An anti-blocking film having a rough structure fiber and a method for manufacturing the same

Abstract

The present application belongs to the technical field of anti-adhesion material in biomedical engineering, and relates to an anti-adhesion film with rough structure fibers and a preparation method thereof. The method comprises the following steps: soaking an electrospun fiber film containing a high molecular material and a hydrophilic anti-adhesion component in a treatment liquid containing the high molecular material and composed of a poor solvent and a good solvent for a specific time, and then rinsing and drying to obtain the anti-adhesion film; the ratio of the poor solvent to the good solvent in the treatment liquid is such that the swelling rate of the high molecular material in the treatment liquid at 25 DEG C is 1% to 10% in 10 minutes. The fiber surface of the prepared anti-adhesion film forms a stable integrated nanometer string crystal structure, and without exogenous drugs, the physical topological structure limits the spreading of fibroblasts and blocks the transformation of fibroblasts into myofibroblasts, so that the anti-adhesion effect is good and the biocompatibility is good.

Description

Technical Field

[0001] This invention belongs to the field of anti-adhesion materials technology in biomedical engineering, and relates to an anti-adhesion membrane with rough fiber structure and its preparation method. Background Technology

[0002] Postoperative adhesions are a common and serious complication following surgery or tissue injury. They refer to the abnormal deposition of connective tissue around the wound, causing previously separated adjacent tissues or organs to adhere together, and even forming scar tissue. With an incidence rate of approximately 60% to 90%, adhesions can lead to various clinical problems such as chronic abdominal pain, intestinal obstruction, and infertility, severely impacting patients' physical and mental health and quality of life. Therefore, the development of functional materials that can effectively inhibit adhesions and even scar tissue formation is of clear clinical necessity.

[0003] The pathological essence of adhesion formation is an abnormal fibrosis process caused by the imbalance of tissue repair after trauma. This process typically involves three stages: the inflammatory phase, the fibroblast proliferation phase, and the tissue repair phase. Among these, the activation and differentiation of fibroblasts into myofibroblasts during the proliferation phase, followed by excessive secretion of extracellular matrix (such as type I collagen), is the core link in the final formation and fixation of adhesions. Therefore, effectively intervening in this cellular behavior has become a key direction in the design of anti-adhesion materials.

[0004] Current clinical strategies for preventing adhesions mainly include surgical procedure optimization, systemic drug therapy, and local physical barrier isolation. Among these, constructing implantable physical barrier materials has become the mainstream method for preventing adhesions due to its ability to achieve precise local isolation and relatively controllable biocompatibility. These materials inhibit adhesions by forming barriers between wound surfaces, reducing the chance of tissue contact. Among the various forms of physical barriers, membrane-like products are the most widely used in clinical practice due to their more stable spatial barrier capabilities and longer duration of action.

[0005] However, existing commercially available membrane-based anti-adhesion products still have significant drawbacks. For example, Seprafilm® membranes, with hyaluronic acid and carboxymethyl cellulose as their main components, are biodegradable and absorbable, but their brittle texture, poor wet mechanical properties, and rapid degradation rate result in poor clinical operability and long-term anti-adhesion effects. Another commonly used product, Interceed®, has shown some anti-adhesion effects in gynecological surgery, but its poor flexibility and ineffectiveness upon contact with blood, requiring thorough hemostasis in the surgical field, greatly limit its applicability.

[0006] An ideal anti-adhesion barrier not only needs to possess good spatial barrier capabilities but should also allow for the normal exchange of nutrients and metabolites to achieve a physiological microenvironment in the wound. Nanofiber membranes prepared by electrospinning technology, due to their fine fiber diameter, high porosity, and interconnectedness, can effectively block fibroblast migration while maintaining necessary substance exchange. Furthermore, their extracellular matrix-like structure facilitates integration with host tissues, making them a highly promising anti-adhesion material platform.

[0007] Currently, the development of anti-adhesion membranes based on electrospinning technology has shown a trend from passive barrier to active intervention. Existing technologies can be broadly divided into three categories: The first category is basic material-based electrospinned membranes, such as the registered collagen membrane (National Medical Device Registration Certificate 20153140311) and PLGA membrane (National Medical Device Registration Certificate 20173144248, etc.). These mainly rely on the physical barrier properties of the material itself and the fiber structure, with a relatively simple and passive function, making it difficult to actively intervene in the core cellular processes of adhesion. The second category is structure-functional electrospinned membranes, such as the biomimetic bilayer membrane disclosed in patent application CN117547658A and the super-lubricating surface-modified membrane disclosed in CN111304921A. These membranes enhance function through structural design, but often suffer from problems such as weak interlayer bonding, insufficient in-cell stability of the surface-modified layers, or complex processes. The third category is drug-loaded electrospun membranes, such as the membrane material loaded with nintedanib (a multi-target tyrosine kinase inhibitor) disclosed in patent application CN119318741A, and the membrane material loaded with natural extracts disclosed in CN115671404A. This type of technology directly intervenes in the proliferation, differentiation, or inflammatory pathways of fibroblasts through local sustained-release of drugs or active factors, with a clear mechanism of action and strong efficacy. However, a common drawback is the necessity to introduce exogenous chemical or bioactive components, which may lead to a series of problems such as drug burst release, local or systemic toxicity, complex process control, and high costs.

[0008] It is worth noting that in the pursuit of safer and more effective physical intervention strategies, the regulatory role of nanoscale topological structures on material surfaces in cell behavior is receiving increasing attention. Reference 1 (Substratum topography modulates corneal fibroblast to myofibroblast transformation [J]. Invest Ophthalmol VisSci, 2012, 53: 811-816.) discloses that regular groove / ridge-like structures prepared on rigid substrates can regulate the transformation of fibroblasts into myofibroblasts, confirming the potential of nanoscale topological structures in intervening in fibrosis-related cell behaviors. Furthermore, a periodic nanoprotrusion structure called "crystal strands" theoretically possesses the potential to inhibit fibroblast activation due to its ability to physically interfere with cell adhesion and spreading. However, although crystal strand structures have been extensively studied in materials science and related technologies are documented in existing patent literature, the application goals of these technologies are not anti-adhesion, and their designs cannot meet the core requirement of long-term biological stability for anti-adhesion applications.

[0009] For example, patent application CN118987360A discloses a polycaprolactone (PCL) crystalline fiber membrane, but its design aims to utilize the high specific surface area of ​​the crystalline structure to load and release antibiotics (such as levofloxacin). Its function is entirely dependent on exogenous drugs, and it does not explore the physical anti-adhesion effect of the crystalline topology itself. Patent application CN116103919A discloses a process using a crystalline structure as a "sacrificial template" to prepare a fiber membrane with surface-modified gold nanoparticles. This crystalline structure is dissolved and removed in the later stages of the process, therefore it does not possess the stability required for long-term implantation. Another patent application, CN120078944A, although constructing a crystalline structure and applying it to medical patches, aims to utilize this structure to enhance the piezoelectric effect to promote the proliferation and differentiation of tissue cells (such as fibroblasts). This logic of promoting repair is exactly the opposite of the goal of inhibiting excessive cell activation required for anti-adhesion.

[0010] In summary, the current field of anti-adhesion materials, especially electrospun membranes, still faces a key technological bottleneck: the lack of a novel membrane material capable of actively and effectively inhibiting fibroblast activation and differentiation, and thus intervening in adhesion formation at its source, solely through the material's own stable and durable physical topology, without introducing any exogenous drugs or bioactive factors. Existing technologies involving crystalline structures either rely on drugs, have temporary structures, or contradictory objectives, all failing to meet this requirement. Therefore, developing a novel membrane material based on electrospinning technology, possessing an integrated and stable crystalline nanotopological structure, and achieving its anti-adhesion function entirely through physical mechanisms, not only addresses the shortcomings of existing technologies but also provides a new and important approach and solution for the development of this field. Summary of the Invention

[0011] The purpose of this invention is to solve the problems existing in the prior art and to provide an anti-adhesion membrane with coarse fiber structure and its preparation method.

[0012] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0013] A method for preparing an anti-adhesion membrane with coarse fiber structure involves immersing an electrospun fiber membrane in a treatment solution, followed by rinsing and drying to obtain the anti-adhesion membrane with coarse fiber structure.

[0014] The electrospun fiber membrane is obtained by electrospinning from a spinning solution, wherein the solute in the spinning solution is composed of a polymer material and a hydrophilic anti-adhesion component.

[0015] The solute in the treatment solution is the polymer material, and the polymer material serves as a heterogeneous nucleation center to induce in-situ crystallization on the fiber surface.

[0016] The solvent in the treatment solution is denoted as solvent X. Solvent X consists of a poor solvent and a good solvent. The poor solvent is a common poor solvent for both the polymer material and the hydrophilic anti-adhesion component. The good solvent is only a good solvent for the polymer material. The ratio of the poor solvent to the good solvent satisfies the following condition: the swelling rate (weight gain rate) of the polymer material after being placed in solvent X at 25°C for 10 minutes is 1%-10%. This swelling rate is a process parameter controlled by adjusting the volume ratio of the poor solvent to the good solvent, rather than an inherent physical constant of the polymer material.

[0017] The soaking time shall not be less than the minimum time required for the formation of complete and uniform nanocrystals on the surface of the electrospun fiber membrane, and shall not be more than the minimum time required for the electrospun fiber membrane to undergo overall swelling, dissolution or morphological destruction.

[0018] This invention involves immersing an electrospun fiber membrane in a specific treatment solution, which forms a stable nanocrystalline structure on the fiber surface. The objective of this invention is to achieve an anti-adhesion effect entirely through the physical structure of the nanocrystalline topology itself, without introducing exogenous drugs or bioactive factors. To this end, the invention incorporates the following design:

[0019] ① The electrospun fiber membrane contains the hydrophilic anti-adhesion component, meaning that the material of this invention naturally possesses basic anti-adhesion properties, completely eliminating the need for loading exogenous drugs or bioactive factors as in existing technologies. The hydrophilic anti-adhesion component is uniformly distributed throughout the entire fiber, ensuring consistent and good biocompatibility on the surface of the treated crystalline structure. During nucleation and crystallization, the hydrophilic anti-adhesion component in the electrospun fiber membrane plays two main roles: firstly, its uniform dispersion throughout the fiber restricts large-scale migration and disordered aggregation of polymer chains during crystallization, preventing the formation of excessively large blocky crystals and maintaining the nanoscale size and discrete distribution of the newly formed crystals; secondly, its exposure on the fiber surface enhances the hydrophilicity and lubricity of the material interface, reducing protein adsorption and cell adhesion tendencies, thus synergistically exerting an anti-adhesion effect with the nanocrystalline topology. Since the hydrophilic anti-adhesion component in this invention is not dissolved by the treatment solution, it remains stably retained within the fiber matrix throughout the entire treatment process, continuously providing biocompatibility and interface regulation capabilities.

[0020] ② The design of the crystal topology has specific nanoscale size and spatial distribution to effectively limit cell spread.

[0021] ③ The design incorporates a crystalline structure that forms a stable, integrated bond with the fiber substrate, ensuring long-term service life.

[0022] To achieve specific nanoscale dimensions and spatial distribution in the crystal chain topology, this invention employs two aspects of control:

[0023] On the one hand, the solvent in the treatment solution is designed to consist of a poor solvent and a good solvent. The poor solvent is a common poor solvent for both the polymer material and the hydrophilic anti-adhesion component. The good solvent is only a good solvent for the polymer material. The good solvent is responsible for providing the polymer material with appropriate swelling capacity, enabling the molecular chains to move. The poor solvent creates a supersaturated environment, inducing and promoting the nucleation and crystallization of the polymer material's molecular chains. Subsequently, under the induction of the poor solvent, these chain segments tend to re-aggregate and undergo surface crystallization, thereby forming plate-like protrusions.

[0024] By adjusting the ratio of the inferior solvent to the beneficial solvent, this invention precisely controls the space and speed of crystal growth, ensuring that nanoscale flakes are generated, rather than large, disordered crystals. Specifically, this invention controls the ratio of the inferior solvent to the beneficial solvent to satisfy the following: the swelling rate of the polymer material after being placed in solvent X at 25°C for 10 minutes is 1%-10%. If the swelling rate is too small, the swelling is insufficient, and the formation of crystalline strands is inadequate; if the swelling rate is too large, it may lead to over-dissolution and damage to the fiber morphology. This invention has found that when the swelling rate is below 1%, effective nanocrystalline strands cannot be formed on the fiber surface; while when the swelling rate is above 10%, the fiber undergoes excessive swelling, the crystalline strand structure disappears, and the fiber intersections melt and bond together. This means that a swelling rate of 1%-10% is a critical window for structural morphology across the three stages of "no crystalline strands → complete and uniform crystalline strands → structural damage," and is not a linearly adjustable conventional parameter. Only within this limited range can the complete formation of the crystalline strand structure and the structural integrity of the fiber matrix be achieved simultaneously.

[0025] Furthermore, the solvent in the treatment solution designed in this invention is composed of both inferior and superior solvents, and is also compatible with the hydrophilic anti-adhesion component. The intrinsic bioactivity and lubricity of the hydrophilic anti-adhesion component directly contribute to the anti-adhesion function of the material without damaging it, thereby ensuring that cells can directly "sensor" the topological signal designed in this invention.

[0026] In this nucleation and crystallization process, the polymeric materials in the electrospun fiber membrane and the processing solution play different roles. The polymeric materials in the electrospun fiber membrane constitute the main source of tandem crystal formation. The polymeric materials in the processing solution are not simply used to increase the solution concentration, but rather act as "exogenous chain sources" and "nucleation induction centers" during crystallization. When the fiber surface is slightly swollen by a benign solvent, the chain segments released from the fiber interior can entangle and coordinate with the dissolved polymeric chains in the processing solution, significantly reducing the nucleation energy barrier required for surface crystallization. Simultaneously, the polymeric chains in the processing solution can preferentially form local chain aggregation regions on the fiber surface, serving as initial nuclei for subsequent lamellar growth, making the crystallization process tend to occur continuously and uniformly on the fiber surface, rather than randomly precipitating. Ultimately, the newly formed tandem crystal structure not only originates from the original chain segments on the fiber surface but also includes some polymeric chains from the processing solution. These two components interpenetrate, entangle, and grow synergistically during crystallization, thus forming a stable nano-tandem crystal structure highly integrated with the fiber matrix, rather than brittle particles deposited later. If the treatment solution does not contain polymeric materials, the nanocrystalline structure required by this invention cannot be stably formed. This is because the system at this point only contains a small amount of polymeric chains released from the fiber itself, lacking sufficient exogenous chain segments to participate in the surface nucleation process. This results in insufficient chain concentration on the fiber surface to form a stable, continuous nucleation region. Simultaneously, due to the lack of interfacial chain entanglement and synergistic arrangement provided by exogenous polymeric chains, the fiber surface chain segments are more prone to local dissolution or disordered collapse under the action of the solvent, rather than forming controlled crystallization. The resulting structure typically manifests as scattered, discontinuous precipitates, fragmented crystals, or locally remelted regions, making it difficult to form a stable nanocrystalline layer uniformly covering the fiber surface. Furthermore, even if a small amount of crystals can be formed locally, these crystals originate only from limited chain segments on the fiber's surface, lacking sufficient chain interpenetration and entanglement with the fiber substrate, resulting in poor bonding stability. During subsequent rinsing, drying, or immersion in bodily fluids, these loose crystals are prone to detachment, collapse, or further rearrangement, failing to maintain the nano-topological structure for a long period. Therefore, by introducing the same polymer material into the treatment solution, a "exogenous chain segment-surface chain segment" synergistic crystallization system can be formed on the fiber surface, thereby significantly improving the continuity, uniformity, and integration stability of the tandem crystal structure with the fiber substrate.

[0027] On the other hand, the soaking time is designed to be shorter (significantly shorter than the prior art) because if the soaking time is too long, the small crystal flakes will continue to grow and coarse, losing their nanoscale fine structure, and cells can spread on them.

[0028] To ensure a stable and integrated bond between the crystalline structure and the fiber substrate, this invention precisely controls the soaking time. This soaking time is sufficient to allow the beneficial solvent to diffuse to the fiber surface and initiate plasticization, while simultaneously allowing the crystallization process induced by the inferior solvent to complete on the surface. However, it is shorter than the critical time before excessive solvent penetration leads to overall fiber swelling, dissolution, or destruction of the hydrophilic anti-adhesion component structure. Ultimately, crystallization occurs on the outermost surface of the fiber, while the main internal structure remains robust. The newly formed crystalline structure is tightly intertwined with the fiber body and will not detach during use.

[0029] Through the above design, the anti-adhesion membrane prepared by the present invention can achieve the anti-adhesion effect entirely by relying on the physical structure of the crystal topology itself. The specific principle is that the crystal structure can specifically downregulate key markers of fibroblast fibrosis pathway (such as α-SMA expression and TGF-β1 transcription) and inhibit their signal transduction process (such as YAP nuclear translocation), effectively blocking the core fibrosis process of "fibroblast → myofibroblast" transformation.

[0030] As a preferred technical solution:

[0031] In the method for preparing an anti-adhesion membrane with coarse-structured fibers as described above, the mass ratio of the polymeric material to the hydrophilic anti-adhesion component in the spinning solution is 95:5-70:30; the total content of the polymeric material and the hydrophilic anti-adhesion component in the spinning solution is 8wt%-20wt%; the content of the polymeric material in the treatment solution is 0.1wt%-5wt%; and the mass-volume ratio of the electrospun fiber membrane to the treatment solution is 1g:50-100mL, ensuring that the membrane is completely immersed and freely swells, avoiding local concentration gradients.

[0032] In the above-described method for preparing an anti-adhesion membrane with coarse-structured fibers, the immersion temperature is not lower than the glass transition temperature of the polymer material after plasticization in the solvent X (which can be estimated by the Gordon-Taylor equation), not higher than the temperature that would cause the solvent X to volatilize violently, the electrospun fiber membrane to swell or dissolve excessively, or the hydrophilic anti-adhesion component to be structurally damaged and lose its biological activity, and lower than the initial boiling point of the solvent X.

[0033] This invention ensures sufficient mobility of the polymer chains while employing a lower immersion temperature (significantly lower than existing technologies) to prevent excessive solvent evaporation or damage to the fiber structure. The low-temperature treatment avoids damage to the fiber structure caused by high temperatures and also protects the hydrophilic anti-blocking components (such as hyaluronic acid) from losing their bioactivity. This contrasts sharply with existing technologies (such as CN116103919A and CN120078944A) that require high-temperature processes of 130-160°C, demonstrating the mildness and versatility of this invention.

[0034] The method for preparing an anti-adhesion membrane with a rough fiber structure as described above includes the following: the polymer material is PLA (polylactic acid) with an intrinsic viscosity of 1.5-2.5 dL / g; the hydrophilic anti-adhesion component is HA (hyaluronic acid) with an intrinsic viscosity of 0.5-2.0 dL / g; the inferior solvent is one or more of ethanol, methanol, and isopropanol; the beneficial solvent is one or more of acetone, tetrahydrofuran, dichloromethane, and N,N-dimethylformamide; the volume ratio of the inferior solvent to the beneficial solvent is 85:15-95:5; the soaking time is 10-30 min; and the soaking temperature is 25-35℃. The PLA and HA within this intrinsic viscosity range are suitable for the swelling and crystallization induction process of the treatment solution, which is beneficial for forming a stable crystalline structure.

[0035] The method for preparing an anti-adhesion membrane with a rough fiber structure as described above includes the following: the polymer material is PCL with an intrinsic viscosity of 1.0-1.8 dL / g; the hydrophilic anti-adhesion component is chitosan with an intrinsic viscosity of 1.0-3.0 dL / g; the inferior solvent is one or more of ethanol and methanol; the beneficial solvent is one or more of acetone and ethyl acetate; the volume ratio of the inferior solvent to the beneficial solvent is 80:20-95:5; the soaking time is 1-10 min; and the soaking temperature is 20-40℃. PCL and chitosan within this intrinsic viscosity range, combined with a specific ratio of solvent system, can achieve rapid and uniform formation of a crystalline structure.

[0036] The method for preparing an anti-adhesion film with a rough fiber structure as described above includes the following: the polymer material is PLGA with an intrinsic viscosity of 0.5-1.2 dL / g; the hydrophilic anti-adhesion component is PEG200 with a kinematic viscosity of 22-23 mm² / s at 40°C; the inferior solvent is one or more of ethanol and water; the beneficial solvent is one or more of acetone and DMF; the volume ratio of the inferior solvent to the beneficial solvent is 70:30-90:10; the soaking time is 5-20 min; and the soaking temperature is 15-40°C. The specific kinematic viscosity of PEG200 enables it to be well compatible with PLGA and the solvent system, synergistically promoting the formation of a crystalline structure and enhancing the hydrophilicity of the material.

[0037] The method for preparing an anti-adhesion membrane with rough fiber structure as described above includes the following: the polymer material is PLCL with an intrinsic viscosity of 1.5-2.5 dL / g; the hydrophilic anti-adhesion component is HA with an intrinsic viscosity of 0.5-2.0 dL / g; the inferior solvent is one or more of ethanol and isopropanol; the superior solvent is one or more of acetone and THF; the volume ratio of the inferior solvent to the superior solvent is 85:15-95:5; the soaking time is 10-30 min; and the soaking temperature is 25-35℃. This combination of materials and solvents exhibits good compatibility and can stably generate the required nanoscale crystalline structure.

[0038] The method for preparing an anti-adhesion membrane with a rough fiber structure as described above includes the following: the polymer material is PCL with an intrinsic viscosity of 1.0-1.8 dL / g; the hydrophilic anti-adhesion component is sodium alginate with an intrinsic viscosity of 0.2-2.0 dL / g; the inferior solvent is one or more of ethanol and water; the beneficial solvent is one or more of acetone and DMF; the volume ratio of the inferior solvent to the beneficial solvent is 80:20-95:5; the soaking time is 10-30 min; and the soaking temperature is 20-40℃. The intrinsic viscosity of sodium alginate matches that of PCL and the solvent system, ensuring a stable bond between the crystalline structure and the fiber substrate.

[0039] The present invention also provides an anti-adhesion membrane with coarse fiber structure, which is prepared by the preparation method of an anti-adhesion membrane with coarse fiber structure as described in any of the preceding claims;

[0040] The anti-adhesion membrane with rough-structured fibers has a fiber surface uniformly covered with crystalline protrusions. The average thickness of the crystalline protrusions is 10-100 nm, and the average length of the crystalline protrusions is 50-500 nm. The crystalline protrusions of this size can generate effective steric hindrance, physically hindering the effective clustering of integrin receptors on the cell membrane and the maturation of adhesion focals.

[0041] After being immersed in simulated body fluid at 37°C for 14 days, the anti-adhesion membrane with rough-structured fibers did not show significant changes in fiber surface morphology, demonstrating the stability of the bond between the lamellar protrusions and the fiber substrate. This stability ensures that the material can serve for a long time in the dynamic environment in vivo, providing continuous and reliable physical signals throughout the critical treatment window.

[0042] The average surface area of ​​cells spread on an anti-adhesion membrane with rough fibrous structure is 40-50 µm. 2The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 40%-50% and an α-SMA activation rate of 35%-45%; these indicators show that the anti-adhesion membrane can effectively limit fibroblast spread, inhibit its transformation into myofibroblasts, and block the fibrosis core process.

[0043] Beneficial effects:

[0044] (1) The present invention does not require the introduction of exogenous drugs or bioactive factors, and relies entirely on the physical structure of the crystal topology to cause the anti-adhesion effect.

[0045] (2) The present invention uses a treatment solution composed of inferior solvent and good solvent in a specific ratio, and a soaking time set based on polymer crystallization kinetics, to enable the crystalline structure to form a stable integrated bond with the fiber substrate, ensuring long-term service in the in vivo dynamic environment and continuously playing an anti-adhesion role.

[0046] (3) By precisely controlling the ratio of inferior solvent to good solvent in the treatment solution, the present invention controls the swelling rate of polymer materials. Combined with a specific soaking time, a crystalline structure with suitable nanoscale size and spatial distribution is formed on the fiber surface, which can effectively limit the spread of fibroblasts, block their transformation into myofibroblasts, and improve the anti-adhesion effect.

[0047] (4) Compared with the nanotopological regulation technology based on regular grooves on a rigid substrate in Reference 1, the mechanism of action and structural features of this invention are fundamentally different. First, the reference prepares regular groove / ridge structure on a rigid silicon / polyurethane substrate by photolithography etching. Its core mechanism is "contact guidance", that is, guiding cells to oriented along the groove direction through regular linear topography, and thereby regulating cell differentiation behavior. In contrast, the structure of this invention is a random nanocrystal structure formed by solvent-induced in-situ crystallization on the surface of flexible electrospun fibers, which is not a regular groove topology at all. Second, the reference relies on continuous linear topography on a rigid substrate, while this invention relies on discrete crystalline protrusions on the surface of flexible fibers. The two are different in terms of substrate properties, structural order, and formation mode. This invention does not work by guiding the oriented arrangement of cells, but weakens the continuity of cell adhesion through discrete nanoprotrusions, physically hindering the clustering of integrin receptors and the maturation of adhesion focal spots, thereby limiting cell spread and reducing the mechanical coupling between cells and the substrate. Third, since the present invention constructs a nanocrystal topology on a flexible surface, its regulation results are further manifested as the suppression of YAP nuclear translocation and the downregulation of α-SMA expression, thereby blocking the fibrosis process; while the literature only proves that regular grooves on a rigid substrate can affect fibroblast transformation. Attached Figure Description

[0048] Figure 1The images shown are related to the anti-adhesion film with rough fiber structure prepared in Example 1 of the present invention; where a is a physical image (the light blue film in the image is the sterile substrate material of the packaged product), b is the surface SEM of the black circled part in a, and c is an enlarged image of the black circled part in b.

[0049] Figure 2 SEM images of the surface of the anti-adhesion membrane with rough fiber structure prepared in Example 5 of the present invention before and after immersion in simulated body fluid at 37°C for 14 days; where a corresponds to before immersion and b corresponds to after immersion.

[0050] Figure 3 SEM image of the membrane prepared in Comparative Example 1;

[0051] Figure 4 SEM image of the membrane prepared in Comparative Example 2;

[0052] Figure 5 SEM image of the membrane prepared for Comparative Example 3. Detailed Implementation

[0053] The present invention will be further described below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0054] To fully disclose the various embodiments and ensure the completeness of the material properties involved, this specification records the manufacturer information of the relevant materials; at the same time, equivalent products from other manufacturers that meet the technical parameter requirements of this invention are also applicable to the implementation of this invention.

[0055] The following are the test methods for the relevant performance indicators in each embodiment:

[0056] Swelling rate: The immersion method in section 7.2 of GB / T 1034-2008 "Determination of Water Absorption of Plastics" was used for the determination. Specifically, a sample with a known dry mass (m0) was immersed in solvent X at 25°C for 10 minutes. After removal, excess solvent on the surface was quickly blotted with filter paper, and the sample was immediately weighed (m1) to calculate the swelling rate. The calculation formula is: Swelling rate (%) = [(m1-m0) / m0] × 100%. Each sample was tested in parallel three times, and the average value was taken.

[0057] Glass transition temperature: The glass transition temperature was determined using a dynamic mechanical analyzer (DMA, manufacturer: TA Instruments, model: Q800) in accordance with ISO 6721-1:2019 "Determination of dynamic mechanical properties of plastics - Part 1: General rules". The sample was immersed in solvent X for 10 min, then removed, dried, and placed in the DMA fixture. The temperature was increased at 3 °C / min and 1 Hz in tensile mode. The temperature corresponding to the peak value of the loss factor (tanδ) was measured, which is the glass transition temperature after plasticization.

[0058] If the storage modulus drops sharply and the loss factor transition peak shifts completely to below 0°C, it can be clearly determined that the effective glass transition temperature of the material in this swollen and plasticized state is below 0°C. In this case, it can be theoretically estimated using the Gordon-Taylor equation, with the formula Tg,mix=(w1・Tg1+K・w2・Tg2) / (w1+K・w2); where Tg,mix is ​​the glass transition temperature of the polymer mixture after swelling (unit: °C), w1 is the mass fraction of the polymer, w2 is the mass fraction of the solvent, K is an empirical constant related to the interaction between components (unitless, usually taken as 0.3-0.5, requiring experimental fitting and calibration), and Tg1 is the glass transition temperature of the pure polymer (unit: °C, calculated using the same DMA instrument and ISO...). According to the standard 6721-1:2019, the temperature corresponding to the peak value of the loss factor of pure polymer material in tensile mode, heating rate of 3℃ / min, and frequency of 1Hz is taken. Tg2 is the glass transition temperature of pure solvent (for commonly used organic solvents, the melting point can be approximated or regarded as a value much lower than room temperature, such as -100℃).

[0059] Crystallization melting point: The crystallization melting point was determined using a differential scanning calorimeter (DSC, model: DSC8500) in accordance with ISO 11357-3:2018 "Plastics - Differential scanning calorimetry (DSC) - Part 3: Determination of melting and crystallization temperatures". The temperature was increased at a rate of 10℃ / min, and the peak temperature of the melting endothermic peak was recorded as the crystallization melting point.

[0060] Boiling range initial boiling point: determined in accordance with GB / T 7534-2004 "Determination of boiling range of volatile organic liquids for industrial use".

[0061] Intrinsic viscosity: An Ubbelohde viscometer (model: SBQ81834) was used, and the viscosity was measured according to GB / T 1632-2021 "Determination of Viscosity of Dilute Polymer Solutions Using Capillary Viscometers for Plastics". The polymer material was dissolved in the corresponding solvent (common solvents for PLA, PCL, PLC, chitosan, HA, and sodium alginate include chloroform, hexafluoroisopropanol, and acetate buffer, selected according to material characteristics), and the outflow time was measured in a 25℃ constant temperature water bath. The intrinsic viscosity [η] was calculated using the one-point method. Specific solvents and concentrations are as follows:

[0062] PLA, PCL, PLCl: Dissolve in chloroform at a concentration of 0.1 g / dL;

[0063] HA, chitosan, sodium alginate: dissolved in 0.1 mol / L acetate-sodium acetate buffer (pH=4.5), concentration 0.05 g / dL.

[0064] Kinematic viscosity: The kinematic viscosity of the sample was determined in a constant temperature water bath at 40℃ using a kinematic viscometer (manufacturer: Beijing Delite Technology Co., Ltd., model: A1011) in accordance with GB / T 265-2021 "Determination of kinematic viscosity and calculation of dynamic viscosity of petroleum products".

[0065] Average area of ​​cells spread on the anti-adhesion membrane: Human skin fibroblasts (purchased from the Cell Bank of the Chinese Academy of Sciences / Cell Bank of the Chinese Academy of Sciences, catalog number: SCSP-106) were cultured in DMEM medium containing 10% (v / v) fetal bovine serum (FBS) at 37℃ and 5% (v / v) CO2 until passage 3-5. Cells were then sputtered at 5 × 10⁻⁶ cells / cm². 4 cells / cm 2 Density seeding was performed on the sample surface, and after culturing for 24 h, the cells were fixed with paraformaldehyde fixative (4 g paraformaldehyde dissolved in 100 mL phosphate-buffered saline (PBS)). The cytoskeleton was stained with phalloidin, and the cell nuclei were stained with DAPI. Images were taken using a laser confocal microscope (manufacturer: Carl Zeiss AG, model: LSM900). The spreading area of ​​at least 50 cells was measured using ImageJ software, and the average value was calculated.

[0066] YAP activation rate: Human skin fibroblasts (purchased from the Cell Bank of the Chinese Academy of Sciences / Cell Bank of the Chinese Academy of Sciences, catalog number: SCSP-106) were cultured in DMEM medium containing 10% (v / v) fetal bovine serum (FBS) at 37℃ and 5% (v / v) CO2 until passage 3-5 for later use; the cells were then sputtered at 5×10⁻⁶ cells / year. 4 cells / cm 2The cells were seeded densely onto the sample surface and cultured for 24 hours. They were then fixed with paraformaldehyde (4 g paraformaldehyde dissolved in 100 mL phosphate-buffered saline (PBS)). Immunofluorescence staining was performed using anti-YAP antibody (purchased from Thermo Fisher Scientific Inc., catalog number: PA1-46189), and cell nuclei were stained with DAPI. Images were taken using a laser confocal microscope, and the proportion of cells in at least 100 cells where YAP protein was nuclearly localized was counted using ImageJ software, which is the YAP activation rate.

[0067] α-SMA activation rate: Immunofluorescence staining was used to detect the expression of α-SMA protein. Human skin fibroblasts (purchased from the Cell Bank of the Chinese Academy of Sciences / Cell Bank of the Chinese Academy of Sciences, catalog number: SCSP-106) were cultured in DMEM medium containing 10% (v / v) fetal bovine serum (FBS) at 37℃ and 5% (v / v) CO2 until passage 3-5. Cells were then used for further processing. 4 Cells were seeded at a density of cells / cm² on the sample surface and cultured for 24 h. After culturing, the cells were fixed with paraformaldehyde (4 g paraformaldehyde dissolved in 100 mL phosphate-buffered saline (PBS)). The cells were stained with anti-α-SMA antibody (Thermo Fisher Scientific Inc., catalog number: MA5-32479) and DAPI stained the cell nuclei. Images were taken using a laser confocal microscope, and the proportion of cells expressing α-SMA protein positive in at least 100 cells was counted using ImageJ software, which is the α-SMA activation rate.

[0068] In the following embodiments, the simulated body fluid was prepared in accordance with ISO 23317:2014 "Preparation and use of simulated body fluids (SBF) for in vitro bioactivity testing of implantable materials". The specific preparation steps are as follows: 1L of deionized water was measured, and 8.035g of NaCl, 0.355g of NaHCO3, 0.225g of KCl, 0.231g of K2HPO4·3H2O, 0.311g of MgCl2·6H2O, 39mL of 1.0M HCl aqueous solution, 0.292g of CaCl2, 0.072g of Na2SO4, and 6.118g of Tris (tris(hydroxymethyl)aminomethane) were added sequentially. The system temperature was then kept constant at 37℃, and the pH value was adjusted to 7.40 with 1.0M HCl aqueous solution or 1.0M NaOH aqueous solution to obtain the simulated body fluid.

[0069] Example 1

[0070] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0071] (1) Preparation of main materials;

[0072] Polymer material: PLA, manufactured by NatureWorks LLC, grade 4032D, intrinsic viscosity 1.5 dL / g;

[0073] Hydrophilic anti-blocking component: HA, manufactured by Bloomage Biotechnology Co., Ltd., brand name HA-100, intrinsic viscosity is 0.5 dL / g;

[0074] Inferior solvent: Ethanol;

[0075] Beneficial solvent: acetone;

[0076] (2) Prepare spinning solution and treatment solution;

[0077] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 95:5; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 8 wt%.

[0078] The solvent in the spinning solution is hexafluoroisopropanol;

[0079] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 0.1 wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 85:15. According to the test, the boiling point of solvent X is 78℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 1%, and the glass transition temperature of the polymer material after plasticization in solvent X is 25℃.

[0080] (3) Preparation of electrospun fiber membrane;

[0081] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0082] The thickness of the electrospun fiber membrane was 100 μm.

[0083] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0084] The electrospun fiber membrane was immersed in a treatment solution at 25°C for 10 minutes, then removed and rinsed three times in anhydrous ethanol at 0°C for 10 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 50 mL.

[0085] The final anti-blocking membrane with rough fiber structure is shown in the figure below. Figure 1 The fiber surface (as shown) is uniformly covered with crystalline protrusions, with an average thickness of 10 nm and an average length of 50 nm.

[0086] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 41 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 40% and an α-SMA activation rate of 35%.

[0087] Comparative Example 1

[0088] A method for preparing a membrane differs from Example 1 only in that: in step (2), the volume ratio of inferior solvent to good solvent in the treatment solution is adjusted (ethanol:acetone = 99:1), which makes the swelling rate of the polymer material after being placed in solvent X at 25°C for 10 min 0.5%.

[0089] The final membrane (see SEM image) Figure 3 The fiber surface remained largely smooth, failing to form an integrated nanocrystal structure, with only scattered, irregular precipitates; the average area of ​​the cells after spreading on the membrane was 185 µm². 2 The membrane's YAP activation rate was 72%, and its α-SMA activation rate was 65%.

[0090] Compared to Example 1, Comparative Example 1 showed a significantly worse anti-adhesion effect. This is because the ratio of inferior to beneficial solvents did not meet the limitations of this invention. When the swelling rate was too low, the treatment solution could not effectively penetrate the fiber surface and induce sufficient activation and orderly arrangement of polymer chains, resulting in the inability to grow nanocrystalline structures sufficient to restrict cell spread in situ on the fiber surface. At this point, the membrane was essentially still a common electrospun fiber membrane and could not block the transformation of fibroblasts into myofibroblasts through physical topological signals.

[0091] Example 2

[0092] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0093] (1) Preparation of main materials;

[0094] Polymer material: PLA, manufactured by NatureWorks LLC, grade 4032D, intrinsic viscosity 2.5 dL / g;

[0095] Hydrophilic anti-blocking component: HA, manufactured by Bloomage Biotechnology Co., Ltd., brand name HA-100, intrinsic viscosity is 2.0 dL / g;

[0096] Inferior solvent: Ethanol;

[0097] Beneficial solvent: Tetrahydrofuran;

[0098] (2) Prepare spinning solution and treatment solution;

[0099] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 70:30; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 20 wt%.

[0100] The solvent in the spinning solution is hexafluoroisopropanol;

[0101] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 5 wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 95:5. According to the test, the boiling point of solvent X is 66℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 10%, and the glass transition temperature of the polymer material after plasticization in solvent X is 30℃.

[0102] (3) Preparation of electrospun fiber membrane;

[0103] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0104] The thickness of the electrospun fiber membrane was 100 μm.

[0105] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0106] The electrospun fiber membrane was immersed in a treatment solution at 35°C for 30 minutes, then removed and rinsed five times in anhydrous ethanol at 4°C for 30 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 100 mL.

[0107] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 100 nm, and the average length of the crystalline protrusions is 500 nm.

[0108] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 50 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 50% and an α-SMA activation rate of 45%.

[0109] Comparative Example 2

[0110] A method for preparing a membrane differs from Example 2 only in that: in step (2), the volume ratio of the inferior solvent to the good solvent in the treatment solution is adjusted (ethanol:tetrahydrofuran=65:35), which makes the swelling rate of the polymer material after being placed in solvent X at 25°C for 10 min 11%.

[0111] The final membrane (see SEM image) Figure 4 The fibers exhibited significant swelling and deformation, with some fibers showing fusion and adhesion at intersections. The fine topological structure of the fiber surface disappeared, presenting a connected blocky or smooth remelted morphology. After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the fibers changed significantly. The average area of ​​cells spread on the membrane was 152 µm². 2 The membrane's YAP activation rate was 68%, and its α-SMA activation rate was 58%.

[0112] Compared with Example 2, Comparative Example 2 showed significantly worse anti-adhesion performance and structural stability. This is because the ratio of inferior solvent to good solvent does not meet the requirements of this invention. When the swelling rate is too high, the solvent's destructive effect on the fibers is enhanced, leading to excessive dissolution of polymer chain segments instead of controlled recrystallization. This not only destroys the initial topological structure that has been formed, but also causes adhesion between fibers, resulting in a decrease in the flexibility of the membrane and the loss of its specific physical barrier function.

[0113] Comparative Example 3

[0114] A method for preparing a membrane differs from Example 2 only in that the treatment solution contains no polymeric material.

[0115] The final membrane (see SEM image) Figure 5 The fiber surface of the membrane only formed a small amount of scattered, discontinuous sheet-like precipitates, failing to form a stable nanocrystal structure uniformly covering the fiber surface. Local collapse and smoothing phenomena were observed on some fiber surfaces, and slight adhesion was observed at fiber intersections, but a stable integrated topological structure was not formed. After immersion in simulated body fluid at 37°C for 14 days, the fiber surface morphology showed further reduction or detachment of scattered precipitates, rearrangement and collapse in local areas, and a significant change in the overall surface morphology, making it difficult to maintain a stable nanotopology. The average area of ​​cells spread on the membrane was 168 µm². 2 The membrane's YAP activation rate was 63%, and its α-SMA activation rate was 54%.

[0116] Compared to Example 2, Comparative Example 3 showed significantly worse structural stability and anti-adhesion performance. This is because the lack of the same polymer material in the treatment solution prevented the formation of stable heterogeneous nucleation centers in the system. The fiber surface relied solely on a small number of released chain segments for random crystallization, making it difficult to form a continuous, uniform, integrated nanocrystal structure on the fiber surface. Furthermore, due to the lack of chain entanglement and synergistic crystallization between the exogenous polymer chains and the fiber surface chain segments, the locally formed crystallized structures had weak bonding with the fiber substrate. During rinsing, drying, and immersion in simulated body fluids, these structures were prone to detachment, collapse, or further rearrangement, resulting in their inability to maintain effective nanotopological signals over a long period. Therefore, this membrane was unable to effectively restrict cell spreading and focal adhesion maturation, ultimately leading to increased YAP activation rate and α-SMA expression levels, and a significant decrease in anti-adhesion effect.

[0117] Comparative Example 4

[0118] A method for preparing a membrane is basically the same as that of Comparative Example 3, except that in step (4), the electrospun fiber membrane is immersed in the treatment solution at 35°C for 40 minutes.

[0119] The resulting membrane exhibited overall swelling and deformation of the fibers, with a significant increase in fiber diameter and a smoothed surface. Most fibers fused and bonded together at their intersections, forming interconnected sheet-like or network structures. The original independent morphology of the fibers essentially disappeared, and the fine topological structure of the original fiber surface was completely destroyed. After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the fibers changed significantly, and the structure further collapsed. The average area of ​​cells spread on this membrane was 187 µm², with a YAP activation rate of 76% and an α-SMA activation rate of 69%.

[0120] Compared with Examples 2 and 3, Comparative Example 4 showed significantly worse structural stability and anti-adhesion effect. This is because, without the introduction of exogenous nucleating polymer materials (the same treatment solution does not contain polymer materials), simply extending the soaking time allowed the swelling to continue to penetrate deeper, causing the fiber surface chain segments to continuously dissolve and diffuse into the solvent, resulting in large-area fusion at the intersections. Ultimately, this formed a cross-point welding structure similar to that in patent application CN118345627A. This structure is completely different from the nanocrystal structure of this invention. The essential difference is that nanocrystals are independent structural units of surface crystal growth, and the fiber intersections do not fuse; while cross-point welding is a physical fusion between fibers.

[0121] Although both patent application CN118345627A and this invention involve solvent impregnation treatment, their technical objectives and structural evolution paths are completely different. Patent application CN118345627A aims to improve the mechanical strength of materials by forming a stable three-dimensional network structure through swelling, fusion, and solidification bonding at fiber intersections; while this invention aims to construct a uniform and stable nanocrystalline structure on the surface of flexible fibers to regulate cell behavior and achieve anti-adhesion. Therefore, this invention does not pursue intersection welding, but instead requires controlling the swelling within a critical window that can induce in-situ recrystallization of the surface without causing intersection fusion.

[0122] For different purposes, patent application CN118345627A and this invention employ different methods, specifically in the following aspects:

[0123] (1) Differences in the composition of the treatment solution

[0124] The treatment solution in patent application CN118345627A consists only of a benign solvent and a non-solvent. Its mechanism of action is to cause the polymer on the fiber surface to swell and fuse together at the intersections, and then solidify and bond during subsequent rinsing and drying. This invention, however, introduces the same polymer material into the treatment solution, providing heterogeneous nucleation sites on the fiber surface, inducing in-situ rearrangement and crystallization of surface chain segments, ultimately forming integrated nanocrystals. The former is "intersection fusion welding," while the latter is "in-situ surface recrystallization," representing different pathways of action.

[0125] (2) Differences in soaking time control

[0126] Patent application CN118345627A controls the soaking time to ensure sufficient swelling of the fiber surface and effective interdiffusion and fusion at the intersections, with a typically long time window (up to several hours) to ensure weld strength. This invention controls the soaking time to be no less than the minimum time required to generate complete and uniform nanocrystals on the surface of the electrospun fiber membrane, and no more than the minimum time required for overall swelling, dissolution, or morphological destruction of the electrospun fiber membrane. The soaking time window of this invention is significantly shorter than the time required for the welding process, aiming to terminate the treatment immediately after surface crystallization to avoid fusion at the intersections.

[0127] (3) The swelling rate window has different meanings.

[0128] Patent application CN118345627A does not explicitly define the swelling rate value, and its process tends to use solvent ratios that allow the fibers to swell sufficiently (typically corresponding to a swelling rate >10%) to promote sufficient interdiffusion and fusion at the cross-points. This invention, however, controls the swelling rate of the polymer material after being placed in solvent X at 25°C for 10 minutes to be 1%-10%. The 1%-10% swelling rate defined by this invention is not the optimal welding window for patent application CN118345627A. For patent application CN118345627A, this range is closer to an intermediate state where "chain segment flow has been activated, but the cross-points have not yet fully interdiffused and solidified," making it difficult to form the high-strength bonding interface required. Further increasing the swelling (>10%) would be more conducive to cross-point fusion, but would deviate from the restricted recrystallization conditions required by this invention (as shown in Comparative Example 2). Therefore, the 1%-10% swelling rate window has the exact opposite meaning for this invention and for patent application CN118345627A.

[0129] Example 3

[0130] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0131] (1) Preparation of main materials;

[0132] Polymer material: PLA, manufactured by NatureWorks LLC, grade 4032D, intrinsic viscosity 2.0 dL / g;

[0133] Hydrophilic anti-blocking component: HA, manufactured by Bloomage Biotechnology Co., Ltd., brand name HA-100, intrinsic viscosity is 1.2 dL / g;

[0134] Inferior solvent: methanol;

[0135] Beneficial solvent: dichloromethane;

[0136] (2) Prepare spinning solution and treatment solution;

[0137] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 85:15; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 12 wt%.

[0138] The solvent in the spinning solution is hexafluoroisopropanol;

[0139] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 2wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 90:10. According to the test, the boiling point of solvent X is 40℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 5%, and the glass transition temperature of the polymer material after plasticization in solvent X is 28℃.

[0140] (3) Preparation of electrospun fiber membrane;

[0141] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0142] The thickness of the electrospun fiber membrane was 100 μm.

[0143] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0144] The electrospun fiber membrane was immersed in a treatment solution at 30°C for 20 minutes, then removed and rinsed four times in anhydrous ethanol at 2°C for 20 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 75 mL.

[0145] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 50 nm, and the average length of the crystalline protrusions is 200 nm.

[0146] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 44 µm². 2The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 45% and an α-SMA activation rate of 40%.

[0147] Example 4

[0148] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0149] (1) Preparation of main materials;

[0150] Polymer material: PLA, manufactured by NatureWorks LLC, grade 4032D, intrinsic viscosity 1.8 dL / g;

[0151] Hydrophilic anti-blocking component: HA, manufactured by Bloomage Biotechnology Co., Ltd., brand name HA-100, intrinsic viscosity is 1.0 dL / g;

[0152] Inferior solvent: Isopropanol;

[0153] Beneficial solvent: N,N-dimethylformamide;

[0154] (2) Prepare spinning solution and treatment solution;

[0155] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 80:20; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 15 wt%.

[0156] The solvent in the spinning solution is hexafluoroisopropanol;

[0157] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 3wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 88:12. According to the test, the boiling point of solvent X is 153℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 8%, and the glass transition temperature of the polymer material after plasticization in solvent X is 27℃.

[0158] (3) Preparation of electrospun fiber membrane;

[0159] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0160] The thickness of the electrospun fiber membrane was 100 μm.

[0161] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0162] The electrospun fiber membrane was immersed in a treatment solution at 28°C for 15 minutes, then removed and rinsed four times in anhydrous ethanol at 3°C ​​for 15 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 80 mL.

[0163] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 80 nm, and the average length of the crystalline protrusions is 400 nm.

[0164] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 46 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 48% and an α-SMA activation rate of 42%.

[0165] Example 5

[0166] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0167] (1) Preparation of main materials;

[0168] Polymer material: PCL, manufactured by Perstorp Holding AB, brand name Capa 6800, intrinsic viscosity is 1.0 dL / g;

[0169] Hydrophilic anti-blocking component: Chitosan, manufactured by Sigma-Aldrich Corporation, product number 448877, intrinsic viscosity 1.0 dL / g;

[0170] Inferior solvent: Ethanol;

[0171] Beneficial solvent: acetone;

[0172] (2) Prepare spinning solution and treatment solution;

[0173] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 95:5; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 8 wt%.

[0174] The solvent in the spinning solution is acetic acid;

[0175] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 0.1 wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 80:20. According to the test, the boiling point of solvent X is 78℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 1%, and the glass transition temperature of the polymer material after plasticization in solvent X is -5℃.

[0176] (3) Preparation of electrospun fiber membrane;

[0177] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0178] The thickness of the electrospun fiber membrane was 100 μm.

[0179] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0180] The electrospun fiber membrane was immersed in a treatment solution at 20°C for 1 minute, then removed and rinsed three times in anhydrous ethanol at 0°C for 10 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 50 mL.

[0181] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 10 nm, and the average length of the crystalline protrusions is 50 nm.

[0182] like Figure 2 As shown, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly after immersion in simulated body fluid at 37°C for 14 days; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 42 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 40% and an α-SMA activation rate of 35%.

[0183] Example 6

[0184] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0185] (1) Preparation of main materials;

[0186] Polymer material: PCL, manufactured by Perstorp Holding AB, brand name Capa 6800, intrinsic viscosity is 1.8 dL / g;

[0187] Hydrophilic anti-blocking component: Chitosan, manufactured by Sigma-Aldrich Corporation, product number 448877, intrinsic viscosity 3.0 dL / g;

[0188] Inferior solvent: methanol;

[0189] Beneficial solvent: ethyl acetate;

[0190] (2) Prepare spinning solution and treatment solution;

[0191] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 70:30; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 20 wt%.

[0192] The solvent in the spinning solution is acetic acid;

[0193] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 5 wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 95:5. According to the test, the boiling point of solvent X is 77℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 10%, and the glass transition temperature of the polymer material after plasticization in solvent X is 0℃.

[0194] (3) Preparation of electrospun fiber membrane;

[0195] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0196] The thickness of the electrospun fiber membrane was 100 μm.

[0197] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0198] The electrospun fiber membrane was immersed in a treatment solution at 40°C for 10 minutes, then removed and rinsed five times in anhydrous ethanol at 4°C for 30 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 100 mL.

[0199] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 100 nm, and the average length of the crystalline protrusions is 500 nm.

[0200] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 48 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 50% and an α-SMA activation rate of 45%.

[0201] Example 7

[0202] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0203] (1) Preparation of main materials;

[0204] Polymer material: PCL, manufactured by Perstorp Holding AB, brand name Capa 6800, intrinsic viscosity is 1.4 dL / g;

[0205] Hydrophilic anti-blocking component: Chitosan, manufactured by Sigma-Aldrich Corporation, product number 448877, intrinsic viscosity 2.0 dL / g;

[0206] Inferior solvent: Ethanol;

[0207] Beneficial solvent: acetone;

[0208] (2) Prepare spinning solution and treatment solution;

[0209] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 85:15; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 12 wt%.

[0210] The solvent in the spinning solution is acetic acid;

[0211] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 2wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 88:12. According to the test, the boiling point of solvent X is 78℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 5%, and the glass transition temperature of the polymer material after plasticization in solvent X is -2℃.

[0212] (3) Preparation of electrospun fiber membrane;

[0213] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0214] The thickness of the electrospun fiber membrane was 100 μm.

[0215] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0216] The electrospun fiber membrane was immersed in a treatment solution at 30°C for 5 minutes, then removed and rinsed four times in anhydrous ethanol at 2°C for 20 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 75 mL.

[0217] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 50 nm, and the average length of the crystalline protrusions is 200 nm.

[0218] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 45 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 45% and an α-SMA activation rate of 40%.

[0219] Example 8

[0220] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0221] (1) Preparation of main materials;

[0222] Polymer material: PCL, manufactured by Perstorp Holding AB, brand name Capa 6800, intrinsic viscosity is 1.2 dL / g;

[0223] Hydrophilic anti-blocking component: Chitosan, manufactured by Sigma-Aldrich Corporation, product number 448877, intrinsic viscosity 1.5 dL / g;

[0224] Inferior solvent: methanol;

[0225] Beneficial solvent: ethyl acetate;

[0226] (2) Prepare spinning solution and treatment solution;

[0227] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 80:20; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 15 wt%.

[0228] The solvent in the spinning solution is acetic acid;

[0229] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 3wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 90:10. According to the test, the boiling point of solvent X is 77℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 8%, and the glass transition temperature of the polymer material after plasticization in solvent X is -1℃.

[0230] (3) Preparation of electrospun fiber membrane;

[0231] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0232] The thickness of the electrospun fiber membrane was 100 μm.

[0233] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0234] The electrospun fiber membrane was immersed in a treatment solution at 25°C for 8 minutes, then removed and rinsed four times in anhydrous ethanol at 3°C ​​for 15 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 80 mL.

[0235] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 80 nm, and the average length of the crystalline protrusions is 400 nm.

[0236] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 47 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 48% and an α-SMA activation rate of 42%.

[0237] Example 9

[0238] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0239] (1) Preparation of main materials;

[0240] Polymer material: PLGA, manufactured by Evonik Industries AG, grade Resomer RG 504, intrinsic viscosity 0.5 dL / g;

[0241] Hydrophilic anti-blocking component: PEG200, manufactured by Sigma-Aldrich Corporation, catalog number 202371, kinematic viscosity 22.0 mm² / s;

[0242] Inferior solvent: Ethanol;

[0243] Beneficial solvent: acetone;

[0244] (2) Prepare spinning solution and treatment solution;

[0245] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 95:5; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 8 wt%.

[0246] The solvent in the spinning solution is chloroform:acetone = 8:2;

[0247] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 0.1 wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 70:30. According to the test, the boiling point of solvent X is 78℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 1%, and the glass transition temperature of the polymer material after plasticization in solvent X is -15℃.

[0248] (3) Preparation of electrospun fiber membrane;

[0249] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0250] The thickness of the electrospun fiber membrane was 100 μm.

[0251] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0252] The electrospun fiber membrane was immersed in a treatment solution at 15℃ for 5 minutes, then removed and rinsed three times in anhydrous ethanol at 0℃ for 10 seconds each time. It was then vacuum dried at 25℃ for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 50 mL.

[0253] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 10 nm, and the average length of the crystalline protrusions is 50 nm.

[0254] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 40 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 40% and an α-SMA activation rate of 35%.

[0255] Example 10

[0256] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0257] (1) Preparation of main materials;

[0258] Polymer material: PLGA, manufactured by Evonik Industries AG, grade Resomer RG 504, intrinsic viscosity 1.2 dL / g;

[0259] Hydrophilic anti-blocking component: PEG200, manufactured by Sigma-Aldrich Corporation, catalog number 202371, kinematic viscosity 23.0 mm² / s;

[0260] Bad solvent: water;

[0261] Beneficial solvent: DMF;

[0262] (2) Prepare spinning solution and treatment solution;

[0263] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 70:30; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 20 wt%.

[0264] The solvent in the spinning solution is chloroform:acetone = 8:2;

[0265] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 5 wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 90:10. According to the test, the boiling point of solvent X is 153℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 10%, and the glass transition temperature of the polymer material after plasticization in solvent X is -5℃.

[0266] (3) Preparation of electrospun fiber membrane;

[0267] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0268] The thickness of the electrospun fiber membrane was 100 μm.

[0269] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0270] The electrospun fiber membrane was immersed in a treatment solution at 40°C for 20 minutes, then removed and rinsed five times in anhydrous ethanol at 4°C for 30 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 100 mL.

[0271] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 100 nm, and the average length of the crystalline protrusions is 500 nm.

[0272] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 47 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 50% and an α-SMA activation rate of 45%.

[0273] Example 11

[0274] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0275] (1) Preparation of main materials;

[0276] Polymer material: PLGA, manufactured by Evonik Industries AG, grade Resomer RG 504, intrinsic viscosity 0.8 dL / g;

[0277] Hydrophilic anti-blocking component: PEG200, manufactured by Sigma-Aldrich Corporation, catalog number 202371, kinematic viscosity 22.5 mm² / s;

[0278] Inferior solvent: a mixture of ethanol and water in a volume ratio of 1:1;

[0279] Beneficial solvent: a mixture of acetone and DMF in a volume ratio of 1:1;

[0280] (2) Prepare spinning solution and treatment solution;

[0281] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 85:15; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 12 wt%.

[0282] The solvent in the spinning solution is chloroform:acetone = 8:2;

[0283] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 2wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 80:20. According to the test, the boiling point of solvent X is 65℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 5%, and the glass transition temperature of the polymer material after plasticization in solvent X is -8℃.

[0284] (3) Preparation of electrospun fiber membrane;

[0285] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0286] The thickness of the electrospun fiber membrane was 100 μm.

[0287] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0288] The electrospun fiber membrane was immersed in a treatment solution at 25°C for 12 minutes, then removed and rinsed four times in anhydrous ethanol at 2°C for 20 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 75 mL.

[0289] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 50 nm, and the average length of the crystalline protrusions is 200 nm.

[0290] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 43 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 45% and an α-SMA activation rate of 40%.

[0291] Example 12

[0292] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0293] (1) Preparation of main materials;

[0294] Polymer material: PLGA, manufactured by Evonik Industries AG, grade Resomer RG 504, intrinsic viscosity 1.0 dL / g;

[0295] Hydrophilic anti-blocking component: PEG200, manufactured by Sigma-Aldrich Corporation, catalog number 202371, kinematic viscosity 22.8 mm² / s;

[0296] Inferior solvent: a mixture of ethanol and water in a volume ratio of 2:1;

[0297] Beneficial solvent: a mixture of acetone and DMF in a volume ratio of 2:1;

[0298] (2) Prepare spinning solution and treatment solution;

[0299] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 80:20; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 15 wt%.

[0300] The solvent in the spinning solution is chloroform:acetone = 8:2;

[0301] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 3wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 85:15. According to the test, the boiling point of solvent X is 60℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 8%, and the glass transition temperature of the polymer material after plasticization in solvent X is -6℃.

[0302] (3) Preparation of electrospun fiber membrane;

[0303] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0304] The thickness of the electrospun fiber membrane was 100 μm.

[0305] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0306] The electrospun fiber membrane was immersed in a treatment solution at 30°C for 15 minutes, then removed and rinsed four times in anhydrous ethanol at 3°C ​​for 15 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 80 mL.

[0307] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 80 nm, and the average length of the crystalline protrusions is 400 nm.

[0308] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 46 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 48% and an α-SMA activation rate of 42%.

[0309] Example 13

[0310] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0311] (1) Preparation of main materials;

[0312] Polymer material: PLCL, manufactured by Corbion NV, grade Purasorb PLC 7015, intrinsic viscosity 1.5 dL / g;

[0313] Hydrophilic anti-blocking component: HA, manufactured by Bloomage Biotechnology Co., Ltd., brand name HA-100, intrinsic viscosity is 0.5 dL / g;

[0314] Inferior solvent: Ethanol;

[0315] Beneficial solvent: acetone;

[0316] (2) Prepare spinning solution and treatment solution;

[0317] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 95:5; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 8 wt%.

[0318] The solvent in the spinning solution is hexafluoroisopropanol;

[0319] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 0.1 wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 85:15. According to the test, the boiling point of solvent X is 78℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 1%, and the glass transition temperature of the polymer material after plasticization in solvent X is 20℃.

[0320] (3) Preparation of electrospun fiber membrane;

[0321] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0322] The thickness of the electrospun fiber membrane was 100 μm.

[0323] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0324] The electrospun fiber membrane was immersed in a treatment solution at 25°C for 10 minutes, then removed and rinsed three times in anhydrous ethanol at 0°C for 10 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 50 mL.

[0325] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 10 nm, and the average length of the crystalline protrusions is 50 nm.

[0326] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 41 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 40% and an α-SMA activation rate of 35%.

[0327] Example 14

[0328] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0329] (1) Preparation of main materials;

[0330] Polymer material: PLCL, manufactured by Corbion NV, grade Purasorb PLC 7015, intrinsic viscosity 2.5 dL / g;

[0331] Hydrophilic anti-blocking component: HA, manufactured by Bloomage Biotechnology Co., Ltd., brand name HA-100, intrinsic viscosity is 2.0 dL / g;

[0332] Inferior solvent: Isopropanol;

[0333] Beneficial solvent: THF;

[0334] (2) Prepare spinning solution and treatment solution;

[0335] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 70:30; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 20 wt%.

[0336] The solvent in the spinning solution is hexafluoroisopropanol;

[0337] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 5 wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 95:5. According to the test, the boiling point of solvent X is 82℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 10%, and the glass transition temperature of the polymer material after plasticization in solvent X is 25℃.

[0338] (3) Preparation of electrospun fiber membrane;

[0339] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0340] The thickness of the electrospun fiber membrane was 100 μm.

[0341] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0342] The electrospun fiber membrane was immersed in a treatment solution at 35°C for 30 minutes, then removed and rinsed five times in anhydrous ethanol at 4°C for 30 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 100 mL.

[0343] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 100 nm, and the average length of the crystalline protrusions is 500 nm.

[0344] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 49 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 50% and an α-SMA activation rate of 45%.

[0345] Example 15

[0346] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0347] (1) Preparation of main materials;

[0348] Polymer material: PLCL, manufactured by Corbion NV, grade Purasorb PLC 7015, intrinsic viscosity 2.0 dL / g;

[0349] Hydrophilic anti-blocking component: HA, manufactured by Bloomage Biotechnology Co., Ltd., brand name HA-100, intrinsic viscosity is 1.2 dL / g;

[0350] Inferior solvent: Ethanol;

[0351] Beneficial solvent: acetone;

[0352] (2) Prepare spinning solution and treatment solution;

[0353] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 85:15; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 12 wt%.

[0354] The solvent in the spinning solution is hexafluoroisopropanol;

[0355] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 2wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 90:10. According to the test, the boiling point of solvent X is 78℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 5%, and the glass transition temperature of the polymer material after plasticization in solvent X is 22℃.

[0356] (3) Preparation of electrospun fiber membrane;

[0357] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0358] The thickness of the electrospun fiber membrane was 100 μm.

[0359] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0360] The electrospun fiber membrane was immersed in a treatment solution at 30°C for 20 minutes, then removed and rinsed four times in anhydrous ethanol at 2°C for 20 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 75 mL.

[0361] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 50 nm, and the average length of the crystalline protrusions is 200 nm.

[0362] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 44 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 45% and an α-SMA activation rate of 40%.

[0363] Example 16

[0364] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0365] (1) Preparation of main materials;

[0366] Polymer material: PLCL, manufactured by Corbion NV, grade Purasorb PLC 7015, intrinsic viscosity 1.8 dL / g;

[0367] Hydrophilic anti-blocking component: HA, manufactured by Bloomage Biotechnology Co., Ltd., brand name HA-100, intrinsic viscosity is 1.0 dL / g;

[0368] Inferior solvent: Isopropanol;

[0369] Beneficial solvent: THF;

[0370] (2) Prepare spinning solution and treatment solution;

[0371] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 80:20; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 15 wt%.

[0372] The solvent in the spinning solution is hexafluoroisopropanol;

[0373] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 3wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 88:12. According to the test, the boiling point of solvent X is 82℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 8%, and the glass transition temperature of the polymer material after plasticization in solvent X is 23℃.

[0374] (3) Preparation of electrospun fiber membrane;

[0375] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0376] The thickness of the electrospun fiber membrane was 100 μm.

[0377] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0378] The electrospun fiber membrane was immersed in a treatment solution at 28°C for 15 minutes, then removed and rinsed four times in anhydrous ethanol at 3°C ​​for 15 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 80 mL.

[0379] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 80 nm, and the average length of the crystalline protrusions is 400 nm.

[0380] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 46 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 48% and an α-SMA activation rate of 42%.

[0381] Example 17

[0382] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0383] (1) Preparation of main materials;

[0384] Polymer material: PCL, manufactured by Perstorp Holding AB, brand name Capa 6800, intrinsic viscosity is 1.0 dL / g;

[0385] Hydrophilic anti-blocking component: Sodium alginate, manufactured by Sigma-Aldrich Corporation, product number A2033, intrinsic viscosity is 0.2 dL / g;

[0386] Inferior solvent: Ethanol;

[0387] Beneficial solvent: acetone;

[0388] (2) Prepare spinning solution and treatment solution;

[0389] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 95:5; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 8 wt%.

[0390] The solvent in the spinning solution is hexafluoroisopropanol;

[0391] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 0.1 wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 80:20. According to the test, the boiling point of solvent X is 78℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 1%, and the glass transition temperature of the polymer material after plasticization in solvent X is -5℃.

[0392] (3) Preparation of electrospun fiber membrane;

[0393] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0394] The thickness of the electrospun fiber membrane was 100 μm.

[0395] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0396] The electrospun fiber membrane was immersed in a treatment solution at 20°C for 10 minutes, then removed and rinsed three times in anhydrous ethanol at 0°C for 10 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 50 mL.

[0397] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 10 nm, and the average length of the crystalline protrusions is 50 nm.

[0398] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 42 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 40% and an α-SMA activation rate of 35%.

[0399] Example 18

[0400] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0401] (1) Preparation of main materials;

[0402] Polymer material: PCL, manufactured by Perstorp Holding AB, brand name Capa 6800, intrinsic viscosity is 1.8 dL / g;

[0403] Hydrophilic anti-blocking component: Sodium alginate, manufactured by Sigma-Aldrich Corporation, product number A2033, intrinsic viscosity is 2.0 dL / g;

[0404] Bad solvent: water;

[0405] Beneficial solvent: DMF;

[0406] (2) Prepare spinning solution and treatment solution;

[0407] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 70:30; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 20 wt%.

[0408] The solvent in the spinning solution is hexafluoroisopropanol;

[0409] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 5 wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 95:5. According to the test, the boiling point of solvent X is 100℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 10%, and the glass transition temperature of the polymer material after plasticization in solvent X is 0℃.

[0410] (3) Preparation of electrospun fiber membrane;

[0411] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0412] The thickness of the electrospun fiber membrane was 100 μm.

[0413] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0414] The electrospun fiber membrane was immersed in a treatment solution at 40°C for 30 minutes, then removed and rinsed five times in anhydrous ethanol at 4°C for 30 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 100 mL.

[0415] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 100 nm, and the average length of the crystalline protrusions is 500 nm.

[0416] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 48 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 50% and an α-SMA activation rate of 45%.

[0417] Example 19

[0418] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0419] (1) Preparation of main materials;

[0420] Polymer material: PCL, manufactured by Perstorp Holding AB, brand name Capa 6800, intrinsic viscosity is 1.4 dL / g;

[0421] Hydrophilic anti-blocking component: Sodium alginate, manufactured by Sigma-Aldrich Corporation, product number A2033, intrinsic viscosity is 1.0 dL / g;

[0422] Inferior solvent: a mixture of ethanol and water in a volume ratio of 1:1;

[0423] Beneficial solvent: a mixture of acetone and DMF in a volume ratio of 1:1;

[0424] (2) Prepare spinning solution and treatment solution;

[0425] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 85:15; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 12 wt%.

[0426] The solvent in the spinning solution is hexafluoroisopropanol;

[0427] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 2wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 88:12. According to the test, the boiling point of solvent X is 65℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 5%, and the glass transition temperature of the polymer material after plasticization in solvent X is -2℃.

[0428] (3) Preparation of electrospun fiber membrane;

[0429] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0430] The thickness of the electrospun fiber membrane was 100 μm.

[0431] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0432] The electrospun fiber membrane was immersed in a treatment solution at 30°C for 20 minutes, then removed and rinsed four times in anhydrous ethanol at 2°C for 20 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 75 mL.

[0433] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 50 nm, and the average length of the crystalline protrusions is 200 nm.

[0434] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 45 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 45% and an α-SMA activation rate of 40%.

[0435] Example 20

[0436] A method for preparing an anti-adhesion membrane with coarse-structured fibers, comprising the following steps:

[0437] (1) Preparation of main materials;

[0438] Polymer material: PCL, manufactured by Perstorp Holding AB, brand name Capa 6800, intrinsic viscosity is 1.2 dL / g;

[0439] Hydrophilic anti-blocking component: Sodium alginate, manufactured by Sigma-Aldrich Corporation, product number A2033, intrinsic viscosity is 1.5 dL / g;

[0440] Inferior solvent: a mixture of ethanol and water in a volume ratio of 2:1;

[0441] Beneficial solvent: a mixture of acetone and DMF in a volume ratio of 2:1;

[0442] (2) Prepare spinning solution and treatment solution;

[0443] The solute in the spinning solution consists of a polymer material and a hydrophilic anti-blocking component; the mass ratio of the polymer material to the hydrophilic anti-blocking component in the spinning solution is 80:20; the total content of the polymer material and the hydrophilic anti-blocking component in the spinning solution is 15 wt%.

[0444] The solvent in the spinning solution is hexafluoroisopropanol;

[0445] The solute in the treatment solution is a polymer material, and the content of the polymer material in the treatment solution is 3wt%. The solvent in the treatment solution is denoted as solvent X, which is composed of a poor solvent and a good solvent in a volume ratio of 90:10. According to the test, the boiling point of solvent X is 60℃, the swelling rate of the polymer material after being placed in solvent X at 25℃ for 10 minutes is 8%, and the glass transition temperature of the polymer material after plasticization in solvent X is -1℃.

[0446] (3) Preparation of electrospun fiber membrane;

[0447] Electrospinning was performed on the spinning solution to obtain an intermediate product membrane, which was then vacuum dried at 40°C for 24 hours to obtain an electrospun fiber membrane. The electrospinning process parameters were as follows: syringe needle type 21G, spinning voltage +15kV / -5kV, solution feed rate 1mL / h, receiving distance 15cm, collector rotation speed 100rpm, spinning ambient temperature 25°C, and spinning ambient relative humidity 40%.

[0448] The thickness of the electrospun fiber membrane was 100 μm.

[0449] (4) Prepare an anti-adhesion membrane with rough fiber structure;

[0450] The electrospun fiber membrane was immersed in a treatment solution at 25°C for 15 minutes, then removed and rinsed four times in anhydrous ethanol at 3°C ​​for 15 seconds each time. It was then vacuum dried at 25°C for 12 hours to obtain an anti-adhesion membrane with a rough fiber structure. The mass-volume ratio of the electrospun fiber membrane to the treatment solution was 1 g: 80 mL.

[0451] The final anti-adhesion membrane with rough fiber structure has a fiber surface uniformly covered with crystalline protrusions, the average thickness of the crystalline protrusions is 80 nm, and the average length of the crystalline protrusions is 400 nm.

[0452] After immersion in simulated body fluid at 37°C for 14 days, the surface morphology of the anti-adhesion membrane with rough-structured fibers did not change significantly; the average area of ​​cells spread on the anti-adhesion membrane with rough-structured fibers was 47 µm². 2 The anti-adhesion membrane with rough fiber structure has a YAP activation rate of 48% and an α-SMA activation rate of 42%.

Claims

1. A method for preparing an anti-adhesion membrane with coarse-structured fibers, characterized in that, After immersing the electrospun fiber membrane in the treatment solution, it is rinsed and dried in sequence to obtain an anti-adhesion membrane with a rough fiber structure. The electrospun fiber membrane is obtained by electrospinning from a spinning solution, wherein the solute in the spinning solution is composed of a polymer material and a hydrophilic anti-adhesion component. The solute in the treatment solution is the polymer material; The solvent in the treatment solution is denoted as solvent X. Solvent X consists of a poor solvent and a good solvent. The poor solvent is a common poor solvent for both the polymer material and the hydrophilic anti-adhesion component. The good solvent is only a good solvent for the polymer material. The ratio of the poor solvent to the good solvent satisfies the following condition: the swelling rate of the polymer material after being placed in solvent X at 25°C for 10 minutes is 1%-10%. The soaking time shall not be less than the minimum time required for the formation of complete and uniform nanocrystals on the surface of the electrospun fiber membrane, and shall not be more than the minimum time required for the electrospun fiber membrane to undergo overall swelling, dissolution or morphological destruction.

2. The method for preparing an anti-adhesion membrane with coarse fiber structure according to claim 1, characterized in that, The mass ratio of the polymeric material to the hydrophilic anti-adhesion component in the spinning solution is 95:5-70:30; the total content of the polymeric material and the hydrophilic anti-adhesion component in the spinning solution is 8wt%-20wt%; the content of the polymeric material in the treatment solution is 0.1wt%-5wt%; and the mass-volume ratio of the electrospun fiber membrane to the treatment solution is 1g:50-100mL.

3. The method for preparing an anti-adhesion membrane with coarse fiber structure according to claim 1, characterized in that, The soaking temperature is not lower than the glass transition temperature of the polymer material after plasticization in the solvent X, not higher than the temperature that would cause the solvent X to volatilize violently, the electrospun fiber membrane to swell or dissolve excessively, or the hydrophilic anti-adhesion component to be structurally damaged and lose its biological activity, and is lower than the initial boiling point of the solvent X.

4. The method for preparing an anti-adhesion membrane with rough fiber structure according to claim 3, characterized in that, The polymer material is PLA with an intrinsic viscosity of 1.5-2.5 dL / g, the hydrophilic anti-blocking component is HA with an intrinsic viscosity of 0.5-2.0 dL / g, the inferior solvent is one or more of ethanol, methanol and isopropanol, the beneficial solvent is one or more of acetone, tetrahydrofuran, dichloromethane and N,N-dimethylformamide, the volume ratio of the inferior solvent to the beneficial solvent is 85:15-95:5, the soaking time is 10-30 min, and the soaking temperature is 25-35℃.

5. The method for preparing an anti-adhesion membrane with coarse fiber structure according to claim 3, characterized in that, The polymer material is PCL with an intrinsic viscosity of 1.0-1.8 dL / g, the hydrophilic anti-blocking component is chitosan with an intrinsic viscosity of 1.0-3.0 dL / g, the inferior solvent is one or more of ethanol and methanol, the beneficial solvent is one or more of acetone and ethyl acetate, the volume ratio of the inferior solvent to the beneficial solvent is 80:20-95:5, the soaking time is 1-10 min, and the soaking temperature is 20-40℃.

6. The method for preparing an anti-adhesion membrane with rough fiber structure according to claim 3, characterized in that, The polymer material is PLGA with an intrinsic viscosity of 0.5-1.2 dL / g, and the hydrophilic anti-blocking component has a kinematic viscosity of 22-23 mm at 40°C. 2 The PEG200 is of a certain concentration, wherein the inferior solvent is one or more of ethanol and water, the beneficial solvent is one or more of acetone and DMF, the volume ratio of the inferior solvent to the beneficial solvent is 70:30-90:10, the soaking time is 5-20 min, and the soaking temperature is 15-40℃.

7. The method for preparing an anti-adhesion membrane with coarse fiber structure according to claim 3, characterized in that, The polymer material is PLCL with an intrinsic viscosity of 1.5-2.5 dL / g, the hydrophilic anti-blocking component is HA with an intrinsic viscosity of 0.5-2.0 dL / g, the inferior solvent is one or more of ethanol and isopropanol, the superior solvent is one or more of acetone and THF, the volume ratio of the inferior solvent to the superior solvent is 85:15-95:5, the soaking time is 10-30 min, and the soaking temperature is 25-35℃.

8. The method for preparing an anti-adhesion membrane with coarse fiber structure according to claim 3, characterized in that, The polymer material is PCL with an intrinsic viscosity of 1.0-1.8 dL / g, the hydrophilic anti-blocking component is sodium alginate with an intrinsic viscosity of 0.2-2.0 dL / g, the inferior solvent is one or more of ethanol and water, the beneficial solvent is one or more of acetone and DMF, the volume ratio of the inferior solvent to the beneficial solvent is 80:20-95:5, the soaking time is 10-30 min, and the soaking temperature is 20-40℃.

9. An anti-adhesion membrane with coarse-structured fibers, characterized in that, The anti-adhesion membrane with coarse-structured fibers as described in any one of claims 1-8 is prepared by the method described in claims 1-8. The surface of the anti-adhesion membrane with coarse-structured fibers is uniformly covered with crystalline protrusions, the average thickness of which is 10-100 nm and the average length of which is 50-500 nm. The average surface area of ​​cells spread on an anti-adhesion membrane with rough fibrous structure is 40-50 µm. 2 The YAP activation rate of the anti-adhesion membrane with rough fiber structure is 40%-50%, and the α-SMA activation rate is 35%-45%.

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