A calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold material and a preparation method thereof

Abstract

The application discloses a calcium phosphate-starch-polyvinyl alcohol-based bone repair stent material, which comprises the following raw materials: calcium phosphate, starch and a polyvinyl alcohol solution. The natural high-molecular starch with good biocompatibility and high swelling performance is selected as a binder to bond calcium phosphate powder, the starch has a similar polyhydroxy structure to glucose, and the P-O bond of the calcium phosphate framework can form a hydrogen bond with the H-O bond in the starch to realize reinforced connection. The polyvinyl alcohol contacts the starch in a winding interlocking mode, the polyvinyl alcohol long chain has a hydroxyl group, and the starch itself has a polyhydroxy structure. In the freezing process, the contact area of the polyvinyl alcohol and the starch is improved due to space compression, the hydrogen bond effect of the internal polyvinyl alcohol and the starch is promoted, and the polyvinyl alcohol and the starch are wound in a hydrogen bond form, so that the excessive swelling of the starch is inhibited, the stent is prevented from collapsing due to the rapid degradation of the starch, the compression resistance of the stent is improved, and the inherent brittleness of the calcium phosphate stent is overcome.

Description

Technical Field

[0001] This invention relates to the field of biomedical bone repair materials, and in particular to a calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold material and its preparation method. Background Technology

[0002] Human bone possesses self-repairing capabilities, but for large-area critical bone defects (greater than 5 mm) caused by disease or trauma, human bone cannot complete self-repair and requires external assistance to achieve bone healing. Clinically, artificial bone is often considered the "gold standard" for bone repair materials, but its application faces insurmountable obstacles such as raw material scarcity and host immunity issues, thus promoting the development of artificial bone scaffolds. Artificial bone offers advantages such as controllable mechanical properties and functionally oriented design. Commonly used calcium phosphate scaffolds have a composition similar to human bone, but their scaffolds are brittle and prone to fracture. While PMMA scaffolds possess sufficient elasticity and mechanical properties, they also suffer from self-toxicity and difficulty in degradation. Therefore, obtaining calcium phosphate scaffolds with a composition similar to human bone while overcoming its inherent brittleness is the direction for bone repair scaffold applications.

[0003] Calcium phosphate scaffolds are recognized as active scaffolds with osteoinductive properties, but they suffer from inherent brittleness that is difficult to overcome. Studies have shown that polymeric materials possess inherently high toughness, but their strength is relatively low. Starch, a natural polymer compound with high water absorption, can improve the hydrophilicity of scaffolds and enhance their mechanical strength. Its unique wet-response properties can promote in-situ pore formation within the scaffold and have the ability to enlarge existing pores. Starch has been extensively studied in the medical field, and its addition is often used to improve the compressive strength of scaffolds. However, its improvement on scaffold toughness is not significant, and starch degrades rapidly in body fluids, easily causing premature scaffold collapse. Therefore, the introduction of dual polymeric materials is often employed to improve both the degradation rate and toughness of the scaffold.

[0004] Polyvinyl alcohol (PVA) possesses advantages such as good water solubility, low toxicity, high elastic modulus, high mechanical strength, and good biocompatibility, making it widely used in the biomedical field. PVA degrades slowly and, due to its polyhydroxy structure, readily binds to starch via hydrogen bonds, forming an interlocking structure that inhibits excessive starch swelling and slows down starch degradation. Furthermore, the surface entanglement of PVA enhances the mechanical strength of the scaffold. Therefore, calcium phosphate-starch-PVA-based bone repair scaffold materials can be considered as one of the ideal bone repair materials. Summary of the Invention

[0005] The purpose of this invention is to provide a calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold material and its preparation method. This bone repair scaffold material possesses both bone repair activity and the repair capabilities of a calcium phosphate scaffold, as well as mechanical strength and elastic recovery, exhibiting excellent physicochemical properties. After sterilization, the material can be directly placed at the bone defect site. Upon immersion in body fluids, the material absorbs water and swells, increasing its porosity. The binding and interlocking effect of polyvinyl alcohol inhibits excessive swelling of starch and forms an interconnected network with it, facilitating the internal flow of body fluids and promoting the release of active calcium and phosphate ions. This induces osteoblast proliferation, migration, and mineralization, ultimately achieving in-situ bone repair.

[0006] The technical solution adopted in this invention is: a calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold material, comprising the following raw materials: calcium phosphate, starch, and polyvinyl alcohol solution.

[0007] The mass ratio of calcium phosphate to starch is 9:1-7:3.

[0008] The mass ratio of the calcium phosphate and starch to the polyvinyl alcohol solution is 1:1 to 1:6.

[0009] Furthermore, the calcium phosphate used as the active ingredient is one or more of the following: calcium pyrophosphate, α-tricalcium phosphate, β-tricalcium phosphate, hydroxyapatite, or biphasic calcium phosphate.

[0010] Furthermore, the particle size of the calcium phosphate is less than 500 nm.

[0011] Furthermore, the starch may be one or more of the following: tapioca starch, corn starch, potato starch, or gelatinizable starch.

[0012] Starch is a polymer of glucose and has similar properties to glucose. It can combine with a variety of organic substances through hydrogen bonds and has the characteristic of gelatinization at high temperatures. After gelatinization, its viscosity increases, so it can be used as a binder for calcium phosphate scaffolds.

[0013] Furthermore, the concentration of the polyvinyl alcohol solution is 1-5 wt%, wherein the molecular weight of the polyvinyl alcohol is 50,000-150,000.

[0014] Polyvinyl alcohol (PVA) is a linear polymer with secondary hydroxyl groups, and the hydroxyl groups in the molecule are highly reactive. Its degree of polymerization is classified as ultra-high degree of polymerization (molecular weight 250,000-300,000), high degree of polymerization (molecular weight 170,000-220,000), medium degree of polymerization (molecular weight 120,000-150,000), and low degree of polymerization (25,000-35,000). The higher the degree of polymerization, the higher the viscosity of its aqueous solution. Therefore, PVA can undergo hydrogen bonding with starch to form an interlocking network.

[0015] The preparation method of the above-mentioned calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold material includes the following steps:

[0016] S1. A certain amount of calcium phosphate and starch are mixed evenly and sieved to obtain calcium phosphate-starch uniformly mixed granules.

[0017] S2. Add a certain amount of polyvinyl alcohol solution to the calcium phosphate-starch uniformly mixed particles obtained in S1, and stir at room temperature for 0.5-1 hour to form a calcium phosphate-starch-polyvinyl alcohol dispersion.

[0018] S3. The calcium phosphate-starch-polyvinyl alcohol dispersion obtained in S2 is gelatinized in a water bath at 70-90℃ for 5-15 minutes to obtain calcium phosphate-starch-polyvinyl alcohol gelatinized slurry.

[0019] S4. The gelatinized slurry obtained in S3 is frozen at -20℃ for 12-36 hours and then freeze-dried in a freeze dryer to obtain a calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold material. The freezing method compresses the internal space of the scaffold, promoting the formation of hydrogen bonds within the scaffold; the obtained bone repair scaffold can absorb water and generate pores in body fluids.

[0020] Preferably, in S1, the particle size of the calcium phosphate is 200 nm.

[0021] The bone repair scaffold uses calcium phosphate as the active ingredient for bone repair and polyvinyl alcohol solution as a dispersant. Utilizing the high-temperature gelatinization properties of starch, the contact area between starch, calcium phosphate, and polyvinyl alcohol is increased, and hydrogen bonds are formed, creating an interlocking double-network structure. Furthermore, the calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold provided by this invention exhibits good mechanical properties, with enhanced compressive strength and improved tensile strength. The bone repair scaffold provided by this invention also demonstrates good biocompatibility and connectivity with various cell types and possesses excellent bone repair potential. The raw materials for the bone repair scaffold provided by this invention are abundant, readily available, and inexpensive, and the preparation method is simple and easy to implement, enabling large-scale production. The bone repair scaffold provided by this invention has potential clinical application value and socio-economic benefits.

[0022] The present invention has the following advantages over the prior art:

[0023] 1. Natural high-molecular-weight starch with good biocompatibility and high swelling capacity is selected as a binder to bind calcium phosphate powder. Starch has a polyhydroxy structure similar to glucose, and the PO bonds in the calcium phosphate backbone can form hydrogen bonds with the HO bonds in starch for enhanced bonding. Polyvinyl alcohol (PVA) contacts the starch in an interlocking manner. PVA contains hydroxyl groups in its long chain, and starch itself has a polyhydroxy structure. During freezing, the compression of space increases the contact area between PVA and starch, promoting hydrogen bonding between the internal PVA and starch, and interlocking them in the form of hydrogen bonds. This inhibits excessive swelling of starch and prevents the scaffold from collapsing due to rapid starch degradation. This improves the compressive strength of the scaffold and overcomes the inherent brittleness of the calcium phosphate scaffold.

[0024] 2. The network structure of the scaffold promotes the flow of body fluids and nutrients, induces in-situ mineralization of the scaffold, and promotes the proliferation, migration and mineralization of osteoblasts, ultimately achieving in-situ bone repair.

[0025] 3. This bone repair scaffold possesses both suitable mechanical properties and osteogenic activity, making it promising for clinical application. Attached Figure Description

[0026] Figure 1 The compressive strength diagram of the calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold;

[0027] Figure 2 The tensile strength diagram of the calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold;

[0028] Figure 3 Cell adhesion diagram of calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold;

[0029] Figure 4 CT images of a rat skull 4 weeks after implantation of a calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold. Detailed Implementation

[0030] The embodiments of the present invention are described in detail below. The embodiments are implemented based on the technical solution of the present invention, and detailed implementation methods and specific operation processes are given. However, the protection scope of the present invention is not limited to the following embodiments.

[0031] Example 1

[0032] S1. Mix 0.9g of calcium pyrophosphate (particle size of 200nm) with 0.1g of cassava starch evenly and sieve to obtain a uniformly mixed calcium phosphate-starch granule.

[0033] S2. Add 1g of 5wt% polyvinyl alcohol solution to the calcium phosphate-starch mixed particles obtained in S1, and stir at room temperature for 1 hour to form a calcium phosphate-starch-polyvinyl alcohol dispersion.

[0034] S3. The calcium phosphate-starch-polyvinyl alcohol dispersion obtained in S2 is gelatinized in a water bath at 70°C for 15 minutes to obtain calcium phosphate-starch-polyvinyl alcohol gelatinized slurry.

[0035] S4. The gelatinized slurry obtained in S3 is frozen at -20℃ for 36 hours and then freeze-dried in a freeze dryer to obtain calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold material.

[0036] Example 2

[0037] S1. Mix 0.8g of calcium pyrophosphate (particle size 200nm) with 0.2g of cassava starch evenly and sieve to obtain a uniformly mixed calcium phosphate-starch granule.

[0038] S2. Add 4g of 3wt% polyvinyl alcohol solution to the calcium phosphate-starch mixed particles obtained in S1, and stir at room temperature for 1 hour to form a calcium phosphate-starch-polyvinyl alcohol dispersion.

[0039] S3. The calcium phosphate-starch-polyvinyl alcohol dispersion obtained in S2 is gelatinized in a water bath at 80°C for 10 minutes to obtain calcium phosphate-starch-polyvinyl alcohol gelatinized slurry.

[0040] S4. The gelatinized slurry obtained in S3 is frozen at -20℃ for 24 hours and then freeze-dried in a freeze dryer to obtain calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold material.

[0041] Example 3

[0042] S1. Mix 0.7g of calcium pyrophosphate (particle size 200nm) with 0.3g of cassava starch evenly and sieve to obtain a uniformly mixed calcium phosphate-starch granule.

[0043] S2. Add 6g of 1wt% polyvinyl alcohol solution to the calcium phosphate-starch mixed particles obtained in S1, and stir at room temperature for 0.5 hours to form a calcium phosphate-starch-polyvinyl alcohol dispersion.

[0044] S3. The calcium phosphate-starch-polyvinyl alcohol dispersion obtained in S2 is gelatinized in a water bath at 90°C for 5 minutes to obtain calcium phosphate-starch-polyvinyl alcohol gelatinized slurry.

[0045] S4. The gelatinized slurry obtained in S3 is frozen at -20℃ for 12 hours and then freeze-dried in a freeze dryer to obtain calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold material.

[0046] Comparative Example 1

[0047] S1. Mix 0.9g of calcium pyrophosphate (particle size of 200nm) with 0.1g of cassava starch evenly and sieve to obtain a uniformly mixed calcium phosphate-starch granule.

[0048] S2. Add 1g of water to the calcium phosphate-starch mixed granules obtained in S1, and stir at room temperature for 1 hour to form a calcium phosphate-starch dispersion.

[0049] S3. The calcium phosphate-starch dispersion obtained in S2 is gelatinized in a water bath at 70°C for 15 minutes to obtain calcium phosphate-starch gelatinized slurry.

[0050] S4. The gelatinized slurry obtained in S3 is frozen at -20℃ for 36 hours and then freeze-dried in a freeze dryer to obtain calcium phosphate-starch based bone repair scaffold material.

[0051] Comparative Example 2

[0052] The difference from Example 3 is as follows:

[0053] S2. Add 7g of 1wt% polyvinyl alcohol solution to the calcium phosphate-starch mixed particles obtained in S1, and stir at room temperature for 0.5 hours to form a calcium phosphate-starch-polyvinyl alcohol dispersion.

[0054] Mechanical properties and biological evaluation of the bone repair scaffold materials obtained in Examples 1-3, Comparative Examples 1 and 2:

[0055] The calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold materials obtained in Examples 1-3, Comparative Example 1 and Comparative Example 2 were placed under a load of 500N and subjected to compression and tensile tests at a speed of 0.5mm / min.

[0056] The calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold materials obtained in Examples 1-3, Comparative Example 1 and Comparative Example 2 were placed in 24-well plates and co-cultured with 20,000 osteoblasts.

[0057] The calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffolds obtained in Examples 1-3, Comparative Example 1, and Comparative Example 2 were placed at the skull defects of rats.

[0058] like Figure 1 As shown, the bone repair scaffold material of Example 1 has excellent compressive strength;

[0059] like Figure 2 As shown, the bone repair scaffold material of Example 1 has excellent tensile strength;

[0060] like Figure 3 As shown, in Example 1, osteoblasts and the scaffold have good biocompatibility and can adhere to each other;

[0061] like Figure 4 As shown in Example 1, significant new bone growth was observed at the site of the rat skull defect four weeks later. This indicates that the calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold has a good bone repair effect.

[0062] The mechanical properties and biological evaluations of Examples 2 and 3 are similar to those of Example 1;

[0063] Comparative Examples 1 and 2 exhibited reduced compressive strength and were prone to scaffold collapse during cell culture.

[0064] Experiments have demonstrated that the material prepared in this application possesses both excellent mechanical properties and superior bone repair activity. When filling bone defects, the material swells, promotes the release of calcium and phosphorus ions, induces osteoblast adhesion and mineralization, and ultimately induces new bone growth.

[0065] As described above, the present invention can be sufficiently realized. The above description is merely a reasonable implementation example of the present invention; the scope of protection of the present invention includes, but is not limited to, these examples. Any non-substantial modifications or alterations made by those skilled in the art based on the technical solution of the present invention are included within the scope of the present invention.

Claims

1. A calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold material, characterized in that, The ingredients include: calcium phosphate, starch, and polyvinyl alcohol solution; The mass ratio of calcium phosphate to starch is 9:1-7:3; The mass ratio of the calcium phosphate and starch to the polyvinyl alcohol solution is 1:1 to 1:

6. The concentration of the polyvinyl alcohol solution is 1-5 wt%, wherein the molecular weight of the polyvinyl alcohol is 50,000-150,000. In the bone repair scaffold material, polyvinyl alcohol and starch undergo hydrogen bonding to form an interlocking network, and the PO bonds of calcium phosphate and the HO bonds of starch form hydrogen bonds for enhanced connection.

2. The calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold material according to claim 1, characterized in that, The calcium phosphate is one or a mixture of calcium pyrophosphate, α-tricalcium phosphate, β-tricalcium phosphate, or hydroxyapatite.

3. The calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold material according to claim 1, characterized in that, The particle size of the calcium phosphate is less than 500 nm.

4. The calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold material according to claim 1, characterized in that, The starch is one or more of tapioca starch, corn starch, or potato starch.

5. The method for preparing the calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold material according to any one of claims 1-4, characterized in that, Includes the following steps: S1. Mix calcium phosphate and starch evenly and sieve to obtain calcium phosphate-starch uniformly mixed granules; S2. Add the polyvinyl alcohol solution to the calcium phosphate-starch uniformly mixed particles obtained in S1, and stir at room temperature for 0.5-1 hour to form a calcium phosphate-starch-polyvinyl alcohol dispersion. S3. The calcium phosphate-starch-polyvinyl alcohol dispersion obtained in S2 is gelatinized in a water bath at 70-90℃ for 5-15 minutes to obtain calcium phosphate-starch-polyvinyl alcohol gelatinized slurry. S4. The gelatinized slurry obtained in S3 is frozen at -20℃ for 12-36 hours and then freeze-dried in a freeze dryer to obtain calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold material.

6. The method for preparing the calcium phosphate-starch-polyvinyl alcohol-based bone repair scaffold material according to claim 5, characterized in that, In S1, the particle size of the calcium phosphate is 200 nm.

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