One-step photocured electrospun membrane material and preparation method thereof

Abstract

This invention relates to the field of electrospun membranes, and more specifically to a one-step photocurable electrospun membrane material and its preparation method. The photocurable electrospun membrane material is prepared by mixing 5-20 parts of fiber-forming macromolecules, 10-40 parts of collagen, 0.05-3 parts of natural photosensitizer, and a solvent to form a spinning solution. Electrospinning is performed using either needle-type or non-needle-type methods. Simultaneously, the fibers are irradiated with 200-400 nm ultraviolet light in situ to achieve photocuring and cross-linking, thus obtaining a micro / nanofiber membrane in one step. The fiber-forming macromolecules are selected from biodegradable medical polymers, and the photosensitizers are biosafe components such as riboflavin and retinaldehyde. This invention completely solves the problems of uneven cross-linking, fiber morphology damage, collagen denaturation, and internal light filtering effects in traditional two-step methods. The resulting membrane has regular fiber morphology, uniform cross-linking, high mechanical strength, good water resistance, and complete retention of bioactivity. Furthermore, the process is simplified, complies with pharmaceutical quality management standards, and is suitable for medical applications such as tissue engineering and wound repair.

Description

Technical Field

[0001] This invention relates to the field of electrospun films, and more specifically to a one-step photocurable electrospun film material and its preparation method. Background Technology

[0002] Electrospinning is the mainstream technology for preparing micro / nanofiber membranes, enabling the rapid fabrication of biomimetic scaffolds with high specific surface area and interconnected pores. These scaffolds have wide applications in biomedical fields such as tissue engineering, wound repair, and drug delivery. Combining biodegradable polymers such as polylactic acid, polycaprolactone, and polylactic-co-glycolic acid copolymers with natural bioactive components can balance mechanical support and biocompatibility, making it a preferred approach for soft tissue engineering scaffolds. However, pure spun membranes generally suffer from poor water resistance, insufficient mechanical strength, and rapid in vivo degradation, necessitating cross-linking modification to meet clinical requirements.

[0003] Current photocurable electrospun membranes mostly employ a two-step process: spinning followed by crosslinking. This involves first preparing the fiber membrane, then impregnating it with a photosensitizer and irradiating it with ultraviolet light to achieve crosslinking. This method has several drawbacks: First, the photosensitizer relies on penetration into the fiber interior, resulting in uneven distribution. Furthermore, the limited penetration depth of ultraviolet light easily leads to an internal filtering effect—excessive surface crosslinking and insufficient internal crosslinking—resulting in poor crosslinking uniformity and incomplete reaction. Second, post-treatment impregnation and solvent rinsing can easily cause fiber swelling, adhesion, or even dissolution, damaging the micro / nano morphology and significantly reducing the specific surface area and biomimetic structural advantages. Third, bioactive substances such as collagen are prone to denaturation under crosslinking agents, organic solvents, and prolonged irradiation, damaging the triple-helix structure and affecting cell adhesion and tissue integration.

[0004] Existing technology CN111991619A discloses a biodegradable polylactic acid (PLA) catheter for medical intervention and its preparation method. The preparation method includes: preparing the PLA catheter, preparing the silk fibroin spinning solution, surface treatment of the PLA catheter, and finally attaching a silk fibroin film to the PLA surface by electrospinning. However, this method is cumbersome, costly, and struggles to balance structural integrity, crosslinking uniformity, and bioactivity retention, which is detrimental to large-scale production and Good Manufacturing Practice (GMP) production. To address the core bottlenecks in spinning and photocrosslinking, such as uneven photosensitizer distribution and post-treatment damage morphology and activity, there is an urgent need to develop a one-step in-situ crosslinking technology that can complete curing instantaneously during fiber jet forming, achieving synergistic optimization of structure, performance, and process, and promoting the industrial application of biomedical electrospun membranes. Summary of the Invention

[0005] To address the aforementioned technical problems, this invention provides a one-step method for preparing photocurable electrospun film materials, comprising the following steps: According to the mass fraction, 0-20 parts (excluding 0 parts) of fiber-forming macromolecules, 10-40 parts of collagen and 0.05-3 parts of photosensitizer are added to 100 parts of solvent, stirred to dissolve and degas, and then ultraviolet light is applied between the fiber generating unit and the fiber receiving unit to achieve photocrosslinking reaction spinning by needle electrospinning or non-needle electrospinning method to obtain spun film material.

[0006] As an implementable example, the fiber-forming macromolecules include one or more of polylactic acid (PLA), polylactic acid-levulinic acid (PDLA), polylactic acid-dextrorotatory acid (PLLA), racemic polylactic acid (PDLLA), polycaprolactone (PCL), polylactic acid-glycolic acid copolymer (PLGA), polylactic acid-caprolactone copolymer (PLCL), polyethylene oxide (PEO), polydioxanone (PDO), polyvinyl alcohol (PVA), polyethylene glycol (PEG), and chitosan (CS).

[0007] This invention, by precisely defining the mass fractions of fiber-forming macromolecules, collagen, photosensitizers, and solvents, can formulate spinning solutions with excellent solubility, uniform dispersion, and good stability. This ensures a continuous and stable electrospinning process while allowing collagen and photosensitizers to be uniformly distributed in the system, providing a stable foundation for in-situ photocuring. The appropriate component ratio provides the fiber membrane with a reliable mechanical framework and structural support, while fully preserving the biocompatibility and cell adhesion activity of collagen, achieving efficient cross-linking without the problem of excessive photosensitizer residue. Furthermore, this invention employs a one-step photocuring electrospinning process, which can complete in-situ cross-linking simultaneously with fiber formation, fundamentally avoiding fiber dissolution, adhesion, and microstructure damage caused by post-processing. It effectively eliminates the "internal filtering effect" of traditional processes, achieving uniform and thorough cross-linking. The resulting membrane material exhibits significantly improved water resistance and mechanical properties, controllable degradation rate, and maximizes the protection of collagen bioactivity. It also simplifies the process flow, reduces production costs, and is more suitable for industrial and GMP (Good Manufacturing Practice) scaled-up production.

[0008] As an implementable example, the one-step photocurable electrospun film material preparation method includes the following steps: According to the mass fraction, 10-40 parts of collagen and 0.05-3 parts of photosensitizer are added to 100 parts of solvent, stirred to dissolve and degas, and then ultraviolet light is applied between the fiber generating unit and the fiber receiving unit to achieve photocrosslinking reaction spinning by needle electrospinning or non-needle electrospinning method to obtain spun film material.

[0009] This invention does not use fiber-forming macromolecules; only collagen, such as gelatin, can be used for spinning. Other types of collagen, after modification, can also be used to prepare spun membrane materials based on a highly active photosensitive collagen protein system. The collagen modification method involves reacting methacrylic anhydride (MA) or glycidyl methacrylate (GMA) with the amino, hydroxyl, and carboxyl groups in the protein molecule for modification.

[0010] As an implementable example, the collagen includes one or more of the following: collagen, methacrylamide collagen, maleic anhydride modified collagen, vinyl glycidyl ether modified collagen, gelatin, methacrylamide gelatin, maleic anhydride modified gelatin, and vinyl glycidyl ether modified gelatin.

[0011] Furthermore, the collagen includes one or more of type I collagen, type II collagen, type III collagen, type IV collagen, type V collagen, type VI collagen, type VII collagen, type VIII collagen, type IX collagen, and type XII collagen (mainly found in tendons, connective tissues, etc.).

[0012] This invention explicitly defines the types of collagen used, selecting only mature, biocompatible natural active components. This allows for precise matching of the biomimetic repair needs of different human tissues such as skin, cartilage, blood vessels, and basement membranes, significantly enhancing the material's cell adhesion, proliferation, and tissue integration capabilities. The combined use of gelatin and various types of collagen also improves the solubility and processability of the spinning solution, enhancing fiber forming stability. This collagen system is highly compatible with one-step photocuring processes, maximizing the preservation of active structures during in-situ crosslinking and avoiding denaturation and inactivation caused by traditional post-processing. Simultaneously, it synergistically enhances the hydrophilicity, bioactivity, and interfacial affinity of the membrane material.

[0013] As an implementable example, the photosensitizer includes one or more of the following: N-formylkynurenic acid, 3-hydroxykynurenic acid, riboflavin, flavin adenine mononucleotide, flavin adenine dinucleotide, retinaldehyde, porphyrin and its derivatives, polycyclic aromatic hydrocarbon natural photosensitizers, lithium phenyl(2,4,6-trimethylbenzoyl)phosphonate, phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide, 2-hydroxy-2-methyl-1-phenyl-1-propanone, ruthenium compounds, 1-hydroxycyclohexylphenyl ketone, α,α'-dimethoxy-α-phenylacetophenone, dimethoxy-methoxyphenylacetophenone, 2,4,6-trimethylbenzoyl-diphenylphosphine oxide, methyl benzoylformate, and tetrazolium acetic acid.

[0014] Furthermore, the photosensitizer includes one of riboflavin, retinaldehyde, tetrazolium acetic acid, or polycyclic aromatic hydrocarbon natural photosensitizers.

[0015] This invention preferentially uses riboflavin, retinaldehyde, tetrazolium acetic acid, or polycyclic aromatic hydrocarbon natural photosensitizers as photosensitizers. The selected components are all natural or bio-based photosensitizing substances with high biocompatibility and stable cross-linking efficiency. They can efficiently initiate cross-linking under ultraviolet light with wavelengths of 200-400 nm, without the need for toxic chemical cross-linking agents, significantly improving the safety and biocompatibility of medical membrane materials. These photosensitizers are uniformly miscible with fiber-forming macromolecules and collagen, and disperse evenly in the spinning solution, solving the problems of uneven photosensitizer distribution and incomplete cross-linking in traditional impregnation methods from the source. Combined with one-step in-situ curing, the "internal light filtering effect" can be completely eliminated, achieving uniform cross-linking inside and outside the fiber.

[0016] As an implementable example, the solvent includes one or more of hexafluoroisopropanol, chloroform, dichloromethane, DMF (N,N-dimethylformamide), DMAc (N,N-dimethylacetamide), formic acid, acetic acid, and water.

[0017] The solvent selected in this invention can fully dissolve fiber-forming macromolecules such as polylactic acid, polycaprolactone, and chitosan, as well as collagen and photosensitizer components, to form a uniform and stable spinning solution with suitable viscosity. This ensures continuous electrospinning and effectively avoids problems such as droplets, broken fibers, and uneven fiber thickness, providing a stable system support for the preparation of micro / nanofiber membranes with regular morphology.

[0018] As a feasible example, the described needle electrospinning method involves a feed rate of 0.2-5 mL / h, an electrode distance of 8-25 cm, a temperature of 10-40℃, and a humidity of 30-80%. During spinning, the Taylor cone and epitaxial position are irradiated with 200-400 nm wavelength ultraviolet light, with an illuminance of 100-5000 mw / cm². 2 .

[0019] Furthermore, the spinning voltage of the needle electrospinning method is 5-40kV.

[0020] As an feasible example, the described non-needle electrospinning method, such as screw spinning, involves an electrode distance of 10-30 cm, a temperature of 10-40℃, and a humidity of 30-80%. During spinning, the Taylor cone and epitaxial position are irradiated with 200-400 nm wavelength ultraviolet light, with an illuminance of 100-5000 mw / cm². 2 .

[0021] Furthermore, the spinning voltage of the non-needle electrospinning method is 30-100kV.

[0022] This invention controls the ambient temperature at 10-40℃ and humidity at 30-80%, ensuring a stable solvent evaporation rate during spinning to prevent fiber collapse, adhesion, or morphological defects. It also avoids collagen denaturation caused by high temperatures under mild room temperature conditions, keeping the upper temperature limit below the collagen denaturation threshold to maximize the preservation of its natural triple helix bioactivity. Furthermore, it targets irradiation locations of 200-400nm ultraviolet light and 100-5000mw / cm². 2 The limited illuminance allows for photoinitiated crosslinking to be completed instantaneously during fiber jet forming. This efficiently triggers the crosslinking reaction of natural photosensitizers while fundamentally avoiding the internal filtering effect of traditional post-curing, ensuring uniform crosslinking both inside and outside the fiber. Simultaneously, for needle spinning, a push rate of 0.2-5 mL / h, an electrode distance of 8-25 cm, and a spinning voltage of 5-40 kV are set. For non-needle spinning processes such as screw spinning, an electrode distance of 10-30 cm and a corresponding voltage range are adapted. This allows for adaptation to different production scenarios, from laboratory pilot-scale trials to industrial mass production, ensuring a stable electric field is formed under different modes to drive the jet to fully stretch and produce micro / nanofibers with regular morphologies.

[0023] A second aspect of the present invention provides a photocurable electrospun film material prepared from the above-described one-step photocurable electrospun film material.

[0024] Beneficial effects (i) The present invention adopts a one-step process that simultaneously performs spinning and photocuring, which completes cross-linking at the moment of fiber jet forming. It eliminates the need for post-processing steps such as photosensitizer impregnation, solvent rinsing, and secondary irradiation, fundamentally avoiding the problems of fiber swelling, adhesion, dissolution, and damage to micro-nano morphology caused by post-processing in the traditional two-step method. It fully preserves the advantages of high specific surface area and biomimetic structure, and solves the defects of morphology damage and specific surface area reduction in the existing technology.

[0025] (II) In this invention, the photosensitizer is pre-dispersed uniformly in the spinning solution, and then irradiated in situ with 200-400nm ultraviolet light on the Taylor cone and epitaxial section. The fiber diameter is only tens to hundreds of nanometers, and the light penetrates without obstruction. This completely eliminates the internal filtering effect caused by excessive surface crosslinking and insufficient internal crosslinking due to ultraviolet attenuation in traditional post-crosslinking, and achieves uniform and thorough crosslinking inside and outside the fiber. This solves the defects of uneven crosslinking and incomplete reaction in the existing technology.

[0026] (III) This invention uses biosafe natural / bio-derived photosensitizers to complete cross-linking under room temperature, normal pressure, and short-term ultraviolet irradiation. The reaction conditions are mild and do not use toxic chemical cross-linking agents or highly corrosive reagents. This effectively protects the triple helix structure of collagen, reduces protein denaturation and loss of bioactivity, avoids the problem of activity damage caused by cross-linking agents, organic solvents, and long-term irradiation in traditional processes, and solves the defects of poor bioactivity retention, poor cell adhesion and tissue integration in existing technologies. Attached Figure Description

[0027] Figure 1 This is a SEM image of the electrospun film material from Example 1.

[0028] Figure 2 The image shows the SEM test results of the electrospun film material in Comparative Example 1.

[0029] Figure 3 This is a comparison chart of mechanical performance test results. Detailed Implementation

[0030] Example 1 This example provides a one-step method for preparing photocurable electrospun film materials, including the following steps: According to the mass fraction, 12 parts PLA, 20 parts type I collagen and 0.8 parts riboflavin were added to 100 parts hexafluoroisopropanol, stirred to dissolve and degassed, and then photocured by applying ultraviolet light irradiation between the fiber generating unit and the fiber receiving unit through needle electrospinning to obtain photocured electrospun film material.

[0031] The number-average molecular weight of the PLA is 120,000.

[0032] The parameters for the needle electrospinning method are as follows: injection speed 2 mL / h, electrode distance 15 cm, temperature 25℃, humidity 50%, Taylor cone and epitaxial position irradiated with 200-400 nm wavelength ultraviolet light during spinning, spinning voltage 20 kV, and illuminance 1000 mw / cm². 2 .

[0033] The second aspect of this example provides a photocurable electrospun film material prepared from the above-described one-step photocurable electrospun film material. The SEM image of the product is shown below. Figure 1 As shown.

[0034] Example 2 This example provides a one-step method for preparing photocurable electrospun film materials, including the following steps: According to the mass fraction, 12 parts of PLLA, 20 parts of type II collagen and 0.8 parts of retinaldehyde are added to 100 parts of hexafluoroisopropanol, stirred to dissolve and degas, and then photocured by applying ultraviolet light irradiation between the fiber generating unit and the fiber receiving unit through needle electrospinning to obtain photocured electrospun film material.

[0035] The number-average molecular weight of the PLLA is 120,000.

[0036] The parameters for the needle electrospinning method are as follows: injection speed 2 mL / h, electrode distance 15 cm, temperature 25℃, humidity 50%, Taylor cone and epitaxial position irradiated with 200-400 nm wavelength ultraviolet light during spinning, spinning voltage 20 kV, and illuminance 1000 mw / cm². 2 .

[0037] The second aspect of this example provides a photocurable electrospun film material prepared from the above-described one-step photocurable electrospun film material.

[0038] Example 3 This example provides a one-step method for preparing photocurable electrospun film materials, including the following steps: According to the mass fraction, 10 parts PLGA, 20 parts gelatin and 0.8 parts N-formylkynurenic acid are added to 100 parts hexafluoroisopropanol, stirred to dissolve and degas, and then photocured by applying ultraviolet light irradiation between the fiber generating unit and the fiber receiving unit using needle electrospinning to obtain photocured electrospun film material.

[0039] The number-average molecular weight of the PLGA is 120,000.

[0040] The parameters for the needle electrospinning method are as follows: injection speed 2 mL / h, electrode distance 15 cm, temperature 25℃, humidity 50%, Taylor cone and epitaxial position irradiated with 200-400 nm wavelength ultraviolet light during spinning, spinning voltage 20 kV, and illuminance 1000 mw / cm². 2 .

[0041] The second aspect of this example provides a photocurable electrospun film material prepared from the above-described one-step photocurable electrospun film material.

[0042] Example 4 The specific implementation method of this example is the same as that of Example 1, except that non-needle electrospinning is used for photocuring spinning.

[0043] The non-needle electrospinning method, including screw spinning, involves an electrode distance of 20 cm, a temperature of 25°C, and a humidity of 40%. During spinning, 200-400 nm wavelength ultraviolet light is used to irradiate the Taylor cone and its epitaxial position. The spinning voltage is 80 kV, and the illuminance is 2000 mW / cm². 2 .

[0044] Example 5 This example provides a one-step method for preparing photocurable electrospun film materials, including the following steps: According to the mass fraction, 22 parts of gelatin and 0.5 parts of tetrazolium acetic acid were added to 100 parts of 50wt% acetic acid aqueous solution, stirred to dissolve and degas, and then photocured by applying ultraviolet light irradiation between the fiber generating unit and the fiber receiving unit using needle electrospinning to obtain photocured electrospun film material.

[0045] The parameters for the needle-based electrospinning method are as follows: 23G spinning needle, injection speed of 2 mL / h, electrode distance of 15 cm, receiving distance of 16 cm, and liquid supply speed of 0.5 mL / h; temperature of 25℃; humidity of 50%; 200-400 nm wavelength ultraviolet light is used to irradiate the Taylor cone and epitaxial position during spinning; spinning voltage is 15 kV; and illuminance is 1000 mw / cm². 2 .

[0046] The second aspect of this example provides a photocurable electrospun film material prepared from the above-described one-step photocurable electrospun film material.

[0047] Comparative Example 1 This example provides a method for preparing a photocurable electrospun film material, including the following steps: 12 parts PLA and 20 parts type I collagen were added to 100 parts hexafluoroisopropanol to prepare a spinning solution. Electrospinning was performed to obtain fibers. The fibers were then immersed in riboflavin for 1 hour and then subjected to ultraviolet light curing and crosslinking to obtain a photocurable electrospun film material.

[0048] In this example, because a one-step preparation process was not used, but rather an impregnation-photocuring process, the fiber membrane partially dissolved, and the micro-nano morphology was damaged. Specifically, as shown below... Figure 2 As shown.

[0049] Comparative Example 2 This example provides a method for preparing a photocurable electrospun film material, including the following steps: By weight, 12 parts PLA and 20 parts type I collagen were added to 100 parts hexafluoroisopropanol to prepare a spinning solution, which was then electrospun to obtain a spun membrane material.

[0050] Comparative Example 3 The specific implementation method in this example is the same as in Example 5, except that the raw materials do not include photosensitizers.

[0051] Performance testing 1. Mechanical property testing The spun film material was cut into strips of 4cm×1cm and fixed with clips spaced 20mm apart. The tensile strength of the spun film materials in Examples 1-5 and Comparative Examples 1-3 was tested. The test results are detailed in Table 1.

[0052] After soaking the film in 37% water for 4 hours, the microstructure of the spun film materials of Examples 1-5 and Comparative Examples 1-3 was observed using a scanning electron microscope to determine whether fiber dissolution or irregular morphology occurred. The results are recorded in Table 1.

[0053] Table 1

[0054] Examples 1-3 respectively used three types of fiber-forming macromolecules (PLA / PLLA / PLGA), three active components (Type I collagen / Type II collagen / gelatin), and riboflavin / retinaldehyde / N All three photosensitizers—formylkynurenic acid, formyl urate, and formaldehyde—resulted in products with stable performance and good morphology, demonstrating the strong compatibility and wide applicability of the formulation of this invention. Example 4, using non-needle electrospinning, also achieved ideal performance, indicating that the process is compatible with both needle-spinning and industrial non-needle-spinning equipment, is easy to scale up and standardize, and is suitable for GMP production. Example 5 also demonstrated spinning using only gelatin. The comparative examples, with their complex processes, uncontrollable performance, and difficulty in stable mass production, further highlight the outstanding advantages of this invention in industrialization.

[0055] Mechanical test data (such as) Figure 3 As shown in the figures, the tensile strength of Examples 1-5 all reached 3 MPa, exhibiting stable and excellent mechanical properties; the tensile strength of Comparative Examples 1-3 was less than 2 MPa, significantly lower than that of the Examples. The Examples, due to their thorough and uniform in-situ photocrosslinking, formed a stable crosslinked network within and on the surface of the fibers, greatly improving mechanical strength and structural stability. Comparative Example 1 suffered from uneven crosslinking and morphological damage, resulting in decreased strength. Comparative Examples 2-3, lacking crosslinking, relied solely on the strength of the raw materials, resulting in weak mechanical properties that could not meet application requirements. The results indicate that the one-step photocuring method of this invention can significantly improve the mechanical properties of the membrane material. Furthermore, microscopic morphology testing shows that the spun membrane material prepared using the one-step method has a regular fiber morphology, is insoluble, and shows good application prospects.

Claims

1. A method for preparing a one-step photocrosslinking electrospun film material, characterized in that, Includes the following steps: According to the mass fraction, 0-20 parts of fiber-forming macromolecules, 10-40 parts of collagen and 0.05-3 parts of photosensitizer are added to 100 parts of solvent, stirred to dissolve and degas, and then needle electrospinning or non-needle electrospinning is used. Ultraviolet light is applied between the fiber generating unit and the fiber receiving unit to achieve photocrosslinking reaction spinning, thus obtaining the spun film material.

2. The preparation method according to claim 1, characterized in that, The collagen mentioned includes one or more of the following: collagen protein, methacrylamide collagen, maleic anhydride modified collagen, vinyl glycidyl ether modified collagen, gelatin, methacrylamide gelatin, maleic anhydride modified gelatin, and vinyl glycidyl ether modified gelatin.

3. The preparation method according to claim 2, characterized in that, The collagen mentioned includes one or more of type I collagen, type II collagen, type III collagen, type IV collagen, type V collagen, type VI collagen, type VII collagen, type VIII collagen, type IX collagen, and type XII collagen.

4. The preparation method according to claim 1, characterized in that, The photosensitizers include one or more of the following: N-formylkynurenic acid, 3-hydroxykynurenic acid, riboflavin, flavin adenine mononucleotide, flavin adenine dinucleotide, retinaldehyde, porphyrin and its derivatives, polycyclic aromatic hydrocarbon natural photosensitizers, lithium phenyl(2,4,6-trimethylbenzoyl)phosphonate, phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide, 2-hydroxy-2-methyl-1-phenyl-1-propanone, ruthenium compounds, 1-hydroxycyclohexylphenyl ketone, α,α'-dimethoxy-α-phenylacetophenone, dimethoxy-methoxyphenylacetophenone, 2,4,6-trimethylbenzoyl-diphenylphosphine oxide, methyl benzoylformate, and tetrazolium acetic acid.

5. The preparation method according to claim 1, characterized in that, The solvent includes one or more of hexafluoroisopropanol, chloroform, dichloromethane, N,N-dimethylformamide, N,N-dimethylacetamide, formic acid, acetic acid, or water.

6. A photocurable electrospun film material prepared by a one-step photocurable electrospun film material preparation method according to any one of claims 1-5.

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