Biocompatible hydrogel composition for biomedical applications

Abstract

A biocompatible hydrogel composition for use in biomedical applications is disclosed. The composition comprises a silk fibroin-based hydrogel, a crosslinkable compound, a photoinitiator, and upconversion nanoparticles. The silk fibroin-based hydrogel is configured to form filaments and a scaffold in vivo upon exposure to ultraviolet light triggered by near-infrared light. The composition is particularly useful in the treatment of stress urinary incontinence, where it is injected into a patient's urethral tissue (14) and exposed to near-infrared light to trigger ultraviolet light emission from the upconversion nanoparticles, thereby initiating crosslinking of the silk fibroin-based hydrogel.

Description

[0001] BIOCOMPATIBLE HYDROGEL COMPOSITION FOR BIOMEDICAL APPLICATIONS

[0002] Background

[0003] Stress urinary incontinence (SUI) is a prevalent health issue affecting a considerable number of individuals worldwide. It is characterized by the involuntary leakage of urine due to increased intra- abdominal pressure, which can occur during physical exertion, coughing, or sneezing. This condition is often associated with sphincter dysfunction and hypermobility resulting from insufficient support of the urethral tissues.

[0004] Various techniques have been employed to manage SUI, including the use of urethral bulking agents, autologous fascial slings, colposuspension, and mid-urethral polypropylene slings. Urethral bulking agents are substances that can be injected or implanted into the tissues surrounding the urethra to increase its volume and improve the closure mechanism, thereby reducing urinary leakage. However, the effectiveness of these agents is often limited as they do not correct the underlying urethral support mechanisms but rather facilitate urethral closure through mass effect alone.

[0005] Mid-urethral sling procedures involve the placement of a synthetic mesh in a position and tension around the urethra using minimally invasive techniques. These procedures aim to provide support by creating fibrosis and promoting regeneration under the urethra, increasing urethral closure pressure, and limiting urethral mobility. Despite their success, the use of synthetic, non-biodegradable polypropylene mesh has been associated with complications such as pain and mesh erosion, leading to concerns about their safety.

[0006] Silk fibroin, a protein derived from the silk of the Bombyx mori silkworm, has been recognized for its biocompatibility, strength, and slow degradation properties, making it an attractive candidate for biomedical applications. Silk fibroin can self-assemble to form strong and durable materials, with its strength surpassing that of commonly used polymer-based biomaterials. The fibroin structure is dominated by P-sheet regions, which provide protein-based materials with high mechanical strength and resilience.

[0007] Photoinitiators are compounds that convert absorbed light energy into chemical energy in the form of initiating species, typically free radicals or cations. These compounds can be activated by radiation to initiate a crosslinking reaction. Upconversion nanoparticles are a class of materials with photoluminescent properties that can convert low-energy nearinfrared (NIR) light into visible and UV photons through the sequential absorption of two or more photons. NIR light excitation has the ability to deeply penetrate biological tissues and progress to live cells without causing photo-damage, making it a promising technology for biomedical applications.

[0008] Summary of Invention

[0009] In general, in a first aspect, the present disclosure features a biocompatible hydrogel composition for use in biomedical applications. The composition comprises a silk fibroin- based hydrogel, a crosslinkable compound, a photoinitiator, and upconversion nanoparticles. The silk fibroin-based hydrogel is configured to form filaments and a scaffold in vivo upon exposure to ultraviolet light triggered by near-infrared light.

[0010] Embodiments of the disclosure may include one or more of the following features. The silk fibroin-based hydrogel may be derived from Bombyx mori silkworm fibers. The crosslinkable compound may include methacrylate. The upconversion nanoparticles may be lanthanide-doped upconversion nanoparticles. The photoinitiator may be selected from a group consisting of benzophenones, anthraquinones, benzoins, acetophenones, and phosphate and antimonate salts.

[0011] In another aspect, the disclosure features a method for treating stress urinary incontinence. The method comprises injecting the biocompatible hydrogel composition into a patient's urethral tissue and exposing the injected hydrogel composition to nearinfrared light to trigger ultraviolet light emission from the upconversion nanoparticles, thereby initiating crosslinking of the silk fibroin-based hydrogel. Embodiments of the method may include one or more of the following features. The injecting step may be performed using a needle or a cystoscope. The method may further comprise the step of inserting a vaginal support device into the patient's vagina prior to the injecting step, wherein the vaginal support device is designed to maintain the pubourethral ligament in an anatomically positioned state during the exposure to nearinfrared light. The vaginal support device may include a concave section designed to support the urethra from below and C-shaped arms designed to provide support along the pubourethral ligament.

[0012] In yet another aspect, the disclosure features a system for treatment of stress incontinence. The system comprises a vaginal support device, two syringes with the hydrogel composition, hypodermic needles, and a near-infrared light source. The vaginal support device may be inserted into the vagina and pushes the anterior vaginal wall, together with the urethra and bladder neck, towards the symphysis pubis. The vaginal support device may be made of any material determined to be suitable for contact with biocompatible body fluids or tissues.

[0013] Brief Description of Figures

[0014] Figure 1A-E illustrate exemplary chemical structures of hydrogel-forming materials, photoinitiator and upconverting nanoparticles that can be used in compositions of the present invention.

[0015] Figure 2A-C depict the bladder, bladder neck, and urethra, showing the application of the bulking agent using a needle, as well as the initiation of cross-linking through near infrared laser light.

[0016] Figure 3A-C present a side view of a tissue structure with an enlarged urethral lumen surrounded by muscle tissue and wall, before and after the application of the bulking agent and the initiation of cross-linking.

[0017] Figure 4A-C illustrate the urethra, pubourethral ligament, symphysis pubis and vagina, showing the application of the mesh forming agent using a needle, as well as the initiation of cross-linking through near infrared laser light. Figure 5A-B depict the urethra, pubourethral ligament, symphysis pubis bladder and vagina, showing the application of the mesh forming agent using a vaginal device, as well as the initiation of cross-linking through near infrared laser light.

[0018] Figure 6 presents parts of a vaginal pubourethral support device used for laser light application.

[0019] Figure 7 provides a schematic plan view of a needle and syringe assembly in accordance with the present invention.

[0020] The reference numbers in the figures are as follows:

[0021] 10. Urethra

[0022] 12. Tissue

[0023] 14. Periurethral tissues

[0024] 20. Wall

[0025] 30. Enlarged lumen

[0026] 40. Muscle tissue

[0027] 50. Pubourethral ligament

[0028] 52. Vagina

[0029] 60. Bladder

[0030] 62. Bladder neck

[0031] 70. Symphysis pubis

[0032] 80. Needle

[0033] 90. Bulking agent

[0034] 110. Cystoscope 112. Working channel

[0035] 120. Injection device

[0036] 122. Syringe

[0037] 124. Luer hub

[0038] 126. Protecting cap

[0039] 128. Plunger

[0040] 130. Vaginal support device

[0041] 132. C-shaped structure

[0042] 134. Arms

[0043] 136. Wider concave portion

[0044] 138. Convex arms

[0045] 140. Gap

[0046] 142. Infrared light source

[0047] Detailed Description

[0048] The present disclosure introduces a biocompatible hydrogel composition designed for use in various biomedical applications. This composition comprises a silk fibroin-based hydrogel, a crosslinkable compound, a photoinitiator, and upconversion nanoparticles. The silk fibroin-based hydrogel is configured to form filaments and a scaffold in vivo upon exposure to ultraviolet light triggered by near-infrared light.

[0049] In some cases, the silk fibroin-based hydrogel is derived from Bombyx mori silkworm fibers. Silk fibroin, a protein derived from the silk of the Bombyx mori silkworm, is recognized for its biocompatibility, strength, and slow degradation properties, making it an attractive candidate for biomedical applications. Silk fibroin can self-assemble to form strong and durable materials, with its strength surpassing that of commonly used polymer-based biomaterials. The fibroin structure is dominated by P-sheet regions, which provide protein-based materials with high mechanical strength and resilience.

[0050] The crosslinkable compound included in the composition may comprise methacrylate. This compound is capable of crosslinking, which includes small molecules, oligomers, or polymers. The crosslinkable compound contains two or more groups that are capable of crosslinking, providing a defined and limited number of reactive sites.

[0051] The composition also includes upconversion nanoparticles, which may be lanthanide- doped upconversion nanoparticles. Upconversion nanoparticles are a class of materials with photoluminescent properties that can convert low-energy near-infrared (NIR) light into visible and UV photons through the sequential absorption of two or more photons. NIR light excitation has the ability to deeply penetrate biological tissues (12) and progress to live cells without causing photo-damage, making it a promising technology for biomedical applications.

[0052] The photoinitiator included in the composition may be selected from a group consisting of benzophenones, anthraquinones, benzoins, acetophenones, and phosphate and antimonate salts. Photoinitiators are compounds that convert absorbed light energy into chemical energy in the form of initiating species, typically free radicals or cations. These compounds can be activated by radiation to initiate a crosslinking reaction.

[0053] The silk fibroin-based hydrogel is a central component of the disclosed composition. Silk fibroin is a protein that is primarily derived from the silk of the Bombyx mori silkworm. This protein is recognized for its biocompatibility, strength, and slow degradation properties, making it an attractive candidate for biomedical applications. Silk fibroin can self-assemble to form strong and durable materials, with its strength surpassing that of commonly used polymer-based biomaterials. The fibroin structure is dominated by P- sheet regions, which provide protein-based materials with high mechanical strength and resilience.

[0054] In some cases, the silk fibroin in the hydrogel is derived from a variety of sources. While Bombyx mori silkworm fibers are a common source, other sources can also be utilized. These may include other types of silkworms, spiders, genetically engineered cells, transgenic plants and animals, and cultured cells. Additionally, native silk, cloned full or partial sequences of native silk genes, and synthetic genes encoding silk or silk-like sequences can also serve as sources of silk fibroin. This flexibility in the source of silk fibroin allows for the customization of the hydrogel composition based on specific requirements and preferences.

[0055] The silk fibroin-based hydrogel is configured to form filaments and a scaffold in vivo upon exposure to ultraviolet light triggered by near-infrared light. This property is particularly advantageous in biomedical applications where the formation of a supportive structure (132) within the body is desired. The ability of the hydrogel to form filaments and a scaffold in vivo can facilitate tissue (12) regeneration and repair, making it a valuable tool in the treatment of various medical conditions.

[0056] The hydrogel composition includes a crosslinkable compound, which in some cases, may comprise methacrylate. This compound is capable of crosslinking, which includes small molecules, oligomers, or polymers. The crosslinkable compound contains two or more groups that are capable of crosslinking, providing a defined and limited number of reactive sites. This feature is particularly advantageous as it allows for the formation of a network structure within the hydrogel, thereby enhancing its mechanical strength and stability.

[0057] Methacrylate, as a crosslinkable compound, plays a pivotal role in the hydrogel composition. It is a type of acrylate compound that contains a methacryloyl group, which is a reactive group capable of undergoing polymerization. Upon exposure to a suitable initiator, such as a photoinitiator, the methacryloyl groups can react with each other to form covalent bonds, leading to the formation of a crosslinked network structure within the hydrogel. This crosslinked network structure contributes to the mechanical strength and stability of the hydrogel, making it suitable for use in various biomedical applications.

[0058] In some cases, the crosslinkable compound may include other types of acrylate compounds in addition to or instead of methacrylate. These may include acrylate compounds that contain different types of reactive groups, such as acryloyl groups, vinyl groups, or allyl groups. The choice of the crosslinkable compound can be tailored based on specific requirements and preferences, allowing for the customization of the hydrogel composition.

[0059] The hydrogel composition of the present disclosure incorporates upconversion nanoparticles, which play a pivotal role in the crosslinking process of the silk fibroin- based hydrogel. Upconversion nanoparticles are a class of materials with photoluminescent properties that can convert low-energy near-infrared (NIR) light into visible and UV photons through the sequential absorption of two or more photons. This property is particularly advantageous in biomedical applications where deep tissue (12) penetration is desired without causing photo-damage. NIR light excitation has the ability to deeply penetrate biological tissues (12) and progress to live cells without causing photo-damage, making it a promising technology for biomedical applications.

[0060] In some cases, the upconversion nanoparticles used in the hydrogel composition are lanthanide-doped upconversion nanoparticles. Lanthanide-doped upconversion nanoparticles are a specific type of upconversion nanoparticles that incorporate lanthanide ions. These ions, when excited by NIR light, can emit light at shorter wavelengths, including UV light. This UV light emission is particularly useful in the context of the present disclosure, as it can trigger the crosslinking of the silk fibroin- based hydrogel.

[0061] Upon exposure to NIR light, the lanthanide-doped upconversion nanoparticles in the hydrogel composition emit UV light. This UV light can initiate the crosslinking of the silk fibroin-based hydrogel, leading to the formation of a crosslinked network structure within the hydrogel. This crosslinked network structure contributes to the mechanical strength and stability of the hydrogel, making it suitable for use in various biomedical applications, including the treatment of stress urinary incontinence.

[0062] It is worth noting that while lanthanide-doped upconversion nanoparticles are used in the described composition, other types of upconversion nanoparticles may also be utilized based on specific requirements and preferences. The choice of upconversion nanoparticles can be tailored to achieve desired properties, such as the wavelength of emitted light, the efficiency of upconversion, and the biocompatibility of the nanoparticles.

[0063] The hydrogel composition of the present disclosure incorporates a photoinitiator, which plays a pivotal role in the crosslinking process of the silk fibroin-based hydrogel. Photoinitiators are compounds that convert absorbed light energy into chemical energy in the form of initiating species, typically free radicals or cations. These compounds can be activated by radiation to initiate a crosslinking reaction. In the context of the present disclosure, the photoinitiator is activated by the ultraviolet light emitted by the upconversion nanoparticles upon exposure to near-infrared light. This activation triggers the crosslinking of the silk fibroin-based hydrogel, leading to the formation of a crosslinked network structure within the hydrogel. This crosslinked network structure contributes to the mechanical strength and stability of the hydrogel, making it suitable for use in various biomedical applications.

[0064] In some cases, the photoinitiator used in the hydrogel composition may be selected from a group consisting of benzophenones, anthraquinones, benzoins, acetophenones, and phosphate and antimonate salts. These compounds are known for their ability to absorb light and initiate polymerization reactions. The choice of the photoinitiator can be tailored based on specific requirements and preferences, such as the desired wavelength of light for activation, the efficiency of the initiation of the crosslinking reaction, and the biocompatibility of the photoinitiator.

[0065] For instance, benzophenones and anthraquinones are aromatic ketones that can absorb ultraviolet light and generate free radicals, initiating the crosslinking reaction. Benzoins and acetophenones, on the other hand, are alpha-hydroxy ketones that can also absorb ultraviolet light and generate free radicals, but they do so through a different mechanism. Phosphate and antimonate salts are examples of inorganic photoinitiators that can absorb light and generate cations, initiating a cationic polymerization reaction. The selection of the photoinitiator can be made based on the specific requirements of the application, such as the desired speed of the crosslinking reaction, the depth of penetration of the light, and the biocompatibility of the photoinitiator. In some cases, the method for treating stress urinary incontinence involves injecting the biocompatible hydrogel composition into a patient's urethral tissue (14). This procedure can be performed using a needle (80) or a cystoscope (110), depending on the specific requirements and preferences. The needle (80) or cystoscope (110) is used to accurately deliver the hydrogel composition to the desired location within the urethral tissue (14). This precise delivery is particularly advantageous as it allows for the targeted treatment of the affected area, thereby enhancing the effectiveness of the treatment.

[0066] Following the injection of the hydrogel composition, the injected hydrogel composition is exposed to near-infrared light. This exposure triggers ultraviolet light emission from the upconversion nanoparticles present in the hydrogel composition. The emitted ultraviolet light initiates the crosslinking of the silk fibroin-based hydrogel. This crosslinking process results in the formation of a crosslinked network structure within the hydrogel, thereby enhancing its mechanical strength and stability. This enhanced strength and stability contribute to the effectiveness of the hydrogel composition in treating stress urinary incontinence.

[0067] In some cases, the injecting step is performed using a needle (80). The needle (80) is used to puncture the urethral tissue (14) and deliver the hydrogel composition to the desired location. This method allows for a direct and precise delivery of the hydrogel composition, thereby enhancing the effectiveness of the treatment.

[0068] In other cases, the injecting step is performed using a cystoscope (110). The cystoscope (110) is a medical device that is inserted into the urethra (10) to allow for the visual examination of the urethral tissue (14). The cystoscope (110) can also be used to deliver the hydrogel composition to the desired location within the urethral tissue (14). This method allows for a more controlled and accurate delivery of the hydrogel composition, thereby enhancing the effectiveness of the treatment.

[0069] In the method for treating stress urinary incontinence, a pivotal step involves the injection of the biocompatible hydrogel composition into a patient's urethral tissue (14). This procedure can be performed using a needle (80) or a cystoscope (110), depending on the specific requirements and preferences. The needle (80) or cystoscope (110) is used to accurately deliver the hydrogel composition to the desired location within the urethral tissue (14). This precise delivery is particularly advantageous as it allows for the targeted treatment of the affected area, thereby enhancing the effectiveness of the treatment.

[0070] In some cases, the injecting step is performed using a needle (80). The needle (80) is used to puncture the urethral tissue (14) and deliver the hydrogel composition to the desired location. This method allows for a direct and precise delivery of the hydrogel composition, thereby enhancing the effectiveness of the treatment. The needle (80) can be of various sizes, ranging from about 16 gauge to about 24 gauge, and can be attached to a syringe (122) or other injection device (120) containing the bulking agent (90) or mesh forming hydrogel. The needle (80) is then inserted into the tissue (12), and the hydrogel is injected into the desired location.

[0071] In other cases, the injecting step is performed using a cystoscope (110). The cystoscope (110) is a medical device that is inserted into the urethra (10) to allow for the visual examination of the urethral tissue (14). The cystoscope (110) can also be used to deliver the hydrogel composition to the desired location within the urethral tissue (14). This method allows for a more controlled and accurate delivery of the hydrogel composition, thereby enhancing the effectiveness of the treatment. The cystoscope (110)-assisted injection method is generally the preferred approach when operating on male patients, particularly for the area surrounding the urethra (10). Likewise, it is also the preferred method for female patients when addressing the area surrounding the ureter. The working channel (112) is integral to the versatility of cystoscope (110), enabling them to be used for interventions such as injection, cutting or punch. The size of the working channel (112) can vary depending on the specific design of the scope and the intended use.

[0072] In some cases, the method for treating stress urinary incontinence involves an additional step prior to the injection of the biocompatible hydrogel composition. This step involves the insertion of a vaginal support device (130) into the patient's vagina (52). The vaginal support device is designed to maintain the pubourethral ligament (50) in an anatomically positioned state during the exposure to near-infrared light. The vaginal support device (130) can be made of any material determined to be suitable for contact with biocompatible body fluids or tissues (12). In some cases, the vaginal support device (130) may be made from a variety of materials such as metal or plastic. The choice of material is dependent on specific requirements and preferences.

[0073] The vaginal support device (130) includes a concave section (136) designed to support the urethra (10) from below and C-shaped arms (134) designed to provide support along the pubourethral ligament (50). The wider concave portion (136) rests on the posterior vaginal wall (20), and the pushing force created by the convex arms (138) pushes the anterior vaginal wall (20) towards the symphysis pubis (70), allowing the pubourethral ligament (50) to remain in an anatomically positioned state during laser application, resulting in crosslinking.

[0074] The gap (140) in the middle of the C-shaped pubourethral support structure (132) allows contact with the vaginal anterior wall (20) by the laser application device. This design facilitates the application of near-infrared light to the vaginal tissue (12), which is a pivotal step in the crosslinking process of the silk fibroin-based hydrogel.

[0075] Following the insertion of the vaginal support device (130), the biocompatible hydrogel composition is injected into the patient's urethral tissue (14). This procedure can be performed using a needle (80) or a cystoscope (110), depending on the specific requirements and preferences. The needle (80) or cystoscope (110) is used to accurately deliver the hydrogel composition to the desired location within the urethral tissue (14). This precise delivery is particularly advantageous as it allows for the targeted treatment of the affected area, thereby enhancing the effectiveness of the treatment.

[0076] In some cases, the method for treating stress urinary incontinence involves an additional step prior to the injection of the biocompatible hydrogel composition. This step involves the insertion of a vaginal support device (130) into the patient's vagina (52). The vaginal support device (130) is designed to maintain the pubourethral ligament (50) in an anatomically positioned state during the exposure to near-infrared light.

[0077] The vaginal support device (130) can be made of any material determined to be suitable for contact with biocompatible body fluids or tissues (14). In some cases, the vaginal support device (130) may be made from a variety of materials such as metal or plastic. The choice of material is dependent on specific requirements and preferences.

[0078] The vaginal support device (130) includes a concave section (136) designed to support the urethra (10) from below and C-shaped arms (134) designed to provide support along the pubourethral ligament (50). The wider concave portion (136) rests on the posterior vaginal wall (20), and the pushing force created by the convex arms (138) pushes the anterior vaginal wall (20) towards the symphysis pubis (70), allowing the pubourethral ligament (50) to remain in an anatomically positioned state during laser application, resulting in crosslinking.

[0079] In another variation, the vaginal support device (130) includes a concave section (136) designed to support the urethra (10) from below and C-shaped arms (134) designed to provide support along the pubourethral ligament (50). The gap (140) in the middle of the C-shaped pubourethral support structure (132) allows contact with the vaginal anterior wall (20) by the laser application device. This design facilitates the application of nearinfrared light to the vaginal tissue (12), which is a pivotal step in the crosslinking process of the silk fibroin-based hydrogel.

[0080] Following the insertion of the vaginal support device (130), the biocompatible hydrogel composition is injected into the patient's urethral tissue (14). This procedure can be performed using a needle (80) or a cystoscope (110), depending on the specific requirements and preferences. The needle (80) or cystoscope (110) is used to accurately deliver the hydrogel composition to the desired location within the urethral tissue (14). This precise delivery is particularly advantageous as it allows for the targeted treatment of the affected area, thereby enhancing the effectiveness of the treatment.

[0081] In some cases, the biocompatible hydrogel composition may further include an active agent that promotes tissue (12) growth. This active agent can be a substance that stimulates the growth and regeneration of tissues (12) in the body. The inclusion of such an active agent in the hydrogel composition can enhance the therapeutic effects of the composition, particularly in the context of treating conditions that involve tissue (12) damage or degeneration, such as stress urinary incontinence. The active agent can be a variety of substances that are known to promote tissue (12) growth. For instance, it can be a growth factor, a protein that stimulates cell growth, proliferation, and differentiation. Examples of growth factors that can be used as active agents include fibroblast growth factors, vascular endothelial growth factors, and platelet- derived growth factors. These growth factors can stimulate the growth and regeneration of various types of tissues (12), including epithelial tissues, connective tissues, and vascular tissues.

[0082] In other cases, the active agent can be a cytokine, a type of signaling molecule that regulates cell growth and differentiation. Examples of cytokines that can be used as active agents include interleukins, interferons, and tumor necrosis factors. These cytokines can modulate the immune response and promote the healing of damaged tissues (12).

[0083] Alternatively, the active agent can be a hormone, a type of signaling molecule that regulates various physiological processes, including cell growth and differentiation. Examples of hormones that can be used as active agents include insulin, growth hormone, and thyroid hormones. These hormones can stimulate the growth and regeneration of various types of tissues (12), including muscle tissues (40), bone tissues, and skin tissues.

[0084] The active agent can be incorporated into the hydrogel composition in various ways. For instance, it can be mixed with the silk fibroin-based hydrogel, the crosslinkable compound, the photoinitiator, and the upconversion nanoparticles to form a homogeneous composition. Alternatively, it can be encapsulated within the upconversion nanoparticles or attached to the silk fibroin-based hydrogel through chemical bonding or physical adsorption. The choice of the method for incorporating the active agent into the hydrogel composition can be tailored based on specific requirements and preferences, such as the desired release profile of the active agent, the stability of the active agent, and the biocompatibility of the active agent.

Claims

CLAIMS1. A biocompatible hydrogel composition for use in biomedical applications, the composition comprising: a silk fibroin-based hydrogel; a crosslinkable compound; a photoinitiator; and upconversion nanoparticles, wherein the silk fibroin-based hydrogel is configured to form filaments and a scaffold in vivo upon exposure to ultraviolet light triggered by near-infrared light.

2. The biocompatible hydrogel composition of claim 1, wherein the silk fibroin-based hydrogel is derived from Bombyx mori silkworm fibers.

3. The biocompatible hydrogel composition of claim 1, wherein the crosslinkable compound includes methacrylate.

4. The biocompatible hydrogel composition of claim 1, wherein the upconversion nanoparticles are lanthanide-doped upconversion nanoparticles.

5. The biocompatible hydrogel composition of claim 1, wherein the photoinitiator is selected from a group consisting of benzophenones, anthraquinones, benzoins, acetophenones, and phosphate and antimonate salts.

6. The biocompatible hydrogel composition according to any of the preceding claims, for use in treatment of stress urinary incontinence.

7. The biocompatible hydrogel composition according to claim 6, wherein the hydrogel composition is exposed to near-infrared light to trigger ultraviolet light emission from the upconversion nanoparticles, thereby initiating crosslinking of the silk fibroin-based hydrogel.

8. The biocompatible hydrogel composition according to claim 6, wherein the biocompatible hydrogel further comprising an active agent that promotes tissue (12) growth.

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