High-strength and durable silk fibroin contact lens and preparation method thereof
By forming a three-dimensional reinforcing network with chitosan nanofibers and silk fibroin, and combining it with acrylamide molecules, the problem of insufficient mechanical properties of silk fibroin contact lenses was solved, enabling the fabrication of high-strength and durable contact lenses, and improving lens durability and wearing comfort.
Patent Information
- Application Number
- CN202610457795.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-04-08
- Publication Date
- 2026-06-05
AI Technical Summary
Existing silk fibroin contact lenses have insufficient mechanical properties, making the lenses prone to cracking and plastic deformation, which affects durability and wearing comfort. Existing adjustment methods have not been able to effectively improve the strength and toughness of the material.
By mixing chitosan nanofibers with silk fibroin, a three-dimensional reinforcing network is formed through hydrogen bonding and electrostatic interactions. This network is then combined with acrylamide molecules to construct a nanoscale reinforcing network, thereby improving the mechanical properties of the material.
It significantly improves the tensile strength and elongation at break of silk fibroin contact lenses, maintains transparency and oxygen permeability, enhances lens durability and wearing comfort, and has good biocompatibility.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of corneal contact lens technology, and more particularly to a high-strength and durable silk fibroin contact lens and its preparation method. Background Technology
[0002] In the technological development of contact lens materials, silk fibroin has become an important biomaterial direction to replace traditional synthetic polymer materials (such as polymethyl methacrylate, silicone hydrogel, etc.) due to its excellent biocompatibility, optical transparency and renewable properties derived from natural silk. Related preparation schemes have been disclosed.
[0003] Existing technologies typically use pure silk fibroin solutions to fabricate contact lenses through methods such as casting, molding, or spin casting. While these methods achieve basic optical functions and biocompatibility, their core drawback lies in the insufficient inherent mechanical properties of the material, severely limiting the practicality and durability of the products. Specifically, the gel or solid film network structure formed by pure silk fibroin is relatively homogeneous and lacks an effective reinforcing phase, resulting in low key mechanical properties such as tensile strength, elongation at break, and elastic modulus. In actual use, microcracks, plastic deformation, and even tearing can easily occur due to daily wear, rubbing, or cleaning, making it difficult to maintain the dimensional stability and structural integrity of the lenses over the long term.
[0004] Furthermore, the weak mechanical properties limit the possibilities for lens design, making it impossible to achieve both ultra-thinness and high oxygen permeability while maintaining sufficient mechanical toughness, thus affecting wearing comfort and safety. Existing publicly available solutions attempt to optimize the material by changing the concentration of silk fibroin, the type of cross-linking agent, or processing parameters, but these adjustments offer limited improvements in mechanical properties and come at the cost of sacrificing transparency, oxygen permeability, or biocompatibility, failing to fundamentally solve the problem of insufficient material strength and toughness.
[0005] Therefore, how to provide a high-strength and durable silk fibroin contact lens and its preparation method, while ensuring excellent transparency, oxygen permeability or biocompatibility, and improving the durability and mechanical strength of silk fibroin contact lenses, is an urgent problem to be solved in this field. Summary of the Invention
[0006] In view of this, the present invention provides a high-strength and durable silk fibroin contact lens and its preparation method, so as to solve the problem of poor mechanical properties of existing silk fibroin contact lenses.
[0007] To achieve the above objectives, the present invention adopts the following technical solution: A method for preparing a high-strength and durable silk fibroin contact lens includes the following steps: 1) Degumming is performed on silkworm silk, which is then dissolved in lithium bromide solution to obtain silk fibroin solution; 2) Mix the silk fibroin solution with the chitosan nanofiber solution to obtain a silk fibroin-chitosan nanofiber mixed solution; 3) Mix the silk fibroin-chitosan nanofiber mixed solution with an acrylamide solution to obtain a ternary blend solution; 4) The obtained ternary blend solution is transferred to a contact lens mold and then subjected to gradient air drying to obtain silk fibroin contact lenses.
[0008] Preferably, the degumming process in step 1) includes: placing the silkworm silk in a sodium carbonate solution for degumming; The pH value of the sodium carbonate solution is 10-11; The degumming process is carried out under boiling conditions for 25-35 minutes.
[0009] Preferably, the molar concentration of the lithium bromide solution in step 1) is 9.3 mol / L; The mass concentration of the silk fibroin solution is 5-10%.
[0010] Preferably, in step 2), the mass ratio of chitosan nanofibers in the chitosan nanofiber solution to silk fibroin in the silk fibroin solution is 0.5~3:100; The chitosan nanofiber solution has a mass concentration of 0.5-3%. The chitosan nanofibers have a diameter of 10-50 nm and a length of 0.5-3 μm.
[0011] Preferably, the pH value of the mixture in step 2) is 5.5~6.5, the mixing speed is 300~500 rpm, and the mixing time is 10~24h.
[0012] Preferably, in step 3), the mass ratio of the solute in the silk fibroin-chitosan nanofiber mixed solution to the acrylamide in the acrylamide solution is 100:15~30; The mixing speed is 300~500 rpm, and the mixing time is 40~80 min.
[0013] Preferably, the gradient drying process includes sequential high-humidity drying, dehumidification drying, and low-humidity drying.
[0014] Preferably, the high-humidity air drying treatment is performed at room temperature, with a relative humidity of 70-75%, for a duration of 6-12 hours. The temperature of the dehumidification and air-drying treatment is 25~30℃, the relative humidity decreases linearly, the endpoint of the relative humidity decrease is 35~40%, and the time is 6~7 hours; The low-humidity air-drying treatment is carried out under dry conditions, at a temperature of 25~30℃, for a time of 12~48h.
[0015] Another object of the present invention is to provide a high-strength and durable silk fibroin contact lens prepared by the above preparation method.
[0016] This invention primarily utilizes the excellent mechanical properties of chitosan nanofibers and their multiple, synergistic interfacial interactions with silk fibroin molecules to construct a three-dimensional interpenetrating reinforcement network with acrylamide molecules, thereby achieving fundamental material strengthening at the nanoscale.
[0017] As can be seen from the above technical solution, compared with the prior art, the present invention has the following beneficial effects: 1. The chitosan nanofibers added in this invention can generate interfacial interactions with silk fibroin, including hydrogen bonding and electrostatic interactions. The hydroxyl, amino, and carbon-oxygen double bond groups of silk fibroin can form a dense hydrogen bond network with the hydroxyl and amino groups in chitosan. Furthermore, the positively charged amino groups in the chitosan nanofibers can also form electrostatic interactions with the negatively charged amino acid residues in the silk fibroin, further enhancing the binding force between the chitosan nanofibers and silk fibroin. Based on these interactions, when subjected to force, stress can be efficiently transferred from the silk fibroin to the rigid chitosan nanofibers, thereby increasing the mechanical properties of contact lenses.
[0018] 2. Chitosan nanofibers possess a regular molecular chain structure and abundant functional groups on their surface, which may serve as additional and effective heterogeneous nucleation sites. This can guide silk fibroin molecules to accumulate more orderly and rapidly on their surface, forming β-sheet crystals, and synergistically induce crystallization with acrylamide through blending. The dual induction by chitosan nanofibers and acrylamide contributes to a more uniform crystal size distribution, thereby achieving superior mechanical properties. Detailed Implementation
[0019] This invention provides a method for preparing high-strength and durable silk fibroin contact lenses, comprising the following steps: 1) Degumming is performed on silkworm silk, which is then dissolved in lithium bromide solution to obtain silk fibroin solution; 2) Mix the silk fibroin solution with the chitosan nanofiber solution to obtain a silk fibroin-chitosan nanofiber mixed solution; 3) Mix the silk fibroin-chitosan nanofiber mixed solution with an acrylamide solution to obtain a ternary blend solution; 4) The obtained ternary blend solution is transferred to a contact lens mold and then subjected to gradient air drying to obtain silk fibroin contact lenses.
[0020] In this invention, the degumming process in step 1) includes: placing the silkworm silk in a sodium carbonate solution for degumming; the pH value of the sodium carbonate solution is 10~11, specifically 10.2, 10.4, 10.5, 10.6, or 10.8; the pH value of the system will decrease after mixing with the silkworm silk.
[0021] In this invention, the degumming process is carried out under boiling conditions, and the degumming time is 25-35 minutes, specifically 26 minutes, 28 minutes, 30 minutes, 32 minutes, or 34 minutes.
[0022] In this invention, the molar concentration of the lithium bromide solution in step 1) is 9.3 mol / L.
[0023] In this invention, the mass concentration of the silk fibroin solution is 5-10%, specifically 6%, 7%, 8%, or 9%.
[0024] In this invention, the mass ratio of chitosan nanofibers in the chitosan nanofiber solution to silk fibroin in the silk fibroin solution in step 2) is 0.5~3:100, preferably 0.8~2.5:100, more preferably 1~2:100, and even more preferably 1.5:100.
[0025] In this invention, the mass concentration of the chitosan nanofiber solution is 0.5-3%, specifically 0.6%, 0.8%, 1%, 1.2%, 1.5%, 1.8%, 2%, 2.2%, 2.5%, and 2.8%; wherein the diameter of the chitosan nanofibers is 10-50 nm, specifically 15 nm, 20 nm, 25 nm, 30 nm, 35 nm, 40 nm, and 45 nm; and the length is 0.5-3 μm, specifically 0.6 μm, 0.8 μm, 1 μm, 1.2 μm, 1.5 μm, 1.8 μm, 2 μm, 2.2 μm, 2.5 μm, and 2.8 μm. The chitosan nanofibers of the particle size described in this invention have a high specific surface area and a suitable length, which can generate maximum interfacial interactions (hydrogen bonds, electrostatic interactions) with the silk fibroin matrix, entangle with each other, form an effective three-dimensional reinforcing network, and improve mechanical properties. In addition, the diameter of the chitosan nanofibers is much smaller than the wavelength of visible light, which can avoid light scattering and maintain the high transparency of the lens. During the research, it was found that when the diameter is greater than 100 nm, the lens haze will increase significantly.
[0026] In this invention, the pH value of the mixture in step 2) is 5.5~6.5, specifically 5.6, 5.8, 6, 6.2, or 6.4; the mixing speed is 300~500 rpm, specifically 320 rpm, 350 rpm, 380 rpm, 400 rpm, 420 rpm, 450 rpm, or 480 rpm; and the mixing time is 10~24 h, specifically 12 h, 15 h, 18 h, or 20 h. At the pH value specified in this invention, chitosan remains partially protonated, and silk fibroin is also charged, which is beneficial for their binding.
[0027] In this invention, the mass ratio of the solute in the silk fibroin-chitosan nanofiber mixed solution to the acrylamide in the acrylamide solution in step 3) is 100:15~30, preferably 100:20~25, and more preferably 100:22.
[0028] In this invention, the mixing speed is 300~500 rpm, specifically 350 rpm, 400 rpm, or 450 rpm; the mixing time is 40~80 min, specifically 50 min, 60 min, or 70 min.
[0029] In this invention, the gradient drying process includes sequential high-humidity drying, dehumidification drying, and low-humidity drying.
[0030] In this invention, the high-humidity air-drying treatment is performed at room temperature with a relative humidity of 70-75%, specifically 71%, 72%, 73%, or 74%; the time is 6-12 hours, specifically 7 hours, 9 hours, 8 hours, 10 hours, or 11 hours. This process allows moisture to be slowly removed, preventing rapid shrinkage that could lead to internal stress and macroscopic cracks.
[0031] In this invention, the temperature for the dehumidification and air-drying treatment is 25~30℃, specifically 26℃, 27℃, 28℃, and 29℃; the relative humidity decreases linearly, with the endpoint of the relative humidity decrease being 35~40%, specifically 36%, 37%, 38%, and 39%; the time is 6~7 hours, specifically 6.2 hours, 6.4 hours, 6.5 hours, 6.6 hours, and 6.8 hours. This process induces β-lamellae crystallization. Before air-drying, silk fibroin and acrylamide can form a physically entangled nanofiber network with chitosan nanofibers. Silk fibroin is wrapped around the surface of chitosan nanofibers. During the air-drying process, the shrinkage of the silk fibroin matrix further "locks" this composite network, making the structure denser, reducing defects, and effectively preventing the generation and propagation of cracks.
[0032] In this invention, the low-humidity air-drying treatment is carried out under dry conditions at a temperature of 25~30℃, specifically 26℃, 27℃, 28℃, or 29℃; and for a time of 12~48h, specifically 18h, 24h, 30h, or 36h. This process densifies the lens, reduces light scattering, and makes the lens completely transparent or translucent.
[0033] The present invention also provides a high-strength and durable silk fibroin contact lens prepared by the above preparation method.
[0034] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0035] Example 1
[0036] Silkworm silk was placed in a sodium carbonate solution with a pH of 10, and the solution was heated to boiling and maintained for 30 minutes to degummify the silkworm silk. Then, the treated silkworm silk was dissolved in a 9.3M lithium bromide solution, and after dialysis (with a molecular weight cutoff of 10,000 Daltons) and concentration, a 10% (w / w) silk fibroin solution was obtained.
[0037] A chitosan nanofiber solution with a mass concentration of 1.5% (30 nm in diameter and 1.5 μm in length) was prepared. Then, the silk fibroin solution and the chitosan nanofiber solution were mixed at a mass ratio of chitosan nanofiber to silk fibroin of 1.5:100. The pH was adjusted to 6, and the mixture was stirred at 300 rpm for 12 h to form a pre-binding between the silk fibroin and the chitosan nanofiber.
[0038] The above mixed solution was then mixed with an acrylamide solution (mass concentration of 15%, mass ratio of acrylamide to solute in the mixed solution of 15:100) to obtain a ternary blend. The ternary blend was dropwise added to a contact lens mold, the humidity was adjusted to 75%, and it was air-dried for 8 hours. Then, the temperature was slightly increased to 28°C, and the humidity was linearly reduced, dropping to 40% after 6 hours. The above temperature was maintained, and it was air-dried for another 12 hours in a desiccant environment to obtain silk fibroin contact lenses. The lenses were then repeatedly rinsed with sterile water and physiological saline to remove unbound monomers. The final silk fibroin contact lenses were stored in sterile physiological saline for later use.
[0039] Example 2
[0040] The only difference between this embodiment and Example 1 is that the mass concentration of the chitosan nanofiber solution is adjusted to 0.5%, and the mass ratio of chitosan nanofiber to silk fibroin is 0.5:100.
[0041] Example 3
[0042] The only difference between this embodiment and Example 1 is that the mass concentration of the chitosan nanofiber solution is adjusted to 3%, and the mass ratio of chitosan nanofiber to silk fibroin is 3:100.
[0043] Example 4
[0044] Silkworm silk was placed in a sodium carbonate solution with a pH of 11, and the solution was heated to boiling and maintained for 25 minutes to degummify the silkworm silk. Then, the treated silkworm silk was dissolved in a 9.3M lithium bromide solution, and after dialysis (with a molecular weight cutoff of 10,000 Daltons) and concentration, a 10% (w / w) silk fibroin solution was obtained.
[0045] A chitosan nanofiber solution with a mass concentration of 1.5% (40 nm in diameter and 3 μm in length) was prepared. Then, the silk fibroin solution and the chitosan nanofiber solution were mixed at a mass ratio of chitosan nanofiber to silk fibroin of 1.5:100. The pH was adjusted to 5.5, and the mixture was stirred at 300 rpm for 18 h to form a pre-binding between the silk fibroin and the chitosan nanofiber.
[0046] The above mixed solution was then mixed with an acrylamide solution (mass concentration of 20%, mass ratio of acrylamide to solute in the mixed solution of 20:100) to obtain a ternary blend. The ternary blend was dropwise added to a contact lens mold, the humidity was adjusted to 70%, and it was air-dried for 7 hours. Then, the temperature was slightly increased to 26°C, and the humidity was linearly reduced, dropping to 35% after 7 hours. The above temperature was maintained, and it was air-dried for another 24 hours in a desiccant environment to obtain silk fibroin contact lenses. The lenses were then repeatedly rinsed with sterile water and physiological saline to remove unbound monomers. The final silk fibroin contact lenses were stored in sterile physiological saline for later use.
[0047] Example 5
[0048] Silkworm silk was placed in a sodium carbonate solution with a pH of 10, and the solution was heated to boiling and maintained for 35 minutes to degummify the silkworm silk. Then, the treated silkworm silk was dissolved in a 9.3M lithium bromide solution, and after dialysis (with a molecular weight cutoff of 10,000 Daltons) and concentration, a silk fibroin solution with a mass concentration of 5% was obtained.
[0049] A chitosan nanofiber solution with a mass concentration of 1.5% (diameter 20 nm, length 1.5 μm) was prepared. Then, the silk fibroin solution and the chitosan nanofiber solution were mixed at a mass ratio of chitosan nanofiber to silk fibroin of 1.5:100. The pH was adjusted to 6, and the mixture was stirred at 400 rpm for 10 h to form a pre-binding between silk fibroin and chitosan nanofiber.
[0050] The above mixed solution was then mixed with an acrylamide solution (mass concentration of 30%, mass ratio of acrylamide to solute in the mixed solution of 30:100) to obtain a ternary blend. The ternary blend was dropped into a contact lens mold, the humidity was adjusted to 75%, and it was air-dried for 12 hours. Then, the temperature was slightly increased to 28°C, and the humidity was linearly reduced, dropping to 40% after 7 hours. The above temperature was maintained, and it was air-dried for another 12 hours in a desiccant environment to obtain silk fibroin contact lenses. The lenses were then repeatedly rinsed with sterile water and physiological saline to remove unbound monomers. The final silk fibroin contact lenses were stored in sterile physiological saline for later use.
[0051] Comparative Example 1
[0052] The only difference between this comparative example and Example 1 is that chitosan nanofiber solution is not added; Specifically, a 10% (w / w) silk fibroin solution is directly mixed with an acrylamide solution to prepare silk fibroin contact lenses.
[0053] Comparative Example 2
[0054] The air-drying step in Example 1 was adjusted to be air-dried directly at room temperature and 40% humidity to obtain silk fibroin contact lenses.
[0055] Experimental Example 1
[0056] The relevant performance tests of the silk fibroin contact lenses prepared in Examples 1-3 and Comparative Examples 1-2 of this invention are shown in Table 1: Tensile breaking strength: GB / T1040-2006, Instrong 3365 universal testing machine; Transmittance: Ultraviolet-Visible absorption spectroscopy.
[0057] Table 1 Relevant performance test results
[0058] As shown in Table 1, the silk fibroin contact lenses prepared by this invention exhibit excellent tensile strength, meeting the durability requirements of long-cycle replacement lenses. They also facilitate the design of ultra-thin lenses, improving wearing comfort and reducing foreign body sensation. Their light transmittance also meets relevant product requirements, without becoming excessively low due to improved mechanical properties. Comparative Example 1, without the addition of chitosan nanofiber solution, did not form an interaction between silk fibroin and chitosan nanofibers, resulting in contact lenses with significantly lower tensile strength than those prepared by this invention. Comparative Example 2 did not employ the air-drying method described in this invention. This invention, by controlling the slow decrease in humidity, ensures a uniform crystallization process from the outside in, improving crystal uniformity and optimizing mechanical properties.
[0059] The contact lenses from Examples 1-3 were worn for 30 days under simulated conditions, and their tensile strength was tested again (44.11 MPa, 41.34 MPa, and 44.98 MPa, respectively). The tensile strength retention rate remained above 75% for all three examples. Furthermore, the cytotoxicity of the silk fibroin contact lenses prepared in Examples 1-3 was tested using the CCK-8 assay. The cell survival rate was greater than 95% for all three examples, indicating that the contact lenses prepared according to this invention have good biocompatibility. Additionally, due to the addition of chitosan nanofibers, they also possess antibacterial potential.
[0060] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.
[0061] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims
1. A method for preparing a high-strength and durable silk fibroin contact lens, characterized in that, Includes the following steps: 1) Degumming is performed on silkworm silk, which is then dissolved in lithium bromide solution to obtain silk fibroin solution; 2) Mix the silk fibroin solution with the chitosan nanofiber solution to obtain a silk fibroin-chitosan nanofiber mixed solution; 3) Mix the silk fibroin-chitosan nanofiber mixed solution with an acrylamide solution to obtain a ternary blend solution; 4) The obtained ternary blend solution is transferred to a contact lens mold and then subjected to gradient air drying to obtain silk fibroin contact lenses.
2. The method for preparing a high-strength and durable silk fibroin contact lens according to claim 1, characterized in that, The degumming process described in step 1) includes: placing the silkworm silk in a sodium carbonate solution for degumming; The pH value of the sodium carbonate solution is 10-11; The degumming process is carried out under boiling conditions for 25-35 minutes.
3. The method for preparing a high-strength and durable silk fibroin contact lens according to claim 2, characterized in that, The molar concentration of the lithium bromide solution mentioned in step 1) is 9.3 mol / L; The mass concentration of the silk fibroin solution is 5-10%.
4. A method for preparing a high-strength and durable silk fibroin contact lens according to any one of claims 1 to 3, characterized in that, In step 2), the mass ratio of chitosan nanofibers in the chitosan nanofiber solution to silk fibroin in the silk fibroin solution is 0.5~3:
100. The chitosan nanofiber solution has a mass concentration of 0.5-3%. The chitosan nanofibers have a diameter of 10-50 nm and a length of 0.5-3 μm.
5. The method for preparing a high-strength and durable silk fibroin contact lens according to claim 4, characterized in that, In step 2), the pH value of the mixture is 5.5-6.5, the mixing speed is 300-500 rpm, and the mixing time is 10-24 h.
6. The method for preparing a high-strength and durable silk fibroin contact lens according to claim 5, characterized in that, In step 3), the mass ratio of the solute in the silk fibroin-chitosan nanofiber mixed solution to the acrylamide in the acrylamide solution is 100:15~30. The mixing speed is 300~500 rpm, and the mixing time is 40~80 min.
7. A method for preparing a high-strength and durable silk fibroin contact lens according to claim 5 or 6, characterized in that, The gradient air-drying process includes sequential high-humidity air-drying, dehumidification air-drying, and low-humidity air-drying.
8. The method for preparing a high-strength and durable silk fibroin contact lens according to claim 7, characterized in that, The high-humidity air-drying treatment is performed at room temperature, with a relative humidity of 70-75%, for a duration of 6-12 hours. The temperature of the dehumidification and air-drying treatment is 25~30℃, the relative humidity decreases linearly, the endpoint of the relative humidity decrease is 35~40%, and the time is 6~7 hours; The low-humidity air-drying treatment is carried out under dry conditions, at a temperature of 25~30℃, for a time of 12~48h.
9. High-strength and durable silk fibroin contact lenses prepared by the preparation method according to any one of claims 1 to 8.