Injectable light-cured hydrogel for bone tissue repair as well as preparation method and application of injectable light-cured hydrogel

Abstract

The invention discloses injectable photocuring hydrogel for bone tissue repair and a preparation method and application thereof.The method comprises the steps that at the room temperature, SA, HA, AAm, MBA, Hmpp and Acc-NHS are added into deionized water to be dissolved, and a precursor solution is obtained; under the condition of high-speed mechanical stirring, dropwise adding a CaCl2 aqueous solution into the precursor solution, and continuously stirring, so that a sodium alginate chain segment and calcium ions are subjected to ionic cross-linking, and injectable ionic cross-linking hydrogel with the shear thinning characteristic is obtained; and adding HAp into the injectable ionic crosslinking hydrogel under the condition of keeping high-speed mechanical stirring, and continuously stirring to obtain the injectable photocuring hydrogel with the bone repair function. The hydrogel disclosed by the invention has excellent injectable performance, controllable light curing conversion capability, relatively high mechanical strength, wet interface adhesion performance and bone repair potential, and is expected to be used as a minimally invasive implantable medical device for repairing bone tissue injury.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials, specifically relating to an injectable photocurable hydrogel for bone tissue repair, its preparation method, and its application. Background Technology

[0002] Bone tissue injury is a common and complex medical problem in clinical orthopedics, originating from trauma, tumor resection, infection, and bone defects caused by congenital diseases. For medium to large or irregularly shaped bone defects, the body's own regenerative capacity is often insufficient, requiring exogenous materials for filling and support. Currently, commonly used repair materials include autologous bone, allogeneic bone, decellularized matrix, and various synthetic bone substitutes. However, these materials still have limitations, such as limited donor availability, poor shapeability, difficulty in precisely fitting the defect shape, insufficient fixation stability, and unsatisfactory post-implantation interface integration, which restricts their effectiveness in complex bone defects.

[0003] In recent years, hydrogels have been considered promising bone repair materials due to their high water content, softness, plasticity, and excellent biocompatibility. Injectable hydrogels, in particular, can be inserted into the defect area via minimally invasive techniques to achieve in-situ shaping, helping to reduce surgical trauma and improve fit. However, existing injectable hydrogels generally still face some key challenges: for example, curing methods are limited; some materials have long curing times or are highly dependent on the environment, hindering rapid and stable shaping, and their mechanical strength after curing is insufficient, making it difficult to provide necessary structural support in the early stages; some materials have limited adhesion to moist bone surfaces, easily shifting and affecting repair outcomes; and some materials lack inorganic components that promote bone regeneration, making it difficult to functionally match natural bone tissue.

[0004] Therefore, there is an urgent need to develop a novel composite hydrogel material that combines excellent injectability, controllable photocuring transformation capability, high mechanical strength, wet interface adhesion performance, and bone repair potential to meet the clinical application needs in the repair of complex bone defects. Summary of the Invention

[0005] To address the shortcomings of the prior art, this invention provides an injectable photocurable hydrogel for bone tissue repair, its preparation method, and its application. This injectable hydrogel possesses excellent injectability, controllable photocuring transition capability, high mechanical strength, wet interface adhesion performance, and bone repair potential, thereby enhancing the overall performance of the hydrogel in bone tissue repair scenarios.

[0006] To solve the above-mentioned technical problems and achieve the above-mentioned technical effects, the present invention is implemented through the following technical solution:

[0007] A method for preparing an injectable photocurable hydrogel for bone tissue repair includes the following steps:

[0008] Step 1) At room temperature, sodium alginate, sodium hyaluronate, acrylamide, N,N'-methylenebisacrylamide, p-hydroxyphenylacetone, and N-hydroxysuccinimide acrylate are added to deionized water and stirred until completely dissolved to obtain a homogeneous and transparent precursor solution.

[0009] Step 2) Under high-speed mechanical stirring, calcium chloride aqueous solution is added dropwise to the precursor solution obtained in step 1, and stirring is continued after the addition is completed to allow sodium alginate segments to undergo ionic cross-linking with calcium ions, thereby obtaining an injectable ionic cross-linked hydrogel with shear thinning properties.

[0010] Step 3) While maintaining high-speed mechanical stirring, add nano-hydroxyapatite to the injectable ion-crosslinked hydrogel obtained in Step 2, and continue stirring to mix evenly to obtain an injectable photocurable hydrogel with bone repair function.

[0011] Furthermore, in the precursor solution obtained in step 1:

[0012] The concentration of sodium alginate is 2.0-4.0 wt%;

[0013] The concentration of sodium hyaluronate is 0.4-1.0 wt%;

[0014] The concentration of acrylamide is 20-40 wt%;

[0015] The concentration of N,N'-methylenebisacrylamide was 0.05-0.2 wt%.

[0016] The volume fraction of p-hydroxyphenylacetone is 0.2-1.0 wt% of the total volume.

[0017] The concentration of N-hydroxysuccinimide acrylate is 0.5-2.0 wt%.

[0018] Furthermore, the calcium chloride aqueous solution added in step 2 has a concentration of 0.2-0.4M and a volume of 3-6 mL.

[0019] Furthermore, in step 2, the stirring speed of the high-speed mechanical stirrer is 500-1500 rpm, and the stirring time continues for 5-20 minutes after the droplet addition is completed, so that the sodium alginate can undergo sufficient ionic cross-linking.

[0020] Furthermore, in step 3, the amount of nano-hydroxyapatite added to the obtained injectable ion-crosslinked hydrogel is 1-10 wt% of the total mass of the hydrogel.

[0021] Furthermore, in step 3, the high-speed mechanical stirring speed is 800-2000 rpm, and the stirring time is 5-30 min, to ensure uniform dispersion of nano-hydroxyapatite.

[0022] An injectable photocurable hydrogel for bone tissue repair, prepared by the above method, comprises: sodium alginate, sodium hyaluronate, acrylamide, N,N'-methylenebisacrylamide, p-hydroxyacetone (Hmpp), N-hydroxysuccinimide acrylate, calcium chloride aqueous solution, and nano-hydroxyapatite; wherein,

[0023] Sodium alginate can form an ionic cross-linked structure under the action of calcium chloride aqueous solution to ensure that the injectable photocurable hydrogel maintains suitable shear thinning injectability before curing.

[0024] Acrylamide and N-hydroxysuccinimide acrylate can form a covalent cross-linked structure under ultraviolet light irradiation to achieve rapid in-situ curing of the injectable photocurable hydrogel at the bone defect site, forming a solid block hydrogel.

[0025] N-hydroxysuccinimide acrylate can covalently couple with amino groups exposed on the surface of bone tissue to improve the adhesion stability of the formed solid bulk hydrogel to the bone tissue interface.

[0026] Nano-hydroxyapatite can enhance the bioactivity of the injectable photocurable hydrogel and facilitate the creation of a microenvironment that promotes bone tissue regeneration.

[0027] Furthermore, the injectable photocurable hydrogel for bone tissue repair can be injected into a designated area and returns to a gel state after shearing stops, remaining stationary in situ. Under ultraviolet irradiation, it can initiate a free radical polymerization reaction of acrylamide and N-hydroxysuccinimide acrylate, thereby forming a covalent cross-linked network in the system, resulting in a dense and complete solid block-shaped bone tissue repair hydrogel at the designated location.

[0028] Furthermore, the conditions for ultraviolet radiation are:

[0029] The wavelength of ultraviolet light is 320-420nm;

[0030] The illumination time is 50-200 seconds;

[0031] Light intensity is 20-50 mW / cm 2 .

[0032] The application of the injectable photocurable hydrogel for bone tissue repair prepared by the above method in the preparation of minimally invasive implantable medical devices for repairing bone tissue damage.

[0033] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0034] 1. Excellent injectability: The hydrogel material prepared by this invention is a shear-thinned cream-like gel before photocuring, which can be smoothly delivered by conventional injection equipment and can fill complex and irregular bone defect areas, providing convenience and adaptability for clinical operation.

[0035] 2. Controllable photocuring transformation capability: The hydrogel material prepared by this invention can rapidly solidify and form a stable three-dimensional structure under light irradiation after injection into the target site. The controllable curing process and short curing time help avoid material displacement during treatment, achieving in-situ molding. The cured hydrogel has sufficient tensile strength and ductility, is not easily cracked or detached due to external stress, and can provide necessary structural support during bone tissue repair, providing a stable mechanical environment for new bone formation.

[0036] 3. Interfacial adhesion properties to bone tissue and applications in bone repair: The active ester groups in the hydrogel material system prepared in this invention can covalently bond with the amino groups in proteins on the bone tissue surface, enabling the cured hydrogel to adhere to moist bone tissue, improving the material's fixation effect in vivo and helping to maintain its stable position in bone defects. The uniform dispersion of nano-hydroxyapatite in the hydrogel can mimic the inorganic phase composition of bone tissue, potentially promoting osteoblast attachment, proliferation, and differentiation, thereby accelerating the bone regeneration process and improving repair efficiency.

[0037] The above description is merely an overview of the technical solution of the present invention. In order to better understand the technical means of the present invention and to implement it according to the contents of the specification, the preferred embodiments of the present invention are described in detail below with reference to the accompanying drawings. Specific embodiments of the present invention are given in detail below with reference to the accompanying drawings. Attached Figure Description

[0038] The accompanying drawings, which are included to provide a further understanding of the invention and form part of this application, illustrate exemplary embodiments of the invention and, together with their description, serve to explain the invention and do not constitute an undue limitation thereof. In the drawings:

[0039] Figure 1 This is a schematic diagram of the process for preparing the injectable photocurable hydrogel for bone tissue repair according to the present invention.

[0040] Figure 2 These are field photos taken during the in-situ curing experiment of the injectable photocurable hydrogel for bone tissue repair prepared according to the present invention. Figure 2 Figure 'a' illustrates that the injectable photocurable hydrogel for bone tissue repair prepared in this invention can be injected into a culture dish using a syringe. Figure 2Figure b illustrates the solid block-shaped bone tissue repair hydrogel that can be formed by curing the injectable photocurable hydrogel for bone tissue repair prepared in this invention in a culture dish with ultraviolet light.

[0041] Figure 3 This is a schematic diagram of the injectable photocurable hydrogel prepared according to the present invention for bone tissue repair and bone injury repair.

[0042] Figure 4 The results of hydrogel structure and morphology tests in Test Example 1 of this invention are shown below. Figure 4 Figure 'a' illustrates the microstructure of nano-hydroxyapatite in the injectable photocurable hydrogel for bone tissue repair prepared according to this invention. Figure 4 Figure b shows the distribution of the four elements Ca, P, C and O in the injectable photocurable hydrogel for bone tissue repair prepared in this invention.

[0043] Figure 5 The results of the photocured hydrogel tensile stress-strain performance test in Test Example 2 of this invention are shown.

[0044] Figure 6 The results of the photocuring hydrogel bone adhesion test in Test Example 3 of this invention are shown. Detailed Implementation

[0045] The preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings to provide a clearer understanding of the invention's purpose, features, and advantages. It should be understood that the embodiments shown in the drawings are not intended to limit the scope of the invention, but are merely illustrative of the essential spirit of the invention's technical solution.

[0046] In the following description, certain specific details are set forth for the purpose of illustrating various disclosed embodiments in order to provide a thorough understanding of the various disclosed embodiments. However, those skilled in the art will recognize that embodiments may be practiced without one or more of these specific details. In other instances, well-known apparatuses, structures, and techniques associated with this application may not have been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments.

[0047] Unless the context requires otherwise, throughout the specification and claims, the word “comprising” and its variations, such as “including” and “having”, shall be understood to have an open, inclusive meaning, that is, to be interpreted as “including, but not limited to”.

[0048] Throughout this specification, references to "an embodiment" or "an embodiment" indicate that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Therefore, the appearance of "in an embodiment" or "an embodiment" in various places throughout the specification does not necessarily refer to the same embodiment. Furthermore, a particular feature, structure, or characteristic may be combined in any manner in one or more embodiments.

[0049] The singular forms “a” and “the” used in this specification and the appended claims include plural references unless otherwise expressly stated herein. It should be noted that the term “or” is generally used to mean “and / or” unless otherwise expressly stated herein.

[0050] Furthermore, the technical features involved in the different embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other. Unless otherwise specified, all reagents and materials used in the present invention are commercially available.

[0051] This invention provides a method for preparing an injectable photocurable hydrogel for bone tissue repair, comprising the following steps:

[0052] Step 1) At room temperature, sodium alginate, sodium hyaluronate, acrylamide, N,N'-methylenebisacrylamide, p-hydroxyacetone, and N-hydroxysuccinimide acrylate are added to deionized water and stirred until completely dissolved to obtain a homogeneous and transparent precursor solution.

[0053] Preferably, low-viscosity sodium alginate can be selected.

[0054] Preferably, the molecular weight of sodium hyaluronate is 1.5-2.5 million.

[0055] Preferably, in the obtained precursor solution, the concentration of sodium alginate is 2.0-4.0 wt%, the concentration of sodium hyaluronate is 0.4-1.0 wt%, the concentration of acrylamide is 20-40 wt%, the concentration of N,N'-methylenebisacrylamide is 0.05-0.2 wt%, the volume fraction of p-hydroxyacetone is 0.2-1.0 wt% of the total volume, and the concentration of N-hydroxysuccinimide acrylate is 0.5-2.0 wt%.

[0056] Step 2) Under high-speed mechanical stirring at 500-1500 rpm, 3-6 mL of 0.2-0.4 M calcium chloride aqueous solution is added dropwise to the precursor solution obtained in Step 1. After the addition is completed, stirring is continued for 5-20 min to allow the sodium alginate segments to fully undergo ionic cross-linking with calcium ions, thereby obtaining an injectable ionic cross-linked hydrogel with shear thinning properties.

[0057] Preferably, the concentration of the added calcium chloride aqueous solution can be 0.2M and the volume can be 3mL.

[0058] Preferably, the mechanical stirring speed can be 1000 rpm, and the stirring time can be 10 min.

[0059] Step 3) While maintaining high-speed mechanical stirring at 800-2000 rpm, add 1-10 wt% of nano-hydroxyapatite (by mass fraction of total hydrogel mass) to the injectable ion-crosslinked hydrogel obtained in Step 2, and continue stirring for 5-30 min to ensure uniform dispersion of nano-hydroxyapatite, and finally obtain injectable photocurable hydrogel with bone repair function.

[0060] Preferably, the amount of nano-hydroxyapatite added can be 5 wt% of the total mass of the hydrogel.

[0061] Preferably, the mechanical stirring speed can be 1500 rpm and the stirring time can be 10 min.

[0062] This invention introduces natural polysaccharides such as sodium alginate and sodium hyaluronate into the material system to ensure that the hydrogel maintains suitable shear-thinning injectability before curing; it achieves rapid in-situ curing of the material at the defect site by forming a stable covalent cross-linked structure through photosensitive cross-linking monomers under light irradiation; it enhances the interfacial adhesion performance of the hydrogel in a humid environment by enabling covalent interactions between the active ester groups in the material system and proteins on the tissue surface; and it enhances the bioactivity of the material and facilitates the creation of a microenvironment that promotes bone regeneration by adding nano-hydroxyapatite to the material system.

[0063] The present invention also provides an injectable photocurable hydrogel for bone tissue repair using the above preparation method. This injectable photocurable hydrogel for bone tissue repair is synergistically constructed from photocurable polymers containing active ester groups, natural polysaccharides or their derivatives, and nano-hydroxyapatite through physical action and photocrosslinking. Its components include sodium alginate, sodium hyaluronate, acrylamide, N,N'-methylenebisacrylamide, p-hydroxyacetone, N-hydroxysuccinimide acrylate, calcium chloride aqueous solution, and nano-hydroxyapatite.

[0064] Sodium alginate can form an ionic cross-linked structure under the action of calcium chloride aqueous solution, so as to ensure that the injectable photocurable hydrogel maintains suitable shear-thinning injectability before curing, which is convenient for injection.

[0065] Acrylamide and N-hydroxysuccinimide acrylate can form a covalent cross-linked structure under ultraviolet light irradiation, so as to achieve rapid in-situ curing of the injectable photocurable hydrogel at the bone defect site, forming a solid block hydrogel.

[0066] The N-hydroxysuccinimide acrylate can covalently couple with the amino groups exposed on the surface of bone tissue to improve the adhesion stability of the formed solid block hydrogel to the bone tissue interface.

[0067] The nano-hydroxyapatite in the hydrogel can enhance its bioactivity and facilitate the creation of a microenvironment that promotes bone tissue regeneration.

[0068] The injectable, light-curable hydrogel for bone tissue repair of this invention exists in a shear-thinning cream state in its uncured state, exhibiting excellent injectability and allowing for precise filling of irregularly shaped bone defects via injection. Under light irradiation conditions (UV wavelength 320-420nm, irradiation time 50-200s, light intensity 20-50mW / cm²), it is effective. 2 Under ultraviolet light irradiation, the injectable photocurable hydrogel for bone tissue repair of this invention can rapidly undergo a photocuring transition, initiating a free radical polymerization reaction of acrylamide and N-hydroxysuccinimide acrylate to form a stable covalent gel network structure, thereby forming a dense, complete solid block-shaped bone tissue repair hydrogel. The active ester groups in the injectable photocurable hydrogel for bone tissue repair of this invention can covalently bond with amino groups in proteins on the bone tissue surface, improving their adhesion stability on moist bone surfaces. The addition of nano-hydroxyapatite endows the injectable photocurable hydrogel for bone tissue repair of this invention with good bioactivity and osteogenic promoting effects. Therefore, the injectable photocurable hydrogel for bone tissue repair of this invention combines high extensibility, high mechanical strength, wet adhesion, and the "injectable-photocurable" transition characteristics, making it suitable for tissue engineering-related fields such as bone defect repair.

[0069] Based on the injectable photocurable hydrogel for bone tissue repair prepared above, the present invention also provides the application of such injectable photocurable hydrogel for bone tissue repair in the preparation of minimally invasive implantable medical devices for repairing bone tissue damage.

[0070] Medical personnel can first inject the injectable photocurable hydrogel for bone tissue repair prepared according to this invention into the patient's bone defect area using a syringe. Once the hydrogel enters the bone defect area and stops shearing, it returns to a gel state and remains stationary in the bone defect area. Medical personnel then use an ultraviolet light curing device to irradiate the bone defect area containing the injected hydrogel, thereby initiating a free radical polymerization reaction of acrylamide and N-hydroxysuccinimide acrylate in the hydrogel. This further forms a covalent cross-linked network, ultimately obtaining a 1-10 mm solid block-shaped bone repair hydrogel in the bone defect area, achieving bone tissue damage repair.

[0071] Example 1: Preparation of an injectable photocurable hydrogel for bone tissue repair.

[0072] See Figure 1 As shown, at room temperature, 640 mg sodium alginate (SA), 160 mg sodium hyaluronate (HA), 6 g acrylamide (AAm), 15 mg N,N'-methylenebisacrylamide (MBA), 200 mg N-hydroxysuccinimide acrylate (Acc-NHS) and 120 μL p-hydroxyacetone (Hmpp) were added sequentially to 20 mL of deionized water and stirred at 1000 rpm with a magnetic stirrer until the above components were completely dissolved, resulting in a homogeneous and transparent precursor solution.

[0073] Subsequently, under mechanical stirring at 1000 rpm, 3 mL of 0.2 M calcium chloride aqueous solution (CaCl2) was added dropwise to the above precursor solution. After the calcium chloride aqueous solution was added, stirring was continued for 10 min to allow the sodium alginate segments to react with the CaCl2. 2+ Fully ionic cross-linking occurs, forming an injectable ionic cross-linked hydrogel with shear-thinning properties.

[0074] Finally, 1.5g of nano-hydroxyapatite (HAp) was added to the mechanical stirrer at 1500rpm and stirred for 10min to ensure that the nano-hydroxyapatite particles were uniformly dispersed in the system, thereby obtaining an injectable photocurable hydrogel for bone tissue repair.

[0075] Example 2: In-situ photocuring of injectable photocurable hydrogels for bone tissue repair.

[0076] See Figure 2 As shown in Figure a, the injectable photocurable hydrogel for bone tissue repair prepared in Example 1 was loaded into a 5 mL syringe. It was smoothly ejected through the syringe and returned to a gel state after shearing ceased, remaining in situ and non-flowing. After filling a culture dish as a mold, the injected hydrogel was irradiated using a UV curing device. The irradiation conditions were: wavelength 395 nm, light intensity 30 mW / cm². 2 The irradiation time was 100 seconds. During the photocuring process, acrylamide and N-hydroxysuccinimide acrylate underwent free radical polymerization, further forming a covalently cross-linked network. See also... Figure 2 As shown in Figure b, the injectable photocurable hydrogel for bone tissue repair prepared in the final example 1 forms a dense, complete solid block-shaped bone repair hydrogel in situ. The cured hydrogel can firmly adhere to bone tissue, exhibiting good mechanical stability and adhesion properties.

[0077] See Figure 3As shown, the injectable photocurable hydrogel for bone tissue repair prepared in Example 1 can be injected into the bone defect cavity of a patient using a syringe. After injection, applying ultraviolet light to the gel allows for rapid curing and interfacial adhesion at the defect site. The resulting hydrogel is able to solidify and adhere to the inner wall of the bone defect, providing support for subsequent bone tissue regeneration and defect repair.

[0078] To verify the structural uniformity, injection performance, curing performance, and mechanical and bone adhesion properties of the injectable photocurable hydrogel for bone tissue repair prepared in this invention, the injectable photocurable hydrogel for bone tissue repair prepared in Example 1 and the solid block bone repair hydrogel prepared in Example 2 were subjected to the following tests.

[0079] Test Example 1: Hydrogel structure and morphology test.

[0080] Freeze-dried samples of the injectable photocurable hydrogel for bone tissue repair prepared in Example 1 were examined using a field emission scanning electron microscope (Field Emission Scanning Electron Microscope, Model: Regulus 8230, manufactured by Hitachi, Japan). An accelerating voltage of 15 kV and a working distance of approximately 8 mm were used to obtain high-resolution surface morphology images suitable for soft porous materials. Energy dispersive spectroscopy (EDS) analysis system connected to the scanning electron microscope was used to perform surface energy dispersive spectroscopy (EDS) to detect the Ca and P elements in the samples, obtaining elemental distribution maps. See [link to relevant documentation]. Figure 4 The surface morphology diagram of the material shown in image a reveals a large number of particulate structures dispersed within the hydrogel, a structure consistent with that of nano-hydroxyapatite. See also... Figure 4 The energy dispersive spectroscopy (EDS) distribution diagrams of the same region shown in b (including mapping diagrams of four elements: Ca, P, C, and O) show that the signals of Ca and P are uniformly presented within the material, indicating that the hydroxyapatite nanoparticles are uniformly dispersed in the three-dimensional hydrogel network, and no obvious particle aggregation or cluster structure was observed. The distribution of C and O corresponds to the organic network structure of the hydrogel. The distribution regions of Ca, P, C, and O overlap, further proving that the preparation method of the present invention can stably load nano-hydroxyapatite within the hydrogel system, forming a composite material with an inorganic-organic synergistic structure.

[0081] Test Example 2: Mechanical property testing of the photocured hydrogel.

[0082] The solid, blocky bone repair hydrogel formed in Example 2 was cut into regular tensile test strips (typical dimensions: length 14 mm, width 2.5 mm, thickness approximately 1 mm). Uniaxial tensile tests were performed on the specimens using an electronic universal testing machine, and stress-strain curves were plotted. Figure 5As shown, the test results indicate that the hydrogel exhibits continuous extensibility under tensile conditions and can withstand significant deformation. Its maximum tensile strain reaches approximately 650%, corresponding to a tensile strength of approximately 210 kPa. The test results demonstrate that the injectable photocurable hydrogel for bone tissue repair prepared in this invention possesses good tensile extensibility and high mechanical strength after photocuring, maintaining structural integrity under external forces. This facilitates its stable existence in bone defects or irregular cavities and makes it suitable for filling bone defects and providing mechanical support.

[0083] Test Example 3: Test on the bone adhesion properties of the light-cured hydrogel.

[0084] Fresh chicken leg bones were selected as model bone tissue to verify the adhesion ability of the hydrogel to the bone surface. The solid block bone repair hydrogel formed in Example 2 was attached to the surface of the chicken leg bone, and light pressure was applied to form a contact interface. When the hydrogel comes into contact with the bone tissue surface, the active ester groups can undergo an amidation reaction with the amino groups in the proteins on the bone tissue surface, thereby forming stable covalent bonds at the interface. See also Figure 6 As shown in the experimental results, the hydrogel can form a certain adhesive force on the bone tissue surface and maintain its attachment state, providing a basis for its application in bone defect repair. While maintaining its softness and plasticity, the hydrogel can achieve stable adhesion to the bone surface, which is beneficial for filling irregular bone defect areas and maintaining its position at the injury site, thus providing a favorable microenvironment for subsequent tissue regeneration.

[0085] In summary, the injectable photocurable hydrogel for bone tissue repair provided by this invention exhibits excellent characteristics in terms of material composition, injectability, photocuring ability, and adhesion to the bone tissue interface. The preparation process and performance test results in the embodiments show that this hydrogel can rapidly form a stable covalent gel structure under light irradiation and effectively adhere to moist bone surfaces, providing necessary support for its fixation and positioning in bone defect areas. Furthermore, the nano-hydroxyapatite introduced into the material in this invention possesses certain bioactivity, potentially creating a favorable microenvironment for subsequent bone tissue regeneration. Based on these comprehensive characteristics, the injectable photocurable hydrogel material for bone tissue repair prepared by this invention has potential value in related tissue engineering fields such as bone defect repair.

[0086] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for preparing an injectable photocurable hydrogel for bone tissue repair, characterized in that, Includes the following steps: Step 1) At room temperature, sodium alginate, sodium hyaluronate, acrylamide, N,N'-methylenebisacrylamide, p-hydroxyphenylacetone, and N-hydroxysuccinimide acrylate are added to deionized water and stirred until completely dissolved to obtain a homogeneous and transparent precursor solution. Step 2) Under high-speed mechanical stirring, calcium chloride aqueous solution is added dropwise to the precursor solution obtained in step 1, and stirring is continued after the addition is completed to allow sodium alginate segments to undergo ionic cross-linking with calcium ions, thereby obtaining an injectable ionic cross-linked hydrogel with shear thinning properties. Step 3) While maintaining high-speed mechanical stirring, add nano-hydroxyapatite to the injectable ion-crosslinked hydrogel obtained in Step 2, and continue stirring to mix evenly to obtain an injectable photocurable hydrogel with bone repair function.

2. The preparation method according to claim 1, characterized in that, In the precursor solution obtained in step 1: The concentration of sodium alginate is 2.0-4.0 wt%; The concentration of sodium hyaluronate is 0.4-1.0 wt%; The concentration of acrylamide is 20-40 wt%; The concentration of N,N'-methylenebisacrylamide was 0.05-0.2 wt%. The volume fraction of p-hydroxyphenylacetone is 0.2-1.0 wt% of the total volume. The concentration of N-hydroxysuccinimide acrylate is 0.5-2.0 wt%.

3. The preparation method according to claim 1, characterized in that, The calcium chloride aqueous solution added in step 2 has a concentration of 0.2-0.4M and a volume of 3-6 mL.

4. The preparation method according to claim 1, characterized in that, In step 2, the stirring speed of the high-speed mechanical stirrer is 500-1500 rpm, and the stirring time continues for 5-20 minutes after the droplet addition is completed, so that the sodium alginate can undergo sufficient ionic cross-linking.

5. The preparation method according to claim 1, characterized in that, In step 3, the amount of nano-hydroxyapatite added to the obtained injectable ion-crosslinked hydrogel is 1-10 wt% of the total mass of the hydrogel.

6. The preparation method according to claim 1, characterized in that, In step 3, the high-speed mechanical stirring speed is 800-2000 rpm and the stirring time is 5-30 min to ensure uniform dispersion of nano-hydroxyapatite.

7. An injectable photocurable hydrogel for bone tissue repair, prepared by the method according to any one of claims 1-6, characterized in that: It contains sodium alginate, sodium hyaluronate, acrylamide, N,N'-methylenebisacrylamide, p-hydroxyphenylacetone (Hmpp), N-hydroxysuccinimide acrylate, calcium chloride aqueous solution, and nano-hydroxyapatite; among which, Sodium alginate can form an ionic cross-linked structure under the action of calcium chloride aqueous solution to ensure that the injectable photocurable hydrogel maintains suitable shear thinning injectability before curing. Acrylamide and N-hydroxysuccinimide acrylate can form a covalent cross-linked structure under ultraviolet light irradiation to achieve rapid in-situ curing of the injectable photocurable hydrogel at the bone defect site, forming a solid block hydrogel. N-hydroxysuccinimide acrylate can covalently couple with amino groups exposed on the surface of bone tissue to improve the adhesion stability of the formed solid bulk hydrogel to the bone tissue interface. Nano-hydroxyapatite can enhance the bioactivity of the injectable photocurable hydrogel and facilitate the creation of a microenvironment that promotes bone tissue regeneration.

8. The injectable photocurable hydrogel for bone tissue repair according to claim 7, characterized in that, The injectable photocurable hydrogel can be injected into a designated area and returns to a gel state after shearing stops, remaining stationary in situ. Under ultraviolet irradiation, it can initiate a free radical polymerization reaction of acrylamide and N-hydroxysuccinimide acrylate, causing the system to further form a covalent cross-linked network, thereby forming a solid block-shaped bone tissue repair hydrogel at the designated location.

9. The injectable photocurable hydrogel for bone tissue repair according to claim 8, characterized in that, The conditions for ultraviolet light irradiation are: The wavelength of ultraviolet light is 320-420nm; The illumination time is 50-200 seconds; Light intensity is 20-50 mW / cm 2 .

10. The use of the injectable photocurable hydrogel for bone tissue repair prepared by any one of the preparation methods of claims 1-6 and / or the use of the injectable photocurable hydrogel for bone tissue repair prepared by any one of claims 7-9 in the preparation of minimally invasive implantable medical devices for repairing bone tissue damage.

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