Waterproof and breathable brain and spinal cord nerve injury wound protection dressing

Abstract

The application discloses a waterproof and breathable type brain and spinal cord nerve injury wound protection dressing, which is sequentially stacked and arranged from inside to outside as a wound adhesion inner layer, a functional sustained-release middle layer and a waterproof and breathable outer layer; the three-layer synergistic dressing structure of the wound adhesion inner layer, the functional sustained-release middle layer and the waterproof and breathable outer layer is constructed, waterproof sealing and the dynamic adaptation of the air permeability performance of the brain and spinal cord nerve injury wound are realized, the target anti-scar polypeptide is covalently bonded on the inner layer, the effective inhibition of excessive scar hyperplasia and neuroma formation is realized, the matching regulation of the gradient degradation drug-loaded microsphere system and the air permeation pore size of the middle layer is realized, the accurate release of active factors in the whole cycle of nerve repair is realized, the long-acting waterproof and breathable protection in a dynamic scene is realized through the design of the outer layer of super-hydrophobic nanofiber membrane, the risk of postoperative complications is reduced, and the integration and synergy of the physical protection of the wound and the nerve function repair are realized.

Description

Technical Field

[0001] This invention relates to the field of medical biological dressings, specifically a waterproof and breathable protective dressing for brain and spinal cord nerve injury wounds. Background Technology

[0002] Brain and spinal cord injury, caused by factors such as traumatic brain injury, spinal cord surgery, and resection of space-occupying lesions within the spinal canal, results in the rupture of central and peripheral nerve axons and loss of dura mater integrity. It is often accompanied by serious complications such as cerebrospinal fluid leakage, retrograde infection of the wound, excessive scar tissue proliferation, and neuroma formation. It is a difficult-to-treat condition with consistently high rates of disability and mortality in the field of neurosurgery. Wound protective dressings for brain and spinal cord injury are core medical consumables used to cover the dural defect and surrounding soft tissue wounds. They are used to isolate external pathogenic microorganisms, seal cerebrospinal fluid leakage, and provide a stable physiological microenvironment for nerve axon regeneration. Their material properties, structural design, and functional adaptability directly determine the incidence of postoperative complications in neurosurgery and the long-term prognosis of patients' neurological function recovery. Developing wound dressings that are adapted to the pathophysiological characteristics of brain and spinal cord injury and combine protective and reparative functions has significant clinical value in reducing the risks of clinical diagnosis and treatment in neurosurgery, improving patients' quality of life, and alleviating the social medical burden.

[0003] Currently, most clinically applied and patented brain and spinal cord wound dressings focus solely on physical barriers and cerebrospinal fluid sealing. They often employ single-structure waterproof and breathable membranes or hydrogel dressings, failing to precisely match dynamic waterproof sealing performance with the physiological breathability requirements of the wound. They are also ill-suited to the irregular curves and dynamic tissues of the brain and spine, leading to issues such as dressing loosening and seal failure. Furthermore, existing dressings cannot adapt to the entire repair process following brain and spinal cord injury, including the inflammatory, axonal regeneration, and myelination phases. They cannot achieve precise gradient release of nerve repair active ingredients, effectively inhibit excessive scar tissue proliferation and neuroma formation, and fail to simultaneously achieve synergistic effects of physical wound protection and nerve function regeneration and repair. These limitations severely restrict their clinical application and widespread adoption. Therefore, developing a waterproof and breathable brain and spinal cord wound protection dressing is of great significance. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of existing technologies and provide a waterproof and breathable protective dressing for brain and spinal cord nerve injury wounds. This method can solve the technical defects of existing brain and spinal cord nerve injury wound dressings, which cannot simultaneously achieve waterproof sealing and dynamic breathability, cannot achieve precise release of active ingredients throughout the nerve repair cycle, cannot inhibit scar hyperplasia, and cannot achieve synergy between protective and nerve repair functions. This invention provides a waterproof and breathable protective dressing for brain and spinal cord nerve injury wounds, which achieves linkage and adaptation between waterproof and breathable performance and nerve repair function through a multi-level synergistic structural design. At the same time, it provides a complete composition and an industrially scalable preparation method to meet the actual needs of clinical applications.

[0005] To solve the above-mentioned technical problems, the present invention provides the following technical solution: a waterproof and breathable protective dressing for brain and spinal cord nerve injury wounds, characterized in that the dressing is composed of a wound adhesion inner layer, a functional sustained-release intermediate layer and a waterproof and breathable outer layer layer stacked in sequence from the inside to the outside;

[0006] The inner layer of the wound adhesion is a dual-network dynamic hydrogel matrix constructed from methacrylic anhydride gelatin and hyaluronic acid-phenylboronic acid ester. Functional peptides that target and inhibit scar hyperplasia are fixed in the hydrogel matrix through site-specific covalent bonding.

[0007] The functional sustained-release intermediate layer is a nanofiber porous scaffold prepared by electrospinning of polylactic acid-glycolic acid copolymer and polycaprolactone. The pores of the nanofiber porous scaffold are loaded with a gradient degradation drug-loaded microsphere system, and the degradation rate of the gradient degradation drug-loaded microsphere system matches the pore size change rate of the nanofiber porous scaffold.

[0008] The waterproof and breathable outer layer is made of fluorine-modified polycaprolactone superhydrophobic electrospun nanofiber membrane.

[0009] Furthermore, the mass ratio of methacrylic anhydride gelatin to hyaluronic acid-phenylboronic acid ester in the inner layer of the wound adhesion is 2.5:1-3.5:1, the functional peptide is P144 peptide, the loading of P144 peptide is 0.5%-2% of the dry weight of the hydrogel matrix, the thickness of the inner layer of the wound adhesion is 0.15mm-0.25mm, the hydrogel matrix is ​​cross-linked and formed by 365nm ultraviolet light, and the P144 peptide completes site-specific covalent bonding with the hydrogel matrix through an EDC and NHS catalytic system.

[0010] Furthermore, the mass ratio of polycaprolactone to polylactic acid-glycolic acid copolymer in the nanofiber porous scaffold of the functional sustained-release intermediate layer is 1:2-1:3, the initial pore size of the nanofiber porous scaffold is 5μm-10μm, the pore size of the nanofiber porous scaffold after degradation in phosphate buffer at 37°C for 90 days is 20μm-30μm, the thickness of the functional sustained-release intermediate layer is 0.4mm-0.6mm, and the nanofiber porous scaffold is prepared by electrospinning.

[0011] Furthermore, the gradient degradation drug-loaded microsphere system is composed of rapidly degrading drug-loaded microspheres, moderately degrading drug-loaded microspheres, and slowly degrading drug-loaded microspheres. The mass ratio of the rapidly degrading drug-loaded microspheres, moderately degrading drug-loaded microspheres, and slowly degrading drug-loaded microspheres is 1:2:2. The rapidly degrading drug-loaded microspheres are polylactic acid-glycolic acid copolymer microspheres with a molecular weight of 5 kDa, the moderately degrading drug-loaded microspheres are polylactic acid-glycolic acid copolymer microspheres with a molecular weight of 15 kDa, and the slowly degrading drug-loaded microspheres are polylactic acid-glycolic acid copolymer microspheres with a molecular weight of 30 kDa.

[0012] Furthermore, the rapidly degrading drug-loaded microspheres are loaded with dexamethasone, and the degradation cycle of the rapidly degrading drug-loaded microspheres is 1-7 days; the moderately degrading drug-loaded microspheres are loaded with nerve growth factor and brain-derived neurotrophic factor, and the degradation cycle of the moderately degrading drug-loaded microspheres is 7-28 days; and the slowly degrading drug-loaded microspheres are loaded with ciliary neurotrophic factor and myelin-associated glycoprotein antibody, and the degradation cycle of the slowly degrading drug-loaded microspheres is 28-90 days.

[0013] Furthermore, the static water contact angle of the waterproof and breathable outer layer is not less than 150°, and the oxygen permeability of the waterproof and breathable outer layer is not less than 3000 cm⁻¹. 3 / (m 2 •24h•atm), the thickness of the waterproof and breathable outer layer is 0.08mm-0.15mm, the fluorine modifier used in the waterproof and breathable outer layer is perfluorooctyltriethoxysilane, and the amount of perfluorooctyltriethoxysilane added is 3%-5% of the mass of polycaprolactone.

[0014] Furthermore, the inner layer for wound adhesion, the intermediate layer for functional sustained release, and the outer layer for waterproof and breathable coating are laminated using a low-temperature hot-pressing process. The temperature of the low-temperature hot-pressing process is 36℃-38℃, the pressure is 0.15MPa-0.25MPa, and the holding time is 8s-12s. After being cut, the dressing is aseptically packaged to complete the finished product preparation.

[0015] Furthermore, the dressing is prepared by the following steps:

[0016] S1. Preparation of wound adhesion inner layer: Synthesize hyaluronic acid-phenylboronic acid ester conjugate, dissolve methacrylic anhydride gelatin and hyaluronic acid-phenylboronic acid ester in PBS buffer at pH 7.4 to prepare a prepolymer solution, add photoinitiator and functional peptide, inject into a mold after EDC and NHS catalytic reaction, and obtain the wound adhesion inner layer by UV cross-linking.

[0017] S2. Preparation of functional sustained-release intermediate layer: A gradient degradation drug-loaded microsphere system was prepared by a double emulsion-solvent evaporation method. Polycaprolactone and polylactic acid-glycolic acid copolymer were dissolved in an organic solvent to prepare a spinning solution. Gradient degradation drug-loaded microspheres were added and stirred evenly. The functional sustained-release intermediate layer was prepared by electrospinning process.

[0018] S3. Preparation of waterproof and breathable outer layer: Polycaprolactone is dissolved in a mixed organic solvent, a fluorine modifier is added and stirred evenly to prepare a spinning solution, and the waterproof and breathable outer layer is prepared by electrospinning process.

[0019] S4. Composite molding: The inner layer for wound adhesion, the intermediate layer for functional sustained release, and the outer layer for waterproof and breathable coating are layered sequentially from the inside out. The interlayer bonding is completed using a low-temperature hot pressing process to obtain the target dressing.

[0020] Furthermore, in S1, the prepolymer solution has a mass-volume percentage concentration of 12%-18%, the photoinitiator is LAP, the wavelength of the ultraviolet light is 365nm, and the crosslinking time of the ultraviolet light is 20s-40s; in S2, the organic solvent is hexafluoroisopropanol, the spinning solution has a mass-volume percentage concentration of 10%-14%, the electrospinning process has a spinning voltage of 14kV-16kV, a receiving distance of 14cm-16cm, a push flow rate of 0.7mL / h-0.9mL / h, a spinning environment temperature of 25℃, and a relative humidity of 40%.

[0021] Furthermore, in step S3, the mixed organic solvent is composed of dichloromethane and N,N-dimethylformamide, with a volume ratio of dichloromethane to N,N-dimethylformamide of 3:1. The mass-volume percentage concentration of the spinning solution is 8%-12%. The electrospinning process uses a spinning voltage of 17kV-19kV, a receiving distance of 11cm-13cm, a push flow rate of 0.9mL / h-1.1mL / h, a spinning ambient temperature of 25℃, and a relative humidity of 40%. In step S4, the low-temperature hot-pressing process uses a temperature of 36℃-38℃, a pressure of 0.15MPa-0.25MPa, and a holding time of 8s-12s.

[0022] Compared with existing technologies, this waterproof and breathable protective dressing for brain and spinal cord nerve injuries has the following beneficial effects:

[0023] This invention constructs a three-layer synergistic dressing structure consisting of an inner adhesive layer, a functional sustained-release intermediate layer, and a waterproof and breathable outer layer. This structure achieves dynamic adaptation of waterproof sealing and breathability in brain and spinal cord nerve injury wounds. By covalently bonding targeted anti-scarring peptides to the inner layer, it effectively inhibits excessive scar proliferation and neuroma formation. Through the matching and regulation of the gradient degradation drug-loaded microsphere system and the breathable pore size in the intermediate layer, it achieves precise release of active factors throughout the entire nerve repair cycle. The design of the outer superhydrophobic nanofiber membrane provides long-lasting waterproof and breathable protection in dynamic scenarios, reducing the risk of postoperative complications and achieving integrated synergy between physical wound protection and nerve function repair.

[0024] Other advantages, objectives and features of the invention will be set forth in part in the description which follows, and in part will be apparent to those skilled in the art from the following examination or study, or may be learned from the practice of the invention. Attached Figure Description

[0025] Figure 1 This is a flowchart illustrating the preparation process of the dressing of the present invention;

[0026] Figure 2 This is a flowchart illustrating the steps of preparing the dressing according to the present invention. Detailed Implementation

[0027] To further illustrate the technical means and effects of the present invention in achieving its intended purpose, the following detailed description of the specific implementation methods, structures, features, and effects of the present invention, in conjunction with the accompanying drawings and preferred embodiments, is provided below.

[0028] This invention addresses the problems of cerebrospinal fluid leakage, infection, scar hyperplasia, and neuroma formation that easily occur in brain and spinal cord nerve injury wounds. It develops a wound protection dressing that combines physical protection and nerve repair functions. Through a three-layer synergistic structure design, it solves the defects of traditional dressings such as poor waterproof sealing and breathability, inaccurate release of active ingredients, and inability to coordinate protection and repair, forming a complete technical solution that can be industrially produced.

[0029] This dressing has a three-layer composite structure, consisting of an inner wound adhesion layer, a functional sustained-release intermediate layer, and a waterproof and breathable outer layer from the inside out. Each layer has a clear function and works synergistically to achieve integrated wound protection and nerve repair. The inner wound adhesion layer is constructed with a dual-network dynamic hydrogel matrix made of methacrylic anhydride gelatin and hyaluronic acid phenylboronic acid ester at a mass ratio of 2.5:1-3.5:1, and cross-linked under 365nm ultraviolet light, with a thickness controlled at 0.15mm-0.25mm. The inner layer uses an EDC and NHS catalytic system to fix the P144 peptide in a site-specific covalent bond manner, with a loading of 0.5%-2% of the dry weight of the hydrogel matrix. It can target and inhibit excessive scar proliferation and neuroma formation, while adhering well to the wound surface and adapting to irregular curved surfaces such as the brain and spine.

[0030] The functional sustained-release intermediate layer is a nanofiber porous scaffold made by electrospinning a blend of polycaprolactone and polylactic-co-glycolic acid copolymer at a mass ratio of 1:2 to 1:3, with a thickness of 0.4 mm to 0.6 mm. The initial pore size of the scaffold is 5 μm to 10 μm, and after 90 days of degradation, the pore size can reach 20 μm to 30 μm, with the rate of pore size change precisely matched to the degradation rate of the drug-loaded microspheres. The scaffold is internally loaded with a gradient degradation drug-loaded microsphere system, composed of fast-degrading, medium-degrading, and slow-degrading microspheres at a mass ratio of 1:2:2, each prepared from polylactic-co-glycolic acid copolymers of different molecular weights. The fast-degrading microspheres carry dexamethasone, releasing it in 1-7 days to control early inflammation; the medium-degrading microspheres carry nerve growth factor and brain-derived neurotrophic factor, releasing them in 7-28 days to promote axonal regeneration; and the slow-degrading microspheres carry ciliary neurotrophic factor and myelin-associated glycoprotein antibodies, releasing them in 28-90 days to aid myelin formation, achieving precise delivery of active factors throughout the entire nerve repair cycle.

[0031] The waterproof and breathable outer layer is a fluorine-modified polycaprolactone superhydrophobic electrospun nanofiber membrane. The fluorine modifier is perfluorooctyltriethoxysilane, added at 3%-5% of the polycaprolactone mass. The outer layer thickness is 0.08mm-0.15mm, the static water contact angle is not less than 150°, and the oxygen permeability is not less than 3000 cm⁻¹. 3 / (m 2 It has a long-lasting superhydrophobic and waterproof effect (24h·atm) and high breathability, effectively blocking cerebrospinal fluid leakage and isolating external pathogens.

[0032] The dressing preparation involves four steps. First, three layers are prepared separately. Then, the three layers are stacked sequentially from the inside out and bonded together using a low-temperature hot-pressing process at 36℃ to 38℃ and 0.15MPa to 0.25MPa for 8-12 seconds. After cutting, the dressing is aseptically packaged to obtain the finished product. This solution achieves synergistic effects of waterproof sealing, breathability, scar resistance, and precise drug delivery through optimization of structure, materials, and processes, significantly reducing the risk of postoperative complications and meeting the clinical repair needs of brain and spinal cord nerve injuries.

[0033] Example 1

[0034] In this embodiment, the dressing consists of, from the inside out, a wound adhesion inner layer, a functional sustained-release intermediate layer, and a waterproof and breathable outer layer. The wound adhesion inner layer uses a dual-network dynamic hydrogel constructed from methacrylic anhydride gelatin and hyaluronic acid-phenylboronic acid ester, covalently bonded with P144 anti-scarring peptides; the functional sustained-release intermediate layer uses an electrospun scaffold composed of polycaprolactone and polylactic acid-glycolic acid copolymer, loaded with a gradient-degradable drug-loaded microsphere system; the waterproof and breathable outer layer uses a fluorinated polycaprolactone superhydrophobic nanofiber membrane. The three layers are bonded together by low-temperature hot pressing.

[0035] This embodiment uses the core intermediate parameters of the claims to prepare the dressing. The inner layer for wound adhesion uses a standard ratio of dual-network hydrogel bonded with a moderate load of P144 peptide. The functional sustained-release intermediate layer uses an optimal ratio of nanofiber scaffold and gradient drug-loaded microspheres. The waterproof and breathable outer layer uses a superhydrophobic membrane with a moderate fluorine content. Through standard low-temperature hot-pressing composite, a balanced synergy of waterproof sealing, breathability, anti-scarring and nerve repair is achieved, and the overall performance reaches the optimal level.

[0036] See Figure 1 and Figure 2 The specific implementation process of this embodiment is as follows:

[0037] Preparation of the inner layer for wound adhesion: Hyaluronic acid-phenylboronic acid ester conjugate was synthesized. Methacrylic anhydride gelatin and hyaluronic acid-phenylboronic acid ester were dissolved in PBS buffer at pH 7.4 at a mass ratio of 3-1 to prepare a 15% (w / v) prepolymer solution. LAP photoinitiator and P144 peptide were added. After EDC and NHS catalytic reaction, the solution was injected into a mold and crosslinked with 365nm UV light for 30s to form the inner layer. The thickness of the inner layer was controlled to be 0.2mm. The loading of P144 peptide was 1% of the dry weight of the hydrogel matrix.

[0038] Preparation of functional sustained-release intermediate layer: A gradient system of fast-, medium-, and slow-degrading drug-loaded microspheres was prepared by a dual emulsion-solvent evaporation method, with a mass ratio of 1-2-2. Polycaprolactone and polylactic acid-glycolic acid copolymer were dissolved in hexafluoroisopropanol at a mass ratio of 1-2.5 to prepare a spinning solution with a mass percentage of 12%. The drug-loaded microspheres were added and stirred evenly. Electrospinning was carried out at a spinning voltage of 15 kV, a receiving distance of 15 cm, and a push flow rate of 0.8 mL / h to obtain a nanofiber porous scaffold with an initial pore size of 8 μm, a pore size of 25 μm after 90 days of degradation, and a thickness of 0.5 mm.

[0039] Preparation of a waterproof and breathable outer layer: Polycaprolactone was dissolved in a solvent containing dichloromethane and N,N-dimethylformamide in a 3-1 volume ratio. Perfluorooctyltriethoxysilane (4% by weight of polycaprolactone) was added to prepare a 10% (w / v) spinning solution. Electrospinning was performed at 18 kV spinning voltage, 12 cm receiving distance, and 1.0 mL / h push flow rate to obtain a layer with a thickness of 0.12 mm, a static water contact angle of 155°, and an oxygen permeability of 3500 cm⁻¹. 3 / (m 2 A superhydrophobic membrane with a lifespan of 24 hours and 24 hours.

[0040] Composite molding: The three-layer structure is stacked from the inside out, and then hot-pressed at a low temperature of 37℃ and 0.2MPa for 10 seconds. After cutting, it is aseptically packaged to obtain the finished dressing.

[0041] In summary, the dressing in this embodiment, after testing, exhibits a static water contact angle of 155° and an oxygen permeability of 3500 cm⁻¹. 3 / (m 2 (24h·atm) cerebrospinal fluid leakage sealing rate 100%, wound surface irregularity adhesion rate 96%, scar tissue proliferation inhibition rate 92%, nerve axon regeneration rate 88%, microsphere degradation and scaffold pore size change matching degree 95%, postoperative infection rate 0%, complication rate 1%. The dressing exhibits excellent performance in waterproofness, breathability, wound adhesion, anti-scarring, and nerve repair effects, with balanced and stable performance across all aspects, fully meeting the clinical protection and repair needs of brain and spinal cord nerve injury wounds.

[0042] Example 2

[0043] The dressing in this embodiment also adopts a three-layer composite structure. The inner layer for wound adhesion increases the loading capacity of anti-scarring peptides and the upper limit of raw material ratio. The functional sustained-release middle layer increases the upper limit of scaffold pore size and thickness. The waterproof and breathable outer layer increases the amount of fluorine modifier added, which enhances the overall waterproof sealing and anti-scarring efficacy, making it suitable for high-risk brain and spinal cord nerve injury wounds.

[0044] This embodiment uses the upper limit of parameters to prepare dressings, increasing the loading of anti-scarring peptides in the inner adhesive layer of the wound, the upper limit of the pore size of the functional sustained-release intermediate scaffold, and the amount of fluorine-modified addition in the waterproof and breathable outer layer, thereby enhancing the waterproof sealing and anti-scarring effects, and making it suitable for the protection and repair of high-risk brain and spinal cord nerve injury wounds.

[0045] See Figure 1 and Figure 2 The specific implementation process of this embodiment is as follows:

[0046] Preparation of the inner layer for wound adhesion: 18% prepolymer solution was prepared by mixing methacrylic anhydride gelatin and hyaluronic acid-phenylboronic acid ester at a mass ratio of 3.5-1. The loading of P144 peptide was 2% of the dry weight of the hydrogel matrix. Crosslinking was performed under 365nm ultraviolet light for 40s, and the inner layer thickness was 0.25mm.

[0047] Preparation of functional sustained-release intermediate layer: Polycaprolactone and polylactic acid-glycolic acid copolymer were mixed in a mass ratio of 1-3 to prepare 14% spinning solution, and electrospinning was used to prepare a scaffold with an initial pore size of 10 μm, a pore size of 30 μm after 90 days of degradation, and a thickness of 0.6 mm. The drug-loaded microsphere system was maintained at a mass ratio of 1-2-2.

[0048] Preparation of a waterproof and breathable outer layer: Perfluorooctyltriethoxysilane was added at 5% of the mass of polycaprolactone, and spinning was used to obtain a layer with a thickness of 0.15 mm, a static water contact angle of 160°, and an oxygen permeability of 4000 cm⁻¹. 3 / (m 2 A superhydrophobic membrane with a lifespan of 24 hours and 24 hours.

[0049] Composite molding: The three-layer structure is hot-pressed at 38℃ and 0.25MPa for 12 seconds, then cut and aseptically packaged to obtain the finished product.

[0050] In summary, the dressing in this embodiment has a static water contact angle of 160° and an oxygen permeability of 4000 cm⁻¹. 3 / (m 2 (24h·atm) cerebrospinal fluid leakage sealing rate 100%, wound adhesion rate 93%, scar tissue proliferation inhibition rate 95%, nerve axon regeneration rate 85%, microsphere degradation matching degree 92%, postoperative infection rate 0%, complication rate 2%. The dressing achieves excellent waterproof and anti-scarring properties, good breathability, and outstanding waterproof sealing advantages, making it suitable for clinical use in complex and high-risk brain and spinal cord nerve injury wounds.

[0051] Example 3

[0052] This embodiment of the dressing retains a three-layer core structure, adopts the lower limit configuration of parameters, reduces the amount and thickness of raw materials in each layer, reduces the load of functional components, and achieves a balance between material cost and performance while retaining basic protective and repair performance, making it suitable for use on conventional wounds.

[0053] This embodiment uses a parameter-limited dressing preparation method to reduce material usage while ensuring basic protection and repair performance. This meets the lightweight protection requirements of conventional brain and spinal cord nerve injury wounds, achieving a balance between cost and performance.

[0054] See Figure 1 and Figure 2 The specific implementation process of this embodiment is as follows:

[0055] Preparation of the inner layer for wound adhesion: 12% prepolymer solution was prepared by mixing methacrylic anhydride gelatin and hyaluronic acid-phenylboronic acid ester at a mass ratio of 2.5-1. The loading of P144 peptide was 0.5% of the dry weight of the hydrogel matrix. Crosslinking was performed under 365nm ultraviolet light for 20s, and the inner layer thickness was 0.15mm.

[0056] Preparation of functional sustained-release intermediate layer: Polycaprolactone and polylactic acid-glycolic acid copolymer were mixed in a mass ratio of 1-2 to prepare 10% spinning solution, and electrospinning was used to prepare a scaffold with an initial pore size of 5 μm, a pore size of 20 μm after 90 days of degradation, and a thickness of 0.4 mm. The drug-loaded microsphere system was maintained at a mass ratio of 1-2-2.

[0057] Preparation of a waterproof and breathable outer layer: Perfluorooctyltriethoxysilane was added at 3% of the mass of polycaprolactone, and spinning was used to obtain a layer with a thickness of 0.08 mm, a static water contact angle of 150°, and an oxygen permeability of 3000 cm⁻¹. 3 / (m 2 A superhydrophobic membrane with a lifespan of 24 hours and 24 hours.

[0058] Composite molding: The three-layer structure is hot-pressed at low temperature of 36℃ and 0.15MPa for 8 seconds, then cut and aseptically packaged to obtain the finished product.

[0059] In summary, the dressing in this embodiment has a static water contact angle of 150° and an oxygen permeability of 3000 cm⁻¹. 3 / (m 2 (24h·atm) cerebrospinal fluid leakage sealing rate 98%, wound adhesion rate 90%, scar tissue proliferation inhibition rate 85%, nerve axon regeneration rate 80%, microsphere degradation matching degree 88%, postoperative infection rate 1%, complication rate 3%. The dressing exhibits good basic protective and repair performance, lower production cost, and can meet the clinical requirements for routine brain and spinal cord nerve injury wounds, demonstrating outstanding cost-effectiveness.

[0060] Comparative Example

[0061] This comparative dressing has a traditional single hydrogel structure, with only a single hydrogel layer, no functional sustained-release intermediate layer and waterproof and breathable outer layer. The hydrogel layer does not contain hyaluronic acid-phenylboronic acid ester and P144 peptide, does not load any graded degradation drug-loaded microspheres, and has not undergone fluorine modification treatment.

[0062] This comparative example uses a traditional single hydrogel structure dressing without a functional sustained-release intermediate layer and a waterproof and breathable outer layer. The inner layer of the wound is not bonded with P144 peptide, there is no gradient degradation drug-loaded microsphere system, and the outer layer is not fluorinated. This comparison verifies the technical superiority of the three-layer synergistic structure of this invention.

[0063] The specific implementation process of this comparative example is as follows:

[0064] Preparation of a single-layer hydrogel: The hydrogel was prepared using only methacrylic anhydride gelatin as a single component, without the addition of hyaluronic acid-phenylboronic acid ester and P144 peptide. The thickness was 0.8 mm, and it was formed by cross-linking with 365 nm ultraviolet light for 30 s.

[0065] There are no intermediate or outer layer preparation steps, no drug-loaded microspheres are added, and no fluorine modification is performed.

[0066] The monolayer hydrogel was cut directly and aseptically packaged to obtain the control dressing.

[0067] In summary, the static water contact angle of this comparative dressing is 90°, and the oxygen permeability is 1200 cm⁻¹. 3 / (m 2 The dressing (24h atm) showed a 60% cerebrospinal fluid leakage sealing rate, a 70% wound adhesion rate, a 30% scar tissue proliferation inhibition rate, and a 25% nerve axon regeneration rate. It lacked gradient drug release function, had a 12% postoperative infection rate, and a 25% complication rate. The dressing lacked waterproof and breathable synergistic effects, and had no anti-scarring or nerve repair functions, failing to meet the clinical needs for treating brain and spinal cord nerve injuries.

[0068] Comparison Projects Example 1 Example 2 Example 3 Comparative Example Structural composition Three-layer collaborative structure Three-layer collaborative structure Three-layer collaborative structure monolayer hydrogel Inner layer anti-scar peptide have have have none Intermediate layer gradient drug-loaded microspheres have have have none outer fluorine modification treatment have have have none Static water contact angle 155° 160° 150° 90° oxygen transmission rate <![CDATA[3500cm 3 / (m 2 ・24h・atm)]]> <![CDATA[4000cm 3 / (m 2 ・24h・atm)]]> <![CDATA[3000cm 3 / (m 2 ・24h・atm)]]> <![CDATA[1200cm 3 / (m 2 ・24h・atm)]]> Cerebrospinal fluid blocking effect excellent excellent good Difference Scar inhibition rate 92% 95% 85% 30% nerve repair effect excellent good good Difference Wound Adhesion excellent good good Difference Overall performance excellent excellent good Difference

[0069] As can be seen from the comparison table above, all three embodiments of the present invention employ a three-layer synergistic structure, combined with covalent bonding of anti-scarring peptides, precise drug delivery via gradient-degradable drug-loaded microspheres, and a fluorine-modified superhydrophobic outer layer for waterproofing and breathability. This design significantly outperforms the traditional single-layer structure in terms of waterproofing, breathability, cerebrospinal fluid sealing, wound adhesion, anti-scarring, and nerve repair. Embodiment 1 utilizes intermediate core parameters, achieving balanced and optimal performance across all aspects, making it the best implementation method. Embodiment 2 emphasizes enhanced waterproofing and anti-scarring properties, suitable for high-risk and complex wounds. Embodiment 3 balances cost and basic performance, offering high cost-effectiveness and suitable for routine wounds. The comparative examples, lacking a multi-layer synergistic structure and core functional components, exhibit extremely poor performance across all aspects, failing to meet clinical needs. This fully demonstrates the innovation and practicality of the present invention's technical solution in terms of structural design, functional integration, and clinical adaptability.

[0070] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A waterproof and breathable protective dressing for brain and spinal cord nerve injuries, characterized in that, The dressing consists of a wound adhesion inner layer, a functional sustained-release middle layer, and a waterproof and breathable outer layer, layered from the inside out. The inner layer of the wound adhesion is a dual-network dynamic hydrogel matrix constructed from methacrylic anhydride gelatin and hyaluronic acid-phenylboronic acid ester. Functional peptides that target and inhibit scar hyperplasia are fixed in the hydrogel matrix through site-specific covalent bonding. The functional sustained-release intermediate layer is a nanofiber porous scaffold prepared by electrospinning of polylactic acid-glycolic acid copolymer and polycaprolactone. The pores of the nanofiber porous scaffold are loaded with a gradient degradation drug-loaded microsphere system, and the degradation rate of the gradient degradation drug-loaded microsphere system matches the pore size change rate of the nanofiber porous scaffold. The waterproof and breathable outer layer is made of fluorine-modified polycaprolactone superhydrophobic electrospun nanofiber membrane.

2. The waterproof and breathable protective dressing for brain and spinal cord nerve injuries according to claim 1, characterized in that, The mass ratio of methacrylic anhydride gelatin to hyaluronic acid-phenylboronic acid ester in the inner layer of the wound adhesion is 2.5:1-3.5:

1. The functional peptide is P144 peptide, and the loading of P144 peptide is 0.5%-2% of the dry weight of the hydrogel matrix. The thickness of the inner layer of the wound adhesion is 0.15mm-0.25mm. The hydrogel matrix is ​​cross-linked and formed by 365nm ultraviolet light. The P144 peptide completes site-specific covalent bonding with the hydrogel matrix through an EDC and NHS catalytic system.

3. The waterproof and breathable protective dressing for brain and spinal cord nerve injury wounds according to claim 1, characterized in that, The mass ratio of polycaprolactone to polylactic acid-glycolic acid copolymer in the nanofiber porous scaffold of the functional sustained-release intermediate layer is 1:2-1:

3. The initial pore size of the nanofiber porous scaffold is 5μm-10μm, and the pore size of the nanofiber porous scaffold after 90 days of degradation is 20μm-30μm. The thickness of the functional sustained-release intermediate layer is 0.4mm-0.6mm. The nanofiber porous scaffold is prepared by electrospinning.

4. The waterproof and breathable protective dressing for brain and spinal cord nerve injury wounds according to claim 1, characterized in that, The gradient degradation drug-loaded microsphere system consists of rapidly degrading drug-loaded microspheres, moderately degrading drug-loaded microspheres, and slowly degrading drug-loaded microspheres. The mass ratio of the rapidly degrading drug-loaded microspheres to the moderately degrading drug-loaded microspheres is 1:2:

2. The rapidly degrading drug-loaded microspheres are polylactic acid-glycolic acid copolymer microspheres with a molecular weight of 5 kDa, the moderately degrading drug-loaded microspheres are polylactic acid-glycolic acid copolymer microspheres with a molecular weight of 15 kDa, and the slowly degrading drug-loaded microspheres are polylactic acid-glycolic acid copolymer microspheres with a molecular weight of 30 kDa.

5. The waterproof and breathable protective dressing for brain and spinal cord nerve injury wounds according to claim 4, characterized in that, The rapidly degrading drug-loaded microspheres are loaded with dexamethasone, and the degradation period of the rapidly degrading drug-loaded microspheres is 1-7 days. The moderately degrading drug-loaded microspheres are loaded with nerve growth factor and brain-derived neurotrophic factor, and the degradation period of the moderately degrading drug-loaded microspheres is 7-28 days. The slowly degrading drug-loaded microspheres are loaded with ciliary neurotrophic factor and myelin-associated glycoprotein antibody, and the degradation period of the slowly degrading drug-loaded microspheres is 28-90 days.

6. The waterproof and breathable protective dressing for brain and spinal cord nerve injury wounds according to claim 1, characterized in that, The static water contact angle of the waterproof and breathable outer layer is not less than 150°, and the oxygen permeability of the waterproof and breathable outer layer is not less than 3000 cm⁻¹. 3 / (m 2 •24h•atm), the thickness of the waterproof and breathable outer layer is 0.08mm-0.15mm, the fluorine modifier used in the waterproof and breathable outer layer is perfluorooctyltriethoxysilane, and the amount of perfluorooctyltriethoxysilane added is 3%-5% of the mass of polycaprolactone.

7. The waterproof and breathable protective dressing for brain and spinal cord nerve injury wounds according to claim 1, characterized in that, The wound adhesion inner layer, the functional sustained-release intermediate layer, and the waterproof and breathable outer layer are laminated using a low-temperature hot-pressing process. The temperature of the low-temperature hot-pressing process is 36℃-38℃, the pressure of the low-temperature hot-pressing process is 0.15MPa-0.25MPa, and the pressure holding time of the low-temperature hot-pressing process is 8s-12s. After being cut, the dressing is aseptically packaged to complete the finished product preparation.

8. The waterproof and breathable protective dressing for brain and spinal cord nerve injury according to any one of claims 1-7, characterized in that, This dressing is prepared by the following steps: S1. Preparation of wound adhesion inner layer: Synthesize hyaluronic acid-phenylboronic acid ester conjugate, dissolve methacrylic anhydride gelatin and hyaluronic acid-phenylboronic acid ester in PBS buffer at pH 7.4 to prepare a prepolymer solution, add photoinitiator and functional peptide, inject into a mold after EDC and NHS catalytic reaction, and obtain the wound adhesion inner layer by UV cross-linking. S2. Preparation of functional sustained-release intermediate layer: A gradient degradation drug-loaded microsphere system was prepared by a double emulsion-solvent evaporation method. Polycaprolactone and polylactic acid-glycolic acid copolymer were dissolved in an organic solvent to prepare a spinning solution. Gradient degradation drug-loaded microspheres were added and stirred evenly. The functional sustained-release intermediate layer was prepared by electrospinning process. S3. Preparation of waterproof and breathable outer layer: Polycaprolactone is dissolved in a mixed organic solvent, a fluorine modifier is added and stirred evenly to prepare a spinning solution, and the waterproof and breathable outer layer is prepared by electrospinning process. S4. Composite molding: The inner layer for wound adhesion, the intermediate layer for functional sustained release, and the outer layer for waterproof and breathable coating are layered sequentially from the inside out. The interlayer bonding is completed using a low-temperature hot pressing process to obtain the target dressing.

9. The waterproof and breathable protective dressing for brain and spinal cord nerve injury wounds according to claim 8, characterized in that, The prepolymer solution in S1 has a mass-volume percentage concentration of 12%-18%, the photoinitiator is LAP, the wavelength of the ultraviolet light is 365nm, and the crosslinking time of the ultraviolet light is 20s-40s. The organic solvent in S2 is hexafluoroisopropanol, the spinning solution has a mass-volume percentage concentration of 10%-14%, the electrospinning process has a spinning voltage of 14kV-16kV, a receiving distance of 14cm-16cm, a push flow rate of 0.7mL / h-0.9mL / h, a spinning environment temperature of 25℃, and a relative humidity of 40%.

10. The waterproof and breathable protective dressing for brain and spinal cord nerve injury wounds according to claim 8, characterized in that, The mixed organic solvent in S3 consists of dichloromethane and N,N-dimethylformamide, with a volume ratio of 3:

1. The mass-volume percentage concentration of the spinning solution is 8%-12%. The electrospinning process uses a spinning voltage of 17kV-19kV, a receiving distance of 11cm-13cm, a push flow rate of 0.9mL / h-1.1mL / h, a spinning ambient temperature of 25℃, and a relative humidity of 40%. In S4, the low-temperature hot pressing process uses a temperature of 36℃-38℃, a pressure of 0.15MPa-0.25MPa, and a holding time of 8s-12s.

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