Flexible optical fiber and method of making and using same

Abstract

The application provides a flexible optical fiber and a preparation method and application thereof, and the preparation method comprises the following steps: providing an A-component ink, which comprises a combination of an acrylamide monomer, sodium alginate, a crosslinking agent, a photoinitiator and water; providing a B-component ink, which comprises a combination of a calcium salt, a natural polymer and water; coaxially printing and photocuring the A-component ink in a core layer of a coaxial printing needle and the B-component ink in a cladding layer of the coaxial printing needle to obtain the flexible optical fiber. Through the design of the two-component ink and the combination of the two-component ink and the coaxial printing technology, the preparation method can reliably and conveniently obtain the flexible optical fiber with a customized size, uniform texture, high light transmittance, good flexibility and good stretchability, so as to meet the demand of the biological level on the regulation of large deformation nerve tissues in the optical genetic technology.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, specifically relating to a flexible optical fiber, its preparation method, and its application. Background Technology

[0002] 3D bioprinting technology has been widely applied to life science fields such as tissue engineering and neuroscience. The formulation and development of bio-inks has received widespread attention from researchers. Many bio-inks that have been developed are mainly used for printing cell scaffolds and tissue models.

[0003] Optogenetics is a rapidly developing biotechnology that integrates genetic engineering, optics, neuroelectrophysiology, and biomedical engineering. Its main principle is to use gene technology to express photosensitive genes in specific types of nerve cells, causing them to form photosensitive ion channels on the cell membrane. Then, light of a specific wavelength is used to selectively excite or inhibit these nerve cells, achieving selective neuromodulation. To achieve optogenetic regulation in vivo, optical waveguides of a specific wavelength are typically implanted within the body to guide laser light to the target location. Therefore, the two fundamental pillars of optogenetics are photosensitive gene technology and laser conduction technology. One key aspect of laser conduction technology is the selection of optical fiber materials.

[0004] Due to its high transparency, glass optical fiber has been widely used in central nervous system applications. For example, CN117101019A discloses a multi-channel fiber optic optogenetic stimulation system, including an optogenetic light source, a biaxial scanning mirror, and a multimode fiber with multiple transmission fibers. These transmission fibers provide multiple fiber channels for laser transmission, and multiple stimulation fibers fan out from the tail of the multimode fiber. The multimode fiber is an all-glass fiber, including a glass sheath and multiple transmission fibers disposed within the sheath. Each transmission fiber includes a core and a cladding, where the refractive index of the cladding is less than that of the core, and the refractive index of the core is greater than or equal to that of the glass sheath, which in turn is greater than or equal to that of the cladding. This multi-channel fiber optic optogenetic stimulation system utilizes a combination of fan-out glass fiber bundles and biaxial scanning mirror scanning to achieve multi-point stimulation, making it suitable for large-scale manipulation and research of neural circuits. However, with the development of optogenetics, glass optical fibers can no longer meet the application requirements. The reason is that the central nervous system is supported by the skull, and the various positions in the brain are basically fixed. Glass optical fibers are also easy to fix, so they are widely used. However, in the peripheral system, many peripheral nerves do not have skeletal attachments, have complex pathways, and the free behavior of living organisms will cause large deformations of nerve tissue. It is difficult for glass optical fibers to fix and irradiate a specific point, so they are not suitable for use.

[0005] To meet the application requirements of optogenetics in the peripheral nervous system, researchers have proposed using flexible optical fibers to replace traditional high-modulus glass fibers. For example, CN111939472A discloses an intracranial stimulation recording system, which includes a flexible optical fiber, a laser, and flexible deep brain electrodes. The flexible optical fiber is connected to the laser, and the flexible deep brain electrodes are fixed to the flexible optical fiber by clamps. This intracranial stimulation recording system attaches the flexible deep brain electrodes to the surface of the flexible optical fiber, uses the laser as the light source, and can integrate the functions of optical pulse nerve stimulation and neurophysiological signal acquisition, while simultaneously realizing optogenetic excitation and inhibition. Using silk protein as the main material for the substrate, insulating layer, and encapsulation layer of the flexible deep brain electrodes, combined with flexible optical fiber materials, can improve the mechanical compliance of the implanted device with brain tissue.

[0006] Currently, most flexible optical fibers are fabricated using 3D bioprinting technology. However, 3D-printed flexible fibers have poor light conductivity and do not meet the requirements for flexible and stretchable optical fibers. Fibers fabricated using other processes also suffer from weak flexibility and limited stretchability, failing to meet the modulation needs of peripheral neural tissues with large deformations. Furthermore, these processes are costly, result in high light loss, and have poor light conductivity, which is detrimental to laser transmission within the body. Therefore, there is an urgent need in this field to develop an optical fiber material with good light conductivity, flexibility, stretchability, and convenient fabrication methods to meet the application requirements of optogenetics. Summary of the Invention

[0007] To address the shortcomings of existing technologies, the present invention aims to provide a flexible optical fiber, its preparation method, and its application. By designing a two-component ink and combining it with coaxial printing technology, the preparation method can reliably and conveniently obtain flexible optical fibers with customized dimensions, uniform texture, high light conductivity, and good flexibility and stretchability, thus meeting the needs of optogenetic technology for the regulation of large-deformation neural tissues at the biological level.

[0008] To achieve this objective, the present invention adopts the following technical solution:

[0009] In a first aspect, the present invention provides a method for fabricating a flexible optical fiber, the method comprising the following steps:

[0010] Provide component A ink, said component A ink comprising a combination of acrylamide monomers, sodium alginate, crosslinking agent, photoinitiator and water;

[0011] A component B ink is provided, the component B ink comprising a combination of calcium salt, natural polymer and water;

[0012] The flexible optical fiber is obtained by placing the A component ink in the core layer of the coaxial printing needle and the B component ink in the cladding layer of the coaxial printing needle for coaxial printing and photocuring.

[0013] This invention designs a specific two-component bio-ink, wherein component A comprises acrylamide monomers, sodium alginate, a crosslinking agent, and a photoinitiator, and component B comprises calcium salts and natural polymers. This bio-ink forms a flexible optical fiber using coaxial printing technology. Component A ink is extruded through a coaxial printing needle with a smaller inner diameter to form the fiber core, while component B ink is extruded through a coaxial printing needle with a larger inner diameter to form the fiber cladding. During the coaxial printing process, photocuring promotes the photocrosslinking of acrylamide monomers, sodium alginate, and the crosslinking agent, thus forming the core. Simultaneously, calcium ions in component B ink also complex with sodium alginate for secondary crosslinking, stabilizing the formation of the cladding.

[0014] This invention proposes a novel method for preparing customized, uniform, stretchable, flexible optical fibers by designing a two-component bio-ink and combining it with coaxial printing technology. The preparation method is convenient and reliable, and the resulting flexible optical fiber has excellent biocompatibility, high optical conductivity, and excellent tensile properties. It can be implanted in freely moving organisms for a long time and applied to optogenetic regulation of peripheral nerve tissue, fully meeting the needs of optogenetic technology for the regulation of highly deformable neural tissues at the biological level.

[0015] It should be noted that the coaxial printing needle includes a core layer and a cladding layer arranged coaxially, with the core layer nested within the cladding layer, and the diameter of the core layer being smaller than the diameter of the cladding layer; that is, the cross-section of the coaxial printing needle has a concentric circular structure, with the core layer being the inner circle and the cladding layer being the outer circle; the A component ink is extruded from the core layer of the coaxial printing needle, and the B component ink is extruded from the cladding layer of the coaxial printing needle, thereby achieving coaxial printing.

[0016] The following are preferred technical solutions of the present invention, but are not intended to limit the technical solutions provided by the present invention. The purpose and beneficial effects of the present invention can be better achieved and realized through the following preferred technical solutions.

[0017] Preferably, the acrylamide monomer includes any one or a combination of at least two of acrylamide, methacrylamide, N-isopropylacrylamide, N,N-dimethylacrylamide, and N,N-diethylacrylamide, with acrylamide being more preferred.

[0018] Preferably, the mass percentage of acrylamide monomers in component A ink is 20-40%, for example, it can be 22%, 25%, 28%, 30%, 32%, 35% or 38%, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0019] Preferably, the sodium alginate content in component A ink is 0.5-5% by mass, for example, it can be 0.6%, 0.8%, 1%, 1.2%, 1.5%, 1.8%, 2%, 2.2%, 2.5%, 2.8%, 3%, 3.2%, 3.5%, 3.8%, 4%, 4.2%, 4.5%, or 4.8%, as well as specific values ​​between the above values. Due to space limitations and for the sake of brevity, this invention will not exhaustively list the specific values ​​included in the range, but 1-3% is further preferred.

[0020] Preferably, the crosslinking agent is a bisacrylamide crosslinking agent.

[0021] Preferably, the crosslinking agent includes any one or a combination of at least two of N,N'-methylenebisacrylamide, N,N'-ethylidenebisacrylamide, and N,N'-(propane-1,3-diyl)diacrylamide.

[0022] Preferably, based on 100% of the acrylamide monomer, the crosslinking agent has a mass of 0.1-3%, for example, 0.2%, 0.5%, 0.6%, 0.8%, 1%, 1.2%, 1.5%, 1.8%, 2%, 2.2%, 2.5%, or 2.8%, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range, but 0.5-2% is further preferred.

[0023] Preferably, the photoinitiator comprises any one or a combination of at least two of 2-hydroxy-2-methyl-1-phenyl-1-propanone (photoinitiator 1173), 2,4,6-trimethylbenzoyl-diphenylphosphine oxide (photoinitiator TPO), and 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylpropanone (photoinitiator 2959), and more preferably 2-hydroxy-2-methyl-1-phenyl-1-propanone (photoinitiator 1173).

[0024] Preferably, based on the mass of the acrylamide monomer as 100%, the mass of the photoinitiator is 0.01-1%, for example, it can be 0.02%, 0.05%, 0.08%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, or 0.9%, as well as specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range, but 0.1-1% is further preferred.

[0025] Preferably, the preparation method of the A component ink includes: mixing sodium alginate with water, stirring until the sodium alginate is completely dissolved, then adding acrylamide monomer, crosslinking agent and photoinitiator, and mixing thoroughly to obtain the A component ink.

[0026] Preferably, the calcium salt comprises calcium chloride and / or calcium nitrate, and more preferably calcium chloride.

[0027] Preferably, the concentration of calcium ions in the B component ink is 0.01-0.5 mol / L, for example, it can be 0.02 mol / L, 0.05 mol / L, 0.08 mol / L, 0.1 mol / L, 0.15 mol / L, 0.2 mol / L, 0.25 mol / L, 0.3 mol / L, 0.35 mol / L, 0.4 mol / L or 0.45 mol / L, as well as specific values ​​between the above values. Due to space limitations and for the sake of brevity, this invention will not exhaustively list the specific values ​​included in the range, but 0.05-0.3 mol / L is further preferred.

[0028] Preferably, the natural polymer includes gelatin and / or collagen, with gelatin being more preferred.

[0029] Preferably, the mass percentage of natural polymer in the B component ink is 15-40%, for example, it can be 16%, 18%, 20%, 22%, 25%, 28%, 30%, 32%, 35% or 38%, and specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range, but 20-30% is further preferred.

[0030] Preferably, the preparation method of the B component ink includes: mixing a natural polymer (preferably gelatin) with water to fully dissolve the natural polymer (preferably gelatin), then adding calcium salt and mixing evenly to obtain the B component ink.

[0031] Preferably, the temperature at which the natural polymer is mixed with water is 50-70°C, for example, 52°C, 55°C, 58°C, 60°C, 62°C, 65°C, or 68°C, as well as specific values ​​between the above-mentioned values. Due to space limitations and for the sake of brevity, this invention will not exhaustively list all the specific values ​​included in the range.

[0032] Preferably, the ink component A is injected into the ink cartridge A of the printing device, and the ink cartridge A is in communication with the core layer of the coaxial printing needle; the ink component B is injected into the ink cartridge B of the printing device, and the ink cartridge B is in communication with the cladding layer of the coaxial printing needle.

[0033] The ink component A is extruded from barrel A through the core layer of the coaxial printing needle, and the ink component B is extruded from barrel B through the cladding layer of the coaxial printing needle, thus achieving coaxial printing.

[0034] Preferably, the volume ratio of component A ink to component B ink in the coaxial printing is (4-8):1, for example, it can be 4.5:1, 4.8:1, 5:1, 5.2:1, 5.5:1, 5.7:1, 6:1, 6.2:1, 6.5:1, 6.8:1, 7:1, 7.2:1, 7.5:1 or 7.8:1, etc., and more preferably (5-6):1.

[0035] Preferably, the temperature of the coaxial printing is 40-60℃, for example, it can be 42℃, 45℃, 48℃, 50℃, 52℃, 55℃ or 58℃, as well as specific point values ​​between the above point values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific point values ​​included in the range.

[0036] Preferably, the light source for photocuring is an ultraviolet light source.

[0037] Preferably, the wavelength of the ultraviolet light source is 350-400nm, for example, it can be 355nm, 360nm, 365nm, 370nm, 375nm, 380nm, 385nm, 390nm or 395nm, as well as specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range.

[0038] Preferably, the preparation method includes the following steps:

[0039] The ink comprises component A, which includes acrylamide monomers, sodium alginate, bisacrylamide crosslinking agents, photoinitiators, and water; the mass percentage of acrylamide monomers in component A is 20-40%, and the mass percentage of sodium alginate is 1-3%; the mass ratio of acrylamide monomers, bisacrylamide crosslinking agents, and photoinitiators is 100%:(0.5-2%):(0.1-1%).

[0040] Provide a component B ink comprising a combination of calcium salt, gelatin and water, wherein the concentration of calcium ions in the component B ink is 0.05-0.3 mol / L and the mass percentage of gelatin is 20-30%;

[0041] The ink component A is injected into the ink cartridge A of the printing device, and the ink cartridge A is in communication with the core layer of the coaxial printing needle; the ink component B is injected into the ink cartridge B of the printing device, and the ink cartridge B is in communication with the cladding layer of the coaxial printing needle.

[0042] The A component ink is extruded from barrel A through the core layer of the coaxial printing needle, and the B component ink is extruded from barrel B through the cladding layer of the coaxial printing needle. Coaxial printing and ultraviolet curing are performed to obtain the flexible optical fiber.

[0043] In the coaxial printing, the volume ratio of component A ink to component B ink is (4-8):1, and the temperature of the coaxial printing is 40-60℃.

[0044] In a second aspect, the present invention provides a flexible optical fiber, which is prepared by the preparation method described in the first aspect.

[0045] Preferably, the diameter of the flexible optical fiber is 100-500μm, for example, it can be 150μm, 180μm, 200μm, 220μm, 250μm, 280μm, 300μm, 320μm, 350μm, 380μm, 400μm, 420μm, 450μm or 480μm, as well as specific values ​​between the above values. Due to space limitations and for the sake of brevity, the present invention will not exhaustively list the specific values ​​included in the range, and 200-400μm is further preferred.

[0046] Preferably, the optical fiber has a light conductivity of ≥60%, for example, it can be 62%, 65%, 68%, 70%, 75%, 80%, 85%, 90% or 95%, etc.

[0047] Thirdly, the present invention provides an application of the flexible optical fiber as described in the second aspect in optical fiber implants, biosensors, or implantable medical devices.

[0048] Compared with the prior art, the present invention has the following beneficial effects:

[0049] The method for preparing flexible optical fibers provided by this invention, through the design of a two-component bio-ink and its combination with coaxial printing technology, enables the convenient and reliable acquisition of customized, uniformly textured flexible optical fibers. These flexible optical fibers possess excellent biocompatibility, high optical conductivity, and superior flexibility and tensile properties. With an optical conductivity ≥60%, low optical loss, and good optical transmission performance, they can be implanted long-term in freely moving organisms and applied to the optogenetic regulation of peripheral nerve tissues, fully meeting the needs of optogenetic technology for the regulation of highly deformed neural tissues at the biological level. Attached Figure Description

[0050] Figure 1 A schematic diagram of the coaxial printing process in a preparation method provided for a specific embodiment;

[0051] Among them, 10-barrel A, 20-barrel B, 30-connecting tube, 40-light source, 50-flexible optical fiber, 60-coaxial printing needle, 71-optical fiber core extruded through the core layer of the coaxial printing needle, and 72-optical fiber cladding extruded through the cladding of the coaxial printing needle.

[0052] Figure 2 A physical image of the flexible optical fiber provided in Example 1;

[0053] Figure 3 The image shows a test diagram of the light guiding effect of the flexible optical fiber provided in Example 1. Detailed Implementation

[0054] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention.

[0055] The terms “comprising,” “including,” “having,” “containing,” or any other variations thereof, as used herein, are intended to cover non-exclusive inclusion. For example, a composition, step, method, article, or apparatus that includes the listed elements is not limited to those elements and may also include other elements not expressly listed or elements inherent to such composition, step, method, article, or apparatus.

[0056] "Optional" or "any one" means that the matter or event described thereafter may or may not occur, and the description includes both the possibility that the event may occur and the possibility that the event may not occur.

[0057] The indefinite articles “a” and “an” preceding an element or component of this invention do not impose any limitation on the quantity (i.e., number of times) of the element or component. Therefore, “an” or “a” should be interpreted as including one or at least one, and the singular form of an element or component also includes the plural form, unless the quantity clearly refers only to the singular form.

[0058] In one specific embodiment, the method for fabricating the flexible optical fiber includes:

[0059] The ink is provided as component A, which comprises a combination of acrylamide monomers, sodium alginate, crosslinking agent, photoinitiator and water.

[0060] Component B ink is provided, which comprises a combination of calcium salts, natural polymers, and water.

[0061] A schematic diagram of the process of coaxial printing of component A ink and component B ink is shown below. Figure 1 As shown: Component A ink is injected into the printing device's cartridge A ( Figure 1 As shown in Figure 10), the barrel A is connected to the core layer of the coaxial printing needle 60; component B ink is injected into the barrel B of the printing device. Figure 1 As shown in Figure 20), the cladding of the barrel B and the coaxial printing needle 60 are connected through the connecting tube 30;

[0062] During the coaxial printing process, component A ink is extruded from barrel A through the core layer of the coaxial printing needle to form the fiber core 71, and component B ink is extruded from barrel B through the cladding layer of the coaxial printing needle to form the fiber cladding 72. The extruded material is photocured under the irradiation of light source 40 to obtain the flexible optical fiber 50.

[0063] Example 1

[0064] A flexible optical fiber and its fabrication method, the fabrication method comprising the following steps:

[0065] (1) Provide component A ink: which includes acrylamide, sodium alginate, N,N'-methylenebisacrylamide, photoinitiator (Darocur 1173) and pure water; in component A ink, the mass percentage of acrylamide is 30%, the mass percentage of sodium alginate is 2%; the mass ratio of acrylamide:bisacrylamide:photoinitiator is 100%:1%:0.5%; the preparation method of component A ink is as follows:

[0066] According to the formula, first dissolve sodium alginate in pure water and stir at room temperature for 2 hours until the sodium alginate is completely dissolved. Then dissolve acrylamide in the sodium alginate solution, and then add N,N'-methylenebisacrylamide and photoinitiator. Mix well to obtain component A ink.

[0067] (2) Provide component B ink: which includes calcium chloride, gelatin and pure water; the concentration of calcium ions in component B ink is 0.1 mol / L, and the mass percentage of gelatin is 30%; the preparation method of component B ink is as follows:

[0068] According to the formula, dissolve the gelatin in pure water and stir at 60°C for 2 hours until the gelatin is completely dissolved, forming a pale yellow transparent liquid; dissolve calcium chloride in the above gelatin solution at room temperature and mix well to obtain component B ink;

[0069] (3) Fabrication of flexible optical fiber: Component A ink is drawn into cylinder A of the printing device, the cylinder is sealed and centrifuged to eliminate air bubbles; component B ink is drawn into cylinder B of the printing device; component A ink is extruded from cylinder A through the core layer of the coaxial printing needle, and component B ink is extruded from cylinder B through the cladding layer of the coaxial printing needle for coaxial printing and UV curing (365nm UV light source). The coaxial printing temperature is 50℃, and the volume ratio of component A ink to component B ink during coaxial printing is 85%:15%, resulting in the flexible optical fiber with a diameter of 400μm. A physical image of the flexible optical fiber is shown below. Figure 2 As shown.

[0070] The flexible optical fiber provided in this embodiment is tested using the following method:

[0071] (1) Light guiding effect test

[0072] The flexible optical fiber is inserted into the ferrule, and a blue or red laser transmitter is inserted into it. The laser transmitter is turned on and irradiated with a laser of known intensity. Then, the intensity of the laser transmitted from the other end of the optical fiber is measured with a light intensity meter, thereby calculating the optical conductivity.

[0073] Figure 3 The light guiding effect test diagram of the flexible optical fiber provided in Example 1 is shown below. Figure 3 As can be seen from the above, the flexible optical fiber can effectively transmit the light emitted by the blue laser emitter, has excellent light guiding effect, and has a light guiding rate of over 60%.

[0074] (2) Tensile properties and flexibility

[0075] The tensile modulus of the flexible optical fiber was tested using a universal testing machine. The test results showed that the flexible optical fiber has excellent tensile properties and flexibility.

[0076] The applicant declares that this invention illustrates the flexible optical fiber, its fabrication method, and its applications through the above embodiments. However, this invention is not limited to the above-described process steps, meaning that this invention does not necessarily rely on the above-described process steps to be implemented. Those skilled in the art should understand that any improvements to this invention, equivalent substitutions of the raw materials used in this invention, additions of auxiliary components, and selection of specific methods, etc., all fall within the protection and disclosure scope of this invention.

Claims

1. A method for fabricating a flexible optical fiber, characterized in that, The preparation method includes the following steps: Provide component A ink, said component A ink comprising a combination of acrylamide monomers, sodium alginate, crosslinking agent, photoinitiator and water; A component B ink is provided, the component B ink comprising a combination of calcium salt, natural polymer and water; The flexible optical fiber is obtained by placing the A component ink in the core layer of the coaxial printing needle and the B component ink in the cladding layer of the coaxial printing needle for coaxial printing and photocuring. The natural polymers include gelatin and / or collagen; The B component ink contains 15-40% by mass of natural polymers.

2. The preparation method according to claim 1, characterized in that, The acrylamide monomers include acrylamide, methacrylamide, N -Isopropylacrylamide, N,N -Dimethylacrylamide, N,N - Any one or a combination of at least two of diethylacrylamides.

3. The preparation method according to claim 1, characterized in that, The mass percentage of acrylamide monomers in component A ink is 20-40%.

4. The preparation method according to claim 1, characterized in that, The sodium alginate content in component A ink is 0.5-5% by mass.

5. The preparation method according to claim 4, characterized in that, The sodium alginate content in component A ink is 1-3% by mass.

6. The preparation method according to claim 1, characterized in that, The crosslinking agent is a bisacrylamide crosslinking agent.

7. The preparation method according to claim 1, characterized in that, The crosslinking agent includes N,N' -methylenebisacrylamide, N,N' -Ethylenebisacrylamide, N,N' Any one or a combination of at least two of the following: -(propane-1,3-diyl)diacrylamide.

8. The preparation method according to claim 1, characterized in that, The crosslinking agent comprises 0.1-3% of the acrylamide monomer by mass, which is 100% by mass.

9. The preparation method according to claim 8, characterized in that, The crosslinking agent comprises 0.5-2% of the acrylamide monomer by mass, which is 100% by mass.

10. The preparation method according to claim 1, characterized in that, The photoinitiator includes any one or a combination of at least two of 2-hydroxy-2-methyl-1-phenyl-1-propanone, 2,4,6-trimethylbenzoyl-diphenylphosphine oxide, and 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylpropanone.

11. The preparation method according to claim 1, characterized in that, Based on the mass of the acrylamide monomer being 100%, the mass of the photoinitiator is 0.01-1%.

12. The preparation method according to claim 11, characterized in that, The photoinitiator comprises 0.1-1% of the acrylamide monomer by mass, which is 100% by mass.

13. The preparation method according to claim 1, characterized in that, The calcium salts include calcium chloride and / or calcium nitrate.

14. The preparation method according to claim 1, characterized in that, The concentration of calcium ions in the B component ink is 0.01-0.5 mol / L.

15. The preparation method according to claim 14, characterized in that, The concentration of calcium ions in the B component ink is 0.05-0.3 mol / L.

16. The preparation method according to claim 1, characterized in that, The B component ink contains 20-30% by mass of natural polymers.

17. The preparation method according to claim 1, characterized in that, The ink component A is injected into the ink cartridge A of the printing device, and the ink cartridge A is in communication with the core layer of the coaxial printing needle; the ink component B is injected into the ink cartridge B of the printing device, and the ink cartridge B is in communication with the cladding layer of the coaxial printing needle. The ink component A is extruded from barrel A through the core layer of the coaxial printing needle, and the ink component B is extruded from barrel B through the cladding layer of the coaxial printing needle, thus achieving coaxial printing.

18. The preparation method according to claim 17, characterized in that, In the coaxial printing, the volume ratio of component A ink to component B ink is (4-8):

1.

19. The preparation method according to claim 18, characterized in that, In the coaxial printing, the volume ratio of component A ink to component B ink is (5-6):

1.

20. The preparation method according to claim 17, characterized in that, The temperature for coaxial printing is 40-60℃.

21. The preparation method according to claim 1, characterized in that, The light source for photocuring is an ultraviolet light source.

22. The preparation method according to claim 21, characterized in that, The wavelength of the ultraviolet light source is 350-400nm.

23. The preparation method according to claim 1, characterized in that, The preparation method includes the following steps: The ink comprises component A, which includes acrylamide monomers, sodium alginate, bisacrylamide crosslinking agents, photoinitiators, and water; the mass percentage of acrylamide monomers in component A is 20-40%, and the mass percentage of sodium alginate is 1-3%; the mass ratio of acrylamide monomers, bisacrylamide crosslinking agents, and photoinitiators is 100%:(0.5-2%):(0.1-1%). Provide a component B ink comprising a combination of calcium salt, gelatin and water, wherein the concentration of calcium salt in the component B ink is 0.05-0.3 mol / L and the mass percentage of gelatin is 20-30%; The ink component A is injected into the ink cartridge A of the printing device, and the ink cartridge A is in communication with the core layer of the coaxial printing needle; the ink component B is injected into the ink cartridge B of the printing device, and the ink cartridge B is in communication with the cladding layer of the coaxial printing needle. The A component ink is extruded from barrel A through the core layer of the coaxial printing needle, and the B component ink is extruded from barrel B through the cladding layer of the coaxial printing needle. Coaxial printing and ultraviolet curing are performed to obtain the flexible optical fiber. In the coaxial printing, the volume ratio of component A ink to component B ink is (4-8):1, and the temperature of the coaxial printing is 40-60℃.

24. A flexible optical fiber, characterized in that, The flexible optical fiber is prepared by the preparation method according to any one of claims 1-23.

25. The flexible optical fiber according to claim 24, characterized in that, The diameter of the flexible optical fiber is 100-500 μm.

26. The flexible optical fiber according to claim 25, characterized in that, The diameter of the flexible optical fiber is 200-400 μm.

27. The flexible optical fiber according to claim 24, characterized in that, The optical fiber has a light conductivity of ≥60%.

28. The application of a flexible optical fiber as described in any one of claims 24-27 in an optical fiber implant, a biosensor, or an implantable medical device.

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