A biomimetic directional gel dressing and its preparation method and application

Abstract

The present application belongs to the technical field of medical biomaterials, and particularly relates to a kind of biomimetic directional gel dressings and its preparation method and application.The dressing includes a hydrophilic directional gel matrix, which has directional microchannels arranged in parallel along the axial direction inside;And the super-hydrophobic functional layer coated on the side wall and top of the matrix.The bottom surface hydrophilic directional channel actively pumps the wound blood by virtue of strong capillary force, uses the spatial confinement effect to extract water and activates platelets, constructs in-situ composite embolism, and provides contact guidance topography to promote tissue repair and regeneration;The super-hydrophobic side wall is used to contact the wound to remove water and trap cells, and the super-hydrophobic top is used as a fluid sealing boundary to force blood to be confined in the channel, and all are used to resist postoperative tissue adhesion.The present application realizes the integration and cooperation of rapid hemostasis, anti-adhesion and repair promotion in the non-compression trunk massive hemorrhage scene, and solves the technical problems that the existing dressing cannot consider thrombus stability, anti-adhesion and tissue ordered repair.

Description

Technical Field

[0001] This invention belongs to the field of medical biomaterials technology, specifically relating to a directional gel dressing based on the biomimetic design of taro stems, its preparation method, and its application. Background Technology

[0002] Non-compression trunk hemorrhage (NCTH) typically involves high-grade injuries to major organs in the thoracic and abdominal cavities or the large blood vessel system. Because external compression is impossible, the peacetime mortality rate is as high as 70.4%, and in wartime it rises to 85.5%. Massive blood loss can quickly induce a "fatal triad" of acidosis, coagulation disorders, and hypothermia, and postoperative secondary bleeding and tissue adhesions constitute the main complications. Existing packing materials, such as chitosan sponges, gelatin, or collagen sponges, suffer from disordered fluid absorption and lateral escape of whole blood due to their strong hydrophilicity; they also readily adhere to blood clots and newly formed tissue. Postoperative removal of the packing material forcibly tears and ruptures the newly formed blood vessels in the wound, resulting in a secondary rebleeding rate greater than 20%, causing severe secondary wound damage. To address the aforementioned issues, existing technologies also employ hydrophobic anti-adhesion packing materials, such as hydrophobic dressings coated with silicone oil or fluoropolymers, resulting in Janus patch-like dressings with a hydrophobic lower layer and a hydrophilic upper layer. While these dressings can reduce tissue adhesion, the interface lacks effective capture dynamics for whole blood. Blood slips or spreads on the surface and cannot concentrate in situ at the wound site. The resulting thrombus is easily dislodged under the impact of non-compression dynamic blood flow and is unable to withstand arterial bleeding with high pressure greater than 140 mmHg, which can easily lead to secondary massive hemorrhage.

[0003] The dilemma of rapid hemostasis, tissue adhesion prevention, and orderly repair of the aforementioned packing materials lies in the fact that increasing hydrophilic pores can enhance blood absorption and coagulation capabilities, but the disordered space lacks boundary constraints, causing severe adhesion of the wound surface; while applying a hydrophobic coating can prevent adhesion, it loses the fluid capture power, causing blood to slip, and the closed structure cannot provide contact guidance morphology for the subsequent directional migration of cells and tissue repair. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention is inspired by the natural mechanism of taro stems, which features "superhydrophobic external drainage of the outer epidermis and directional high-speed water transport of the internal vascular bundles." It provides a biomimetic directional gel dressing for non-compression-induced trunk bleeding and its preparation method. The biomimetic directional gel dressing provided by this invention has a dual-functional structure: a vertically oriented microchannel hydrophilic gel matrix and superhydrophobic functional layers on the sidewalls and top. The directional microchannels provide a 43% increase in initial blood absorption speed, actively pumping and concentrating blood components to achieve rapid in-situ coagulation against arterial bleeding with hypertension greater than 140 mmHg. The superhydrophobic functional layers on the sidewalls and top act as fluid-sealing boundaries to block blood escape, reducing tissue adhesion strength in the blood environment to approximately 2 kPa. This helps prevent pathological adhesions and guides directional cell migration, achieving non-destructive removal and orderly repair.

[0005] To achieve the above objectives, the present invention is specifically implemented through the following technical solutions.

[0006] The first objective of this invention is to provide a biomimetic directional gel dressing comprising a hydrophilic gel matrix with a columnar structure; the interior of the hydrophilic gel matrix contains multiple channels with a diameter of 75 μm to 100 μm along the axial direction; the channels are used to contact the wound surface to achieve efficient confined fluid absorption, hemostasis, and promote repair; the channel diameter of 75 μm to 100 μm provides a strong anisotropic capillary driving force to rapidly pump whole blood from the wound surface, and utilizes the spatial confined filtration effect of the narrow channels to quickly remove fluid moisture, resulting in high-density physical enrichment and concentration of red blood cells and platelets within the channels, significantly accelerating the intrinsic coagulation cascade reaction.

[0007] This invention utilizes a hydrophilic gel matrix as a cylindrical colloid, with additional superhydrophobic coatings added to its sidewalls and top to prepare a cylindrical hemostatic dressing. This dressing achieves hemostasis through the absorption of liquid on the hydrophilic surface, while the hydrophobic surface at the top of the hydrophilic gel matrix displaces water and attracts blood cells for further hemostasis. The hydrophilic surface at the bottom of the hydrophilic gel matrix rapidly absorbs liquid, and the top seals the surface to attract blood cells for clotting. The sidewalls displace water and adhere to blood cells for hemostasis, while the internal directional channels guide cell growth to accelerate healing. The cylindrical structure and the superhydrophobic functional layers on the top and sidewalls effectively solve the problem of existing Janus patch-like dressings with a hydrophobic bottom layer and a hydrophilic top layer being unable to withstand arterial bleeding with hypertension exceeding 140 mmHg.

[0008] The biomimetic directional gel dressing provided by this invention can withstand arterial bleeding pressures exceeding 140 mmHg, and in a preferred embodiment exceeding 280 mmHg, wherein the high-pressure flushing threshold for non-compression-induced massive truncal hemorrhage is 140 mmHg. This dressing meets the need for rapid in-situ coagulation after deep large vessel rupture. When the dressing's bottom surface contacts the wound, its in vitro blood bulk coagulation index (BCI) is below 30% within 30 seconds, and in a preferred embodiment below 25%, meeting the need for efficient confined enrichment and coagulation promotion through the vertical channels of the bottom surface. When the dressing's sidewall environment contacts whole blood, its BCI index can rapidly decrease to below 20% within 60 seconds, and in a preferred embodiment below 10% within 120 seconds. This dressing achieves spatial control of the internal conduction and external septation of whole blood. The adhesion strength between the superhydrophobic functional layer and the wound tissue is <2 kPa; when the adhesion strength is >15 kPa, it can lead to tearing of newly formed granulation tissue and new blood vessels, increasing the risk of secondary bleeding by 200%. The dressing of this invention can effectively reduce the risk of secondary bleeding from the wound caused by adhesion.

[0009] The hydrophilic gel matrix has a superhydrophobic functional layer at one end and on the sidewall; The hydrophilic gel matrix has a superhydrophobic functional layer at one end as the top and the other end as the bottom. The sidewall is provided with a superhydrophobic functional layer for contact with the wound surface to drain water and retain cells, and the top is provided with a superhydrophobic functional layer for use as a fluid sealing boundary to force blood to be transported in a confined manner within the channel. Both are used to resist tissue adhesion.

[0010] Preferably, the material of the superhydrophobic functional layer is at least one of a composite of dimethylsiloxane and TiO2, fluorinated carbon nanotubes, and perfluorosilane.

[0011] Preferably, the superhydrophobic functional layer has a tissue adhesion strength of 2kPa to 5kPa in a blood environment, which endows the material with excellent interfacial bioinertness and low wettability, thereby significantly reducing the mechanical traction force on the granulation tissue and new blood vessels of the wound when the dressing is removed, and avoiding secondary peeling damage caused by pathological adhesion from the source.

[0012] Preferably, the raw material of the hydrophilic gel matrix includes at least one of gelatin / sodium alginate, quaternary ammonium chitosan / sodium β-glycerophosphate, or polyvinyl alcohol / cellulose. It should be noted that the aqueous gel matrix of the present invention can be any gel in the prior art suitable for hemostasis after non-compression-induced trunk bleeding. The gel is loaded with water, and then, using the directional freeze-drying method of the present invention, a channel structure is formed in the aqueous gel matrix, with each channel perpendicular to the hydrophilic bottom surface. The sidewalls and top surface of the gel matrix with the channel structure are immersed in a superhydrophobic functional layer solution, and then dried to obtain a biomimetic directional gel dressing.

[0013] The second objective of this invention is to provide a method for preparing the above-mentioned biomimetic directional gel dressing, comprising the following steps: A hydrophilic gel matrix containing water is subjected to directional freeze-drying, in which liquid nitrogen is used to directionally freeze the matrix in a direction perpendicular to the bottom, thereby forming multiple parallel channels along the axial direction inside the hydrophilic gel matrix, resulting in a hydrophilic gel matrix with channels. One end of the hydrophilic gel matrix is ​​immersed in a superhydrophobic functional layer solution to obtain a superhydrophobic functional layer, which is used as the top of the hydrophilic gel matrix, and the other end of the hydrophilic gel matrix is ​​used as the bottom. The sidewalls of the hydrophilic gel matrix are immersed in a superhydrophobic functional layer solution to obtain a superhydrophobic functional layer, thus obtaining a biomimetic directional gel dressing. When the superhydrophobic functional layer material is a composite of polydimethylsiloxane and TiO2, the superhydrophobic functional layer solution refers to a mixture prepared by dispersing polydimethylsiloxane and TiO2 nanoparticles in cyclohexane and anhydrous ethanol in equal volume ratios; the mass of TiO2 nanoparticles is 30% to 50% of the mass of polydimethylsiloxane, and the concentration of polydimethylsiloxane in the mixture is 1 wt% to 4 wt%. When the superhydrophobic functional layer material is fluorinated carbon nanotubes and perfluorosilane, the superhydrophobic functional layer solution refers to the solution obtained by dispersing fluorinated carbon nanotubes and perfluorosilane in an organic solvent; the mass ratio of fluorinated carbon nanotubes to perfluorosilane is 1~5:1, and the concentration of fluorinated carbon nanotubes in the organic solvent is 0.5mg / mL~5mg / mL; the organic solvent is at least one of ethanol, isopropanol or tetrahydrofuran; preferably, the perfluorosilane is heptadecafluorodecyltriethoxysilane.

[0014] The channel structure provides excellent confined liquid absorption performance and high compressive mechanical strength; the superhydrophobic functional layer is tightly bonded to the directional gel matrix, giving the dressing low adhesion, rapid hemostasis, and fluid-blocking properties. The gel matrix prepared by directional cryotherapy in this invention has a degradation time of 7 to 28 days, and the degradation rate matches the orderly repair and angiogenesis cycle of deep trunk tissues.

[0015] Preferably, the directional freeze-drying method refers to directional freezing in liquid nitrogen in a direction perpendicular to the bottom surface, followed by freeze-drying. Specifically, directional freezing in liquid nitrogen in a direction perpendicular to the bottom surface involves pouring a water-containing gel matrix into a cylindrical polytetrafluoroethylene mold and directionally freezing it in liquid nitrogen at -180°C at a cooling rate of 2°C / min to 5°C / min in a direction perpendicular to the bottom of the hydrophilic gel matrix. Under these conditions, the size of the ice crystals formed is mainly determined by the ice crystal growth rate, which is controlled by the cooling rate and the temperature field. The above parameter range can effectively guide the ice crystal diameter to 75μm~100μm.

[0016] Preferably, the hydrophilic gel matrix containing water has a mass percentage of 20% to 100%.

[0017] The third objective of this invention is to provide the application of the above-mentioned biomimetic directional gel dressing in the preparation of products for rapid hemostasis, anti-tissue adhesion, and wound repair of non-compression-induced massive trunk bleeding.

[0018] Preferably, the bottom of the biomimetic directional gel dressing is in perpendicular contact with the damaged wound surface for confined fluid absorption, and the superhydrophobic functional layer on the sidewalls and top of the biomimetic directional gel dressing acts as a fluid-blocking boundary and an anti-adhesion barrier.

[0019] In application, the hydrophilic bottom surface of the biomimetic directional gel dressing is brought into contact with the damaged wound, with the directional microchannels perpendicular to the wound. Through the highly efficient confined liquid absorption of the vertically oriented channels and the low wettability of the superhydrophobic functional layers on the top and sidewalls, the dressing simultaneously achieves rapid in-situ coagulation, efficient anti-adhesion, fluid pressure closure, and promotion of orderly tissue repair. While actively pumping and concentrating blood components through anisotropic capillary forces, the dressing primarily uses the superhydrophobic functional layer at the top as a high-wetting-resistance fluid closure boundary to force high-pressure blood to be transported confined within the channels, achieving rapid in-situ coagulation against arterial bleeding exceeding 140 mmHg. Due to the dressing's excellent compressive mechanical strength and degradation rate highly matched to the tissue repair cycle, it effectively provides topological contact guidance morphology to support directional cell migration and improve the quality of in-situ wound healing.

[0020] Preferably, the non-compression trunk hemorrhage rapid hemostasis, anti-tissue adhesion and wound repair product is used for emergency treatment, anti-adhesion and in-situ tissue repair care after fatal trunk hemorrhage, solid organ damage or severe trauma and rupture of large blood vessels.

[0021] Compared with the prior art, the present invention has the following beneficial effects: The present invention provides a biomimetic directional gel dressing, comprising a hydrophilic gel matrix with a columnar structure, wherein the interior of the hydrophilic gel matrix has multiple channels with diameters of 75μm to 100μm arranged parallel along the axial direction, each channel being perpendicular to the hydrophilic bottom; and a superhydrophobic functional layer is coated on the sidewalls and top of the gel matrix. Compared to existing patch structures with a hydrophobic lower layer and a hydrophilic upper layer, the biomimetic directional gel dressing of this invention features a cylindrical structure with three hydrophobic surfaces. The superhydrophobic functional layer at the top acts as a fluid-sealing boundary, forcing blood to be transported within a confined space. This effectively solves the problem of secondary massive bleeding caused by the lack of effective capture of whole blood at the interface, leading to blood slippage or spreading on the surface. It effectively combats arterial bleeding at high pressures exceeding 140 mmHg, up to a maximum of 280 mmHg. The low adhesion of the sidewalls and top prevents tissue adhesion, significantly reducing the adhesion strength between the dressing and the wound tissue to 2 kPa~5 kPa. This allows for non-destructive removal of the dressing postoperatively, preventing secondary tearing and bleeding caused by fibrin adhesion. This invention solves the problem that existing non-compression trunk hemostatic dressings cannot simultaneously achieve postoperative hemostasis, reduce adhesion, and promote healing. In this invention, the bottom of the biomimetic directional gel dressing is a hydrophilic surface for vertical contact with the injured wound. The anisotropic capillary force of the bottom directional channel actively pumps whole blood, increasing the initial blood absorption speed by 43%. Attached Figure Description

[0022] Figure 1 The images show the morphology of different parts of the taro stem; (a) is the morphology of the bottom surface of the taro stem, (b) is the morphology of the inside of the taro stem, and (c) is the morphology of the side wall of the taro stem.

[0023] Figure 2 The images show the morphology of different parts of the biomimetic directional gel dressings prepared in Example 1 and Comparative Example 1, respectively; where (a) is the morphology of the bottom surface of Example 1; (b) is the morphology of the interior of Example 1; (c) is the morphology of the sidewall of Example 1; (d) is the morphology of the bottom surface of Comparative Example 1; (e) is the morphology of the interior of Comparative Example 1; and (f) is the morphology of the sidewall of Comparative Example 1.

[0024] Figure 3 The images show the EDS analysis results of the biomimetic directional gel dressings prepared in Example 1 and Comparative Example 1, respectively; where (a) is the EDS analysis result of the hydrophobic layer on the sidewall of Example 1, and (b) is the EDS analysis result of the hydrophobic layer on the sidewall of Comparative Example 1.

[0025] Figure 4 Figure 1 shows the hydrophobicity analysis results of different biomimetic directional gel dressings; (a) is a bar chart of the contact angle of the bottom and sidewalls of Example 1 and Comparative Example 1; (b) is the water and blood rolling angle of the sidewall of Example 1 and Comparative Example 2.

[0026] Figure 5 The following graphs show the blood absorption analysis results of different biomimetic directional gel dressings: (a) is a graph showing the blood absorption rate of Example 1, Comparative Example 1, and Comparative Example 2; (b) is a graph showing the blood absorption capacity of Example 1, Comparative Example 1, and Comparative Example 2.

[0027] Figure 6 The images show the coagulation results of the sidewalls of different biomimetic directional gel dressings; (a) shows the gross morphology of in vitro whole blood coagulation at 1 min and 2 min after rabbit whole blood containing 0.1 mol / L CaCl2 was added to the sidewalls of Example 1, Comparative Example 1, Comparative Example 2, and the blank control group; (b) shows the in vitro whole blood coagulation index (BCI) curves for each group at different time points. D-NHS is the cryogel prepared in Example 1, and R-NHS is the cryogel prepared in Comparative Example 1.

[0028] Figure 7 The images show the coagulation results of different biomimetic directional gel dressings. (a) shows the gross morphology of in vitro whole blood coagulation at 1 min and 2 min after rabbit whole blood containing 0.1 mol / L CaCl2 was added to the hydrophilic bottom surface of Example 1, the hydrophilic bottom surface of Comparative Example 1, the hydrophilic bottom surface of Comparative Example 2, and the blank control group. (b) shows the in vitro whole blood coagulation index (BCI) curves of each group at different time points.

[0029] Figure 8 The dynamic adhesion force-displacement curves of the sidewalls of Example 1, Comparative Example 1, and Comparative Example 2 during droplet dynamic contact tensile testing are used to characterize the low physical adhesion properties of the superhydrophobic functional layer during droplet contact and separation.

[0030] Figure 9 The stress-strain curves of the sidewalls of Example 1, Comparative Example 1, and Comparative Example 2, obtained by overlapping shear tests with pig skin tissue under a simulated whole blood wetting environment, are used to characterize the extremely low tissue adhesion strength of the superhydrophobic functional layer in the blood environment. Figure 10 Example 1, Comparative Example 1, and Comparative Example 2 are bar charts applied to simulated ruptured blood vessel wounds to characterize the dressing's ability to resist fluid occlusion pressure against normal arterial blood pressure and hypertensive arterial bleeding.

[0031] Figure 11 The figures show the bleeding volume and hemostasis time of penetrating wounds in rat livers in Example 1, Comparative Example 1, Comparative Example 2, blank control group, and commercially available product group. (a) is a statistical graph of hemostasis time, and (b) is a statistical graph of bleeding volume.

[0032] Figure 12These are macroscopic images of the adhesion between the dressings of Example 1 and the commercial group 7 days after implantation in the body. (a) is a macroscopic image of the adhesion between the dressings of Example 1 and the wound tissue, and (b) is a macroscopic image of the adhesion between the commercial group and the wound tissue. The commercial group uses IRegene. In the images, "No adhesion" indicates no adhesion, and "adhesion" indicates adhesion. Detailed Implementation

[0033] To enable those skilled in the art to better understand and implement the technical solutions of the present invention, the present invention will be further described below with reference to specific embodiments and accompanying drawings. However, the embodiments described are not intended to limit the present invention. Unless otherwise specified, the experimental methods and detection methods described in the following embodiments are conventional methods; unless otherwise specified, the reagents and materials described are commercially available.

[0034] Existing non-compression packing materials for massive trunk bleeding cannot simultaneously achieve rapid postoperative hemostasis, prevention of tissue adhesion, and guidance of orderly repair. To address this issue, this invention provides a biomimetic directional gel dressing, specifically a directional cryogel dressing with a superhydrophobic functional layer, comprising an interconnected hydrophilic gel matrix and a superhydrophobic functional layer.

[0035] The hydrophilic gel matrix has a channel structure with directional microchannels perpendicular to the hydrophilic bottom surface, which are used to contact the wound surface to achieve efficient confined fluid absorption, hemostasis, and promote repair.

[0036] A superhydrophobic functional layer is coated on the sidewalls and top of the gel matrix, wherein the sidewalls are used to contact the wound surface to drain water and trap cells, and the top is used as a fluid-sealing boundary to force blood to transport within a confined channel, and both serve to resist tissue adhesion.

[0037] The superhydrophobic functional layer has a contact angle of 90°~160°, more preferably ≥150°, and a roll-off angle <5°. Specifically, the superhydrophobic functional layer coated on the top of the gel matrix is ​​mainly used to construct a fluid-sealing boundary on the top of the dressing; the superhydrophobic functional layer coated on the sidewall of the gel matrix is ​​mainly used to contact the wound surface to drain water and retain cells for hemostasis and reduce adhesion to tissues.

[0038] This invention provides a dressing with superior non-compression rapid hemostasis, in-situ degradation, and highly efficient anti-tissue adhesion properties. It aims to fundamentally solve the problem of simultaneously achieving rapid hemostasis, preventing postoperative adhesion, and in-situ tissue repair after massive trunk bleeding and solid organ injury. The dressing uses a biodegradable vertically oriented microchannel cryogel as its matrix, with a superhydrophobic functional layer applied to its sidewalls and top. Its key hemostatic and anti-adhesion mechanisms are: the hydrophilic bottom surface and the vertically oriented channels utilize strong anisotropic capillary forces to actively pump and enrich whole blood from the wound; simultaneously, the superhydrophobic functional layer at the top acts as a fluid-sealing boundary with high wetting resistance, allowing high-pressure blood to be transported within the channels and undergo efficient physical filtration and concentration, thus synergistically achieving rapid coagulation to combat high-pressure arterial bleeding. In this process, because the dressing is designed for in-situ degradation without the need for secondary surgical removal, the superhydrophobic functional layers on the sidewalls and top endow the material with extremely strong interfacial bioinertness, significantly reducing the tissue adhesion strength in a whole blood environment to 2kPa~5kPa. This effectively blocks the disordered spread of blood in non-wound areas, preventing pathological complications such as adhesion between the dressing and surrounding healthy organs or peritoneum from the source. Furthermore, the dressing of this invention possesses a degradation rate highly matched to the in-situ tissue repair and angiogenesis cycle. While undergoing autonomous in-situ degradation, the vertically oriented channels continuously act as microscopic topological signals to guide fibroblasts and new blood vessels to grow orderly along the channels, thereby blocking disordered scar hyperplasia. This comprehensively optimizes the in-situ tissue regeneration and repair effect after fatal trunk hemorrhage and solid organ injury, and has broad clinical application prospects.

[0039] As an example, the mass percentage of the hydrogel matrix in the aqueous hydrogel matrix was set to 20 wt%, 40 wt%, 60 wt%, 80 wt%, and 100 wt%, respectively, thus preparing five cryogel matrices with differentiated pore structures. The contact angle of the hydrophobic layer can be 90°, 100°, 120°, 130°, 140°, 150°, and 160°.

[0040] In use, the biomimetic directional gel dressing is packed into the interior of a penetrating wound. When there is a large amount of bleeding from the wound, the blood comes into contact with the superhydrophobic functional layer on top of the dressing, and the pressure increases. Due to the directional freezing process used in the cryogel matrix (significantly improving the compressive modulus for 20wt%~100wt%), the material contains channel structures perpendicular to the hydrophilic bottom surface, rather than a chaotic porous structure. This forces the surging, high-pressure blood to be transported and concentrated within the channels, preventing it from escaping uncontrollably from the boundary of the superhydrophobic functional layer on top. At the same time, the longitudinally aligned channel structure perpendicular to the bottom surface maintains excellent anisotropic compressive strength while ensuring that the initial blood absorption rate of the dressing bottom surface is increased by more than 43%, far exceeding the pumping rate required in a massive bleeding environment. At this time, the vertically oriented channels on the bottom surface continuously utilize strong anisotropic capillary forces to filter and enrich coagulation factors, reducing the in vitro blood bulk coagulation index (BCI) of the dressing bottom surface to below 25% within 30 seconds, ensuring rapid in-situ coagulation of the wound. At the same time, the low adhesion properties of the superhydrophobic surface of the sidewall cause its BCI index to drop rapidly to below 20% within 60 seconds and further to below 10% within 120 seconds, effectively blocking the disorderly spread and infiltration of spilled blood in the sidewall area and preventing the formation of a strong fibrin adhesion complex in non-wound areas.

[0041] When the amount of bleeding decreases, the pressure of blood on the biomimetic directional gel dressing decreases. Because the top superhydrophobic functional layer locks the fluid boundary, and the tissue adhesion strength of the sidewall superhydrophobic functional layer in a blood environment is <2 kPa (or preferably 2 kPa~5 kPa), the dressing completely blocks high-pressure blood penetration. Comparative experiments show that the control group (R-NHS) using a random freezing process, due to its disordered pore structure, cannot provide anisotropic confined pumping and liquid sealing capabilities (burst pressure significantly lower than the normal arterial pressure range), and also causes large-scale infiltration of blood components into the disordered pores, leading to tissue adhesion and tearing.

[0042] Therefore, the biomimetic directional gel dressing provided by this invention, through the synergistic effect of the vertical channel structure constructed by directional cryopreservation technology and the superhydrophobic interface, not only meets the stringent requirements of the in vivo environment for high pressure resistance and in-situ degradation, but also achieves: ① immediate blocking of pathological adhesions in non-wound areas (tissue adhesion strength in whole blood environment <2kPa, and dynamic detachment adhesion force of the superhydrophobic layer to whole blood droplets <40 μN); ② extremely excellent immediate hemostasis capability in in vivo liver bleeding (hemostasis time <15s, blood loss <0.1g in a live animal rat liver injury model). While ensuring in-situ autonomous degradation, it significantly reduces the risk of organ pathological complications and adhesions after massive in vivo hemorrhage. Hemostasis speed and burst pressure resistance are improved by more than 90%, resulting in an improvement of more than 50% in the quality of in-situ wound repair and angiogenesis.

[0043] The present invention will be specifically described below through the following examples and comparative examples. Polydimethylsilane was purchased from Dow Corning, and TiO2 particles with a diameter of 100 nm (before coating) were purchased from Golden Red, which is oleophilic.

[0044] Example 1 A method for preparing a biomimetic directional gel specifically includes the following steps: Step 1: Preparation of hydrophilic gel matrix: Polyvinyl alcohol (PVA), quaternary ammonium salt chitosan (QCS), and NaIO4 were selected as the main raw materials.

[0045] (1) First, PVA 1799 (hydroxyl content 22.7 mmol) was dissolved in DMSO and heated to 100°C. Then, it was cooled to 25°C and, under nitrogen protection, 0.58 mmol of p-toluenesulfonic acid and 5.68 mmol of 3,4-dihydroxybenzaldehyde were added. Subsequently, the temperature was raised to 75°C and the reaction was carried out for 6 hours. After the reaction was completed, the reaction solution was cooled to room temperature. The reaction solution was added dropwise to a large amount of deionized water to obtain a light white precipitate, which was repeatedly washed with deionized water until neutral. Then, unreacted 3,4-dihydroxybenzaldehyde was washed away with a large amount of deionized water. Finally, catechol-modified PVA was obtained by precipitation, named Ch-PVA (1.1 g), and dried under vacuum at 50°C.

[0046] (2) 1.1 g of Ch-PVA was dissolved in water to prepare a 20 wt% aqueous solution. This solution was then slowly mixed with a 4 wt% QCS aqueous solution at 0 °C at a volume ratio of 1:1 to obtain a homogeneous ch-PVA-QCS composite solution. A 1.8 mg / mL NaIO4 solution was added dropwise to the composite solution, with the added amount being 2.5% of the total volume of the ch-PVA-QCS composite solution, triggering catechol oxidative crosslinking. After oxidation, the solution was injected into a cylindrical polytetrafluoroethylene mold and oriented frozen in liquid nitrogen at -180 °C at a cooling rate of 3 °C / min in a direction perpendicular to the bottom surface. The mixture was then freeze-dried to form a cryogel matrix with highly oriented vertical channels. This matrix possesses both high liquid absorbency and excellent mechanical strength, simultaneously meeting the requirements for rapid hemostasis and hemostatic support.

[0047] Step 2: Preparation of the superhydrophobic coating: Polydimethylsiloxane (PDMS) was dissolved in a mixture of cyclohexane and anhydrous ethanol solvent. The concentration of PDMS in the mixture was 4 wt%, and the volume ratio of cyclohexane to anhydrous ethanol was 1:1. TiO2 particles were added and stirred evenly to form a uniform coating solution. The mass of TiO2 nanoparticles was 30% of the mass of PDMS. The above coating solution was coated on the sidewalls and top of the hydrophilic gel matrix using the immersion method to ensure a tight bond between the coating and the hydrophilic gel matrix.

[0048] Step 3: Completion of the biomimetic directional gel dressing: After coating, it is dried at 80℃ for 120 minutes to obtain a biomimetic directional gel dressing with a superhydrophobic coating, denoted as D-NHS. PDMS and TiO2 in the coating together endow the dressing surface with superhydrophobicity, resulting in a sidewall contact angle of 150.2° and a roll-off angle of 2°.

[0049] Example 2 A method for preparing a biomimetic directional gel specifically includes the following steps: Step 1: Compared with Example 1, Ch-PVA from Step 1 is dissolved in water to prepare an 80wt% aqueous solution. It should be noted that the dilution here refers to diluting the composite solution at the concentration in Step (2) of Example 1 to 80% of the original concentration.

[0050] Step 2 is the same as in Example 1.

[0051] Step three is the same as in Example 1. The prepared dressing has a sidewall contact angle of 135±5° and a roll-off angle of 0°.

[0052] Example 3 A method for preparing a biomimetic directional gel specifically includes the following steps: Step 1: Compared with Example 1, Ch-PVA from Step 1 is dissolved in water to prepare a 60 wt% aqueous solution.

[0053] Step 2 is the same as in Example 1.

[0054] Step three is the same as in Example 1. The prepared dressing has a sidewall contact angle of 120±3.2° and a roll-off angle of 0°.

[0055] Example 4 A method for preparing a biomimetic directional gel specifically includes the following steps: Step 1: Compared with Example 1, Ch-PVA from Step 1 is dissolved in water to prepare a 40 wt% aqueous solution.

[0056] Step 2 is the same as in Example 1.

[0057] Step three is the same as in Example 1. The prepared dressing has a sidewall contact angle of 100±4° and a roll-off angle of 0°.

[0058] Example 5 A method for preparing a biomimetic directional gel specifically includes the following steps: Step 1: Compared with Example 1, the composite solution in step (2) is diluted to a 20 wt% aqueous solution; Step 2 is the same as in Example 1.

[0059] Step three is the same as in Example 1. The prepared dressing has a sidewall contact angle of 90±1.7° and a roll-off angle of 0°.

[0060] Example 6 A method for preparing a biomimetic directional gel specifically includes the following steps: Step 1: Preparation of hydrophilic gel matrix: Sodium alginate and gelatin are selected as the main raw materials.

[0061] First, gelatin and sodium alginate were dissolved separately in deionized water to prepare stock solutions of single polymers, each with a mass percentage of 6%. Then, the gelatin and sodium alginate solutions were mixed at a mass ratio of 50:50 to obtain a mixed polymer solution. A 2% (by volume) and 0.1% (by mass) genipin solution and a 2% (by volume) and 1% (by mass) calcium chloride solution were added to the mixed polymer solution as crosslinking agents. After stirring continuously at 45°C for 2 hours, the mixture was poured into a cylindrical polytetrafluoroethylene mold and freeze-dried in liquid nitrogen in a direction perpendicular to the bottom, forming a hydrophilic gel matrix with channels oriented along the height of the cylinder and perpendicular to the bottom.

[0062] Step 2 is the same as in Example 1.

[0063] Step 3 is the same as in Example 1.

[0064] The taro stems were characterized as follows: SEM images of each side of the taro stems were taken using a field emission scanning electron microscope (GeminiSEM 300, Carlzeiss GmbH, Germany). The results are as follows: Figure 1 As shown, (a), (b) and (c) are morphological diagrams of the bottom, interior and sidewalls of the taro stem.

[0065] The biomimetic directional gel dressing (D-NHS) prepared in Example 1 above was characterized as follows: The D-NHS prepared in Example 1 was photographed on each side using a field emission scanning electron microscope (GeminiSEM 300, Carl Zeiss GmbH, Germany). The results are as follows: Figure 2 As shown, (a), (b) and (c) are morphological images of the bottom surface, interior and sidewalls of D-NHS, respectively. (a) and (b) show the morphology of the bottom surface, interior and sidewalls of the hydrophilic gel matrix (without hydrophobic layer) prepared in step one. The prepared D-NHS has a transversely aligned channel structure with an average pore size of 100 μm.

[0066] Further EDS scanning of the hydrophobic coating on the sidewall of Example 1 (D-NHS) revealed that it contained a large amount of PDMS with C, O, and Si, and TiO2 containing Ti and O. Figure 3As shown in (a), the fiber surface is covered by particles, and there are grooves and pores between the particles. This reflects that the superhydrophobic coating gives the material a micro-nano structure similar to the surface of a lotus leaf. EDS characterization proves that PDMS and TiO2 construct a superhydrophobic surface.

[0067] Subsequently, the contact angle and roll-off angle of Example 1 (D-NHS) were measured, such as... Figure 4 As shown in (a), the bottom contact angle is 45.3° ± 1.4°; the sidewall contact angle is 150.2° ± 2.1° (CA > 150°), as... Figure 4 As shown in (b), the roll-off angle is 2° (SA < 5°), which verifies the superhydrophobic properties of its sidewalls.

[0068] Apply the hydrophilic side of the dressing to the blood, such as Figure 5 As shown in (a), Example 1 (D-NHS) exhibited an extremely high initial blood absorption rate upon initial contact with whole blood, reaching 0.010 mL / s. This indicates that the vertically oriented microchannel structure constructed through directional freezing technology endowed D-NHS with a strong anisotropic capillary active pumping effect. Figure 5 As shown in (b), the blood absorption of D-NHS in Example 1 increased significantly within 40 seconds of whole blood exposure, reaching 0.28 mL / m³ in a short period of time. 3 Furthermore, the extremely high stable fluid confinement state is maintained thereafter, which fully demonstrates that the extremely fast active pumping of the vertical channel on the bottom surface of the D-NHS of this invention, together with the high fluid wetting resistance boundary of the side wall and the top superhydrophobic layer, forms a perfect spatial functional synergy.

[0069] like Figure 6 As shown in (a), after adding rabbit whole blood containing 0.1 mol / L CaCl2 to the sidewall of Example 1 (D-NHS), a distinct, locally concentrated, dark red whole blood clot was observed at the edge of the sidewall surface within 1 minute. Complete coagulation was achieved within 2 minutes, forming a complete thrombus protection interface. The results of this morphological photograph are consistent with... Figure 6 (b) The in vitro whole blood coagulation index (BCI) curves show a completely consistent trend. In the early stage of whole blood contact, the BCI index of D-NHS in Example 1 dropped sharply to about 36% in 30s, and further plummeted to about 15% within 60s, and finally dropped to below 10% within 120s, demonstrating the excellent coagulation-promoting ability of the dressing sidewall.

[0070] like Figure 7As shown in (a), after adding rabbit whole blood containing 0.1 mol / L CaCl2 to the hydrophilic bottom of Example 1 (D-NHS), anisotropic pumping enrichment was observed within 1 minute, with the hydrophilic bottom and internal vertical microchannels rapidly exhibiting anisotropic pumping. The supernatant in the well plate showed extremely high clarity, indicating that the whole blood was efficiently confined and spontaneously procoagulated. Procoagulation was achieved by 2 minutes, forming a complete in-situ procoagulant embolization interface. The results of this macroscopic morphology photograph are consistent with... Figure 7 (b) The in vitro whole blood coagulation index (BCI) curves show a completely consistent trend. In the early stage of whole blood contact, the BCI of D-NHS in Example 1 dropped to 25% in 30s, further decreased to 18% in 60s, and finally decreased to 8% in 120s, demonstrating the excellent coagulation-promoting ability of the hydrophilic bottom and vertical channel structure of the dressing.

[0071] like Figure 8 As shown, the sidewall of Example 1 (D-NHS) exhibited extremely superior adhesion properties during the droplet dynamic contact tensile test. During the droplet contact and gradual detachment process, the maximum dynamic detachment adhesion force of the sidewall of Example 1 against the whole blood droplet was less than 40µN, and the droplet was completely and quickly broken apart at a tensile detachment displacement of only about 1.0 mm.

[0072] like Figure 9 As shown, the sidewall of Example 1 (D-NHS) exhibited excellent anti-tissue adhesion properties when subjected to an overlap-shear test with porcine skin tissue under simulated whole blood wetting conditions. The tissue adhesion strength of the sidewall of Example 1 under whole blood conditions was 2 kPa, indicating that it can effectively block pathological cross-linking between fibrin and surrounding healthy tissue.

[0073] like Figure 10 As shown, the burst pressure test value of Example 1 (D-NHS) reached approximately 280 mmHg, which is significantly higher than the yellow shaded area (90 mmHg~140 mmHg) of normal arterial blood pressure. This result indicates that the superhydrophobic functional layer coated on the top enables confined transport and physical filtration of liquid within the vertical microchannel, achieving effective closure against hypertensive arterial bleeding.

[0074] like Figure 11 As shown, in a rat model of penetrating liver wounds, Example 1 (D-NHS) demonstrated excellent hemostatic effects. Figure 10 As shown in (a), regarding hemostasis time, the time required in Example 1 was controlled within 15 seconds, significantly shorter than that in the control group, indicating that it can rapidly promote blood coagulation and effectively control bleeding. Figure 10 As shown in (b), in terms of bleeding volume, the blood loss corresponding to Example 1 was close to 0g, which was significantly lower than that of the control group, further quantitatively confirming its excellent hemostatic ability.

[0075] like Figure 12 As shown, 7 days after implantation of the dressing, the wound in the Example 1 (D-NHS) group showed no adhesion, and the boundaries between the wound and the dressing were clear and clean. This indicates that the hydrophobic design effectively blocked the pathological cross-linking of fibrin in the non-wound area and reduced the risk of complication adhesion between organs.

[0076] Comparative Example 1 The preparation method of the heterogeneous random gel dressing in this comparative example specifically includes: Step 1: Preparation of hydrophilic gel matrix: Polyvinyl alcohol (PVA), chitosan quaternary ammonium salt (QCS), and NaIO4 were selected as the main raw materials.

[0077] (1) First, PVA was functionalized with catechol using 3,4-dihydroxybenzaldehyde. After washing and vacuum drying, catechol-modified PVA (Ch-PVA) was obtained. The specific preparation method of Ch-PVA is the same as that in Example 1.

[0078] (2) Dissolve Ch-PVA into a 20 wt% aqueous solution; then slowly mix the solution with a 4 wt% QCS solution at a volume ratio of 1:1 at low temperature to obtain a homogeneous Ch-PVA-QCS composite solution; add 1.8 mg / mL NaIO4 solution dropwise to the composite solution, the amount of which is 2.5% of the total volume of the composite solution, to trigger catechol oxidative crosslinking; after oxidation, the solution is injected into a cylindrical polytetrafluoroethylene mold, placed in a -20℃ freezer, and then freeze-dried to form a cryogel matrix with random channels.

[0079] Step 2, Preparation of superhydrophobic coating: Same as in Example 1.

[0080] Step 3: Completion of heterogeneous random gel dressing: After coating, the resulting dressing is dried at 80°C for 120 minutes to obtain the final heterogeneous random gel dressing, denoted as R-NHS.

[0081] The R-NHS prepared in Comparative Example 1 was characterized as follows: The R-NHS prepared in Comparative Example 1 was photographed on each side using a field emission scanning electron microscope (GeminiSEM 300, Carl Zeiss GmbH, Germany). The results are as follows: Figure 2 As shown, (d), (e) and (f) are morphological images of the bottom surface, interior and sidewalls of R-NHS prepared in Comparative Example 1. The prepared random cryogel is a random porous material.

[0082] EDS scanning of the hydrophobic coating on the sidewall of Comparative Example 1 (R-NHS) revealed the presence of abundant C, O, and Si PDMS and TiO2 containing Ti and O. Figure 3 As shown in Figure (b), the content of Si and Ti in Comparative Example 1 is slightly less than that in Example 1, and the Si and Ti elements show a sparse and discontinuous distribution trend on the sidewall surface. This indicates that the disordered porous structure constructed by the random freezing process has a large fluid resistance when the superhydrophobic functional layer is dip-coated, which limits the convection and deposition efficiency of the microfluidic fluid. As a result, PDMS and TiO2 particles cannot form a high-density and continuous covering network on the sidewall, thus the hydrophobicity is slightly worse than that in Example 1.

[0083] The contact angle and roll-off angle of Comparative Example 1 (R-NHS) will then be measured, such as... Figure 4 As shown in (a), the bottom contact angle is 56.5° ± 2.7°; the sidewall contact angle is 138.3° ± 6.7° (CA < 150°), as... Figure 4 As shown in (b), the roll-off angle is 13° (SA > 5°). The sidewall of Comparative Example 1 has excellent hydrophobicity but does not achieve the superior superhydrophobic performance of Example 1.

[0084] Apply the hydrophilic side of the dressing to the blood, such as Figure 5 As shown in (a), Comparative Example 1 (R-NHS) exhibited the lowest initial blood absorption rate upon initial contact with whole blood, and its initial blood absorption rate curve was significantly lower than that of Example 1. Figure 5 As shown in (b), the absorption of the liquid in Comparative Example 1 increased slowly, and the final saturation absorption was significantly lower than that in Example 1. The above results indicate that this disordered three-dimensional network disrupts the continuous transport path of the fluid and fails to generate directional concentrated anisotropic capillary forces in the vertical direction, resulting in high fluid permeation resistance and preventing the rapid pumping and spatial enrichment of the initial blood.

[0085] like Figure 6 As shown in (a), after adding rabbit whole blood containing 0.1 mol / L CaCl2 to the sidewall of Comparative Example 1 (R-NHS), a large area of ​​disordered spreading and infiltration of whole blood was observed on the sidewall surface at 1 min, without the formation of discrete blood clots with localized erythrocyte enrichment. The supernatant in the well plate remained turbid and dark red. At 2 min, there was still obvious free whole blood and hemolysis on the surface, indicating that complete coagulation was not achieved. The results of this gross morphology photograph are consistent with... Figure 6 (b) The in vitro whole blood coagulation index (BCI) curves showed a completely consistent trend. During whole blood contact, the BCI index of Comparative Example 1 was above 53% at 30 s, and the overall decline slope from 60 s to 120 s was significantly lower than that of Example 1. This indicates that the sidewall of Comparative Example 1 could not induce an effective interfacial drainage effect, thereby limiting the local enrichment efficiency of blood cells and fibrin, resulting in a significant slowdown in its bulk coagulation rate.

[0086] like Figure 7 As shown in (a), after adding rabbit whole blood containing 0.1 mol / L CaCl2 to the hydrophilic bottom surface of Comparative Example 1 (R-NHS), a slow, disordered permeation and diffusion of the whole blood was observed at 1 min. The supernatant in the well plate maintained a high concentration of pink turbidity, indicating that the bottom surface and internal pores failed to achieve rapid retention and localized coagulation of blood components. By 2 min, the blood clot at the bottom of the well plate had poor formation, blurred edges, and still contained incompletely converted free blood components. The results of this macroscopic morphology photograph are consistent with... Figure 7 (b) The in vitro whole blood coagulation index (BCI) curves show a completely consistent trend. During whole blood contact, the BCI of Comparative Example 1 was significantly lower than that of Example 1, indicating that the poor liquid absorption efficiency caused by the disordered structure inside Comparative Example 1 significantly slowed down the enrichment of blood cells and coagulation factors in the matrix and the bulk coagulation response speed.

[0087] like Figure 8 As shown, the sidewall of Comparative Example 1 (R-NHS) exhibited lower physical adhesion properties during the droplet dynamic contact tensile test. During the droplet contact and gradual detachment process, the maximum dynamic detachment adhesion force of the sidewall of Comparative Example 1 against the entire blood droplet was approximately 100 µN, significantly higher than that of Example 1.

[0088] like Figure 9 As shown, the sidewall of Comparative Example 1 (R-NHS) exhibited good anti-tissue adhesion properties when subjected to an overlap shear test with porcine skin tissue under a simulated whole blood wetting environment. The maximum tissue adhesion strength of the sidewall in the whole blood environment measured in Comparative Example 1 was approximately 3.5 kPa, which was higher than that in Example 1, indicating that it could also effectively prevent pathological cross-linking between fibrin and surrounding healthy tissue.

[0089] like Figure 10 As shown, the burst pressure test value of Comparative Example 1 (R-NHS) reached approximately 200 mmHg, which is higher than the yellow shaded area of ​​normal arterial blood pressure (90 mmHg~140 mmHg) but lower than that of Example 1. This result indicates that the cross-linked network of Comparative Example 1 itself has a certain pressure resistance and fluid barrier capability. However, due to its disordered internal structure, it lacks highly longitudinally aligned vertical microchannels to guide fluid for anisotropic confined transport, and its surface does not form a uniform and continuous superhydrophobic functional layer, resulting in uneven distribution of fluid permeation resistance and inability to achieve stable sealing at higher pressures.

[0090] like Figure 11As shown, in a rat model of penetrating liver wounds, Comparative Example 1 (R-NHS) demonstrated good hemostatic effects. Regarding hemostasis time, Comparative Example 1 required significantly less time than the control group, but was still twice that of Example 1, indicating its effective promotion of blood coagulation and control of bleeding. Regarding blood loss, Comparative Example 1 showed significantly less blood loss than the control group, but was 2.3 times that of Example 1, further quantitatively confirming its good hemostatic ability.

[0091] Comparative Example 2 The superhydrophobic layer was not prepared on the surface of the hydrophilic gel matrix, specifically including the following steps: First, PVA 1799 (hydroxyl content 22.7 mmol) was dissolved in DMSO and heated to 100°C. Then, under nitrogen protection, p-toluenesulfonic acid (0.58 mmol) and 3,4-dihydroxybenzaldehyde (5.68 mmol) were added after cooling to room temperature. The reaction mixture was then heated to 75°C and reacted for 6 hours. After the reaction, the reaction solution was cooled to room temperature. The solution was added dropwise to a large amount of deionized water, resulting in a light white precipitate. This precipitate was repeatedly washed with deionized water until neutral, and then unreacted 3,4-dihydroxybenzaldehyde was washed away with a large amount of deionized water. Finally, catechol-modified PVA, named Ch-PVA (1.1 g), was obtained through precipitation and dried under vacuum at 50°C.

[0092] Ch-PVA was dissolved into a 20 wt% aqueous solution. This solution was then slowly mixed with a 4 wt% QCS aqueous solution at a volume ratio of 1:1 at low temperature to obtain a homogeneous ch-PVA-QCS solution. A 1.8 mg / mL NaIO4 solution was added dropwise to the composite solution, with the added amount being 2.5% of the total volume of the composite solution, triggering the oxidative crosslinking of catechol. After oxidation, the solution was injected into a cylindrical polytetrafluoroethylene mold and oriented frozen in liquid nitrogen at a cooling rate of 3 °C / min in a direction perpendicular to the bottom surface. The mixture was then freeze-dried to form a cryogel matrix with highly oriented vertical channels, denoted as D-NS.

[0093] The hydrophilic bottom surface of the dressing prepared in Comparative Example 2 came into contact with blood, such as... Figure 5 As shown in (a), Comparative Example 2 (D-NS) had a lower initial blood absorption rate in the early stages of contact with whole blood than Example 1, and as Figure 5 As shown in (b), the cumulative blood absorption in the early stage increases slowly, showing a trend of disordered increase in the later stage. The above results indicate that although Comparative Example 2 without modified superhydrophobic functional layer has directional channels, it lacks a surface high wetting resistance boundary, which prevents it from locking the fluid boundary and triggering an effective interfacial drainage effect. This leads to disordered spread and uncontrolled escape of liquid at the material boundary, significantly reducing the efficiency of fluid physical filtration and spatial confinement concentration in the early stage.

[0094] like Figure 6 As shown in (a), after adding rabbit whole blood containing 0.1 mol / L CaCl2 to the sidewall of Comparative Example 2 (D-NS), the liquid in the well plate remained a turbid pink color at 1 min and 2 min, without showing obvious spontaneous in-situ coagulation behavior; the results of this morphological photograph are consistent with... Figure 6 (b) The BCI curves show a consistent trend, with Comparative Example 2 having a BCI above 60% at 30s. These results indicate that Comparative Example 2, without the introduction of a superhydrophobic sidewall functional layer, lacks a high fluid wetting resistance barrier, thus failing to induce an effective interfacial drainage effect and spatial fluid confinement. This leads to disordered spreading and infiltration of whole blood components upon contact, significantly slowing down the local accumulation of blood cells and the procoagulant rate in the sidewall region.

[0095] like Figure 7 As shown in (a), after adding rabbit whole blood containing 0.1 mol / L CaCl2 to the hydrophilic bottom of Comparative Example 2 (D-NS), the clarity of the liquid in the well plate was lower than that in Example 1 at 1 min and 2 min, the blood clot boundaries were blurred and surrounded by free blood components; the results of this morphological photograph are consistent with... Figure 7 (b) shows a consistent trend in the BCI curve, with its BCI value at 30s being significantly higher than that of Example 1. These results indicate that although Comparative Example 2, without the modified superhydrophobic functional layer, possesses a vertical channel structure, the lack of overall spatial fluid wetting boundary confinement prevents the physical filtration and concentration rates of whole blood components from reaching their optimal state in the early contact phase, thus limiting the effective enrichment of blood cells within the matrix and the procoagulant response.

[0096] like Figure 8 As shown, during the droplet dynamic contact tensile test, the sidewall of Comparative Example 2 (D-NS) was rapidly pumped and wetted into the matrix upon contact with the material surface because it lacked a superhydrophobic coating. Therefore, it could not form an effective external droplet, and its maximum dynamic detachment adhesion force was close to zero. These results indicate that the sidewall of Comparative Example 2 without a modified superhydrophobic layer lacks a high fluid wetting resistance barrier, thus failing to impart an anti-tissue adhesion effect on the dressing sidewall.

[0097] like Figure 9 As shown, the sidewall of Comparative Example 2 (D-NS) exhibited the worst anti-tissue adhesion properties when subjected to an overlap shear test with porcine skin tissue under simulated whole blood wetting conditions. The maximum tissue adhesion strength measured in whole blood environment for the sidewall of Comparative Example 2 was approximately 17 kPa, significantly higher than that of Example 1 and Comparative Example 1, indicating that it could not prevent pathological cross-linking between fibrin and surrounding healthy tissue.

[0098] like Figure 10As shown, the burst pressure test value of Comparative Example 2 (D-NS) reached approximately 75 mmHg, which is lower than the yellow shaded area (90-140 mmHg) of normal arterial blood pressure. This result indicates that although Comparative Example 2 without the modified superhydrophobic functional layer has directional microchannels, it lacks a fluid boundary control layer with high wetting resistance on its top and sidewalls. When faced with continuous impact from high-pressure fluid, it cannot form an effective spatial confinement and blockage, causing the liquid to easily spread disorderly and leak out along the material edges and channels. As a result, it cannot resist arterial hypertension bleeding and limits its pressure resistance performance.

[0099] like Figure 11 As shown, in the rat liver penetrating wound model, Comparative Example 2 (D-NS) exhibited poor hemostatic effect. Regarding hemostasis time, although Comparative Example 1 required less time than the control group, it was significantly longer than Example 1, being 5 times longer, indicating poor procoagulant ability. In terms of bleeding volume, Comparative Example 1 showed 5.3 times the blood loss of Example 1, demonstrating poor hemostatic ability.

[0100] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, it is intended to include any modifications and variations that fall within the scope of the claims and their equivalents.

Claims

1. A biomimetic directional gel dressing, characterized in that, It includes a hydrophilic gel matrix with a columnar structure; the interior of the hydrophilic gel matrix has multiple channels with a diameter of 75μm~100μm arranged parallel to each other along the axial direction; The hydrophilic gel matrix has a superhydrophobic functional layer at one end and on the sidewall; The hydrophilic gel matrix has a superhydrophobic functional layer at one end as the top and the other end as the bottom; The tissue adhesion strength of the superhydrophobic functional layer in a blood environment is 2 kPa to 5 kPa.

2. The biomimetic directional gel dressing according to claim 1, characterized in that, The superhydrophobic functional layer is made of at least one of the following: a composite of dimethylsiloxane and TiO2, fluorinated carbon nanotubes, and perfluorosilane.

3. The biomimetic directional gel dressing according to claim 1, characterized in that, The hydrophilic gel matrix includes at least one of gelatin, sodium alginate, quaternary ammonium chitosan, sodium β-glycerophosphate, polyvinyl alcohol, and cellulose.

4. A method for preparing the biomimetic directional gel dressing according to any one of claims 1 to 3, characterized in that, Includes the following steps: A hydrophilic gel matrix containing water is subjected to directional freeze-drying, in which liquid nitrogen is used to directionally freeze the matrix in a direction perpendicular to the bottom, thereby forming multiple parallel channels along the axial direction inside the hydrophilic gel matrix, resulting in a hydrophilic gel matrix with channels. One end of the hydrophilic gel matrix is ​​immersed in a superhydrophobic functional layer solution to obtain a superhydrophobic functional layer, which is used as the top of the hydrophilic gel matrix, and the other end of the hydrophilic gel matrix is ​​used as the bottom. The sidewall of the hydrophilic gel matrix is ​​immersed in a superhydrophobic functional layer solution to obtain a superhydrophobic functional layer, thus obtaining a biomimetic directional gel dressing. When the superhydrophobic functional layer material is a composite of polydimethylsiloxane and TiO2, the superhydrophobic functional layer solution refers to a mixture prepared by dispersing polydimethylsiloxane and TiO2 nanoparticles in cyclohexane and anhydrous ethanol in equal volume ratios; the mass of TiO2 nanoparticles is 30% to 50% of the mass of polydimethylsiloxane, and the concentration of polydimethylsiloxane in the mixture is 1 wt% to 4 wt%. When the superhydrophobic functional layer material is fluorinated carbon nanotubes and perfluorosilane, the superhydrophobic functional layer solution refers to the solution obtained by dispersing fluorinated carbon nanotubes and perfluorosilane in an organic solvent; the mass ratio of fluorinated carbon nanotubes to perfluorosilane is 1~5:1, and the concentration of fluorinated carbon nanotubes in the organic solvent is 0.5mg / mL~5mg / mL; the organic solvent is at least one of ethanol, isopropanol or tetrahydrofuran.

5. The method for preparing the biomimetic directional gel dressing according to claim 4, characterized in that, The directional freezing via liquid nitrogen in a direction perpendicular to the bottom specifically refers to: pouring a water-containing gel matrix into a cylindrical mold, and directional freezing in liquid nitrogen at -180°C at a cooling rate of 2°C / min to 5°C / min in a direction perpendicular to the bottom of the hydrophilic gel matrix.

6. The method for preparing the biomimetic directional gel dressing according to claim 4, characterized in that, In a hydrophilic gel matrix containing water, the mass percentage of the hydrophilic gel matrix is ​​20% to 100%.

7. The use of the biomimetic directional gel dressing according to any one of claims 1 to 3 in the preparation of products for rapid hemostasis, anti-tissue adhesion and wound repair of non-compression trunk hemorrhage.

8. The application according to claim 7, characterized in that, The bottom of the biomimetic directional gel dressing is brought into perpendicular contact with the damaged wound for confined fluid absorption. The superhydrophobic functional layer on the sidewalls and top of the biomimetic directional gel dressing acts as a fluid-sealing boundary and an anti-adhesion barrier.

9. The application according to claim 7, characterized in that, The product is used for any one of the following: emergency treatment, anti-adhesion, and in-situ tissue repair care after fatal massive trunk hemorrhage, substantial organ damage, or severe trauma and rupture of major blood vessels.

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