Oral bone repair hydrogel periosteum material and preparation method thereof

Abstract

The present invention discloses a method for preparing a hydrogel periosteum material for oral bone repair: a natural polysaccharide solution and a metal salt are reacted to obtain a gel-like substance, which is then dried to obtain a membrane-like substance, and the membrane-like substance is placed in a metal salt solution for mineralization and drying to obtain a hydrogel periosteum material for oral bone repair. The present invention obtains a periosteum material with one side being hydrophilic and the other side being hydrophobic by mineralization with metal ions, drying and reforming. The obtained periosteum material has high tensile strength and plastic shape, and meets the requirements of higher mechanical properties required in oral bone repair. The periosteum can be well attached to the surrounding bone defect tissue, and the degradation cycle matches the treatment cycle of oral bone repair. The preparation method of the present invention is simple, low-cost, and suitable as a periosteum material for oral bone repair.

Description

Technical Field

[0001] The invention relates to an oral bone repair hydrogel periosteum material based on a polysaccharide raw material and a preparation method thereof. Background Art

[0002] Bone defects caused by various reasons, including accidents, congenital malformations, bone tumors, dental implants, periodontal disease, and craniotomy, are common in clinical practice. Currently, orthopedic clinicians often choose to use the patient's own bone (commonly found in the ilium, ribs, and fibula) for bone grafting, a "rob Peter to fill Paul" approach. Although autologous bone is considered the "gold standard" for bone grafting, this is merely an evaluation of its effectiveness in repairing bone defects. Autologous bone grafting poses a range of challenges, including secondary injury to the patient, donor site complications, prolonged surgery time, increased blood loss, and limited bone stock, making it a non-perfect clinical solution.

[0003] In the dental field, bone grafting is often used to repair bone defects. During the bone grafting process, bone powder from synthetic or allogeneic bone is first used to fill the alveolar bone defect to increase bone volume. The periosteum is then placed over the bone powder. The main function of the periosteum is to prevent soft tissue from invading the defect area through physical isolation, create a sterile environment during the dental implant process, prevent bone powder loss, maintain the spatial stability of bone powder, and promote the combination of bone powder and surrounding bone tissue. Based on their degradation characteristics, periosteum can be divided into two categories:

[0004] 1. Non-absorbable periosteum

[0005] Polytetrafluoroethylene (PTFE) membranes and titanium mesh, for example, offer high strength and spatial retention, meeting the requirements for bone powder fixation. However, their non-degradability requires secondary surgery for removal after recovery, and limitations such as membrane exposure and a high risk of infection limit their widespread application.

[0006] 2. Absorbable periosteum

[0007] These materials, primarily made of natural or synthetic polymers such as collagen and polylactic acid (PLA), have similar compositions to natural periosteum, offering excellent biocompatibility and eliminating the need for secondary surgery, thus alleviating patient pain. However, issues such as uncontrollable degradation rates and insufficient mechanical strength (for example, collagen-based periosteum has a strength of only 0.42 kPa) limit their widespread clinical application in bone defect repair. Degradation products from some materials can also cause a local decrease in pH, leading to oral inflammation.

[0008] Hydrogel has great potential as a new generation of periosteum candidate material due to its biocompatibility and biodegradability. For example:

[0009] Current hydrogel research focuses on: 1. Enhancing mechanical properties through cross-linker optimization (such as the introduction of bisphosphonates) or composite inorganic fillers (such as nanohydroxyapatite) to meet the mechanical performance requirements of the oral and dental field; 2. Enabling long-term retention in the body and ensuring that degradation products are harmless to the human body.

[0010] Patent application number CN202311447542.9 discloses the preparation of a periosteal material, which uses natural polymer materials and inorganic materials to compound to improve the mechanical strength of the periosteal material and improve the mechanical properties to meet clinical application needs. The preparation method uses natural polymer materials, natural polysaccharides, and dopamine hydrochloride, bone organic component type I collagen (ColI) and bone inorganic component nanohydroxyapatite (nHAP) for compounding, and by optimizing the reaction conditions (solution concentration, reaction time, reaction temperature), a composite membrane material with good adhesion and ductility is prepared. Although the periosteal material prepared by this patent has improved the mechanical properties to a certain extent and can meet the treatment of some bone defects, it is difficult to effectively anchor or combine with the bone scaffold in oral bone repair, and the degradation cycle is uncontrollable, thus limiting its application in the field of oral repair. Summary of the Invention

[0011] In order to overcome the shortcomings of the application of hydrogel materials in bone repair materials, the purpose of the present invention is to provide a hydrogel for use in the field of dental bone repair, which can produce a mineralized hard material with controllable morphology through in situ mineralization, high mechanical strength, and good adhesion to the defective part of the tooth, and can be used as periosteum.

[0012] In order to achieve this purpose, the technical solution of the present invention is as follows:

[0013] A method for preparing a hydrogel periosteum material for oral bone repair, comprising:

[0014] A natural polysaccharide solution and a metal salt are reacted to obtain a gel-like substance, which is then dried to obtain a membrane-like substance. The membrane-like substance is placed in a metal salt solution for mineralization and drying to obtain the oral bone repair hydrogel periosteum material.

[0015] Furthermore, the mass concentration of the natural polysaccharide solution is 1-3%.

[0016] The natural polysaccharide is one or more of hydroxypropyl carboxymethyl cellulose, xanthan gum, hyaluronic acid, and sodium alginate, preferably hydroxypropyl carboxymethyl cellulose.

[0017] The metal salt is one or more of calcium salt, magnesium salt, zinc salt, copper salt, strontium salt, iron salt, ferrous salt and barium salt.

[0018] Furthermore, the calcium salt includes hydroxyapatite, calcium gluconate, calcium chloride, calcium sulfate, calcium carbonate or calcium phosphate.

[0019] The zinc salt is preferably zinc sulfate.

[0020] Furthermore, preferably, the metal salt is zinc sulfate, calcium chloride or calcium sulfate.

[0021] The metal salt is configured into an aqueous solution, and the mass fraction of the metal salt solution is 0.1-15%, preferably 0.2-13%.

[0022] The mass ratio of the natural polysaccharide to the metal salt is 1:0.01-5, preferably 1:0.02-3.

[0023] More preferably, the method is carried out according to the following steps:

[0024] (1) Add metal salt solution to a natural polysaccharide solution with a mass concentration of 1-3%, stir and mix, remove bubbles, and dry to obtain a film-like substance;

[0025] (2) The membrane-like material is added to a metal salt solution for mineralization and dried to obtain the oral bone repair hydrogel periosteum material.

[0026] In the step (1), the drying can be carried out at 40-50° C. for 5-6 hours.

[0027] In the step (1), the concentration of the metal salt solution is 0.1-15%, preferably 0.1-13%.

[0028] In the step (1), when the metal salt solution is a zinc sulfate solution, the concentration is preferably 0.35-10%; when the metal salt solution is a calcium chloride solution, the concentration is preferably 5-15%; when the metal salt solution is a calcium sulfate solution, the concentration is preferably 0.1-0.2%.

[0029] In the step (2), the metal salt solution is preferably calcium chloride or zinc sulfate solution, more preferably zinc sulfate solution; the mass concentration is preferably 1% to 7.5%, more preferably 3 to 5%.

[0030] In the step (2), when the metal salt solution is calcium sulfate, the mass concentration is preferably 0.2%.

[0031] In step (2), the mineralization is single-sided mineralization, that is, one side of the membrane material is immersed in the metal salt solution, and the other side does not contact the metal salt solution;

[0032] In the step (2), the membrane material can be first moistened with a small amount of water and then added to a metal salt solution for mineralization.

[0033] The mineralization time is preferably 1 hour to 4 hours, and the temperature is room temperature.

[0034] In the step (2), the drying is generally carried out at room temperature, and is generally dried to a moisture content of less than 3%.

[0035] The present invention also provides an oral bone repair hydrogel periosteum material prepared by the above method.

[0036] The oral bone repair hydrogel periosteum material has a thickness of 100 to 300 microns (0.1 to 0.3 mm), a tensile strength of 60 to 90 MPa, and a degradation time of 3 to 6 months.

[0037] The oral bone repair hydrogel periosteum material of the present invention can be used as periosteum in dental bone repair.

[0038] The present invention mainly uses natural polysaccharides of different structural types (cellulose, hyaluronic acid, etc.) and metal ions of different valence states as the main matrix, and supplemented with various metal salts of different solubility (such as zinc sulfate, hydroxyapatite, calcium gluconate, calcium chloride, calcium carbonate, calcium phosphate, etc.) to prepare biomineralized gels with different mechanical properties and mineralization behaviors. This hydrogel with controllable mechanical properties can meet the mechanical performance requirements of bone defect repair in the field of orthopedic repair, especially in stomatology.

[0039] Compared with existing bone repair materials, the present invention has the following advantages:

[0040] 1. The raw materials used are natural polysaccharides, which have good biocompatibility and good adaptability to the human body when used as bone repair materials. After degradation, the biological toxicity to the human body can be reduced to the lowest level.

[0041] 2. The preparation method adopted by the present invention is simple and does not require complicated processes. The gel network structure is formed by drying and reforming, eliminating the need for tedious preparation processes. The gel network is regulated by adjusting the different ratios of raw materials and the concentration of metal ions. The addition of metal salt ions for mineralization strengthens the gel network, making the material soft yet tough. Different mechanical strengths and degradation cycles can be adjusted to meet different clinical application requirements.

[0042] 3. Periosteum materials prepared from mineralized hydrogels can adhere well to bone defect tissue. When one side is mineralized, the mineralized side is rougher, the surface roughness increases, the contact angle decreases, and it becomes more hydrophilic. The unmineralized side is left untreated and is more hydrophobic. This results in a periosteal material that is hydrophilic on one side and hydrophobic on the other. In clinical use, when the hydrophilic side is moistened, the membrane will spontaneously adhere to the hydrophilic side, allowing it to better fit irregular bone defects in the oral cavity.

[0043] 4. According to experimental data, the mechanical properties of the film after metal ion mineralization have been greatly improved compared with before mineralization, which can meet the clinical requirements for the mechanical strength of the periosteum.

[0044] 5. The hydrogels of the present invention can regulate their degradation cycle by adjusting their segment structure and mineralization pathways. The repair cycle for oral bone defects is typically 3–6 months (depending on defect size and location). The hydrogel periosteum material produced by the present invention can gradually degrade during this period. Natural periosteum is gradually replaced by new tissue during bone healing. The ideal degradation rate of the periosteum should be synchronized with the rate of bone formation (e.g., slow degradation in the early stages to maintain support, accelerated degradation in the later stages to give way). Therefore, the degradation time of the periosteum should also be between 3 and 6 months, aligning the degradation cycle with the treatment period. Stable in the early stages of bone healing and rapidly degrading in the later stages, the periosteum is absorbed by the body, eliminating the need for postoperative removal and reducing patient pain.

[0045] The present invention provides a biomass hydrogel membrane material that achieves high strength, shape plasticity, and controllable mineralization through metal ion mineralization, drying and reforming, to meet the high mechanical performance requirements needed in oral bone repair. The prepared periosteum can be well attached to the surrounding bone defect tissue. At the same time, based on the histological structure of the periosteum, a multi-layer structure is designed to achieve stability in the early healing stage and rapid degradation in the later healing stage, thereby maximizing bone repair while rapidly degrading without causing other effects on the human body. The preparation method of the present invention is simple, low-cost, and suitable as a periosteum material for oral bone repair. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 SEM images of the network morphology of the freeze-dried gel before and after mineralization.

[0047] Figure 2 Infrared spectra of hydrogel before and after mineralization.

[0048] Figure 3 This is a real photo of the hydrogel after mineralization.

[0049] Figure 4 This is a SEM image of the microscopic morphology of the mineralized hydrogel (before drying) in Example 1. The left image shows the outer layer of the hydrogel surface that has been mineralized with metal ions, and the right image shows the three-dimensional network structure inside the gel.

[0050] Figure 5 These are the XRD spectra of the film sample before mineralization and the final product after mineralization, where the left picture is before mineralization and the right picture is after mineralization.

[0051] Figure 6 SEM images of the surface micromorphology of the hydrogels after mineralization after immersion in solutions with different metal ion concentrations and freeze-drying.

[0052] Figure 7 This is a real picture of the transparent high-strength hydrogel film.

[0053] Figure 8The left figure shows the mechanical strength data of the hydrogel with different water contents, and the right figure shows the effect of different concentrations of metal ion mineralization on the mechanical properties of the gel.

[0054] Figure 9 Graph showing the compressive strength of mineralized gels with different metal ion concentrations.

[0055] Figure 10 The degradation curve of gel over time. DETAILED DESCRIPTION

[0056] The technical solution of the present invention is further described in detail below through examples, and the protection scope of the present invention includes but is not limited to these.

[0057] Example 1: 0.5 g of hydroxypropyl carboxymethyl cellulose was weighed and slowly poured into a round-bottom flask containing 50 g of distilled water. The mixture was stirred at 700 rpm / min for 2 h until the solution became clear and transparent, thereby obtaining a uniformly mixed hydroxypropyl carboxymethyl cellulose solution A.

[0058] Weigh 0.035 g of zinc sulfate, add 10 g of distilled water to prepare a zinc sulfate solution, shake well, and slowly add the zinc sulfate solution to the prepared hydroxypropyl carboxymethyl cellulose solution A and stir. Initially maintain the speed at 800 rpm / min, then gradually reduce the speed to 500 rpm / min to reduce the generation of bubbles, to obtain solution B;

[0059] Pour solution B obtained in the above step into a watch glass, observe the bubbles, and remove most of the bubbles with a dropper to prevent them from affecting the performance of the sample. The thickness of the resulting gel-like substance is 4.5-5mm.

[0060] Then, the watch glass was placed in an oven, the temperature was set to 40°C, and dried for 6 hours to obtain a film sample. It was scraped off with a cutter, moistened with 1-2 mL of water, and then 20 mL of 5% zinc sulfate solution was added for single-sided mineralization. The film-like material floated on the surface of the zinc sulfate solution, with one side immersed in the zinc sulfate solution and the other side not in contact with the zinc sulfate solution. After treatment for 2 hours, it was washed with deionized water 2-3 times and dried at room temperature to a water content of less than 3% to obtain the final product with a thickness of 100~200 μm.

[0061] Example 2: 1.0 g of hydroxypropyl carboxymethyl cellulose was weighed and slowly poured into a round-bottom flask containing 50 g of distilled water. The mixture was stirred at 700 rpm / min for 2 h until the solution became clear and transparent, thereby obtaining a uniformly mixed hydroxypropyl carboxymethyl cellulose solution A.

[0062] Weigh 0.035 g of zinc sulfate, add 10 g of distilled water to prepare a zinc sulfate solution, shake well, and slowly add the zinc sulfate solution to the prepared hydroxypropyl carboxymethyl cellulose solution A and stir. Initially maintain the speed at 800 rpm / min, then gradually reduce the speed to 500 rpm / min to reduce the generation of bubbles, to obtain solution B;

[0063] Pour solution B obtained in the above steps into a watch glass, observe the bubbles, and use a dropper to remove most of the bubbles to prevent them from affecting the sample performance.

[0064] Then place the watch glass in an oven, set the temperature to 40°C, and dry it for 6 hours to obtain a film sample. Scrape it off with a cutter, moisten it with 1-2 mL of water, and add 20 mL of 5% zinc sulfate solution for single-sided mineralization. One side of the film material is immersed in the zinc sulfate solution, and the other side does not contact the zinc sulfate solution. After treatment for 1 hour, wash it with deionized water 2-3 times and dry it at room temperature to obtain the final product.

[0065] Example 3: 0.5 g of xanthan gum was weighed and slowly poured into a round-bottom flask containing 50 g of distilled water. The mixture was stirred at 700 rpm / min for 2 h until the solution became clear and transparent, thereby obtaining a uniformly mixed xanthan gum solution A.

[0066] Weigh 0.035 g of zinc sulfate, add 10 g of distilled water to prepare a zinc sulfate solution, shake well, and slowly add the zinc sulfate solution to the prepared xanthan gum solution A, stirring. Initially maintain the speed at 800 rpm / min, and then gradually reduce the speed to 500 rpm / min to reduce the generation of bubbles, to obtain solution B;

[0067] Pour solution B obtained in the above steps into a watch glass, observe the bubbles, and use a dropper to remove most of the bubbles to prevent them from affecting the sample performance.

[0068] Then place the watch glass in an oven, set the temperature to 40°C, and dry it for 6 hours to obtain a film sample. Scrape it off with a cutter, moisten it with 1-2 mL of water, and add 20 mL of 5% zinc sulfate solution for single-sided mineralization. One side of the film material is immersed in the zinc sulfate solution, and the other side does not contact the zinc sulfate solution. After treatment for 2 hours, wash it with deionized water 2-3 times and dry it at room temperature to obtain the final product.

[0069] Example 4: 1.5 g of hydroxypropyl carboxymethyl cellulose was weighed and slowly poured into a round-bottom flask containing 50 g of distilled water. The mixture was stirred at 700 rpm / min for 2 h until the solution became clear and transparent, thereby obtaining a uniformly mixed hydroxypropyl carboxymethyl cellulose solution A.

[0070] Weigh 0.035 g of zinc sulfate, add 10 g of distilled water to prepare a zinc sulfate solution, shake well, and slowly add the zinc sulfate solution to the prepared hydroxypropyl carboxymethyl cellulose solution A, stirring. Initially maintain the speed at 800 rpm / min, and then gradually reduce the speed to 500 rpm / min to reduce the generation of bubbles, to obtain solution B;

[0071] Pour solution B obtained in the above steps into a watch glass, observe the bubbles, and use a dropper to remove most of the bubbles to prevent them from affecting the sample performance.

[0072] Then place the watch glass in an oven, set the temperature to 40°C, and dry it for 6 hours to obtain a film sample. Scrape it off with a cutter, moisten it with 1-2 mL of water, and add 20 mL of 5% zinc sulfate solution for single-sided mineralization. One side of the film material is immersed in the zinc sulfate solution, and the other side does not contact the zinc sulfate solution. After treatment for 4 hours, wash it with deionized water 2-3 times and dry it at room temperature to obtain the final product.

[0073] Example 5: 0.5 g of hydroxypropyl carboxymethyl cellulose was weighed and slowly poured into a round-bottom flask containing 50 g of distilled water. The mixture was stirred at 700 rpm / min for 2 h until the solution became clear and transparent, thereby obtaining a uniformly mixed hydroxypropyl carboxymethyl cellulose solution A.

[0074] Weigh 0.5 g of calcium chloride, add 10 g of distilled water to prepare a calcium chloride solution, shake well, and slowly add it to the prepared hydroxypropyl carboxymethyl cellulose solution A and stir. Initially maintain the speed at 800 rpm / min, and then gradually reduce the speed to 500 rpm / min to reduce the generation of bubbles, to obtain solution B;

[0075] Pour solution B obtained in the above steps into a watch glass, observe the bubbles, and use a dropper to remove most of the bubbles to prevent them from affecting the sample performance.

[0076] Then place the watch glass in an oven, set the temperature to 40°C, and dry it for 6 hours to obtain a film sample. Scrape it off with a cutter, moisten it with 1-2 mL of water, and add 20 mL of 5% calcium chloride solution for single-sided mineralization. One side of the film material is immersed in the calcium chloride solution, and the other side does not contact the calcium chloride solution. After treatment for 2 hours, wash it with deionized water 2-3 times and dry it at room temperature to obtain the final product.

[0077] Example 6: 0.5 g of sodium alginate was weighed and slowly poured into a round-bottom flask containing 50 g of distilled water. The mixture was stirred at 700 rpm / min for 2 h until the solution became clear and transparent, thereby obtaining a uniformly mixed sodium alginate solution A.

[0078] Weigh 1.0 g of zinc sulfate, add 10 g of distilled water to prepare a zinc sulfate solution, shake well, and slowly add the zinc sulfate solution to the prepared sodium alginate solution A. Initially maintain the speed at 800 rpm / min, then gradually reduce the speed to 500 rpm / min to reduce the generation of bubbles, to obtain solution B.

[0079] Pour solution B obtained in the above steps into a watch glass, observe the bubbles, and use a dropper to remove most of the bubbles to prevent them from affecting the sample performance.

[0080] Then place the watch glass in an oven, set the temperature to 40°C, and dry it for 6 hours to obtain a film sample. Scrape it off with a cutter, moisten it with 1-2 mL of water, and add 20 mL of 5% zinc sulfate solution for single-sided mineralization. One side of the film material is immersed in the zinc sulfate solution, and the other side does not contact the zinc sulfate solution. After treatment for 2 hours, wash it with deionized water 2-3 times and dry it at room temperature to obtain the final product.

[0081] Example 7: 0.5 g of sodium alginate was weighed and slowly poured into a round-bottom flask containing 50 g of distilled water. The mixture was stirred at 700 rpm / min for 2 h until the solution became clear and transparent, thereby obtaining a uniformly mixed sodium alginate solution A.

[0082] Weigh 1.5 g of calcium chloride, add 10 g of distilled water to prepare a calcium chloride solution, shake well, and slowly add it to the prepared sodium alginate solution A and stir. Initially maintain the speed at 800 rpm / min, then gradually reduce the speed to 500 rpm / min to reduce the generation of bubbles, to obtain solution B;

[0083] Pour solution B obtained in the above steps into a watch glass, observe the bubbles, and use a dropper to remove most of the bubbles to prevent them from affecting the sample performance.

[0084] Then place the watch glass in an oven, set the temperature to 40°C, and dry it for 6 hours to obtain a film sample. Scrape it off with a cutter, moisten it with 1-2 mL of water, and add 20 mL of 5% calcium chloride solution for single-sided mineralization. One side of the film material is immersed in the calcium chloride solution, and the other side does not contact the calcium chloride solution. After treatment for 2 hours, wash it with deionized water 2-3 times and dry it at room temperature to obtain the final product.

[0085] Example 8: 1.0 g of hydroxypropyl carboxymethyl cellulose was weighed and slowly poured into a round-bottom flask containing 50 g of distilled water. The mixture was stirred at 700 rpm / min for 2 h until the solution became clear and transparent, thereby obtaining a uniformly mixed hydroxypropyl carboxymethyl cellulose solution A.

[0086] Weigh 0.01 g of calcium sulfate, add 10 g of distilled water to prepare a zinc sulfate solution, shake well, and slowly add the solution to the prepared hydroxypropyl carboxymethyl cellulose solution A and stir. Initially maintain the speed at 800 rpm / min, then gradually reduce the speed to 500 rpm / min to reduce the generation of bubbles, to obtain solution B;

[0087] Pour solution B obtained in the above steps into a watch glass, observe the bubbles, and use a dropper to remove most of the bubbles to prevent them from affecting the sample performance.

[0088] Then put the watch glass into the oven, set the temperature to 40℃, and dry it for 6 hours to obtain the film sample we need. Scrape it with a cutter, moisten it with 1-2mL of water, add 20mL of 0.2% calcium sulfate solution for single-sided mineralization, treat it for 2 hours, wash it with deionized water 2-3 times, and dry it at room temperature to obtain the final product.

[0089] Example 9: 1.0 g of xanthan gum was weighed and slowly poured into a round-bottom flask containing 50 g of distilled water. The mixture was stirred at 700 rpm / min for 2 h until the solution became clear and transparent, thereby obtaining a uniformly mixed xanthan gum solution A.

[0090] Weigh 0.01 g of calcium sulfate, add 10 g of distilled water to prepare a calcium sulfate solution, shake well, and slowly add it to the prepared xanthan gum solution A and stir. Initially maintain the speed at 800 rpm / min, then gradually reduce the speed to 500 rpm / min to reduce the generation of bubbles, to obtain solution B;

[0091] Pour solution B obtained in the above steps into a watch glass, observe the bubbles, and use a dropper to remove most of the bubbles to prevent them from affecting the sample performance.

[0092] Then put the watch glass into the oven, set the temperature to 40℃, and dry it for 6 hours to obtain the film sample we need. Scrape it with a cutter, moisten it with 1-2mL of water, add 20mL of 0.2% calcium sulfate solution for single-sided mineralization, treat it for 2 hours, wash it with deionized water 2-3 times, and dry it at room temperature to obtain the final product.

[0093] Example 10: 1.0 g of xanthan gum was weighed and slowly poured into a round-bottom flask containing 50 g of distilled water. The mixture was stirred at 700 rpm / min for 2 h until the solution became clear and transparent, thereby obtaining a uniformly mixed xanthan gum solution A.

[0094] Weigh 0.01 g of calcium sulfate, add 10 g of distilled water to prepare a calcium sulfate solution, shake well, and slowly add it to the prepared xanthan gum solution A and stir. Initially maintain the speed at 800 rpm / min, then gradually reduce the speed to 500 rpm / min to reduce the generation of bubbles, to obtain solution B;

[0095] Pour solution B obtained in the above steps into a watch glass, observe the bubbles, and use a dropper to remove most of the bubbles to prevent them from affecting the sample performance.

[0096] Then put the watch glass into the oven, set the temperature to 40℃, and dry it for 6 hours to obtain the film sample we need. Scrape it with a cutter, moisten it with 1-2mL of water, add 20mL of 0.1% calcium sulfate solution for single-sided mineralization, treat it for 2 hours, wash it with deionized water 2-3 times, and dry it at room temperature to obtain the final product.

[0097] The concentration of the metal salt solution and the cation of the metal salt used in the mineralization of Examples 1 and 3 were changed. The mechanical properties of the periosteum prepared after mineralization and drying under different mineralization conditions were tested. The data results of the tensile strength and elongation at break are shown in Table 1:

[0098] Table 1

[0099]

[0100] The results in Table 1 show that for the hydrogels prepared in Examples 1 and 3, after being mineralized with a metal salt solution, the tensile strength and elongation at break are significantly improved compared to before mineralization.

[0101] As the concentration of zinc sulfate solution increases from 1% to 5%, the mechanical properties improve as the degree of mineralization increases. Tensile strength increases with increasing concentration, reaching its maximum at 5%. Above 5%, excessive concentration leads to uneven crosslinking, which in turn affects mechanical properties. When the concentration increases from 5% to 7.5%, the tensile strength decreases.

[0102] Comparison of Examples 1, 5, and 8 shows that the mechanical properties of the zinc salt solution after mineralization are superior to those of the calcium salt solution. Furthermore, from the experimental process, calcium chloride gels fastest. Although calcium sulfate has a low solubility and a low concentration, it can still form a mineralized layer and improve mechanical properties.

[0103] The polysaccharide in Example 3 is xanthan gum. In the mineralization step, the concentration of zinc sulfate is increased to improve the mechanical properties. However, the mechanical properties after mineralization with zinc sulfate solution are not as good as those of calcium sulfate.

[0104] Comparison of Examples 1, 3, and 6 shows that different polysaccharide raw materials have an impact on the properties of the periosteum. The mechanical properties of the periosteum prepared with xanthan gum and sodium alginate as raw materials are inferior to those of the hydroxypropyl carboxymethyl cellulose in Example 1.

[0105] By changing the mineralization time of Example 1, it can be seen that when the mineralization time is less than 1 hour, the degree of mineralization is insufficient, and the mechanical properties of the periosteum are still poor and do not meet the requirements; when the mineralization time is greater than 4 hours, excessive mineralization and uneven mineralization will occur, resulting in the film formed by the product being too brittle and the strength being reduced, which affects the clinical use effect.

[0106] Example 1: The network morphology SEM images of the membrane sample before mineralization and the final product after mineralization are as follows: Figure 1 As shown, Figure 1 In the figure, Figure a shows the structure before mineralization, with a scale of 50 μm, and Figure b shows the structure after mineralization, with a scale of 100 μm. Figure 1 The results show that after mineralization, the network structure becomes denser due to the complexation of metal ions.

[0107] Figure 2 This is the infrared contrast spectrum of the periosteum before and after mineralization in Example 1. Figure 2 It shows that Zn 2+ Ionic complexation leads to the enhancement of the hydroxyl peak and the formation of glycosidic bonds;

[0108] Figure 3 The left picture is the product of Example 1 (5% ZnSO4 mineralization), and the right picture is the product of Example 1 with a different mineralization concentration (7.5% ZnSO4 mineralization, mineralization time 1 h).

[0109] Figure 4 This is the SEM image of the microscopic morphology of the hydrogel after mineralization (before drying) in Example 1. Figure 4 The scale bars are all 100 μm. The left image shows the outer layer of the hydrogel surface that has been mineralized with metal ions, and the right image shows the three-dimensional network structure inside the gel. Figure 3 、 4 The results showed that the metal ions mineralized the hydrogel to form a core-shell structure. This structure primarily refers to the inner core and outer shell being composed of materials with different morphologies. After mineralization, the hydrogel membrane formed a dense, wrinkled mineralized layer on the surface, while the interior contained a three-dimensional network structure of hydroxypropyl carboxymethyl cellulose gel. This core-shell structure allows the shell to cover the interior, enhancing its mechanical strength.

[0110] The XRD spectra of the film sample before mineralization and the final product after mineralization in Example 1 are as follows: Figure 5 The left picture is before mineralization, and the right picture is after mineralization. Figure 5The results show that new peaks appear after mineralization by immersion in metal salt solution, the crystal forms are partially different after surface mineralization, and there is the existence of mixed phases, which proves the formation of mineralization.

[0111] In Example 1, 20 mL of 5% zinc sulfate solution (0.3 mol / L) was used for mineralization, and the zinc sulfate solution was changed to 0 (i.e., pure water), 0.1, 0.2, 0.4, 0.5, 0.6, 1.0, 1.5, and 2.0 M zinc sulfate solutions, respectively, and the mineralization was carried out for 2 h.

[0112] The surface micromorphology SEM images of the hydrogels after immersion and mineralization at different metal ion concentrations and freeze-drying are shown in Figure 2. Figure 6 shown Figure 6 The scale bars in the figures are all 50 μm. Figure 6 The results show that the greater the metal ion concentration, the more obvious the wrinkles produced by mineralization will be, resulting in a more obvious difference in the smoothness of the two sides, which in turn affects its hydrophilicity and hydrophobicity. Therefore, the preferred metal ion concentration is 3%-5%. The higher the metal ion concentration, the more wrinkles there are, which will easily cause stress concentration points, make it brittle, and lead to poor mechanical properties.

[0113] The actual photo of the transparent high-strength hydrogel film (after drying) prepared in Example 2 is as follows: Figure 7 As shown. The thickness of the hydrogel film is 100-200μm. Figure 7 It can be seen that the hydrogel is very transparent and the text under the membrane can be clearly seen.

[0114] The stress-strain curve of the hydrogel during the drying process is shown in Figure 2. Figure 8 As shown, the left figure shows the data of mechanical strength of gels with different water contents, and the right figure shows the effect of mineralization of metal ions with different concentrations on the mechanical properties of gels.

[0115] Figure 8 In the left figure, the 90% water content curve refers to the mechanical strength data tested when the water content of the hydrogel is 90% after mineralization and before drying.

[0116] The 50% water content curve refers to the mechanical strength data measured after the hydrogel is mineralized, dried to a water content of less than 3%, and then rehydrated to a water content of 50%.

[0117] In actual applications, after the periosteum material is dried to less than 3% and placed in the oral environment, the periosteum will gradually absorb water. According to existing data, equilibrium will be reached at a water content of 50%. The mechanical strength at this water content can represent the mechanical properties of the periosteum in actual applications. Therefore, the 50% water content is used for comparison.

[0118] Figure 8The left figure shows that the mechanical properties of the gel will be significantly improved after drying and reforming. During the drying and reforming process, the inorganic phase introduced by mineralization will form a rigid inorganic network, limiting the swelling of the polymer chain. At the same time, drying will affect the interface between the mineralized layer and the gel layer, causing irreversible deformation.

[0119] According to experimental data, the mechanical properties of periosteum materials dried to less than 3% water content will be improved compared to periosteum with a water content of 50%.

[0120] Therefore, in the present invention, drying is performed after mineralization to improve the mechanical properties.

[0121] Figure 8 The right figure shows the effect of mineralization of metal ions at different concentrations on the mechanical properties of the gel. Compared with Example 1, the concentration of zinc sulfate in the first step of the hydrogel preparation method is changed to 0.1%, and the concentration of hydroxypropyl carboxymethyl cellulose is 0.5%. The obtained membrane material is mineralized with 1%, 2.5%, 5%, and 7.5% zinc sulfate solutions for 2 hours, respectively. Figure 8 The results in the right figure show that mineralization with different metal ion concentrations can maintain the mechanical properties of the gel at a high level.

[0122] The compressive strength of the gel mineralized by adding different concentrations of metal ions is as follows Figure 9 As shown, the left picture is a line chart and the right picture is a bar chart. Figure 9 In the XG-Ca-27, XG-Ca-39, and XG-Ca-50 hydrogels, the calcium ion mass fraction (the ratio of calcium ion mass to the dry weight of the hydrogel after dehydration) after calcium ion mineralization was 27%, 39%, and 50%, respectively. Increasing calcium ion content indirectly reflects the degree of mineralization. Figure 9 It shows that before mineralization, the compression modulus is very low, and as the degree of mineralization increases, the compression modulus can be increased to a strength of 200-700 kPa.

[0123] The degradation curve of the gel prepared in Example 1 over time is shown in FIG. Figure 10 shown. Figure 10 It shows that after 12 weeks, the remaining mass is about 55%. The treatment period of periosteum is generally between 3 and 6 months, so the degradation period and treatment period match.

[0124] In the present invention, zinc ion mineralization significantly improves mechanical properties compared to calcium ion mineralization. Furthermore, in practical applications (bone defect repair), zinc ions offer superior performance compared to calcium ions. Therefore, zinc ions are preferred for mineralization to meet clinical needs, achieving both tensile strength and toughness, and satisfying material performance requirements.

Claims

1. A method for preparing a hydrogel periosteum material for oral bone repair, characterized in that The method is: A natural polysaccharide solution and a metal salt react to produce a gel-like substance, which is then dried to obtain a membrane-like substance. The membrane-like substance is placed in a metal salt solution for mineralization and drying to produce the oral bone repair hydrogel periosteum material. The metal salt is one or more of calcium salts, magnesium salts, zinc salts, copper salts, strontium salts, iron salts, ferrous salts, and barium salts. The mineralization is single-sided, with one side of the membrane-like substance immersed in the metal salt solution and the other side not in contact with the metal salt solution. The mineralization time is 1 hour to 4 hours. The mass concentration of the natural polysaccharide solution is 1-3%; The metal salt is configured into an aqueous solution, and the mass fraction of the metal salt solution is 0.1-15%; The oral bone repair hydrogel periosteum material has a core-shell structure, the mineralized surface is hydrophilic, and the unmineralized surface is hydrophobic; The thickness of the oral bone repair hydrogel periosteum material is 100-300 microns, the tensile strength is 60-90 MPa, and the degradation time is 3-6 months; The natural polysaccharide is one or more of hydroxypropyl carboxymethyl cellulose, xanthan gum, hyaluronic acid and sodium alginate.

2. The method according to claim 1, wherein The method is carried out according to the following steps: (1) Add metal salt solution to a natural polysaccharide solution with a mass concentration of 1-3%, stir and mix, remove bubbles, and dry to obtain a film-like substance; (2) The membrane-like material is added to a metal salt solution for mineralization and drying to obtain the oral bone repair hydrogel periosteum material; the mineralization is single-sided mineralization, where one side of the membrane-like material is immersed in the metal salt solution and the other side does not contact the metal salt solution; the mineralization time is 1 hour to 4 hours.

3. The method according to claim 2, wherein: In the step (1), the mass ratio of the natural polysaccharide to the metal salt is 1:0.01-5; the concentration of the metal salt solution is 0.1-15%; in the step (2), the metal salt solution is calcium chloride or zinc sulfate solution; the mass concentration is 1%-7.5%.

4. The oral bone repair hydrogel periosteum material prepared by the method according to any one of claims 1 to 3.

5. Use of the oral bone repair hydrogel periosteum material according to claim 4 in the preparation of dental bone repair products.

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