A photocurable 4D printable self-adhesive shape memory tough hydrogel component and its preparation method and application

Abstract

This invention discloses a 4D-printed, self-adhesive, shape-memory, and tough hydrogel component, as well as its preparation method and application, relating to the technical field of printed liquid resin materials. The method comprises mixing a functional monomer with an antibacterial micellar crosslinker, an acrylate-based crosslinker, and a photoinitiator to form a printing resin solution. After photocuring and 3D printing, a three-dimensional hydrogel component is obtained. This invention utilizes DLP 3D printing technology to achieve high-precision, high-complexity, and faster manufacturing.

Description

Technical Field

[0001] The present invention belongs to the field of material technology and relates to the preparation of printing liquid resin materials, and specifically to a photocurable 4D printing self-adhesive shape memory tough hydrogel part and its preparation method and application. Background Art

[0002] 4D printing is an emerging technology that combines 3D printing with intelligent, deformable materials. This means that 3D-printed structures can respond to environmental changes (such as temperature, humidity, acidity, and light) by changing their shape, function, and properties. 4D printing is typically achieved using responsive intelligent soft materials, particularly hydrogels and shape-memory polymers. These materials have been widely applied in various fields, including smart devices, origami, tissue engineering, metamaterials, and biomedicine.

[0003] The fundamental components of 4D printing are 3D printing technology, environmental stimuli, stimuli-responsive materials, interaction mechanisms, and mathematical modeling. These elements enable the targeted and predictable evolution of 4D-printed structures over time. Common 3D printing technologies can be applied to 4D printing. External stimuli are required to trigger changes in the shape, properties, or functions of 4D-printed structures. To date, researchers have used stimuli such as water, heat, magnetic fields, and electric fields in 4D printing. The choice of stimulus depends on the requirements of the specific application.

[0004] In 2009, the ASTM International Committee on Additive Manufacturing (ASTM) defined and categorized different 3D printing technologies. Common extrusion-based 3D printing technologies, such as FDM and DIW, are limited by physical dimensions like nozzles, resulting in low precision. With the increasing demand for complex, personalized implants and high-precision medical devices, 3D printing technologies with higher precision are becoming increasingly necessary. 3D printing technologies that use photopolymerization to create three-dimensional structures (SLA and DLP) are not limited by physical dimensions like nozzles and can be used to create complex structures with ultrafine features, achieving precision ranging from a few microns to hundreds of nanometers. This makes them ideal 3D printing technologies. DLP 3D printing is a development of SLA. Its principles are essentially the same as SLA, both using light to selectively cross-link photosensitive resins to build a desired three-dimensional structure layer by layer. While SLA utilizes a point light source to expose and cure the photosensitive resin point by point within each layer, DLP 3D printing uses a single projection of a digital image onto an entire surface to expose and cure the photosensitive resin. This means that the DMD controls the projection of a surface light source to create a single pattern, which is then exposed and formed in a single exposure. The information of each layer of the structure is provided in the form of a black and white image. This binary pattern is presented by the DMD. Because each layer (slice) of the structure is produced in one exposure step, based on this advantage, the time spent is the same whether the entire plane or only a part is exposed. Therefore, the printing speed of DLP 3D printing is only related to the number of slice layers, while the printing speed of SLA 3D printing technology also depends on the size of the light spot and the movement rate of the light spot. Therefore, DLP 3D printing can shorten the printing time compared to SLA 3D printing. It is an ideal 3D printing technology that combines high precision, high complexity and rapid manufacturing.

[0005] Hydrogels are hydrophilic, three-dimensional cross-linked polymer networks with excellent biocompatibility. They have been widely used in tissue engineering, flexible electronics, drug delivery, and other fields. Currently, some research teams have done some excellent work using DLP 3D printing technology to perform 4D printing of hydrogels.

[0006] As the body's first barrier, the skin is physiologically crucial for protecting internal organs and tissues from external damage, regulating body temperature, and protecting the skin from external damage. Injured skin can lead to pain and infection, placing considerable strain on patients and healthcare systems. Chronic wounds are difficult to heal due to poor blood circulation, which leads to insufficient oxygen and nutrient supply to the wound site, low fibroblast proliferation, and decreased collagen production. Furthermore, the infiltration of activated macrophages prolongs the inflammation of chronic wounds and produces proinflammatory cytokines such as IL-1β and TNF-α. The hypoxic and unbalanced inflammatory environment also increases the production of reactive oxygen species in immune cells, leading to degradation of the extracellular matrix and persistent damage to skin tissue. Considering all these factors, the development of smart wound dressings has garnered significant attention from researchers over the past decade.

[0007] Wound dressings are a key part of the wound healing process. They cover the area around the tissue injury, forming a barrier to protect the wound from contamination, maintain an appropriate humidity level, prevent the loss of body fluids and proteins, and prevent bacterial invasion and inflammation, thereby promoting the healing process. Early traditional skin dressings mainly included gauze, Band-Aids, etc., which were composed of cotton fabrics or composite materials of cotton fabrics and adhesive tape. Although this type of dressing is simple to prepare and inexpensive, its biological properties cannot meet the requirements for skin repair, and it may also cause secondary damage to the skin during the tearing process. In addition, because the adhesive tape on the outer layer of the Band-Aid is not breathable, prolonged use can cause secondary infection in the wound and the surrounding area. In addition, traditional wound dressings have a fundamental problem that has been overlooked, namely, they do not match the irregular contours of the wound, resulting in incomplete coverage or excessive coverage of the wound, which will lead to poor treatment effects.

[0008] To meet the demands of clinical dressings in terms of both physicochemical and biological properties, composite skin dressings have become a research hotspot. These dressings are expected to mimic the structural characteristics of human skin, adapt to the shape and depth of wounds, and meet the physiological needs of skin defect repair. They are also expected to possess the necessary permeability (transparency, air permeability, and water permeability) to effectively prevent the loss of proteins, electrolytes, and heat. They are also expected to be antibacterial, non-toxic, and non-antigenic, minimizing wound size and achieving clinical efficacy superior to any conventional dressing. With the further development of biomedical materials, functionalized hydrogels are increasingly recognized as promising carriers for wound dressings. Their transparency has proven beneficial for monitoring wound healing progress, their porosity allows for good ventilation of the wound area, and their hydrophilic properties allow for the absorption of wound exudate. Furthermore, their programmable properties allow them to carry hydrophilic or even hydrophobic drugs as needed, thereby achieving therapeutic effects on wounds.

[0009] Studies have shown that insufficient wound contraction is a major factor in the difficulty of chronic wound healing, so artificially promoting wound contraction may be an effective treatment option. Several studies have explored dressings that physically contract wounds, offering new possibilities for wound dressing design. For example, Zhao and colleagues' 2021 study used externally pre-stretched polylactic acid sheets to impart an inward contraction tendency to the wound dressing, thereby simultaneously adhering to the skin and shrinking the wound. This is highly forward-looking work. However, fabrication is inconvenient, requiring the application of external forces to both layers. Furthermore, unlike hydrogels, polymer patches still have limitations in terms of drug loading and breathability. There have also been studies on hydrogel-based wound dressings for physical wound contraction. While their contraction force is inferior to pre-stretched polymer patches, their overall functionality is superior. However, hydrogels are often manufactured using thermosetting molding, which requires mold production. In addition to the potential for breakage during demolding, water evaporation during the thermosetting molding process can also compromise the hydrogel's water content. In addition, mold manufacturing needs to be more flexible to produce wound dressings that can adapt to various complex shapes and depths of wounds, and there is room for improvement. Summary of the Invention

[0010] In order to solve the deficiencies in the above-mentioned background technology, the present invention mainly addresses a fundamental problem that has been overlooked in traditional wound dressings, namely, the mismatch with the irregular wound contour, resulting in the wound not being fully covered or over-covered, which will lead to poor treatment effects. The present invention provides a photocurable 4D printable self-adhesive shape memory tough hydrogel component and its preparation method and application. The hydrogel component is used as a wound dressing. It can actively adhere and shrink the wound through the stimulation of body temperature, can significantly reduce the wound area, has strong mechanical properties, is suitable for wounds at large movable joints, and can effectively regulate inflammatory reactions, promote wound healing, and achieve high-precision, high-complexity and faster manufacturing through DLP 3D printing technology. It brings more possibilities to promote the recovery of chronic wounds, reduces the patient's physical pain, improves the quality of life, and reduces the possibility of psychological diseases caused by physical pain.

[0011] In order to achieve the above objectives, the first aspect of the present invention provides a composition for preparing 4D printed self-adhesive shape memory tough hydrogel parts, the composition comprising: a functional monomer and an antibacterial micelle crosslinker, an acrylate-based crosslinker and a photoinitiator; the functional monomer is N-isopropylacrylamide.

[0012] Preferably, the antibacterial micelle cross-linking agent is PF127 or PF127 loaded with curcumin.

[0013] Preferably, the curcumin-loaded PF127 is prepared by dissolving curcumin and PF127 polymer in dichloromethane and self-assembling into micelles.

[0014] Preferably, the photoinitiator is (2,4,6-trimethylbenzoyl)diphenylphosphine oxide or phenyl (2,4,6-trimethylbenzoyl) lithium phosphate.

[0015] Preferably, the acrylate-based crosslinking agent includes polyethylene glycol diacrylate, or a crosslinking agent prepared by reacting dopamine hydrochloride and polyethylene glycol diacrylate.

[0016] Preferably, the mass ratio of the functional monomer to the antibacterial micelle crosslinker, the acrylate-based crosslinker, and the photoinitiator is (55-70):(7-11):(20-30):1.

[0017] The second aspect of the present invention provides a use of the above-mentioned composition in the preparation of 4D printed self-adhesive shape memory tough hydrogel parts.

[0018] A third aspect of the present invention provides a 4D-printed self-adhesive shape-memory tough hydrogel component, which is produced by photocuring 3D printing of raw materials containing the above-mentioned composition.

[0019] Preferably, the method comprises the following steps:

[0020] The functional monomer is mixed with an antibacterial micelle crosslinker, an acrylate-based crosslinker, and a photoinitiator to form a printing resin solution. After light-curing 3D printing, a three-dimensional hydrogel product is obtained.

[0021] A fourth aspect of the present invention provides a 4D printed self-adhesive shape memory tough hydrogel product for use as a wound dressing.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] The present invention provides a photocurable 4D-printable, self-adhesive, shape-memory, and tough hydrogel component, as well as its preparation method and application. Specifically, a 4D-printable hydrogel component has been developed that adapts to wound shape and depth, features rapid manufacturing, high precision, and temperature-responsive wound contraction, along with antibacterial, self-adhesive, and strong stretch resistance, among other synergistic therapeutic benefits. The hydrogel component, used as a wound dressing, primarily utilizes poly(N-isopropylacrylamide) (PNIPAm) formed by photopolymerization of the temperature-sensitive monomer N-isopropylacrylamide (NIPAm). Curcumin-loaded PF127 is also introduced as a tough, antibacterial micelle crosslinker (Cur-PF127). Dopamine, first discovered in mussel adhesive proteins, has been extensively studied and applied to the production of highly viscous materials. Dopamine is combined with polyethylene glycol diacrylate (MW 575) to form a novel polymer structure, PEGDA575-Do, which provides excellent tissue adhesion in the system. NIPAm was chosen because its LCST temperature is near body temperature. Above this temperature, it undergoes a phase transition, leading to mechanical contraction. When applied to wound dressings, this results in mechanical contraction of the wound, triggered by body temperature. Curcumin encapsulated in PF127 micelles can effectively regulate inflammation and promote angiogenesis. DLP 3D printing aims to allow the dressing to more closely conform to the shape and depth of the wound, while also enabling faster manufacturing. This results in a multifunctional, integrated hydrogel wound dressing capable of high-precision, high-complexity DLP 3D printing.

[0024] This invention provides a 4D-printed, self-adhesive, shape-memory, and tough hydrogel wound dressing. This thermally responsive, shrinking hydrogel dressing is self-activated by human body temperature, adhering spontaneously to the skin without the need for additional tape. Simultaneously, the dressing contracts uniformly in response to human body temperature. It also exhibits excellent mechanical properties and can withstand significant movement, making it suitable for wounds located near joints. Furthermore, the controlled release of anti-inflammatory factors within the dressing during application has multiple benefits for wound healing, making it a promising treatment for chronic wounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 is a flow chart of the present invention; wherein, Figure 1 (a) shows the flow chart of preparing hydrogel parts; 1(b) shows the flow chart of 3D printing.

[0026] Figure 2 It is PEGDA575-Do 1 H NMR.

[0027] Figure 3 Represents the relevant data of Cur-PF127 provided in Example 2;

[0028] in, Figure 3 (a) Particle size of Cur-PF127 aqueous solution at different temperatures; Figure 3 (b) TEM image of Cur-PF127 aqueous solution; Figure 3 (c) Display of the water solubility of Cur and Cur-PF127, where ① is Cur and ② is Cur-PF127.

[0029] Figure 4 is the thermal response related performance of C-PNPD hydrogel parts; Figure 4 (a) Demonstration of thermal responsive shrinkage of C-PNPD hydrogel. Figure 4 (b) Demonstration of thermal responsive shrinkage of DLP 3D printed C-PNPD hydrogel structure. Figure 4 (c) SEM images of C-PNPD hydrogel at room temperature and body temperature.

[0030] Figure 5 represents the mechanical properties of C-PNPD hydrogel parts, where Figure 5 (a) Stress-strain curve of C-PNPD hydrogel after 100 cycles of compression. Figure 5 (b) Tensile stress-strain curve of C-PNPD hydrogel. Figure 5 (c) C-PNPD hydrogel stretching demonstration. Figure 5 (d) C-PNPD hydrogel adhesion demonstration.

[0031] Figure 6 The relevant performance data of HaCAT cells co-incubated with C-PNPD hydrogel, Figure 6 (a) Live / Dead staining results of HaCAT cells co-incubated with C-PNPD hydrogel on the first and fifth days. Figure 6 (b) Proliferation activity of HaCAT cells on the first day (24 h) and the second day (48 h) of co-incubation with C-PNPD hydrogel.

[0032] Figure 7 It shows the healing effect of C-PNPD hydrogel on the wounds of diabetic rats infected with MRSA. DETAILED DESCRIPTION

[0033] In order to enable those skilled in the art to better understand and implement the technical solution of the present invention, the present invention is further described below with reference to specific embodiments and drawings, but the embodiments are not intended to limit the present invention.

[0034] The present invention provides a composition for preparing 4D-printed self-adhesive shape-memory tough hydrogel parts, the composition comprising: a functional monomer and an antibacterial micelle crosslinker, an acrylate-based crosslinker, and a photoinitiator; the functional monomer is N-isopropylacrylamide.

[0035] The composition provided by this invention primarily uses the temperature-sensitive monomer N-isopropylacrylamide (NIPAm) as the primary network, formed by photopolymerization of poly(N-isopropylacrylamide) (PNIPAm). By introducing an antimicrobial micellar crosslinker and an acrylate-based crosslinker, and with the participation of a photoinitiator, it can be used to prepare 4D-printed self-adhesive, shape-memory, and tough hydrogel components. This lays the foundation for the preparation of functional hydrogel components.

[0036] In one embodiment, poly(N-isopropylacrylamide) (PNIPAm) is formed by photopolymerization of temperature-sensitive monomer N-isopropylacrylamide (NIPAm).

[0037] According to the present invention, the antibacterial micelle cross-linking agent is PF127 or PF127 loaded with curcumin;

[0038] The photoinitiator is (2,4,6-trimethylbenzoyl)diphenylphosphine oxide or phenyl (2,4,6-trimethylbenzoyl) lithium phosphate (Li-TMPP).

[0039] The curcumin-loaded PF127 (Cur-PF127) is prepared by dissolving curcumin and PF127 polymer in dichloromethane and self-assembling into micelles.

[0040] In one embodiment, a method for preparing curcumin-loaded PF127 (Cur-PF127) comprises:

[0041] A certain amount of curcumin and PF127 polymer were dissolved in dichloromethane with gentle stirring. Co-evaporation was then performed using a rotary evaporator at 40°C. Continued stirring allowed the mixture to self-assemble into micelles, which were then freeze-dried to yield a yellow Cur-PF127 powder. The Cur-PF127 solution was stored at 4°C before use. Because the curcumin to PF127 polymer ratio was 1:99, the mixture formed Cur-PF127 micelles. TEM and DLS were used to monitor the reaction.

[0042] According to the present invention, the acrylate-based crosslinking agent includes polyethylene glycol diacrylate, or a crosslinking agent prepared by reacting dopamine hydrochloride and polyethylene glycol diacrylate.

[0043] In one embodiment, a method for preparing a crosslinker (PEG575-Do) prepared by reacting dopamine hydrochloride and polyethylene glycol diacrylate (PEGDA575) comprises:

[0044] Dopamine hydrochloride (5 g, 26.4 mmol, 1 eq.) and 5 mg of hydroquinone were dissolved in 20 mL of dry DMF in a two-necked flask and dehydrated and deoxygenated. PEGDA575 (MP 575 g / mol; 15.2 g, 13.5 mL, 26.4 mmol, 1 eq.) was added dropwise, followed by TEA (2.7 g, 3.7 mL, 26.36 mmol, 1 eq.). The suspension was stirred in an 85°C oil bath. After 24 hours, PEGDA575 (3 g, 2.7 mL, 5.3 mmol, 0.2 eq.) was added to ensure sufficient acrylate end groups in the final product. After an additional 48 hours, the reaction mixture was cooled to 4°C and stored for 30 minutes before being filtered. The crude product was isolated by four precipitations with 300 mL of ethyl acetate / hexane (1:1 v / v). The precipitate was collected by centrifugation, 3 mg of vitamin E was added, and the final product was dried under vacuum (PEG575-Do, 11.8 g, 60%). 20 μL of the reaction mixture and 500 μL of deuterated chloroform were placed in an NMR tube and eluted with 1 The reaction progress was monitored by H NMR.

[0045] According to the present invention, the mass ratio of the functional monomer to the antibacterial micelle crosslinker, the acrylate-based crosslinker, and the photoinitiator is (55-70): (7-11): (20-30): 1. Preferably, the mass ratio of the functional monomer to the antibacterial micelle crosslinker, the acrylate-based crosslinker, and the photoinitiator is 65:9:25:1.

[0046] The present invention provides the use of the above-mentioned composition in preparing 4D printed self-adhesive shape memory tough hydrogel parts.

[0047] The present invention provides a 4D-printed self-adhesive shape-memory tough hydrogel product, which is produced by light-curing 3D printing of raw materials containing the above-mentioned composition.

[0048] The present invention provides a method for preparing the above-mentioned 4D printed self-adhesive shape memory tough hydrogel product, see Figure 1 As shown, the following steps are included:

[0049] The functional monomer is mixed with an antibacterial micelle crosslinker, an acrylate-based crosslinker, and a photoinitiator to form a printing resin solution. After light-curing 3D printing, a three-dimensional hydrogel product is obtained. Figure 1 (a) shows a flow chart for preparing hydrogel products. Figure 1 In (b), the laser used in the light-curing 3D printing process of the present invention is ultraviolet light, and the ultraviolet post-curing treatment time is 10miP; the 3D printing parameters are: exposure time 1.8s, bottom layer exposure time 7-9s, and layer thickness 0.05mm.

[0050] In one embodiment, Cur-PF127 micelles are synthesized by a one-step solid dispersion method, and curcumin is encapsulated in the micelles; dopamine hydrochloride reacts with PEGDA575 to prepare PEGDA575-Do; a certain proportion of Cur-PF127, PEGDA575-Do, NIPAm, and a photoinitiator are mixed to form a 3D printing resin precursor solution, and a three-dimensional structure is printed using a DLP 3D printer. After printing is completed, the printed three-dimensional structure is removed from the resin tank, and uncured monomers are flushed with deionized water to obtain a 4D printed self-adhesive shape memory tough hydrogel component.

[0051] The present invention provides a 4D-printed self-adhesive shape-memory tough hydrogel product for use as a wound dressing.

[0052] Users can customize hydrogel parts as wound dressings according to the size of the wound, and can print hydrogel parts that fit the wound size.

[0053] The hydrogels prepared in this invention are used as wound dressings primarily because they actively adhere and contract wounds through stimulation by body temperature, significantly reducing wound size. Their strong mechanical properties make them suitable for wounds on large, mobile joints, effectively modulating inflammatory responses and promoting wound healing. Furthermore, DLP 3D printing technology enables high-precision, high-complexity, and rapid manufacturing. This opens up new possibilities for promoting the recovery of chronic wounds, reducing patients' physical pain, improving their quality of life, and reducing the likelihood of psychological illnesses caused by physical pain.

[0054] The technical solutions of the present invention will be described in further detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are encompassed within the scope of protection that the present invention is intended to protect.

[0055] It should be noted that the experimental methods used in the present invention are all conventional methods unless otherwise specified; the reagents and materials used are all commercially available unless otherwise specified.

[0056] Example 1

[0057] The preparation method of a cross-linking agent (PEG575-Do) prepared by reacting dopamine hydrochloride and polyethylene glycol diacrylate (PEGDA575) comprises:

[0058] Dopamine hydrochloride (5 g, 26.4 mmol, 1 eq.) and 5 mg of hydroquinone were dissolved in 20 mL of dry DMF in a two-necked flask and dehydrated and deoxygenated. PEGDA575 (MP 575 g / mol; 15.2 g, 13.5 mL, 26.4 mmol, 1 eq.) was added dropwise, followed by TEA (2.7 g, 3.7 mL, 26.36 mmol, 1 eq.). The suspension was stirred in an 85°C oil bath. After 24 hours, PEGDA575 (3 g, 2.7 mL, 5.3 mmol, 0.2 eq.) was added to ensure sufficient acrylate end groups in the final product. After an additional 48 hours, the reaction mixture was cooled to 4°C and stored for 30 minutes before being filtered. The crude product was isolated by four precipitations with 300 mL of ethyl acetate / hexane (1:1 v / v). The precipitate was collected by centrifugation, 3 mg of vitamin E was added, and the final product was dried under vacuum (PEG575-Do, 11.8 g, 60%). 20 μL of the reaction mixture and 500 μL of deuterated chloroform were placed in an NMR tube and eluted with 1 The reaction process was monitored by H NMR. Figure 2 As shown, its structure was determined by hydrogen nuclear magnetic resonance spectroscopy (1H NMR), confirming that PEGDA575-Do was successfully prepared.

[0059] Example 2

[0060] The preparation method of curcumin-loaded PF127 (Cur-PF127) comprises:

[0061] A certain amount of curcumin and PF127 polymer were dissolved in dichloromethane with gentle stirring. Co-evaporation was then performed using a rotary evaporator at 40°C. Continued stirring allowed the mixture to self-assemble into micelles, which were then freeze-dried to yield a yellow Cur-PF127 powder. The Cur-PF127 solution was stored at 4°C before use. Because the curcumin to PF127 polymer ratio was 1:99, the mixture formed Cur-PF127 micelles. TEM and DLS were used to monitor the reaction.

[0062] See also Figure 3 As shown, Figure 3 Represents the relevant data of Cur-PF127 provided in Example 2; wherein, Figure 3 (a) Particle size of Cur-PF127 aqueous solution at different temperatures; Figure 3 (b) TEM image of Cur-PF127 aqueous solution; Figure 3 (c) Display of water solubility of Cur and Cur-PF127, where ① is Cur and ② is Cur-PF127. The particle size of Cur-PF127 aqueous solution at different temperatures was measured by DLS ( Figure 3 a). Then the TEM sample was prepared for photography, and the results are as follows Figure 3 As shown in (b), Cur-PF127 can self-assemble into spherical micelles in water. After curcumin is loaded into the micelles, the particle size of the micelles increases. The size of Cur-PF127 observed by TEM is basically consistent with the results of DLS test. Curcumin appears as a turbid yellow suspension in water, indicating that curcumin cannot be dissolved in aqueous solution ( Figure 3 (c①)). Obviously, the Cur-PF127 mixture ( Figure 3 (c②)) formed a transparent solution in water, indicating that PF127 greatly promoted the solubility of curcumin in water due to the formation of PF127 micelles.

[0063] Example 3

[0064] A method for preparing a photocurable 4D printable self-adhesive shape memory tough hydrogel part comprises the following steps:

[0065] NIPAm (1.3 g), PF127 (0.18 g), and PEGDA575-Do (0.5 g) were mixed evenly, and 1% of the initiator (Li-TMPP) relative to the monomer mass was added to the mixed solution and shaken to mix evenly to obtain a printing resin. The resin was added to a 3D printer and photocuring printing was performed to obtain a 4D printed self-adhesive shape memory tough hydrogel part.

[0066] Example 4

[0067] NIPAm (1.3 g), Cur-PF127 (0.18 g), and PEGDA575 (0.5 g) were mixed evenly, and 1% of the initiator (Li-TMPP) relative to the monomer mass was added to the mixed solution and shaken to mix evenly to obtain the printing resin. The resin was added to a 3D printer and photocuring printing was performed to obtain a 4D printed self-adhesive shape memory tough hydrogel part (C-PNP).

[0068] Example 5

[0069] NIPAm (1.3 g), Cur-PF127 (0.18 g), and PEGDA575-Do (0.5 g) were mixed evenly, and 1% of the initiator (Li-TMPP) relative to the monomer mass was added to the mixed solution and shaken to mix evenly to obtain the printing resin. The resin was added to a 3D printer and photocuring printing was performed to obtain a 4D printed self-adhesive shape memory tough hydrogel part (C-PNPD).

[0070] In order to illustrate the relevant performance of the hydrogel product provided by the present invention as a wound dressing, the present invention analyzes and illustrates the hydrogel product prepared in Example 5 in conjunction with the accompanying drawings. Figures 4 to 7 .

[0071] Figure 4 is the thermal response related performance of C-PNPD hydrogel parts; Figure 4 (a) Demonstration of thermal responsive shrinkage of C-PNPD hydrogel. Figure 4 (b) Demonstration of thermal responsive shrinkage of DLP 3D printed C-PNPD hydrogel structure. Figure 4 (c) SEM images of C-PNPD hydrogel at room temperature and body temperature.

[0072] PNIPAm has good amphiphilicity due to its hydrophilic amide group (-CONH-) and hydrophobic isopropyl group [-CH(CH3)2], and its phase transition temperature is near the physiological temperature of human body and slightly higher than the ambient temperature. Figure 4 (a) It can be seen that when the temperature of PNIPAm polymer chain in aqueous solution is higher than 32℃, the hydrophobic interaction is enhanced, causing the gel to shrink, showing the characteristics of thermal response shrinkage. Figure 4 (b) It can be seen that the fine C-PNPD hydrogel structure printed by DLP-based 3D printing technology also shows the contraction effect stimulated by body temperature. Therefore, we studied the changes in the spatial structure of chemically cross-linked hydrogels containing PNIPAm by scanning electron microscopy imaging. Figure 4 (c) As shown in the scanning electron microscopy image, the pore size of the C-PNPD hydrogel at 37 °C is significantly reduced compared with the hydrogel at 25 °C, indicating that the hydrogel containing PNIPAm exhibits good temperature-sensitive shrinkage properties.

[0073] Figure 5 represents the mechanical properties of C-PNPD hydrogel parts, where Figure 5 (a) Stress-strain curve of C-PNPD hydrogel after 100 cycles of compression. Figure 5 (b) Tensile stress-strain curve of C-PNPD hydrogel. Figure 5 (c) C-PNPD hydrogel stretching demonstration. Figure 5 (d) C-PNPD hydrogel adhesion demonstration.

[0074] Since large movable joints need to bend frequently, the top priority in designing wound dressings for joints is to design them with ideal mechanical properties, including stretching, compression, recovery, and mechanical stability. A comprehensive study of stretching, compression, and recovery properties was conducted. The C-PNPD hydrogel system combines the dynamic Schiff base (covalent bond) and micelle cross-linking (non-covalent bond) of PF127 in one system, giving the hydrogel stretchable, compressible, and recoverable mechanical properties. Figure 5 (a) shows the good reversibility of C-PNPD hydrogel during compression and relaxation. Figure 5(b) shows that the C-PNPD hydrogel can be stretched to 1.83 times its original length. Due to its good stretchability, compressive properties and recovery, when the C-PNPD hydrogel is applied to the elbow joint Figure 5 (c) The subjects were able to bend their elbows freely (rotation angle from 0° to 180°), which confirmed the mechanical and adhesion properties of the system. Figure 5 As can be seen in (d), when subjected to 60% strain, the C-PNPD hydrogel neither underwent severe plastic deformation nor experienced a decrease in strength, indicating that it has good mechanical properties and rebound performance.

[0075] Figure 6 The relevant performance data of HaCAT cells co-incubated with C-PNPD hydrogel, Figure 6 (a) Live / Dead staining results of HaCAT cells co-incubated with C-PNPD hydrogel on the first and fifth days. Figure 6 (b) Proliferation activity of HaCAT cells on the first day (24 h) and the second day (48 h) of co-incubation with C-PNPD hydrogel.

[0076] Good cell compatibility is a prerequisite for designing excellent materials in the biomedical field. The cell compatibility of C-PNPD hydrogel was evaluated using CCK-8 and LIVE / DEAD viability / cytotoxicity kits. HaCAT cells were seeded in 48-well plates with the same initial density using the direct contact method, and TCP was selected as a control. Figure 6 In (a), each hydrogel group showed a clear trend of cell proliferation within five days, with almost no cell death occurring and maintaining an elongated spindle-shaped morphology, with no statistically significant difference from the control group without the material. Figure 6 (b) shows that at 24 and 48 hours, there was no statistically significant difference in cell activity between the hydrogel groups and the control group, and there was some trend towards promoting proliferation. All these data demonstrate that these materials have no significant toxicity to cells and have potential applications in the biomedical field.

[0077] Figure 7 It shows the healing effect of C-PNPD hydrogel on the wounds of diabetic rats infected with MRSA.

[0078] Subsequently, in order to study whether C-PNPD hydrogel dressing has the effect of accelerating the healing of chronic wounds, we used hydrogel to treat the wounds of diabetic rats infected with methicillin-resistant Staphylococcus aureus (MRSA) and constructed a diabetic animal model induced by streptozotocin (STZ). After confirming hyperglycemia for 3 weeks, SD (Sprague Dawley) rats with blood glucose levels higher than 17mM were used to establish MRSA-infected wounds. A full-thickness wound (8 mm in diameter) was established on the back of diabetic SD rats. Then, MRSA infection was implemented. One hour after bacterial inoculation, the wound was treated with C-PNPD hydrogel, and 0.9% NaCl was used as a control to observe and record the infection status and size changes of the wound. Figure 7 The following images show the entire wound healing process, showing skin wounds at days 0, 1, 3, 5, 7, and 14. On the first day, the 0.9% NaCl-treated wounds showed significant yellow exudate and severe suppuration, indicating that the inoculated MRSA had successfully infected the wounds. The wounds treated with the C-PNPD hydrogel group were relatively dry, with no visible yellow exudate, demonstrating that the hydrogel effectively prevented MRSA infection. On the third and fifth days of treatment, the wounds in the hydrogel group began to shrink significantly, while the wounds in the 0.9% NaCl group began to scab. After seven days of treatment, the wounds in both groups began to scab, dry, and free of pus exudate. The wounds gradually decreased in size, with more significant shrinkage in the hydrogel group. After 14 days, the scabs in the 0.9% NaCl group had not completely fallen off, indicating that the wounds were not fully healed. In contrast, the wounds in the C-PNPD group had scabs that had fallen off, with visible new tissue formation, indicating near-complete wound healing.

[0079] The present invention describes preferred embodiments and their effects. However, those skilled in the art, once informed of the basic inventive concept, may make additional changes and modifications to these embodiments. Therefore, it is intended that the appended claims be interpreted to include the preferred embodiments and all changes and modifications that fall within the scope of the invention.

[0080] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A composition for preparing 4D printed self-adhesive shape memory tough hydrogel parts, characterized in that: The composition comprises: a functional monomer, an antibacterial micelle crosslinker, an acrylate-based crosslinker, and a photoinitiator; the functional monomer is N-isopropylacrylamide; The antibacterial micelle cross-linker is PF127 loaded with curcumin; The curcumin-loaded PF127 is prepared by dissolving curcumin and PF127 polymer in dichloromethane and self-assembling into micelles; The photoinitiator is (2,4,6-trimethylbenzoyl)diphenylphosphine oxide or phenyl (2, 4, 6-trimethylbenzoyl) lithium phosphate; The acrylate-based cross-linking agent is a cross-linking agent prepared by reacting dopamine hydrochloride and polyethylene glycol diacrylate; The mass ratio of the functional monomer to the antibacterial micelle crosslinker, the acrylate-based crosslinker, and the photoinitiator is (55-70): (7-11): (20-30):

1.

2. Use of the composition according to claim 1 in preparing 4D printed self-adhesive shape memory tough hydrogel parts.

3. A 4D printed self-adhesive shape memory tough hydrogel component, characterized in that: The hydrogel article is made by photocuring 3D printing of raw materials comprising the composition according to claim 1.

4. The method for preparing a 4D printed self-adhesive shape memory tough hydrogel component according to claim 3, characterized in that: The following steps are involved: The functional monomer is mixed with an antibacterial micelle crosslinker, an acrylate-based crosslinker, and a photoinitiator to form a printing resin solution. After light-curing 3D printing, a three-dimensional hydrogel product is obtained.

5. Use of the 4D printed self-adhesive shape memory tough hydrogel product according to claim 3 as a wound dressing.

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