely dry before photographing.

[0086] The Masson staining procedure is as follows:

[0087] Tissue samples were fixed in 4% paraformaldehyde for 3-5 days, routinely embedded in paraffin, and sectioned to a thickness of 5 μm. Dewaxing was performed by soaking in xylene 1, xylene 2, and xylene 3 for 10 minutes each, followed by a gradient of alcohols (100%, 100%, 100%, 95%, 80%, 75%) for 5 minutes each. The sections were washed three times with 1×PBS, 5 minutes each time. Sections were then mordanted and incubated overnight at room temperature or for 1 hour at 57℃-60℃, followed by rinsing with running water for 10 minutes. Azurite blue staining solution was applied for 2-3 minutes, followed by two 10-15 second rinses with water. Mayer's hematoxylin staining solution was applied for 2-3 minutes, followed by two 10-15 second rinses with distilled water. Differentiation was terminated with acidic differentiation solution for a few seconds, followed by a 10-15 second rinse with distilled water. Ponceau S and fuchsin staining solutions were applied for 10 minutes, followed by two 10-15 second rinses with distilled water. Treat with phosphomolybdic acid solution for approximately 10 minutes. Pour off the supernatant, and without washing the sections with water, directly add aniline blue staining solution for 5 minutes. After washing away the aniline blue solution with a weak acid solution, continue to add weak acid working solution to cover the sections for 2 minutes. Dehydrate with 95% ethanol for 30 seconds, then dehydrate twice with anhydrous ethanol, the first time for 30 seconds and the second time for 1 minute. Clear the sections twice with xylene, each time for 1-2 minutes. Mount with neutral resin, and after the resin has completely dried, photograph or scan the slide.

[0088] like Figure 7As shown, H&E staining and Masson staining were used to further study skin regeneration. H&E staining showed that in control groups 1 (gauze treatment) and control groups 2 (elastomer treatment), the epidermis was basically covered at the wound site, but the epidermis was not tightly integrated with the underlying tissue, and obvious separation was visible. The epidermis was also significantly thicker than normal. Parakeratosis was visible in the stratum corneum. The granular layer consisted of stratified squamous epithelial cells with a significantly higher number of cell layers. The spinous layer cells were immature and not densely or neatly arranged. The wound cavity was filled with granulation tissue, and small blood vessel congestion and local bleeding were visible. There was still a large amount of inflammatory cell infiltration in the granulation tissue. Compared with the wound covered by gauze and elastomer fiber dressings, the wound covered by AP-GA fiber dressing in the experimental groups had the smallest gaps. Meanwhile, in the experimental group treated with AP-GA healing patches, more follicles and better connective tissue arrangement were formed. The spinous cell layer cells were arranged more neatly and tightly integrated with the underlying granulation tissue. No inflammatory cells containing macrophages and neutrophils were observed around the tissue, indicating that AP-GA is more beneficial for anti-inflammation. Masson staining images showed that the wound covered with AP-GA healing patches had uniform and organized collagen fibers similar to normal skin, while the collagen deposits in the gauze and elastomer groups were significantly sparse and disordered. These results demonstrate that AP-GA healing patches have great potential in promoting wound healing, anti-inflammation, and skin regeneration, which are of great significance in intelligent wound healing.

[0089] The above detailed description is a specific description of feasible embodiments of the invention. These embodiments are not intended to limit the patent scope of the invention. All equivalent implementations or modifications that do not depart from the invention should be included within the patent scope of the invention.

[0090] Furthermore, those skilled in the art can make various modifications, additions, and substitutions in other forms and details within the scope and spirit of the claims of this invention. Of course, all such modifications, additions, and substitutions made in accordance with the spirit of this invention should be included within the scope of protection claimed by this invention.

Claims

1. A photodegradable healing patch, characterized in that, Its matrix is ​​an elastic network composed of aliphatic polycarbonate with photoresponsive groups at the ends, wherein the chemical structure of the aliphatic polycarbonate with photoresponsive groups at the ends is shown in Formula V, Formula VI or Formula VII: Wherein, R2 is a C1~C12 n-alkyl or n-alkoxy, nitro, cyano, or carboxyl group; M1 is a hydrogen atom or methyl; M2 is a hydrogen atom, cyano, carboxyl, ester, substituted or unsubstituted C1~C15 alkyl, substituted or unsubstituted C6~C20 aryl, substituted or unsubstituted C1~C15 alkoxy, substituted or unsubstituted C1~C15 heteroalkyl, or substituted or unsubstituted C6~C20 heteroaryl; n represents the degree of polymerization.

2. The photodegradable healing patch as described in claim 1, characterized in that, The heteroalkyl group is at least one C-substituted alkyl or cycloalkyl group, wherein the substituted C1-C15 alkyl group, the substituted C6-C20 aryl group, the substituted C1-C15 alkoxy group, the substituted C1-C15 heteroalkyl group, and the substituted C6-C20 heteroaryl group have one or more substituents selected from hydroxyl, cyano, carboxyl, mercapto, carbonyl, ester, and phenyl groups.

3. The photodegradable healing patch as described in claim 1, characterized in that, The aliphatic polycarbonate containing photoresponsive groups at its terminals has a molecular weight between 30,000 and 90,000.

4. The photodegradable healing patch as described in claim 1, characterized in that, The photodegradable healing patch contains a drug that promotes wound healing. It is prepared by electrospinning a mixture of aliphatic polycarbonate with photoresponsive groups at the ends and the drug.

5. The photodegradable healing patch as described in claim 4, characterized in that, The medicine in question is a traditional Chinese medicine.

6. The photodegradable healing patch as described in claim 5, characterized in that, The Chinese medicinal materials are selected from one or more of the following: honeysuckle, houttuynia cordata, isatis root, indigo leaf, purslane, and glycyrrhizic acid.

7. The photodegradable healing patch as described in claim 5, characterized in that, The healing patch contains 0.2% to 4% Chinese medicinal herbs by weight.

8. A method for preparing the photodegradable healing patch according to any one of claims 1 to 7, comprising the following steps: 1) Using the photoresponsive compound shown in Formula II, Formula III or Formula IV as an initiator, the aliphatic carbonate monomer shown in Formula I is used to initiate ring-opening polymerization to obtain the aliphatic polycarbonate containing photoresponsive groups at the terminal position. Wherein, M1, M2 and R2 are as defined in claim 1, R1 is a hydrogen atom or a C1~C12 alkyl group, and R3 is a hydrogen atom or a cyano group; 2) A healing patch is prepared by electrospinning a mixture of aliphatic polycarbonate with photoresponsive groups at the ends and a drug.

9. The preparation method according to claim 8, characterized in that, The aliphatic carbonate monomers shown in Formula I are selected from one or more of the following compounds: 。 10. The preparation method according to claim 8, characterized in that, In step 1), the molar ratio of aliphatic carbonate monomer to photoresponsive compound is in the range of 10:1 to 1000:1, and the polymerization reaction temperature is in the range of 80 to 130°C. In step 2), aliphatic polycarbonate with photoresponsive groups at the end and the drug are ultrasonically mixed in an organic solvent, and then the mixed solution is transferred to an electrospinning machine to prepare a healing patch.

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