Gelatin fiber film and method for producing the same

Abstract

This application relates to the field of polymer materials technology, specifically to a gelatin fiber membrane and its preparation method. The preparation method includes: dissolving gelatin in a solvent to obtain a gelatin spinning solution; performing electrospinning to form a gelatin nanofiber membrane; subjecting the gelatin nanofiber membrane to a crosslinking reaction; and subjecting the crosslinked gelatin nanofiber membrane to vacuum drying and heat setting treatment to obtain the gelatin fiber membrane. This application effectively avoids fiber damage and improves crosslinking consistency by using closed-loop dynamic monitoring and control of the crosslinking agent vapor concentration; simultaneously, the combination of vacuum drying and heat setting treatment eliminates internal stress, significantly inhibiting membrane shrinkage and deformation, and ensuring the dimensional stability of the product.

Description

Technical Field

[0001] This application relates to the field of polymer materials technology, and more specifically, to a gelatin fiber membrane and its preparation method. Background Technology

[0002] Gelatin, due to its excellent biocompatibility, biodegradability, and cell adhesion-promoting properties, is often processed into fibrous membrane materials and applied in various fields. However, untreated gelatin fiber membranes typically exhibit characteristics such as high water solubility, weak mechanical strength, and rapid degradation rates, often failing to meet the demands of practical applications. Therefore, cross-linking modification reactions are usually required to form a stable network structure between gelatin molecular chains, thereby improving the water resistance and mechanical properties of the fibrous membrane.

[0003] Currently, aldehyde-containing crosslinking agents are commonly used for steam crosslinking of gelatin fiber membranes. Most existing steam crosslinking processes employ open-loop or semi-closed-loop control modes with preset fixed parameters (such as fixed temperature, time, or vacuum level). During the crosslinking process, the fiber membrane and crosslinking agent are typically placed in a chamber, and a crosslinking atmosphere is created through heating or vacuuming. The reaction process is passively driven by a preset fixed duration or ambient temperature.

[0004] However, the aforementioned conventional crosslinking methods have certain limitations. On the one hand, the crosslinking process relies heavily on fixed environmental parameters, lacking the ability to perceive and dynamically adjust the actual concentration of crosslinking agent vapor within the chamber, which can easily lead to an uncontrollable crosslinking atmosphere. On the other hand, conventional methods often fail to fully consider the gravitational settling effect of crosslinking agent vapor due to density differences in a static environment, which can easily create a vertical spatial concentration gradient within the chamber, resulting in uneven crosslinking at different locations of the membrane material. Furthermore, when processing membrane materials of a certain thickness, conventional crosslinking processes often lead to significant shrinkage and deformation of the material, and the crosslinking process can easily cause fiber swelling or adhesion, making it difficult to maintain good fiber morphological integrity.

[0005] In summary, existing fiber membrane crosslinking processes, when scaled up for production, often suffer from significant performance fluctuations between different batches or even within the same batch due to a lack of precise dynamic control over the crosslinking reaction environment and a lack of synergistic treatment strategies to suppress shrinkage and deformation of thicker membranes. Therefore, providing a preparation process that can effectively control the reaction atmosphere, suppress membrane crosslinking shrinkage, and ensure batch-to-batch product consistency is a pressing technical challenge in this field. Summary of the Invention

[0006] The purpose of the present application is to provide a preparation method of a gelatin fiber membrane and a gelatin fiber membrane. By means of closed-loop dynamic regulation of the cross-linking agent vapor concentration and combined with post-treatment of stress relaxation and shaping, the cross-linking shrinkage of the membrane material is effectively inhibited, and the batch consistency and morphological integrity of the product are significantly improved.

[0007] In order to achieve the above object of the present application, the following technical solutions are specifically adopted: In a first aspect, the present application provides a preparation method of a gelatin fiber membrane, including: Dissolving gelatin in a solvent to obtain a gelatin spinning solution; Performing electrospinning on the gelatin spinning solution to form a gelatin nanofiber membrane; Placing the gelatin nanofiber membrane in a cross-linking chamber, and introducing cross-linking agent vapor into the cross-linking chamber to carry out a cross-linking reaction; wherein, during the cross-linking reaction, the concentration of the cross-linking agent vapor in the cross-linking chamber is monitored in real time, and the intake flow rate and / or exhaust flow rate of the cross-linking chamber are dynamically regulated according to the monitored current concentration value, so that the concentration of the cross-linking agent vapor in the cross-linking chamber is maintained within a preset target concentration range; Performing vacuum drying and heat setting treatment on the gelatin nanofiber membrane after the cross-linking reaction to obtain a gelatin fiber membrane.

[0008] In an optional embodiment, the real-time monitoring of the concentration of the cross-linking agent vapor in the cross-linking chamber includes: Independently monitoring the concentration of the cross-linking agent vapor in the upper layer region and the lower layer region of the cross-linking chamber respectively to obtain the upper layer current concentration and the lower layer current concentration.

[0009] In an optional embodiment, the upper layer current concentration is C1, and the lower layer current concentration is C2; the cross-linking chamber is preset with an upper layer concentration upper limit H1, a lower layer concentration upper limit H2, a lower layer concentration lower limit L2, and a concentration difference threshold ΔC; The dynamic regulation of the intake flow rate and / or exhaust flow rate of the cross-linking chamber according to the monitored current concentration value includes at least one of the following control logics: A. When C2 < L2, increase the supply of the cross-linking agent vapor; B. When C1 > H1, stop the supply of the cross-linking agent vapor and terminate the heating operation for generating the cross-linking agent vapor; C. When |C1 - C2| < ΔC, weaken the air flow intensity in the cross-linking chamber caused by the intake and / or exhaust; D. When C1 > H1 and C2 < H2, enhance the air flow intensity in the cross-linking chamber caused by the intake and / or exhaust; E. When C1>H1 and C2>H2, initiate the exhaust operation and increase the airflow intensity in the cross-linking chamber caused by the intake and / or exhaust, until C1

[0010] In an optional embodiment, the crosslinking agent vapor concentration in both the upper and lower regions of the crosslinking chamber is controlled within the range of 10 ppm to 250 ppm; and / or, The concentration difference threshold is ≤10%.

[0011] In an optional embodiment, the step of introducing crosslinking agent vapor into the crosslinking chamber to carry out the crosslinking reaction further includes a step of temperature control of the crosslinking chamber: Before introducing the crosslinking agent vapor, the crosslinking chamber is heated to a preset crosslinking compensation temperature; When the crosslinking agent vapor is introduced, the crosslinking chamber is cooled to a preset crosslinking reaction temperature; At the end of the crosslinking reaction, the crosslinking chamber is slowly cooled to room temperature.

[0012] In an optional embodiment, the target temperature for generating the crosslinking agent vapor is 20°C to 80°C; and / or, The crosslinking compensation temperature is 30℃~90℃; and / or, The crosslinking reaction temperature is 20℃~80℃; and / or, The cross-linking reaction takes 5 to 60 minutes.

[0013] In an optional embodiment, after the crosslinking reaction is completed, the concentration of the crosslinking agent vapor in the crosslinking chamber is continuously monitored, and the access control lock on the crosslinking chamber is released after the concentration of the crosslinking agent vapor in the crosslinking chamber is detected to drop below a preset safe concentration threshold. Preferably, the preset safe concentration threshold is 0.1 ppm.

[0014] In an optional embodiment, the step of vacuum drying and heat setting of the cross-linked gelatin nanofiber membrane includes: The vacuum drying is carried out at 100℃~120℃ for 5 hours to 10 hours, and the air is vented every 1 hour to 3 hours during the vacuum drying process. The vacuum-dried gelatin nanofiber membrane is placed on a hot press plate covered with nonwoven fabric, and the four sides are fixed. The heat setting treatment is carried out at 100℃~120℃ for 5 hours~10 hours.

[0015] ​In an optional embodiment, dissolving gelatin in a solvent to obtain a gelatin spinning solution includes: dissolving gelatin in a mixed solvent containing hexafluoroisopropanol and water, and adding acetic acid to obtain a gelatin spinning solution; preferably, in the gelatin spinning solution, the mass percentage of gelatin is 10%~30%, the mass percentage of hexafluoroisopropanol is 30%~50%, the mass percentage of acetic acid is 2%~8%, and the balance is water; preferably, in the gelatin spinning solution, the mass percentage of gelatin is 15%~25%, the mass percentage of hexafluoroisopropanol is 35%~45%, the mass percentage of acetic acid is 3.5%~5.5%, and the balance is water; preferably, after adding acetic acid to the mixed solvent, the solution further includes a static defoaming treatment; In an optional embodiment, the electrospinning voltage is 10kV~30kV; and / or, The electrospinning spacing is 10cm~18cm; and / or, The crosslinking agent is glutaraldehyde.

[0016] Secondly, this application provides a gelatin fiber membrane, which is prepared by the gelatin fiber membrane preparation method described in any of the foregoing embodiments.

[0017] In an optional embodiment, the thickness of the gelatin fiber film is 0.05 mm to 0.6 mm; and / or, The water absorption rate of the gelatin fiber membrane is ≤800%~1700%; and / or, The crosslinking degree deviation at different locations within the same batch of the gelatin fiber membrane is ≤10%; and / or, The shrinkage rate of the gelatin fiber membrane is ≤10%, and the fiber morphology is intact and without adhesion.

[0018] Compared with existing technologies, the preparation method provided in this application monitors the concentration of crosslinking agent vapor in the crosslinking chamber in real time during the vapor crosslinking process, and dynamically adjusts the inlet and / or outlet flow rates based on the monitored current concentration value, ensuring that the concentration of crosslinking agent vapor in the chamber remains stable within the preset target concentration range. This closed-loop dynamic control mechanism changes the traditional static blind crosslinking mode, achieving precise perception and intervention of the crosslinking reaction atmosphere. This effectively avoids insufficient crosslinking due to vapor concentration decay or unevenness, and prevents morphological damage such as fiber swelling, adhesion, or even collapse caused by excessively high local concentrations. Thus, while maintaining good fiber structural integrity, it significantly improves the stability and consistency of product performance between different batches.

[0019] Simultaneously, after the crosslinking reaction is completed, this application further combines vacuum drying and heat setting processes to perform subsequent shaping processing on the gelatin nanofiber membrane. This process can effectively and gradually release and eliminate the internal stress accumulated in the fiber membrane during the early forming and crosslinking process. Through the precise control of the front-end reaction atmosphere and the synergistic effect of the back-end stress relief treatment, the severe shrinkage and deformation that easily occur in the membrane material (especially thicker membrane materials) during crosslinking and subsequent stages are comprehensively and greatly suppressed, effectively ensuring the dimensional stability and excellent physical properties of the final gelatin fiber membrane product. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the specific embodiments of this application or the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this application. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0021] Figure 1 These are comparative images showing the appearance of the gelatin fiber membranes in the upper and lower regions of the crosslinking chamber in various embodiments and comparative examples of the present invention. Figure 2 These are scanning electron microscope (SEM) comparison images of the microscopic surface morphology of gelatin fiber membranes in the upper and lower regions of the cross-linking chamber in various embodiments and comparative examples of the present invention. Detailed Implementation

[0022] The embodiments of this application will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of this application. Unless otherwise specified in the examples, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0023] In one embodiment of this application, a method for preparing a gelatin fiber membrane is provided. This method aims to obtain a fiber membrane product with complete morphology, uniform cross-linking, and stable dimensions through closed-loop dynamic synergistic control of the preparation process and the reaction atmosphere. Specifically, the preparation method includes the following steps: Step S1: Dissolve gelatin in a solvent to obtain gelatin spinning solution.

[0024] It should be noted that the solvent mentioned above is a solvent capable of dissolving gelatin and acceptable to the preparation method provided in this embodiment. For example, it can be a mixture of hexafluoroisopropanol and water, or glycerol, organic acids, etc.

[0025] In an optional embodiment, a mixed solvent comprising hexafluoroisopropanol and water is used, followed by the addition of acetic acid. Typically, hexafluoroisopropanol and water are chosen as the mixed solvent because they effectively disrupt the secondary structure of the gelatin macromolecules, allowing for good dissolution and expansion. The addition of acetic acid helps adjust the pH of the solution, clarifying a turbid solution and effectively eliminating agglomerates within the system.

[0026] In practice, after the materials are mixed, they can be continuously stirred at room temperature until the solution is clear and homogeneous. Then, the tiny air bubbles trapped in the system can be removed by letting it stand, thereby ensuring the excellent quality and homogeneity of the precursor solution.

[0027] Step S2: Electrospin the gelatin spinning solution to form a gelatin nanofiber membrane.

[0028] In practice, the gelatin spinning solution can be pumped into the liquid supply device of the electrospinning equipment. By setting appropriate positive and negative voltages, a high-voltage electrostatic field is constructed between the spinneret and the receiving device. Under the traction of the electric field, the spinning solution overcomes the surface tension, forms a jet, and is significantly stretched. With the rapid evaporation of the solvent, it eventually solidifies and interweaves on the receiving substrate, forming a nascent gelatin nanofiber membrane with high porosity and a porous network structure.

[0029] Step S3: Place the gelatin nanofiber membrane in the crosslinking chamber and introduce crosslinking agent vapor into the crosslinking chamber to carry out the crosslinking reaction; wherein, during the crosslinking reaction, the concentration of the crosslinking agent vapor in the crosslinking chamber is monitored in real time, and the air inlet flow rate and / or exhaust flow rate of the crosslinking chamber are dynamically adjusted according to the monitored current concentration value, so as to maintain the concentration of the crosslinking agent vapor in the crosslinking chamber within a preset target concentration range.

[0030] It is important to note that "real-time monitoring" and "dynamic control" are the core mechanisms that distinguish this step from conventional open-loop reactions. In practical applications, the chemical reaction rate of the crosslinking agent is directly positively correlated with the actual gas phase concentration within the chamber. However, traditional static crosslinking often results in concentration decay or unevenness due to vapor condensation, adsorption consumption, or local leakage, leading to insufficient local crosslinking of fibers or adhesion caused by high concentration impacts. By installing a concentration detection device within the crosslinking chamber, the current crosslinking agent vapor concentration data is continuously acquired as a feedback variable, allowing the control system to intelligently determine the state of the reaction atmosphere. When the detected concentration is below the ideal range, the system can proactively increase the inlet flow rate of the crosslinking agent vapor to replenish it; when the detected concentration approaches or exceeds the safety limit, the system reduces the inlet flow rate or opens the exhaust flow rate to dilute it.

[0031] This closed-loop control strategy transforms the crosslinking process from a "black box blind test" to a "transparent and visible" process, ensuring that the crosslinking reaction is always in a stable and safe environment. This effectively protects the integrity of the fiber's microstructure and significantly improves the high uniformity of product performance during large-scale production in multiple batches.

[0032] Step S4: The gelatin nanofiber membrane after cross-linking reaction is subjected to vacuum drying and heat setting treatment to obtain a gelatin fiber membrane.

[0033] Because the high-stretching process of electrospinning and the initial cross-linking and curing process both accumulate considerable internal stress in the fiber network, without intervention, membranes of a certain thickness will experience severe macroscopic shrinkage and deformation. Therefore, after cross-linking, a vacuum drying process can effectively remove residual solvents and free substances from the membrane. The subsequent heat setting treatment eliminates internal stress in the material under controlled physical boundaries by imparting thermal energy for polymer chain rearrangement and relaxation.

[0034] This post-processing step, in synergy with the mild and stable steam crosslinking process in the preceding stage, fundamentally suppresses the shrinkage tendency of the membrane material and significantly improves the dimensional stability of the finished product.

[0035] In some embodiments, step S3, which involves real-time monitoring of the concentration of the crosslinking agent vapor in the crosslinking chamber, includes: Step S31: Independently monitor the concentration of the crosslinking agent vapor in the upper and lower regions of the crosslinking chamber to obtain the current concentration of the upper layer and the current concentration of the lower layer.

[0036] In this step, the system divides the crosslinking chamber into different monitoring areas in the vertical space and performs multi-node data acquisition. The basic principle of this zoned monitoring method is that in conventional crosslinking processes, the crosslinking chamber is often regarded as an ideal "uniform concentration field." However, in actual physical environments, since the density of commonly used crosslinking agent vapors (such as glutaraldehyde vapor) is usually greater than that of air, in relatively static or closed environments with only weak convection, the crosslinking agent vapors will inevitably undergo a gravitational settling effect. This gravitational settling will lead to a significant spatial concentration gradient in the vertical direction within the crosslinking chamber, that is, the vapor concentration in the lower region is often higher than that in the upper region.

[0037] If this objectively existing concentration gradient is not effectively perceived, membrane materials placed at different heights within the same batch will be in cross-linking atmospheres of different concentrations, thus passively receiving different cross-linking doses, ultimately causing a systematic change and unevenness in the degree of cross-linking from top to bottom within the same batch of products.

[0038] To overcome the bias brought by this conventional assumption, in this embodiment, independent concentration sensing devices are respectively arranged in the upper layer area and the lower layer area of the crosslinking chamber to obtain the concentration data of these two areas in real time and separately (i.e., the current upper layer concentration and the current lower layer concentration). This processing method not only breaks the limitation of a single measurement point in the traditional process, realizes the accurate perception of the three-dimensional space concentration gradient in the crosslinking chamber, but also the obtained current upper layer concentration and current lower layer concentration data provide the necessary data basis and perception premise for the system to subsequently judge the uniformity of the crosslinking atmosphere inside the chamber and further dynamically eliminate the spatial concentration difference. This helps to fundamentally ensure that the membrane materials placed in different spatial positions within the same batch can be in a consistent crosslinking atmosphere, meeting the strict requirements for performance uniformity of products such as medical materials.

[0039] In some embodiments, the current upper layer concentration is C1, and the current lower layer concentration is C2; the crosslinking chamber is preset with an upper layer concentration upper limit H1, a lower layer concentration upper limit H2, a lower layer concentration lower limit L2, and a concentration difference threshold ΔC.

[0040] The intake flow rate and / or exhaust flow rate of the crosslinking chamber are dynamically regulated according to the monitored current concentration value, and the control logic is shown in Table 1: Table 1. Different control logics and corresponding processes

[0041] During the crosslinking reaction process, the controller receives the C1 and C2 values fed back by the concentration sensor in real time and executes at least one of the following control logics to dynamically regulate the states of the intake and exhaust valves and the air supply system: A. When the system determines that C2 < L2, that is, when the lower layer concentration is lower than the preset minimum process lower limit, the system automatically increases the supply of crosslinking agent vapor. Based on the physical characteristics that crosslinking agent vapor is often denser and prone to gravitational sedimentation, when there is a lack of concentration in the lower layer area, it usually means that the total amount of crosslinking agent in the entire chamber is no longer sufficient to maintain the normal reaction rate. At this time, supplementing vapor through the intake valve in a timely manner can effectively avoid the stagnation of the crosslinking reaction caused by too low concentration and ensure that the mechanical strength of the membrane material is fully improved.

[0042] B. When the system determines that C1 > H1, that is, when the upper layer concentration exceeds the preset safety upper limit, the system stops the supply of crosslinking agent vapor and simultaneously terminates the heating operation for generating the crosslinking agent vapor (for example, closing the heater of the liquid storage tank). Under the gravitational sedimentation effect, the upper layer usually belongs to the area with a lower concentration; if the upper layer concentration has exceeded the standard, it indicates that the entire chamber is in a serious supersaturated state. This logic fundamentally blocks the further deterioration of the concentration by means of "cutting off the gas source and heat source" to prevent the high-concentration vapor from causing impact damage such as swelling and adhesion to the nanofiber network structure.

[0043] C. When the system determines that |C1 - C2| < ΔC, that is, when the absolute difference in concentration between the upper and lower layers is less than the preset difference threshold, the system weakens the air flow intensity in the crosslinking chamber caused by the intake and / or exhaust. This state indicates that the vapor in the chamber has been fully mixed, and the concentration gradient in the vertical direction has been basically eliminated. Appropriately reducing the rotational speed of the air supply fan or the circulation fan can, on the one hand, save energy, and on the other hand, avoid mechanical tearing or surface structure damage to the fragile initial nano - fiber membrane caused by strong air flow, thus completing crosslinking gently in a uniform steady - state atmosphere.

[0044] D. When the system determines that C1 > H1 and C2 < H2, it indicates that there is local concentration enrichment exceeding the standard in the upper layer, while the lower layer has not reached the upper limit. This phenomenon that violates the conventional sedimentation law is often caused by a thermodynamic inversion layer or local air flow stagnation. At this time, the system actively increases the air flow intensity in the crosslinking chamber, uses the forced convection mechanism to break the air flow stagnation, and blows the gas enriched above downward. Without additional increasing the total intake air volume, the re - balance of the gas distribution in the chamber is achieved.

[0045] E. When the system determines that C1 > H1 and C2 > H2, it indicates that the chamber as a whole faces a serious risk of concentration exceeding the limit. At this time, the system immediately starts the exhaust operation (such as opening the exhaust fan and the outlet valve), and increases the air flow intensity in the crosslinking chamber for strong purging. By quickly discharging the excess high - concentration vapor out of the system, the absolute concentration value in the chamber is rapidly reduced. This exhaust and purging action will continue to be executed until the system re - determines that the upper - layer concentration has returned to the safe range (i.e., C1 < H1), thus forming a perfect self - correction closed - loop, ensuring that the product is always in a safe and controllable crosslinking environment, and greatly improving the consistency of product performance within batches and between different batches.

[0046] In some embodiments, the control range of the crosslinking agent vapor concentration in the upper - layer region and the lower - layer region of the crosslinking chamber is both 10 ppm to 250 ppm.

[0047] The concentration of the crosslinking agent vapor is controlled within a range of 10 ppm to 250 ppm (e.g., 10 ppm, 30 ppm, 50 ppm, 80 ppm, 120 ppm, 150 ppm, 180 ppm, 210 ppm, 230 ppm, 250 ppm, etc.). Within this range, 250 ppm is a safety threshold established based on considerations of fiber morphology integrity. Untreated gelatin nanofibers have extremely high specific surface areas and are relatively fragile. When exposed to a high concentration of crosslinking agent vapor, the instantaneous intrusion of high-concentration chemical reagents can easily lead to severe swelling of the fibers, causing adhesion and fusion between adjacent fibers, and even causing local collapse of the entire porous network structure. This significantly reduces the porosity of the material and results in the loss of the excellent physical structure of the biomimetic extracellular matrix. Strictly controlling the concentration below 250 ppm can fundamentally avoid this impact-induced structural damage.

[0048] At the same time, maintaining a concentration of no less than 10 ppm is to ensure the basic chemical reaction kinetic rate and avoid incomplete curing due to a lack of crosslinking agent.

[0049] In some implementations, the concentration difference threshold is ≤10%.

[0050] The concentration difference threshold is ≤10% (e.g., it can be 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, etc.). This parameter is established to address the problem of uneven spatial distribution of the crosslinking atmosphere. During scale-up production, the volume of the crosslinking chamber increases, and the gravitational settling effect of the crosslinking agent vapor due to density differences becomes more significant. Forcibly controlling the concentration difference between the upper and lower layers to within 10% means that regardless of whether the membrane material is placed on the top or bottom rack of the crosslinking chamber, the concentration of the gas phase in its microenvironment is highly similar. This spatial consistency directly translates into consistency in physicochemical reactions, effectively eliminating the gradual changes in crosslinking degree caused by height differences. This ensures high stability in water absorption, crosslinking degree, etc., for products in different spatial locations within the same batch, meeting the stringent requirements for product performance uniformity in fields such as medical dressings.

[0051] In some embodiments, step S3, which involves introducing crosslinking agent vapor into the crosslinking chamber to carry out the crosslinking reaction, further includes a step of temperature control of the crosslinking chamber. This temperature control step complements the aforementioned dynamic concentration regulation and aims to solve the technical problem of drastic macroscopic shrinkage that easily occurs in thick-sized films during the crosslinking process. Specifically, this step-by-step temperature control step includes: Step S32: Before introducing the crosslinking agent vapor, the crosslinking chamber is heated to a preset crosslinking compensation temperature.

[0052] This stage is the pre-crosslinking heat treatment. Because gelatin molecular chains can undergo moderate rearrangement under specific thermal conditions, pre-applying heat in a dry environment without chemical vapors promotes the pre-construction and stabilization of hydrogen bond networks between gelatin macromolecules. This "temperature compensation" mechanism effectively improves the structural tolerance of the membrane material (especially thicker membranes) to subsequent vapor intrusion, providing a solid physical structural foundation for the upcoming chemical crosslinking and preventing stress collapse of the fiber network upon initial contact with chemical reagents.

[0053] Step S33: When the crosslinking agent vapor is introduced, the crosslinking chamber is cooled to a preset crosslinking reaction temperature.

[0054] The "cooling" operation introduced at this stage is to precisely control the kinetic rate of the chemical reaction. When processing thicker membrane materials, the penetration path of steam into the material's interior is relatively long. If the reaction temperature is too high, the fibers on the membrane surface will preferentially contact the steam and undergo intense cross-linking instantly, prematurely forming a highly cross-linked "hard shell." This hard shell not only prevents steam from penetrating deeper into the interior but also prevents the effective release of shrinkage stress generated by the internal fibers during subsequent cross-linking. Ultimately, this stress concentration leads to severe shrinkage and deformation of the entire membrane. In this embodiment, by actively cooling while introducing steam, the initial cross-linking rate of the surface fibers is deliberately slowed down, effectively eliminating the difference in cross-linking rates between the surface and the interior. This allows the cross-linking agent steam sufficient time window to uniformly penetrate into the interior of the membrane, ensuring the consistency of cross-linking degree between the thick membrane and its interior, thereby effectively suppressing the shrinkage trend of the membrane.

[0055] Step S34: When the crosslinking reaction is completed, the crosslinking chamber is slowly cooled to room temperature.

[0056] This stage is similar to thermodynamic stress relaxation or annealing. The chemical crosslinking process causes internal stress to accumulate within the polymer network. If the temperature drops sharply after the reaction, the movement of the polymer chains is instantly frozen, locking the internal stress within the membrane. By controlling the chamber for slow cooling, sufficient time is given for the polymer chains to undergo conformational adjustment and thermal relaxation. This gentle physical transition mechanism effectively releases and eliminates the residual internal stress accumulated during crosslinking, preventing warping or dimensional shrinkage after the membrane leaves the processing environment, ultimately resulting in a gelatin fiber membrane product with extremely stable dimensions.

[0057] In some preferred embodiments of this application, in order to further precisely control the physical and chemical processes of the crosslinking reaction and effectively overcome the technical problem that thicker films are prone to severe shrinkage during crosslinking, this application has strictly limited the ranges of key temperature and time parameters in the crosslinking process. Specifically, this includes: In some preferred embodiments, the target temperature for generating the crosslinking agent vapor is 20°C to 80°C.

[0058] In this parameter system, the target temperature for generating the crosslinking agent vapor defines the power source for crosslinking agent vaporization. Controlling this temperature between 20°C and 80°C (e.g., 20°C, 25°C, 30°C, 40°C, 50°C, 60°C, 70°C, 75°C, 80°C, etc.) ensures that the crosslinking agent (such as glutaraldehyde) stably and continuously provides a sufficiently saturated gaseous reagent without high-temperature thermal degradation, thus meeting the diverse process requirements from conventional slow crosslinking to extreme rapid crosslinking.

[0059] In some preferred embodiments, the crosslinking compensation temperature is 30°C to 90°C.

[0060] In some preferred embodiments, the crosslinking reaction temperature is 20°C to 80°C.

[0061] The crosslinking compensation temperature (30℃~90℃, for example, 30℃, 35℃, 40℃, 50℃, 60℃, 70℃, 80℃, 85℃, 90℃, etc.) and the crosslinking reaction temperature (20℃~80℃, for example, 20℃, 25℃, 30℃, 40℃, 50℃, 60℃, 70℃, 75℃, 80℃, etc.) together constitute the core of the stepped temperature control strategy. When processing membrane materials of a certain thickness, vapor permeation requires a relatively long path. Preheating the crosslinking chamber to a higher compensation temperature can promote the microscopic rearrangement of gelatin macromolecular chains under thermal action, pre-constructing a stable physical hydrogen bond network, and significantly improving the structural tolerance of the membrane material to subsequent steam. Subsequently, when steam is introduced for the actual reaction, the chamber temperature is actively reduced to the reaction temperature, deliberately slowing down the kinetic rate of the chemical reaction. This operation is extremely crucial, as it effectively prevents the surface fibers of the membrane from forming a "hard shell" that blocks steam penetration due to premature and rapid cross-linking. By eliminating the difference in cross-linking rates between the surface and the interior, steam can penetrate evenly and achieve simultaneous curing inside and out, thereby fundamentally releasing and eliminating the concentrated stress that causes severe shrinkage of the thick film.

[0062] In some preferred embodiments, the crosslinking reaction takes 5 to 60 minutes.

[0063] The crosslinking reaction time is 5 to 60 minutes (e.g., 5 minutes, 10 minutes, 15 minutes, 20 minutes, 30 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes, 60 minutes, etc.). This time range is the optimal range established based on the balance between the degree of crosslinking and morphological integrity. A minimum time window of 5 minutes, combined with a high-temperature, high-speed process, can achieve the basic crosslinking indicators; while the maximum setting of no more than 60 minutes effectively avoids side reactions such as excessive crosslinking, fiber brittleness, or reduced porosity caused by prolonged exposure to the crosslinking atmosphere, ensuring consistent and stable performance between product batches.

[0064] In a preferred embodiment of this application, to ensure the personal safety of operators and the inherent safety of equipment operation in a scale-up production environment, this preparation method further introduces a concentration feedback-based access control interlocking safety mechanism after the crosslinking reaction process is completed. Specifically, after the crosslinking reaction is completed, the concentration of the crosslinking agent vapor in the crosslinking chamber is continuously monitored, and the access control lock on the crosslinking chamber is released after the concentration of the crosslinking agent vapor in the crosslinking chamber is detected to drop below a preset safe concentration threshold.

[0065] Furthermore, in some optional embodiments, the preset safe concentration threshold is 0.1 ppm.

[0066] In actual industrial manufacturing, due to the need to improve the water resistance and mechanical properties of membrane materials, crosslinking agents are usually selected from chemical reagents with a certain degree of volatility and irritating odor. When the preset crosslinking reaction time is reached, although the chemical curing process has been completed, the sealed crosslinking chamber is usually still filled with a high concentration of residual reagent vapor. If the chamber door is opened manually at this time, the high concentration of irritating gas will instantly diffuse outward, not only polluting the workshop environment but also causing strong irritation and potential health threats to the eyes and respiratory tracts of on-site operators.

[0067] To completely eliminate this safety hazard, this embodiment uses a central control unit to enforce a logical interlock between the gas concentration detection system inside the crosslinking chamber and the electronic access control lock on the door. After the crosslinking reaction phase ends, the concentration sensor does not stop working but continues to monitor, feeding back the residual vapor concentration inside the chamber to the control unit in real time. As the equipment's exhaust system operates or the vapor dissipates naturally, the control unit continuously compares the current actual concentration with a preset safe concentration threshold. Only when the system clearly confirms that the current crosslinking agent vapor concentration inside the chamber has dropped to an extremely low level that is safe for human contact—that is, below the preset 0.1 ppm threshold (e.g., the actual detected concentration drops to 0.01 ppm, 0.05 ppm, or 0.09 ppm, etc.)—will the control unit output an unlock command to release the electronic lock on the crosslinking chamber door.

[0068] By setting a stringent quantitative safety threshold of 0.1 ppm, this mechanism replaces subjective human judgment or simple delays with objective physical detection data, minimizing the exposure risks faced by personnel due to premature door opening, and constructing a robust and reliable safety production protection system without affecting overall production efficiency.

[0069] In some embodiments, step S4 involves vacuum drying and heat setting of the cross-linked gelatin nanofiber membrane. This post-treatment stage aims to further remove residual material within the material and completely eliminate microscopic internal stress through physical mechanisms, and is a key synergistic process to ensure that thicker membranes do not experience drastic macroscopic shrinkage. Specifically, it includes: Step S41: Vacuum drying is performed at 100℃~120℃ for 5 hours to 10 hours, and the air is vented every 1 hour to 3 hours during the vacuum drying process.

[0070] This step involves a vacuum drying process, with the temperature controlled within the range of 100℃ to 120℃ (e.g., 100℃, 105℃, 110℃, 115℃, 120℃, etc.). This higher temperature provides sufficient kinetic energy to the crosslinking agent and solvent residues to induce a vaporization phase change. The drying time lasts for 5 to 10 hours (e.g., 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, etc.) to ensure sufficient diffusion time for the volatiles. Specifically, during the drying period, venting is performed every 1 to 3 hours (e.g., 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, etc.). This periodic venting (vacuum breaking) operation aims to disrupt the dynamic pressure balance formed within the sealed vacuum chamber due to the accumulation of volatiles. By periodically removing the extracted waste gas, the concentration difference and pressure drop driving force between the membrane material's interior and the external environment can be continuously restored, thereby significantly improving the removal efficiency of deep residual gases and preventing incomplete drying caused by continuous quiescent vacuum.

[0071] Step S42: Place the vacuum-dried gelatin nanofiber membrane on a hot press plate covered with nonwoven fabric, fix the four sides, and perform the heat setting treatment at 100℃~120℃ for 5 hours~10 hours.

[0072] After initial vacuum impurity removal, heat setting is then carried out. The membrane material is placed in a high-temperature environment of 100℃~120℃ (e.g., 100℃, 105℃, 110℃, 115℃, 120℃, etc.) for 5 to 10 hours (e.g., 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, etc.). During this process, the huge internal stress accumulated in the gelatin fibers during the high-stretching and chemical cross-linking curing stages of electrospinning is activated and attempts to be released. Without physical intervention, thicker membrane materials (e.g., those thicker than 0.020mm) often undergo significant shrinkage deformation. In this embodiment, by using a "fixed four sides" method (e.g., using fixing clamps or magnetic strips to press the edges), a strong macroscopic boundary constraint is applied to the membrane material, forcing it to maintain its original geometric dimensions while releasing stress. Meanwhile, a layer of non-woven fabric is placed between the membrane material and the hot press plate as an isolation medium. The porous structure of the non-woven fabric not only effectively prevents rigid thermal adhesion between the gelatin film and the metal hot press plate at high temperatures, but also retains microscopic exhaust channels for the escape of trace amounts of water vapor and gas from the bottom layer. Through the above-mentioned controlled heat treatment mechanism, the molecular chain segments complete conformational rearrangement and internal stress elimination at the microscopic level, while no deformation occurs at the macroscopic level. This effectively overcomes the problem of severe dimensional instability of thick membrane materials after cross-linking, endowing the product with excellent dimensional stability and structural integrity.

[0073] In some embodiments, dissolving gelatin in a solvent to obtain a gelatin spinning solution includes: dissolving gelatin in a mixed solvent containing hexafluoroisopropanol and water, and adding acetic acid to obtain a gelatin spinning solution.

[0074] In an optional embodiment of this application, in order to obtain a precursor solution with excellent spinnability and stable film-forming properties, the raw material components and their mass percentage ratios of the gelatin spinning solution are defined. Specifically, in the gelatin spinning solution, the mass percentage of gelatin is 10%~30%, the mass percentage of hexafluoroisopropanol is 30%~50%, the mass percentage of acetic acid is 2%~8%, and the balance is water.

[0075] In some optional embodiments, the gelatin spinning solution contains 15% to 25% gelatin by mass, 35% to 45% hexafluoroisopropanol by mass, 3.5% to 5.5% acetic acid by mass, and the balance being water.

[0076] In this hybrid system, gelatin serves as the core backbone polymer for constructing the nanofiber network, and its concentration directly determines the rheological properties of the solution. Controlling the mass percentage of gelatin between 10% and 30% (e.g., 10%, 12%, 15%, 18%, 20%, 22%, 25%, 28%, 29%, 30%, etc.) ensures sufficient entanglement of the polymer segments within the solution. This entanglement is crucial for resisting capillary rupture during electrostatic stretching, effectively preventing electrospraying (i.e., droplet formation instead of fiber formation) caused by excessively low concentrations; simultaneously, it also prevents the problem of spinning needle clogging caused by excessively high concentrations leading to a dramatic increase in solution viscosity and surface tension. Hexafluoroisopropanol (HFIP), as the main solvent in the system, is controlled at a mass percentage between 30% and 50% (e.g., 30%, 32%, 35%, 38%, 40%, 42%, 45%, 48%, 49%, 50%, etc.). HFIP possesses a strong ability to disrupt intermolecular hydrogen bonds, enabling gelatin to fully expand and dissolve at room temperature. Furthermore, its high volatility ensures rapid solvent evaporation during the extremely short flight time from the spinneret to the receiver, promoting rapid polymer curing and preventing severe cross-linking and adhesion when the fibers reach the substrate due to incomplete drying. Acetic acid primarily functions as a co-solvent and pH adjuster in the system, with its mass percentage controlled between 2% and 8% (e.g., 2%, 3%, 3.5%, 4%, 5%, 5.5%, 6%, 7%, 7.5%, 8%, etc.). The introduction of an appropriate amount of acetic acid improves the acidic microenvironment of the solution, utilizing the like charge repulsion mechanism to further expand the gelatin macromolecular chains and effectively eliminate microscopic molecular aggregation. Macroscopically, this results in the transformation of a turbid, stratified precursor solution into a highly clear and homogeneous solution system. Simultaneously, the addition of acetic acid optimizes the overall conductivity of the solution, improving spinning stability under an electrostatic field. Deionized water, as a supplementary component, synergistically fine-tuned the dielectric constant and evaporation gradient of the entire ternary solvent system.

[0077] In a preferred embodiment, to further improve the continuity of the spinning process, after adding acetic acid to the mixed solvent, a static defoaming treatment is also included.

[0078] In the spinning solution preparation stage, a static defoaming process was introduced. During the mixing of gelatin, solvent, and acetic acid, some air inevitably gets mixed into the system, forming tiny bubbles. If these bubbles enter the spinning needle with the spinning solution, they can easily cause electrostatic instability, fiber breakage, or even nozzle clogging. By allowing the bubbles to float and dissipate naturally under static conditions using their own buoyancy, the precursor solution can be purified from a physical standpoint. This ensures that the entire spinning process can operate for a long time, with high efficiency and without interruption, thereby guaranteeing that the prepared gelatin nanofiber membrane has a highly uniform spatial distribution.

[0079] In some optional embodiments, the Bloom value of the gelatin is preferably 200g to 250g. This range of gelatin molecular weight is suitable for forming a uniform entangled network in the mixed solvent, further improving the continuity and film strength of electrospinning.

[0080] To further optimize the continuity of the spinning process and the uniformity of the produced fiber morphology, the gelatin has a mass percentage of 15% to 25% (e.g., 15%, 16%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, etc.), the hexafluoroisopropanol has a mass percentage of 35% to 45%, the acetic acid has a mass percentage of 3.5% to 5.5% (e.g., 35%, 36%, 37%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, etc.), and the balance is water. Within the aforementioned preferred narrow ratio window, an excellent physicochemical balance is achieved between the solute entanglement degree and the solubility, volatility, and conductivity of the ternary solvent, enabling the continuous and stable preparation of high-quality gelatin nanofiber membranes with no beading defects and uniform pore distribution.

[0081] In a preferred embodiment of this application, to further optimize the stability of fiber preparation and product performance, the electrical parameters and physical pretreatment conditions of the electrospinning process are systematically defined. Specifically, the electrospinning voltage is 10kV~30kV.

[0082] In some embodiments, the electrospinning spacing is 10cm to 18cm.

[0083] In the electrospinning process, the spinning voltage (10kV~30kV, for example, 10kV, 15kV, 20kV, 25kV, 30kV, etc.) provides the core driving force to overcome the surface tension of the solution. Within this voltage range, the electric field strength can stably induce the jet to form a "Taylor cone" and precisely stretch the polymer droplets into nanoscale filaments. If the voltage is too low, it is difficult to achieve fiberization; if it is too high, it may cause unstable arc discharge, thereby damaging the membrane structure. The corresponding spinning spacing is set to 10cm~18cm (for example, 10cm, 12cm, 14cm, 16cm, 18cm, etc.). This physical distance range ensures that the solvent has sufficient time to evaporate before the fibers are deposited onto the receiving substrate, thereby avoiding adhesion caused by wet fiber shedding and ensuring that the deposit has a clear nanoscale fiber morphology and excellent pore structure.

[0084] In some embodiments, the crosslinking agent is glutaraldehyde.

[0085] Glutaraldehyde, as an active reagent containing two aldehyde groups, can efficiently react with the amino groups in the gelatin molecular chain to form a chemical Schiff base reaction during the cross-linking process. This chemical bridging mechanism enables the construction of a robust three-dimensional covalent network structure between gelatin molecules, fundamentally solving the industry pain points of easy hydrolysis and weak mechanical properties of gelatin materials. This endows nanofiber membranes with excellent mechanical strength and wet stability.

[0086] This application also provides a gelatin fiber membrane prepared using the aforementioned method. Its internal network structure exhibits high chemical cross-linking uniformity, effectively meeting the performance requirements of complex medical applications. This gelatin fiber membrane not only possesses excellent mechanical strength and dimensional stability, but its microstructure also retains the porous nanofiber morphology imparted by electrospinning, exhibiting good permeability and biocompatibility, making it suitable for use as wound dressings, scaffold materials, and other biomedical products. The gelatin fiber membrane obtained through the above method effectively overcomes the severe shrinkage problem that easily occurs during the production and processing of thicker materials while maintaining structural integrity and clear fiber morphology (no adhesion, no severe fusion).

[0087] In one embodiment of this application, a gelatin fiber membrane product obtained based on the above-described preparation process is provided. This gelatin fiber membrane exhibits excellent performance indicators in terms of physical properties, chemical water resistance, spatial uniformity, and dimensional stability.

[0088] Specifically, in some embodiments, the thickness of the gelatin fiber membrane is 0.05 mm to 0.6 mm. For example, it can be 0.05 mm, 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, etc. Thanks to the aforementioned stepped temperature control and constrained heat setting process, the membrane material can still maintain excellent dimensional integrity even within this thickness range.

[0089] In some embodiments, the gelatin fiber membrane exhibits a water absorption rate of 800% to 1700% in terms of chemical properties. For example, it can be 800%, 1000%, 1100%, 1300%, 1500%, 1600%, or 1700%. This range of values ​​fully meets the application requirements of biomedical wound dressings, and its excellent water absorption performance effectively absorbs wound exudate, maintaining a suitable moist environment and preventing excessive dehydration. Simultaneously, this value reflects the moderate and uniform cross-linking effect achieved through closed-loop dynamic concentration control: it avoids membrane degradation or loss of mechanical strength due to insufficient cross-linking, while effectively preventing "over-cross-linking" caused by excessively vigorous local reactions (over-cross-linking leads to an overly dense material network, causing a sharp drop in water absorption rate and making it difficult to meet dressing requirements). This indicates that the covalent network structure constructed by this process achieves a good balance between structural stability and liquid absorption performance while maintaining high porosity.

[0090] In some embodiments, the crosslinking degree deviation at different locations within the same batch of the gelatin fiber membrane is ≤10%.

[0091] To verify the effect of the preparation process on improving product uniformity, testing revealed that the crosslinking degree deviation of the gelatin fiber membrane at different spatial locations within the same batch was ≤10% (e.g., 1%, 2%, 5%, 8%, 10%, etc.). This low deviation performance is directly attributed to the real-time monitoring and independent dynamic control of the concentration in the upper and lower regions of the crosslinking chamber, effectively solving the problem of uneven spatial crosslinking degree caused by the gravity sedimentation effect.

[0092] In some embodiments, the shrinkage rate of the gelatin fiber membrane is ≤10%, and the fiber morphology is intact and non-adhesive.

[0093] In terms of macroscopic morphology, the shrinkage rate of the gelatin fiber membrane is ≤10% (e.g., it can be 1%, 3%, 5%, 7%, 10%, etc.), and the fiber morphology is intact and non-adhesive. The vacuum drying and heat setting treatment with fixed four sides introduced in this application effectively release the internal stress of the fiber network while forcibly fixing the geometric dimensions of the product, overcoming the technical defect of the high shrinkage rate of 75% for thick film materials in conventional processes. At the same time, since the vapor concentration is always controlled within a safe threshold during the crosslinking stage, the instantaneous impact of high-concentration reagents on the nanofibers is effectively avoided, so that the fibers of the final product maintain an excellent independent filament morphology, maintaining the high specific surface area porous network structure constructed by electrospinning, enabling it to be applied more efficiently in the biomedical field.

[0094] The present application is further illustrated below with specific embodiments. However, it should be understood that these embodiments are merely for the purpose of more detailed illustration and should not be construed as limiting the present application in any way.

[0095] I. Preparation of Examples and Comparative Examples: This section provides a series of examples and comparative examples of gelatin nanofiber membrane preparation, mainly examining the effects of dynamic control of crosslinking agent vapor concentration, step temperature control, and different parameter ranges on product performance (especially membrane material appearance shrinkage, surface morphology, water absorption rate, and crosslinking uniformity) used in this invention.

[0096] It should be noted that, due to the use of specific ranges of process parameters in steps S1 and S2 in each embodiment of this application, the thickness of the gelatin nanofiber membranes finally prepared in each embodiment and comparative example is distributed in the range of 0.05 mm to 0.6 mm. This thickness range significantly exceeds the scope of conventional films (thickness less than or equal to 0.02 mm) and belongs to the level of relatively thick film materials that are extremely prone to severe macroscopic shrinkage in existing conventional crosslinking processes. Using this as a test sample can objectively verify the effect of the process of this application on suppressing shrinkage defects in thick film materials.

[0097] Example 1 (Low-strength process, preset crosslinking time 60 min): This embodiment provides a method for preparing a gelatin nanofiber membrane, specifically including the following steps: Preparation of S1 spinning solution: Weigh 800g of gelatin (Bloom value 200-250) into a reagent bottle, measure 2000mL of hexafluoroisopropanol and 2000mL of deionized water, add slowly while stirring. Add acetic acid to the turbid, layered solution until the solution becomes clear, and record the amount of acetic acid consumed. Stir continuously at room temperature until no obvious agglomerates are found, then allow to stand to remove bubbles, obtaining the gelatin spinning solution. The preferred mass composition of this spinning solution is: 15%-22% gelatin, 35%-47% hexafluoroisopropanol, 2%-8% acetic acid, and the balance being water.

[0098] S2 Electrospinning: Install 100 clean and dried spinning needles onto the spinning module, and install a clean nonwoven fabric receiving substrate. Place 2L of the aforementioned spinning solution into the supply tank, and set the electrospinning parameters: positive electrode voltage +10~16kV, negative electrode voltage -8~14kV, spinning air pressure 0.015-0.020MPa. Start the supply pump to begin spinning. After the spinning solution is used up, ventilate for 2 hours and remove the gelatin nanofiber membrane. The membrane thickness range of the gelatin nanofiber membrane is 0.05~0.6mm.

[0099] S3 Steam Crosslinking: The spun gelatin nanofiber membrane is placed on a fixture and then placed into the steam crosslinking chamber. The crosslinking parameters used in this embodiment are: target temperature for generating crosslinking agent vapor 20°C, crosslinking compensation temperature 30°C, crosslinking reaction temperature 20°C, and preset crosslinking time 60 min. The crosslinking agent vapor concentration control range for both the upper and lower regions of the crosslinking chamber is set to 10 ppm to 250 ppm, the upper and lower layer concentration difference threshold is set to 10%, and the gate release safety concentration is set to 0.1 ppm. Upon initiating the crosslinking program, the device automatically performs concentration zoning monitoring and dynamic closed-loop control: increasing steam supply when the lower layer concentration is below 10 ppm; stopping supply and terminating heating when the upper layer concentration is above 250 ppm; reducing airflow intensity when the upper and lower layer concentration difference is less than 10%; increasing airflow intensity when the upper layer concentration is above 250 ppm and the lower layer concentration is below 250 ppm; and initiating exhaust when both upper and lower layers are above 250 ppm.

[0100] S4 Post-processing: After cross-linking, once the gas concentration in the chamber drops below 0.1 ppm, the access control is released, and the sample is removed. The sample is placed in a vacuum drying oven at 100~120℃ for 5~10 hours, with venting every 1~3 hours during this period. Subsequently, the sample is placed on a hot press plate covered with nonwoven fabric, and the four sides are fixed with magnetic strips. It is then heat-set in a vacuum environment at 110℃ for 6 hours to finally obtain a stable gelatin nanofiber membrane product.

[0101] Example 2 (medium strength process, preset crosslinking time 40 min): The preparation steps are basically the same as in Example 1, except for the steam crosslinking parameters in step S3: the target temperature for generating crosslinking agent vapor is 40°C, the crosslinking compensation temperature is 50°C, the crosslinking reaction temperature is 40°C, and the preset crosslinking time is 40 min. Other concentration control logic and post-processing are consistent with those in Example 1.

[0102] Example 3 (High-strength process, preset crosslinking time 20 min): The preparation steps are basically the same as in Example 1, except for the steam crosslinking parameters in step S3: the target temperature for generating crosslinking agent vapor is 60°C, the crosslinking compensation temperature is 70°C, the crosslinking reaction temperature is 60°C, and the preset crosslinking time is 20 min. Other control logic and post-processing are consistent with those in Example 1.

[0103] Example 4 (Extremely rapid process, preset crosslinking time 5 min): The preparation steps are basically the same as in Example 1, except for the steam crosslinking parameters in step S3: the target temperature for generating crosslinking agent vapor is 80°C, the crosslinking compensation temperature is 90°C, the crosslinking reaction temperature is 90°C, and the preset crosslinking time is significantly shortened to 5 minutes. Other concentration control logic and post-processing are consistent with those in Example 1.

[0104] Comparative Example 1 (without dynamic concentration control of upper and lower strata): The process flow is the same as in Example 1, except that in the S3 crosslinking step, only the preset crosslinking parameters are retained, and the control of the crosslinking agent vapor concentration range in the upper and lower layers of the crosslinking chamber and the dynamic adjustment function of the gas concentration difference between the upper and lower layers are cancelled. That is, the traditional open-loop single-point environmental control is adopted.

[0105] Comparative Example 2 (without stepped temperature control): The process flow is the same as in Example 1, except that in the S3 crosslinking step, the stepped temperature control of the crosslinking chamber is not performed (i.e., no compensation temperature and cooling reaction steps are set), and the chamber is kept at room temperature during crosslinking.

[0106] Comparative Example 3 (Traditional Static Slow Crosslinking Process): The process flow is the same as in Example 1, except that the most traditional crosslinking method is used. In step S3, neither temperature control of the crosslinking chamber nor dynamic feedback control of gas concentration is performed (only the safety concentration unlocking function is retained). The static crosslinking reaction is carried out at room temperature (20°C) for the same preset time (60 min) as in Example 1.

[0107] Comparative Example 4 (Excessive Crosslinking Process): The process flow is the same as that in Example 1, except that the preset time limit of this application is broken and the preset crosslinking time is greatly extended to 80 minutes.

[0108] Comparative Example 5 (Extreme process exceeding the safe concentration threshold): Compared to Example 4 (Extremely Rapid Process), the safety upper limit of concentration control was exceeded in step S3. The crosslinking agent vapor concentration range in both the upper and lower regions of the crosslinking chamber was allowed to exceed 250 ppm (>250 ppm). In actual crosslinking, the 5-minute countdown was only started when the concentration in both the upper and lower layers exceeded 250 ppm, and no exhaust ventilation or concentration reduction was performed during this period.

[0109] II. Experimental Testing Methods: For the gelatin nanofiber membranes prepared in the above embodiments and comparative examples, samples were taken from the upper and lower layers of the crosslinking chamber, respectively, and the following performance tests were performed: 1. Surface morphology test: The surface micromorphology of the fiber membrane was observed by scanning electron microscopy (SEM).

[0110] 2. Water Absorption Test: Cut an appropriate amount of fiber membrane and weigh its dry mass $W_1$ (g); immerse it in deionized water for 24 hours, remove it, absorb the surface moisture, and weigh it as the wet mass W2 (g). The formula for calculating the water absorption rate is: Water absorption rate (%) = (W2 - W1) / W1 × 100%.

[0111] 3. Crosslinking Degree Test: The extract was prepared according to ISO 10993-12 standard. 2 mL of the extract was mixed with 500 μL of ninhydrin colorimetric solution and heated in a 100℃ oven for 10 min. The absorbance of the solution at 570 nm was measured using a UV spectrophotometer. Since the absorbance ratio directly reflects the proportion of free amino groups consumed, the crosslinking degree (CD) was calculated accordingly. The specific calculation formula is as follows: Crosslinking degree (%) = (absorbance of uncrosslinked sample - absorbance of crosslinked sample) / absorbance of uncrosslinked sample × 100%.

[0112] Acceptance criteria: Products with a crosslinking degree in the range of 88% to 98% are considered qualified.

[0113] 4. Shrinkage Rate Test (%): A 50×50cm uncrosslinked fiber membrane is placed in the crosslinking chamber for crosslinking. After crosslinking, the crosslinked fiber membrane is removed, and the length of each side is measured to calculate the area. The specific formula is: Shrinkage rate (%) = (Area of ​​uncrosslinked sample - Area of ​​crosslinked sample) / Area of ​​uncrosslinked sample × 100%.

[0114] III. Experimental Results and Analysis / Discussion: To verify the scientific validity of the process parameters of this invention and their effect on improving product performance, samples were taken from the "upper layer" and "lower layer" of the crosslinking chamber of the gelatin nanofiber membranes prepared in the above embodiments and comparative examples for comparative testing.

[0115] Test standard description: According to the conventional application standards in this field and the experimental verification of this application, when the degree of crosslinking of the membrane material is in the range of 88% to 98% and the water absorption rate is in the range of 800% to 1700%, it is judged as a qualified product with a balance of various mechanical and hydrophilic properties; if the water absorption rate drops to 250% to 350%, it indicates that excessive crosslinking has occurred.

[0116] The water absorption rate test results and crosslinking degree test results of each embodiment and comparative example are shown in Table 1 and Table 2 below, respectively: Table 2. Data on water absorption rate test results of gelatin nanofiber membranes

[0117] Table 3. Test Results of Crosslinking Degree of Gelatin Nanofiber Membrane

[0118] Based on the above data and observation of appearance, this application conducts an in-depth comparative analysis from three dimensions: dynamic concentration control, temperature step control, and parameter boundaries.

[0119] Table 4. Comparison of Example 1 and Comparative Example 1

[0120] 1. Validation of the advantages of dynamic closed-loop concentration control (Example 1 vs. Comparative Example 1): This comparison mainly examines the role of dynamic closed-loop control of steam concentration in the upper and lower layers in solving the spatial cross-linking gradient.

[0121] (1) Appearance and morphology: such as Figure 1 and Figure 2 As shown.

[0122] See Figure 1 and Figure 2 In Example 1, due to the dynamic control of the concentration between the upper and lower layers, neither the upper nor lower membrane material underwent macroscopic shrinkage, and the fibers were clear and unadhesive at the microscopic level. In contrast, Comparative Example 1, which lacked this control mechanism, showed an appearance difference of "the upper membrane material did not shrink, while the lower membrane material shrank," and some adhesion of the microfibers in the lower layer was observed.

[0123] (2) Crosslinking uniformity: The water absorption rate is shown in Table 2. In Example 1, the water absorption rates of the upper and lower layers are both within the acceptable range of 1250%~1360%, with a small difference (about 101%). However, in Comparative Example 1, the water absorption rates of the upper and lower layers differ greatly (the upper layer is nearly 1789%, while the lower layer is only 351%).

[0124] The crosslinking degree test reference Table 3 further confirms this point: the crosslinking degree deviation between the upper and lower layers in Example 1 is extremely small (only 4.61%, which meets the design target of ≤5%); while Comparative Example 1 shows that the lower layer is over-crosslinked (close to 97.6%) and the upper layer is not sufficiently crosslinked (only 75.5%), with a difference of up to 22.1% between the upper and lower layers.

[0125] Conclusion Analysis: Due to the high vapor density of the crosslinking agent, gravity sedimentation is likely to occur. Without zoned concentration monitoring and flow field intervention, the concentration in the lower region will be abnormally high, leading to over-crosslinking. Example 1 demonstrates that the closed-loop concentration control method of this application can actively eliminate concentration gradients, greatly improving the uniformity of crosslinking degree of membrane materials in the same batch with spatial distribution.

[0126] 2. Validation of the synergistic effect of stepped temperature control (Example 1 vs. Comparative Example 2 and Comparative Example 3): This comparison mainly examines the effects of temperature compensation and stepped control on crosslinking efficiency and uniformity.

[0127] (1) Crosslinking efficiency and uniformity: Table 5. Comparison of Example 1 and Comparative Example 2

[0128] Referring to Table 5, and combining the experimental results in Tables 2 and 3, a comparison between Example 1 and Comparative Example 2 (which did not undergo temperature control) revealed that although the membrane produced in Comparative Example 2 did not shrink in appearance, its degree of crosslinking (85.3% for the upper layer and 91.3% for the lower layer) was generally lower than that of Example 1, and the difference in the degree of crosslinking between the upper and lower layers (approximately 6.05%) was also slightly greater than that of Example 1.

[0129] (2) Comparison of dynamic steam crosslinking and static crosslinking: Table 6. Comparison of Example 1 and Comparative Example 3

[0130] Conclusion: Pure static room temperature crosslinking efficiency is too low. The stepped temperature control introduced in the examples (especially preheating compensation) not only significantly shortens the required crosslinking time (improving production efficiency), but also the thermal compensation effect constructs a stronger pre-crosslinked physical network, and the synergistic concentration control further improves the uniformity of crosslinking of membrane materials within a batch.

[0131] 3. Verification of the rationality of core process parameter boundaries (Example 4 vs. Comparative Examples 4 and 5): Table 7. Comparison of Examples 1-4

[0132] (1) Parameter optimization comparison: Refer to Table 7, combined with Figure 1 and Figure 2 As can be seen from Examples 1-4, the water absorption rate of the products prepared in all examples is within the acceptable range of 800% to 1700% (with an average value between 1100% and 1600%). (It should be noted that the water absorption rate data shows a wide range, which is due to the objective fluctuation between 0.05mm and 0.6mm in the thickness of the produced membrane material caused by the wide range of process parameters. Different thicknesses and pore distributions directly endow the material with multi-level liquid absorption capacity, which precisely meets the differentiated needs of wound dressings with different exudate volumes.) The crosslinking degree deviation between the upper and lower layers is controlled within the excellent range of ≤8% (Among them, Example 2 has the best uniformity between the upper and lower layers, with a crosslinking degree deviation of only about 3.71%). This fully demonstrates that the process parameter range claimed in this application is reasonable and widely applicable.

[0133] (2) Adverse consequences of exceeding the time limit (Example 1 vs. Comparative Example 4): Table 8. Comparison of Example 1 and Comparative Example 4

[0134] Referring to Table 8, in conjunction with Figure 1 and Figure 2 As can be seen, in Comparative Example 4, although the fibers did not stick together after the time was extended to 80 minutes, both the upper and lower membrane materials showed "severe shrinkage" and deteriorated appearance. Meanwhile, the crosslinking degree test showed "over-crosslinking," and the water absorption rate was significantly lower than in Example 1 (both decreased to approximately 300%). This confirms that the crosslinking time (≤60 minutes) defined in Examples 1-4 is the key upper limit for maintaining the macroscopic dimensional stability and appropriate crosslinking of the material.

[0135] (3) Adverse consequences of exceeding the concentration limit (Example 1 vs. Comparative Example 5): Table 9. Comparison of Examples and Comparative Example 5

[0136] Referring to Table 9, in conjunction with Figure 1 and Figure 2 As can be seen, under the same pursuit of extremely rapid processing, Example 4 (concentration controlled below 250 ppm) yielded a qualified product with intact structure and uniform cross-linking; while Comparative Example 5 (concentration exceeding 250 ppm) resulted in significant deterioration of the membrane material structure: not only did the upper and lower membrane materials undergo "severe shrinkage", but SEM showed that the surface morphology "both showed large-area adhesion". Its degree of cross-linking also showed a state of "over-cross-linking", and the water absorption rate was abnormally low (as low as 259%~284%).

[0137] Conclusion Analysis: The above data further validates the technical significance of controlling the vapor concentration below 250 ppm. Excessively high instantaneous concentration shocks can destroy the microstructure of nanofibers, leading to material swelling and fusion. Only through dynamic feedback within a controlled, safe concentration threshold can high-end medical nanofiber membrane dressings with good morphology and uniform performance be prepared.

[0138] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit them. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of this application.

Claims

1. A method for producing a gelatin fiber film, characterized by, Comprising: Dissolve gelatin in a solvent to obtain a gelatin spinning solution; Perform electrospinning on the gelatin spinning solution to form a gelatin nanofiber membrane; Place the gelatin nanofiber membrane in a crosslinking chamber, and introduce crosslinking agent vapor into the crosslinking chamber to carry out a crosslinking reaction; wherein, during the crosslinking reaction, the concentration of the crosslinking agent vapor in the crosslinking chamber is monitored in real time, and the inlet gas flow rate and / or exhaust gas flow rate of the crosslinking chamber are dynamically adjusted according to the monitored current concentration value, so that the concentration of the crosslinking agent vapor in the crosslinking chamber is maintained within a preset target concentration range; Perform vacuum drying and heat setting on the gelatin nanofiber membrane after the crosslinking reaction to obtain a gelatin fiber membrane.

2. The method for preparing the gelatin fiber membrane as described in claim 1, characterized in that, The real-time monitoring of the concentration of the crosslinking agent vapor in the crosslinking chamber includes: Independently monitor the concentration of the crosslinking agent vapor in the upper region and the lower region of the crosslinking chamber respectively to obtain the upper current concentration and the lower current concentration.

3. The method for preparing the gelatin fiber membrane as described in claim 2, characterized in that, Let the upper current concentration be C1 and the lower current concentration be C2; the crosslinking chamber is preset with an upper concentration limit H1, a lower concentration limit H2, a lower concentration limit L2, and a concentration difference threshold ΔC; The dynamic adjustment of the inlet gas flow rate and / or exhaust gas flow rate of the crosslinking chamber according to the monitored current concentration value includes at least one of the following control logics: A. When C2 < L2, increase the supply of the crosslinking agent vapor; B. When C1 > H1, stop the supply of the crosslinking agent vapor and terminate the heating operation for generating the crosslinking agent vapor; C. When |C1 - C2| < ΔC, weaken the air flow intensity in the crosslinking chamber caused by the inlet and / or exhaust; D. When C1 > H1 and C2 < H2, enhance the air flow intensity in the crosslinking chamber caused by the inlet and / or exhaust; E. When C1 > H1 and C2 > H2, start the exhaust operation and enhance the air flow intensity in the crosslinking chamber caused by the inlet and / or exhaust until C1 < H1.

4. The method for preparing the gelatin fiber membrane as described in claim 3, characterized in that, The control range of the concentration of the crosslinking agent vapor in the upper region and the lower region of the crosslinking chamber is both 10 ppm to 250 ppm; and / or, The concentration difference threshold ≤ 10%.

5. The method for preparing the gelatin fiber membrane as described in claim 1, characterized in that, In the step of introducing crosslinking agent vapor into the crosslinking chamber to carry out a crosslinking reaction, it further includes a step of controlling the temperature of the crosslinking chamber: Before introducing the crosslinking agent vapor, heat the crosslinking chamber to a preset crosslinking compensation temperature; When introducing the crosslinking agent vapor, cool the crosslinking chamber to a preset crosslinking reaction temperature; At the end of the crosslinking reaction, slowly cool the crosslinking chamber to room temperature.

6. The method of claim 5, wherein the gelatin fiber film is prepared by the steps of: The target temperature for generating the crosslinking agent vapor is 20°C to 80°C; and / or, The crosslinking compensation temperature is 30°C to 90°C; and / or, The crosslinking reaction temperature is 20°C to 80°C; and / or, The time of the crosslinking reaction is 5 minutes to 60 minutes.

7. The method of claim 1, wherein the gelatin fiber film is prepared by the steps of: After the crosslinking reaction is completed, the concentration of the crosslinking agent vapor in the crosslinking chamber is continuously monitored, and the access control lock on the crosslinking chamber is released after the concentration of the crosslinking agent vapor in the crosslinking chamber is detected to drop below a preset safe concentration threshold; preferably, the preset safe concentration threshold is 0.1 ppm; And / or, The process of vacuum drying and heat setting of the cross-linked gelatin nanofiber membrane includes: vacuum drying at 100℃~120℃ for 5 to 10 hours, with degassing every 1 to 3 hours during the vacuum drying process; placing the vacuum-dried gelatin nanofiber membrane on a hot press plate covered with nonwoven fabric, fixing the four sides, and performing heat setting at 100℃~120℃ for 5 to 10 hours; and / or, The step of dissolving gelatin in a solvent to obtain a gelatin spinning solution includes: dissolving gelatin in a mixed solvent containing hexafluoroisopropanol and water, and adding acetic acid to obtain a gelatin spinning solution; preferably, in the gelatin spinning solution, the mass percentage of gelatin is 10%~30%, the mass percentage of hexafluoroisopropanol is 30%~50%, the mass percentage of acetic acid is 2%~8%, and the balance is water; preferably, in the gelatin spinning solution, the mass percentage of gelatin is 15%~25%, the mass percentage of hexafluoroisopropanol is 35%~45%, the mass percentage of acetic acid is 3.5%~5.5%, and the balance is water; preferably, after adding acetic acid to the mixed solvent, the solution further includes a static defoaming treatment.

8. The method for preparing the gelatin fiber membrane as described in claim 1, characterized in that, The electrospinning voltage is 10kV~30kV; and / or, The electrospinning spacing is 10cm~18cm; and / or, The crosslinking agent is glutaraldehyde.

9. A gelatin fiber membrane, characterized in that, The gelatin fiber membrane is prepared by the gelatin fiber membrane preparation method according to any one of claims 1-8.

10. The gelatin fiber film according to claim 9, wherein The thickness of the gelatin fiber film is 0.05 mm to 0.6 mm; and / or, The gelatin fiber membrane has a water absorption rate of 800%~1700%; and / or, The crosslinking degree deviation at different locations within the same batch of the gelatin fiber membrane is ≤10%; and / or, The shrinkage rate of the gelatin fiber membrane is ≤10%, and the fiber morphology is intact and without adhesion.

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